Congenital pancreatic cysts in children

The authors report a case of an 11-year-old girl with a solitary, congenital pancreatic cyst and review the literature. Such cysts are very rare and typically are diagnosed in childhood. As a neonate, this patient’s paternal half brother also had undergone resection of a congenital pancreatic cyst. The authors believe this is the first documented familial incidence of a congenital pancreatic cyst.     

Use of a phage display library to identify oligopeptides binding to the lumenal surface of polarized endothelium by ex vivo perfusion of human umbilical veins

Human endothelial-specific targeting peptides were identified by biopanning within freshly-obtained human umbilical cords. Umbilical veins were cleaned in situ and M13 phage display libraries were passed through the cords. Tightly bound phage were recovered following isolation of endothelial cells by collagenase digestion and homogenisation, allowing production of enriched phage libraries for subsequent rounds of panning. After five rounds of biopanning, five promising sequences were selected and the binding of the corresponding phage clones was compared in perfused umbilical veins. Each of these peptides showed substantial binding, although the clone encoding the heptapeptide KPSGLTY showed the greatest, some 89-times greater than insertless phage. Binding of this phage clone was examined to cells in vitro, where it demonstrated at least five-times greater binding to isolated human umbilical vein endothelial cells than to 911, SKOV3, B16F10 and Cos7 cells. These initial peptides may prove useful targeting agents for endothelial-selective delivery, and this powerful approach should be readily applicable to biopanning in a broad range of human vessels ex vivo.     

Assessment of transient changes in corneal hydration using confocal Raman spectroscopy

PURPOSE: The degree of corneal hydration has been linked to excimer laser corneal ablation rates. Enhanced precision with excimer laser refractive surgery may result from a better understanding of the transient changes in corneal hydration. To better understand the dynamic nature of corneal hydration, bovine corneas were investigated under different surface treatments. METHODS: Confocal micro-Raman spectroscopy was used to quantify corneal hydration. Water and acetone solutions were used to establish a quantitative response of the relative OH/CH Raman bands, which are consistent with the water and collagen protein bands in cornea, respectively. Intact bovine corneas were manually debrided (designated MD group) or lamellar flaps were created to expose stromal tissue (designated lamellar keratectomy or LK group). Raman spectra were recorded every 30 seconds for 6 minutes while the prepared cornea surfaces were exposed to quiescent air or to a forced nitrogen gas flow across the surface. RESULTS: The OH and CH Raman bands yielded a linear response while the percentage of acetone was varied from 0% to 100%. For the bovine cornea under forced flow drying, the OH/CH Raman band ratio was found to decrease by 41% from the initial value for both the MD and LK treatment groups. These decreases were significantly more (p = 0.0051 and 0.054, respectively) than the 26% decrease in the OH/CH band ratio measured for the control corneas. In quiescent air, the control and MD groups exhibited a 7% and 6% decrease in the OH/CH ratio, respectively, while the LK treatment group revealed a 19% decrease in the OH/CH ratio. CONCLUSIONS: The bovine eye experiments demonstrate that significant changes in corneal hydration are realized under different drying conditions and treatment methodologies. This study elucidates the nature of transient changes in corneal hydration in a bovine model and suggests the need for further study of the role of such variations in surgical outcome for excimer laser corneal refractive procedures.     

Müller cell and neuronal remodeling in retinal detachment and reattachment and their potential consequences for visual recovery: a review and reconsideration of recent data

Recent evidence suggests that the adult mammalian retina is far more plastic than was previously thought. Retinal detachment induces changes beyond the degeneration of outer segments (OS). Changes in photoreceptor synapses, second- and even third-order neurons may all contribute to imperfect visual recovery that can occur after successful reattachment. Changes that occur in Müller cells have obvious effects through subretinal fibrosis and proliferative vitreoretinopathy, but other unidentified effects seem likely as well. Reattachment of the retina induces its own set of responses aside from OS re-growth. Reattachment halts the growth of Müller cell processes into the subretinal space, but induces their growth on the vitreal surface. It also induces the outgrowth of rod axons into the inner retina.     

Selection of the first-time dose in humans: comparison of different approaches based on interspecies scaling of clearance

The authors describe four approaches to selecting a safe starting dose for humans in clinical drug trials based on interspecies scaling of clearance. Human clearance was predicted by scaling for 10 example drugs for which animal clearance values were available in the literature. The predicted human clearance values were then used to select the estimated starting dose in humans. These doses were then compared with the actual doses given to humans during clinical trials. All four approaches used to estimate the first-time dose in humans provided values that were within the dose range given to humans from Phases I to III. This work demonstrates that animal pharmacokinetic data can be used to estimate a suitable human starting dose, provided the data have been obtained from a dose that produces no adverse effects.     

Assessing the toxicity of dodecylbenzene sulfonate to the midge Chironomus riparius using body residues as the dose metric

Dodecylbenzene sulfonate (DBS) is a component of linear alkylbenzene sulfonate (LAS), an anionic surfactant, mainly used in household detergents. Due to the large quantity of DBS in use, there is concern over adverse environmental effects. This work examined the toxicokinetics and toxicity of the 2-phenyl isomer of dodecylbenzene sulfonate in 4-d, 10-d, and partial life-cycle tests on the midge, Chironomus riparius, exposed to aqueous solutions. Toxicokinetics were determined in 10-d uptake and 5-d elimination tests. The toxicokinetics were based on parent compound concentration in water and yielded an uptake coefficient (ku) of 17.5 (14.87-20.20) ml/g/h, an elimination rate constant (ke) of 0.073 (0.062-0.085) per h, a bioconcentration factor (BCF) of 56 to 240, and a half-life (t 1/2) of 9.5 (8.0-11.0) h. Biotransformation measurements did not reveal evidence for DBS metabolism. Thus, body residues, determined in the toxicity study, represent parent compound. In toxicity tests, 4- and 10-d LR50s (the body residue required to cause 50% mortality) in live midges were 0.72 (0.65-0.79) and 0.18 (0.08-0.42) mmol/kg, respectively. Thirty-day LR50s were 0.18 (0.09-1.64) and 0.21 (0.15-0.39) mmol/kg in duplicate studies. Of the sublethal endpoints, only developmental time increase was significant, with the lowest-observed-effect residues of 0.085 (0.067-0.105) and 0.100 (0.087-0.114) mmol/kg for male and female midges, respectively. Deformities in surviving larvae were also observed as chronic responses for body residues exceeding the 30-d LR50. The body residues required for mortality suggest that DBS acts like a polar narcotic in the midge.     

Relationship of hospital volume to outcome in cardiac surgery programs in California

There are more than 120 cardiac surgery programs in California. More than half perform less than 200 coronary artery bypass graft (CABG) procedures per year. This study queried the state of California discharge abstract database to analyze the relationship between annual procedural volume and outcomes of all 119 nonfederal hospitals performing cardiac surgery during 1997 through 1999. Unadjusted in-hospital mortality for CABG surgery was 3.91 per cent (923 of 23,619) in hospitals performing fewer than 200 procedures per year and 2.09 per cent (496 of 23,704) in hospitals performing > or = 500 procedures annually (P = 0.001 by Chi-square). Similar findings were noted for CABG + valve and/or aneurysm and for valve procedures. Risk-adjusted CABG data obtained from 78 of 119 hospitals found that a significant difference persisted between a volume of < 200 and > or = 200 procedures per year (P = 0.03 by t test). There was wider variation in outcome among lower-volume hospitals. However, many low-volume providers had excellent results. It is concluded that although volume is clearly related to outcome patient-related factors and process variables may be more important. Performance improvement programs should be developed to improve communication between providers with differing outcomes.