Benefits of ambulatory blood pressure monitoring in the design of antihypertensive drug trials

REVIEW IN DEPTH: Ambulatory blood pressure monitoring (ABPM) offers substantial advantages over conventional clinic measurement in the assessment of antihypertensive agents. There is a greater reproducibility of an average blood pressure taken from multiple readings,s and in the setting of a clinical trial this translates into increased precision of the assessment of mean antihypertensive effect. The temporal profile of blood pressure and the antihypertensive effect of an agent can be studied directly, and times of the day of particular clinical importance, such as the end of the dosing period and the early morning period, can be studied more easily than for conventional blood pressure measurement. ABPM reduces the size of any placebo effect on blood pressure to very low values, and it can be used to exclude white-coat hypertensives from clinical trials, thereby reducing the noise in a clinical trial. The role of ABPM in drug evaluation looks set to increase further with new developments in blood pressure measurement technology.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

The timing of disability measurements following injury

Disability following trauma has profound personal, social and economic costs. Currently, measurement of disability is not standardised and no agreed time interval between injury and disability measurement exists. This study was designed to define the best time at which to measure disability following trauma. The functional independence measurement (FIM) and Glasgow outcome scale (GOS) were assessed at 3, 6, 12 and more than 24 months after injury for 201 trauma patients. The best time to measure was defined as the point at which a steady state was reached, i.e. when further functional improvement ceased. Motor FIM showed significant change between 3 and 6 month assessments (p < 0.002) and 6 and 12 months (p < 0.002). No statistically significant change occurred beyond 12 months (p > 0.02). For Cognitive FIM, there was significant change between 3 and 6 months (p = 0.02), but not beyond 6 months (p > 0.2). For GOS there was significant change between 3 and 6 months (p < 0.002) and 6 and 12 months (p < 0.002) but not beyond 12 months (p > 0.2). Disability measurements should be performed 12 months after injury, when patients have reached a steady state. This time of measurement should be adopted as the standard for trauma databases and outcome studies.