In Japan, tuberculosis has been recognized as one of the major infections requiring urgent measures because of its high morbidity rate even now especially in elderly people suffering from tuberculosis during the past epidemic and its reactivation. Hence, many Japanese clinicians have made efforts to suppress the onset of tuberculosis and treat it effectively. The objectives of this study are to (1) identify covariate(s) that may explain the variation of rifampicin, which is the key antitubercular agent, under the steady-state by evaluating its population pharmacokinetics and (2) to propose an appropriate dosing method of rifampicin to Japanese patients. For this purpose, serum concentration–time data were obtained from 138 patients receiving rifampicin (300–450 mg) and isoniazid (300–400 mg) every day over 14 days, and analyzed using nonlinear mixed effects model. Thereby, population pharmacokinetic parameters were estimated followed by elucidating relations between the parameters and statistical factors. The analysis adopted one-compartment model including Lag-time by assuming that the absorption process is 0+1st order. The analyses demonstrate that meal affected the bioavailability, primary absorption rate constant, and zero order absorption time in the constructed model. A body weight calculated from the power model was selected as the covariate by the Stepwise Covariate Model method and found to highly affect the clearance in the range from −31.6% to 47.4%. We conclude that the dose in Japanese tuberculous patients can be well estimated by the power model formula and should be taken into consideration when rifampicin is administered.

T. High-dose growth hormone (GH) treatment in prepubertal GH-deficient children. Acta Pzdiatr 1999; Suppl 428:76-9. Stockholm. ISSN 0803-5326 Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH-deficient boys. In one study, GH doses of 1.0 and 1.5 IUkglweek (0.33 and 0.5 mglkglweek) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose-dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IUkg/week for the third year and 0.5 IUkg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in 'waning' of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency. 0 Growth hormone, growth hormone deficiency, high dose To achieve a satisfactory final height in children with growth hormone deficiency (GHD), it is essential to increase body height sufficiently before the children enter spontaneous puberty (1). Although conventional growth hormone (GH) treatment leads to an obvious improvement in height velocity during the first year, it is likely that an increased dose of GH would result in a much better growth response (2). Attenuation of height velocity, the so-called waning phenomenon, which occurs during the course of GH treatment, may also be reduced in children with GHD by stepwise increases in the GH dose, as is the case in girls with Turner syndrome (3). Two pilot studies were therefore conducted to determine whether higher than conventional doses of GH and stepwise increases in the GH dose can augment catch-up growth during the first year of treatment, minimize the waning effect in subsequent years and increase height before the onset of spontaneous puberty in children with GHD. Patients and methodsInclusion criteria for the studies included a chronological age over 4.0 years, a skeletal age below 7.5 years, a height below -2 SD for age and sex, peak serum GH levels of less than 10 pg/l in two cr more GH stimulation tests, and an average of the GH peaks of less than 10 pgA in all the stimulation tests undertaken.In the first study, two high fixed doses were used throughout the study period of more than 3 years (highdose study). Five boys were given subcutaneous injections of GH at a dose of 1.0 IU/kg/week (0.33 m...

No abstract

No abstract

We herein report a case study of a female newborn with multiple pituitary hormone deficiencies who presented with generalized seizures, hypoglycemia and hyperammonemia at 18 h after birth. In addition, we review the association of hyperammonemia in neonates with multiple pituitary hormone deficiencies reported in the previous literature. This unrecognized association should be taken into account for the early diagnosis and treatment of these patients.