Yearly stepwise increments of the growth hormone dose results in a better growth response after four years in girls with Turner syndrome. Dutch Working Group on Growth Hormone

To optimize the growth promoting effect of growth hormone (GH), 65 previously untreated girls with Turner syndrome (TS), chronological age (CA) 2-11 yr, were randomized into 3 dosage regimen groups: A, B, and C, with a daily recombinant-human GH dose during 4 study years of 4-4-4-4, 4-6-6-6, and 4-6-8-8 IU/m2 b.s. The first GH dosage increase in groups B and C resulted in a significantly higher mean height velocity (HV) compared with constant dose group A. During the third year, when the dose was raised again only in group C, mean HV was significantly higher in groups B and C than in group A, and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA (Dutch-Swedish-Danish Turner references) was identical; however, in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment, the following was determined. 1) The mean delta HSDSCA was significantly higher for groups B and C compared with group A, but not significantly different between groups B and C. 2) Although significantly higher compared with estimated values for untreated Dutch girls with TS, bone maturation of the GH treated girls was not significantly different between groups. 3) It was positively related with the degree of bone age (BA) retardation at start of study and negatively with baseline CA. 4) Both the modified Index of Potential Height (mIPHRUS) and a recently developed Turner-specific final height (FH) prediction method (PTSRUS), based on regression coefficients for H, CA, and bone age, showed significant increases in mean FH prediction, without significant differences between groups. PTSRUS values were markedly higher than the mIPHRUS values. Dose dependency could be shown for the area under the curve (AUC) for GH, but delta HSDSCA was not linearly related with AUC. Baseline GH binding protein (BP) levels were in 84% of the cases within the normal age range; the decrease in mean levels after 6 months GH was not significant. Mean insulin-like growth factor I (IGF-I) and IGFBP-3 plasma levels increased significantly, without significant differences between groups. delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period, beta-0.002 and beta-0.0004. Thus, a stepwise GH-dosing approach reduced the "waning" effect of the growth response after 4 yr treatment without undue bone maturation. FH prediction was not significantly different between treatment groups. Irrespective of the GH dose used, initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction, but was not statistically significant when expressed as delta HSDSCA over the study period.     

Education and training programs for expatriate and Saudi nurses at KKESH

The purpose of this second article in a series of "Ophthalmic nursing in Saudi Arabia: A western expatriate's perspective" is to acquaint readers with the education and training programs for the expatriate nursing staff and Saudi nurses at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia.     

Expanding the application of facial ceramic veneers

"Full veneers," restorations similar in depth to ceramic veneers but extending over the lingual or occlusal surface as well as the facial surface, are a conservative option to conventional crowns. They have been used successfully at the UCLA Center for Esthetic Dentistry for three years. Indications, technique and a patient study are presented.     

Perthes' disease treated by prolonged recumbency and femoral head containment: a long-term appraisal

The results of a long-term review of 102 hips in eighty-seven patients with Perthes' disease are described, the mean follow-up interval being seventeen years. All had been treated by an extremely rigorous conservative regime in which the patients were kept in hospital for an average period of twenty-six months, during which time they were confined to bed with the legs in wide abduction, first in traction and later in "broomstick" plasters to ensure "containment" of the femoral head. The patients were assessed by the joint clincial and radiological method described by Ratliff (1956). The results were very satisfactory, with only 2 per cent poor results and 10 per cent fair. The remaining 88 per cent were good. The radiological results at the end of treatment have also been compared with control series described by Catterall (1972) and with the osteotomy series of Lloyd-Roberts, Catterall and Salamon (1976). From this it appears that the described regime offers no benefit compared with the natural history in Catterall's Groups I and II, and in Group III the results were only marginally better than those following osteotomy. In Group IV cases, however, where the femoral head was totally involved, the benefit was important, and since these are the cases which carry the worst natural prognosis it is suggested that the use of the method described in such instances must be seriously considered in spite of its social disadvantages. The theoretical implications of the findings are considered, and it is concluded that the benefits of the method cannot be ascribed wholly to the application of the "containment" principle.     

Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes

Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.     

Scratch hardness and deformation maps for polycarbonate and polyethylene

This paper presents results obtained from the scratching of an ultrahigh molecular weight polyethylene (UHMWPE) and a polycarbonate (PC). The data are used to obtain various surface mechanical properties such as the hardness and also the prevailing deformation mechanisms. Scratch results are reported for the case of rigid conical indenters for various tip included angles, bulk temperatures, scratch velocities, and applied normal loads. Scanning electron microscopy (SEM) and laser profilometry data are used to study the surface deformation and damage mechanisms, and to assess the topography of the surfaces after scratching. Deformation maps are provided for these polymers under different experimental conditions, which describe the various deformation characteristics. In general, these polymers show both increasing and decreasing trends for the scratch hardness values with variation of cone angle, (4qW/ηd²; where W is the normal load, d the width of the residual scratch, and q is a characteristic contact parameter, which ranges between 1 and 2). The scratch velocity, which governs the imposed strain rate, imparts an increasing effect on the hardness values, whereas a higher bulk temperature of the material decreases the scratch hardness. The measured responses of the surface properties of these polymers are shown to greatly depend upon the kind of deformation mechanism prevalent during the scratching and associated material removal processes.     

Simulation of the fracture behavior of elastomeric composites: Mechanical interactions at material interfaces

The fracture mechanics of multilayered elastomeric composites was simulated by the Blister Test using a polyurethane (PU)/A1 base plate interfacial assembly. In the various systems studies, and hard or soft intrposed layer (∼50 μm) separated the bulk matrix (∼ 1000 μm) from the metal counterface, with a hard-to-soft modules ratio of 1.70. Debonding was performed at a constant pressurization rate 1 × 10⁻⁸ m³/s corresponding to an average delamination rate of 0.25 m/s. Lateral hardening of the composite modules (negative transversal gradient of modulus) improved the fracture resistance (by 35%) at the material interface, in conformance with analytical predictions. Particle-dispersed and liquid-doped systems exhibited a sharp attenuation (40 to 90%) in the debond pressure. The latter results were substantiated by subjective assessement using optical microscopy, and were found consistent with stress concentration and weak conhesive fracture at the resin-substrate interface, respectively.     

O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6-benzylguanine derivatives and their rate of hydrolysis by cellular esterases

To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types.