Circadian blood pressure variability in adrenocorticotrophin-induced hypertension in the rat

OBJECTIVES: Secondary hypertension is often characterized by loss of diurnal blood pressure variability. This study examined circadian (24 h) blood pressure variability in adrenocorticotrophin (ACTH)-induced hypertension in the Sprague-Dawley rat. METHODS: Male Sprague-Dawley rats were randomly allocated to sham (0.9% saline, s.c.), n = (9), ACTH (0.5 microg/kg per day, s.c., n = 8) or ACTH (100 microg/kg per day, s.c., n = 7) in a room with a 12 h light/dark cycle (0600 h to 1800 h). A radio telemetry transducer was used to measure blood pressure in unrestrained animals over 3 control days (C1-C3) and 10 treatment days (T1-T10). Heart rate, systolic (SBP), mean arterial (MAP) and diastolic (DBP) blood pressure were continuously recorded. Body weight was measured daily and serum corticosterone concentration ([B]) prior to death. RESULTS: Sham treatment had no effect on any parameters. ACTH 100 microg/kg per day increased SBP from 124+/-2 pooled control (PC) to 134+/-2 mmHg (T10), MAP from 105+/-2 to 115+/-2 mmHg and DBP from 87+/-1 to 99+/-2 mmHg and decreased heart rate from 305+/-6 to 249+/-5 beats/min and body weight from 299+/-6 (C3) to 280+/-8 g (T10) (all P' < 0.0036). Serum [B] was higher in ACTH- (881+/-44 ng/ml) than sham-treated rats (384+/-17 ng/ml, P < 0.001). There were no differences between sham treatment and ACTH 0.5 microg/kg per day. SBP, MAP, DBP and heart rate were consistently higher for ACTH 100 microg/kg per day and sham-treated animals during the dark cycle (1800 h to 0600 h) than the light cycle (0600 h to 1800 h). CONCLUSIONS: ACTH 100 microg/kg per day raises blood pressure in conscious unrestrained Sprague-Dawley rats without any change in normal diurnal rhythm.     

Tuberculosis in aged gammadelta T cell gene disrupted mice

In young mice exposed to aerosol infection with Mycobacterium tuberculosis removal of the gammadelta T cell population by targeted gene disruption does not affect the expression of host resistance, but does influence the integrity of the early granulomatous response. The current study demonstrates that in aged gammadelta T cell gene disrupted mice similar immunopathologic changes ensued in both gene knockout and wild type control mice. Changes in cell surface marker expression, evident in other gene knockout models, was not observed in the aged gammadelta T cell knockout mice. These data imply that gammadelta T cell functions previously observed in young mice become much less important as the animal ages.     

The continuing HIV epidemic among men who have sex with men

OBJECTIVES: This study characterized the AIDS epidemic among urban men who have sex with men (MSM). METHODS: A probability sample of MSM was obtained in 1997 (n = 2881; 18 years and older) from New York, Los Angeles, Chicago, and San Francisco, and HIV status was determined through self-report and biological measures. RESULTS: HIV prevalence was 17% (95% confidence interval = 15%, 19%) overall, with extremely high levels in African Americans (29%), MSM who used injection drugs (40%), "ultraheavy" noninjection drug users (32%), and less educated men (< high school, 37%). City-level HIV differences were non-significant once these other factors were controlled for. In comparing the present findings with historical data based on public records and modeling, HIV prevalence appears to have declined as a result of high mortality (69%) and stable, but high, incidence rates (1%-2%). CONCLUSIONS: Although the findings suggest that HIV prevalence has declined significantly from the mid-1980s, current levels among urban MSM in the United States approximate those of sub-Saharan countries (e.g., 14%-25%) and are extremely high in many population subsegments. Despite years of progress, the AIDS epidemic continues unabated among subsegments of the MSM community.     

Bayesian methods of analysis for cluster randomized trials with binary outcome data

We explore the potential of Bayesian hierarchical modelling for the analysis of cluster randomized trials with binary outcome data, and apply the methods to a trial randomized by general practice. An approximate relationship is derived between the intracluster correlation coefficient (ICC) and the between-cluster variance used in a hierarchical logistic regression model. By constructing an informative prior for the ICC on the basis of available information, we are thus able implicitly to specify an informative prior for the between-cluster variance. The approach also provides us with a credible interval for the ICC for binary outcome data. Several approaches to constructing informative priors from empirical ICC values are described. We investigate the sensitivity of results to the prior specified and find that the estimate of intervention effect changes very little in this data set, while its interval estimate is more sensitive. The Bayesian approach allows us to assume distributions other than normality for the random effects used to model the clustering. This enables us to gain insight into the robustness of our parameter estimates to the classical normality assumption. In a model with a more complex variance structure, Bayesian methods can provide credible intervals for a difference between two variance components, in order for example to investigate whether the effect of intervention varies across clusters. We compare our results with those obtained from classical estimation, discuss the relative merits of the Bayesian framework, and conclude that the flexibility of the Bayesian approach offers some substantial advantages, although selection of prior distributions is not straightforward.     

Meta-analysis of continuous outcome data from individual patients

Meta-analyses using individual patient data are becoming increasingly common and have several advantages over meta-analyses of summary statistics. We explore the use of multilevel or hierarchical models for the meta-analysis of continuous individual patient outcome data from clinical trials. A general framework is developed which encompasses traditional meta-analysis, as well as meta-regression and the inclusion of patient-level covariates for investigation of heterogeneity. Unexplained variation in treatment differences between trials is considered as random. We focus on models with fixed trial effects, although an extension to a random effect for trial is described. The methods are illustrated on an example in Alzheimer's disease in a classical framework using SAS PROC MIXED and MLwiN, and in a Bayesian framework using BUGS. Relative merits of the three software packages for such meta-analyses are discussed, as are the assessment of model assumptions and extensions to incorporate more than two treatments.     

The General Medical Council's Performance Procedures: peer review of performance in the workplace

The General Medical Council procedures to assess the performance of doctors who may be seriously deficient include peer review of the doctor's practice at the workplace and tests of competence and skills. Peer reviews are conducted by three trained assessors, two from the same speciality as the doctor being assessed, with one lay assessor. The doctor completes a portfolio to describe his/her training, experience, the circumstances of practice and self rate his/her competence and familiarity in dealing with the common problems of his/her own discipline. The assessment includes a review of the doctor's medical records; discussion of cases selected from these records; observation of consultations for clinicians, or of relevant activities in non-clinicians; a tour of the doctor's workplace; interviews with at least 12 third parties (five nominated by the doctor); and structured interviews with the doctor. The content and structure of the peer review are designed to assess the doctor against the standards defined in Good Medical Practice, as applied to the doctor's speciality. The assessment methods are based on validated instruments and gather 700-1000 judgements on each doctor. Early experience of the peer review visits has confirmed their feasibility and effectiveness.     

What does it mean to be a donor offspring? The identity experiences of adults conceived by donor insemination and the implications for counselling and therapy

In the absence of research with adult donor offspring, this study begins to bridge that gap by asking individuals about their experiences as donor offspring and considering the implications for psychotherapeutic and counselling practice. Sixteen participants (13 male, three female, age range 26-55 years) recruited through donor insemination support networks in the UK, USA, Canada and Australia, were sent semi-structured questionnaires by E-mail and post. Using identity process theory as a framework for understanding participants' accounts, the data were qualitatively analysed using interpretative phenomenological analysis. Participants consistently reported mistrust within the family, negative distinctiveness, lack of genetic continuity, frustration in being thwarted in the search for their biological fathers and a need to talk to a significant other (i.e. someone who would understand). These experiences could be postulated as being indicative of a struggle to assimilate, accommodate and evaluate information about their new identities as donor offspring. Psychotherapists and counsellors need to be aware of these identity issues if they are to meet the needs of donor offspring within therapeutic practice.     

Genes on the X chromosome are important in undiagnosed mental retardation

The clinical genetic diagnosis was reviewed in 429 subjects with intellectual disability in the Australian Child and Adolescent Development (ACAD) study of behavioural problems. With minor differences, the overall "general distribution by causation" was similar to that to that found by the Consensus Conference of the American College of Medical Genetics in 1995. There was a significant male excess in the whole series which was shown to reside in those with "autism," those with undiagnosed nonsyndromic mental retardation (NSMR) and those with X-linked monogenic disorders. It is argued that a substantial proportion of undiagnosed NSMR is caused by genes on the X chromosome. Some of the practical problems of assigning individuals to diagnostic groups are discussed.