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Articles by C Smith
Total Records ( 6 ) for C Smith
  J Gribbin , R Hubbard , J. R. F Gladman , C Smith and S. Lewis
 

Background: antihypertensive medications have long been implicated as a potential cause of falls in older people but, despite their widespread prescribing, the size of class-specific adverse effects remains unclear.

Aim: to determine the role of antihypertensive medications in older people with a recorded fall in primary care.

Design: case–control study.

Setting: UK general practices contributing data to The Health Improvement Network primary care database.

Methods: patients over 60 years of age with a first fall recorded between 2003 and 2006 were selected, and up to six controls per case matched by age, gender and general practice. We used conditional logistic regression to estimate odds ratios for ever exposure, and current/previous exposure to the main classes of antihypertensives, adjusting for co-morbidity. We also examined the effect of the time interval from first prescription to first fall.

Results: amongst our 9,682 cases, we found an increased risk of current prescribing of thiazides (odds ratio (OR) 1.25; 95% confidence interval 1.15–1.36). At 3 weeks after first prescribing the risk remained 4.28 (1.19–15.42). We found a reduced risk for current prescribing of beta blockers (OR 0.90; 0.85–0.96). There was no significant association with current prescribing of any other class of antihypertensive.

Conclusions: the study provides evidence that current prescribing of thiazides is associated with an increased risk of falling and that this is strongest in the 3 weeks following the first prescription.

  D. G Kent , M. R Copley , C Benz , S Wohrer , B. J Dykstra , E Ma , J Cheyne , Y Zhao , M. B Bowie , M Gasparetto , A Delaney , C Smith , M Marra and C. J. Eaves
 

Hematopoietic stem cells (HSCs) are generally defined by their dual properties of pluripotency and extensive self-renewal capacity. However, a lack of experimental clarity as to what constitutes extensive self-renewal capacity coupled with an absence of methods to prospectively isolate long-term repopulating cells with defined self-renewal activities has made it difficult to identify the essential components of the self-renewal machinery and investigate their regulation. We now show that cells capable of repopulating irradiated congenic hosts for 4 months and producing clones of cells that can be serially transplanted are selectively and highly enriched in the CD150+ subset of the EPCR+CD48CD45+ fraction of mouse fetal liver and adult bone marrow cells. In contrast, cells that repopulate primary hosts for the same period but show more limited self-renewal activity are enriched in the CD150 subset. Comparative transcriptome analyses of these 2 subsets with each other and with HSCs whose self-renewal activity has been rapidly extinguished in vitro revealed 3 new genes (VWF, Rhob, Pld3) whose elevated expression is a consistent and selective feature of the long-term repopulating cells with durable self-renewal capacity. These findings establish the identity of a phenotypically and molecularly distinct class of pluripotent hematopoietic cells with lifelong self-renewal capacity.

  W. M Wolf , H. A Vlachos , O. C Marroquin , J. S Lee , C Smith , W. D Anderson , J. T Schindler , E. M Holper , J. D Abbott , D. O Williams , W. K Laskey , K. E Kip , S. F Kelsey and S. R. Mulukutla
 

Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry.

Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed.

Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

  J. M Thurman , R Marians , W Emlen , S Wood , C Smith , H Akana , V. M Holers , M Lesser , M Kline , C Hoffman , E Christen and H. Trachtman
 

Background and objectives: Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common cause of acute kidney injury in children. Mutations in alternative pathway (AP) complement regulatory proteins have been identified in severe cases of thrombotic microangiopathy, but the role of the AP in D+HUS has not been studied. Therefore, we determined whether plasma levels of markers of activation of the AP are increased in D+HUS and are biomarkers of the severity of renal injury that predict the need for dialysis.

Design, setting, participants, & measurements: Patients were randomly selected from among participants in the HUS-SYNSORB Pk trial. Plasma samples were collected on days 1, 4, 7, and 10 after enrollment and day 28 after discharge from the hospital. Levels of two complement pathway products, Bb and SC5b-9, were determined by ELISA.

Results: Seventeen children (6 boys and 11 girls; age, 5.4 ± 3.5 yr) were studied. Eight (47%) required dialysis support, and two had serious extrarenal events. On the day of enrollment, plasma levels of Bb and SC5b-9 were significantly increased in all patients compared with healthy controls (P < 0.01). The elevated concentrations normalized by day 28 after discharge. Circulating levels of complement pathway fragments did not correlate with severity of renal injury or occurrence of complications.

Conclusions: Patients with acute-onset D+HUS manifest activation of the AP of complement that is temporally related to the onset of disease and that resolves within 1 mo. Therapies to inhibit the AP of complement may be useful in attenuating the severity of renal injury and extrarenal complications.

  J Gribbin , R Hubbard , C Smith , J Gladman and S. Lewis
 

Background: Despite the role of primary care in the falls care pathway, there are almost no data on the extent of falls seen in general practices.

Aim: To quantify the incidence and mortality of falls amongst older people in primary care in the UK.

Methods: Cohort study of people aged >=60 years and registered in a UK practice contributing data to The Health Improvement Network primary care database (THIN) throughout 2003–06. Analysis of crude incidence and estimation of incidence rate ratios using negative binomial regression, and survival using Cox regression. Sensitivity analysis of criteria for distinguishing discrete fall events from follow-up appointments.

Results: Amongst people aged >=60 years the overall crude incidence rate of recorded falls was 3.58/100 person-years (95% CI 3.56–3.61). The rate of recurrent falls was 0.67/100 person-years (95% CI 0.66–0.68). The incidence rate of recorded falls and recurrent falls was higher in older age groups, in women and least advantaged social groups. Incidence of recorded falls was constant through the time period 2003–06. Mortality for recurrent fallers was about twice that of general population controls.

Conclusions: These data suggest that more than 475 000 fall events in older people are recorded in general practice each year in the UK, and are associated with increased mortality and relative deprivation. The underlying incidence rate has remained stable in recent years.

  D Souvannakitti , B Kuri , G Yuan , A Pawar , G. K Kumar , C Smith , A. P Fox and N. R. Prabhakar
 

We recently reported that adrenomedullary chromaffin cells (AMC) from neonatal rats treated with intermittent hypoxia (IH) exhibit enhanced catecholamine secretion by hypoxia (Souvannakitti D, Kumar GK, Fox A, Prabhakar NR. J Neurophysiol 101: 2837–2846, 2009). In the present study, we examined whether neonatal IH also facilitate AMC responses to nicotine, a potent stimulus to chromaffin cells. Experiments were performed on rats exposed to either IH (15-s hypoxia-5-min normoxia; 8 h/day) or to room air (normoxia; controls) from ages postnatal day 0 (P0) to P5. Quantitative RT-PCR analysis revealed expression of mRNAs encoding 3-, 5-, 7-, and β2- and β4-nicotinic acetylcholine receptor (nAChR) subunits in adrenal medullae from control P5 rats. Nicotine-elevated intracellular Ca2+ concentration ([Ca2+]i) in AMC and nAChR antagonists prevented this response, suggesting that nAChRs are functional in neonatal AMC. In IH-treated rats, nAChR mRNAs were downregulated in AMC, which resulted in a markedly attenuated nicotine-evoked elevation in [Ca2+]i and subsequent catecholamine secretion. Systemic administration of antioxidant prevented IH-evoked downregulation of nAChR expression and function. P35 rats treated with neonatal IH exhibited reduced nAChR mRNA expression in adrenal medullae, attenuated AMC responses to nicotine, and impaired neurogenic catecholamine secretion. Thus the response to neonatal IH lasts for at least 30 days. These observations demonstrate that neonatal IH downregulates nAChR expression and function in AMC via reactive oxygen species signaling, and the effects of neonatal IH persist at least into juvenile life, leading to impaired neurogenic catecholamine secretion from AMC.

 
 
 
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