SURVEY OF CARDIAC ARRESTS AND CARDIAC ARREST TROLLEYS IN A DISTRICT GENERAL HOSPITAL

SUMMARY In a 12-month period there were 137 cardiac arrests in a district general hospital. Cardiopulmonary resuscitation was instituted within 3 minutes in 82%. Delay in 18% was due to equipment failure. Survival at 6 months was 12%. Of the 18% of inappropriate arrests, 42% had ‘do-not-resuscitate’ orders in the casenotes. Survival did not depend on age, sex, location, presence of an anaesthetist, experience of house officer, time of day or admission diagnosis. Survival was more likely in the presence of ventricular fibrillation and absence of intubation. Of the 32 arrest trolleys, 66% were geographically acceptable to the area they served and 9% had significant deficiencies (these were situated in patient waiting areas and were infrequently checked).     

Molecular requirements for inhibition of the chemokine receptor CCR8 – probe-dependent allosteric interactions

BACKGROUND AND PURPOSE

Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes.

EXPERIMENTAL APPROACH

The compounds were tested as inverse agonists and as antagonists against CCL1-induced activity in Gα_i signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus-encoded antagonist MC148.

KEY RESULTS

All compounds were highly potent inverse agonists with EC₅₀ values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC₅₀ values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100-fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [¹²⁵I]-CCL1 (K_i 3.4–842 nM), whereas the affinities measured against [¹²⁵I]-MC148 were less widely spread (K_i 0.37–27 nM), and matched the inverse agonist potencies.

CONCLUSION AND IMPLICATIONS

Despite highly potent and direct effects as inverse agonists, competition-binding experiments against radiolabelled agonist and tests for antagonism revealed a probe-dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.     

Gastric cancer incidence and geographical variations: the influence of gender and rural and socioeconomic factors, Zaragoza (Spain)

Background

Socioeconomic status (SES) and rural factors have been shown to be associated with gastric cancer epidemiology. The aim of this study was to identify geographical variations in gastric cancer incidence in Zaragoza province (Spain) during the period 1993–2002, and their association with SES and rural factors.

Methods

Incident cases were extracted from the population-based Zaragoza Cancer Registry. The geographical analysis unit was the census tract (CT) in Zaragoza city (N = 462) and the municipalities for the rest of the province (N = 292). Four indexes were applied: two deprivation and two rurality indexes, included in a Bayesian risk model discretized in quartiles. Standardized incidence ratios (SIRs) were calculated using the incidence rates in Spain. SIRs were adjusted by a Bayesian generalized linear mixed model (GLMM).

Results

From 1993 to 2002, 1,309 cases of gastric cancer were registered in Zaragoza city and 578 in the rest of the province. High risk was observed in CTs for the peripheral areas of the city. The incidence risk in men was 2 (95 % confidence interval [CI] 1.22–2.98) times higher in the most deprived CTs compared with the least deprived CTs, but no statistically significant differences were found in women. Municipalities with higher risk were observed in the north of the province, but no significant association was found with SES. Regarding the rurality index, a positive trend was observed in women, but it was statistically significant only for the most rural quartile (2.49, 95 % CI 1.07–4.92).

Conclusions

Geographical differences in gastric cancer incidence were detected. Although these differences could be partially explained by the deprivation index for men in Zaragoza city, deprivation index cannot explain geographical differences for women. In the rest of the province, the rurality index 1991 could explain, at least for women, geographical differences. It is still necessary to develop a deprivation index suitable for small municipalities.