Therapeutic drug monitoring in pediatrics: a need for improvement

Therapeutic drug monitoring (TDM) is practiced for a number of frequently used drugs in infants and children. It is believed that monitoring drug levels will increase the probability of a therapeutic response and minimize the probability of adverse drug sequelae. Dose adjustments are based on measured drug levels interpreted relative to published therapeutic ranges which may or may not reflect the true relationship with either therapeutic or adverse effects. Potential errors derive from many sources, some amenable to solutions based on current knowledge, others awaiting improved understanding of the causes and consequences of unreliable therapeutic ranges.     

Intellectual deficits after transient tyrosinemia in the term neonate

An analysis was made of the obstetric history of 1,360 patients who were delivered in 1971. It involved 3,185 pregnancies. The aim of the study was to evaluate the risk of spontaneous termination of the pregnancy, worked out from its demographic aspect. Several ideas are worthy of consideration. The risk of spontaneous intra-uterine death is cumulative, sharply increased by a repetition of such cessation of pregnancy. The same patients often undergo intentional abortion repeatedly. The respective risks of spontaneous and provoked interruption of pregnancy have been studied in greater detail as a function of parity.     

Isolated premature breast development in young girls. Results of the LH-RH test

Thirty-six cases of premature thelarche in girls 9 months to 7 years old have been studied. In most cases, breast development began before 3 years and came to regression. Onset after 3 years was less common and led usually to breast persistance. Height was lightly but significantly advanced. Plasma levels of estrone, estradiol (in 21 cases) and gonadotropins (FSH and LH, in 12 cases) were not significantly increased. However, LH-RH test (in 12 cases) suggested prolongation and/or increase of the physiologic gonadotropic hyperactivity of normal female infants.     

The place of one-year training courses for construction management

The structure and philosophy of a one-year course in construction management are described. Emphasis is placed on the importance of forgetting old methods and ideas, in order to take full advantage of new technologies, and on the need to allow enough time for effective training.     

Remote control of a robot in a map network

The automated control of manufacturing devices on a common communications network is a necessity for the factory of the future. The manufacturing automation protocol (MAP) represents a major effort by a group of companies towards meeting this need, and apparently is becoming a standard for factory-floor communications. In this project, an ASEA 2000 robot was used with a computer-controlled ply-cutting machine in a simulated factory sheet-metal cell to demonstrate coordinated inter- and intra-cell communications. Both machines used a MAP network to send and receive information from the cell-controller computer, and to coordinate cell operation. The methodology, hardware and software required to adapt the ASEA robot to the MAP network are described. This methodology will be useful in adapting other computer-controlled manufacturing devices to MAP networks.     

Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells

The CD94/NKG2 receptors expressed by subpopulations of NK cells and T cells have been implicated as receptors for a broad range of both classical and nonclassical HLA class I molecules. To examine the ligand specificity of CD94/NKG2 proteins, a soluble heterodimeric form of the receptor was produced and used in direct binding studies with cells expressing defined HLA class I/peptide complexes. We confirm that CD94/NKG2A specifically interacts with HLA-E and demonstrate that this interaction is dependent on the association of HLA-E with peptide. Moreover, no interaction between CD94/NKG2A and classical HLA class I molecules was observed, as assayed by direct binding of the soluble receptor or by functional assays using CD94/NKG2A+ NK cells. The role of the peptide associated with HLA-E in the interaction between HLA-E and CD94/NKG2A was also assessed. All class I leader sequence peptides tested bound to HLA-E and were recognized by CD94/NKG2A. However, amino acid variations in class I leader sequences affected the stability of HLA-E. Additionally, not all HLA-E/peptide complexes examined were recognized by CD94/NKG2A. Thus CD94/NKG2A recognition of HLA-E is controlled by peptide at two levels; first, peptide must stabilize HLA-E and promote cell surface expression, and second, the HLA-E/peptide complex must form the ligand for CD94/NKG2A.