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Biomedical subjects

M Ishii

Publications and source records attributed to M Ishii.

At least 127 records · Page 7Linked to original sources

Tolerability and safety of a calcium channel blocker in comparison with a diuretic in the treatment of elderly patients with hypertension: secondary analysis of the NICS-EH.

A randomized prospective controlled study, the National Interventional Cooperative Study in Elderly Hypertensives (NICS-EH), previously demonstrated that the preventive effect of the long-acting calcium channel blocker nicardipine on the cardiovascular endpoint was similar to that of the diuretic, trichlormethiazide. The present report is a sub-analysis in which we compare the tolerability and safety of the calcium channel blocker with that of a diuretic in the long-term treatment of elderly hypertensives. A total of 429 elderly patients with hypertension were assigned to the nicardipine group or the diuretic group by the double-dummy method and were followed up for 5 years. Two hundred four patients in the nicardipine group and 210 patients in the diuretic group were analyzed. The incidences of fatal and nonfatal cardiovascular (CV) events in the two groups were comparable, and there was no significant difference in the cumulative event-free rate. However, the total incidence of adverse reactions, including non-CV events and unfavorable BP changes, was 31 cases (15.2%) in the nicardipine group, which was significantly lower than the 47 cases (22.4%) in the diuretic group (log-rank: p=0.026, G. Wilcoxon: p=0.01). The total number of medical endpoints, including CV events, the withdrawal of the patient from the study, was 52 (25.5%) in the nicardipine group, which was significantly lower than the 65 (31.0%) in the diuretic group (log-rank: p=0.078, G. Wilcoxon: p=0.044). It was concluded that sustained-release nicardipine is better tolerated, as it exhibits a lower incidence of medical-related withdrawals such as adverse drug reactions, non-cardiovascular events and unfavorable BP responses during the treatment.

Aged↗

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Aged↗

[Mechanism of development of space motion sickness].

Astronauts and scientists are scheduled to stay aboard the International Space Station (ISS) for three-month periods, and various problems relating to the human ability to live in space for such long periods of time, as well as medical problems, are being studied. For the crews that have operated and worked on the US space shuttle, the longest time spent in the gravity-free (accurately speaking, microgravity) environment of space has been about two weeks. Even such short periods have generated reports of various physical changes and symptoms caused by the absence of gravity. Particularly striking effects are circulatory system changes, muscular atrophy and decalcification of bones. In addition, serious problems arise during the time in space due to the symptoms of space motion sickness, caused by neuro-otological changes. Space motion sickness is experienced by nearly 70% of the first-time astronauts, in the form of such symptoms as nausea, and vomiting. It is said that space motion sickness develops at the time of adaptation of the body to the gravity-free environment. Unlike motion sickness on Earth, space motion sickness is characterized by a feeling of fullness of the head, a hot face and reduced sweating. The provocative factors include movement of the head in the pitch and roll directions and the unusual visual field. This paper reviews the research that has been carried out to date on space motion sickness, and its counter measures comprehensively, in terms of the changes in the otolith organ as well as asynchronization of information between the movements of the head and eyeballs, the deep sensations and body fluid shifts. Other problems, which may be encountered as a result of yet longer stays in space, are also discussed.

Adaptation, Physiological↗

Curative resection of both primary and second primary lung cancer.

Curative resection of a second primary lung cancer in a patient who survived small-cell lung cancer is reported. Small-cell cancer had been treated with chemotherapy followed by surgical resection 12 years before. The patient developed squamous cell cancer as the second primary tumor and underwent lobectomy with mediastinal node dissection. Patients who undergo two curative pulmonary resections of both primary and second primary lung cancer are extremely rare. The patient is alive 176 months after the initial diagnosis of small-cell lung cancer and 28 months after resection for his second primary lung cancer. Careful follow-up at an interval of 3-6 months beyond 10 years is very important because adequate treatments could lead to longer survival of patients with primary small-cell lung cancer.

Carcinoma, Small Cell↗

[Effects of cernitin pollen-extract (Cernilton) on inflammatory cytokines in sex-hormone-induced nonbacterial prostatitis rats].

Cernitin pollen-extract (Cernilton, CN) is a preparation made from eight kinds of pollen and has been used for various prostatic diseases in Japan and Europe. We reported previously that CN possessed a recovery action on the sex-hormone-induced nonbacterial prostatitis in rats. To clarify the possible mechanism of action of CN, we investigated the effects of CN on inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the same model. Aged Wistar rats were castrated and injected 17 beta-estradiol (0.25 mg/kg/day, s.c.) for 30 days. CN (630 and 1,260 mg/kg, p.o.) or testosterone (2.5 mg/kg, s.c.) was administered for the last 14 days of the treatment of 17 beta-estradiol. In control rats, prostatic IL-6 and TNF-alpha contents were increased approximately 2-3 fold, and acinar glandular inflammation and stromal proliferation were found histopathologically, as compared with those of intact rats. On the other hand, CN decreased the increased contents of cytokines in a dose-dependent manner. The histopathological changes mentioned above were restored in rats treated with 1,260 mg/kg. Testosterone also ameliorated them significantly. These results indicate that CN has an anti-inflammatory action, and that the inhibitory effect of CN on the prostatic inflammatory cytokine is an important factor in its action.

Animals↗

[A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system].

AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions.

Aged↗

Malaria infections in crews of Japanese ships.

Plasmodium falciparum malaria is the most dangerous infection for seafarers in West Africa. In December 1998, five cases of this infection occurred among Japanese seafarers in West Africa, two of them died, one on board ship, and another died five days after the admission to the hospital in Reunion island, East Africa. Six other cases of falciparum malaria infection occurred among Japanese seafarers on another ship in December 1999. Three infected persons were admitted to hospitals in Abidjan (Ivory Coast) and Point Noire (Congo). In Japan, over 100 cases of imported malaria were recorded each year during the period from 1990 to 1997, and about 40% of these cases were falciparum infections. It is not known how many of them occurred among seafarers. We estimate that at least 5% of all malaria cases in Japan are seafarers. Measures to protect crews of ships against malaria are discussed.

Adult↗

Messenger ribonucleic acid expression of 16 matrix metalloproteinases in bone-implant interface tissues of loose artificial hip joints.

Matrix metalloproteinases (MMPs) have been reported to be the major factors responsible for aseptic loosening of artificial hip joints. So far, messenger ribonucleic acid (mRNA) expression patterns of seven MMPs have been reported, but that of many other MMPs which have been newly discovered or recently considered to be responsible for prosthetic loosening is still unknown. In this study, mRNA expression pattern of 16 different types of MMPs were analyzed to evaluate which MMPs were locally produced and contributed to prosthetic loosening. Synovium-like interface tissues between bone and prosthesis were collected from 18 cases of aseptic loose artificial hip joint at revision surgery. Six cases of normal synovium were used as controls. Total RNA was extracted by single-step acid guanidinium-thiocyanate-phenol-chloroform procedure. mRNA expression of MMPs was analyzed by semiquantitative reverse transcription-polymerase chain reaction. Based on local expression pattern of MMPs at the mRNA level, aseptic loose artificial hip joint was characterized by elevated expression of MMP-1, MMP-9, MMP-10, MMP-12, and MMP-13; moderate expression of MMP-2, MMP-7, MMP-8, MMP-11, membrane type (MT)1-MMP (MMP-14), MT2-MMP (MMP-15), MT3-MMP (MMP-16), MT4-MMP (MMP-17), and MMP-19; lower expression of MMP-3; and little significance of MMP-20. The MMPs detected in this study can potentially degrade almost all components of the periprosthetic extracellular matrix. Thus, many MMP type enzymes possibly contribute to prosthetic loosening and osteolysis through pathologic extracellular matrix degradation and connective tissue/bone remodeling around prostheses.

Aged↗

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy.

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Antibiotics, Antineoplastic↗

Effect of left ventricular wall mass on Doppler filling patterns in the developing normal human heart.

To assess gestational age- and growth-related changes in left ventricular (LV) size, LV wall, and LV transmitral flow velocity patterns, 2-dimensional (2-D) and Doppler echocardiographic studies were performed in 89 normal fetuses aged 16 to 38 weeks. Serial studies were designed in 7 fetuses. Variables measured from 4-chamber views were chamber areas and myocardial wall areas. From these measurements, area shortening fraction and ratio of myocardial wall area to end-diastolic chamber area were calculated. LV end-diastolic chamber area and myocardial wall area increased exponentially with advancing gestational age (r = 0.88 and 0.90, respectively, p < 0.001). Area shortening fraction showed no significant changes with gestational age. Ratio of myocardial wall area to LV end-diastolic chamber area decreased gradually with increasing gestational age (r = -0.77, p < 0.001). With increasing gestational age, mitral peak velocities of early diastole increased (r = 0.82, p < 0.01) with little change in peak velocity during atrial contraction. Multiple regression analysis showed that age-related increases in peak velocity of early diastole were related to advancing gestational age and also to decreases in ratio of myocardial wall area to LV end-diastolic chamber area. Low peak filling velocities during early diastole in younger fetuses may be related partly to relative increase in LV wall mass. The gestational age-related decreases in LV wall mass may be one of the important mechanisms of gestational age-related alterations in diastolic properties, especially relaxation processes.

Blood Flow Velocity↗

Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis.

Among the high-throughput, comprehensive technological methods used to analyze transcript expression levels, array-based hybridization and serial analysis of gene expression (SAGE) are currently the most common approaches. To compare the quantitative accuracy of oligonucleotide array and SAGE, both methods were carried out on identical RNA specimens prepared from human blood monocytes and granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages. For SAGE analysis, 57,560 and 57,463 tags were obtained from monocytes and macrophages, respectively, resulting in approximately 28,000 different tags, while oligo array hybridization was performed with GeneChip (Affymetrix), which represents approximately 6000 transcripts. These two methods correlated quite well in both absolute expression analyses and comparative analyses during differentiation. The correlation was better for genes with higher expression levels and greater changes in expression. This finding suggests that GeneChip technology is reasonably reliable for quantitative analysis of expression profiling and would be appropriate as a common platform upon which to build a gene expression database.

Gene Expression Profiling↗

Rapid and sensitive XAFS using a tunable X-ray undulator at BL10XU of SPring-8.

The design and performance of the high-brilliance XAFS facility at BL10XU of SPring-8, aimed at rapid and sensitive measurement of X-ray absorption fine structure (XAFS), is reported. Both undulator gap and double-crystal monochromator have been successfully controlled covering a wide energy range (5-30 keV). A versatile goniometer system, consisting of two independent high-precision goniometers, is capable of polarized XAFS in fluorescence mode and surface-sensitive experiments using a grazing-incidence geometry. By sharing major components, i.e. a monolithic Ge 100-pixel array detector and a closed-cycle He cryostat, both polarized XAFS and X-ray standing wave (XSW) experiments can be performed at low temperature (15-300 K). The performance of the spectrometer has been evaluated by recording XAFS spectra in transmission mode.

Journal Article↗

Scleroderma-like reaction induced by uracil-tegafur (UFT), a second-generation anticancer agent.

UFT, a combination of uracil and tegafur, is a second-generation anticancer agent. UFT has been used in Japan, other Asian countries, South America, and Russia. Recently, UFT has been extensively studied for colorectal, pancreatic, and various types of cancer in North America and Europe, especially with leukovorin. We report a case of a scleroderma-like reaction induced by long-term administration of UFT. This is the first report of UFT-induced scleroderma-like reaction.

Antimetabolites, Antineoplastic↗

alpha2-Adrenergic-receptor response in reversible increase in hemoglobin concentration in intermittent hypoxia.

We have previously shown that intermittent hypoxia (IHx, 10% O(2), 60 min/day) leads to an increase in the splenic alpha2-adrenoceptor response and results in a splenic contraction-induced reversible increase in hemoglobin concentration ([Hb]). In the present study, we determined whether IHx of shorter duration (15 min/day (15-min) and 30 min/day (30-min)), produced this phenomenon in rats. A significant increase in [Hb] during hypoxia was observed in both the groups, but its magnitude was larger in the 30-min IHx rats. Even when the cumulative exposure time (time/dayxdays) was shorter, the [Hb] increase was larger in the rats with longer daily hypoxic exposure. The alpha2-adrenoceptor antagonist yohimbine abolished the [Hb] increase of 15- and 30-min IHx. The increase in [Hb] following administration of the alpha2-adrenoceptor agonist oxymetazoline was also higher in 30-min IHx; indicating that the higher [Hb] produced by longer daily hypoxic exposure times is the result of increases in alpha2-adrenergic-receptor response of greater magnitude. In conclusion, IHx for periods as short as 15 and 30 min/day increases the splenic alpha2-adrenoceptor response and its magnitude reaches the maximum value depending on the daily hypoxic exposure time. A reversible increase in [Hb] constitutes a useful mechanism that protects organ oxygen supply during hypoxic episodes of variable duration and intensity.

Journal Article↗

In vitro cytokine production of peripheral blood mononuclear cells in response to HCV core antigen stimulation during interferon-beta treatment and its relevance to sCD8 and sCD30.

We investigated the responses of peripheral blood mononuclear cells (PBMCs) to hepatitis C virus core protein in ten patients with chronic hepatitis C during interferon (IFN)-beta treatment to determine if the modulation of the immune reaction to hepatitis C virus by IFN treatment is associated with the viral clearance. Interleukin-2, interleukin-4, interleukin-10, and interferon-gamma in the supernatant of the patients' PBMC co-cultured with the HCV core antigen-presenting autologous PBMCs were measured by ELISA. Serum levels of soluble CD (sCD) 8 and sCD30 in these patients were also measured by ELISA. The production of interleukin-2 and interferon-gamma by PBMCs of sustained responders (SRs) increased after IFN-treatment, although it did not reach a significant level. Interleukin-10 was detected only in non-responders (NRs) at 0 and 4 weeks after the start of IFN treatment. Serum sCD8 level increased significantly in SR with IFN treatment. A close correlation between the serum sCD8 levels and interferon-gamma levels in the supernatant at week 8 was observed in SR. These results suggest that IFN treatment potentiates the cellular immune reaction against HCV core protein more efficiently in SR than in NR.

Journal Article↗

Analysis of biochemical and virological efficacy of human lymphoblastoid interferon (IFN) in patients with compensated type C liver cirrhosis: comparative study between increase in individual IFN dose and prolonging of treatment period, using a multicenter randomized controlled trial.

A controlled trial was conducted to compare the efficacy of interferon (IFN) between two groups of patients with type C liver. Thirty-five patients were randomly assigned to group A (17 patients) or group B (18 patients). The former received 3 megaunits (MU) of human lymphoblastoid IFN six days per week for two weeks, followed by three days per week for 50 weeks; the latter group received 6 MU six days per week for two weeks followed by three days per week for 24 weeks. The percentages of biological sustained responders (B-SR) and virological sustained responders (V-SR) were 29.4 and 23.5%, respectively, in group B, and 17.6% for both in group A. The therapeutic effects were not different between two groups. HCV genotype 2 accounted for significantly higher percentage of B-SR and V-SR (both 57.1%, respectively). These findings indicate that IFN is effective in type C cirrhosis with genotype 2.

Adult↗

Involvement of reactive oxygen species and nitric oxide in gastric ischemia-reperfusion injury in rats: protective effect of tetrahydrobiopterin.

The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.

Animals↗