KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

Removing the by-products acetic acid and NH4 + from the L-tryptophan broth by vacuum thin film evaporation during L-tryptophan production

Background: During L-tryptophan production by Escherichia coli, the by-products, acetic acid and NH4 +, accumulate in the fermentation broth, resulting in inhibited cell growth and activity and decreased L-tryptophan production. To improve the L-tryptophan yield and glucose conversion rate, acetic acid and NH4 + were removed under low-temperature vacuum conditions by vacuum scraper concentrator evaporation; the fermentation broth after evaporation was pressed into another fermenter to continue fermentation. To increase the volatilisation rate of acetic acid and NH4 + and reduce damage to bacteria during evaporation, different vacuum evaporation conditions were studied. Results: The optimum operating conditions were as follows: vacuum degree, 720 mm Hg; concentration ratio, 10%; temperature, 60°C; and feeding rate, 300 mL/min. The biomass yield of the control fermentation (CF) and fermentation by vacuum evaporation (VEF) broths was 55.1 g/L and 58.3 g/L at 38 h, respectively, (an increase of 5.8%); the living biomass yield increased from 8.9 (CF) to 10.2 pF (VEF; an increase of 14.6%). L-tryptophan production increased from 50.2 g/L (CF) to 60.2 g/L (VEF) (an increase of 19.9%), and glucose conversion increased from 18.2% (CF) to 19.5% (VEF; an increase of 7.1%). The acetic acid concentrations were 2.74 g/L and 6.70 g/L, and the NH4 + concentrations were 85.3 mmol/L and 130.9 mmol/L in VEF and CF broths, respectively. Conclusions: The acetic acid and NH4 + in the fermentation broth were quickly removed using the vacuum scraper concentrator, which reduced bacterial inhibition, enhanced bacterial activity, and improved the production of L-tryptophan and glucose conversion rate.

Influence of intensive insulin therapy on insulin resistance of patients with severe burn or trauma / 中华烧伤杂志

<p><b>OBJECTIVE</b>To discuss the influence of intensive insulin therapy on insulin resistance of patients with severe burn or trauma.</p><p><b>METHODS</b>Sixty patients with severe burn or trauma hospitalized in the Third People's Hospital of Chongqing or Southwest Hospital of the Third Military Medical University from January 2010 to December 2011 were randomly divided into intensive insulin therapy group (IT, treated with intensive insulin therapy to control the blood glucose to the level of 6.0-8.0 mmol/L) and control group (C, treated with routine therapy) according to the paired grouping method, with 30 patients in each group. Before treatment and on post treatment day (PTD) 1, 3, 7, 10, 14, the levels of fasting blood glucose and fasting plasma insulin were determined. Insulin resistance index and β-cell function index were calculated using homeostasis model assessment. Data were processed with t test, analysis of variance, and LSD test.</p><p><b>RESULTS</b>On PTD 1, 3, 7, 10, levels of fasting blood glucose in group IT [(6.8 ± 1.4), (6.7 ± 1.3), (5.8 ± 1.9), (5.4 ± 1.6) mmol/L] were significantly lower than those of group C [(14.8 ± 4.9), (12.7 ± 3.7), (7.7 ± 1.9), (6.6 ± 1.3) mmol/L, with t values respectively 12.453, 11.386, 5.563, 4.731, P < 0.05 or P < 0.01]. On PTD 3, 7, levels of fasting insulin in group IT [(14 ± 5), (10 ± 3) mU/L] were significantly lower than those of group C [(16 ± 4), (13 ± 4) mU/L, with t values respectively 4.212, 4.364, P values below 0.05]. Levels of fasting blood glucose and fasting insulin in the two groups at each time point were statistically significantly different from those before treatment (with P values below 0.01), except for the level of fasting blood glucose on PTD 3. On PTD 1, 3, 7, 10, levels of insulin resistance index in group IT (1.60 ± 0.80, 1.46 ± 0.70, 0.96 ± 0.21, 0.90 ± 0.23) were significantly lower than those in group C (2.15 ± 1.35, 2.21 ± 1.21, 1.50 ± 0.95, 1.17 ± 0.66, with t values respectively 8.316, 10.607, 7.825, 5.217, P < 0.05 or P < 0.01). Levels of insulin resistance index of patients in the two groups at each time point after treatment were significantly lower than those before treatment (with P values below 0.01). On PTD 1, 3, 7, levels of β-cell function index in group IT (4.6 ± 2.9, 4.5 ± 3.3, 4.5 ± 3.6) were significantly higher than those in group C (3.4 ± 2.5, 3.6 ± 2.2, 4.2 ± 2.5, with t values respectively 8.243, 7.914, 4.338, P < 0.05 or P < 0.01). Levels of β-cell function index in group C on PTD 1 and 3 were significantly lower than that before therapy (with P values below 0.05).</p><p><b>CONCLUSIONS</b>Intensive insulin therapy can alleviate insulin resistance of patients with severe burn or trauma.</p>

Magnetic resonance image of sellar region in pituitary stalk interruption syndrome in children and adolescents / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the magnetic resonance imaging (MRI) manifestations of sellar region of children and adolescents with pituitary stalk interruption syndrome (PSIS).</p><p><b>METHODS</b>Thirty-one PSIS cases were selected from February 2001 to August 2010 in Peking Union Medical College Hospital. MRI images were collected to calculate the volume and coronary area of the pituitary based on its measured height, width, and anteroposterior diameter. The results of the measurement were retrospectively analyzed together with clinical data.</p><p><b>RESULTS</b>The patients in this study included 28 males and 3 females, aged 16.5∓3.8 years (range, 6~25 years). MRI images showed pituitary stalk rupture associated with ectopic posterior pituitary in 16 cases, significantly thinner or unclear pituitary stalk in 15 cases, in which 7 cases were found with vacuole turcica. All the 31 patients presented with reduced pituitary volume and dysfunction of anterior pituitary.</p><p><b>CONCLUSION</b>PSIS may show pituitary stalk interruption with ectopic posterior, thinning or unclear of pituitary stalk, and with a variety of anterior pituitary hormone deficiency.</p>

Effects of intensive insulin therapy on inflammatory response and prognosis of patients with severe trauma / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effects of intensive insulin therapy on inflammatory response and prognosis of patients with severe trauma.</p><p><b>METHODS</b>Eighty severely injured patients were divided into intensive insulin therapy group (n = 40, IT) and routine therapy group (n = 40, RT) in random pair. At the time of admission, a continuous infusion of insulin (2-4 U/h) was pumped into the patients of IT group to maintain blood glucose level at 6-8 mmol/L. Patients in RT group were given routine treatment without administration of insulin. Fever, organ injury, and mortality of patients in 2 groups were recorded. Venous blood was drawn from patients of 2 groups on the morning of post treatment day (PTD) 1, 3, 5, and 7. Values of TNF-alpha, C-reactive protein (CRP), IL-2, and IL-10 in plasma were assayed.</p><p><b>RESULTS</b>High fever appeared in 9 patients in IT group, and WBC exceeded 10.0 x 10(9) for more than 3 days in 17 patients in this group, versus 20 and 29 patients respectively in RT group. Dysfunction of 1 organ appeared in 31 patients in IT group and 30 patients in RT group. Dysfunction of 3 organs appeared in 10 patients in IT group and 19 patients in RT group. Dysfunction of 4 organs appeared in 7 patients in IT group and 12 patients in RT group. In IT group, 4 patients died within 3 post-injury day (PID), and 1 patient died after PID 3 (total case fatality: 12.5%). In RT group, 5 patients died within 3 PID, and 4 patient died after PID 3 (total case fatality: 22.5%). Plasma levels of TNF-alpha and CRP of patients in IT group were significantly lower than those of patients in RT group on PID 3-7 ( P < 0.05 or P < 0.01), while levels of IL-2 and IL-10 of patients in IT group were significantly higher than those of patients in RT group (P < 0.05 or P < 0.01). Plasma levels of TNF-alpha (1.3 +/- 0.6 microg/L) and CRP (55 +/- 16 mg/L) of patients in IT group on PTD 7 were lowered to the trough level, and they were significantly lower than those of patients in RT group (3.0 +/- 0.8 microg/L, 89 +/- 20 mg/L, respectively, P < 0.01).</p><p><b>CONCLUSIONS</b>Intensive insulin therapy can mitigate systemic inflammatory response and improve prognosis of patients with severe trauma.</p>

Influence of delayed rapid fluid resuscitation on oxygen metabolism in dogs with burn shock / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of delayed rapid fluid resuscitation on oxygen metabolism in dogs with burn shock.</p><p><b>METHODS</b>Twenty-four mongrel dogs inflicted with 40% TBSA full thickness scald were enrolled in the study and randomly divided into burn control (C), delayed even fluid replacement (E), and delayed rapid fluid replacement (R) groups, with 8 dogs in each group. The changes in oxygen delivery (DO(2)), oxygen consumption (VO(2)), oxygen extraction (O(2)ext) and blood base deficit (BD), and lactate (LA) were determined before scalding and at 2, 6, 8, 12, 24, 36 and 48 post scalding hours (PSHs).</p><p><b>RESULTS</b>The DO(2) in each group was decreased obviously after scalding and was evidently lower than that before injury (P < 0.01), while the O(2)ext value markedly increased compared with that before scalding (P < 0.01). After fluid resuscitation, DO(2) and VO(2) in E and R groups increased, but O(2)ext decreased. The values of DO(2), VO(2) and O(2)ext showed significant differences between R and E groups at 8 PSH (R group vs E group, DO(2): 7.35 +/- 0.21 L.min(-1).m(2) vs 5.32 +/- 0.96 L.min(-1).m(2), P < 0.01; VO(2): 2.02 +/- 0.58 L.min(-1).m(2) vs 1.71 +/- 0.38 L.min(-1).m(2), P < 0.01); The blood BD levels in each group were remarkably lower after scald than that before scald (P < 0.01), and they gradually increased after fluid replacement. The blood BD level in R group at 8 PSH (-6.5 +/- 0.7 mmol/L) was obviously higher than that in E group (-9.3 +/- 1.4 mmol/L, P < 0.01). The blood LA level in each group were evidently higher than that before scald (P < 0.01), and they decreased after fluid replacement. The blood LA level in R group at 8 PSH (2.30 +/- 0.20 mmol/L) was obviously lower than that in E group (2.67 +/- 0.30 mmol/L, P < 0.01)</p><p><b>CONCLUSION</b>Rapid fluid replacement could improve tissue oxygen metabolism, which was beneficial to the correction of tissue oxygen supply when fluid resuscitation was delayed.</p>

Effect of delayed rapid fluid resuscitation on blood viscosity in burn shock dogs / 第三军医大学学报

Objective　To investigate the effect of rapid fluid replacement on hemorheology in delayed resuscitation after burn. Methods　A total of 32 dogs inflicted with 40%TBSA full thickness scalding were randomly divided into 4 groups: scald control group(C group), delayed Gelofusion even replacement group (GE group), rapid fluid replacement group (GR group), and delayed plasma rapid fluid replacement group (PR group). The femoral arterial pressure, viscosity of blood and plasma, packed cell volume and aggregation of RBC were detected at the intervals of before and 2, 6, 8, 12, 24, 36 and 48 hours after scalding. Results　The viscosity of blood markedly increased at 2 hours after scalding, and the hemorheology parameters decreased after fluid resuscitation. The hemorheologic parameters were obviously lower in GR group than in GE group at 2 hours after rapid resuscitation, the viscosity of blood and RBC aggregation in GR group were obviously lower than those in PR group. Conclusion　Under the condition of delayed resuscitation after burn, rapid fluid replacement can quickly decreased the state of blood high viscosity and may play a role in improving microcirculation and treating burn shock.

Effect of delayed rapid fluid resuscitation on blood viscosity in burn shock dogs / 第三军医大学学报

Objective　To investigate the effect of rapid fluid replacement on hemorheology in delayed resuscitation after burn. Methods　A total of 32 dogs inflicted with 40%TBSA full thickness scalding were randomly divided into 4 groups: scald control group(C group), delayed Gelofusion even replacement group (GE group), rapid fluid replacement group (GR group), and delayed plasma rapid fluid replacement group (PR group). The femoral arterial pressure, viscosity of blood and plasma, packed cell volume and aggregation of RBC were detected at the intervals of before and 2, 6, 8, 12, 24, 36 and 48 hours after scalding. Results　The viscosity of blood markedly increased at 2 hours after scalding, and the hemorheology parameters decreased after fluid resuscitation. The hemorheologic parameters were obviously lower in GR group than in GE group at 2 hours after rapid resuscitation, the viscosity of blood and RBC aggregation in GR group were obviously lower than those in PR group. Conclusion　Under the condition of delayed resuscitation after burn, rapid fluid replacement can quickly decreased the state of blood high viscosity and may play a role in improving microcirculation and treating burn shock.