Reactive oxygen species: a breath of life or death?

New insights into cancer cell-specific biological pathways are urgently needed to promote development of rationally targeted therapeutics. Reactive oxygen species (ROS) and their role in cancer cell response to growth factor signaling and hypoxia are emerging as verdant areas of exploration on the road to discovering cancer's Achilles heel. One of the distinguishing and near-universal hallmarks of cancer growth is hypoxia. Unregulated cellular proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. The resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival, including apoptosis suppression, altered glucose metabolism, and an angiogenic phenotype. Ironically, recent investigations suggest that oxygen depletion stimulates mitochondria to elaborate increased ROS, with subsequent activation of signaling pathways, such as hypoxia inducible factor 1alpha, that promote cancer cell survival and tumor growth. Because mitochondria are key organelles involved in chemotherapy-induced apoptosis induction, the relationship between mitochondria, ROS signaling, and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel avenues to facilitate discovery of cancer-specific therapies. Preclinical and clinical evaluation of agents that modify ROS signaling in cancer offers a novel avenue for intervention. This review will cover recent work in ROS-mediated signaling in cancer cells and its potential as a target for developmental therapeutics.     

Survey of psychiatric disorders in a Taiwanese village population six months after a major earthquake.

BACKGROUND AND PURPOSE: The catastrophic Chi-Chi earthquake of September 21, 1999 in Taiwan provided a unique opportunity to study the disaster's psychiatric impact on survivors. This study assessed the development of psychiatric disorders among residents in a Taiwanese village near the epicenter of the earthquake within 6 months of the disaster. METHODS: A total of 442 of the 602 actual living residents of Tong-Chi village who were over 16 years of age and were present in the community at the time of the earthquake were included in this population survey. Subjects were interviewed by psychiatrists using the Mini-International Neuropsychiatric Interview and questionnaires to collect demographic information and risk factors for psychiatric disorders 4 to 6 months after the earthquake. RESULTS: The prevalence rates were 9.5% for current major depression, 2.8% for past major depressive episode, and 7.9% for post-traumatic stress disorder (PTSD). Females had significantly higher rates of most psychiatric disorders. After controlling for covariates, the significant risk factors for PTSD were female gender and having sought medical service after the earthquake. Significant risk factors for major depressive episode were divorced/widowed status, education level equal to or below primary school, and prominent house damage. CONCLUSION: This population survey of earthquake disaster survivors found an increased prevalence of psychiatric disorders after exposure to a catastrophic earthquake. These results highlight the need for prompt therapeutic attention to residents of earthquake disaster areas after the event.     

Is herpes zoster a marker for occult or subsequent malignancy?

BACKGROUND: It has been suggested that herpes zoster may be a marker for occult malignancy. AIM: To examine the emergence of a subsequent cancer diagnosis in patients with and without herpes zoster. DESIGN OF STUDY: Retrospective cohort study. SETTING: Results were based on the database of Intego, an ongoing Belgian general practice-based morbidity registry, covering 37 general practitioners and including about 311 000 patient years between the years 1994 and 2000. METHOD: Survival analysis comparing the emergence of malignancy in patients with and without herpes zoster. RESULTS: The number of patients below the age of 65 years with herpes zoster, cancer or both was too low to draw any sensible conclusions. Above the age of 65 years we identified a significant increase of cancer emergence in the whole group and in females (hazard ratio = 2.65, 95% confidence interval = 1.43 to 4.90), but not in males. No difference could be identified in the first year after the herpes zoster infection. CONCLUSION: Our results do not justify extensive testing for cancer in herpes zoster patients. The association we identified, however, leaves open a number of questions with respect to the physiopathology behind it.     

Isolated complete orbital infarction: a common carotid artery occlusion syndrome

When blood flow through the internal and external carotid arteries is completely interrupted by ipsilateral common carotid artery occlusion, the arterial orbital circulation may be more compromised than the brain supply. We studied a pure and extreme example of this situation in a patient who presented with acute orbital infarction, but no cerebral ischemia on clinical, CT and single-photon emission computerized tomography (SPECT) grounds. Ipsilateral blindness corresponded to retinal, choroidal and optic nerve infarction. The pattern of ophthalmoplegia, with relative sparing of adduction, was more compatible with a muscle than a nerve dysfunction, but a reactive dilated pupil, corneal anesthesia, and orbital pain suggested that the intraorbital branches of the ocular motor nerves and ophthalmic division of the trigeminal nerve were not spared. In addition, signs of widespread ocular ischemia were present. Sequential examinations documented the evolution pattern over 1 year. The absence of an orbital collateral supply from the contralateral external carotid and muscular cervical arteries systems, which contrasted with an adequate middle cerebral artery supply via the contralateral internal carotid artery, may explain this isolated and complete form of orbital ischemia due to common carotid artery occlusion.     

Current status of colorectal cancer chemoprevention

Chemoprevention refers to suppression or reversal of the carcinogenic process using pharmacologic or nutritional agents. Colorectal carcinogenesis is a protracted, multistep process that offers opportunities for prevention. Aspirin and selective cyclooxygenase-2 inhibitors (coxibs) have been evaluated for the prevention of sporadic adenoma recurrence. Aspirin was shown to reduce adenoma recurrence rates in patients with prior colorectal neoplasms; however, the optimal dosage remains unclear. Recent studies of coxibs indicate that these agents are effective in reducing sporadic adenoma recurrence, but chronic use can result in serious cardiovascular toxicity. These data underscore the need for chemopreventive agents with acceptable risk-to-benefit ratios. In this regard, nitric-oxide-releasing aspirin shows chemopreventive efficacy in preclinical models and holds promise for reduced toxicity in humans. Furthermore, ongoing chemoprevention trials are evaluating nutritional supplements, such as folic acid and selenium, and results are eagerly awaited.     

The effects of severe visual challenges on steering performance in visually healthy young drivers.

PURPOSE: Two experiments explored the extent to which induced blur, reduced luminance, and reduced visual fields affect drivers' steering performance in a driving simulator. METHODS: In experiment 1, ten young participants (M = 21.2 years) drove at approximately 89 km/h (55 mph) along a curvy roadway while being exposed to blur (0 to + 10 D), luminance (0.003 to 16.7 cd/m), and visual field (1.7 and 150 degrees) manipulations. In experiment 2, a new group of ten young participants (M = 18.5 years) drove while exposed to seven visual field sizes (1.7 to 150 degrees). RESULTS: Steering was sensitive to a reduced field size but not to the blur and luminance challenges. Acuity, on the other hand, was sensitive to the blur and luminance challenges but not to reduced field size. DISCUSSION: In healthy young drivers, steering performance is remarkably robust to severe blur and to extremely low luminances. These results support a key element of the selective degradation hypothesis advanced by Leibowitz and colleagues--that steering abilities are preserved at night even when the ability to recognize objects and hazards is not. Additional research should address the other element of this hypothesis--that drivers fail to appreciate the extent to which their visual abilities are degraded at night.     

Delta hepatitis virus infection in China

To assess the prevalence, epidemiological features and prognostic implications of hepatitis D (Delta) in Sichuan Province, The People's Republic of China, 649 sera (515 from HBsAg positive patients and 134 from HBsAg negative subjects) were tested by radioimmunoassay (RIA) for antibody to the hepatitis D virus (anti-HD). Forty-seven sera (7.2%) showed some degree of reactivity. Serial dilutions of these sera indicated that prozoning was not responsible for the equivocal results. Thirty-four of the 47 sera were submitted under code to a second laboratory for independent analysis. According to those results anti-HD antibodies were detected in four of these sera. The overall prevalence of anti-HD in the HBsAg positive patients therefore was 0.8% (4/515). On the basis of clinical, biochemical and histological data 427 HBsAg positive sera were further divided into acute Type B hepatitis, chronic Type B hepatitis, healthy carrier state and hepatocellular carcinoma (HCC) subgroups. Two of 65 (3.1%) anti-HD positive sera belonged to the acute Type B hepatitis group; one of 104 (0.9%), the chronic Type B hepatitis group and one of 246 (0.4%), the healthy carrier group. No antibody was detected in sera from 12 HBsAg positive HCC patients. All HBsAg negative patients were negative for anti-HD antibody. The results of this study indicate that despite a high prevalence of hepatitis B virus infection, positive serology for delta virus is uncommon in Sichuan Province, The People's Republic of China.     

Working memory after severe traumatic brain injury.

The aim of the present study was to assess the functioning of the different subsystems of working memory after severe traumatic brain injury (TBI). A total of 30 patients with severe chronic TBI and 28 controls received a comprehensive assessment of working memory addressing the phonological loop (forward and backward digit span; word length and phonological similarity effects), the visuospatial sketchpad (forward and backward visual spans), and the central executive (tasks requiring simultaneous storage and processing of information, dual-task processing, working memory updating). Results showed that there were only marginal group differences regarding the functioning of the two slave systems, whereas patients with severe TBI performed significantly poorer than controls on most central executive tasks, particularly on those requiring a high level of controlled processing. These results suggest that severe TBI is associated with an impairment of executive aspects of working memory. The anatomic substrate of this impairment remains to be elucidated. It might be related to a defective activation of a distributed network, including the dorsolateral prefrontal cortex.