Obstacles and Opportunities for Multi-disciplinary Working in Drug Misuse: a case study

This paper examines the lack of congruence between national policy documents and local practice in multi-disciplinary working with drug users, by reporting on a case study within one English county. It gives an analysis of the roles and responsibilities of generic service providers and a minority of specialists, based on 100 interviews and questionnaires with representatives from professional groups involved with drug issues. The respondents worked with a range of young people and adults. Whilst professionals worked well within broad disciplines such as health or education, they did not operate as well across disciplinary boundaries. Many of the respondents were unsure about the specific role of their own profession, and which group they should target for drug interventions. There was a lack of clarity about what approach was appropriate to their traditional target group in terms of drugs, and consequently many did not utilize their established approach for that group. When the reasons for the lack of co-working were examined, it was found that there were many misconceptions among professionals concerning what other professional groups actually did in response to drugs. The authors clarify the reasons for the apparent confusion and highlight the possibility that a traditional generic approach and target group may not provide an appropriate match in terms of drug intervention. They make recommendations for overcoming these obstacles to multi-disciplinary working and consider the implications for training.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Calcification and ossification of chronic encapsulated intracerebral haematoma: case report.

We report a case of calcified chronic encapsulated intracerebral haematoma (ICH) in a 29-year-old female who presented with progressive left sided weakness and intermittent seizures since childhood. The preoperative magnetic resonance (MR) imaging of the head initially suggested that a partially thrombosed aneurysm or vascular malformation was present. However, no vascular stain was found on the digital subtraction angiography (DSA) of both the carotid and vertebral arteries. The excised mass was histologically diagnosed as a chronic ICH. We traced the patient's medical history and found that at the age of one she sustained a head injury after a fall. So far, to our knowledge, no case of epilepsy secondary to a calcified chronic encapsulated ICH occurring 28 years after head injury has been reported. Calcified chronic encapsulated ICH concomitant with new bone formation within is even rarer. The possible pathogenesis of this case is discussed.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Evaluation and assessment of high sensitivity thyrotropin methods as an index for thyroid function

We report the evaluation of four new commercially available sensitive assay kits for determination of thyrotropin (TSH) and their clinical utility in normal subjects and patients with thyroidal and non-thyroidal illnesses. The sensitivity for the reliable detection of serum TSH by these methods ranged from 0.1-0.4 mU/L and their decreasing order was : NML greater than Serono greater than Abbott EIA greater than Hybritech. The coefficient of variation ranged from 2.0-5.8% for intra-assay and 2.3-8.6% for interassay at different concentration levels. Patients studied (n = 130) were assigned into four groups on the basis of the serum thyroxine value and their clinical findings. In total, there were 17 discrepancies (five with Hybritech, three with NML, five with Abbott EIA, and four with Serono) in making the correct diagnosis using these sensitive TSH methods as a single diagnostic test. These discrepancies were mainly in the same patients who were clinically euthyroid but had subnormal TSH values. There were no discrepancies in making the correct diagnosis for patients with hyperthyroidism or hypothyroidism using these sensitive TSH methods. Our observations indicate that the sensitive TSH methods are reliable in measuring subnormal levels and may be used to detect hyperthyroidism without affecting in any way their value in detecting hypothyroidism.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.