The impact of geographic unit of analysis on socioeconomic inequalities in cancer survival and distant summary stage – a population‐based study

Objective: When using area‐level disadvantage measures, size of geographic unit can have major effects on recorded socioeconomic cancer disparities. This study examined the extent of changes in recorded socioeconomic inequalities in cancer survival and distant stage when the measure of socioeconomic disadvantage was based on smaller Census Collection Districts (CDs) instead of Statistical Local Areas (SLAs). Methods: Population‐based New South Wales Cancer Registry data were used to identify cases diagnosed with primary invasive cancer in 2000–2008 (n=264,236). Logistic regression and competing risk regression modelling were performed to examine socioeconomic differences in odds of distant stage and hazard of cancer death for all sites combined and separately for breast, prostate, colorectal and lung cancers. Results: For all sites collectively, associations between socioeconomic disadvantage and cancer survival and distant stage were stronger when the CD‐based socioeconomic disadvantage measure was used compared with the SLA‐based measure. The CD‐based measure showed a more consistent socioeconomic gradient with a linear upward trend of risk of cancer death/distant stage with increasing socioeconomic disadvantage. Site‐specific analyses provided similar findings for the risk of death but less consistent results for the likelihood of distant stage. Conclusions: The use of socioeconomic disadvantage measure based on the smallest available spatial unit should be encouraged in the future. Implications for public health: Disadvantage measures based on small spatial units can more accurately identify socioeconomic cancer disparities to inform priority settings in service planning.     

Bacterial meningitis in infants: sonographic findings

A retrospective study was performed on 78 patients (newborn to 2 years old) with clinically proved bacterial meningitis. Sonograms were obtained during the acute illness and medical records were reviewed. The spectrum of sonographic features of meningitis included normal scans (30 patients), ventriculomegaly (11 patients), echogenic sulci (31 patients), extra-axial fluid collections (26 patients), abnormal parenchymal echogenicity (9 patients), evidence of ventriculitis (5 patients), and brain abscess (1 patient). In 46 patients, correlation between the sonographic findings and neurologic outcome on clinical follow-up (6 months to 4 years) was made. Findings of abnormal parenchymal echogenicity and/or moderate-to-marked ventriculomegaly were associated with significant neurologic sequelae; however, echogenic sulci and small extra-axial fluid collections did not appear to have any prognostic significance. Twenty-nine of the 78 patients had sonography without clinical indication of complications of meningitis, and in no patient was a significant abnormality found. Our study suggests that sonography is indicated only when there is clinical suspicion of complications.     

Design and Clinical Application of the Helix Reservoir Pump-Oxygenator System for Extracorporeal Circulation

A series of 154 allergic patients were treated with Vistaril. The drug was effective in allergic rhinitis, urticaria, and pruritus of any allergic cause. It was not effective in asthma. Vistaril has a wide spectrum of action and had a high degree of patient acceptance. Duration of action in most cases was 8 to 10 hours or more. The main side effect was drowsiness. Serious side effects were not encountered.     

Antimicrobial Susceptibility and Resistance Patterns among Helicobacter pylori Strains from The Gambia,West Africa

Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtz^r) strains were rendered Mtz susceptible (Mtz^s) by transformation with a functional rdxA gene; conversely, Mtz^s strains were rendered Mtz^r by rdxA inactivation. Many mutations were found by Gambian H. pylorirdxA sequencing; mutations that probably inactivated rdxA in Mtz^r strains were identified and explained using RdxA protein''s structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.     

Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells

The p21 RAS product has been implicated as part of the downstream signaling of certain nonreceptor tyrosine kinase oncogenes and several growth factor receptor-ligand interactions. We have reported that the chronic myelogenous leukemia oncogene p210 bcr-abl transforms a growth- factor-dependent myeloid cell line NFS/N1.H7 to interleukin-3 (IL-3) independence. In these p210 bcr-abl-transformed cells (H7 bcr-abl.A54) and in two other murine myeloid cell lines transformed to IL-3 independence by p210 bcr-abl, endogenous p21 RAS is activated as determined by an elevated ratio of associated guanosine triphosphate (GTP)/guanosine diphosphate (GDP), assayed by thin-layer chromatography of the nucleotides eluted from p21 RAS after immunoprecipitation with the Y13-259 antibody. Treatment of p210 bcr-abl-transformed cells with a specific tyrosine kinase inhibitor herbimycin A resulted in diminished tyrosine phosphorylation of p210 bcr-abl and associated proteins, without major reduction in expression of the p210 bcr-abl protein itself. Inhibition of p210 bcr-abl-dependent tyrosine phosphorylation resulted in a reduction of active p21RAS-GTP complexes in the transformed cells, in diminished expression of the nuclear early response genes c-jun and c-fos, and in lower cellular proliferation rate. To further implicate p21 RAS in these functional events downstream of p210 bcr-abl tyrosine phosphorylation, we targeted G- protein function directly by limiting the availability of GTP with the inosine monophosphate dehydrogenase inhibitor, tiazofurin (TR). In p210 bcr-abl-transformed cells treated for 4 hours with TR, in which the levels of GTP were reduced by 50%, but GDP, guanosine monophosphate, and adenosine triphosphate (ATP) were unaffected, p210 bcr-abl tyrosine phosphorylation was at control levels. However, expression of c-fos and c-jun nuclear proto-oncogenes were strongly inhibited and p21 RAS activity was downregulated. These findings show that p210 bcr-abl transduces proliferative signals, in part, through downstream activation of p21 RAS. Furthermore, p21 RAS activity is linked to pathways that regulate c-jun and c-fos expression.     

New 5-Factor Modified Frailty Index Predicts Morbidity and Mortality in Primary Hip and Knee Arthroplasty

Background

While the 11-factor modified frailty index (mFI) has been shown to predict adverse outcomes in patients undergoing total joint arthroplasty, the 5-factor index has not been evaluated in this patient population. The goal of this study was to evaluate the utility of the mFI-5 as a predictor of morbidity and mortality in patients undergoing primary total hip and knee arthroplasty.