National Hospital Organization Hokkaido Medical Center

Sapporo, Japan

National Hospital Organization Hokkaido Medical Center

Sapporo, Japan
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Tanaka S.,Saitama University | Yoshida A.,Yoshida Orthopedics Clinic | Kono S.,Saitama University | Ito M.,National Hospital Organization Hokkaido Medical Center
Journal of Orthopaedic Science | Year: 2017

Background Evidence related to the effectiveness of combination drug therapy for the treatment of osteoporosis is currently considered insufficient. Therefore, this study was performed to clarify the effects of monotherapy, and combination therapy, with a bisphosphonate (minodronic acid hydrate), a bone resorption inhibitor, and calcitonin (elcatonin), which is effective for the alleviation of pain due to vertebral fractures in osteoporotic patients. Methods Study participants comprised of 51 female subjects with post-menopausal osteoporosis, whose main complaint was acute lower back pain caused by vertebral fractures. Subjects were randomly allocated into three groups and then administered with either intramuscular injections of elcatonin at a dose of 20 units weekly, minodronic acid hydrate at a dose of 1 mg daily, or a combination of these two drugs. As primary endpoints, time-dependent changes in levels of pain were assessed using a visual analog scale from baseline to 6 months of duration. In addition, we examined the effects of monotherapies, and a combination therapy on bone resorption, with changes in bone mineral density at 4 sites and advanced hip assessment parameters from baseline to 6 months. A two-tailed significance level of 5% was used for hypothesis testing. Results Elcatonin monotherapy showed some alleviation of pain immediately after any vertebral fractures, which was more than in the minodronic acid hydrate monotherapy group. In addition, the minodronic acid hydrate monotherapy group experienced more effective inhibited bone resorption than the elcatonin monotherapy group. In the combination therapy, the efficacy for alleviating pain and inhibiting bone resorption was equivalent to the effect observed in the elcatonin and minodronic acid hydrate monotherapy groups respectively, with further improved values of bone mineral density observed in the femoral neck and lumbar vertebrae, and in parameters of advanced hip assessment compared with both monotherapy groups. Conclusions Combination therapy with elcatonin and minodronic acid hydrate appears to be an effective treatment for osteoporosis patients with lower back pain, caused by fresh vertebral fractures. © 2017 The Authors

PubMed | Shinshu University, National Hospital Organization Hokkaido Medical Center, Murdoch Childrens Research Institute, Osaka Medical Center and Research Institute for Maternal and Child Health and 4 more.
Type: Case Reports | Journal: Clinical genetics | Year: 2016

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.

PubMed | Fukuoka University, University of Massachusetts Medical School, Juntendo University, Kyoto Shijo Hospital and 15 more.
Type: Journal Article | Journal: Movement disorders clinical practice | Year: 2014

The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinsons Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results.In this trial, the MDS-UPDRS was translated into Japanese, underwent cognitive pre-testing, and the translation was modified after taking the results into account. The final translation was approved as Official Working Draft of the MDS-UPDRS Japanese version and tested in 365 native-Japanese-speaking patients with PD. Confirmatory analyses were used to determine whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Official Working Draft of the Japanese translation. As a secondary analysis, we used exploratory factor analyses to examine the underlying factor structure without the constraint of a pre-specified factor organization.Confirmatory factor analysis revealed that Comparative Fit Index for all Parts of the MDS-UPDRS exceeded the minimal standard of 0.90 relative to the English version and therefore Japanese translation met the pre-specified criterion to be designated called an OFFICIAL MDS TRANSLATION. Secondary analyses revealed some differences between the English-language MDS-UPDRS and the Japanese translation, however, these differences were considered to be within an acceptable range.The Japanese version of the MDS-UPDRS met the criterion as an Official MDS Translation and is now available for use (

PubMed | Sapporo Orthopaedic Hospital, Sapporo Orthopaedic and Cardiovascular Hospital, Saitama University, Yoshida Orthopedic Clinic and National Hospital Organization Hokkaido Medical Center
Type: | Journal: Journal of bone and mineral metabolism | Year: 2016

Elderly patients with osteoporotic vertebral fractures often experience severe pain that reduces their quality of life (QOL). Calcitonin, a bone resorption inhibitor, has been reported to alleviate pain in such patients; however, few clinical studies have demonstrated this effect. The objective of this study was to compare changes in pain scores, activities of daily living (ADL), QOL, bone resorption, bone mineral density (BMD), and fracture healing among patients with new vertebral fractures who received different treatment modalities. We conducted an open-label, multicenter, randomized, parallel control group study comprising 107 female patients 55years old with acute back pain from vertebral fracture. All subjects received either intramuscular injections of elcatonin, a derivative of calcitonin, or an oral nonsteroidal antiinflammatory drug (NSAID) combined with an active vitamin D

Nagao M.,National Hospital Organization Hokkaido Medical Center | Tanaka T.,National Hospital Organization Hokkaido Medical Center | Furujo M.,National Hospital Organization Okayama Medical Center
Molecular Genetics and Metabolism | Year: 2013

Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 and 2012 in Hokkaido, Japan, the estimated incidence of MAT I/III deficiency was 1 in 107,850. 24 patients (13 males, 11 females) from 11 prefectures in Japan were referred to our laboratory for genetic diagnosis of MAT I/III deficiency. They were all found between 1992 and 2012 by the NBS program in each region. In these 24 individuals, we identified 12 distinct mutations; 14 patients were heterozygous for an R264H mutation; R264H caused an autosomal dominant and clinically benign phenotype in each case. The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. Putative amino acid substitutions at R356 were observed with six alleles (three R356P, two R356Q, and one R356L). MAT I/III deficiency is not always benign because three of our cases involved brain demyelination or neurological complications. DNA testing early in life is recommended to prevent potential detrimental neurological manifestations. © 2013 Elsevier Inc.

Takeda H.,Hokkaido University | Nakagawa K.,Hokkaido University | Okubo N.,Hokkaido University | Nishimura M.,Hokkaido University | And 5 more authors.
Biological and Pharmaceutical Bulletin | Year: 2013

Anorexia is an important issue in the management of elderly patients with cancer because it contributes to the development of malnutrition, increases morbidity and mortality, and negatively affects patients' quality of life. This review summarizes the potential mechanisms of the development of anorexia in three animal models that mimic the situations commonly seen in elderly patients receiving chemotherapy. Cisplatin-induced anorexia is attributable to a decrease in peripheral and central ghrelin secretion caused by the stimulation of serotonin (5-hydroxytryptamine; 5-HT)2B and 5-HT2C receptors via 5-HT secretion. Age-associated anorexia is caused by an increase in plasma leptin, which results from disturbed reactivity of ghrelin in the hypothalamus and regulation of ghrelin secretion. Environmental change causes the activation of central 5-HT1B and 5-HT2C receptors and the melanocortin-4 receptor system, resulting in a decrease in circulating ghrelin levels which lowers food intake. New therapeutic approaches based on these pathophysiological mechanisms are warranted for the treatment of anorexia in cancer patients, especially elderly ones. © 2013 The Pharmaceutical Society of Japan.

PubMed | National Hospital Organization Hokkaido Medical Center and Hokkaido University
Type: Journal Article | Journal: The British journal of oral & maxillofacial surgery | Year: 2014

Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described.

PubMed | Kushiro Rosai Hospital, Teine Keijinkai Hospital, National Hospital Organization Hokkaido Medical Center and Hokkaido University
Type: | Journal: World neurosurgery | Year: 2016

There are no established treatment strategies for aneurysms that recur after clipping. In this study, we present cases of patients who experienced recurrent aneurysms after clipping and subsequently underwent surgical intervention.Between 2004 and 2015, we surgically treated 23 aneurysms that recurred at a previously clipped site. Patient characteristics and clinical history were retrospectively reviewed.Patients included 19 women and 4 men 45-81 years old. Aneurysms recurred 3-31 years (mean, 15.4 years) after the initial operation. For 18 cases, the first clinical presentation was a subarachnoid hemorrhage; aneurysms were incidentally diagnosed in 5 patients. Aneurysm locations were as follows: 9 on the internal carotid artery; 4 on the middle cerebral artery; 7 on the anterior communicating artery; 2 on the distal anterior cerebral artery; and 1 on the basilar artery. The reasons for retreatment included subarachnoid hemorrhage (n= 9) and aneurysm regrowth detected on follow-up examinations (n= 14). Endovascular treatment was performed in 10 cases, and direct surgery was performed in 13 cases (clipping in 8, clipping or trapping with bypass in 5). Various complex vascular reconstructions, including high-flow bypass and intracranial-intracranial in situ bypass, were performed for recurrent aneurysms.In our experience, coil embolization is a safe and effective procedure for treating recurrent aneurysms. When cases are unsuitable for coil embolization, surgical treatment often requires neurosurgeons not only to overcome the general technical difficulty of reoperative clipping but also to perform challenging vascular reconstruction.

PubMed | Shinshu University, Kobe City Medical Center General Hospital, National Hospital Organization Hokkaido Medical Center, Osaka University and 8 more.
Type: Journal Article | Journal: The Lancet. Neurology | Year: 2016

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare cause of demyelinating neuropathy, with multi-organ involvement characterised by plasma cell dyscrasia and VEGF overproduction. No treatments have been established for patients with POEMS syndrome who are not eligible for stem-cell transplantation. Thalidomide suppresses VEGF and plasma cell proliferation. We aimed to assess the safety and efficacy of thalidomide for the treatment of POEMS syndrome.We did a randomised, double-blind, placebo-controlled, phase 2/3 trial at 12 hospitals in Japan. Adults (age 20 years) with POEMS syndrome who were ineligible for autotransplantation were randomly assigned (1:1) by a minimisation method to treatment with oral dexamethasone (12 mg/m(2) per day on the first 4 days of every 28-day cycle) plus either oral thalidomide (200 mg daily) or placebo for six cycles. All study personnel and patients were masked to treatment allocation. The primary endpoint was the reduction rate of serum VEGF concentrations at 24 weeks. Analysis was by intention to treat. This study is registered with the UMIN Clinical Trials Registry, UMIN000004179.Between Nov 11, 2010, and July 3, 2014, we randomly assigned 25 patients to receive either thalidomide (n=13) or placebo (n=12); one patient in the placebo group was excluded from analyses because of a protocol violation. The adjusted mean VEGF concentration reduction rate at 24 weeks was 039 (SD 034) in the thalidomide group compared with -002 (054) in the placebo group (adjusted mean difference 041, 95% CI 002-080; p=004). Mild sinus bradycardia was more frequent in the thalidomide group than in the placebo group (seven [54%] vs zero; p=0006). Five patients had serious adverse events: three in the thalidomide group (transient cardiac arrest, heart failure, and dehydration) and two in the placebo group (ileus and fever). No deaths occurred during the randomised study. In the 48-week open-label study period (n=22), newly developed adverse events were sinus bradycardia (n=4), constipation (n=5), and mild sensory neuropathy (n=5). Two patients died in the open-label study; both patients were initially in the placebo group, and the cause of death was progression of the disease.Thalidomide reduces serum VEGF concentrations and represents a new treatment for patients with POEMS syndrome who are not eligible for stem-cell transplantation. Thalidomide treatment poses a risk of bradycardia; however, the benefits are likely to exceed the risk.Japanese Ministry of Health, Labour, and Welfare, and Fujimoto Pharmaceuticals.

PubMed | Teine Keijinkai Hospital, Sapporo Medical University, Sapporo City General Hospital, National hospital organization Hokkaido Medical Center and Hokkaido University
Type: Journal Article | Journal: Journal of intensive care | Year: 2015

Epinephrine administration has been advocated for cardiopulmonary resuscitation (CPR) for decades. Despite the fact that epinephrine administration during CPR is internationally accepted, the effects of the prehospital epinephrine administration still remain controversial. We investigated the effects of epinephrine administration on patients with out-of-hospital cardiac arrest based on a propensity analysis with regard to the CPR time.From April 1, 2007, to December 31, 2009, 633 out-of-hospital cardiac arrest patients with bystander witnesses were included in the present study. To rule out any survival bias, we used the propensity scores, which included CPR time. CPR time was defined as the time span from when the emergency medical technicians started CPR until either the return of spontaneous circulation or arrival at the hospital. After performing propensity score matching, the epinephrine and no-drug groups each included 141 patients. The primary study endpoint was a favorable neurological outcome at 30days after cardiac arrest.After propensity score matching, the frequency of the return of spontaneous circulation before arrival at the hospital in the matched epinephrine group was higher than that in the matched no-drug group (27% vs. 13%, P=0.002). However, the frequency of a favorable neurological state did not differ between the two groups. With regard to the frequency of a favorable neurological state in the patients, the adjusted odds ratio of the time span from cardiac arrest to the first epinephrine administration was 0.917 (95% confidence interval 0.850-0.988, P=0.023) per minute.In patients with witnessed out-of-hospital cardiac arrest, prehospital epinephrine administration was associated with increase of the return of spontaneous circulation before arrival at the hospital. Moreover, the early administration of epinephrine might improve the overall neurological outcome.

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