A randomized prospective trial of the postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy for the treatment of symptomatic uterine fibroids: clinical trial design

<p>Abstract</p> <p>Background</p> <p>Laparoscopy-assisted vaginal hysterectomy is one of the definite methods for the treatment of symptomatic uterine fibroids with lesser intraoperative bleeding and shorter hospitalization compared with abdominal hysterectomy. However, laparoscopy-assisted vaginal hysterectomy cannot preserve uterus and can show postoperative complications by the change of pelvic structure. Thus, laparoscopic uterine artery ligation has been introduced for relieving the symptoms caused by uterine fibroids in place of hysterectomy. The current study was designed to compare postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy, and to evaluate the efficacy of laparoscopic uterine artery ligation which can treat symptomatic uterine fibroids with the preservation of uterus.</p> <p>Methods and design</p> <p>Patients enrolled the current study are randomized to laparoscopic uterine artery ligation or laparoscopy-assisted vaginal hysterectomy. The primary outcome is to compare postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients version 3.0. Secondary outcomes are to evaluate the volume reduction of uterus, uterine fibroids and ovaries by the 2 treatments, to compare the improvement of subjective symptoms using 11-point symptom score and postoperative clinical outcomes between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy, and to investigate the improvement of postoperative vaginal bleeding by laparoscopic uterine artery ligation.</p> <p>Discussion</p> <p>Among treatment methods for symptomatic uterine fibroids with the preservation of uterus, laparoscopic uterine artery ligation is expected to have the efficacy like uterine artery embolization, which appeared to be safe for routine use with symptomatic relief. The current study fully recruited in June 2008 and the results will be available in June 2009. If there is no difference of postoperative QOL between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy for the treatment of symptomatic uterine fibroids, the comparison of quality of life between laparoscopic uterine artery ligation and uterine artery embolization will be also needed as a surgical treatment for preserving uterus.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN76790866</p

The Impact of Korean Medicine Treatment on the Incidence of Parkinson&apos;s Disease in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study in South Korea

We aimed to investigate the association between Korean medicine (KM) treatment and the risk of Parkinson&apos;s Disease (PD) in patients with inflammatory bowel disease (IBD) in South Korea. This study analyzed data from the National Health Insurance Service-Senior cohort in South Korea. The 1816 IBD patients enrolled in the analysis comprised 411 who received only conventional treatment (monotherapy group) and 1405 who received both conventional and KM treatments (integrative therapy group). The risk of PD in patients with IBD was significantly lower in the integrative therapy group than in the monotherapy group after adjusting for confounding variables (adjusted hazard ratio (HR), 0.56; 95% confidence interval (CI) = 0.34-0.92). In the mild Charlson Comorbidity Index (CCI) group, the risk of PD in patients with IBD in the integrative therapy group was 0.39 times lower (adjusted HR, 95% CI = 0.20-0.77) than that in the monotherapy group. However, there was no significant difference in the risk of PD in patients with IBD between the integrative therapy and monotherapy groups among individuals with severe CCI (adjusted HR, 0.90; 95% CI = 0.41-1.96). IBD patients are at a decreased risk of PD when they receive integrative therapy. KM treatment may prevent PD in IBD patients.Y

E2-25K/Hip-2 regulates caspase-12 in ER stress–mediated Aβ neurotoxicity

Amyloid-β (Aβ) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Aβ neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)–resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. Aβ increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2–mediated cell death. Finally, we find that E2-25K/Hip-2–deficient cortical neurons are resistant to Aβ toxicity and to the induction of ER stress and caspase-12 expression by Aβ. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress–mediated Aβ neurotoxicity

QT Prolongation and Life Threatening Ventricular Tachycardia in a Patient Injected With Intravenous Meperidine (Demerol®)

QT prolongation is a serious adverse drug effect, which is associated with an increased risk of Torsade de pointes and sudden death. Many drugs, including both cardiac and non-cardiac drugs, have been reported to cause prolongation of QT interval. Although meperidine has not been considered proarrhythmic, we present a unique case of a 16-year-old boy without an underlying cardiac disease, who developed polymorphic ventricular tachycardia, ventricular fibrillation and QT prolongation after an intravenous meperidine injection. He had no mutation in long QT syndrome genes (KCNQ1, KCNH2, and SCN5A), but single nucleotide polymorphisms were reported, including H558R in SCNA5A and K897T in KCNH2

The Inhibitory Effect of siRNAs on The High Glucose-Induced Overexpression of TGF-β1 in Mesangial Cells

Diabetic nephropathy is characterized by an expansion of the glomerular mesangium, caused by mesangial cell proliferation and an excessive accumulation of extracellar matrix (ECM) proteins, which eventually leading to glomerulosclerosis. TGF-β1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-β1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-β1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-β1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-β1 mRNA and protein, and TGF-β1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-β1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-β1. The expression of TGF-β1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-β1 siRNAs reduces high glucose-induced TGF-β1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-β1 siRNAs effectively inhibits TGF-β1 mRNA and protein expression in RMCs. These suggest that TGF-β1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy

NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions

<p>Abstract</p> <p>Background</p> <p>To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene <it>NINJ2 </it>would be associated with earlier-onset (vs. late-onset) first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke.</p> <p>Methods</p> <p>We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men) admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR) imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image_QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR) MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images.</p> <p>Results</p> <p>The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126), there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (<it>P </it>= 0.052). Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke.</p> <p>Conclusions</p> <p>The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions prior to the stroke. Further studies are required to confirm our preliminary findings.</p

Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities

Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3–mediated ICAD cleavage. Overexpressed CIIA reduces H2O2- and tumor necrosis factor-α–induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling