Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Congenital myasthenic syndromes are a genetically and clinically heterogeneous group of neuromuscular disorders linked by abnormal signal transmission at the motor endplate caused by various genetic defects. Major clinical symptoms include weakness and fatigue during the first years of life but patients may also present with hypotonia, facial weakness, swallowing difficulties, respiratory dysfunction, ptosis and ophthalmoparesis. Here we report a 10-year-old boy who presented with mild developmental delay and bilateral ptosis caused by a frameshift mutation in the CHRNA1 gene that co-segregated within the family, and finally diagnosed as autosomal dominant congenital myasthenic syndrome.

Congenital myasthenic syndromes are a genetically and clinically heterogeneous group of neuromuscular disorders linked by abnormal signal transmission at the motor endplate caused by various genetic defects. Major clinical symptoms include weakness and fatigue during the first years of life but patients may also present with hypotonia, facial weakness, swallowing difficulties, respiratory dysfunction, ptosis and ophthalmoparesis. Here we report a 10-year-old boy who presented with mild developmental delay and bilateral ptosis caused by a frameshift mutation in the CHRNA1 gene that co-segregated within the family, and finally diagnosed as autosomal dominant congenital myasthenic syndrome.

Purpose: Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. Methods: RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. Results: Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] < –1 or > 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. Conclusion Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

OBJECTIVE: To investigate the predictive index of functional recovery after primary pontine hemorrhage (PPH) using the combined motor evoked potential (MEP) and somatosensory evoked potential (SEP) in comparison to the hematoma volume and transverse diameter measured with computerized tomography. METHODS: Patients (n=14) with PPH were divided into good- and poor-outcome groups according to the modified Rankin Score (mRS). We evaluated clinical manifestations, radiological characteristics, and the combined MEP and SEP responses. The summed MEP and SEP (EP sum) was compared to the hematoma volume and transverse diameter predictive index of global disability, gait ability, and trunk stability in sitting posture. RESULTS: All measures of functional status and radiological parameters of the good-outcome group were significantly better than those of the poor-outcome group. The EP sum showed the highest value for the mRS and functional ambulatory category, and transverse diameter showed the highest value for "sitting-unsupported" of Berg Balance Scale. CONCLUSION: The combined MEP and SEP is a reliable and useful tool for functional recovery after PPH.
Evoked Potentials, Motor ; Evoked Potentials, Somatosensory* ; Gait ; Hematoma ; Hemorrhage* ; Humans ; Posture

BACKGROUND: Chemerin is a novel adipokine that is associated with inflammation and adipogenesis. However, it remains unclear whether chemerin is involved in patients with cardiovascular disease. We investigated whether the serum chemerin levels of Korean patients with coronary artery disease correlated with specific cardiometabolic parameters. METHODS: In total, 131 patients, all of whom had coronary artery stenosis exceeding 50%, participated in this study. Their serum chemerin levels and cardiometabolic parameters were measured. The serum chemerin levels of two groups of patients were compared; those with one stenotic vessel (n=68) and those with multiple stenotic vessels, including left main coronary artery disease (n=63). RESULTS: Serum chemerin levels correlated positively with the degree of coronary artery stenosis and fasting glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high sensitive C-reactive protein levels. The group with multiple stenotic vessels, including left main disease, had higher chemerin levels than the group with one stenotic vessel (t=-2.129, P=0.035). Multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease (odds ratio, 1.018; confidence interval, 0.997 to 1.040; P=0.091). CONCLUSION: Serum chemerin levels have a significant correlation with several cardiometabolic risk factors and the degree of coronary artery stenosis in Korean patients with coronary artery disease. However, multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease. Additional investigations are necessary to fully elucidate the role of chemerin in cardiovascular disease.
Adipogenesis ; Adipokines ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, LDL ; Coronary Artery Disease ; Coronary Stenosis ; Coronary Vessels ; Fasting ; Glucose ; Glycosaminoglycans ; Humans ; Inflammation ; Lipoproteins ; Logistic Models ; Risk Factors

BACKGROUND: The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression. METHODS: The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter. RESULTS: The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression. CONCLUSIONS: This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.
Blotting, Northern ; Blotting, Western ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Gene Expression ; Humans ; Insulin ; Insulin-Secreting Cells ; RNA, Messenger ; Thapsigargin ; Transfection ; Tunicamycin

Growth hormone (GH) and thyroid stimulating hormone (TSH)-secreting pituitary adenomas are very rare and they account for only 0.5% for all pituitary adenomas. These adenomas are usually treated with surgery, but this surgery is not easy because the tumor is usually huge and invasive. We reported here on a case of a GH-TSH-secreting adenoma in a 23-year-old male patient who was initially treated with octreotide LAR. He presented with symptoms of headache, palpitation and a visual defect that he had for the 3 months. He had hypertrophy of the frontal bone and enlargement of both the hands and feet. The visual field test showed bitemporal hemianopsia. The laboratory examinations showed high serum levels of free T4, TSH and free alpha-subunit. Additionally, the serum levels of GH and insulin-like growth factor-I (IGF-I) were increased. GH was not suppressed below 1microg/L by an oral 75g glucose loading test, and TSH was not stimulated by thyrotropin-releasing hormone (TRH). Because sellar MRI showed invasive macroadenoma encasing the vessels, we initially tried octreotide LAR for treatment. A year later, the IGF-I and thyroid function tests were normalized and the size of the tumor was reduced with cystic change. The symptoms of palpitation and headache were improved without a change of the visual field defect.
Acromegaly ; Adenoma ; Foot ; Frontal Bone ; Glucose ; Growth Hormone ; Hand ; Headache ; Hemianopsia ; Humans ; Hypertrophy ; Insulin-Like Growth Factor I ; Male ; Octreotide ; Pituitary Neoplasms ; Thyroid Function Tests ; Thyrotropin ; Thyrotropin-Releasing Hormone ; Visual Field Tests ; Visual Fields ; Young Adult

OBJECTIVE: This study was aimed to compare lipid peroxide level, total peroxyl radical-trapping antioxidative parameter (TRAP) value, and antioxidant vitamin level in the maternal venous plasma between normal pregnancy and preeclampsia. METHODS: Samples of venous plasma were obtained from 38 normal and 24 preeclamptic women. Lipid peroxides levels were measured by thiobarbituric acid reaction. The TRAP values were measured by Wayner's method, although some reaction conditions were modified. Ascorbic acid, retinol, alpah-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. RESULTS: There was no significant correlation between the lipid peroxides level in the maternal venous plasma and gestational age in normal pregnancy (n=38, r=0.04, p=NS). The lipid peroxide level in the maternal venous plasma of preeclampsia (n=24) was significantly higher than that of gestational age-matched normal pregnancy (n=26), (4.39 +/- 0.38 vs. 3.23 +/- 0.15 nmol/mg protein, p<0.01). There was no significant correlation between the TRAP value in the maternal venous plasma and gestational age in normal pregnancy (n=38, r=0.02, p=NS). The TRAP value in the maternal venous plasma of preeclampsia (n=24) was significantly lower than that of gestational age-matched normal pregnancy (n=26), (0.33 +/- 0.02 vs. 0.38 +/- 0.02 mM, p<0.05). Ascorbic acid level in the maternal venous plasma of preeclampsia was significantly lower than that of normal pregnancy (377.8 +/- 23.6 vs. 552.2 +/- 52.1 nmol/mL, p<0.05). However, there was no significant difference in maternal venous plasma retinol, alpah-tocopherol, and gamma-tocopherol levels between normal pregnancy and preeclampsia. CONCLUSION: The above results suggest that the imbalance of increased lipid peroxidation and decreased antioxidant activity were in the maternal blood of preeclampsia, and an antioxidant vitamin, ascorbic acid, may be decreased result from counteracting free radical-mediated cell disturbance.
Antioxidants ; Ascorbic Acid ; Chromatography, Liquid ; Female ; gamma-Tocopherol ; Gestational Age ; Humans ; Lipid Peroxidation ; Lipid Peroxides ; Oxidative Stress ; Plasma* ; Pre-Eclampsia* ; Pregnancy ; Vitamin A ; Vitamins*

OBJECTIVE: To compare the clinical outcomes of GnRH antagonist (cetrorelix(R)) with those of conventional GnRH agonist for down-regulation in assisted reproductive cycle. Materials and Method: Ninety-nine women undergoing IVF or ICSI were treated with either GnRH antagonist (cetrorelix(R)) or GnRH agonist (Lucrin(R)) for pituitary down regulation. The patient characteristics, basal hormone profile and IVF outcome were compared. RESULTS: There were no significant differences in age and duration of infertility between two groups. E2 (pg/mL)/LH (mIU/mL)/FSH (mIU/ mL) on the 3 day of menstrual period as a baseline were also not significantly different between two groups. The number of hMG amples administered (30.5+/-11.2 versus 47.6+/-16.4 ample/cycle) and the duration of stimulation (11.0+/-1.7 versus 14.1+/-2.2 days) were significantly lower in the cetrorelix(R) group. There were no significant differences in the fertilization and pregnancy rates, the number of embryo transferred, the number of mature oocyte and the number of embryo obtained between two groups. CONCLUSION: The cycles using an antagonist protocol shows a shorter duration of stimulation with comparable outcomes with few injections than those with an agonist protocol. GnRH antagonist can be effectively used as GnRH agonist for pituitary down regulation in IVF-ET cycles.
Down-Regulation ; Embryonic Structures ; Female ; Fertilization ; Gonadotropin-Releasing Hormone* ; Humans ; Infertility ; Oocytes ; Pregnancy Rate ; Sperm Injections, Intracytoplasmic