Identification of hemoglobin Q India (α 1–64 Asp–His) through ARMS-PCR. First report from Pakistan

Various hemoglobinopathies have been reported from Pakistan excepting the rare ones like hemoglobin Q India. Our purpose of study was to identify the mutation (α 1 64 aspartate to histidine) through amplification restriction mutation system-polymerase chain reaction (ARMS-PCR) in patients where hemoglobin Q has been detected via high performance liquid chromatography (HPLC) and also to evaluate the cost effectiveness of the two technologies. All patients irrespective of age and gender who underwent HPLC for identification of their hemoglobin variant during January 1, 2006 to January 30, 2007 were studied. The blood samples with unknown peak at a retention time of 4.7 min were evaluated at the molecular level. Analysis of HPLC tracings of 11,008 subjects over a thirteen-month period identified ten individuals with hemoglobin Q. Male to female ratio was 1:1.5 and their age was variable ranging from 1 to 49 (mean 22.8) years. The mean hemoglobin level was 11.3 g/dl while MCV (fl) and MCH (pg) were 73.0 and 20.8 respectively. HPLC showed an unknown peak of 17.7% which was detected as Hb Q. ARMS based PCR showed Hb Q specific product of 370 bp and also an amplified product of 766 bp as the control fragment in these samples. This is the first ever report that documents the presence of Hb Q India (α 64 Asp to His) in Pakistani population. We recommend that HPLC be used as a useful screening tool especially in developing countries where PCR facilities may not be accessible.     

促红素对肝硬化大鼠血清—氧化氮含量的影响

目的探讨血红蛋白（Ｈｂ）对肝硬化大鼠血清一氧化氮（ＮＯ）含量及血流动力学的影响。方法应用５７Ｃｏ标记微球观察促红素长期治疗对肝硬化大鼠血流动力学参数的影响；应用荧光法测定大鼠血清ＮＯ含量。结果肝硬化大鼠全部出现高动力循环状态，且血清ＮＯ含量显著高于对照组、血Ｈｂ含量显著低于对照组；促红素治疗组，高动力循环状态明显改善，与未治疗组比较，Ｈｂ含量显著升高，血清ＮＯ含量显著降低。结论促红素致Ｈｂ增加，进而加速ＮＯ灭活对肝硬化高动力循环状态可能具有潜在治疗作用     

Human Hemoglobin Shares Bioactivities Ascribed to Human Tumor Necrosis Factor‐α

Hemoglobin mediated cytotoxicity and apoptosis has been evaluated in Tumor necrosis factor‐α (TNF‐α) sensitive cell line, U937 and compared with TNF‐α. Both species of hemoglobin, Hemoglobin A₂ and Hemoglobin A₀ induced apoptosis and cytotoxicity in U937 cell as measured by flow cytometry and 3‐(4,5‐dihydro‐6‐(4‐(3,4‐dimethoxybenzooyl)‐1‐piperazinyl)‐2(1H)‐quinoline (MTT) assay respectively. Different concentration of Hemoglobin A₀ (4 ng/mL to 4000 ng/mL) induced apoptosis ranging from 9% to 16% in U937 cells. 4000 ng/mL hemoglobin A₀ showed maximal apoptotic cells. TNF‐α showed 87% apoptotic U937 cells at concentration of 1 pg/mL. HbA₀ displayed cytotoxicity in U937 cell line at higher concentration in comparison to TNF‐α. 4000 ng/mL of hemoglobin A₀ showed optimal cytotoxic response in U937 cells. A dose response curve was also observed with varying doses of hemoglobin A₀. U937 cells pretreated with serum activated LPS for 1 hr and incubated with different concentration of hemoglobin or human TNF‐α for 24 h reduced the cytotoxic effect on U937. Dexamethasone treatment of U937 cells helped in protecting the HbA₀ and HbA₂ mediated cytotoxicity and anti‐TNF‐α antibody neutralized the hemoglobin mediated apoptosis and cytotoxicity. It is therefore apparent that human hemoglobin shares some of the bioactivities previously ascribed to TNF‐α. Sharing of bioactivities of TNF‐α by hemoglobin is interesting and suggests that cell free hemoglobin can mimic TNF‐α functionally.     

Sleep interventions and glucose metabolism: systematic review and meta-analysis

ObjectiveSleep disturbances (insufficient or poor sleep quality) have been linked to abnormal glucose metabolism. This systematic review and meta-analysis aimed to explore the effects of behavioral and pharmacological sleep interventions on glucose metabolism.MethodsMedline and Embase were used for systematic search. Studies reporting behavioral or pharmacological interventions in population with sleep disturbances, with measured outcomes of glucose metabolism and sleep parameters were selected.ResultsTwenty two studies were eligible for review (eight were conducted in people with type 2 diabetes). Studies were grouped into three types of intervention: sleep extension (n = 6), sleep education or cognitive behavioral therapy for insomnia (CBT-I, n = 6) and pharmacological interventions (n = 10). CBT-I and sleep education resulted in significantly improved self-reported sleep quality (Pittsburgh Sleep Quality Index, mean difference, MD, −1.31, 95% confidence interval (CI) −1.83, −0.80), non-significant reduction in hemoglobin A1c level (MD -0.35%, 95% CI -0.84, 0.13), and non-significant reduction in fasting glucose levels (MD -4.76 mg/dL, 95% CI -14.19, 4.67). Other studies were not eligible for meta-analysis due to heterogeneity of interventions or outcomes. Sleep extension was able to increase sleep duration by varying degrees in short sleepers, and five of six studies demonstrated relationships between the intervention and measures of insulin resistance. A majority of pharmacological intervention studies showed improved sleep but the effects on glucose metabolism were mixed.ConclusionsAvailable sleep interventions were effective in improving sleep but the effects on glucose metabolism were inconclusive. Larger randomized studies with consistent outcome measurements are needed to demonstrate this potential causal relationship.     

Effects of preoperative long-term glycemic control on operative outcomes following pancreaticoduodenectomy

Background

Diabetes mellitus is postulated to be both a risk factor and manifestation of pancreatic adenocarcinoma. This study evaluated the effects of preoperative glycemic control as determined by hemoglobin A1c (HbA1c) on outcomes following pancreaticoduodenectomy (PD).

Methods

A prospective cohort study whereby HbA1c was assessed preoperatively in 243 patients undergoing PD was performed. The primary outcome measure was operative morbidity. Secondary outcomes included individual adverse events, time to dietary resumption, and length of stay.

Results

Preoperative HbA1c ranged from 4.0% to 13.5%. Overall morbidity and incidence of specific adverse events were similar regardless of preoperative HbA1c. No correlation between HbA1c and length of stay, dietary resumption, or readmission was observed. Pancreatic fistula formation had a decreased incidence in patients with elevated versus normal HbA1c (2.2% vs 9.6%, P = .083).

Conclusions

PD can be safely performed in patients with HbA1c levels suggestive of poor long-term preoperative glycemic control. Medical efforts to optimize HbA1c should not delay resection.     

Restrictive Transfusion Practice During Extracorporeal Membrane Oxygenation Therapy for Severe Acute Respiratory Distress Syndrome

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials.     

The effects of long-term estradiol-17beta treatment on the growth and physiology of female triploid brook trout (Salvelinus fontinalis)

Triploid female fish show impaired gonadal development, which results in the production of only a few oocytes relative to diploids. The rate of maturation of these few oocytes in much slower relative to those of diploids and is attributed to an insufficient estradiol-17beta (E(2)) stimulus. Female triploid brook trout, aged 2+, were fed E(2) for seven months (i.e., July 1998 to February 1999) in an attempt to increase plasma E(2) comparable to diploid levels and thereby accelerate rates of oocyte growth. Compared to triploids fed a normal diet (i.e., control-triploids), the administration of 30 mg E(2)/kg feed to triploids (i.e., E(2)-treated-triploids) led to the development of secondary sex characteristics, a significant reduction in hematocrit and total blood hemoglobin level, a decrease in plasma testosterone and no weight gain. Plasma vitellogenin was significantly higher in E(2)-treated-triploids than in control-triploids and diploids at every month except October 1999. Although greater than in the control-triploids, plasma E(2) for the E(2)-treated-triploids did not attain the high levels shown by the diploids during the months of peak vitellogenesis (i.e., September and October). Following maturation and spawning of diploids, sacrificed E(2)-treated and control-triploids showed no differences in ovarian development or liver size. The E(2) dose for the treated-triploids was increased to 80 mg E(2)/kg feed for approximately seven more weeks in a further attempt to increase plasma E(2), with no success. It is suggested that the low plasma E(2) of the treated-triploids was the result of a high metabolic clearance rate.     

2010至2012年31省2120131名育龄妇女孕前营养指标趋势分析

目的 分析2010至2012年中国育龄妇女孕前营养状况的变化趋势.方法 研究人群为2010年1月1日至2012年12月31日参加“国家免费孕前优生健康检查项目”覆盖的31个省、市、自治区220个试点县的21～49岁育龄妇女,共2 120 131人.研究孕前营养指标主要包括体质量指数(BMI)、血红蛋白含量(HB)和空腹血糖(FBG).结果 2010至2012年总体上中国育龄妇女孕前平均HB含量持续升高,而孕前平均BM1和FBG水平呈逐年下降趋势.将3个孕前营养指标测定的结果均分为4类,各类构成人群均主要分布在25 ～34岁年龄组.孕前低BMI人群发生率逐年增加,从2010年10.4％(31 649/304307)增加到2012年14.14％(114 159/807 131);孕前超重人群及肥胖人群均在2012年发生率最低,分别为10.65％(85 984/807 131)和2.32％(18 735/807 131).孕前低血糖发生率由2010年5.45％(16 581/304307)降至2012年5.23％(42 199/807 131);孕前空腹血糖受损及糖尿病发生率逐年降低,分别从2010年3.17％ (9 652/304 307)和1.64％(4 982/304307)降至2012年2.71％(21 875/807 131)和1.05％(8 505/807 131).孕前轻度及中重度贫血的发生率在逐年下降,分别从2010年12.29％和0.95％降至2012年9.62％和0.78％;孕前高HB含量人群也呈现不断下降趋势.2010至2012年中国育龄妇女3个孕前营养指标的变化趋势在4个分类中均差异有统计学意义(P ＜0.001).结论 中国育龄妇女总体孕前营养状况良好,肥胖、贫血及糖尿病的发生率呈逐年下降趋势.