Tetrabenazine therapy of pediatric hyperkinetic movement disorders.

Tetrabenazine (TBZ), a presynaptic dopamine depletor and postsynaptic dopamine receptor blocker, is widely used for the treatment of hyperkinetic movement disorders in adults. However, reports of its use in children are limited. We review the efficacy and tolerability of TBZ therapy in 31 children with hyperkinetic movement disorders refractory to other medications. TBZ was effective in reducing the severity of movement disorders resistant to treatment with other medicines. When compared to adult patients, pediatric patients required higher doses. Side effects were similar to the adult population; however, children had a lower incidence of drug-induced Parkinsonism.     

Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role in daunorubicin transport.

To identify the role of protein kinase C (PKC) isoforms in multidrug resistance in tumor cells, we examined the PKC isoform pattern in the multidrug resistant P388/ADR cell line and studied the effect of down regulation of PKC isoforms on intracellular daunorubicin accumulation and P-glycoprotein expression. Using monoclonal antibodies to PKC alpha, beta and gamma and flow cytometry technique we showed that P388/ADR cells overexpressed PKC alpha and beta as compared to drug sensitive P388 cells. Prolonged treatment of P388/ADR cells with phorbol myristate acetate (PMA), a procedure that is known to down regulate PKC, resulted in the down regulation of total PKC activity and the PKC beta isoform (at the protein level) that was accompanied by the correction of daunorubicin accumulation in P388/ADR cells. The level of expression of P-glycoprotein in PMA treated cells was similar to that of untreated cells. These results suggest that PKC beta regulates the drug efflux function of P-glycoprotein.     

Fertility reduction and the quality of family planning services

The purpose of this paper is to determine whether a focus on quality of family planning services is consistent with meeting demographic objectives. An analytical framework that links the six elements of quality with fertility is described. A review of existing literature and analysis suggest that improvements in quality of family planning services by enhancing the choice of contraceptive methods available in a country would increase the overall practice of contraception and thus would result in fertility reduction.     

Self-Concept and Satisfaction With Physical Appearance in Youth With and Without Oral Clefts

This study investigated relationships between child/parent dissatisfaction with child facial appearance and the self-concept/social competence of 8- to 15-year-old children with (N = 34) and without (N = 34) oral clefts. Children in both groups had normative psychosocial adjustment, but also reported moderate dissatisfaction with facial appearance. Cleft group parents were more likely to agree with their child's dissatisfaction. When cleft group parents were more dissatisfied with child facial appearance, their children reported better quality of life. Results suggest that parents of children with clefts reporting greater dissatisfaction may respond in positive ways that enhance quality of life.     

Effect of titanium surface texture on the cell-biomaterial interface.

To improve the in vivo performance of engineered implants, this study examines the independent effects of surface chemistry and topography on fibroblast morphology and density in vitro. Titanium (Ti) was sputter-coated onto smooth and microtextured polyethylene terephthalate (PET). Test specimens were evaluated in 24-h, fibroblast cultures and assessed with scanning electron microscopy (SEM) for cellular morphology and density. Fibroblast density increased, as the Ti film thickness increased. The fibroblasts exhibited contact guidance on the textured test specimens. The greatest cellular density was found on the Ti-coated, textured test specimens. In conclusion, Ti and surface texture appeared to strongly influence fibroblast density and morphology as compared to PET and smooth surfaces.     

Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma

Objective : To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. Methods : Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions. Results : The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z₀, was constant at approximately 6.5 ± 10⁹g/cm³. Below 40 mm Hg, z₀ increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh-works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively. Conclusions : The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.