Juntendo Medical Journal
Online ISSN : 2188-2134
Print ISSN : 0022-6769
ISSN-L : 0022-6769
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Volume 55, Issue 3
Displaying 1-30 of 30 articles from this issue
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Contents
  • Lessons from the Spontaneous Mouse Models for Treatment of Type 2 Diabetic Nephropathy and IgA Nephropathy
    YASUHIKO TOMINO
    2009 Volume 55 Issue 3 Pages 228-234
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.228
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    This review introduces a new strategy for treatment of type 2 diabetic nephropathy and IgA nephropathy based on the findings in animal models, i. e. KK-AY/Ta mouse and ddY mouse. Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with diabetes. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological features of diabetic nephropathy. There have been many reports using various models of type 2 diabetes. Ito et al., my colleagues, reported that the pathological changes of glomeruli in KK-AY/Ta mice were consistent with those in the early stage of human diabetic nephropathy. Advanced glycation end products (AGEs) and transforming growth factor-beta (TGF-β) protein appeared to be localized in the glomerular mesangial matrices. It appears that KK-AY/Ta mice, especially in terms of histopathological findings, are a suitable animal model for type 2 diabetic nephropathy. For therapeutic interventions to reduce AGEs, many compounds have been reported to be AGE inhibitors, such as aminoguanidine, phenacyl thiazolium bromide, 2-isopropylidenehydrazono-4-oxo-thiazolidine-5-yl-acetanilide (OPB-9195), 2, 3-diaminophenazine, vitamin C, vitamin E, angiotensin II receptor inhibitor and pyridoxamine. It is indicated that pyridoxamine ameliorated lipid peroxidation and insulin resistance in KK-AY/Ta mice. Eicosapentaenoic acid (EPA) showed multiple effects such as anti-thrombotic, hypolipidemic, anti-atherogenic, anti-inflammatory and anti-mitogenic actions. EPA improved type 2 diabetic nephropathy in such mice. IgA nephropathy is the most common primary chronic glomerulonephritis, which was described by J. Berger. Histopathologically, IgA nephropathy is characterized by expansion of glomerular mesangial matrix with mesangial cell proliferation. Glomeruli typically contain generalized-diffuse granular mesangial deposits of IgA (IgAl), IgG and C3. In 1985, Imai et al. first reported that the ddY strain of mouse can serve as a spontaneous animal model for IgA nephropathy. These mice show mild proteinuria without hematuria, and mesangioproliferative glomerulonephritis with severe glomerular IgA deposits in association with an increase of serum IgA level. Electron dense deposits are observed in the glomerular mesangial areas by electron microscopy. These immunohistopathological findings in ddY mice resemble those in IgA nephropathy patients. These findings from the ddY mouse appear to be useful in determining the pathogenesis and treatment of patients with IgA nephropathy. Although glucocorticoids and immunosuppressants are effective for IgA nephropathy patients demonstrating minor to moderate glomerular injuries, it is necessary to use large doses of these drugs for prolonged periods, which causes severe adverse effects. It appears that PSL-liposome-treated ddY mice showed a marked decrease. Treatments with mizoribine (an immunosuppressant), a monoclonal antibody to murine CD4 molecules and bone marrow transplantation (BMT) also improved glomerular injury in IgA nephropathy in ddY mice. BMT from quiescent ddY mice resulted in the reduction of not only glomerular injury but also mesangial IgA and IgG depositions in recipient-quiescent ddY mice. It appears that bone marrow cells assumed to be IgA-producing cells, may initiate IgA nephropathy.
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  • Perioperative Safety of Caparoscopic Roux-en-Y Gastric Bypass : A Children's Hospital Experience
    GO MIYANO
    2009 Volume 55 Issue 3 Pages 256-262
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.256
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    Background/Purpose : To evaluate the perioperative safety of laparoscopic Roux-en-Y gastric bypass (LRYGB) in a children's hospital setting. Patients and Methods : Perioperative (≤90 days) clinical outcomes of a consecutive series of 77 patients (16.8±2.1 yrs : 13 to 23 years, 52 female : 25 male), who underwent LRYGB between 2002 and2007were examined. In this series, the mean patient BMI was 59.4, was first stratified into two groups based on BMI : Group-A, BMI<60kg/m2 (n=46), and Group-B, BMI≥60kg/m2 (n=31). For assessment of any relationship between bariatric surgical experience and perioperative outcome, outcomes were examined as a function of the timing of the procedure in the first half (patients 1-40) vs. second half (cases 41-77) of the series. Results : There was no perioperative mortality or conversion to open surgery in this super-obese cohort. Intraoperative complications were uncommon (2.6%); there were no anesthetic complications and transfusion was not required in any case. Median hospital stay was 3.8±1.7 days. The common types of postoperative complications included gastrojejunal anastomotic stricture (18.2%), leak (6.5%), dehydration (6.5%), and small bowel obstruction (5.2%). Reoperation was required in 8 cases (4 leaks, 4 small bowel obstructions). Patients with BMI≥60kg/m2 and those with BMI<6kg/m2 had similar rates of perioperative complications. Perioperative complication rates did not significantly differ between the first half of the series were and the second half of the series. Surgical duration decreased significantly from 333 minutes in the first quartile of cases to 216 minutes in the last quartile of cases. Conclusions : The largest single institutional series of adolescent bariatric patients with LRYGB demonstrated that LRYGB can be accomplished safely in super-obese adolescents in a children's hospital setting, with complication rates similar to that reported in adult populations. In this series, there was no correlation between the complication rate and the level of surgical experience. Surgical duration improved with experience in a relatively small number of cases.
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  • Pathology and protective strategy for ischemic brain injuries with cerebral infarction
    TAKAO URABE
    2009 Volume 55 Issue 3 Pages 263-272
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.263
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    There is increased evidence supporting the contribution of oxidative stress to ischemia/reperfusion-induced damage in a consecutive two-phase pattern : immediate direct cytotoxic effects and subsequent redox-mediated inflammatory injury. It is thought that research into the pleiotropic effects of several drugs would be a useful strategy for the development of new brain protective therapies. From this perspective, we have attempted to evaluate the potential brain protective effects of several drugs. Cognitive impairment, swallowing disturbance, and depression are crucial complications causing specifically attributable proportions of disability in patients with stroke. We established an animal model by permanent occlusion of both common carotid arteries causing chronic cerebral ischemia, and assessed the effect of several drugs. Recently, a few reports have indicated that type III phosphodiesterase inhibitor (PDE III-1), which is clinically used for the treatment of chronic cerebral infarction as an anti-platelet agent, has neuroprotective effects. We assessed the neuroprotective mechanisms of PDE III-I through signaling pathways, which lead to the activation of cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB) phosphorylation using this chronic cerebral hypoperfusion model. In the future, we expect that the clinical utility of new brain protective agents will be developed based on a multi-target mechanism.
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  • Challenges to enigmas in the pathogenesis of IgA nephropathy
    YUSUKE SUZUKI
    2009 Volume 55 Issue 3 Pages 273-280
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.273
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    IgA nephropathy (IgAN) is a disease with a poor prognosis, but its pathogenesis remains unknown. Large numbers of studies have demonstrated that abnormal humoral and cellular immunity may contribute to the pathogenesis of IgAN. However, clinical evidence indicates that bone marrow cells and mucosal immunity may also play a key role in the pathogenesis. Based on these findings, impaired immune regulation in the “mucosa-bone marrow axis” has been postulated in IgAN, although the underlying mechanisms remain unclear. This is mainly due to difficulty in the clinical approach to the complicated immune system. Therefore, appropriate animal models are required to facilitate research on this disease. Accumulating evidence from a number of animal models suggests that dysregulation of the innate and cellular immunity in IgAN results in changes to the mucosal immune system. Our group recently established several useful animal models, and is currently per-forming research using these models. To date, results obtained from these models along with clinical feedback have suggested that these immune changes appear to be closely linked to a disruption of mucosal tolerance, resulting in the abnormal priming and dissemination of cells to sites such as the bone marrow and spleen where they are responsible for the synthesis of aberrantly glycosylated nephritogenic IgA. These findings suggest that future treatment strategies should focus on manipulating the priming and dissemination of these memory cells in order to prevent the appearance of nephritogenic IgA in the systemic compartment.
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  • New Approaches to Infertility Treatment Challenges
    ATSUSHI TANAKA
    2009 Volume 55 Issue 3 Pages 281-288
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.281
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    In vitro fertilization and embryo transfer (IVF-ET) has been applied to human fertility treatments for 30 years and its clinical usefulness has been established, its safety and availability have improved and steady success rates have been achieved. However, the pregnancy rate per cycle has not changed over the years and remains not more than 30%. In order to improve the success rate, certain problems must be addressed and resolved. These problems are (1) primary azoospermia, (2) aging oocytes, (3) habitual miscarriage and (4) X linked recessive inheritance. We have tried new approaches to resolve these problems through microfertilization using spermatids, in vitro culture of immature spermatogenic cells, oocyte donation, nuclear transfer, pre-implantation genetics diagnosis and X or Y sperm separation using infrared spectroscopy.
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  • A overview of Hemodialysis Therapy in our Insititution Between 1980 and 2008
    HIROTAKA NAKAMOTO, MICHIKO SATOH, YOSHIMI SEKIGUCHI, TOMOHITO GOUDA, H ...
    2009 Volume 55 Issue 3 Pages 289-293
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.289
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    In this paper, we estimated trends in 1262 end-stage kidney disease (ESKD) patients who started hemodialysis (HD) therapy at our institution between 1980 and 2008. The number of patients treated at our institution has been increasing and shows a tendency similar to the national average. The mean age of dialysis patients at the end of 1988 was 49.1 years, and that of dialysis patients at the end of 2008 was 67.7 years. With regard to underlying diseases in 1997, diabetic nephropathy (DMN) exceeded chronic glomerulonephritis (CGN) for the first time. Of patients who started dialysis in 2008, DMN was the underlying disease in about 40%. With regard to the main underlying diseases, the mean age of dialysis patients at our institution was less than the national average. DMN is the most frequent cause of ESKD. For a decrease in the number of HD patients, it is important to diagnose DMN in the early stage by detection of microalbuminuria levels, and establish early treatment of DMN by strict blood pressure and blood sugar management.
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  • Condition of Stroke Patients at Transfer to Care Facilities and Patients' Concerns Prior to Discharge
    SHINKO MINOTANI, MASAKO SUGIMOTO, RYUUKO FUKUSHIMA, YUUKI KOMATSU
    2009 Volume 55 Issue 3 Pages 294-302
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.294
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    Objective: To investigate patients transferred to care facilities following hospitalization for stroke focusing on patients' recognition of their own physical condition and their concerns prior to discharge in order to develop materials that provide adequate discharge support that respects, to the greatest extent possible, the feelings and preferences of patients. Subjects: Patients or families of patients admitted to elderly care facilities in the Tokyo Metropolitan Area within 3 months after discharge following hospitalization for stroke. Methods: An original questionnaire was used to conduct a survey directly among patients ; in cases where patients were unable to complete the survey, their family members responded. The survey, which retrospectively analyzed hospitalization and discharge of patients prior to their admission to care facilities, was conducted for approximately 5 months beginning in February 2007. Survey items included individual characteristics, duration of hospitalization, time between discharge and admission to care facilities, physical and mental conditions at discharge, concerns prior to discharge, willingness to prepare for discharge, problems anticipated prior to discharge, and implementation of preparations for life after discharge. Results: A total of 52 responses (19 men, 33 women) were obtained. Mean patient age was 78.2 years and the mean duration of hospitalization was 217 days. For 45 patients, there was no interval between discharge and admission to a care facility. The survey was completed by the patients themselves (n = 24), both the patient and the patient's family (n = 10), or completely by the patient's family (n = 18). Paralysis (n = 46) and depressive tendencies (n = 27) were observed among patients, and > 80 % of patients had discomfort or difficulty during bathing, standing, dressing, and other activities. A total of 25 patients had concerns prior to discharge, and these concerns were common among patients with depressive tendencies, those who were willing to prepare for discharge, and those who had anticipated problems, but there were no apparent differences in the implementation of preparations for life after discharge. Preparations for life after discharge were implemented significantly more often among patients whose family members responded on their behalf. Conclusion ; 1. The mean duration of hospitalization was high (105.3 days) for patients with cerebrovascular disease, and many of these patients were immediately transferred to care facilities following discharge. This suggests that the duration of hospitalization for these patients was longer because they were waiting for vacancies at care facilities. Patients were thought to have decided to enter care facilities in consideration of the concerns and problems they had anticipated prior to discharge. 2. For patients with depressive tendencies, care facilities may have been selected based on the wishes of individuals other than the patient without waiting for the patient to prepare for discharge. 3. Although patients who anticipated problems and were willing to prepare for discharge had more concerns prior to discharge, these characteristics were not related to implementation of discharge preparation. 4. As differences were observed in the implementation of preparations between patients and their families, measures targeting both are necessary.
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  • Choice of Supplementary Therapy in Elderly Asthmatic Patients Comparison Between a Leucotriene Receptor Antagonist (Zafirlukast) and an Inhaled Steroid (Fluticasone Propionate)
    OSAMU NAGASHIMA, RYO ATSUTA, NORIHIRO HARADA, FUMIHIKO MAKINO, JUN ITO ...
    2009 Volume 55 Issue 3 Pages 303-308
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.303
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    Objective: To compare increased dosage of an inhaled steroid to additional administration of a leucotriene receptor antagonist as therapy for elderly asthmatic patients. Patients and methods: The subjects were patients with moderate persistent asthma in whom airway hyperresponsiveness was progressing. All patients were given 400μg fluticasone propionate dry powder inhaler (FP-DPI). The patients were divided into an elderly group (aged ≥ 65 years) and a younger group (aged < 65 years), and were given either 40 mg zafirlukast, a leucotriene receptor antagonist (LTRA) (elderly group, n = 5 ; younger group, n = 11) or an extra dose of 400μg FP-DPI (elderly group, n = 5 ; younger group, n = 8) as supplementary treatment. The effectiveness of this supplementary treatment was serially investigated in terms of respiratory function, including airway hyperresponsiveness at the initial administration, after 4 weeks, and after 8 weeks. Results: In the elderly group, a significant improvement in airway hyperresponsiveness was seen only in the LTRA supplementary therapy group (after 8 weeks) (P = 0.04). In the younger group, significant improvement was observed in the FP-DPI group after 4 (P = 0.04) and 8 weeks (P = 0.04), while in the LTRA group significant improvement was also seen after 4 weeks (P = 0.01) and 8 weeks (P = 0.01). There was no improvement in forced expiration volume in 1 s (FEV1) in any of the groups, and there were no significant changes in total serum immunoglobulin E (IgE) levels or peripheral blood eosinophil count. Conclusion: In elderly asthmatic patients, significant improvement of airway hyperresponsiveness was seen with supplementary administration of LTRA rather than an increased dose of inhaled corticosteroids (ICS), suggesting that supplementary administration of LTRA may be more effective than increased ICS in these patients.
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  • Evaluation of a Cell-phone Mediated E-mail Reminder System for Drug Compliance
    YOSHIHISA SATOH, HIDEKO AIDA, YASUO SUMOMOZAWA, YU YUMOTO, SHOUZOU KOM ...
    2009 Volume 55 Issue 3 Pages 309-318
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.309
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    Recently, there has been a tendency to prescribe high-dose medication and the dose regimens have become increasingly complicated. For patients prescribed such high-dose medicines to be taken once weekly, it is difficult for patients to consistently take their medication on the same day each week because the interval is too long for the patient to remember their dosing regimen. In this study, a cell phone-based reminder system advising patients of the day and time they should take their medication was developed using the e-mail function, and the validity and usefulness of this system was evaluated. This e-mail reminder system functions as follows : The patient accesses the server computer using their individual cell phones via the Internet and sets up the day and time when they should take the once-weekly medication ; the system will then automatically send an e-mail reminder to the patients both the day before and on the day they are supposed to take the medication. In this study, we validated the system operation, the system registration process by patients, and the reliability of continuous operation. We also investigated whether patients recognized the incoming e-mail messages. There were no system failures during the entire process. Of sixteen subjects (hospital clerks), ten (62.5%) completed the registration procedure without any problem. In addition, of thirty-eight subjects (nurses), thirty-five (92.1%) received all e-mails for four weeks, and thirty-one (81.5%) confirmed that they received the e-mails within one hour of the time they set up on the system. Seventeen subjects (44.7%) did not look at the e-mail message after they received it, because they knew it was the e-mail reminder to take their medication. These findings showed that a periodic e-mail reminder service itself might contribute to patients becoming accustomed to taking medications on time because of the repeated reminder e-mails, and that a simplified registration procedure and a way to encourage patients to consistently read the message body would be required.
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  • A Case of “Flashback” in a Patient with Methamphetamine Dependence
    KOJI KASANUKI, HIDEHO SHIMADA, TOSHIHITO SUZUKI, HEII ARAI
    2009 Volume 55 Issue 3 Pages 347-350
    Published: September 30, 2009
    Released on J-STAGE: November 11, 2014
    DOIhttps://doi.org/10.14789/pjmj.55.347
    JOURNAL FREE ACCESS
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    In Japan, especially since 1995, there has been a rapid increase in users of methamphetamine (MAP), which has created a social problem. In the medical field, psychostimulant dependence is a serious problem. Therefore, we should properly understand various disorders that are derived from psychostimulant dependence. In this article, we report a case of “flashback” in a patient with psychostimulant dependence. Though the pathophysiology of this phenomenon has not yet been fully clarified, the mechanism of stimulant-induced behavioral sensitization seems to play a main role. Once this mechanism is built, patients easily lapse into a psychotic state in response to using a small amount of the substance. Furthermore, even without use of the specific substance, such patients show the same symptoms in response to mild psychosocial stressors or other substances such as alcohol.
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