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1.
Br J Dermatol ; 180(6): 1430-1437, 2019 06.
Article in English | MEDLINE | ID: mdl-30637718

ABSTRACT

BACKGROUND: Cutaneous lupus erythematosus (CLE) is a potentially disfiguring, chronic autoimmune disease with variable skin manifestations, negatively affecting patients' quality of life (QoL). Patient-reported outcome (PRO) measures assessing QoL in patients with CLE have been generic or developed without input from patients. OBJECTIVES: To demonstrate the reliability and validity of a disease-specific QoL measure for CLE - the cutaneous lupus erythematosus quality of life (CLEQoL). METHODS: One hundred and one patients with CLE were recruited, and each patient was asked to complete the CLEQoL. Internal consistency was used as a measure of reliability. Validity was measured in two ways - structural validity via exploratory factor analysis and convergent validity via Spearman correlations between CLEQoL and the Short Form 36 (SF-36), visual analogue scales and clinical variables. Patient demographic and disease characteristics were collected. RESULTS: The mean ± SD age of patients with CLE was 48 ± 13 years, with discoid lupus (n = 72; 71.3%) being the most predominant CLE subtype. Patients were mostly female (n = 88; 87·1%) and African American/Black (n = 59; 58·4%). Internal consistency ranged from 0·67 to 0·97. Five domains (functioning, emotions, symptoms, body image/cosmetic effects and photosensitivity) were extracted with a total explained variance of 71·1%. CLEQoL-related domains correlated with SF-36 domains (r range -0·39 to -0·65). CONCLUSIONS: The CLEQoL was found to be a valid and reliable PRO measure for assessing QoL in patients with CLE. Demonstrating that the CLEQoL has strong psychometric properties is an important step towards the development of a disease-specific PRO measure that future clinical trials can use.


Subject(s)
Lupus Erythematosus, Cutaneous/complications , Patient Reported Outcome Measures , Quality of Life , Surveys and Questionnaires , Adult , Female , Humans , Lupus Erythematosus, Cutaneous/psychology , Male , Middle Aged , Psychometrics/methods , Reproducibility of Results
2.
Clin Radiol ; 73(2): 216.e1-216.e8, 2018 02.
Article in English | MEDLINE | ID: mdl-28859852

ABSTRACT

AIM: To compare the long-term therapeutic outcomes of repeated radiofrequency ablation (RFA) with that of transarterial chemoembolisation (TACE) in patients with local tumour progression (LTP) after initial RFA treatment for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between July 2006 and February 2012, 713 patients underwent RFA for single HCC as a first-line treatment. Fifty-eight patients who showed LTP as initial tumour recurrence post-RFA treatment were included. Patients were treated with either repeated RFA (n=33) or TACE (n=25). TACE was performed as an alternative therapeutic option when repeated RFA was not feasible based on the planning ultrasonography. Recurrence-free and overall survival rates were estimated using the Kaplan-Meier method. Prognostic factors for outcomes were evaluated using the Cox proportional hazards model. RESULTS: Both groups did not show significant differences in terms of baseline characteristics, with the exception being the proportion of subphrenic tumours (p=0.031). The RFA and TACE groups did not differ significantly in their 5-year recurrence-free and overall survival rates (17% versus 10.7% and 72.7% versus 51.9%, respectively, with all p-values >0.05). In addition, multivariate analyses revealed that type of treatment was not associated with recurrence-free or overall survival in patients with post-RFA LTP. CONCLUSION: TACE is an effective treatment, comparable to repeated RFA, in patients with LTP after initial RFA when repeated RFA is not feasible.


Subject(s)
Carcinoma, Hepatocellular/therapy , Catheter Ablation/methods , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Disease-Free Survival , Female , Follow-Up Studies , Humans , Liver/diagnostic imaging , Liver/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Male , Middle Aged , Retreatment , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography
3.
Clin Radiol ; 72(2): 141-149, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27742104

ABSTRACT

AIM: To evaluate the efficacy of radiofrequency ablation (RFA) and transarterial chemoembolisation (TACE) as a first-line treatment for isolated intrahepatic recurrent hepatocellular carcinoma (IIR-HCC) after liver transplantation (LT). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. Between January 2005 and January 2015, 588 consecutive patients underwent LT for the treatment of HCC. Among them, 27 patients with IIR-HCCs after LT who were treated with RFA (n=6) or TACE (n=21) as a first-line treatment were retrospectively included in this study. Disease-free and overall survival rates were estimated using the Kaplan-Meier method. Risk factors affecting these outcomes were assessed with Cox regression models. RESULTS: Except for the total number of recurrent tumours and time-to-tumour recurrence after LT, baseline characteristics were not significantly different between the groups. The 2-year disease-free survival rates for RFA and TACE (20% versus 14%, respectively; p=0.180) and 4-year overall survival rates (33% versus 25%, respectively; p=0.065) were not significantly different between groups. In addition, the types of treatment were not associated with disease-free or overall survival in multivariate analyses. CONCLUSION: TACE may be an effective treatment comparable to RFA in patients with IIR-HCC after LT when RFA is not feasible.


Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Catheter Ablation/mortality , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Liver Transplantation/mortality , Neoplasm Recurrence, Local/mortality , Adult , Catheter Ablation/statistics & numerical data , Chemoembolization, Therapeutic/mortality , Chemoembolization, Therapeutic/statistics & numerical data , Combined Modality Therapy/mortality , Combined Modality Therapy/statistics & numerical data , Comorbidity , Female , Humans , Liver Transplantation/statistics & numerical data , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Prevalence , Republic of Korea/epidemiology , Retrospective Studies , Survival Rate , Treatment Outcome
4.
Biomater Sci ; 3(7): 1124-33, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26221945

ABSTRACT

Polyplexes, complexed nucleic acids by cationic polymers, are the most common forms of nonviral gene delivery vectors. In contrast to a great deal of efforts in synthesizing novel cationic polymers and exploring their extracellular and intracellular delivery pathways, polyplex preparation methods of mixing nucleic acids and cationic polymers are often overlooked. In this study, the mixing sequence, that is adding nucleic acids to polymers or vice versa, was found to greatly affect complexation of both plasmid DNA and siRNA, polyplexes' size, and polyplexes' surface charge, which all collaboratively affected the transfection efficiency and cytotoxicity. Adding polyethylenimine (PEI), the most conventionally used standard in nonviral gene delivery, to plasmid DNA and siRNA resulted in larger polyplexes, higher gene expression and silencing, but higher cytotoxicity than polyplexes prepared in the reverse order. Based on the experimental results, the authors developed a model that gradual addition of cationic polymers (e.g., PEI) to nucleic acids (e.g., plasmid DNA and siRNA) incorporates more copies of nucleic acids in larger polyplexes in a smaller number, results in higher gene expression and silencing levels in transfected cells, and generates higher cytotoxicity by leaving more free polymers upon complete mixing than the other mixing sequence. The proposed model can be explored using a broad range of cationic polymers and nucleic acids, and provide insightful information about how to prepare polyplexed nonviral vectors for efficient and safe gene delivery.


Subject(s)
Cytoplasm/chemistry , DNA/chemistry , Nucleic Acids/chemistry , Plasmids/chemistry , Polyethyleneimine/chemistry , Polymers/chemistry , RNA, Small Interfering/chemistry , Transfection/methods , Cytoplasm/metabolism , DNA/genetics , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors , Particle Size , Plasmids/metabolism , RNA, Small Interfering/genetics , Transfection/instrumentation
5.
Osteoarthritis Cartilage ; 23(3): 487-96, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25534363

ABSTRACT

BACKGROUND: Chronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD. OBJECTIVE: To examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators. DESIGN: NC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR. RESULTS: NCCM (10 & 100%), CS (10 and 100 µg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 µg inhibited tubules in Basal conditions whereas CS 10 µg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression. CONCLUSIONS: We provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Carrier Proteins/pharmacology , Chondroitin Sulfates/pharmacology , Cytokines/genetics , Human Umbilical Vein Endothelial Cells/drug effects , Intervertebral Disc/metabolism , Neovascularization, Pathologic/metabolism , RNA, Messenger/metabolism , Animals , Cytokines/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/physiology , Interleukin-6/genetics , Interleukin-8/drug effects , Interleukin-8/genetics , Intervertebral Disc/embryology , Matrix Metalloproteinase 7/drug effects , Matrix Metalloproteinase 7/genetics , Notochord/embryology , Notochord/metabolism , RNA, Messenger/drug effects , Swine , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/genetics , Vascular Endothelial Growth Factor A/drug effects , Vascular Endothelial Growth Factor A/genetics
6.
Bone Joint J ; 96-B(7): 950-5, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24986950

ABSTRACT

C5 nerve root palsy is a rare and potentially debilitating complication of cervical spine surgery. Currently, however, there are no guidelines to help surgeons to prevent or treat this complication. We carried out a systematic review of the literature to identify the causes of this complication and options for its prevention and treatment. Searches of PubMed, Embase and Medline yielded 60 articles for inclusion, most of which addressed C5 palsy as a complication of surgery. Although many possible causes were given, most authors supported posterior migration of the spinal cord with tethering of the nerve root as being the most likely. Early detection and prevention of a C5 nerve root palsy using neurophysiological monitoring and variations in surgical technique show promise by allowing surgeons to minimise or prevent the incidence of C5 palsy. Conservative treatment is the current treatment of choice; most patients make a full recovery within two years.


Subject(s)
Brachial Plexus Neuropathies/epidemiology , Cervical Vertebrae/injuries , Decompression, Surgical/adverse effects , Spinal Nerve Roots/injuries , Brachial Plexus Neuropathies/prevention & control , Decompression, Surgical/methods , Female , Humans , Intraoperative Complications/epidemiology , Intraoperative Complications/prevention & control , Intraoperative Neurophysiological Monitoring , Laminectomy/adverse effects , Male , Ossification of Posterior Longitudinal Ligament/epidemiology , Postoperative Complications/epidemiology
7.
J Biomed Nanotechnol ; 10(7): 1267-76, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24804547

ABSTRACT

Nanomaterial-directed, photothermal ablation is a practical future approach for the treatment of early-stage bladder cancer. Using a new PEGylation technique with bi-functional nitrophenyl carbonate PEG (bi-NPC-PEG) that promotes uniform suspension of the nanomaterial in solution, we have shown that gold nanorods conjugated to an anti-EGFR antibody (nano-alphaEGFR) bind effectively to EGFR-expressing bladder cancer cells. The subsequent application of infrared light, specifically tuned to the plasmon resonance of the nanorods used in this work, allows for the specific heating of nano-alphaEGFR to the point of localized cellular death. Such an approach, administering nano-alphaEGFR intravesically via a urinary catheter and infrared light via a modified cystoscope, represents a novel, future clinical application of this technology, which avoids the problem of systemic exposure and clearance of nanoparticles from body.


Subject(s)
Ablation Techniques , Gold/therapeutic use , Hyperthermia, Induced , Nanotubes/chemistry , Urinary Bladder Neoplasms/therapy , Cell Death , Cell Line, Tumor , ErbB Receptors/metabolism , Humans , Microscopy, Fluorescence , Nanoconjugates/ultrastructure , Nanotubes/ultrastructure , Polyethylene Glycols/chemistry , Spectrophotometry, Atomic
8.
Lupus ; 22(13): 1336-40, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24014567

ABSTRACT

OBJECTIVE: Two transcription factors in the type I interferon pathway, IRF5 and STAT4, have been genetically associated with susceptibility to both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to determine whether these two genes interact with each other to affect the disease susceptibilities. METHODS: The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software. This study analyzes the genetic data from 2558 unrelated Korean participants including 589 SLE patients, 987 RA patients, and 982 controls. RESULTS: All 12 polymorphisms were individually associated with SLE susceptibility (p = 2.49 × 10(-8) to 0.00360). Among the three SLE-associated polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3-4) indel, exhibited the lowest p value (4.60 × 10(-5)) and accounted for the observed associations of the other two single-nucleotide polymorphisms (SNPs). Among the nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49 × 10(-8)) and accounted for all the other associations. These two polymorphisms, rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE susceptibility in a redundant manner (ORinteraction = 0.77, P epistasis = 0.040). Furthermore, these two polymorphisms, which had been individually associated with RA susceptibility, also interacted for RA susceptibility in the same manner (ORinteraction = 0.75, P epistasis = 0.014). CONCLUSIONS: A redundant interaction between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling for further studies on confirmation of these findings.


Subject(s)
Arthritis, Rheumatoid/genetics , Epistasis, Genetic , Interferon Regulatory Factors/genetics , Interferon Type I/metabolism , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , STAT4 Transcription Factor/genetics , Adult , Aged , Arthritis, Rheumatoid/immunology , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Phenotype , Republic of Korea , Risk Factors , Signal Transduction
9.
Bone Joint J ; 95-B(7): 868-73, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23814234

ABSTRACT

Dysphagia is a common complication of anterior surgery of the cervical spine. The incidence of post-operative dysphagia may be as high as 71% within the first two weeks after surgery, but gradually decreases during the following months. However, 12% to 14% of patients may have some persistent dysphagia one year after the procedure. It has been shown that female gender, advanced age, multilevel surgery, longer operating time and severe pre-operative neck pain may be risk factors. Although the aetiology remains unclear and is probably multifactorial, proposed causes include oesophageal retraction, prominence of the cervical plate and prevertebral swelling. Recently, pre-operative tracheal traction exercises and the use of retropharyngeal steroids have been proposed as methods of reducing post-operative dysphagia. We performed a systematic review to assess the incidence, aetiology, risk factors, methods of assessment and management of dysphagia following anterior cervical spinal surgery.


Subject(s)
Cervical Vertebrae/surgery , Deglutition Disorders/epidemiology , Orthopedic Procedures/adverse effects , Postoperative Complications/etiology , Deglutition Disorders/etiology , Deglutition Disorders/surgery , Female , Humans , Incidence , Male , Postoperative Complications/surgery , Risk Factors , Treatment Outcome
10.
Clin Pharmacol Ther ; 94(1): 23-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23778707

ABSTRACT

This Commentary focuses on genetic polymorphisms in membrane transporters. We present two polymorphisms for which there is a compelling body of literature supporting their clinical relevance: OATP1B1 (c.521T>C, p.V174A, rs4149056) and BCRP (c.421C>A, p.Q141K, rs2231142). The clinical evidence demonstrating their role in variation in pharmacokinetics and pharmacodynamics is described along with their allele frequencies in ethnic populations. Recommendations for incorporating studies of transporter polymorphisms in drug development are provided, along with the regulatory implications.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Membrane Transport Proteins/genetics , Neoplasm Proteins/genetics , Organic Anion Transporters/genetics , Polymorphism, Genetic/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 2 , Clinical Trials as Topic , Drug Discovery , Gene Frequency/genetics , Humans , Liver-Specific Organic Anion Transporter 1 , Pharmacogenetics
11.
Global Spine J ; 3(3): 201-18, 2013 Jun.
Article in English | MEDLINE | ID: mdl-24436871

ABSTRACT

An understanding of the processes that occur during development of the intervertebral disk can help inform therapeutic strategies for discogenic pain. This article reviews the literature to identify candidates that are found in or derived from the notochord or notochordal cells and evaluates the theory that such factors could be isolated and used as biologics to target the structural disruption, inflammation, and neurovascular ingrowth often associated with discogenic back pain. A systematic review using PubMed was performed with a primary search using keywords "(notochordal OR notochord) And (nerves OR blood vessels OR SHH OR chondroitin sulfate OR notch OR CTGF) NOT chordoma." Secondary searches involved keywords associated with the intervertebral disk and pain. Several potential therapeutic candidates from the notochord and their possible targets were identified. Studies are needed to further identify candidates, explore mechanisms for effect, and to validate the theory that these candidates can promote structural restoration and limit or inhibit neurovascular ingrowth using in vivo studies.

12.
Br J Anaesth ; 108(6): 990-7, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22434266

ABSTRACT

BACKGROUND: Patients undergoing Caesarean delivery under inhalation anaesthesia are at a high risk of awareness, especially in the period before delivery. We assessed the effects of pre-exposure to sevoflurane on the bispectral index (BIS) in the interval before delivery. METHODS: Sixty-four patients undergoing elective Caesarean delivery were randomly assigned to receive 1.0-1.1 vol% (control 1) or 1.2-1.3 vol% (control 2) end-tidal sevoflurane, or the same concentrations of end-tidal sevoflurane combined with pre-exposure to 1 vol% sevoflurane for the last 1 min of the preoxygenation period (the preSevo 1 and preSevo 2 groups, respectively). We assessed BIS values, arterial pressure, and heart rate at the time of induction; before intubation; and upon skin incision, uterine incision, and delivery. We also determined the maternal incidence of intraoperative awareness and the neonatal Apgar scores, and conducted umbilical blood gas analysis. RESULTS: At skin incision, BIS values were significantly lower in the preSevo 1 group than in the control 1 group [50 (13) vs 72 (8), P<0.001] and in the preSevo 2 group than in the control 2 group [44 (11) vs 67 (10), P<0.001]. The mean BIS values in the preSevo 1 and 2 groups were maintained below 60 in the period before delivery. No other parameter differed among groups, and no patient exhibited intraoperative awareness. CONCLUSIONS: Pre-exposure to low concentrations of sevoflurane reduced BIS values in the interval before delivery, suggesting that this approach may reduce the risk of maternal awareness. Clinical Research Information Service (code KCT0000069, http://cris.cdc.go.kr).


Subject(s)
Anesthesia, Obstetrical , Anesthetics, Inhalation/pharmacology , Cesarean Section , Electroencephalography/drug effects , Methyl Ethers/pharmacology , Adult , Anesthesia, General , Awareness , Blood Pressure/drug effects , Female , Humans , Pregnancy , Prospective Studies , Sevoflurane
13.
Biomed Chromatogr ; 26(10): 1157-62, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22290690

ABSTRACT

The extraction and identification of bioactive compounds from herbs is of great interest. In this study, accelerated solvent extraction (ASE) technique was used to analyze the secondary volatile profiles in Nigella sativa seeds obtained from two different origins, Egypt and Bangladesh. The main extraction parameters, including extraction temperature, pressure and static extraction time, were investigated and optimized. Identification and quantification of the major constituents in nonpolar extracts (hexane) were achieved by means of GC-FID/GC-MS analysis with external standards. The two seeds showed a similar variety of chemical composition; however, the secondary volatiles profile of Bangladesh seed was higher than that of the Egyptian seed. A total of 25 compounds were identified from the ASE extract under the following optimum extraction conditions: 100°C, 1500 psi and 5 min, for extraction temperature, pressure and static time, respectively. The proposed technique can be used for the characterization of N. sativa varieties or cultivars.


Subject(s)
Chemical Fractionation/methods , Gas Chromatography-Mass Spectrometry/methods , Nigella sativa/chemistry , Seeds/chemistry , Volatile Organic Compounds/analysis , Bangladesh , Benzoquinones/analysis , Cymenes , Egypt , Fatty Acids/analysis , Hexanes/chemistry , Least-Squares Analysis , Monoterpenes/analysis , Volatile Organic Compounds/isolation & purification
14.
Transplant Proc ; 43(5): 1654-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21693252

ABSTRACT

BACKGROUND: Prolonged corrected QT (QT(c)) interval and vagal dysfunction are common occurrences in liver cirrhosis and are determinants of mortality in patients with chronic liver disease. We evaluated whether propranolol can affect the relationship between QT(c) interval and cardiac vagal control of heart rate variability (HRV) in cirrhotic patients awaiting liver transplantation. METHODS: We compared 50 cirrhotic patients (M/F = 43/7, 52.6 ± 8.4 years, Child-Pugh class A/B/C: 9/24/17) receiving propranolol with a sex-, age-, and liver disease severity-matched control group of 50 patients (M/F = 43/7, 52.0 ± 8.3 year, Child-Pugh class A/B/C: 9/24/17) not receiving propranolol. Among the parameters evaluated were QT(c) interval and cardiac vagal indices of HRV, including the root mean square of successive differences in R-R intervals (RMSSD); spectral power in the high-frequency range (HF); standard deviation (SD)1 in Poincare plot; and sample entropy. Correlations between QT(c) interval and vagal indices of HRV were analyzed. RESULTS: The mean duration of preoperative propranolol treatment in the propranolol group was 19.4 ± 24.7 months. QT(c) interval was significantly lower, whereas RMSSD, HF, SD1, and sample entropy were significantly higher in the propranolol group than in the control group. Correlation coefficients between QT(c) interval and RMSSD, HF, SD1, and sample entropy were higher in the propranolol group than in the control group. CONCLUSIONS: The prolonged QT(c) interval observed in cirrhotic patients may be reduced by propranolol administration, an effect attributable to improved vagal cardiac modulation. These findings suggest that propranolol may have a beneficial effect on perioperative mortality in cirrhotic patients awaiting liver transplantation.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Heart Rate/drug effects , Liver Cirrhosis/physiopathology , Liver Transplantation , Propranolol/pharmacology , Adult , Electrocardiography , Female , Humans , Male , Middle Aged
15.
Lupus ; 20(8): 809-19, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21562017

ABSTRACT

Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi's disease, is a benign and self-limiting lymphadenopathy that typically affects young Asian females. It presents with lymphadenopathy, usually cervical, accompanied by fever, chills and leukopenia. Although the association between systemic lupus erythematosus (SLE) and HNL is rare, the number of reports of HNL in SLE patients is increasing. We present nine cases of HNL in patients with SLE. Among the seven patients with diverse skin manifestations, three had skin manifestations that were histologically compatible with SLE. A review of previous reports in the literature showed that cutaneous involvement was commonly found in HNL in association with SLE. In the patients who had simultaneous onset of both diseases, lupus flare-ups were commonly observed. We suggest that HNL in SLE patients is associated with cutaneous manifestations. This report contributes to our understanding of the relationship between these diseases.


Subject(s)
Histiocytic Necrotizing Lymphadenitis/pathology , Lupus Erythematosus, Systemic/pathology , Skin/pathology , Adolescent , Adult , Asian People , Comorbidity , Female , Histiocytic Necrotizing Lymphadenitis/epidemiology , Histiocytic Necrotizing Lymphadenitis/physiopathology , Humans , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Retrospective Studies , Young Adult
16.
Acta Anaesthesiol Scand ; 55(5): 558-64, 2011 May.
Article in English | MEDLINE | ID: mdl-21342149

ABSTRACT

BACKGROUND: Hyperlactatemia can predict the prognosis of patients undergoing liver resection. The effects of lactated Ringer's solution on liver function have not been evaluated in patients undergoing major liver resection. We therefore compared the effects of two different crystalloid solutions, with and without lactate, on liver function test data and serum lactate level in living donors undergoing right hepatectomy. METHODS: A total of 104 donors undergoing right hepatectomy for liver transplantation were randomly allocated to receive lactated Ringer's (LR) solution (n=52) or Plasmalyte (n=52). Anesthetic and fluid management were standardized. Acid-base status, lactate concentration, and liver function tests were analyzed at predetermined time points during the first 5 post-operative days. RESULTS: The lactate concentrations were significantly higher in the LR group than in the Plasmalyte group 1 h after hepatectomy [4.2 (3.2-5.7) vs. 3.3 (2.6-4.6) mmol/l; P=0.005, median (interquartile ranges)]. In addition, the nadir concentration of albumin was significantly lower and the peak total bilirubin concentration and prothrombin time were significantly higher in the LR group compared with the Plasmalyte group. However, these changes in the LR group subsided within the first or second post-operative days, without apparent complications or prolongation of hospital stay. Post-operative peak concentrations of lactate were not correlated with nadir albumin concentration, peak bilirubin, or peak prothrombin time, in either group. CONCLUSION: This prospective randomized study showed that non-lactate-containing crystalloid solution may have important advantages over LR solution, concerning lactate and liver profiles, in living donors undergoing right hepatectomy.


Subject(s)
Hepatectomy , Isotonic Solutions/therapeutic use , Lactates/blood , Lactates/therapeutic use , Liver Function Tests , Living Donors , Plasma Substitutes/therapeutic use , Acid-Base Equilibrium , Adult , Anesthesia, General , Crystalloid Solutions , Female , Gluconates/therapeutic use , Humans , Magnesium Chloride/therapeutic use , Male , Postoperative Period , Potassium Chloride/therapeutic use , Prospective Studies , Ringer's Solution , Serum Albumin/metabolism , Sodium Acetate/therapeutic use , Sodium Chloride/therapeutic use , Solutions , Tissue and Organ Harvesting , Young Adult
17.
Clin Pharmacol Ther ; 89(3): 416-21, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21270793

ABSTRACT

We evaluated the effect of the pregnane X receptor (PXR) agonist rifampin on metformin pharmacokinetics, organic cation transporter 1 (OCT1) and OCT2 mRNA levels, and glucose levels, using the oral glucose tolerance test (OGTT) in 16 healthy subjects. The glucose-lowering effects of metformin were evaluated by OGTT before and after metformin treatment on days 1 and 2 and again on days 13 and 14 after a 10-day course of rifampin. Rifampin increased the difference in maximum glucose levels (ΔG(max)) by 41.9% (P = 0.024) and the area under the concentration-time curve (AUC) during the first 60 min after glucose ingestion (ΔAUC(gluc60)) by 54.5% (P = 0.020). Renal clearance (CL(R)) of metformin was increased by 16% (P = 0.008), but the systemic exposure was only slightly increased (13%, P = 0.049), possibly because of increased absorption. Rifampin increased OCT1 mRNA levels 4.1-fold in peripheral blood cells (P = 0.001); however, OCT2 mRNA was not detected. Our results suggest that rifampin increases OCT1 expression and hepatic uptake of metformin, leading to enhanced glucose-lowering action.


Subject(s)
Hypoglycemic Agents/pharmacokinetics , Metformin/pharmacokinetics , Octamer Transcription Factor-1/genetics , Organic Cation Transport Proteins/genetics , Rifampin/pharmacology , Adult , Antibiotics, Antitubercular/pharmacology , Area Under Curve , Blood Glucose/drug effects , Drug Interactions , Female , Glucose Tolerance Test , Humans , Hypoglycemic Agents/pharmacology , Liver/metabolism , Male , Metformin/pharmacology , Octamer Transcription Factor-1/drug effects , Organic Cation Transport Proteins/drug effects , Organic Cation Transporter 2 , Pregnane X Receptor , Prospective Studies , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Receptors, Steroid/agonists , Time Factors , Young Adult
18.
J Bone Joint Surg Br ; 92(8): 1061-5, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20675747

ABSTRACT

There are three basic concepts that are important to the biomechanics of pedicle screw-based instrumentation. First, the outer diameter of the screw determines pullout strength, while the inner diameter determines fatigue strength. Secondly, when inserting a pedicle screw, the dorsal cortex of the spine should not be violated and the screws on each side should converge and be of good length. Thirdly, fixation can be augmented in cases of severe osteoporosis or revision. A trajectory parallel or caudal to the superior endplate can minimise breakage of the screw from repeated axial loading. Straight insertion of the pedicle screw in the mid-sagittal plane provides the strongest stability. Rotational stability can be improved by adding transverse connectors. The indications for their use include anterior column instability, and the correction of rotational deformity.


Subject(s)
Bone Screws , Spinal Fusion/instrumentation , Biomechanical Phenomena , Equipment Design , Humans , Reoperation/methods , Spinal Fusion/methods , Spine/physiopathology
19.
Genes Immun ; 10(5): 397-403, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19369946

ABSTRACT

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.


Subject(s)
Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , src-Family Kinases/genetics , Age Factors , Case-Control Studies , Female , Genome-Wide Association Study , Humans , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology
20.
Eur J Vasc Endovasc Surg ; 37(5): 572-7, 2009 May.
Article in English | MEDLINE | ID: mdl-19208448

ABSTRACT

OBJECTIVES: To observe the clinical features and angiographic findings in patients with a spontaneous isolated superior mesenteric artery dissection (SISMAD) and to identify any correlation between them. METHODS: From a single institution, 32 patients (22 symptomatic patients at presentation; mean age 54years; men 97%) with SISMAD were retrospectively reviewed. All patients were available for clinical follow-up after treatment (conservative, n=28, 88%, open or endovascular superior mesenteric artery (SMA) reconstruction, n=4, 12%), and follow-up CT scans were available in 28 patients (mean 22months, range 1-80months). RESULTS: We found a positive correlation between pain severity and dissection length (p=0.03, rho=0.50, Spearman's partial correlation analysis). After conservative treatment, only one patient (3%) required bowel resection, and there was no difference in outcome between patients who were treated with anticoagulation or anti-platelet therapy and those who were not (p=1.00, Fisher's exact test). No patients had progression of their lesion on the follow-up CT angiography. CONCLUSIONS: In SISMAD patients, dissection length is positively associated with more severe clinical symptoms. After conservative treatment, we observed a benign clinical course and no CT progression of the dissection, even without anticoagulation or anti-platelet therapy. Based on our observation, patients with SISMAD can be treated conservatively without anticoagulation therapy.


Subject(s)
Abdominal Pain/etiology , Angiography/methods , Aortic Dissection/diagnostic imaging , Mesenteric Artery, Superior , Vascular Diseases/diagnostic imaging , Vascular Surgical Procedures/methods , Abdominal Pain/diagnosis , Abdominal Pain/surgery , Adult , Aged , Aged, 80 and over , Aortic Dissection/complications , Aortic Dissection/surgery , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Vascular Diseases/complications , Vascular Diseases/surgery
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