Attitudes of veterinary nurses to the assessment of pain and the use of pain scales.

In April 2004, a questionnaire was distributed to veterinary nurses across the UK to assess their attitudes towards the assessment and management of pain in practice. During the six-week collection period, a total of 541 questionnaires were returned, of which 24 (4.25 per cent) were discounted due to completion errors. Overall, the pain scores for procedures involving dogs were higher than those for cats; the veterinary nurses' pain scores were higher for all procedures than those of veterinary surgeons in a previous study. Both veterinary nurses and veterinary surgeons were primarily involved with monitoring pain postoperatively, and 96 per cent of veterinary nurses felt that their knowledge of pain management could be enhanced; 8.1 per cent of the practices used a formal pain scoring system, with the simple descriptive scale most commonly used; 80.3 per cent of the veterinary nurses agreed that a pain scale was a useful clinical tool.

The scholarship of application.

The scholarship of application encompasses a broad range of different types of scholarship in the sciences and humanities that involves translation of new knowledge to practical applications to solve problems of individuals and of society. The authors discuss this form of scholarship broadly, but focus on how it applies to patient-oriented research and to service performed by physicians. They distinguish between a clinician's use of his or her expertise (not scholarship) and a clinician's activities such as systematically assessing the effectiveness of different techniques and communicating the findings in a way that allows others to benefit (scholarship). They (1) review the importance of scholarship of application (i.e., society depends on the application of new knowledge), with special attention to the benefits to academic institutions; (2) discuss incentives for such scholarship (e.g., readiness of funding for directly applicable research) and disincentives (e.g., shortcomings in methods; lower prestige); (3) explain how it should be evaluated (create a more expansive peer-review process); (4) explain how it should be rewarded (rewards should be similar to those given for other forms of scholarship); and (5) describe how it should be nurtured (rigorous training in methodology, protected time for research, tangible support). They conclude that the interdependence of academic institutions and of society requires that the scholarship of application be conducted with rigor and relevance, and that institutions must develop strategies to promote applied scholarship.

A sensitive and specific radioimmunoassay for LY309887, a potent inhibitor of glycinamide ribonucleotide formyltransferase.

LY309887, a reduced analogue of folic acid, is a potent inhibitor of glycinamide ribonucleotide formyltransferase and possesses a broad spectrum of antitumor activity. During preclinical studies using supplementation with oral folic acid, this second-generation inhibitor displayed both the desired safety profile and the pharmacology to warrant clinical investigation. A sensitive analytical method was needed to assess the pharmacokinetics of LY309887 due to the low doses planned for Phase I studies and the potential for low concentrations in plasma long after i.v. administration. We therefore undertook the development of a competitive RIA. A highly specific antiserum was raised in rabbits following immunization with LY309887 coupled to BSA. A RIA tracer was prepared by radioiodination of compound 389753, the adduct of LY309887 with p-tyramine. We developed a competitive-binding RIA procedure and used superparamagnetic particles coated with goat antirabbit IgG as a method for separating the bound and free forms of LY309887. The RIA is sensitive (0.5 ng/ml in serum and 25 ng/ml in urine), specific (negligible interference from endogenous folates), and reproducible (interassay coefficients of variation ranging from 8.1 to 15.4% and 7.6 to 8.3% for serum and urine controls, respectively). We used the RIA to assess the i.v. pharmacokinetics of LY309887 in both patients with metastatic cancer and dogs. The sensitivity of the RIA permitted the demonstration that serum concentrations of LY309887 decline in a multiexponential manner with a prolonged terminal elimination phase. We conclude that the RIA is a valid method for quantifying LY309887 in biological fluids.

Glomerular epithelial cell products stimulate mesangial cell proliferation in culture.

Glomerular epithelial cells (GEC) and mesangial cells (MC) are both involved in glomerular diseases. To elucidate potential interactions between these glomerular cell types, we examined whether products of GEC affect the proliferative activity of MC. We found that cultured rat GEC secrete soluble factors into the supernate (GEC-CM) that induce proliferation of quiescent rat MC. The mitogenic activity was trypsin sensitive and partially heat-labile. Biochemical analysis of GEC-CM by gel filtration HPLC, reverse phase HPLC, and isoelectric focusing revealed at least three mitogenic fractions as well as inhibitory activity present in GEC-CM. Competitive binding assays with 125I-labeled PDGF did not show significant amounts of PDGF in GEC-CM. The biochemical features of the GEC-derived MC growth factors are distinct from IL-6, PDGF, bFGF, and endothelin, previously described GEC-derived MC growth factors. Additionally, significant contributions of known growth factors such as IL-1, IL-2, IL-3, IL-4, IL-5, TNF alpha, TGF beta, and GM-CSF are unlikely. The results indicate that GEC produce several biochemically-distinct MC growth regulators. While these epithelial cell-derived mitogens for MC require further characterization, they may play an important role in the regulation of MC replication, such as during embryogenesis and glomerular disease.

Crushing your health plan's legal protection.

Enacted in the pre-managed care days, ERISA has shielded health plans from liability in a way the nation's lawmakers may never have intended. The business community watches warily as this blanket protection erodes.

Tonsillar tissue penetration of dirithromycin after multiple doses.

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (+/-standard deviation) of erythromycylamine and erythromycin were 0.20 +/- 0.07 microgram/mL and 0.12 +/- 0.25 microgram/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 microgram/mL and 1.57 +/- 3.16 micrograms/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of > 8 micrograms/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 micrograms/ g after 5 days and 3.47 +/- 2.84 micrograms/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis with dirithromycin.