The vascular-targeting fusion toxin VEGF121/rGel inhibits the growth of orthotopic human bladder carcinoma tumors

Vascular endothelial growth factor (VEGF) and its receptors (FLT-1 and KDR) are overexpressed by human bladder cancer cells and tumor endothelial cells, respectively. Strategies that target VEGF receptors hold promise as antiangiogenic therapeutic approaches to bladder cancer. A fusion protein of VEGF121 and the plant toxin gelonin (rGel) was constructed, expressed in bacteria, and purified to homogeneity. Cytotoxicity experiments of VEGF121/rGel on the highly metastatic 253J B-V human bladder cancer cell line demonstrated that the VEGF121/rGel does not specifically target these cells, whereas Western blot analysis showed no detectable expression of KDR. Treatment with VEGF121/rGel against orthotopically implanted 253J B-V xenografts in nude mice resulted in a significant suppression of bladder tumor growth (approximately 60% inhibition; P < .05) compared to controls. Immunohistochemistry studies of orthotopic 253J B-V tumors demonstrated that KDR is highly overexpressed in tumor vasculature. Immunofluorescence staining with antibodies to CD-31 (blood vessel endothelium) and rGel demonstrated a dramatic colocalization of the construct on tumor neovasculature. Treated tumors also displayed an increase in terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling staining compared to controls. Thus, VEGF121/rGel inhibits the growth of human bladder cancer by cytotoxic effects directed against the tumor vascular supply and has significant potential as a novel antiangiogenic therapeutic against human bladder cancer.     

Perceptions of health status and play activities in parents of overweight Hispanic toddlers and preschoolers

Childhood overweight among lower socioeconomic, Hispanic children has increased. Interviews regarding health status and play patterns were conducted with 76 predominantly Hispanic mothers of overweight toddlers and preschoolers served by Women, Infants, and Children (WIC). Most participants believed their child was healthy and half were unconcerned about their child's weight. Most parents reported having a safe place to play and access to a playground, although gender differences were found. Access to an outside play area was related to amount of active play activities. Children watched an average of 1.7 hours per day of television. Health professionals must partner with parents to address childhood obesity.     

Experimental and modeling investigation of metal release from metal-spiked sediments

In sediments that contain iron monosulfide, cadmium, nickel, lead, zinc, and silver(I) form insoluble metal sulfides that lower the metal ion activity in the sediment-pore water system, thereby reducing toxicity. However, metal sulfides are susceptible to oxidation by molecular oxygen resulting in metal solubilization. To better understand the sources and sinks of metal sulfides in sediments, iron monsulfide-rich freshwater sediments were spiked with cadmium, nickel, lead, zinc, or silver(I) and placed into cylindrical cores with an overlying layer of oxygen-saturated water. Measurements of the dissolved metal concentration in the overlying water were made as a function of time and the vertical profiles of acid-volatile sulfide (AVS) and simultaneously extracted metal (SEM) were measured after 150 d. A one-dimensional reactive and transport model has been employed to help elucidate processes controlling the fate of metals in sediments. The model incorporates metal-sulfide formation, metal-sulfide oxidation, and metal partitioning onto sediment organic carbon and iron oxyhydroxide to simulate the vertical transport of metals throughout the sediment core.     

Case study: delicate skin cutting: management beyond the skin and implications of superficial habitual self-mutilation

A 16-year-old girl accompanied by her mother was noted to have several thin, well healed brown lines on the distal third of her left flexural forearm (Figure). She admits to having recently made these marks by skin cutting. She feels depressed and at times feels life "is not worth living." She denies alcohol or substance abuse or true suicidal ideation, plan, or intent. Her mother describes her as previously well adjusted and a good student who has become erratic and moody in the past 6 months, with worsening school performance. Her father had a history of depression and alcoholism and died 3 years ago. She is undergoing psychotherapy and pharmacotherapy with sertraline with good results. She has not cut her skin in 3 months. Her mood and behavior have improved.     

Pediatric reference intervals for FSH, LH, estradiol, T3, free T3, cortisol, and growth hormone on the DPC IMMULITE 1000

BACKGROUND: We studied serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), triiodothyronine (T3), free T3 (FT3), cortisol and growth hormone (GH) concentrations in a population of pediatric patients. The reference intervals were determined separately for females and males stratified by age groups to assess age- and sex-related differences. Our objective was to obtain reference intervals for the 7 serum analytes for our pediatric population using the IMMULITE 1000 system. METHODS: Serum samples of 800 in- and out-patients, newborn to 19 years old were analyzed using the DPC IMMULITE 1000 chemiluminescent immunoassay system. RESULTS AND CONCLUSIONS: We report pediatric reference intervals for FSH, LH, E2, T3, FT3, cortisol, and GH. These reference intervals provide the basis for clinical interpretation of laboratory results using the IMMULITE 1000 system and the assessment of child development.     

Oxytocin is not a valid biomarker when measured in saliva by immunoassay

The integration of oxytocin (OT) into behavioral science seems to hold considerable promise for advancing our understanding of human health and development but methodological issues restrict the measurement of OT in large studies, in everyday social settings, or when repeated sampling is required. Measuring OT in saliva could overcome many of these limitations. In this paper, we rigorously evaluate the feasibility of doing so. A series of experiments leads to the conclusion that saliva does not contain oxytocin in measurable amounts, and that OT is not a valid salivary biomarker when measured by currently available immunological methods. Levels of immuno-reactive OT in saliva are primarily due to non-specific interference with antibody-antigen binding. We can state with a high degree of certainty that measurement of OT in saliva does not yield meaningful indices of individual differences or intra-individual change.     

Improving pilot response to in-flight strokes: a randomized controlled trial

BACKGROUND: When a passenger suffers an in-flight stroke (IFS), the pilot decides when to expedite access to ground care. Pilot pro-activeness towards IFS could improve outcome and should be promoted. Unfortunately, little is known about a pilot's stroke pro-activeness or limiting factors. METHODS: Randomized controlled trial of an educational intervention (American Stroke Association, 30-slide stroke awareness lecture) through an internet-based computer system using pilot students and instructors as subjects. Pilots completed pre-intervention and post-intervention tests of 25 simulated in-flight scenarios that describe strokes and other neurological and medical symptoms. Outcomes chosen were the percentage of pilots that would use a medical radio service, declare an emergency on board, or divert to the nearest airport for each scenario. RESULTS: Participant pilots (n = 104) were less likely to respond to IFS than to myocardial infarction (p < 0.001). Fear of retaliation by an employer was the most important modifiable limitation. The educational program increased the simulated rate of emergency declarations for in-flight vertebrobasilar strokes (p < 0.001) and subarachnoid hemorrhage (p < 0.001). CONCLUSIONS: Pilot-simulated response to certain IFS improves immediately after this educational intervention, which should be disseminated in schools and airlines. Further studies are needed to determine the long-term benefits of this intervention and the impact on actual diversion rates. Companies should also review their policies to shield pilots from retaliation when altering the flight plan for patients.     

Cost-effectiveness of whole-body CT screening

PURPOSE: To make preliminary estimates of the effectiveness (in life-years) and cost-effectiveness (in costs per life-year) of whole-body computed tomographic (CT) screening. MATERIALS AND METHODS: Costs and effectiveness (in life-years) of onetime whole-body CT screening relative to those of no screening were calculated by using a decision-analytic model. It was assumed that any benefits from screening were due to earlier detection of disease and improvement in survival relative to survival with routine care. Eight conditions were included in the model: ovarian, pancreatic, lung, liver, kidney, and colon cancer; abdominal aortic aneurysm; and coronary artery disease. Costs of the screening examination, follow-up tests, and patient care were estimated. The base-case analysis was performed for a hypothetical cohort of 500 000 self-referred asymptomatic 50-year-old men. For sensitivity analyses, the age and sex of the cohort were varied. Results were expressed in 2001 U.S. dollars per life-year gained. RESULTS: Compared with routine care, whole-body CT screening provided minimal gains in life expectancy (0.016 6 years or 6 days) at an average additional cost of 2513 dollars per patient, or an incremental cost-effectiveness ratio of 151 000 dollars per life-year gained. Most patients (90.8%) had at least one positive finding, but only 2.0% had disease; work-up in patients with a false-positive result of screening accounted for 32.3% of total costs (1720 dollars of 5332 dollars). Results were sensitive to the prevalence of disease, the effect of screening on stage of disease at diagnosis, the specificity of screening, and the costs of follow-up for false-positive findings. CONCLUSION: Even with assumptions favorable to whole-body CT, implementation of onetime screening would not be cost-effective compared with currently funded medical interventions; follow-up for false-positive findings would add a substantial financial burden to the health care system.