SELF-REPORTED HEARING LOSS AMONG WORKERS EXPOSED TO INDUSTRIAL NOISE. ANALYSIS OF U.S. SURVEILLANCE DATA WITH REFERENCE TO THE AUSTRALIAN ENVIRONMENT

Aging and noise are the two main causes of hearing loss. To estimate the extent to which hearing loss is due to noise and is therefore preventable, an analysis was undertaken, using U.S. surveillance data, of the prevalence of hearing loss in workers in industries categorised according to the percentages of the workforce exposed to noise levels of 85 dBA or more. It was estimated that 13 per cent of the U.S. workforce was exposed to these noise levels, and that occupational noise exposure accounted for 20 per cent of self-reported hearing loss in the male workforce. Applying the industry-specific exposures to Australia, it is estimated that some 657,000 workers are exposed to noise levels of 85 dBA or more in this country. Australian Bureau of Statistics data indicate that constant noise accounts for 38 per cent of self-reported hearing loss in Australian adult males (although this figure would include hearing loss due to non-occupational noise). Data from both countries indicate that the prevalence of noise-induced hearing loss in females is negligible.     

Quantitative structure-activity relationships in MAO-inhibitory 2-phenylcyclopropylamines: Insights into the topography of MAO-A and MAO-B

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno ⁻, m⁻, p⁻ isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows: pI₅₀=0.804 Π² Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI₅₀=1.815 π-0.825 Π² R+0.900 Es²+0.869 Es³+0.796 Es⁴−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group, a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position, and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.     

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

抗凝血酶Ⅲ测定在评价肝脏功能中的应用

测定110例肝病的抗凝血酶Ⅲ(AT-Ⅲ)活性,62例低于正常(56.4％),均值为60.1±38.2％。50例正常对照为100.0±26.7％。重症肝炎、慢性活动性肝炎及失代偿期肝硬化活性显著下降,均值分别为12.9±13.0％、51.0±34.6％、43.3±29.6％.AT-Ⅲ活性在评价肝脏功能方面较凝血酶原时间敏感,具有一定的实用意义。     

Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.     

选择性靶动脉栓塞在骶骨肿瘤切除术中的价值

目的 探讨和评估选择性靶动脉栓塞骶骨肿瘤后对外科切除肿瘤的价值和方法。方法 运用Seldinger技术，对9例骶骨肿瘤患者进行肿瘤供血动脉及肿瘤内血管全部彻底栓塞，栓塞材料应用明胶海绵，栓塞后1周内行手术切除术。结果 彻底的术前栓塞手术中失血量明显减少，9例骶骨肿瘤均得到彻底切除，平均失血量为1090ml。术后平均随访15个月，未见肿瘤局部复发。结论 骶骨肿瘤切除术前选择性靶动脉栓塞可有效减少术中出血，有利于肿瘤的彻底切除，为顺利切除骶骨肿瘤提供了有价值的方法。     

Synthesis of two nitro analogs of tranylcypromine: Relations of aromatic substitution of nitro groups to MAO-Inhibitory activity

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH₃CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10^?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC₅₀ values, 2.5×10^?7M and 1.4×10^?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions.     

N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats

Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.