PCTs/health improvement. The object of the exercise

A study of six primary care trusts showed that those most successful in tackling health improvement had certain common characteristics. Strong board-level support and leadership, combined with development funding, were the most effective. Successful PCTs also showed a corporate recognition of local health and socio-economic inequalities.     

Supporting community-based prevention and health promotion initiatives: developing effective technical assistance systems.

As research evidence for the effectiveness of community-based prevention has mounted, so has recognition of the gap between research and community practice. As a result, state and local governments are taking a more active role in building the capacity of community-based organizations to deliver evidence-based prevention interventions. Innovations are taking place in the establishment of technical assistance or support systems to influence the prevention and health education activities of community-based organizations. Several challenges for technical assistance systems are described: (1) setting prevention priorities and allocating limited technical assistance resources, (2) balancing capacity-building versus program dissemination efforts, (3) collaborating across categorical problem areas, (4) designing technical assistance initiatives with enough "dose strength" to have an effect, (5) balancing fidelity versus adaptation in program implementation, (6) building organizational cultures that support innovation, and (7) building local evaluative capacity versus generalizable evaluation findings.     

Treatment of joint pain in Crohn's patients with budesonide controlled ileal release

1. Joint pain is a frequent manifestation of Crohn's disease. Budesonide controlled ileal release (CIR) is a predominantly topically acting glucocorticosteroid, which is effective in treating active ileal or ileocaecal Crohn's disease. 2. Therefore, it was of interest to study the effect of this predominantly topically acting therapy on the treatment of an extraintestinal symptom of Crohn's disease by analysing data collected from budesonide CIR (Entocort; Astra Draco AB, Lund, Sweden) trials. 3. Three large studies of budesonide CIR treatment in active Crohn's disease provided a reliable source of clinical data. Of the 611 patients treated in the prospective double-blind controlled trials, 291 had joint pain (arthritis/arthralgia) at entry, which was recorded as part of the Crohn's Disease Activity Index. Statistical analysis was based on all patients treated, provided that the patient had joint pain at the start of treatment. 4. Daily oral budesonide CIR (9mg) resulted in clinical remission of joint pain in 74% (95% confidence intervals (CI) 67-82%) of patients. This outcome was nearly twice as good as placebo (41%; 95% CI 34-57%) and as good as the outcome effected by daily oral prednisolone (40mg; 72%; 95% CI 60-84%). The favourable response to budesonide CIR (9 mg) did not correlate with glucocorticosteroid-associated side effects or with adrenal suppression, which were half those in the prednisolone (40 mg/day) group. 5. The favourable outcome may relate to restitution of normal intestinal immune function.     

Effects of azapropazone on pain-related brain activity in human subjects.

1. The dose-related effects of azapropazone on (i) event-related and spontaneous EEG-activity and (ii) the subjects' pain ratings were investigated using an experimental human pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjects' pain ratings. 2. Healthy subjects (n = 20) participated in a placebo-controlled, randomized, double-blind, four-way cross-over study. Single doses of azapropazone (300 mg, 600 mg and 1200 mg) and placebo were administered intravenously. Each experiment consisted of five sessions (before and 1, 2, 4 and 8 h after administration of the medication). Each session lasted for approximately 40 min. In the first 20 min, pain was induced by short CO2-stimuli presented to the right nostril (phasic pain; interstimulus interval 30 s) and EEG was recorded from five positions. CSSERPs were obtained in response to painful CO2-stimuli. In the following 20 min period, tonic pain was induced by a constant stream of dry air introduced in the left nostril. Subjects rated the intensity of both phasic and tonic pain by means of a visual analogue scale. Additionally, a frequency analysis of the spontaneous EEG was performed. 3. Azapropazone reduced the pain-related CSSERP-amplitudes at frontal and parietal recording positions. This topographical pattern was observed in previous studies with opioids, while NSAIDs such as flurbiprofen and ketoprofen exerted effects at frontal and central positions. In contrast to other NSAIDs, administration of azapropazone resulted in a reduction of the frequency bands alpha 1, delta and theta of the spontaneous EEG. At the subjective level, analgesic effects of azapropazone were observed in the ratings of tonic pain. 4. Analgesic properties of azapropazone were demonstrated in man. The topographical pattern of the changes in the CSSERPs and the effects on EEG background activity suggest a central component of the analgesic action of azapropazone.     

Tumour necrosis factor inhibitors

The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of many chronic inflammatory and rheumatic diseases, in particular, Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Controlled trials have shown that the TNF inhibitors (etanercept, infliximab and adalimumab) significantly reduce symptoms and signs, improve function and quality of life, and reduce radiologically evident damage in patients with rheumatoid diseases. For reasons that are not entirely clear, etanercept does not work in Crohn's disease. Injection site and intravenous reactions and increased risk of infection (in particular, reactivation of tuberculosis) are associated with the use of these agents. Increased risk of lymphoproliferative disease, the development of lupus-like syndromes and demyelination, including optic neuritis and reactivation of multiple sclerosis, are under evaluation in long-term follow-up studies. The TNF inhibitors are expensive (about $18 000 per year), and in some patients need to be given continuously to maintain benefit, even in the presence of other immunosuppressive therapy.     

Nonneuronal origin of CO2-related DC EEG shifts: an in vivo study in the cat

We studied the mechanisms underlying CO(2)-dependent DC potential shifts, using epicranial, epidural, epicortical, intraventricular, and intraparenchymal (intraneuronal, intraglial, and field) recordings in ketamine-xylazine-anesthetized cats. DC shifts were elicited by changes in artificial ventilation, causing end-tidal CO(2) variations within a 2-5% range. Hypercapnia was consistently associated with negative scalp DC shifts (average shift -284.4 microV/CO(2)%, range -216 to -324 microV/CO(2)%), whereas hypocapnia induced positive scalp DC shifts (average shift 307.8 microV/CO(2)%, range 234 to 342 microV/CO(2)%) in all electrodes referenced versus the nasium bone. The former condition markedly increased intracranial pressure (ICP), whereas the latter only slightly reduced ICP. Breakdown of the blood-brain barrier (BBB) resulted in a positive DC shift and drastically reduced subsequent DC responses to hypo-/hypercapnia. Thiopental and isoflurane also elicited a dose-dependent positive DC shift and, at higher doses, hypo-/hypercapnia responses displayed reverted polarity. As to the possible implication of neurons in the production of DC shifts, no polarity reversal was recorded between scalp, various intracortical layers, and deep brain structures. Moreover, the membrane potential of neurons and glia did not show either significant or systematic variations in association with the scalp-recorded CO(2)-dependent DC shifts. Pathological activities of neurons during spike-wave seizures produced DC shifts of significantly smaller amplitude than those generated by hyper-/hypocapnia. DC shifts were still elicited when neuronal circuits were silent during anesthesia-induced burst-suppression patterns. We suggest that potentials generated by the BBB are the major source of epicortical/cranial DC shifts recorded under conditions affecting brain pH and/or cerebral blood flow.     

Modification of the peritoneoscopic technique of peritoneal dialysis catheter insertion: experience of an interventional nephrology program

Bowel perforation is a well-recognized complication of peritoneal dialysis catheter insertion and is associated with increased morbidity and cost of medical care. In this article we describe our 2-year experience (August 2001-October 2003) with a modified peritoneoscopic technique of peritoneal dialysis catheter insertion to minimize the incidence of bowel perforation. Seventy patients underwent 82 consecutive peritoneal dialysis catheter insertions using the innovative technique. The modified technique is very similar to the traditional peritoneoscopic procedure except for the following differences. To gain access to the peritoneal cavity, a Veress insufflation needle (Ethicon Endo-Surgery Inc., Cincinnati, OH) is utilized instead of the trocar. In contrast to the sharp tip of the trocar, the Veress needle has a blunt, self-retracting end. In addition, the Veress needle is only 14 gauge as opposed to the 2.2 mm diameter of the trocar. Upon introduction of the Veress needle into the abdominal cavity, two "pops" are discerned similar to the trocar. After introduction, 400-500 cc of air are infused and the needle is removed. The infusion of air creates a space between the peritoneal surface of the anterior abdominal wall and the bowel loops. At this point, the cannula with trocar is inserted into the space created. The rest of the steps of the procedure are the same as the traditional peritoneoscopic technique. Utilizing the innovative technique, all 82 catheter insertions were performed successfully without a single bowel perforation. No other complications except for catheter migration (n = 2) were noted. The extra cost of the needle (35 USD) should be viewed in the context of the costs associated with management of a bowel perforation. Large-scale studies are needed to confirm the superiority of this innovative technique over the traditional peritoneoscopic insertion found in our case series. In the interim, however, the increased morbidity and cost associated with bowel perforation calls for logical measures to be taken to avoid this dreaded complication.     

An unsupervised approach to identify molecular phenotypic components influencing breast cancer features

To discover a biological basis for clinical subgroupings within breast cancers, we applied principal components (PCs) analysis to cDNA microarray data from 36 breast cancers. We correlated the resulting PCs with clinical features. The 35 PCs discovered were ranked in order of their impact on gene expression patterns. Interestingly, PC 7 identified a unique subgroup consisting of estrogen receptor (ER); (+) African-American patients. This group exhibited global molecular phenotypes significantly different from both ER (-) African-American women and ER (+) or ER (-) Caucasian women (P < 0.001). Additional significant PCs included PC 4, correlating with lymph node metastasis (P = 0.04), and PC 10, with tumor stage (stage 2 versus stage 3; P = 0.007). These results provide a molecular phenotypic basis for the existence of a biologically unique subgroup comprising ER (+) breast cancers from African-American patients. Moreover, these findings illustrate the potential of PCs analysis to detect molecular phenotypic bases for relevant clinical or biological features of human tumors in general.