The aim of this study was to evaluate the pharmacodynamics and safety of midazolam after intravenous infusion or oral administration in preterm infants. METHODS PATIENTS WERE RANDOMLY ASSIGNED TO ...INITIALLY RECEIVE MIDAZOLAM 0.1 MG/KG AS A 30-MINUTE INTRAVENOUS INFUSION OR AN ORAL BOLUS DOSE. IF PATIENTS STILL MET THE INCLUSION CRITERIA, THEY THEN RECEIVED MIDAZOLAM VIA THE ALTERNATE ROUTE (AFTER AN INTERVAL OF ≥72 HOURS). PHARMACODYNAMIC MEASUREMENTS CONSISTED OF A COMFORT® SCORE (A PREVIOUSLY VALIDATED SEDATION SCALE FOR PAEDIATRIC PATIENTS) AT BASELINE AND AT 0.5, 1, 2, 4 AND 6 HOURS POSTDOSE. MIDAZOLAM AND 1-OH-MIDAZOLAM CONCENTRATIONS WERE MEASURED AND VITAL SIGNS WERE RECORDED AT ALL PHARMACODYNAMIC MEASUREMENT TIMEPOINTS:
A total of 24 infants were enrolled of whom seven received both intravenous and oral midazolam, 13 received only intravenous midazolam, and four received only oral midazolam. Overall, mean COMFORT® scores decreased (i.e. sedation increased) significantly within 30 minutes after intravenous (p S 0.05) and within 1 hour after oral (p = 0.003) midazolam administration. In 45% of patients the COMFORT® scores decreased little or not at all after midazolam, which was similar after both oral and intravenous administration. The sedative response to midazolam did not differ after intravenous or oral administration. No relationship was found between overall COMFORT® scores or change in COMFORT® score from baseline and midazolam, 1-OH-midazolam, or midazolam plus 1-OH-midazolam concentrations. Diastolic blood pressure decreased significantly after intravenous (approximately 11%) but not after oral midazolam administration. No serious adverse events were reported.
Midazolam administered as a 30-minute intravenous infusion or oral bolus dose appears to be effective and well tolerated in a small majority of preterm infants. However, a considerable number of neonates do not appear to respond to midazolam. The lack of response may be due to the fact that patients truly experienced therapeutic failure and/or consequent to the inability of the COMFORT® score to adequately reflect sedation uniformly in sick preterm infants.
Only partial resistance is available for sheath blight, the second most important disease of rice (Oryza sativa L.) worldwide. This partial resistance has been considered to be polygenic. The partial ...resistance of the cultivars Jasmine 85 (J-85) and Teqing (TQNG) was studied by evaluating the resistance of F(1), F(2), F(3), F(4), and backcross F(1) generations of crosses between the resistant parents and the susceptible cultivars Maybelle (MBLE) and Cypress (CPRS). F(1) plants from the crosses were resistant. Segregating F(2) populations from both crosses showed ratios of 3:1 resistant/susceptible plants. Segregating backcross F(1) populations showed a ratio of 1:1 resistant/susceptible plants when the F(1) was crossed to a susceptible parent and no segregation occurred when the F(1) was crossed to a resistant parent. These results were consistent with the partial resistance from the two resistant cultivars being controlled by single dominant genes. When the resistant cultivars were crossed, the segregation F(2) population showed a 15:1 resistant/susceptible ratio. The results suggested that the two resistant parents each possessed a nonallelic dominant major resistance gene that segregated independently. Some of the F(4) lines from this cross appeared to have both resistance genes and a higher level of resistance than either resistant parent. This suggests that major genes conferring high levels of partial resistance to sheath blight may be incorporated together into lines to give near complete resistance. This makes the identification of major genes for partial resistance to sheath blight critically important to rice breeding programs.
We have developed a solid-phase procedure for protein−protein conjugation that gives greater control over product size and composition than previous methods. Conjugates are assembled by sequential ...addition of activated proteins to the support under conditions suitable for maintaining the activity of the proteins. The total number of conjugate units to be prepared is fixed in the first step by the quantity of the first protein absorbed by the support. In each following step, the added protein links only to previously bound protein. The final conjugate is released to solution by cleaving the linker holding the first protein to the support. This stepwise assembly provides uniformly sized conjugates of the desired size and composition with placement of components at the desired positions within the structure. Using this approach, we have prepared a series of conjugates containing R-phycoerythrin as the central protein, with varying quantities of alkaline phosphatase and IgG with expected molecular masses ranging from 1.6 to 11.5 MDa. Size-exclusion chromatography and atomic force microscopy demonstrate homogeneity and control of the conjugate size. In an immunoassay for human thyroid stimulating hormone, the conjugates show signals consistent with their compositions.
