A Curated Review of Recent Literature of Biomarkers Used for Assessing Air Pollution Exposures and Effects in Humans

This is a cross-sectional review of biomarkers used in air pollution research from January 2009 through December 2012. After an initial keyword search in PubMed retrieving 426 articles, a comprehensive abstract review identified 54 articles of experimental design that used biomarkers of exposure or effect in human studies in the area of air pollution research during this specified time period. A thorough bibliographic search of the included articles retrieved an additional 65 articles meeting the inclusion criteria. This review presents these 119 studies and the 234 biomarkers employed in these air pollution research investigations. Data presented are 70 biomarkers of exposure with 54% relating to polycyclic aromatic hydrocarbons, 36% volatile organic carbons, and 10% classified as other. Of the 164 biomarkers of effect, 91 and 130 were used in investigating effects of short-term and chronic exposure, respectively. Results of biomarkers used in short-term exposure describe different lag times and pollutant components such as primary and secondary pollutants, and particle number associated with corresponding physiological mechanisms including airway inflammation, neuroinflammation, ocular, metabolic, early endothelial dysfunction, coagulation, atherosclerosis, autonomic nervous system, oxidative stress, and DNA damage. The review presents three different exposure scenarios of chronic, occupational, and extreme exposure scenarios (indoor cooking) with associated biomarker findings presented in three broad categories of (1) immune profile, (2) oxidative stress, and (3) DNA damage. This review offers a representation of the scope of data being explored by air pollution researchers through the use of biomarkers and has deliberately been restricted to this particular subject rather than an extensive or in-depth review. This article provides a contextualization of air pollution studies conducted with biomarkers in human subjects in given areas while also integrating this complex body of information to offer a useful review for investigators in this field of study.     

微创伤显微外科治疗高血压脑出血118例的临床分析

1临床资料本组118(男75,女43)例患者均为高血压脑出血.入院后查头颅CT显示:基底节区出血102例,脑叶出血16例,其中破入脑室56例,根据多田公式计算,出血量均大于35 mL,最大出血量约120 mL,伴中线结构移位者78例;年龄40~85(平均63)岁.     

42Gastric emptying response to temporary gastric electrical stimulation is independent of symptom improvement but dependent on baseline emptying

Introduction:  Gastric electrical Stimulation (GES) is an accepted therapy for drug refractory gastroparesis, but its effect on gastric emptying is controversial.
Patients:  To examine the effect of GES on GET we examined 140 consecutive patients undergoing temporary endoscopic GES as previously described (GIE 2005: 61:455–461). Patients were 29 m, 14 f , mean age 41 years with diagnosis (DX): 44 diabetes (DM), 14 post-surgical (PS) and 82 idiopathic (ID).
Methods:  Symptom Assessment, Gastric emptying and EGG were evaluated at baseline and after temporary endoscopic GES (mean 3 day of therapy). Patients at baseline were stratified into 3 groups based on GET: Delayed, Normal and Rapid, as previously described (AGC 2001: 95:1456–1461). Symptoms (SX) of nausea (N), vomiting (V), and total SX (TSS), and GET were compared by paired t-tests and reported as mean values.
Results:  All patients had Symptoms improvement, irrespective of their DX or baseline GET: (N: 3.5 baseline to 0.9 after; V: 2.5–0.6; TSS: 15.2–5.1 for all patients with uniform changes in subgroups. There were no significant changes in GET for the whole patient group. However, when stratified by baseline GET: the delayed group accelerated (and the rapid group slowed (see table).
Conclusion:  Temporary GES performed on patients with the SX of gastroparesis shows an immediate symptom improvement, which is independent of baseline GET. The effect of temporary GES on gastric emptying is dependent on baseline emptying, with improvements seen in both delayed and rapid gastric emptying sub-groups. Conclusions about the effect of electrical stimulation on gastric emptying need stratification for baseline gastric emptying.
 

     

23A multi-component model can predict gastric emptying in diabetic gastroparesis

Introduction:  We have previously reported that a multi-component model of autonomic and enteric factors can help predict gastric emptying in diabetes mellitus. (Aslam N. Abell T. A four component model can quantitatively profile gastric emptying in diabetic gastropathy. Supplement to Gastroenterology Vol 118, April 2000, Number 4, Suppl 2. (Abstract No. 5341).
Patients:  Eighty-seven patients with Diabetes mellitus presenting with signs and symptoms of Gastroparesis. It included 38 males, 49 females with mean age of 39 ± 10 years.
Methods:  Autonomic tests included adrenergic tests by VC (vasoconstriction to cold) and PAR (postural ratio), and cholinergic function measured by EKG R to R interval (RRI). The Enteric measure (EGG) was measured by cutaneous electrogastrogram. The data was compared to results of standardized solid gastric emptying T50 in minutes (GE above), by linear regression.
Results:  The patients were distributed in five groups according to mean T50 of solid gastric emptying: 24 (28%) were very delayed, 13 (15%) delayed, 19 (22%) were normal, 15 (17%) were rapid, and 16 (18%) very rapid. There were statistically significant differences among the five group means for VC, RRI, and EGG, but not for PAR. (See table).
Conclusions:  In this group of patients with symptoms of Diabetic gastropathy, there is a wide range of gastric emptying values. A multi-component model demonstrates specific autonomic and enteric differences in subgroups of diabetic gastroparesis. Therapies for diabetic gastropathy, including drug and device studies, may need to take into account these physiologic differences when looking at therapeutic outcomes. Autonomic and enteric measure appear useful as part of the evaluation of patients with symptoms of diabetic gastropathy.
Means
 

     

Radical resection of focal brainstem gliomas： is it worth doing？

OBJECTIVES： Despite revolutionary technical advancement in neuroimaging and operative neurosurgery, surgical extirpation of focal brainstem glioma （BSG） remains steeped in controversy. In this study, we evaluated our senior author＇s （CT） surgical experience in radically treating these turnouts in children to determine the safety and efficacy of such approach. MATERIALS AND METHODS： Thirty-four consecutive patients aged between 3 and 16 years who underwent endoscope-asslsted microsurgery for focal BSG with the intent of radial resection from 1999 to 2005 were evaluated.     

10A multi-component model can predict outcome of restrictive surgery for obesity at baseline and 3 months

Introduction:  We previously reported that a multi-component model of autonomic and enteric factors may correlate with ultimate weight loss or gain after restrictive obesity surgery (NGM 2005; 17:472).
Patients:  We report on 39 patients, 4 male, 35 female, mean age 37.2 years, followed for up to 16 years post-operatively after vertical banded gastroplasty.
Methods:  Two autonomic measures (adrenergic: PAR and VC and cholinergic: RRI) and one enteric measure (electrogastrogram: EGG) were recorded at baseline as previously described (DDS 44: 74s–78s, 1999). We performed a discriminant function analysis to investigate whether a patient's EGG, PAR, RRI, and VC values could be used to classify that patient as a loser or gainer following weight control surgery. The patients were divided into two categories (10 gainers, 29 losers), depending on the latest weight compared to baseline; discriminant criterion derived from the patient's data was applied to each patient's autonomic and enteric values to determine whether these measurements separated the patients into their true weight category.
Results:  A discriminate model based on baseline measures successfully predicted ultimate weight gain in 8/10 (80%) of patients who subsequently gained weight and weight loss in 24/29 (83%) of patients who in subsequently lost weight for a total correct classification rate of 32/39 (82%). The same model with data at 3 months post-operatively predicted weight gain in 9 of 10 (90%) of patients and weight loss in 24 of 29 (83%) of patients, for a total correct classification rate of 34/39 pts (87%) (See table).
Conclusions:  A multi-component model demonstrates that baseline and 3 months post-operative measures can predict ultimate weight outcome from restrictive obesity surgery.
 

     

Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype

This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH- DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis.      

Mechanism of erythrocyte aggregation and sedimentation

Unstirred suspensions of erythrocytes form stable spherical aggregates of uniform size. The radius of the spheres depends upon the suspending medium and the hematocrit. Erythrocyte suspensions will undergo sedimentation only after these aggregates are formed. Aggregation is a two-step process: first, erythrocytes associate in long chains (rouleau formation). Next, these chains form spheres of uniform size. The requirements for this well-defined process are an electrolyte and a neutral or negatively charged macromolecule in the solution and a metabolically active red cell. If these conditions are not met, red cells either will not aggregate at all or will form amorphous aggregates. Rouleau formation and sedimentation are inhibited by 4,4'- diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor of anion transport, but not by ouabain, a cation transport inhibitor. The kinetics of erythrocyte sedimentation reflects the aforementioned mechanism: no sedimentation occurs during rouleau formation. Once the spheres of uniform size are formed, they will settle according to the Einstein-Stokes equation. In this model, parameters of sedimentation kinetics are the delay before sedimentation starts, the rate of sedimentation in the steady state, and the radius of the sedimenting aggregate. The radius can be calculated from the rate of fall of the aggregates and agrees well with the microscopically observed radius. It is inversely proportional to the hematocrit, which explains the elevated sedimentation rates in anemia.     

Sp alpha I/65: a new variant of the alpha subunit of spectrin in hereditary elliptocytosis

Two molecular defects involving the spectrin heterodimer (SpD) contact site of the alpha chain (the alpha I domain) were previously identified using limited tryptic digestion followed by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both are characterized by atypical peptide maps which reveal a marked decrease of the 80,000-dalton alpha I domain and a formation of new major peptides of either 74,000 (Sp alpha I/74) or 46,000 (Sp alpha I/46) daltons. We now report a third variant of the spectrin alpha chain, designated Sp alpha I/65, in three unrelated black families. In all three probands, the percentage of SpD in the low ionic strength (O degrees C) membrane extracts was increased to 19% to 32%. One- and two- dimensional electrophoretic separations of limited tryptic digests of spectrin from all three probands revealed a decrease of the alpha I domain of spectrin and the concomitant appearance of peptides at 65,000 daltons and isoelectric points ranging from 5.2 to 5.3. The abnormal 65,000-dalton peptides could be stained with an antiserum which had been raised against the alpha I domain, indicating that it was derived from the alpha I domain.