Morphology of corticotectal cells in the primary visual cortex of hooded rats

In primary visual cortex of hooded rats, pyramidal cells in layer V may be classified as long, medium, or short, on the basis of the layer in which the apical dendrite terminates. The present study determines which of these types of pyramidal cells project to the superior colliculus. Two different strategies were used to label corticotectal cells with horseradish peroxidase (HRP). In the first set of experiments, a large number of corticotectal cells were labeled by retrograde transport following injection of HRP into the superior colliculus. In the second set of experiments, single unit recording was used to identify corticotectal cells physiologically by antidromic activation from the superior colliculus. These cells were then impaled and labeled by intracellular iontophoresis of HRP. The results from both techniques suggest that only long pyramidal cells send an axon to the superior colliculus. These cells are distinguished by an apical dendrite that extends into layer I. We conclude that in hooded rats corticotectal cells in primary visual cortex are the long pyramids in layer V.     

Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities.

An unusual, elongated, refractile cell morphology was observed in keratinocytes cultured from three patients with non-lethalis forms of junctional epidermolysis bullosa (JEB). To determine whether these changes might be related to altered cell adhesion, keratinocyte strains established from one patient were examined for adhesive, structural, and functional characteristics. JEB keratinocytes expressed keratin tonofilaments, as determined by staining with AE1 monoclonal antibodies and direct observation of tonofilaments by electron microscopy. JEB keratinocytes showed diminished cell-substratum adhesions, judged by interference reflection microscopy. Areas of diminished cell-substratum adhesion corresponded to F-actin-rich cell adhesions (focal adhesions) and not to cellular areas that abundantly express hemidesmosomal antigens. Analysis of cell-substratum adhesion by electron microscopy revealed extensive areas of cell-substratum separation in JEB keratinocytes that were not present in normal keratinocytes maintained in serum-free medium. Normal keratinocytes displayed numerous regions of focal contact between the ventral plasma membrane and the culture substratum, but these structures were not seen in JEB keratinocytes. Bundled actin filaments (stress fibers) were greatly diminished in expected regions of cell-substratum adhesion in JEB keratinocytes and, instead, displayed disorganized individual filaments. The growth rate of JEB keratinocytes was quite slow in culture, with a population doubling time of 2.7 d versus 1.5 d for normal keratinocytes under identical conditions. JEB keratinocytes also displayed a reduced ability to aggregate into colonies upon exposure to medium with increased extracellular calcium. JEB keratinocytes thus display adhesive, structural, and functional abnormalities that suggest this cell type may be central to the pathogenesis of junctional epidermolysis bullosa. Study of affected keratinocytes could be important to characterize associated molecular pathologies.     

Development of a risk-adjusted capitation model based on principal inpatient diagnoses in Taiwan.

BACKGROUND AND PURPOSE: Taiwan's National Health Insurance (NHI) program has considered the use of capitation payments to health care providers as a method for control of the rising costs of the system. The establishment of capitation payments usually requires the performance of risk adjustment. The purposes of this study were to develop a diagnosis-based risk adjustment model for the NHI and to evaluate its predictability. METHODS: Using a 2% random sample of 371,620 NHI enrollees, the authors developed a Taiwan version of the Principal Inpatient Diagnosis Cost Groups (TPIPDCGs) from 1996 claim records to predict an individual's expenditure in 1997. Weighted least squares regression models were built in an estimation sample (two-thirds of the study sample), and were cross-validated in a validation sample (the remaining one-third of the study sample). Predictive R2 and predictive ratios were used to evaluate the model's predictability. RESULTS: Only 7.88% of the study sample could be classified into 1 of the 16 TPIPDCGs. Combined with demographic variables, which alone could explain 3.7% of the variation in an individual's future expenditure, the risk adjustment model based on TPIPDCGs could explain 12.2% of expenditure variation. In addition, the finding that the predictive ratios of the TPIPDCG model approximated unity better than those of the demographic model in all subgroups indicates that the capitation payment as predicted by the TPIPDCG model for each subgroup would better correlate to the actual spending. CONCLUSION: Taiwan's risk-adjusted capitation model based on principal inpatient diagnoses has higher predictability on individual's future expenditure than its counterpart in the USA. This finding provides insight into not only the development of Taiwan's diagnosis-based risk adjustment models but also the necessity of modification when applying foreign-developed risk adjustment models to the NHI.     

Lecithin vesicles for topical delivery of diclofenac.

Skin penetration of topically applied diclofenac is important for the treatment of rheumatic diseases and actinic keratoses. We have studied the permeation of diclofenac across human cadaver epidermis in-vitro from four lecithin vesicle formulations and a few marketed semi-solid preparations. The lecithin vesicle formulations were prepared by dissolving the lipid contents (lecithin and sodium cholate) in a 1:1 mixture of methanol-chloroform, evaporating the solvents under vacuum, and hydrating the lipid layer with the drug solution in water or 10% ethanol. The vesicles were sonicated for 5 min to reduce the vesicle size and their size and Zeta potential were characterized. The cumulative amount and maximum flux of diclofenac was 69.7+/-40.3 micrograms and 4.77+/-3.16 micrograms/hcm(2) from lecithin vesicles containing sodium cholate and 10% ethanol, and is the highest of all formulations studied. The cumulative amount and mean maximum flux obtained from other formulations were in the range of 2.46+/-1.98-29.9+/-10.1 micrograms and 0.53+/-0.46-3.61+/-0.86 micrograms/hcm(2). Based on the results, lecithin vesicles of diclofenac appear to be advantageous for the topical delivery of diclofenac.     

Working‐correlation‐structure identification in generalized estimating equations

Selecting an appropriate working correlation structure is pertinent to clustered data analysis using generalized estimating equations (GEE) because an inappropriate choice will lead to inefficient parameter estimation. We investigate the well‐known criterion of QIC for selecting a working correlation structure, and have found that performance of the QIC is deteriorated by a term that is theoretically independent of the correlation structures but has to be estimated with an error. This leads us to propose a correlation information criterion (CIC) that substantially improves the QIC performance. Extensive simulation studies indicate that the CIC has remarkable improvement in selecting the correct correlation structures. We also illustrate our findings using a data set from the Madras Longitudinal Schizophrenia Study. Copyright © 2008 John Wiley & Sons, Ltd.     

Biochemical analysis of human milk treated with sodium dodecyl sulfate, an alkyl sulfate microbicide that inactivates human immunodeficiency virus type 1.

Reduction of transmission of human immunodeficiency virus type 1 (HIV-1) through human milk is needed. Alkyl sulfates such as sodium dodecyl sulfate (SDS) are microbicidal against HIV-1 at low concentrations, have little to no toxicity, and are inexpensive. The authors have reported that treatment of HIV-1-infected human milk with < or = 1% (10 mg/mL) SDS for 10 minutes inactivates cell-free and cell-associated virus. The SDS can be removed with a commercially available resin after treatment without recovery of viral infectivity. In this article, the authors report results of selective biochemical analyses (ie, protein, immunoglobulins, lipids, cells, and electrolytes) of human milk subjected to SDS treatment and removal. The SDS treatment or removal had no significant effects on the milk components studied. Therefore, the use of alkyl sulfate microbicides to treat milk from HIV-1-positive women may be a simple, practical, and nutritionally sound way to prevent or reduce transmission of HIV-1 while still feeding with mother's own milk.