ABSTRACT
With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.
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OBJECTIVES: Acceptable limb salvage rates underlie the widespread use of endovascular therapy (EVT) for patients with critical limb ischemia (CLI) secondary to isolated infrapopliteal lesions; however, post-EVT delayed wound healing remains a challenge. Predictors of delayed wound healing and their use in risk stratification of EVT in patients with CLI due to isolated infrapopliteal lesions are explored. METHODS: This was a retrospective multicenter study. 871 consecutive critically ischemic limbs were studied. There was tissue loss in 734 patients (age: 71 ± 10 years old; 71% male) who had undergone EVT between April 2004 and December 2012. The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between baseline characteristics and delayed wound healing was assessed by the Cox proportional hazard model. RESULTS: Diabetes mellitus and regular dialysis were present in 75% (553/734) and 64% (476/734) of patients, respectively; 67% of limbs (585/871) had Rutherford class 5 CLI; 8% (67/871) of wounds were located in the heel only; 25% (219/871) of limbs had Rutherford 6 (involving not only the heel); and 42% (354/871) of wounds were complicated by infection. The rate of freedom from major amputation at 1 year reached 88%, whereas the wound healing rate was 67%. Median time to wound healing was 146 days. By multivariate analysis, non-ambulatory status (hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.31-1.91) serum albumin <3 g/dL (HR 1.42; 95% CI 1.08-1.86), Rutherford 6 (not only heel) (HR 1.68; 95% CI 1.33-2.14), wound infection (HR 1.24; 95% CI 1.03-1.50), EVT not based on angiosome concept (HR 1.28; 95% CI 1.06-1.55), and below the ankle (BTA) 0 vessel runoff after EVT (HR 1.45; 95% CI 1.14-1.86) were independent predictors of delayed wound healing. CONCLUSIONS: Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows estimation of the wound healing rate.
Subject(s)
Diabetes Mellitus/epidemiology , Ischemia/epidemiology , Limb Salvage , Lower Extremity/surgery , Renal Dialysis/statistics & numerical data , Wound Healing , Adult , Aged , Aged, 80 and over , Female , Humans , Ischemia/surgery , Limb Salvage/methods , Lower Extremity/blood supply , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Treatment Outcome , Wound Healing/physiologyABSTRACT
OBJECTIVES: To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. MATERIALS AND METHODS: This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. RESULTS: Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. CONCLUSIONS: Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.
Subject(s)
Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/instrumentation , Aortic Diseases/therapy , Iliac Artery , Ischemia/therapy , Peripheral Arterial Disease/therapy , Stents , Adult , Age Factors , Aged , Aged, 80 and over , Aortic Diseases/diagnosis , Constriction, Pathologic , Critical Illness , Female , Humans , Iliac Artery/diagnostic imaging , Ischemia/diagnosis , Japan , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Peripheral Arterial Disease/diagnosis , Proportional Hazards Models , Radiography , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: To investigate factors in patients with critical limb ischemia (CLI) and isolated infrapopliteal lesions that adversely affect outcomes of endovascular therapy (EVT) with or without angiosome-oriented revascularization. METHODS: This was a retrospective multicenter study. We used a database of 718 consecutive CLI patients (70 ± 11 years, 75% diabetics, 68% on hemodialysis, 24% Rutherford class 6) with ischemic tissue loss due to isolated infrapopliteal lesions undergoing primary EVT. Primary outcome was MALE (major adverse limb event). Association between indirect EVT (recanalization of a non-angiosome-based artery) and outcome was assessed by Cox proportional hazard regression model. RESULTS: C-reactive protein (CRP) level was >3 mg/dL in 32% of cases. Indirect EVT (in 307 CLI patients, 43%), was associated with MALE (p = .04, hazard ratio [95% confidence interval] 1.25 [1.01, 1.55]), and interacted with CRP >3 mg/dL (p < .004) but not with other baseline characteristics. Indirect EVT with CRP >3 mg/dL had higher MALE risk (HR 2.08), and interacted with diabetes mellitus (DM) presence. Indirect EVT with CRP >3 mg/dL and DM had higher MALE risk (HR 2.17). CONCLUSION: Limb prognosis was equivalent for direct and indirect endovascular revascularization except in the presence of both diabetes and wound infection, when indirect revascularization has a poorer outcome.
Subject(s)
Diabetic Angiopathies/surgery , Endovascular Procedures/adverse effects , Ischemia/surgery , Wound Infection/epidemiology , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , Critical Illness , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/epidemiology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/therapy , Female , Humans , Ischemia/blood , Ischemia/diagnosis , Ischemia/epidemiology , Japan/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Prevalence , Proportional Hazards Models , Renal Dialysis , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Wound Infection/blood , Wound Infection/diagnosisABSTRACT
We demonstrate a high-sensitive transient absorption technique for detection of excited states in an organic thin film by time-resolved optical waveguide spectroscopy. By using a laser beam as a probe light, we detect small change in the transient absorbance which is equivalent to 10-7 absorbance unit in a conventional method. This technique was applied to organic thin films of blue phosphorescent materials for organic light emitting diodes. We directly observed the back energy transfer from emitting guest molecules to conductive host molecules.
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The unbound excited states of the neutron drip-line isotope 24O have been investigated via the 24O(p,p')23O + n reaction in inverse kinematics at a beam energy of 62 MeV/nucleon. The decay energy spectrum of 24O* was reconstructed from the momenta of 23O and the neutron. The spin parity of the first excited state, observed at E(x) = 4.65±0.14 MeV, was determined to be J(π) = 2+ from the angular distribution of the cross section. Higher-lying states were also observed. The quadrupole transition parameter ß2 of the 2(1)+ state was deduced, for the first time, to be 0.15±0.04. The relatively high excitation energy and small ß2 value are indicative of the N = 16 shell closure in 24O.
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OBJECTIVE: To assess 3- and 12-month angiographic restenosis rates and their clinical impact after infrapopliteal angioplasty. DESIGN: Prospective multicenter study. MATERIALS AND METHODS: We analyzed 68 critical ischemic limbs (tissue loss: 58 limbs) from 63 consecutive patients due to isolated infrapopliteal lesions who underwent angioplasty alone. Primary endpoint was 3-month angiographic restenosis rate; secondary endpoints were 12-month angiographic restenosis rate, and 3- and 12-month rates of mortality, major amputation and reintervention. Three- and 12-month frequency of ambulatory status and of freedom from ischemic symptoms, and time to wound healing in the ischemic wound group, were compared between restenotic and non-restenotic groups. Angiographic restenosis predictors were assessed by multivariable analysis. RESULTS: 95% of cases had 3-month angiography; restenosis rate was 73%: 40% restenosis and 33% re-occlusion. Twelve-month follow-up angiography was conducted for the patients without 3-month angiographic restenosis, and restenosis rate at 12 months was 82%. Non-administration of cilostazol and statin, and chronic total occlusion were 3-month angiographic restenosis predictors. Three- and 12-month mortality was 5% and 12%, respectively. Despite no patients having undergone amputation, 15% had persistent ischemic symptoms, and 48% of limbs underwent reintervention within 12 months. During the same study period, ambulatory status and limbs with complete healing were more frequently observed in the non-restenosis group than in the restenosis group. In the tissue loss group, time to wound healing in the restenosis group was longer than in the non-restenosis group (127 days vs. 66 days, p = 0.02). CONCLUSION: The extremely high angiographic restenosis rate after infrapopliteal angioplasty may adversely impact clinical status improvement.
Subject(s)
Angiography , Angioplasty/methods , Graft Occlusion, Vascular/diagnostic imaging , Popliteal Artery/surgery , Aged , Amputation, Surgical/statistics & numerical data , Female , Follow-Up Studies , Graft Occlusion, Vascular/epidemiology , Graft Occlusion, Vascular/surgery , Humans , Incidence , Ischemia/diagnostic imaging , Ischemia/surgery , Japan/epidemiology , Leg/blood supply , Male , Popliteal Artery/diagnostic imaging , Prognosis , Prospective Studies , Prosthesis Failure , Reoperation/statistics & numerical data , Survival Rate , Time FactorsABSTRACT
OBJECTIVE: To identify anatomical factors associated with major adverse limb events (MALE) after angioplasty as the basis for a novel morphology-driven classification of infrapopliteal lesions. DESIGN: Retrospective-multicenter study. MATERIALS AND METHODS: Between March 2004 and October 2010, 1057 limbs from 884 patients with CLI due to isolated infrapopliteal lesions were studied. Freedom-from MALE, defined as major amputation or any reintervention, was assessed out to 2 years by the Kaplan-Meier methods. Anatomical predictors and risk stratification for MALE were analyzed by multivariate analysis. RESULTS: Freedom-from MALE was 47 ± 1% at 2 years. Lesion calcification, target vessel diameter<3.0 mm, lesion length>300 mm and no below-the-ankle (BA) run-off were positively associated with MALE by multivariate-analysis. The total number of risk factors was used to calculate the risk score for each limbs for subsequent categorization into 3 groups with 0 or 1 (low-risk), 2 (moderate-risk) and 3 or 4 (high-risk) factors. Freedom-from MALE at 2 year-rates was 59% in low-risk, 46% in moderate-risk, and 29% in high-risk, respectively. CONCLUSION: Target vessel diameter <3.0 mm, lesion calcification, lesion length > 300 mm and no-BA run-off were associated with MALE after infrapopliteal angioplasty. Risk stratification based on these predictors allows estimation of future incidence of MALE in CLI with isolated infrapopliteal lesions.
Subject(s)
Angioplasty, Balloon/adverse effects , Arterial Occlusive Diseases/therapy , Ischemia/therapy , Popliteal Artery , Vascular Calcification/therapy , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Ankle Brachial Index , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/physiopathology , Chi-Square Distribution , Constriction, Pathologic , Critical Illness , Female , Hemodynamics , Humans , Ischemia/diagnosis , Ischemia/etiology , Ischemia/physiopathology , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Popliteal Artery/diagnostic imaging , Popliteal Artery/physiopathology , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Ultrasonography, Doppler, Duplex , Vascular Calcification/complications , Vascular Calcification/diagnosis , Vascular Calcification/physiopathologyABSTRACT
The cerebellar uvula (lobule IX), a part of the vestibulocerebellum, is extensively connected to the areas of the brainstem that participate in cardiovascular regulation and vestibular signal processing. This suggests that the uvula regulates blood pressure (BP) during postural alterations. Previous studies showed that lesions of the uvula affected the baroreceptor reflex and cardiovascular responses during postural alterations. To investigate the mechanisms underlying this BP regulation, it is necessary to have a method to selectively modulate the activity of Purkinje cells (PCs), the sole output neurons from the cerebellar cortex, without affecting other neuronal types such as local interneurons or nonlocal neurons that send their axons to the cerebellar cortex. We recently developed a novel technique using optogenetics to manipulate PC activity and showed that activation and inhibition of PCs in the uvula either decreased or increased the resting BP, respectively. This technique was employed in the current study to examine the roles of the uvula in BP regulation during postural alterations in anesthetized rats. Enhanced Natronomonas pharaonis halorhodopsin (eNpHR), a light-driven chloride ion pump, was selectively expressed in uvular PCs using a lentiviral vector containing the PC-specific L7 promoter. The eNpHR-expressing PCs were then illuminated by orange laser (593 nm) either during 30° head-up or 30° head-down tilts. The eNpHR-mediated photoinhibition of the uvula attenuated the extent of BP recovery after a BP increase induced by postural changes during head-down tilts. By contrast, photoinhibition had no statistically significant effect on BP recovery during head-up tilts. The effects of photoinhibition on BP during tilts were significantly different from those observed during the resting condition, indicating that cerebellar control of BP during tilts is dynamic rather than static. Taken together, these results suggest that PCs in the uvula dynamically regulates BP maintenance during postural alterations.
Subject(s)
Blood Pressure/physiology , Genetic Techniques , Posture/physiology , Purkinje Cells/physiology , Animals , Halorhodopsins/genetics , Halorhodopsins/metabolism , Male , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , TransfectionABSTRACT
OBJECTIVES: To assess and risk stratify midterm clinical outcomes after endovascular therapy (EVT) by angioplasty only of patients with critical limb ischaemia (CLI) due to isolated below-the-knee (BTK) lesions. DESIGN: Retrospective multicenter study. MATERIALS AND METHODS: Between March 2004 and October 2010, 465 limbs (Rutherford 5 and 6: 79%) from 406 patients were studied. Overall survival, limb salvage, and re-intervention were examined out to 3 years by the Kaplan-Meier method and the log-rank test. Their independent predictors and risk stratification were analysed. RESULTS: Patient age was 71 ± 11 yrs, with 69% diabetics and 60% on dialysis. Mean follow-up was 18 ± 15 months. Overall survival was 76 ± 2 and 57 ± 4% at 1 and 3, years, respectively. Survival predictors were body mass index <18, non-ambulatory status and ejection fraction <45%. Two-year limb salvage rate was 80 ± 2%. Factors associated with major amputation were ulcers (Rutherford 6), diabetes mellitus, C-reactive protein>5 mg/dL, and age < 60 years. Two-year freedom from re-intervention was 66 ± 3%; age and below-the-ankle runoff number after angioplasty was negatively associated with re-intervention. CONCLUSIONS: Despite relatively high mortality and re-intervention rates, limb salvage rate was acceptable after EVT for CLI patients with isolated BTK lesions. Risk stratification allows occurrence estimation for each end point.
Subject(s)
Angioplasty, Balloon , Ischemia/surgery , Leg/blood supply , Leg/surgery , Limb Salvage/methods , Limb Salvage/statistics & numerical data , Aged , Amputation, Surgical , Cardiovascular Diseases/epidemiology , Cause of Death , Comorbidity , Diabetes Mellitus/epidemiology , Dyslipidemias/epidemiology , Female , Follow-Up Studies , Humans , Hypertension/epidemiology , Ischemia/mortality , Kidney Failure, Chronic/epidemiology , Male , Middle Aged , Reoperation , Retrospective Studies , Risk Factors , Smoking/epidemiology , Survival Rate , Treatment OutcomeABSTRACT
The low-lying states in ¹°6Zr and ¹°8Zr have been investigated by means of ß-γ and isomer spectroscopy at the radioactive isotope beam factory (RIBF), respectively. A new isomer with a half-life of 620 ± 150 ns has been identified in ¹°8Zr. For the sequence of even-even Zr isotopes, the excitation energies of the first 2⺠states reach a minimum at N = 64 and gradually increase as the neutron number increases up to N = 68, suggesting a deformed subshell closure at N = 64. The deformed ground state of ¹°8Zr indicates that a spherical subshell gap predicted at N = 70 is not large enough to change the ground state of ¹°8Zr to the spherical shape. The possibility of a tetrahedral shape isomer in ¹°8Zr is also discussed.
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The ß-decay half-lives of 38 neutron-rich isotopes from (36)Kr to (43)Tc have been measured; the half-lives of (100)Kr, (103-105)Sr, (106-108)Y, (108-110)Zr, (111,112)Nb, (112-115)Mo, and (116,117)Tc are reported here. The results when compared with previous standard models indicate an overestimation in the predicted half-lives by a factor of 2 or more in the A≈110 region. A revised model based on the second generation gross theory of ß decay better predicts the measured half-lives and suggests a more rapid flow of the rapid neutron-capture process (r-matter flow) through this region than previously predicted.
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AIMS: Glimepiride, a third generation sulfonylurea (SU), is known to have extrapancreatic effects, but its vascular effect is unclear. We investigated the efficacy of glimepiride in improving arterial stiffness assessed by cardio-ankle vascular index (CAVI) in type 2 diabetic patients, compared with glibenclamide, a conventional SU. METHODS: Forty type 2 diabetic patients were randomly assigned to two groups. One group was administered glimepiride 1.5 mg/day, and the other group was administered glibenclamide 1.25 mg/day for 6 months. RESULTS: No significant difference in hypoglycaemic effect was observed between two groups. CAVI significantly decreased only in glimepiride group (9.4 ± 1.4â8.9 ± 0.8, p < 0.05). Decrease in CAVI was greater in glimepiride group than in glibenclamide group (-0.50 ± 0.98 vs. -0.04 ± 0.57, p = 0.048). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased in glimepiride group and increased in glibenclamide group, and the changes were significantly different between groups (-1.5 ± 3.5 vs. + 1.8 ± 3.6, p = 0.009); whereas serum lipoprotein lipase mass increased in glibenclamide group and decreased in glibenclamide group, and the changes tended to be different between groups (+ 2.1 ± 19.1 vs. -7.4 ± 19.2, p = 0.096). Change in urinary 8-OHdG was a significant independent predictor for change in CAVI in all subjects. CONCLUSIONS: These results suggest that glimepiride improves CAVI compared with glibenclamide. Reduced oxidative stress and improved insulin resistance may contribute to the improvement of CAVI by glimerpiride.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Angiopathies/drug therapy , Glyburide/therapeutic use , Hypoglycemic Agents/therapeutic use , Sulfonylurea Compounds/therapeutic use , Vascular Stiffness/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Aged , Ankle/blood supply , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/physiopathology , Female , Glycated Hemoglobin/metabolism , Humans , Lipids/blood , Male , Middle Aged , Vascular Resistance/drug effectsSubject(s)
Graft vs Host Disease/complications , Inferior Wall Myocardial Infarction/etiology , Adolescent , Anemia, Aplastic/complications , Angioplasty , Bone Marrow Transplantation/adverse effects , Female , Graft vs Host Disease/drug therapy , Humans , Inferior Wall Myocardial Infarction/therapy , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/therapy , Stents , Treatment OutcomeABSTRACT
BACKGROUND: Recent studies have shown that thiazolidinediones reduce neointimal hyperplasia after bare metal stent (BMS) implantation, but this drug group sometimes cause fluid retention that may lead to heart failure. OBJECTIVES: To examine the safety and efficacy of pioglitazone in patients with ST elevation myocardial infarction (STEMI) treated with primary BMS implantation. METHODS: Diabetic or non-diabetic patients with STEMI (<12 h from onset) successfully treated with primary BMS implantation were randomised to either the pioglitazone (15 mg, up to 30 mg) or control groups. Patients in cardiogenic shock were excluded. Primary efficacy end point was percentage neointimal volume within the stented segment at 6 months using three-dimensional intravascular ultrasound. Safety end point was a composite of all-cause mortality, reinfarction, or heart failure requiring hospitalisation. RESULTS: Between October 2005 and July 2007, 96 patients were randomised into the pioglitazone (n = 48) or control group (n = 48). At follow-up, mean (SD) percentage neointimal volume and neointimal volume index were significantly reduced in the pioglitazone group (22 (13)% vs 28 (13)%, p = 0.04; 1.5 (0.9) vs 2.0 (0.8) mm(3)/mm, p = 0.02, respectively). During 6 months, two control patients died, four patients (one in the pioglitazone group, three controls) had stent thrombosis resulting in reinfarction and three patients (two in the pioglitazone group, one control) had heart failure, resulting in a similar incidence of safety end point (3 vs 6). CONCLUSIONS: Treatment of pioglitazone reduced neointimal hyperplasia in patients with STEMI treated with primary stent implantation without placing the patient at increased risk of complications. Additional larger trials will be necessary to establish the clinical benefit of pioglitazone.
Subject(s)
Hypoglycemic Agents/therapeutic use , Myocardial Infarction/drug therapy , Stents , Thiazolidinediones/therapeutic use , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , Coronary Angiography , Coronary Restenosis/diagnosis , Coronary Restenosis/pathology , Coronary Restenosis/prevention & control , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Female , Follow-Up Studies , Heart Failure/prevention & control , Humans , Hyperplasia/prevention & control , Male , Middle Aged , Myocardial Infarction/therapy , Patient Compliance , Pioglitazone , Treatment Outcome , Tunica Intima/diagnostic imaging , Tunica Intima/pathology , UltrasonographyABSTRACT
The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5-FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma/drug therapy , Fluorouracil/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/administration & dosage , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/mortality , Disease Progression , Female , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Paclitaxel/adverse effects , Stomach Neoplasms/mortality , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone. RESULTS AND METHODS: The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control. CONCLUSION: These results suggest that HGF secreted from 3T3-L1 cells may be the major factor regulating the tube formation, and agents that enhance the differentiation of adipocytes may promote tube formation of HUVECs mediated by HGF secreted by adipocytes.
Subject(s)
Adipocytes/metabolism , Endothelial Cells/physiology , Hepatocyte Growth Factor/physiology , Neovascularization, Physiologic/physiology , 3T3 Cells , Animals , Cells, Cultured , Culture Media , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Endothelial Cells/drug effects , Female , Hepatocyte Growth Factor/metabolism , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Male , Mice , Middle Aged , Neovascularization, Physiologic/drug effects , Pioglitazone , RNA, Messenger/analysis , RNA, Small Interfering/pharmacology , Thiazolidinediones/pharmacology , Thiazolidinediones/therapeutic use , Vascular Endothelial Growth Factor A/analysisABSTRACT
The severity of metabolic syndrome depends on the degree of insulin resistance. However, currently there is no adequate clinical marker for quantitative analysis of insulin resistance. A small quantity of lipoprotein lipase (LPL) protein, which is an inactive form and commonly called 'preheparin LPL mass', exists in serum and is detected by a sensitive immunoassay system. Recent studies have reported the clinical significance of serum preheparin LPL mass levels in various aspects. For example, preheparin LPL mass is negatively related to serum triglyceride and positively related to HDL-cholesterol, is low in type 2 diabetes mellitus, is increased by administration of insulin sensitizer, and shows an inverse relationship with visceral adiposity. Furthermore, preheparin LPL mass level is significantly lower in patients with coronary atherosclerosis compared to patients with no lesion, and correlates negatively with the severity of these lesions. From these reports, preheparin LPL mass may be considered to be the most important quantitative indicator of insulin resistance of the whole body.
Subject(s)
Biomarkers , Lipoprotein Lipase/metabolism , Metabolic Syndrome/physiopathology , Coronary Artery Disease/enzymology , Humans , Intra-Abdominal Fat , Metabolic Syndrome/enzymologyABSTRACT
OBJECTIVE: To evaluate the effect and safety of treatment with low-calorie formula diet on renal function and proteinuria in obese patients with diabetic nephropathy. DESIGN: Prospective study on safety and efficacy of a 4-week low-calorie (11-19 kcal/kg/day) normal-protein (0.9-1.2 g/kg/day) diet partly supplemented with formula diet. SUBJECTS: In all, 22 obese patients with diabetic nephropathy (BMI: 30.4+/-5.3 kg/m(2), HbA1c: 7.1+/-1.4%, serum creatinine: 172.4+/-57.5 micromol/l, urinary protein: 3.3+/-2.6 g/day). RESULTS: The mean body weight decreased by 6.2+/-3.0 kg. The mean systolic blood pressure, creatinine, blood urea nitrogen, urinary protein, and 8-hydroxydeoxyguanosine decreased significantly by 7.5+/-12.7 mmHg, 41.6+/-23.9 micromol/l, 1.50+/-1.61 mmol/l, 1.8+/-1.7 g/day, and 3.1+/-3.6 ng/mg creatinine, respectively. No patient had increased serum creatinine and urinary protein. Mean creatinine clearance (40.6+/-17.9 to 46.1+/-14.6 ml/s/1.73 m(2)) and serum albumin showed no significant changes. Delta serum creatinine and Delta urinary protein correlated with Delta body weight (r=0.62 and 0.49, respectively) and Delta visceral fat area (r=0.58 and 0.58, respectively), but did not correlate with Delta systolic blood pressure, Delta fasting blood glucose and Delta subcutaneous fat area. CONCLUSION: These results suggested that weight reduction using formula diet might improve renal function and proteinuria safely for a short term in obese patients with diabetic nephropathy.