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1.
Phys Rev Lett ; 126(4): 047403, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33576652

ABSTRACT

We characterize the coherent dynamics of a two-level quantum emitter driven by a pair of symmetrically detuned phase-locked pulses. The promise of dichromatic excitation is to spectrally isolate the excitation laser from the quantum emission, enabling background-free photon extraction from the emitter. While excitation is not possible without spectral overlap between the exciting pulse and the quantum emitter transition for ideal two-level systems due to cancellation of the accumulated pulse area, we find that any additional interactions that interfere with cancellation of the accumulated pulse area may lead to a finite stationary population inversion. Our spectroscopic results of a solid-state two-level system show that, while coupling to lattice vibrations helps to improve the inversion efficiency up to 50% under symmetric driving, coherent population control and a larger amount of inversion are possible using asymmetric dichromatic excitation, which we achieve by adjusting the ratio of the intensities between the red- and blue-detuned pulses. Our measured results, supported by simulations using a real-time path-integral method, offer a new perspective toward realizing efficient, background-free photon generation and extraction.

2.
Neuropathol Appl Neurobiol ; 46(2): 125-141, 2020 02.
Article in English | MEDLINE | ID: mdl-31179553

ABSTRACT

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.


Subject(s)
Forkhead Box Protein M1/metabolism , Gene Expression Regulation, Neoplastic , Meningioma/metabolism , Animals , Brain/metabolism , Cell Line, Tumor , Cell Proliferation , Disease Progression , Humans , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/metabolism , Progression-Free Survival
3.
Dis Esophagus ; 33(5)2020 May 15.
Article in English | MEDLINE | ID: mdl-31665266

ABSTRACT

Robots are increasingly used in minimally invasive surgery. We evaluated the clinical benefits of robot-assisted minimally invasive esophagectomy (RAMIE) in comparison with the conventional open esophageal surgery. From 2012 to 2016, 371 patients with esophageal squamous cell carcinoma underwent an Ivor Lewis or McKeown procedure at our institution. Of these, 130 patients underwent laparoscopic gastric conduit formation followed by RAMIE, whereas 241 patients underwent conventional esophageal surgery, including laparotomy and open esophagectomy (OE). We compared the short- and long-term clinical outcomes of these patients using the propensity score-based inverse probability of treatment weighting technique (IPTW). Among the early outcomes, the OE group showed a higher incidence of pneumonia (P = 0.035) and a higher requirement for vasopressors (P = 0.001). Regarding the long-term outcomes, all-cause mortality was significantly higher (P = 0.001) and disease-free survival was lower (P = 0.006) in the OE group. Wound-related problems also occurred more frequently in the OE group (P = 0.020) during the long-term follow-up. There was no statistical intergroup difference in the recurrence rates (P = 0.191). The Cox proportional-hazard analysis demonstrated that wound problems (HR 0.16, 95% CI 0.02-0.57; P = 0.017), pneumonia (HR 0.23, 95% CI 0.06-0.68; P = 0.019), and use of vasopressors (HR 0.14, 95% CI 0.08-0.25; P = 0.001) were independent predictors of mortality. RAMIE could be a better surgical option for selected patients with esophageal squamous cell carcinoma.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Head and Neck Neoplasms , Robotic Surgical Procedures , Robotics , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/surgery , Esophagectomy/adverse effects , Humans , Minimally Invasive Surgical Procedures , Neoplasm Recurrence, Local , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Propensity Score , Treatment Outcome
4.
Phys Rev Lett ; 123(16): 167402, 2019 Oct 18.
Article in English | MEDLINE | ID: mdl-31702372

ABSTRACT

Coherent generation of indistinguishable single photons is crucial for many quantum communication and processing protocols. Solid-state realizations of two-level atomic transitions or three-level spin-Λ systems offer significant advantages over their atomic counterparts for this purpose, albeit decoherence can arise due to environmental couplings. One popular approach to mitigate dephasing is to operate in the weak-excitation limit, where the excited-state population is minimal and coherently scattered photons dominate over incoherent emission. Here we probe the coherence of photons produced using two-level and spin-Λ solid-state systems. We observe that the coupling of the atomiclike transitions to the vibronic transitions of the crystal lattice is independent of the driving strength, even for detuned excitation using the spin-Λ configuration. We apply a polaron master equation to capture the non-Markovian dynamics of the vibrational manifolds. These results provide insight into the fundamental limitations to photon coherence from solid-state quantum emitters.

5.
Int J Obes (Lond) ; 41(4): 660-663, 2017 04.
Article in English | MEDLINE | ID: mdl-28100915

ABSTRACT

Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10-4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher's combined P-value=3.76 × 10-5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.


Subject(s)
Asian People/genetics , Cadherins/genetics , DNA Copy Number Variations/genetics , Exome Sequencing , Exome/genetics , Pediatric Obesity/genetics , Adolescent , Child , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Reproducibility of Results , Republic of Korea
6.
Diabetes Obes Metab ; 18(1): 104-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26381793

ABSTRACT

We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography-electrospray ionization-tandem mass spectrometry. When metformin was co-administered with pyrimethamine, its area under the concentration-time curve from 0 to 12 h was 2.58-fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2-h-post-OGTT serum glucose concentration were -0.6 (-1, -0.2), -0.9 (-1.6, -0.3) and -0.5 (-1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal-based pharmacology of metformin.


Subject(s)
Hypoglycemic Agents/blood , Hypoglycemic Agents/pharmacokinetics , Metformin/blood , Organic Cation Transport Proteins/drug effects , Pyrimethamine/pharmacokinetics , Adult , Blood Glucose/drug effects , Cross-Over Studies , Drug Interactions , Glucose Tolerance Test , Healthy Volunteers , Humans , Male , Metformin/pharmacokinetics
7.
Dis Esophagus ; 26(6): 609-15, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23237428

ABSTRACT

The clinical course and outcome of isolated anastomotic leaks (IALs) after esophagectomy are significantly different from those of necrotic leaks. The purpose of this study was to investigate the clinical features, diagnosis, treatment, and long-term outcome in patients with IALs after esophagectomy with reconstruction for esophageal cancer. A total of 663 patients underwent esophagectomy with esophageal reconstruction because of esophageal cancer between 2000 and 2010 at the Seoul Asan Medical Center. IALs occurred in 23 patients (3.5%). All patients with IAL were male, with a median age of 61 years. Patients with IAL were divided into three groups based on their clinical course. group A comprised patients who had definite clinical symptoms and/or signs indicating mediastinal contamination or leak before routine contrast esophagography was performed. Groups B and C comprised patients who had no definite clinical symptoms and/or signs of leaks before the routine contrast examination. Furthermore, group B contained those patients who resumed oral intake because no leak was found in the routine contrast examination and was diagnosed some days after resuming oral intake. Group C contained those patients who kept fasting because the leak was found in the routine contrast examination. The median follow-up period was 30 months. The mean time to closure of the IAL was 70.1 ± 96.0 days (range 4-364). There was a 72.7% overall closure rate within 60 days. By univariate analysis, the mean time to closure of the IAL was found to be significantly longer for group A patients or in cases where the patients had an uncontained leak, leukocytosis, or empyema. However, there was no statistically significant differences in age, neoadjuvant treatment, site of anastomosis (cervical vs. thoracic), fever, or treatment of the leak. By multivariate analysis, group A was found to be an independent predictive factor for the time to closure of the IAL. Repeat contrast studies revealed no anastomotic leaks in 18 patients and the formation of contained fistula in four cases (excluding one patient who died in hospital). The four patients with a contained fistula showed no clinical symptoms or signs, and tolerated resumed oral intake. IALs were resolved in most cases with low leak-related mortality, and resolution of the leaks occurred within 2 months in the majority of patients.


Subject(s)
Anastomotic Leak/therapy , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Adult , Age Factors , Aged , Aged, 80 and over , Anastomotic Leak/diagnostic imaging , Anastomotic Leak/surgery , Contrast Media , Eating/physiology , Empyema/etiology , Esophageal Fistula/etiology , Fasting , Female , Fever/etiology , Follow-Up Studies , Humans , Laparotomy/methods , Leukocytosis/etiology , Lymph Node Excision/methods , Male , Mediastinum/diagnostic imaging , Middle Aged , Neoadjuvant Therapy , Radiography , Plastic Surgery Procedures/methods , Retrospective Studies , Survival Rate , Thoracotomy/methods , Treatment Outcome
8.
J Oral Rehabil ; 39(6): 421-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22471834

ABSTRACT

Posterior maxillary region is considered to be the most challenging area for dental implant placement. Lateral window opening is the gold standard procedure for maxillary sinus augmentation in this area. The purpose of this study is to evaluate lateral wall thickness of the maxillary sinus for sinus augmentation using computed tomography (CT) in edentulous patients. Computed tomography images of 302 patients were analysed. Using the maxillary sinus floor as the reference point in edentulous regions, lateral wall thickness was measured on CT scans. After drawing a tangent line at the lowest point of the sinus floor, another perpendicular line to the tangent line was drawn at the same point of the sinus floor. Thickness of the lateral wall of the maxillary sinus was measured using 10DR implant software at 3 (R1), 10 (R2) and 15 mm (R3) from the sinus floor. The mean thickness of the lateral wall of the maxillary sinus from the first premolar to second molar was 1·69 ± 0·71, 1·50 ± 0·72, 1·77 ± 0·78 and 1·89 ± 0·85 mm, respectively. The thickness differed significantly at the R2 and R3 points. Women had thinner lateral walls at the R1 and R2 points at the premolars than did men. At the R2 and R3 points at the second premolar, the mean thickness of smokers was larger than that of non-smokers. There were no significant differences on age or reasons for tooth loss. The changes in the thickness of the lateral wall at different reference points were observed, and CT examinations may help make lateral window without membrane perforation.


Subject(s)
Maxillary Sinus/diagnostic imaging , Mouth, Edentulous/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Bicuspid/anatomy & histology , Bicuspid/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Maxillary Sinus/anatomy & histology , Middle Aged , Molar/anatomy & histology , Molar/diagnostic imaging , Sex Factors , Tomography, X-Ray Computed , Young Adult
9.
Ann Oncol ; 22(2): 288-94, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20682548

ABSTRACT

BACKGROUND: The second-line chemotherapeutic treatment for metastatic urothelial cancer (UC) after failure of cisplatin-based first-line therapy needs to be improved. Based on encouraging phase II data of gemcitabine and paclitaxel (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a prolonged (arm B) second-line combination chemotherapy of GP. PATIENTS AND METHODS: Of 102 randomized patients, 96 were eligible for analysis. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rates (ORR) and toxicity. RESULTS: Neither OS [arm A: 7.8 (95% CI: 4.2-11.4), arm B: 8.0 (95% CI: 4.9-11.1) months] and PFS [arm A: 4.0 (95% CI: 0-8.0), arm B: 3.1 (95% CI: 1.9-4.2) months] nor ORR (arm A: 37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV anemia; P = 0.011). In six patients, treatment was stopped during the first cycle due to disease progression or toxicity. Two patients died due to treatment-related toxic effects. CONCLUSION: Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Urinary Bladder Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Disease-Free Survival , Humans , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Gemcitabine
10.
Gene Ther ; 17(8): 1052-61, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20485381

ABSTRACT

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.


Subject(s)
Adenoviridae/genetics , Cell-Penetrating Peptides/chemistry , Genetic Therapy/methods , Mesenchymal Stem Cells/metabolism , Transduction, Genetic/methods , Animals , Bone Diseases/genetics , Bone Diseases/therapy , Bone Morphogenetic Protein 2/genetics , Gene Transfer Techniques , Genetic Vectors , Humans , Male , Mesenchymal Stem Cells/cytology , Osteogenesis/genetics , Rats , Rats, Sprague-Dawley , Skull/growth & development
11.
J Fish Dis ; 33(11): 865-77, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21039606

ABSTRACT

Shewanella marisflavi isolate AP629 is described as a novel pathogen of sea cucumber. The LD(50) values (14 days) in sea cucumber, mice and swordtail fish were 3.89 × 10(6) , 6.80 × 10(4) and 4.85 × 10(4) CFU g(-1) body weight, respectively. Studies on S. marisflavi were conducted, including morphology, physiological and biochemical characteristics, haemolysis, whole-cell protein and 16S rDNA gene sequence. Colonies of S. marisflavi appeared faint red on marine agar and green on thiosulphate-citrate-bile salt-sucrose media. Shewanella marisflavi had polar flagella. The cells were Gram-negative, oxidase- and catalase-positive and not sensitive to O/129. The bacterium exhibited ß-haemolysis on sheep blood agar and produced H(2) S. Shewanella marisflavi survived and grew at 4-35°C, pH 6.0-9.2 and in the presence of 0-8% NaCl. The whole-cell proteins included 13 discrete bands, and proteins of molecular weight 87, 44 and 39 kDa were found in all five strains of Shewanella spp. The difference in 16S rDNA gene sequences in S. marisflavi was at the 446 bp site: S. marisflavi (KCCM 41822) - G, isolate AP629 - A. This is the first report that Shewanella is pathogenic to sea cucumber.


Subject(s)
Shewanella/physiology , Stichopus/microbiology , Animals , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Base Sequence , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Mice , Microscopy, Electron, Transmission , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Alignment , Shewanella/genetics , Shewanella/pathogenicity , Shewanella/ultrastructure , Virulence
12.
Ann Oncol ; 20(6): 1032-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19193704

ABSTRACT

BACKGROUND: This study was to investigate the prognostic significance of clinicopathologic characteristics in patients with clear-cell carcinoma (CCC) of the ovary. MATERIALS AND METHODS: Two hundred and one patients with CCC of the ovary were registered in the Korean Gynecologic Oncology Group. The Korean Gynecologic Pathology Study Group reviewed the pathological slides centrally, using a universal grading system. The prognostic significances of clinicopathologic factors were evaluated by multivariate analysis. RESULTS: Most of the patients were diagnosed at an early stage (stage I, 61.3%), and the overall 5-year survival rate was 57%. Early-stage disease showed a favorable prognosis, but advanced diseases showed poor prognosis. Stage of disease was the only significant prognostic factor on multivariate analysis (P < 0.001). However, universal grade and residual tumor also showed prognostic significance on the forward stepwise likelihood ratio test. There was no survival difference observed between patients treated with paclitaxel-based and those treated with platinum-based combination chemotherapy. CONCLUSIONS: The stage, residual tumor, and universal grade were significant prognostic factors in patients with CCC of the ovary. The universal grading system is applicable in determining prognosis of CCC of the ovary. Further clinical trials for optimal chemotherapy are in need.


Subject(s)
Adenocarcinoma, Clear Cell/pathology , Ovarian Neoplasms/pathology , Registries , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/surgery , Adult , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Korea , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Prognosis , Retrospective Studies
13.
Cell Tissue Res ; 335(1): 249-59, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18815812

ABSTRACT

Src family kinases (SFKs) are signaling enzymes that have long been recognized to regulate critical cellular processes such as proliferation, survival, migration, and metastasis. Recently, considerable work has elucidated mechanisms by which SFKs regulate normal and pathologic processes in vascular biology, including endothelial cell proliferation and permeability. Further, when inappropriately activated, SFKs promote pathologic inflammatory processes and tumor metastasis, in part through their effects on the regulation of endothelial monolayer permeability. In this review, we discuss the roles of aberrantly activated SFKs in mediating endothelial permeability in the context of inflammatory states and tumor cell metastasis. We further summarize recent efforts to translate Src-specific inhibitors into therapy for systemic inflammatory conditions and numerous solid organ cancers.


Subject(s)
Capillary Permeability , Endothelial Cells/enzymology , Endothelium, Vascular/enzymology , Inflammation Mediators/metabolism , Neoplasm Proteins/metabolism , Neoplasms/enzymology , src-Family Kinases/metabolism , Animals , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Capillary Permeability/drug effects , Enzyme Activation/drug effects , Humans , Inflammation/drug therapy , Inflammation/enzymology , Inflammation Mediators/antagonists & inhibitors , Neoplasm Metastasis , Neoplasm Proteins/antagonists & inhibitors , Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Signal Transduction/drug effects , src-Family Kinases/antagonists & inhibitors
14.
J Biomed Biotechnol ; 2008: 547428, 2008.
Article in English | MEDLINE | ID: mdl-18317521

ABSTRACT

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.


Subject(s)
Electric Stimulation/instrumentation , Evoked Potentials, Visual/physiology , Retina/physiology , Animals , Choroid/cytology , Electric Stimulation/adverse effects , Equipment Design , Equipment Failure Analysis , Feasibility Studies , Materials Testing , Prostheses and Implants , Rabbits , Retina/cytology
15.
Braz J Med Biol Res ; 40(4): 457-65, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17401488

ABSTRACT

Chronic allograft nephropathy is among the major causes of graft loss even in low-risk kidney transplant recipients and correlates with acute nephrotoxic events during the first year post-transplant. Therefore, calcineurin inhibitor-free regimens may improve patient and graft survival among recipients of living-related kidney transplants. To confirm this hypothesis, we evaluated the efficacy and safety of two calcineurin inhibitor-free regimens in 92 low-risk recipients of one-haplotype living-related kidney transplants. Immunosuppression consisted of tacrolimus, azathioprine and prednisone (group I, GI, N = 38), 2 doses of daclizumab, mycophenolate mofetil (MMF), and prednisone (GII, N = 33) and 2 doses of daclizumab, MMF, sirolimus and prednisone (GIII, N = 21). At 12 months, treatment failure (biopsy-confirmed acute rejection, graft loss or death) was higher in GII compared to GIII and GI (54.5 vs 24.0 vs 13.1%, P < 0.01, respectively). In patients of black ethnicity the incidence of acute rejection was 25 vs 83.3 vs 20% (P = 0.055), respectively. Patient and graft survival was comparable. There were no differences in mean creatinine or calculated creatinine clearance at 12 months. Overall incidence of post-transplant diabetes mellitus (3.3%) and cytomegalovirus disease (4.3%) was similar in all groups. Further development of effective calcineurin inhibitor-free regimens should exclude patients of black ethnicity and may need full-induction therapy, perhaps with depleting agents, and concentration-controlled use of sirolimus and MMF.


Subject(s)
Calcineurin Inhibitors , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/immunology , Adult , Clinical Protocols , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/physiology , Male , Prospective Studies
16.
Transplant Proc ; 39(2): 463-4, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362760

ABSTRACT

UNLABELLED: Thymoglobulin is used as an induction agent in kidney transplantation, but the optimal dose is not well established. However, its use may be associated with increased infectious complications after transplantation. METHODS: This retrospective study of 61 high-risk renal recipients of transplants from deceased donors performed between June 2001 and April 2004 included patients treated with thymoglobulin. Patients were divided into two groups according to the total thymoglobulin dose (G1, n = 30, <7 mg/kg; G2, n = 31, >7 mg/kg) and followed for at least 1 year. RESULTS: Mean recipient age was 43 +/- 14 years; 41% were males; 63% non-Whites. Mean cold ischemia time was 26.3 +/- 7 hours. Mean PRA was 23% (0-100%). Second transplantation was performed in 18 (29.5%) patients. Mean donor age was 42.1 +/- 16 years, and 59% had a cerebral vascular accident as the cause of death. Patient- and death-censored graft survival at 12 months were 86% and 88%, respectively. There were 149 infectious episodes among 47 (78%) patients. The incidence of infection was 1.7 +/- 0.24 infections per patient per year in G1 (lower dose) vs 3.12 +/- 0.23 in G2 (P < .001). Bacterial (0.66 +/- 1.0 vs 1.48 +/- 1.26 infections per patient per year, P = .009) and viral infections (0.9 +/- 0.71 vs 1.41 +/- 0.71; P = .006) were more frequent in the higher dose group. CONCLUSION: This study suggested that a greater number of infectious episodes were present when the total dose of thymoglobulin was higher than 7 mg/kg.


Subject(s)
Antibodies, Monoclonal/blood , Infections/epidemiology , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Postoperative Complications/epidemiology , Adult , Antilymphocyte Serum , Cadaver , Female , Histocompatibility Testing , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors
17.
Pediatr Obes ; 12(2): 93-101, 2017 04.
Article in English | MEDLINE | ID: mdl-26910390

ABSTRACT

BACKGROUND: Childhood and adolescent obesity may lead to obesity and related complications in adulthood. Biomarkers of obesity can be useful for screening for obesity complications and promoting early intervention during school age. Thus, the metabolomic differences in obese children and adolescents should be investigated for identification of potential biomarkers. OBJECTIVES: We investigated urinary biomarkers to distinguish metabolomic characteristics between obesity and normal weight in adolescents. METHODS: Adolescent subjects were divided into non-obese (n = 91) and obese (n = 93) groups according to body mass index. Untargeted and targeted metabolomic profiling of urine was performed using high-performance liquid chromatography (LC)-quadrupole time-of-flight mass spectrometry (MS), LC-MS/MS and flow injection analysis-MS/MS systems, respectively. RESULTS: Multivariate statistical analysis showed clear discrimination between the untargeted metabolomes of non-obese and obese groups. Seven endogenous metabolites were distinguished in the obese group, and inflammation-related metabolite markers showed strong predictive power for group classification. From targeted metabolomics, 45 metabolites mostly related to inflammation were significantly different in the obese group. CONCLUSIONS: Significantly different metabolome signatures were identified between normal-weight and obese adolescents. Combined untargeted and targeted metabolomics demonstrated that inflammation-driven insulin resistance, ammonia toxicity and oxidative stress may represent crucial metabolomic signatures in obese adolescents.


Subject(s)
Biomarkers/urine , Metabolomics/methods , Pediatric Obesity/diagnosis , Adolescent , Child , Chromatography, High Pressure Liquid , Female , Flow Injection Analysis , Humans , Male , Metabolome , Multivariate Analysis , Registries , Tandem Mass Spectrometry
18.
Cardiovasc Intervent Radiol ; 40(12): 1866-1872, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28779218

ABSTRACT

PURPOSE: To evaluate the incidence, management methods and follow-up results of arterial embolism during percutaneous thrombectomy of hemodialysis grafts. MATERIALS AND METHODS: After Institutional Review Board approval, the radiologic database of our department for percutaneous thrombectomy procedure in hemodialysis access was retrospectively reviewed. Between 1998 and June 2014, 2975 percutaneous thrombectomy procedures using thromboaspiration technique were performed in 1524 patients with thrombosed hemodialysis grafts. After thrombectomy, angioplasty was performed for significant stenoses. The incidence of arterial embolism was analyzed according to the location/shape of the arteriovenous graft. Percutaneous management methods of arterial embolism and long-term follow-up results by fistulography were also evaluated. RESULTS: Arterial embolism was documented by angiography in 117 cases (3.9%). Of these, three were symptomatic and subsided after embolectomy. The incidence was significantly correlated with the location/shape of the graft (p = 0.001). Arterial emboli were retrieved using occlusion balloon/Fogarty balloon (n = 58), guiding catheter-assisted aspiration (n = 36), sheath-assisted aspiration (n = 2) and back-bleeding technique (n = 3). Others were observed without intervention (n = 17) or surgically removed (n = 1). Arterial emboli were completely retrieved in 86 cases and partially retrieved in 13 cases. Ulnar artery rupture occurred in one case due to over-inflation of the occlusion balloon. Follow-up fistulography performed in 60 patients among whom 99 percutaneous embolectomies were done revealed arterial stenosis/occlusion in 7 and residual emboli in one patient. In observed patients without intervention, follow-up documented complete resolution of the emboli without arterial stenosis in 9 patients. CONCLUSION: Radiologically perceivable arterial embolism is uncommon during percutaneous thrombectomy of thrombosed dialysis grafts. The majority of the emboli can be retrieved by percutaneous techniques, but may induce arterial damage in some patients. Clinical observation can be another option for patients without ischemic symptoms.


Subject(s)
Arteriovenous Shunt, Surgical , Postoperative Complications/epidemiology , Renal Dialysis , Thrombectomy/methods , Thromboembolism/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Angiography/methods , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Retrospective Studies , Thromboembolism/diagnostic imaging , Young Adult
19.
Braz J Med Biol Res ; 39(1): 19-30, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16400461

ABSTRACT

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (CavCHOL) or triglyceride (CavTG) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (> 229 or > 274 mg/dL) and triglyceride (> 198 or > 282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration > 205 mg/dL was independently associated with development of persistent hypercholesterolemia (CavCHOL > 240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration > 150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or > 211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (CavTG > 200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.


Subject(s)
Cyclosporine/adverse effects , Hyperlipidemias/chemically induced , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Lipid Metabolism/drug effects , Sirolimus/adverse effects , Adult , Azathioprine/administration & dosage , Cyclosporine/administration & dosage , Cyclosporine/blood , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Incidence , Male , Prednisone/administration & dosage , Severity of Illness Index , Sirolimus/administration & dosage , Sirolimus/blood , Time Factors
20.
Braz J Med Biol Res ; 39(1): 43-52, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16400463

ABSTRACT

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13% of the patients. Patients also received azathioprine (2 mg kg(-1) day(-1), N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg(-1) day(-1), N = 148). Mean time on dialysis was 79 +/- 41 months, 12% of the cases were re-transplants, and 21% had panel reactive antibodies > 10%. In 43% of donors the cause of death was cerebrovascular disease and 27% showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60%, respectively. Mean time to last dialysis and to nadir creatinine were 18 +/- 15 and 34 +/- 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 +/- 0.50 mg/dL (DGF 1.68 +/- 0.65 vs SGF 1.67 +/- 0.66 vs immediate graft function (IGF) 1.41 +/- 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22% (DGF 31%, SGF 10%, IGF 8%). One-year patient and graft survival was 92.6 and 78.4%, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0%, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.


Subject(s)
Calcineurin Inhibitors , Cyclosporine/therapeutic use , Delayed Graft Function/drug therapy , Graft Rejection/etiology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Adult , Azathioprine/administration & dosage , Biopsy , Creatinine/blood , Cyclosporine/administration & dosage , Delayed Graft Function/complications , Drug Administration Schedule , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Male , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Prednisone/administration & dosage , Retrospective Studies , Risk Factors , Severity of Illness Index , Tacrolimus/administration & dosage , Treatment Outcome
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