Head and neck cancer end of life care: complex challenges.

Head and neck cancers frequently carry a poor prognosis and are commonly associated with complex medical needs and symptoms. Timing of referral to specialist palliative care teams (SPCTs) is challenging. We present the case of a 57-year-old woman with locally highly advanced head and neck cancer. The patient had highly complex medical needs including a tracheostomy to maintain airway patency, artificial feeds via jejunostomy and impaired communication due to hearing loss, tracheostomy and fatigue. She required support with advance care planning and complex symptom management of pain related to abdominal skin excoriation due to leakage of gastric contents; bleeding of necrotic tumour; anxiety and discomfort due to displacement of tracheostomy. Care by an integrated SPCT allowed smooth transition from hospital to community settings with smooth ongoing management despite highly complex needs. This complex symptom management included tracheostomy removal in the home towards the end of life.

Discovery and Optimization of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic Acid, an Improved PDE4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease (COPD).

Herein we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although compound 2 produces emesis in humans when given as a single dose, its exemplary pharmacokinetic properties enabled a novel dosing regime comprising multiple escalating doses and the resultant achievement of high plasma drug levels without associated nausea or emesis.

Solubility-driven optimization of phosphodiesterase-4 inhibitors leading to a clinical candidate.

The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

Emergency care for people with dementia.

As part of its commitment to improving dementia services, the Scottish Government has published six recommendations for developing care in emergency departments. This article looks at how each of these recommendations can be implemented by emergency nurses to make departments safer places for older people with confusion.

Making a broader case for the narrow view: where to begin?

PURPOSE: This final article covering the topic of the interplay between decoding, comprehension, and content versus structure knowledge describes a set of language initiatives that are focused toward content area learning. Inspired by the work of their colleagues from diverse fields and their own work, the authors offer suggestions to clinicians who are interested in creating and delivering curriculum-relevant and strategic-based language intervention to school-age students with language learning disabilities (LLD). METHOD: The discussion covers selected topics that form the foundation for an evolving intervention framework, including (a) understanding the content and structural requirements of textbooks, (b) integrating metacognitive and metalinguistic techniques into intervention goals and objectives, and (c) emphasizing meaning-based activities that cut across connected discourse (macrostructure levels) and sentence/word components (microstructure levels) of spoken and written language. CONCLUSION: Starting with ways to find clues about "what to do" with students by looking in their textbooks, the authors continue with examples that integrate content and structure knowledge using social studies and science as backdrops for language intervention. The article ends with a reminder to clinicians to consider ways that preschool language intervention can be more effective in helping children prepare for the academic demands of the future.

The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection.

Trichinella spiralis and Trichuris muris are nematode parasites of the mouse, dwelling in the small and large intestines, respectively: worm expulsion requires development of a Th2 immune response. The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites. The role of CCL11 in gastrointestinal helminth infection has not been previously studied. We challenged wild-type (WT) BALB/c, CCL11 single knockout (SKO) and CCL11 IL-5 double knockout (DKO) mice with either T. spiralis muscle larvae or T. muris eggs in order to examine eosinophil recruitment to the small and large intestine during helminth infection. A peripheral eosinophilia was seen in WT and SKO mice during T. spiralis infection but not with T. muris. Gastrointestinal eosinophilia was markedly reduced but not ablated in SKO mice -- and negligible in DKO mice -- infected with either nematode. The residual eosinophilia and up-regulation of CCL24 mRNA in the gastrointestinal tract of SKO mice infected with either nematode, together with the presence of an eosinophil-active factor in T. spiralis and T. muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection.

Management factors affecting stereotypies and body condition score in nonracing horses in Prince Edward Island.

In North America, there are few representative data about the effects of management practices on equine welfare. In a randomized survey of 312 nonracing horses in Prince Edward Island (response rate 68.4%), owners completed a pretested questionnaire and a veterinarian examined each horse. Regression analyses identified factors affecting 2 welfare markers: body condition score (BCS) and stereotypic behavior. Horses' BCSs were high (mean 5.7, on a 9-point scale) and were associated with sex (males had lower BCSs than females; P < 0.001) and examination date (P = 0.052). Prevalences of crib biting, wind sucking, and weaving were 3.8%, 3.8%, and 4.8%, respectively. Age (OR = 1.07, P = 0.08) and hours worked weekly (OR = 1.12, P = 0.03) were risk factors for weaving. Straw bedding (OR = 0.3, P = 0.03), daily hours at pasture (OR = 0.94, P = 0.02), and horse type (drafts and miniatures had a lower risk than light horses; P = 0.12) reduced the risk of horses showing oral stereotypies. Some of these results contradict those of other studies perhaps because of populations concerned.

A preliminary equine abuse policy with potential application to veterinary practice.

An equine abuse policy was developed as an adjunct to an equine management survey. If at least 3 of 5 categories caused concern, a report to the authorities was indicated. The policy was not used but, in the absence of other guidelines, it might assist veterinarians considering potential abuse cases.

A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential.

The synthesis and SAR of 5-heterocycle-substituted aminothiazole adenosine receptor antagonists is described. Several compounds show high affinity and selectivity for the A2B and A3 receptors. One compound (5f) shows good ADME properties in the rat and as such may be an important new compound in testing the current hypotheses proposing a therapeutic role for a dual A2B/A3 antagonist in allergic diseases.

Demographics, management, and welfare of nonracing horses in Prince Edward Island.

There are no detailed, representative, horse-level data about equine management practices in different parts of Canada. To help address this, the demographics, management, and welfare of 312 nonracing horses in Prince Edward Island were examined in a randomized, horse-level survey during summer 2002. Owners completed a pretested questionnaire, and a veterinarian examined each horse. Owners were experienced caregivers and the horses were generally in good condition. Areas for improvement included parasite control, dental and hoof care, and tail docking. The mean fecal egg count was 428 eggs per gram; 76% of owners never removed manure from the pasture. Sixty-two percent of horses had never had a veterinary dental examination. Many horses had hoof defects (excessively long hooves, 26.8%; hoof wall breaks, 32.0%; and white line disease, 8.5%). Many (54.9%) draft horses had docked tails. These results suggest owners might benefit their horses by receiving education in aspects of equine care.

Expression of fibronectin-binding protein FbpA modulates adhesion in Streptococcus gordonii.

Fibronectin binding is considered to be an important virulence factor in streptococcal infections. Adhesion of the oral bacterium Streptococcus gordonii to immobilized forms of fibronectin is mediated, in part, by a high molecular mass wall-anchored protein designated CshA. In this study, a second fibronectin-binding protein of S. gordonii is described that has been designated as FbpA (62.7 kDa). This protein, which is encoded by a gene located immediately downstream of the cshA gene, shows 85 and 81% identity to the fibronectin-binding proteins PavA, of Streptococcus pneumoniae, and FBP54, of Streptococcus pyogenes, respectively. Purified recombinant FbpA bound to immobilized human fibronectin in a dose-dependant manner, and isogenic mutants in which the fbpA gene was inactivated were impaired in their binding to fibronectin. This effect was apparent only for cells in the exponential phase of growth, and was associated with reduced surface hydrophobicity and the surface expression of CshA. Cells in the stationary phase of growth were unaffected in their ability to bind to fibronectin. By utilizing gene promoter fusions with cat (encoding chloramphenicol O-acetyltransferase), it was demonstrated that cshA expression was down-regulated during the exponential phase of growth in the fbpA mutant. Expression of fbpA, but not cshA, was sensitive to atmospheric O2 levels, and was found to be up-regulated in the presence of elevated O2 levels. The results suggest that FbpA plays a regulatory role in the modulation of CshA expression and, thus, affects the adhesion of S. gordonii to fibronectin.