Activation of amylin gene transcription by LIM domain homeobox gene isl-1

The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.     

Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats

Animal experiments suggest that the fetal brain is sensitive to nicotine. Although much attention has been given to the relation between cigarette smoking during pregnancy and neurodevelopment in children, this remains controversial. Our study describes the relationship between maternal cigarette smoking during pregnancy and babbling abilities of the 8-month-old infant. In a longitudinal cohort, information was collected at the 16th week of gestation, at delivery and when the infant was about 8 months old. At this age babbling abilities of the infant were evaluated by a health visitor during a home visit. Singleton infants without any disability born at Aarhus University Hospital, Denmark, 1991-92 and still living in the Community of Aarhus at the age of 8 months were eligible (n = 2302). Complete follow-up was obtained for 1871 children (81.3%). A dose-response-like relationship between number of cigarettes smoked per day during pregnancy and babbling abilities was found after controlling for potential confounders. Smoking 10 or more cigarettes per day during pregnancy almost doubled the risk (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.1-3.6) of the infant being a non-babbler at the examination at 8 months. Among children who were breast fed for less than 4 months this risk was even higher (OR = 2.7, CI 1.3-5.8).     

Expression of hepatocyte-enriched nuclear transcription factors in mouse liver tumours

The pharmacokinetics of amphotericin B administered in a conventional 5% dextrose (glucose) (5% D) solution and in a 20% fat emulsion formulation (Intralipid; 20% IL) were compared in 16 patients (mean age, 42 years [range, 18 to 70 years]) who had been hospitalized for hematological malignancies and with proven or suspected fungal infections. All of the patients received 50 mg (approximately 1 mg/kg of body weight per day) of amphotericin B daily in random order, either as a 50-ml lipid emulsion (20% IL) (group I) or in 500 ml of 5% D (group II). Five serum samples were taken during the 24 h after drug administration, and the levels of amphotericin B were measured by high-pressure liquid chromatography. Serum amphotericin B concentrations declined rapidly during the first 6 h, and subsequent measurements revealed a slow terminal elimination phase in both groups. The maximum serum amphotericin B concentration was significantly lower when the drug was administered in 20% IL (1.46 +/- 0.61 versus 2.83 +/- 1.17 micrograms/ml; P = 0.02). The area under the concentration-time curve from 0 to 24 h was also much lower in group I (17.22 +/- 11.15 versus 28.98 +/- 15.46 micrograms.h/ml). The half-life of the distribution phase was approximately three times longer in group I (2.92 +/- 2.34 h versus 0.64 +/- 0.24 h; P = 0.011). Conversely, the half-lives of the elimination phase were approximately equal in the two groups (11.44 +/- 5.18 versus 15.23 +/- 5.25 h). The mean residence times were also similar in both groups (19.41 +/- 11.13 versus 19.65 +/- 7.86 h). The clearance and the steady-state volume of distribution of amphotericin B in group I were about twice as great as those in group II (62.97 +/- 35.51 versus 33.01 +/- 14.33 ml/kg/h and 1,043.92 +/- 512.10 versus 562.32 +/- 152.05 ml/kg [P = 0.034], respectively). Finally, the volume of distribution in the central compartment was greater in group I than in group II (618.17 +/- 231.80 versus 328.19 +/- 151.71 ml/kg; P = 0.013), but there were no differences in the volume of distribution in the peripheral compartment (425.75 +/- 352.87 versus 234.14 +/- 75.92 ml/kg). These results suggest that amphotericin B has a different pharmacokinetic profile when it is administered in 20% IL than when it is administered in the standard 5% D form and that the main difference is due to a clear-cut difference in the steady-state volume of distribution, especially that in the central compartment.