Isolated neurofibroma of the orbit with extensive myxoid changes: a clinicopathologic study including MRI and electron microscopic findings

Isolated orbital neurofibroma (INO) without systemic neurofibromatosis is rare. Previous reports including MRI with elaboration of the ultrastructural features of the cellular and extracellular components in INO do not exist. A 44-year-old male presented with painless, slowly progressive proptosis (6 mm) and downward displacement (3 mm) of the left eye of two years duration. MRI revealed a suprabulbar mass hypointense to fat, isointense to brain on T1-weighted images with small hyperintense areas following contrast enhancement. T2-weighted images showed a predominantly hyperintense mass with a few hypointense islands. The lesion was excised using an anterior superior transseptal orbitotomy. Histopathologically, large areas of a paucicellular myxoid stroma containing mucopolysaccharides made up approximately three-quarters of the mass. Focal hypercellular areas showed marked collagen deposition. Blood vessels were distributed at the periphery of the lesion and in association with nodules of nerve sheath cells. Ultrastructurally, perineural and fibroblast-like cells were loosely arranged in a myxoid stroma. Schwann cells were embedded in a dense collagenous matrix. Variable differentiation of Schwann cells, perineural cells and fibroblast-like cells associated with a more solid (collagenous) or loose (myxoid) extracellular matrix may determine the characteristic, though not specific, MRI features in isolated neurofibromas of the orbit.     

The in vitro and in vivo proliferative capacity of serum-free cultivated human conjunctival epithelial cells

PURPOSE: To investigate the in vitro and in vivo proliferative capacity of human conjunctival epithelial cells cultured in serum-free media, and to compare this with current methods that utilize serum-containing media and 3T3 feeder layers. METHODS: Human conjunctival epithelial cells were cultivated in serum-free media alone, serum-free media with a 3T3 feeder layer, and serum-containing media with a 3T3 feeder layer. The areas of outgrowth, colony-forming efficiencies and number of population doublings were compared. The in vivo proliferative potential was assessed by analyzing the number of cells generated by the implantation of cultured cells into athymic mice. Cultured cells were evaluated for the expression of cytokeratins K3, K4, K12, K19, as well as the gel-forming goblet cell mucin, MUC5AC. RESULTS: Cells cultivated in serum-free media, serum-free media and feeder cells, and serum-containing media and feeder cells achieved colony-forming efficiencies of 14.5 +/- 4.1%, 10.1 +/- 3.1%, and 20.4 +/- 6.7%, respectively, and number of population doublings of 24.8 +/- 4.3, 14.8 +/- 3.6, and 30.0 +/- 5.0, respectively. Nine-day old athymic mice conjunctival cysts derived from serum-free cultures comprised 1.29 x 10(6) +/- 0.46 x 10(6) cells, while cysts derived from serum-containing cultures comprised 1.30 x 10(6) +/- 0.53 x 10(6) cells. The degree of epithelial stratification was similar in both conditions. Serum-free cultivated conjunctival cells retained their in vivo characteristics and expressed K4, K19 and MUC5AC. The presence of MUC5AC mRNA in these cells was confirmed by RT-PCR. CONCLUSIONS: Conjunctival epithelial cells propagated in serum-free media demonstrated a similar in vivo proliferative capability, as compared to serum-containing media with 3T3 feeder cells. This has important clinical implications, as the serum-free ex vivo expansion of cells for clinical transplantation overcomes the problems associated with the use of animal serum and cells.     

Blackberry extracts inhibit activating protein 1 activation and cell transformation by perturbing the mitogenic signaling pathway

Blackberries are natural rich sources of bioflavonoids and phenolic compounds that are commonly known as potential chemopreventive agents. Here, we investigated the effects of fresh blackberry extracts on proliferation of cancer cells and neoplastic transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as well as the underlying mechanisms of signal transduction pathways. Using electron spin resonance, we found that blackberry extract is an effective scavenger of free radicals, including hydroxyl and superoxide radicals. Blackberry extract inhibited the proliferation of a human lung cancer cell line, A549. Pretreatment of A549 cells with blackberry extract resulted in an inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation induced by ultraviolet B (UVB) irradiation. Blackberry extract decreased TPA-induced neoplastic transformation of JB6 P+ cells. Pretreatment of JB6 cells with blackberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 transactivation. Furthermore, blackberry extract also blocked UVB- or TPA-induced phosphorylation of ERKs and JNKs, but not p38 kinase. Overall, these results indicated that an extract from fresh blackberry may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh blackberry may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1 and mitogen-activated protein kinase activation.     

Physical workload, ergonomic problems, and incidence of low back injury: a 7.5-year prospective study of San Francisco transit operators

BACKGROUND: The etiologic role of biomechanical factors for low back injury (LBI) needs to be confirmed in prospective studies that control for psychosocial factors. METHODS: Complete baseline information on 1,233 vehicle operators was gathered during medical examinations and by questionnaire. First LBI during 7.5 years of follow-up was ascertained from insurance records. Hazard ratios and etiologic fractions were analyzed with Cox regression models stratified by injury severity and controlling for age, sex, height, weight, ethnicity, and biomechanical and psychosocial job factors. Severe LBI was defined as medically diagnosed postlaminectomy syndrome, spinal stenosis, herniated lumbar disc, sciatica, or spinal instability. RESULTS: An exponential dose-response relationship was found between weekly driving hours and incidence of first LBI. Indicators of physical workload were more strongly associated with more severe low back injuries compared to less severe injuries. Rates of severe LBI increased 39% for every 10-hr increase in weekly driving (hazard ratio 1.39, 95% confidence interval 1.15-1.68). Higher risks of severe LBI were also found among operators performing heavy physical labor on cable cars (hazard ratio 2.76, 95% confidence intervals 1.24-6.14) or reporting more ergonomic problems at baseline (HR for upper quartile 1.65 (95% confidence interval 1.08-2.50). Estimates of etiologic fractions suggest that reduction of ergonomic problems to the low level currently experienced by 25% of drivers would result in a 19% reduction of severe LBI among all drivers. A change from full- (more than 30 hr) to part-time driving (20-30 hr) could reduce the number of severe LBI by 59%, although this gain would be reduced to 28% at the company level if injuries expected among additional employees, hired to maintain full service are included. CONCLUSIONS: Duration of professional driving and ergonomic problems are independent and preventable risk factors for LBI even after adjustment for psychosocial factors.     

Tools from the new institutional economics for reforming the delivery of veterinary services

The new institutional economics offers a range of analytical tools and insights which can be used in restructuring the animal health services of a country. This paper discusses three of the most important--externalities, transaction costs and asymmetric (unequal) information. These tools can be used to craft a system which is sensitive to the particular institutional heritage of a country and to its political, social and economic realities. Institutions are important in this process and the best way for one society is often not the optimal choice for another.     

Development of a model microbial predator-prey system suitable for studies of the behavior of toxic trace metals

Interactions between microbial predators and their prey can significantly influence the behavior of toxic trace metals. Ingested bacterial prey-bound metals can either accumulate within a predator or be excreted and potentially reintroduced into the dissolved phase. A defined predator-prey system suitable for developing a more fundamental understanding of metal behavior in simple microbial food chains was designed and tested by using lead (Pb) as a representative cationic transition metal. Desired features of this system were the ability to define the chemical speciation of dissolved metals as well as to distinguish between prey- and predator-bound metals. Pseudomonas putida and the ciliate protozoan Tetrahymena thermophila were selected as representative bacterial prey and predator species, respectively. In addition, the use of fluorescent microspheres was evaluated as an experimental surrogate for bacterial prey. Filtration techniques for size-selective separation were developed so that the distribution of Pb between cells of T. thermophila, cells of P. putida or microspheres, and the dissolved phase could be assessed. Filtration units were selected based on their ability to perform separations with minimal metal loss at circumneutral pH. Five-micron polycarbonate filter membranes successfully separated T. thermophila from P. putida with good cell retention and low metal loss. Centrifuge filters successfully separated dissolved and particle-bound metal (<5,000 nominal molecular wt limit). Exemplary experimental results are presented and show that predation on Pb-exposed cells of P. putida or microspheres increases uptake of Pb by T. thermophila.     

The business case for better buildings

The buildings in which customers receive services are inherently part of the service experience. Given the high stress of illness, healthcare facility designs are especially likely to have a meaningful impact on customers. In the past, a handful of visionary "healing environments" such as the Lucille Packard Children's Hospital at Stanford University in Palo Alto, California; Griffin Hospital in Derby, Connecticut; Woodwinds Health Campus in St. Paul, Minnesota; and San Diego Children's Hospital were built by values-driven chief executive officers and boards and aided by philanthropy when costs per square foot exceeded typical construction costs. Designers theorized that such facilities might have a positive impact on patients' health outcomes and satisfaction. But limited evidence existed to show that such exemplary health facilities were superior to conventional designs in actually improving patient outcomes and experiences and the organization's bottom line. More evidence was needed to assess the impact of innovative health facility designs. Beginning in 2ooo, a research collaborative of progressive healthcare organizations voluntarily came together with The Center for Health Design to evaluate their new buildings. Various "Pebble Projects" are now engaged in three-year programs of evaluation, using comparative research instruments and outcome measures. Pebble Projects include hospital replacements, critical care units, cancer units, nursing stations, and ambulatory care centers. The Pebble experiences are synthesized here in a composite 3oo-bed "Fable Hospital" to present evidence in support of the business case for better buildings as a key component of better, safer, and less wasteful healthcare. The evidence indicates that the one-time incremental costs of designing and building optimal facilities can be quickly repaid through operational savings and increased revenue and result in substantial, measurable, and sustainable financial benefits.     

Reading disorders in children

Reading difficulties are a complex set of disorders. Current research indicates that these disorders are not caused by vision abnormalities. Treatment of these disorders requires a multidisciplinary approach involving educators, psychologists, and physicians. Parents, physicians, and school officials should understand that there are no quick cures for these children.