Effect of indomethacin on arachidonic acid metabolism in human leukocytes stimulated ex vivo.

We had previously shown that inhibition of cyclooxygenase in vitro by indomethacin can cause increased formation of products of the 5-lipoxygenase pathway of arachidonic acid metabolism in leukocytes. To determine if this effect also occurred in vivo, we studied leukocyte arachidonic acid metabolism in 12 volunteers before and after ingestion of 150 mg indomethacin daily for 3 days. Blood was collected before treatment and 2 hours, 2 days, and 5 days after the final dose of indomethacin. Serum thromboxane B2, a measure of platelet cyclooxygenase activity, was profoundly suppressed 2 hours after the final dose of indomethacin but had recovered to control values at 2 days. Mixed leukocyte suspensions and purified neutrophil suspensions were prepared and stimulated with calcium ionophore A23187 and the resultant 5-lipoxygenase metabolites were quantified by HPLC. Two hours after the final dose of indomethacin, the stimulated levels of 5-hydroxyeicosatetraenoic acid, leukotriene B4, and leukotriene C4 were significantly increased to 247% +/- 68%, 135% +/- 14%, and 149% +/- 23% of pretreatment values, respectively. Two days after the final dose of indomethacin, 5-hydroxyeicosatetraenoic acid levels were still significantly elevated. By 5 days all parameters had returned to baseline. Similar effects were not observed in purified neutrophil suspensions, probably because of the loss of indomethacin from the cells during the multiple washing procedures used in their preparation. This is in accord with the reversible nature of the inhibitory effect of indomethacin on cyclooxygenase. We conclude that indomethacin at a commonly used dose increases the ability of circulating leukocytes to produce 5-lipoxygenase products.     

Expression of functional postjunctional alpha 2-adrenoceptors in rabbit isolated distal saphenous artery--a permissive role for angiotensin II?

In the rabbit isolated distal saphenous artery, the population of postjunctional adrenoceptors is of the alpha 1 variety under normal in vitro experimental conditions, based on the potency order of selective agonists and on the effects of the antagonists prazosin and rauwolscine against responses to UK-14304. Angiotensin II (A II, 0.05 microM) however, without affecting resting baseline tension, markedly enhanced responses to UK-14304, particularly at low concentrations. This previously unseen component of the response to UK-14304 was resistant to prazosin (0.1 microM) but susceptible to rauwolscine (1 microM). A II would therefore appear to have a permissive role for the expression of a quiescent population of postjunctional alpha 2-adrenoceptors in the rabbit distal saphenous artery.     

Glutamergic Action on Alpha-Melanocyte-Stimulating Hormone Release from the Rat Hypothalamus

Release of α-melanocyte-stimulating hormone (α-MSH) synthesized in the hypothalamus is regulated by monoaminergic neuronal systems. An endogenous dopaminergic system inhibits α-MSH release (1, 2) whilst serotoninergic systems exert a biphasic effect on peptide release (3). The toxic effects of neonatal peripheral administration of monosodium glutamate on hypothalamic neurons containing proopiomelanocortin- (POMC-) derived peptides (4, 5) suggest additionally the presence of glutamate receptors on or indirectly influencing the POMC neuron. By comparison of the effect of the excitatory amino-acid agonists N-methyl-D-aspartate (NMDA), quisqualate and kainate on the release of α-MSH from superfused slices of rat hypothalamus, we have demonstrated a stimulatory glutamergic action on α-MSH release mediated through NMDA-type receptors.     

Systematic reviews – triumph of form over substance?

? Cochrane systematic reviews are conducted to identify level 1a evidence. So far the ENT group have published 24 reviews, while around 70 titles are in various stages of the review process. Only one review has been able to produce Ia evidence and the rest recommended further trials. ? The majority of otorhinolaryngology reviews are unable to identify level 1a evidence due to the paucity of high quality randomised control trials. ? This presents a challenge, therefore – to identify and discuss alternate methods of evidence gathering for future research?     

Stingray spine foreign body in the foot

An unusual case report of a retained stingray spine foreign body in the foot is presented. The case is interesting in that the foreign body, although visualized on radiograph, was difficult to locate intraoperatively. A review of techniques for localizing foreign bodies in the foot is presented as well as a discussion on stingray injuries in general. Because of the possibility of spine breakage in a stingray puncture wound, radiographs should be considered in injuries of this type.     

Work disability in adults with cystic fibrosis and its relationship to quality of life.

With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.     

Determinants of health-service use by low-income people.

Poverty influences health status, life expectancy, health behaviours, and use of health services. This study examined factors influencing the use of health-related services by people living in poverty. In the first phase, 199 impoverished users of health-related services in 2 large Canadian cities were interviewed by their peers. In the second phase, group interviews with people living in poverty (n = 52) were conducted. Data were analyzed using thematic content analysis. Diverse health-related services were used to meet basic and health needs, to maintain human contact, and to cope with life's challenges. Use of services depended on proximity, affordability, convenience, information, and providers' attitudes and behaviours. Use was impeded by inequities based on income status. To promote the health of people living in poverty, nurses and other health professionals can enhance the accessibility and quality of services, improve their interactions with people living in poverty, provide information about available programs, offer coordinated community-based services, collaborate with other sectors, and advocate for more equitable services and policies.