Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene

Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be specific biomarkers of exposure to benzene. We analyzed BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19 workers and 19 controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. The adducts were analyzed by gas chromatography-mass spectrometry following reaction of the protein with trifluoroacetic anhydride and methanesulfonic acid. When subjects were divided into controls (n = 42) and workers exposed to < or =31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure: Spearman r = 0.67, P < 0.0001). To our knowledge, these results represent the first observation in humans that BO-Hb levels are significantly correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting a significant correlation with exposure (Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from both Hb and Alb adducts was very similar. These results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of exposure to high levels of benzene. As part of our investigation of the background levels of BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the observed background adducts reflect an artifact of the assay, while other portions are indicative of either unknown exposures or endogenous production of adducts.      

Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene

Two of the most common cytogenetic changes in therapy- and chemical- related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.      

新生儿复苏培训项目十年回顾

每年约2000万新生儿出生的中国，鼓励一对夫妻只生一个孩子，随着国民经济迅速发展，生活水平不断提高，每一个新生儿的健康都受到家庭及社会的高度关注。1991年中国要儿死亡率为50．2‰，1998年降至33．3‰，地区性差别很大，贫困地区最高可达56‰，一些条件较好的城市低至7．5‰。围产医学界公认围产窒息为要儿患病及死亡的首要原因，如合并早产、严重肺、脑疾病等后果更为严重。     

Tetraplegia in the immediate postoperative period of stapedectomy

Management of the cervical spine in orotracheal intubation for general anesthesia is an important aspect of daily practice in anesthesiology. Also important are the requirements, techniques and consequences of patient position during surgery. We report a case of tetraplegia during the early postoperative period after stapedectomy for otosclerosis. After surgery, the spontaneously breathing patient was transferred to the recovery room, where a clinical picture of anesthesia and paralysis of all four limbs was evident. We ordered an emergency magnetic resonance image of the cervical spine, which revealed a massive acutely herniated disk at C6-C7 with signs of ischemia or necrosis of the medulla at the same level. After eight months, the patient was still paraplegic and lacked sensation in the lower limbs. Sensation and motor function in the upper limbs was nearly normal. We review the etiopathogenetic mechanisms that might be responsible for this clinical profile.     

Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.     

Hemorragia y morbilidad asociada al uso de ácido tranexámico en cirugía cardiaca. Estudio multicéntrico de cohortes retrospectivo

IntroductionPostoperative bleeding is common complication, affecting up to 20% of patients, after cardiac bypass surgery. Fibrinolysis is one of the causes of this excessive bleeding, and for this reason the use of tranexamic acid is recommended. The problem with using this is that there are numerous guidelines and differences in the dose to be administered. Our aim was to evaluate whether there were any differences in postoperative bleeding and morbidity after cardiac surgery with the administering of different tranexamic acid doses in three university hospitals.Material and methodsA retrospective, multicentre cohort study was conducted. A total of 146 patients who were subjected to elective cardiac bypass surgery according to the anaesthetic-surgical protocol of each hospital were included in the study. The clinical histories were reviewed, and they were divided into two groups according to the tranexamic acid dose: Group A (high doses), initial dose of 20 mg/kg and continuous infusion of 4 mg/kg/hour until closure of the sternotomy. A further 100 mg was added to prime the bypass machine. Group B (low doses), initial dose of 10 mg/kg followed by a continuous infusion of 2 mg/kg/hour until closure of the sternotomy. A further 50 mg was added to prime the bypass machine. Variables, such as age, sex, weight, height, type of surgical procedure (valvular, coronary or mixed), haematocrit, INR, and preoperative platelet count, time and temperature of the bypass machine, and haematocrit on sternum closure, were recorded. Among the post-operative variables collected were: debit due to drainage at 6, 12 and 24 hours after surgery, number and type of blood products transfused in the first 24 hours, need for further surgery due to haemorrhage, CVA, TIA, or a new acute myocardial infarction, convulsions, and mortality.ResultsThe incidence of increased bleeding (patients in the 90 percentile) was higher in Group B at all the study evaluation times (P<.05). The incidence of further surgery due to bleeding, and the need for transfusion of ≥3 units of packed red cells was lower in Group A (5.56%) than in Group B (13.89%). There were no significant differences in the requirements for blood products transfusions between the groups. As regards associated morbidity, there was one isolated case of convulsion and a perioperative AMI in another case in Group A, and three cases of perioperative AMI in Group B.ConclusionsElevated doses of tranexamic acid in cardiac bypass surgery appear to significantly reduce bleeding in the first hours after surgery compared to low doses. However, this decrease did not lead to a reduction in the needs for blood products.     

Limitaciones del tratamiento anticoagulante

Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.     

pH,base deficit or lactate. Which is better for predicting neonatal morbidity?

Objective: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term.

Method: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH?≤?7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index.

Results: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH?≤?7.0 and lactate?≥?7.0?mmol/L presented similar validity to that of pH?≤?7.0 and BD?≥?12?mmol/L, but both were comparable to pH alone.

Conclusions: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes.