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Methicillin-resistant Staphylococcus aureus USA300, belonging to sequence type (ST) 8, is a rare cause of necrotizing fasciitis in the USA. We herein report a case of monomicrobial Fournier's gangrene caused by an ST8, methicillin-susceptible Staphylococcus aureus (designated ksw1). Whole-genome sequencing and analyses for virulence determinants revealed that, unlike USA300, ksw1 lacked virulence genes, such as Panton-Valentine leukocidin and SCCmec, while harboring the toxic shock syndrome toxin-1 gene. These genomic features correlate with ST8 CA-MRSA/J, which is the major genotype of ST8 in Japan.
Assuntos
Toxinas Bacterianas/efeitos adversos , Enterotoxinas/efeitos adversos , Gangrena de Fournier/etiologia , Gangrena de Fournier/microbiologia , Leucocidinas/efeitos adversos , Meticilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/genética , Superantígenos/efeitos adversos , Idoso , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/epidemiologia , Genótipo , Humanos , Japão/epidemiologia , Masculino , Fatores de Virulência/genéticaRESUMO
Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by -2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by -1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Administração Oral , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Quimioterapia Combinada , Glucosídeos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Japão/epidemiologia , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The global pandemic of type 2 diabetes mellitus (T2DM) is an enormous clinical and socioeconomic burden. Biguanides and DPP-4 inhibitors (DPP-4i) are the most commonly used therapies in Japanese T2DM patients. When glycemic control is not adequate despite combination of these drugs, there is no consensus on the next step drug. Systematic reviews and meta-analyses of previous trials have indicated that glycemic control with triple combination therapies yields similar results. Thus, beneficial effects on cardiovascular risk factors may be important. The present study was designed to evaluate body fat percentage and several insulin resistance parameters after addition of tofogliflozin or glimepiride to the regimens of patients being treated with metformin and a DPP-4 inhibitor but failing to attain adequate blood glucose control. METHODS: Sodium glucose cotransporter-2 inhibitor, tofogliflozin versus glimepiride, comparative trial in patients with type 2 diabetes on body composition is an ongoing, multicenter, prospective, randomized, open-label, parallel-group trial. T2DM patients treated with metformin/DPP-4 inhibitor dual therapy have been recruited and randomly assigned to 20 mg/day tofogliflozin (n = 32) or 0.5 mg/day glimepiride (n = 32) groups, with either of these drugs being added to pre-existing regimens for 24 weeks. PLANNED OUTCOMES: The primary endpoint is the change in body fat percentage from baseline to 24 weeks. The secondary outcomes are changes in body composition other than fat percentage, body weight, parameters related to glycemic control and ß-cell function, parameters related to lipids and arteriosclerosis, parameters related to liver function, parameters related to diabetic nephropathy, and uric acid levels. Safety parameters will also be analyzed. This is the first trial comparing the effects and safety of adding an SGLT2i and a sulfonylurea as the third-line oral agent to metformin/DPP-4i dual therapy. The results will provide valuable information for choosing third-line oral agents. TRIAL REGISTRATION: UMIN000026161. FUNDING: Kowa Co. Ltd. and Kowa Pharmaceutical Co. Ltd., Tokyo, Japan.
RESUMO
A 66-year-old woman, who was diagnosed with iritis, visited our hospital due to general malaise. A blood analysis revealed hypercalcemia. Computed tomography revealed mediastinal and hilar lymph node hyperplasia. Moreover, 67Gallium scintigraphy demonstrated strong accumulation in the lesions, suggesting sarcoidosis. A core needle biopsy (CNB) of the hypoechoic areas of the thyroid was performed because the patient refused to undergo a bronchoscopic examination. The scattering of slightly acidophilic epithelioid cell granulomas was observed in the pathological examination of the biopsy specimen. Based on this finding, the patient was diagnosed with sarcoidosis. Although sarcoidosis rarely involves the thyroid gland, in the present case, thyroid CNB was an alternative diagnostic method that allowed a pathological diagnosis to be obtained.
Assuntos
Sarcoidose/diagnóstico por imagem , Doenças da Glândula Tireoide/diagnóstico por imagem , Idoso , Biópsia por Agulha , Feminino , Granuloma/patologia , Humanos , Pulmão , Linfadenopatia/diagnóstico por imagem , Mediastino , Radiografia , Cintilografia , Sarcoidose/patologia , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/patologia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
BACKGROUND: There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks. METHODS: Lipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol) and sd-LDL-C, two characteristic atherogenic risks of DM. RESULTS: The reduction of LDL-C (%), the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST). In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and RLP-C (-19.7 vs. +5.5). In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3) and non-HDL-C (-20.7 vs. -8.3) differed significantly between the two groups. CONCLUSION: Ezetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin) was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin) treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response. TRIAL REGISTRATION: The UMIN Clinical Trials Registry UMIN000002593.
Assuntos
Anticolesterolemiantes/farmacologia , LDL-Colesterol/antagonistas & inibidores , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
AIMS/INTRODUCTION: α-Glucosidase inhibitors (αGIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three αGIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes. MATERIALS AND METHODS: Japanese patients (n = 81) with obese type 2 diabetes (body mass index [BMI] ≥25 kg/m(2)) were enrolled in this multicenter, open-label study. The participants were randomized into the miglitol (n = 18), acarbose (n = 22), voglibose (n = 19) or control (n = 22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low-density lipoprotein and high-density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4 weeks for 12 weeks. RESULTS: In the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12 weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12 weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12 weeks in the miglitol (r = 0.759, P < 0.001) and voglibose groups (r = 0.667, P = 0.002). Serum lipid and adipocytokine levels were not altered in any groups. CONCLUSIONS: αGIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type 2 diabetes. This study was registered with UMIN (no. UMIN000006465).
RESUMO
AIMS: Hypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses. No second-step strategy is established, however, for cases where strong statins fail to bring cholesterol down to target levels. In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia. METHODS: T2DM outpatients (109 patients from 16 institutes) who failed to achieve the target LDL-C value were recruited and randomly assigned to two groups, a double-dose-statin group and ezetimibe-plus-statin group. Follow-ups were scheduled at 0, 12, 26, and 52 weeks. The primary endpoint was the percentage change in the level of LDL-C from baseline to 12 weeks. INTERIM RESULTS: We could successfully create randomized (gender, age, LDL-C, HbA1c, etc.) two groups except for slight differences in apolipoprotein-B and sd-LDL. CONCLUSIONS: RESEARCH is the first prospective, parallel-group, multicenter study comparing a double dose of strong statin with ezetimibe plus strong statin for T2DM patients. The RESEARCH study will provide reliable evidence with which to establish a clinical strategy for diabetics who fail to achieve the target LDL-C value.
Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Sinvastatina/uso terapêutico , Fatores Etários , Idoso , Apolipoproteínas B/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Esquema de Medicação , Quimioterapia Combinada , Ezetimiba , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
OBJECTIVE: We assessed the feasibility and efficacy of dendritic cell (DC) therapy for advanced thyroid papillary and follicular cancer. DESIGN: Six Japanese patients (2 men and 4 women; aged 46-72 years, mean 60 years), who were diagnosed as advanced thyroid cancer with refractory distant metastases (papillary, n=5; follicular, n=1), were enrolled. Patients were first vaccinated weekly for 4 weeks with 10(7) autologous tumor lysate-pulsed monocyte-derived mature DCs followed by fortnightly vaccinations for 8 weeks (total=8 vaccinations). Lowdose (350 KIU) interleukin-2 was also administered for 3 days at each vaccination. Clinical response, adverse effects, delayed-type hypersensitivity skin testing (DTH), and IFN-( ) production by peripheral CD3(+) lymphocytes were evaluated. MAIN OUTCOME: Of the 6 patients, disease was assessed as stable in 2 and as progressive in 4. No adverse events were observed. Results of DTH and IFN-( ) production in peripheral lymphocytes did not correlate to the clinical response. CONCLUSIONS: DC immunotherapy could be administered to patients with thyroid papillary or follicular cancer without substantial side effects.
Assuntos
Vacinas Anticâncer/administração & dosagem , Carcinoma Papilar, Variante Folicular/terapia , Células Dendríticas/transplante , Neoplasias Pulmonares/terapia , Neoplasias da Glândula Tireoide/terapia , Idoso , Vacinas Anticâncer/efeitos adversos , Carcinoma Papilar, Variante Folicular/imunologia , Carcinoma Papilar, Variante Folicular/secundário , Células Cultivadas , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
In this study we confirmed our previous findings on the importance of IgE in Graves' disease and further investigated the relationships existing among Graves' disease, IgE, and interleukin-4. Two hundred and thirty-two newly diagnosed Graves' disease patients were treated with methimazole for 2 years, and were classified into 3 groups according to their response to the therapy. Incidence of IgE elevation (IgE> or =170 IU/ml) before treatment was lowest, 23.8%, in the group who achieved remission without recurrence, while it was 41.7% in the group who achieved remission but recurrence occurred within 4 years. Incidence of IgE elevation before treatment was highest, 60.7%, in the group who failed to achieve remission, significantly higher than that of the group without recurrence. Incidence of IgE elevation before treatment in all these patients of Graves' disease were 35.3%, significantly higher than those of Hashimoto's thyroiditis (17.5%) and of simple goiter (7.0%). Serum IL-4 levels before treatment were significantly higher in the patients of Graves' disease with IgE elevation than in those without IgE elevation. Serum T4 concentration and TSAb titration before treatment were also significantly higher in elevated IgE group than in normal IgE group. These results support our previous findings and suggest that IL-4 may play important roles in the elevation of IgE, TBII, and TSAb in patients of Graves' disease, and that IL-4 and IgE may be involved in the development, progression, and maintenance of Graves' disease.
Assuntos
Autoanticorpos/sangue , Doença de Graves/sangue , Doença de Graves/tratamento farmacológico , Imunoglobulina E/sangue , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Interleucina-4/sangue , Metimazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/fisiopatologia , Humanos , Masculino , Metimazol/administração & dosagem , Pessoa de Meia-Idade , Testes de Função Tireóidea , Glândula Tireoide/fisiopatologia , Fatores de TempoRESUMO
Recently several strategies to treat ischemic diseases have been proposed but the ideal way has to be determined. We explored whether human placenta-derived mesenchymal cells (hPDMCs) can be used for this purpose because placenta is very rich in vessels. First, production of human vascular endothelial growth factor (hVEGF) from hPDMCs was examined. The amount of hVEGF secreted by hPDMCs was similar to the amount produced by HeLa cells. hVEGF was barely detected in human umbilical vein endothelial cells (hUVECs) or human peripheral blood mononuclear cells. hVEGF secreted from hPDMCs stimulated the proliferation of hUVECs, indicating its biological activity. Transplantation of hPDMCs to the ischemic limbs of NOD/Shi-scid mice significantly improved the blood flow of the affected limbs. Blood vessel formation was more prominently observed in the limbs of treated mice as compared to the control mice. Real-time RT-PCR revealed that hPDMCs produced hVEGF for at least 7 days after transplantation. Thus, transplantation of hPDMCs could potentially be a promising treatment for human ischemic diseases.
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Isquemia/terapia , Mesoderma/metabolismo , Neovascularização Fisiológica , Placenta/citologia , Animais , Vasos Sanguíneos/citologia , Vasos Sanguíneos/crescimento & desenvolvimento , Transplante de Células , Células Cultivadas , Feminino , Células HeLa , Membro Posterior/irrigação sanguínea , Membro Posterior/metabolismo , Membro Posterior/patologia , Humanos , Mesoderma/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Gravidez , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
We conducted a pilot study to assess the feasibility and efficacy of immunotherapy for stage IV malignant melanoma patients resistant to conventional therapies involving vaccination with mature dendritic cells (mDCs) combined with administration of low dose interleukin-2. Autologous monocytes were harvested from a single apheresis and cultured for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4, yielding immature dendritic cells (iDCs), which were then cryopreserved until use. For 4 days prior to vaccination, iDCs were exposed to autologous tumour lysate combined with tumour necrosis factor-alpha to induce terminal differentiation into mDCs. Patients were then vaccinated weekly with 107 mDCs for 10 weeks and given 350-700 kIU of interleukin-2 three times per week. Of the 10 patients in the study, one showed stable disease, seven showed progressive disease, and two showed mixed responses, including partial tumour regression, and were therefore given 20 additional injections. Only minimal adverse events were noted, including localized skin reactions and mild fever (NIH-CTC grade 0-1). Median survival from the first vaccination was 240 days (range 31-735 days). In vitro, melanoma patient-derived dendritic cells (DCs) showed reduced cell surface expression of CD1a antigen on iDCs and reduced CD86 and HLA-DR expression on mDCs. In addition, antigen uptake, chemotaxis and antigen presentation were all attenuated in DCs from the patients. In summary, although improvement of clinical efficacy will require further research, autologous tumour lysate-pulsed monocyte-derived mDCs could be safely harvested, cryopreserved and administrated to patients without obvious complications.