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.      

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder.

The symptoms of bipolar disorder suggest dysfunction of anterior limbic networks that modulate emotional behavior and that reciprocally interact with dorsal attentional systems. Bipolar patients maintain a constant vulnerability to mood episodes even during euthymia, when symptoms are minimal. Consequently, we predicted that, compared with healthy subjects, bipolar patients would exhibit abnormal activation of regions of the anterior limbic network with corresponding abnormal activation of other cortical areas involved in attentional processing. In all, 10 unmedicated euthymic bipolar patients and 10 group-matched healthy subjects were studied with fMRI while performing the Continuous Performance Task-Identical Pairs version (CPT-IP). fMRI scans were obtained on a 3.0 T Bruker system using an echo planar imaging (EPI) pulse sequence, while subjects performed the CPT-IP and a control condition to contrast group differences in regional brain activation. The euthymic bipolar and healthy subjects performed similarly on the CPT-IP, yet showed significantly different patterns of brain activation. Specifically, bipolar patients exhibited increased activation of limbic, paralimbic, and ventrolateral prefrontal areas, as well as visual associational cortices. Healthy subjects exhibited relatively increased activation in fusiform gyrus and medial prefrontal cortex. In conclusion, these differences suggest that bipolar patients exhibit overactivation of anterior limbic areas with corresponding abnormal activation in visual associational cortical areas, permitting successful performance of an attentional task. Since the differences occurred in euthymia, they may represent trait, rather than state, abnormalities of brain function in bipolar disorder.     

Pediatric Emotion Dysregulation: Biological and Developmental Evidence for a Dimensional Approach

The following review article examines the value of a dimensional approach to research in relation to recent findings of child and adolescent emotion dysregulation. With the publication of the DSM-5, it is important to keep in mind that difficulties in pinpointing causal mechanisms may result from the collective grouping of different emotional deficits by diagnoses. Evidence available from studies examining pediatric emotion dysregulation indicate strengths in the dimensional approach for research, especially in light of developmental changes to neural activations of emotion regulation. Use of a dimensional approach in research appears to be an effective tactic that could pave the way for a better understanding of pediatric emotion dysregulation and thereby elucidate better treatments and outcomes for those with this behavioral deficit, regardless of diagnosis.