Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.     

The prevalence of premenstrual symptoms in Wellington women

A survey of 1826 women in the Wellington region was carried out. Participants were asked about their general and gynaecological health and their menstrual, contraceptive and obstetric history. Detailed questions were asked about the menstruating women's last menstrual cycle. Subjects were premenopausal women attending a random sample of general practice surgeries for any reason. The achieved sample is not intended as a cross-section of the Wellington community, but is nevertheless reasonably representative of the general adult female population aged 20 to 45. Most women volunteered one or more premenstrual symptoms; and about half of the women said these symptoms were such that they affected their lives.     

An exploration of the role of the nurses'' uniform through a period of non-uniform wear on an acute medical ward

The nursing staff on an acute medical hospital ward elected to wear their own clothes to work for a period of 2 months. The trial was evaluated using a variety of research methods and it raised a number of issues about the role of uniform, about patients' perceptions of nurses and nurses' perceptions of their role. The study has led to questions being raised about the assumptions that are made if uniform is worn and the appropriateness of a uniform dress.     

Prednisolone versus dexamethasone in croup: a randomised equivalence trial.

BACKGROUND: Croup remains a common respiratory problem presenting to emergency departments. A single oral treatment of oral dexamethasone results in improved outcome. Prednisolone has similar pharmacokinetic properties and has a significant advantage in that it is commercially available in liquid preparations. OBJECTIVE: To ascertain whether a single oral dose of prednisolone was equivalent to a single oral dose of dexamethasone (matched for potency) in children with mild to moderate croup. DESIGN: A double blind, randomised, controlled equivalence trial. SETTING: Tertiary paediatric emergency department. Patients: 133 children aged 3 to 142 months presenting with mild to moderate croup. INTERVENTIONS: Children received either a single oral dose of dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg. Outcome: The main outcome measure was unscheduled re-presentation to medical care as determined by telephone follow up at 7 to 10 days. Croup score, adrenaline (epinephrine) use, time spent in the emergency department, and duration of croup and viral symptoms were secondary outcome measures. RESULTS: Children treated with prednisolone were more likely to re-present: 19 of 65 children (29%) reattended medical care compared with 5 of 68 (7%) from the dexamethasone group. The confidence intervals around this 22% difference in outcome were 8% to 35%, outside the 0% to 7.5% range of equivalence. There were no significant differences in other outcome measures. CONCLUSION: A single oral dose of prednisolone is less effective than a single oral dose of dexamethasone in reducing unscheduled re-presentation to medical care in children with mild to moderate croup.     

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Serologic and molecular investigations of a chimera

A chimeric individual possesses two or more genetically distinct cell populations. Although the chimerism may not be evident in all gene systems, various loci display greater numbers of alleles than genetically "normal" individuals. The proposita was referred for further laboratory investigation due to a mixed-field ABO blood group reaction following routine antenatal testing. Various molecular (HLA class II, ABO genotyping, and 10 short tandem repeat [STR] microsatellites) and serologic (HLA class I and red cell blood groups) typing techniques were employed to investigate a number of polymorphic loci located on different chromosomes. Chimerism was identified in 8 out of the 14 chromosomes tested: chromosome 1 (Duffy), 6 (HLA class I and II), 9 (ABO), 11 (HUMTH01), 12 (HUMPLA2A1), 15 (HUMFES/FPS), 18 (Kidd) and 21 (D21S11). The proposita was determined to be a probable dispermic chimera, based on the results of the serology and molecular studies.     

Laboratory stress testing to assess real-life cardiovascular reactivity

Thirty-six normotensive adults received laboratory stress testing (mental arithmetic, short-term memory, isometric handgrip, cold pressor tests) and 24-hour ambulatory blood pressure monitoring on two work days separated by a month. Laboratory and ambulatory measures of cardiovascular reactivity had low test-retest reliability. Increases in blood pressure during the memory and cold pressor tests were related to measures of reactivity obtained outside the laboratory (waking blood pressure variability, responses to home and work environments). However, the portion of ambulatory reactivity accounted for by laboratory reactivity was small. In the best case (r = 0.43), cold pressor diastolic pressure explained only 19% of diastolic pressure variability in the natural environment. Laboratory-ambulatory disagreement in reactivity was related to interindividual variability in physical activity on the day of ambulatory monitoring.