bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony
Authors: Johnson Lauren , Kim Hyung Kook , Tanabe Masaki , Gorcsan John , Schwartzman David , Shroff Sanjeev G. , Pinsky Michael R.
Published: September 2007

The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 ± 0.8 vs. 4.8 ± 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 ± 0.3 vs. 1.4 ± 0.1 l/min and stroke work: 137 ± 22 vs. 60 ± 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 ± 0.2 l/min and stroke work: 113 ± 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony.
Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction
Authors: Swaney James S. , Patel Hemal H. , Yokoyama Utako , Lai N. Chin , Spellman Matthew , Insel Paul A. , Roth David M.
Published: September 2007

Myocardial infarction (MI) results in left ventricular remodeling (e.g., ventricular hypertrophy, dilatation, and fibrosis). Fibrosis contributes to increased myocardial stiffening, impaired ventricular filling and function, and reduced cardiac output. Adenylyl cyclase (AC) expression and activity are reduced in animal models of heart failure. Stimulation of AC can inhibit extracellular matrix production in isolated cardiac fibroblasts; however, a role for reduced AC expression and activity in fibrosis associated with cardiac remodeling after chronic MI has never been determined. We tested the hypothesis that AC expression and activity are reduced in cardiac fibroblasts after chronic (18 wk) MI. Rats underwent coronary artery ligation or sham surgery (control), and echocardiography was used to assess left ventricular remodeling 1, 3, 5, 7, 10, 12, and 18 wk after surgery. Cardiac fibroblasts were isolated from the noninfarcted myocardium and compared for differences in AC activity and collagen synthesis. End-diastolic dimension was increased [control: 0.76 ± 0.02 cm and MI: 1.0 ± 0.02 cm (means ± SE), P < 0.001] and fractional shortening was decreased (control: 44 ± 2% and MI: 17 ± 2%, P < 0.001) in MI compared with control rats. Basal and forskolin-stimulated cAMP production were decreased by 90% and 93%, respectively, and AC5/6 expression was decreased 39% in fibroblasts isolated from MI rats compared with sham controls. Serum-stimulated collagen production was increased twofold and forskolin-mediated inhibition of collagen synthesis was reduced in fibroblasts from MI rats compared with controls. Our data demonstrate that AC expression and activity are reduced and collagen production is increased in cardiac fibroblasts of rats after MI.
The balance between inactivation and activation of the Na+-K+pump underlies the triphasic accumulation of extracellular K+during myocardial ischemia
Authors: Terkildsen Jonna R. , Crampin Edmund J. , Smith Nicolas P.
Published: September 2007

Ischemia-induced hyperkalemia (accumulation of extracellular K+) predisposes the heart to the development of lethal reentrant ventricular arrhythmias. This phenomenon exhibits a triphasic time course and is thought to be mediated by a combination of three mechanisms: 1) increased cellular K+efflux, 2) decreased cellular K+influx, and 3) shrinkage of the extracellular space. These ischemia-induced electrophysiological changes are driven by an impaired cellular metabolism. However, the relative contributions of these mechanisms, as well as the origin of the triphasic profile, have proven to be difficult to determine experimentally. In this study, the changes in metabolite concentrations that arise during 15 min of zero-flow global ischemia were incorporated into a dynamic model of cellular electrophysiology, which was extended to include a metabolically sensitive description of the Na+-K+pump and ATP-sensitive K+channel, in addition to cell volume regulation. The coupling of altered K+fluxes and cell volume regulation enables an integrative simulation of ischemic hyperkalemia. These simulations were able to quantitatively reproduce experimental measurements of the accumulation of extracellular K+during 15 min of simulated ischemia, both with respect to the degree of K+loss as well as the triphasic time course. Analysis of the model indicates that the inhibition of the Na+-K+pump is the dominant factor underlying this hyperkalemic behavior, accounting for ∼85% of the observed extracellular K+accumulation. It was found that the balance between activation and inhibition of the Na+-K+pump, affected by the changing metabolite and ion concentrations (in particular, [ADP]), give rise to the triphasic profile associated with ischemic hyperkalemia.
Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling
Authors: Moro Cécile , Jouan Marie-Gabrielle , Rakotovao Andry , Toufektsian Marie-Claire , Ormezzano Olivier , Nagy Norbert , Tosaki Arpad , de Leiris Joël , Boucher François
Published: September 2007

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-α occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-α can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-α, IL-1β, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3α was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.
Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage
Authors: Ansar Saema , Vikman Petter , Nielsen Marianne , Edvinsson Lars
Published: September 2007

We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 μl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT1) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT2) receptor antagonist PD-123319]. In parallel the ETB, 5-HT1B, and AT1 receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ETB, 5-HT1B, and AT1 receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage.
Vascular smooth muscle Gqsignaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension
Authors: Harris David M. , Cohn Heather I. , Pesant Stéphanie , Zhou Rui-Hai , Eckhart Andrea D.
Published: September 2007

More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because Gqsignaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) Gqsignaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM Gqsignaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of Gqsignaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an α1-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of Gqsignaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC50. We also determined that inhibition of Gqsignaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that Gqsignaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular Gq-coupled receptors involved.
Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH2/TXA2 mediation
Authors: Toth Erika , Racz Anita , Toth Janos , Kaminski Pawel M. , Wolin Michael S. , Bagi Zsolt , Koller Akos
Published: September 2007

Hyperglycemia increases glucose metabolism via the polyol pathway, which results in elevations of intracellular sorbitol concentration. Thus we hypothesized that elevated level of sorbitol contributes to the development of hyperglycemia-induced dysfunction of microvessels. In isolated, pressurized (80 mmHg) rat gracilis muscle arterioles (∼150 μm), high glucose treatment (25 mM) induced reduction in flow-dependent dilation (from maximum of 39 ± 2% to 15 ± 1%), which was significantly mitigated by an aldose reductase inhibitor, zopolrestat (maximum 27 ± 2%). Increasing doses of sorbitol (10−10–10−4 M) elicited dose-dependent constrictions (maximum 22 ± 3%), which were abolished by endothelium removal, a prostaglandin H2/thromboxane A2 (PGH2/TXA2) receptor (TP) antagonist SQ-29548, or superoxide dismutase (SOD) plus catalase (CAT). Incubation of arterioles with sorbitol (10−7 M) reduced flow-dependent dilations (from maximum of 39 ± 2% to 20 ± 1.5%), which was not further affected by inhibition of nitric oxide synthase by Nω-nitro-l-arginine methyl ester but was prevented by SOD plus CAT and mitigated by SQ-29548. Nitric oxide donor sodium nitroprusside-induced (10−9–10−6 M) dilations were also decreased in a SQ-29548 and SOD plus CAT-reversible manner, whereas adenosine dilations were not affected by sorbitol exposure. Sorbitol significantly increased arterial superoxide production detected by lucigenin-enhanced chemiluminescence, which was inhibited by SOD plus CAT. Sorbitol treatment also increased arterial formation of 3-nitrotyrosine. We suggest that hyperglycemia by elevating intracellular sorbitol induces oxidative stress, which interferes with nitric oxide bioavailability and promotes PGH2/TXA2 release, both of which affect regulation of vasomotor responses of arterioles. Thus increased activity of the polyol pathway may contribute to the development of microvascular dysfunction in diabetes mellitus.
CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice
Authors: Benjamin Ivor J. , Guo Yiru , Srinivasan Sathyanarayanan , Boudina Sihem , Taylor Ryan P. , Rajasekaran Namakkal S. , Gottlieb Roberta , Wawrousek Eric F. , Abel E. Dale , Bolli Roberto
Published: September 2007

The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched (∼5–9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion × 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 ± 17.9 vs. 59.8 ± 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice ( P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges.
Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells
Authors: Cheng Gang , Shao Zhifei , Chaudhari Bharti , Agrawal Devendra K.
Published: September 2007

Widespread damage of airway epithelium and defective epithelial repair are hallmarks of chronic asthma. Growth factors and cytokines spatially and temporally regulate epithelial shedding and repair. Within this context, a key function is exerted by transforming growth factor (TGF)-β. Recent growing evidence suggests that chloride (Cl−) channels are critical to cell apoptosis. We examined the effects of TGF-β1 on Cl− channel expression and activity and its relationship with apoptosis in human bronchial epithelial cells (HBECs). The small interfering RNA (siRNA) approach was used to investigate the potential role of CLC-3, a member of the volume-regulated Cl− channel family, in apoptosis of HBECs. TGF-β1 significantly induced HBEC apoptosis, which paralleled to a significant decrease in the endogenous expression of CLC-3 protein and mRNA transcripts. Outward rectifying and voltage-dependent CLC-3-like Cl− currents in HBECs were diminished by TGF-β1. siRNA for CLC-3 abolished Cl− current and enhanced TGF-β1-induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-β1-induced cell apoptosis. Bcl-2 was also downregulated after TGF-β stimulation. TGF-β1-induced cell apoptosis was suppressed in Bcl-2-transfected HBECs. Our data demonstrate that CLC-3-like voltage-gated chloride channels play a critical role in TGF-β-induced apoptosis of human airway epithelial cells.
Proinflammatory responses of human airway cells to ricin involve stress-activated protein kinases and NF-κB
Authors: Wong John , Korcheva Veselina , Jacoby David B. , Magun Bruce E.
Published: September 2007

Ricin is a potential bioweapon because of its toxicity, availability, and ease of production. When delivered to the lungs, ricin causes severe pulmonary damage with symptoms that are similar to those observed in acute lung injury and adult respiratory distress syndrome. The airway epithelium plays an important role in the pathogenesis of many lung diseases, but its role in ricin intoxication has not been elucidated. Exposure of cultured primary human airway epithelial cells to ricin resulted in the activation of SAPKs and NF-κB and in the increased expression of multiple proinflammatory molecules. Among the genes upregulated by ricin and identified by microarray analysis were those associated with transcription, nucleosome assembly, inflammation, and response to stress. Sequence analysis of the promoters of these genes identified NF-κB as one of the transcription factors whose binding sites were overrepresented. Although airway cells secrete TNF-α in response to ricin, blocking TNF-α did not prevent ricin-induced activation of NF-κB. Decreased levels of IκB-α in airway cells exposed to ricin suggest that translational suppression may be responsible for the activation of NF-κB. Inhibition of p38 MAPK by a chemical inhibitor or NF-κB by short interfering RNA resulted in a marked reduction in the expression of proinflammatory genes, demonstrating the importance of these two pathways in ricin intoxication. Therefore, the p38 MAPK and NF-κB pathways are potential therapeutic targets for reducing the inflammatory consequences of ricin poisoning.
Dexamethasone prevents transport inhibition by hypoxia in rat lung and alveolar epithelial cells by stimulating activity and expression of Na+-K+-ATPase and epithelial Na+ channels
Authors: Güney Şevin , Schuler Akelei , Ott Alexandra , Höschele Sabine , Zügel Stefanie , Baloğlu Emel , Bärtsch Peter , Mairbäurl Heimo
Published: September 2007

Hypoxia inhibits Na and lung fluid reabsorption, which contributes to the formation of pulmonary edema. We tested whether dexamethasone prevents hypoxia-induced inhibition of reabsorption by stimulation of alveolar Na transport. Fluid reabsorption, transport activity, and expression of Na transporters were measured in hypoxia-exposed rats and in primary alveolar type II (ATII) cells. Rats were treated with dexamethasone (DEX; 2 mg/kg) on 3 consecutive days and exposed to 10% O2 on the 2nd and 3rd day of treatment to measure hypoxia effects on reabsorption of fluid instilled into lungs. ATII cells were treated with DEX (1 μM) for 3 days before exposure to hypoxia (1.5% O2). In normoxic rats, DEX induced a twofold increase in alveolar fluid clearance. Hypoxia decreased reabsorption (−30%) by decreasing its amiloride-sensitive component; pretreatment with DEX prevented the hypoxia-induced inhibition. DEX increased short-circuit currents (ISC) of ATII monolayers in normoxia and blunted hypoxic transport inhibition by increasing the capacity of Na+-K+-ATPase and epithelial Na+ channels (ENaC) and amiloride-sensitive ISC. DEX slightly increased the mRNA of α- and γ-ENaC in whole rat lung. In ATII cells from DEX-treated rats, mRNA of α1-Na+-K+-ATPase and α-ENaC increased in normoxia and hypoxia, and γ-ENaC was increased in normoxia only. DEX stimulated the mRNA expression of α1-Na+-K+-ATPase and α-, β-, and γ-ENaC of A549 cells in normoxia and hypoxia (1.5% O2) when DEX treatment was begun before or during hypoxic exposure. These results indicate that DEX prevents inhibition of alveolar reabsorption by hypoxia and stimulates the expression of Na transporters even when it is applied in hypoxia.
Cooperative regulation of GSK-3 by muscarinic and PDGF receptors is associated with airway myocyte proliferation
Authors: Gosens Reinoud , Dueck Gordon , Rector Edward , Nunes Raquel O. , Gerthoffer William T. , Unruh Helmut , Zaagsma Johan , Meurs Herman , Halayko Andrew J.
Published: September 2007

Muscarinic receptors and platelet-derived growth factor (PDGF) receptors synergistically induce proliferation of airway smooth muscle (ASM), but the pathways that regulate these effects are not yet completely identified. We hypothesized that glycogen synthase kinase-3 (GSK-3), a kinase that represses several promitogenic signaling pathways in its unphosphorylated form, is cooperatively inhibited by PDGF and muscarinic receptors in immortalized human ASM cell lines. PDGF or methacholine alone induced rapid GSK-3 phosphorylation. This phosphorylation was sustained only for PDGF; however, methacholine potentiated PDGF-induced sustained GSK-3 phosphorylation. Synergistic effects of methacholine also were observed on PDGF-induced retinoblastoma protein (Rb) phosphorylation and cell proliferation. Suppression of GSK-3 inhibitory function using SB 216763 also augmented PDGF-induced Rb phosphorylation and cell cycle progression; this synergy was similar in magnitude to that seen for methacholine with PDGF. GSK-3 phosphorylation induced by methacholine required PKC, since it was abolished by GF 109203X and Gö 6976; however, inhibition of PKC had no effect on cell responses to PDGF. PKC inhibition also specifically abolished the synergistic effect of methacholine on PDGF-induced GSK-3 phosphorylation and cell proliferation. Collectively, these results show that GSK-3 plays a key repressive role in ASM cell proliferation. Moreover, muscarinic receptors mediate PKC-dependent GSK-3 inhibition, and this appears to be a primary mechanism underpinning augmentation of PDGF-induced cell growth.
Child Sexual Abuse: Can Anatomy Explain the Presentation?
Authors: Nazer Dena , Palusci Vincent J.
Published: September 2007

This article discusses a 4-year-old girl who displayed behavioral symptoms consistent with posttraumatic stress disorder. She was recently placed in foster care due to emotional and physical neglect. During her clinic visit, she disclosed being sexually abused by her father with a knife. Results of her general and anogenital physical examinations were normal. The case discussion proposes an explanation for how a maltreated child (1) develops behavioral problems, (2) has a normal genital examination despite the history of sexual abuse, and (3) has an implausible disclosure of her father hurting her with a knife. As part of the Integrating Basic Science into Clinical Teaching Initiative series, basic science principles are the method of explanation. The case discussion is an attempt to understand the science responsible for the disease that is present and make that understanding useful for future clinical problem solving.
Occult Methicillin-Resistant Staphylococcus aureus Abscesses in 2 Pediatric Patients
Authors: Feder Henry M.
Published: September 2007

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become more common over the last decade. Recently, severe MRSA infections including necrotizing pneumonia, purpura fulminans, and rapidly progressive skin abscesses have been reported. These severe infections frequently have been associated with the virulence factor Panton-Valentine leukocidin (PVL). Two unusual cases of occult deep tissue abscesses in children who had family members with a history of severe MRSA skin abscesses are presented in this article. Both children initially presented with fever without a focus. Deep tissue MRSA (PVL positive) abscesses evolved. Empiric antibiotic therapy for MRSA should be considered for infants and children who are hospitalized with occult fever and who have a family member with a history of MRSA infection.
Wheezing Child
Authors: Clark Jeff
Published: September 2007

This case discussion is part of the Integrating Basic Science into Clinical Teaching Initiative. It is intended to examine wheezing as a symptom and to describe the underlying physiology that explains the physical findings and blood gas features in an attempt to localize the site of obstruction. The information contained in this case is a compilation and derived from 2 similar patients. This case discussion describes a 13-month-old girl who presents with wheezing and respiratory distress. A close examination of her physical findings and blood gas analysis indicate that she is experiencing overall alveolar hypoventilation without significant hypoxemia, suggesting her airway obstruction is located above the carina. Subsequent investigations reveal a right aortic arch and vascular ring as the cause of her symptoms. An understanding of the physiology of airway obstruction and pulmonary gas exchange allows for better localization of sites of airway obstruction and the institution of appropriate diagnostic tests and therapy.
Serum Zinc Levels in Children With Simple Febrile Seizure
Authors: Ganesh R. , Janakiraman Lalitha
Published: September 2007

A prospective case—control study was conducted in a major tertiary care hospital for children during June 2005 to May 2006 on children aged between 3 months and 5 years to compare serum zinc levels in 38 cases of simple febrile seizure and 38 age-matched controls. The mean serum zinc levels in cases and controls were 32.17 and 87.6 µg/dL, respectively. This difference was statistically significant ( P < .001). We conclude that Indian children with febrile seizure had low serum zinc levels, and zinc supplementation to reduce the incidence of febrile seizure should be investigated.
Potentially Avoidable Pediatric Hospitalizations as Defined by the Agency for Healthcare Research and Quality: What Do They Tell Us About Disparities in Child Health?
Authors: Herrod Henry G. , Chang Cyril F.
Published: September 2007

This study was conducted to determine if the Agency for Healthcare Research and Quality's newly established pediatric quality monitors, which measure potentially avoidable hospitalizations, are useful in detecting disparities in health care delivery. Data for all hospital discharges in Tennessee in 2002 were evaluated for the 5 pediatric discharge monitors identified by the Agency for Healthcare Research and Quality. These diagnoses were asthma, short-term complications of diabetes, gastroenteritis, urinary tract infection, and perforated appendix. Black children were more likely to be discharged with the diagnoses of asthma and short-term diabetes complications. Publicly insured children were more likely than commercially insured children to be discharged with each of the 5 potentially avoidable hospitalizations. The results show that black children and children insured by public programs have significantly different discharge rates for pediatric potentially avoidable hospitalizations than do white children or commercially insured children. This could be the result of less access to high-quality ambulatory care.
EPSDT Preventive Services in a Low-Income Pediatric Population: Impact of a Nursing Protocol
Authors: Hull Pamela C. , Husaini Baqar A. , Tropez-Sims Susanne , Reece Michelle , Emerson Janice , Levine Robert
Published: September 2007

Medicaid mandates coverage of clinical preventive services for children under the Early and Periodic Screening, Diagnosis, and Treatment program (EPSDT). This article assesses the usefulness of a nursing protocol for delivering comprehensive EPSDT services to pediatric patients during any primary care visit. Secondary data from a recent controlled trial were analyzed. An intervention group received the clinical protocol (n = 514 children in a low-income pediatric clinic), whereas data from a “usual care” comparison group were obtained from medical records (n = 115 children). The nursing protocol included 52 items corresponding to EPSDT services and was administered by a prevention nurse. In the intervention group, 11 605 out of 11 607 (approximately 100.0%) EPSDT service needs were initiated, as compared to 21.2% (572 out of 2695) in the comparison group ( P < .001). The study demonstrates the feasibility of using a nursing protocol to integrate EPSDT clinical preventive services into pediatric visits.
Use of Selective Serotonin Reuptake Inhibitors by Pediatricians: Comparing Attitudes of Primary Care Pediatricians and Child and Adolescent Psychiatrists
Authors: Heneghan Amy , Garner Andrew S. , Storfer-Isser Amy , Kortepeter Karl , Stein Ruth E. K. , McCue Horwitz Sarah
Published: September 2007

To compare attitudes regarding a pediatrician's role in prescribing selective serotonin reuptake inhibitors for children and adolescents, surveys were mailed to 338 primary care pediatricians and 75 child and adolescent psychiatrists; half responded. Child and adolescent psychiatrists were significantly more likely than primary care pediatricians to agree that selective serotonin reuptake inhibitors are safe and effective when used for children and adolescents. Primary care pediatricians were significantly more likely than child and adolescent psychiatrists to agree that black box warnings have changed their prescribing practices. Both had similar beliefs about whether antidepressants should be prescribed only by psychiatrists and whether pediatricians should initiate selective serotonin reuptake inhibitor therapy, without or after consulting a psychiatrist. These data suggest that among child and adolescent psychiatrists and primary care pediatricians, agreement about the pediatrician's role in using selective serotonin reuptake inhibitors therapy is lacking. Strategies that enhance communication and endorse support for defined roles of primary care pediatricians and child and adolescent psychiatrists will ensure that children with mental health needs are treated safely and appropriately.
Effects of the Oral, Direct Factor Xa Inhibitor Rivaroxaban on Platelet‐Induced Thrombin Generation and Prothrombinase Activity1
Authors: Graff Jochen , von Hentig Nils , Misselwitz Frank , Kubitza Dagmar , Becka Michael , Breddin Hans‐Klaus , Harder Sebastian
Published: September 2007

Rivaroxaban (BAY 59‐7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo‐controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5‐ or 30‐mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase‐induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase‐induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen‐induced endogenous thrombin potential was reduced by ∼80% and ∼90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor‐induced endogenous thrombin potential was reduced by ∼40% (5 mg) and ∼65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase‐induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet‐induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma.
Patterns of Use of Handheld Clinical Decision Support Tools in the Clinical Setting
Authors: Yu Feliciano , Houston Thomas K. , Ray Midge N. , Garner Duriel Q. , Berner Eta S.
Published: September 2007

Objectives. To assess the patterns of use of handheld clinical decision support tools by internal medicine residents in clinical settings. Methods. Eighty-two internal medicine residents were given personal digital assistants (PDAs) containing a suite of clinical decision support (CDS) programs. A tracking program was used to prospectively track program use during the study period, and a follow-up survey regarding self-reported program use was administered after the study period. Patterns of program use from the tracking data were compared to the data from the self-report survey. Results. Sixty-eight residents were followed using the tracking data. Residents used an average of 1.81 CDS programs (SD: 1.57; range, 0—5) per month. Forty-nine residents completed the self-report survey. Residents reported using an average of 3.15 (SD: 1.61) and 3.92 (SD: 1.40) CDS programs during a typical clinic session and inpatient day, respectively. In both inpatient and outpatient settings and for both methods of assessing program use, 2 programs (Epocrates and MedCalc) were used more often than the other programs. No association was observed between age, gender, race, and PGY level with the use of handheld clinical decision support tools for either tracked or self-report data. The self-report data show higher estimates of CDS program use than the tracking data in the clinical setting. Conclusions. The data show that physicians prefer to use certain handheld CDS tools in clinical settings. Drug references and medical calculators have been consistently used more than clinical prediction rules and diagnostic systems. Self-report survey instruments may overestimate recorded use of CDS programs.
The Value of Bayes Theorem in the Interpretation of Subjective Diagnostic Findings: What Can We Learn from Agreement Studies?
Authors: Sadatsafavi Mohsen , Moayyeri Alireza , Bahrami Hossein , Soltani Akbar
Published: September 2007

The Bayes theorem is advocated as the appropriate measure for the Weight of evidence in medical decision making. It is based on the calculation of posttest probability as a function of the accuracy of the test and pretest probability. Nevertheless, for subjective diagnostic findings, there might be substantial variability in the accuracy among human observers, making the point estimate of posttest probability imprecise. Although there is limited evidence regarding the actual variability of accuracy among observers for the majority of diagnostic findings, classical observer agreement studies provide us With an indirect estimate of such variability. The aim of this Work Was to explicate the relationship betWeen observer disagreement and variability of posttest probability. Using a random effects signal detection model With 3 stochastic components (betWeen subject, betWeen observer, and residual variations), the authors modeled diagnostic tests With various characteristics and calculated the expected betWeen-observer disagreement and 95% interval of the observers' posttest probability. For the majority of simulated conditions, variation in posttest probability Was surprisingly high, even in the presence of substantial agreement. Although the model is based on parametric assumptions, these results are a clue to a source of inaccuracy in the calculation of posttest probability. Practitioners should be aWare of such variation in their clinical practice, and diagnostic studies need to develop strategies to address this uncertainty.
Primary Prevention of Cardiovascular Diseases in General Practice: Mismatch between Cardiovascular Risk and Patients' Risk Perceptions
Authors: van der Weijden T. , van Steenkiste B. , Stoffers H.E.J.H. , Timmermans D.R.M. , Grol R.
Published: September 2007

Objective. Guidelines on primary prevention of cardiovascular disease (CVD) emphasize identifying high-risk patients for more intensive management, but patients' misconceptions of risk hamper implementation. Insight is needed into the type of patients that general practitioners (GPs) encounter in their cardiovascular prevention activities. How appropriate are the risk perceptions and worries of patients with whom GPs discuss CVD risks? What determines inappropriate risk perception? Method. Cross-sectional study in 34 general practices. The study included patients aged 40 to 70 years with whom CVD risk was discussed during consultation. After the consultation, the GPs completed a registration form, and patients completed a questionnaire. Correlations between patients' actual CVD risk and risk perceptions were analyzed. Results. In total, 490 patients were included. In 17% of the consultations, patients were actually at high risk. Risk was perceived inappropriately by nearly 4 in 5 high-risk patients (incorrect optimism) and by 1 in 5 low-risk patients (incorrect pessimism). Smoking, hypertension, and obesity were determinants of perceiving CVD risk as high, whereas surprisingly, diabetic patients did not report any anxiety about their CVD risk. Men were more likely to perceive their CVD risk inappropriately than women. Conclusion. In communicating CVD risk, GPs must be aware that they mostly encounter low-risk patients and that the perceived risk and worry do not necessarily correspond with the actual risk. Incorrect perceptions of CVD risk among men and patients with diabetes were striking.
Shared Decision Making in the Medical Encounter: Are We All Talking about the Same Thing?
Authors: Moumjid Nora , Gafni Amiram , Brémond Alain , Carrère Marie-Odile
Published: September 2007

Objective. This article aims to explore 1) whether after all the research done on shared decision making (SDM) in the medical encounter, a clear definition (or definitions) of SDM exists; 2) whether authors provide a definition of SDM when they use the term; 3) and whether authors are consistent, throughout a given paper, with respect to the research described and the definition they propose or cite. Methods. The authors searched different databases (Medline, HealthStar, Cinahl, Cancerlit, Sociological Abstracts, and Econlit) from 1997 to December 2004. The keywords used were informed decision making and shared decision making as these are the keywords more often encountered in the literature. The languages selected were English and French. Results. The 76 reported papers show that 1) several authors clearly define what they mean by SDM or by another closely related phrase, such as informed shared decision making. 2) About a third of the papers reviewed (25/76) cite these authors although 8 of them do not use the term in a manner consistent with the definition cited. 3) Certain authors use the term SDM inconsistently with the definition they propose, and some use the terms informed decision making and SDM as if they were synonymous. 4) Twenty-one papers do not provide or cite any definition, or their use of the term (i.e., SDM) is not consistent with the definition they provide. Conclusion. Although several clear definitions of shared decision making have been proposed, they are cited by only about a third of the papers reviewed. In the other papers, authors refer to the term without specifying or citing a definition or use the term inconsistently with their definition. This is a problem because having a clear definition of the concept and following this definition are essential to guide and focus research. Authors should use the term consistently with the identified definition.
Rethinking the Objectives of Decision Aids: A Call for Conceptual Clarity
Authors: Nelson Wendy L. , Han Paul K. J. , Fagerlin Angela , Stefanek Michael , Ubel Peter A.
Published: September 2007

Health decision aids are a potentially valuable adjunct to patient-physician communication and decision making. Although the overarching goal of decision aids— to help patients make informed, preference-sensitive choices—is widely accepted, experts do not agree on the means to achieve this end. In this article, the authors critically examine the theoretical basis and appropriateness of 2 widely accepted criteria used to evaluate decision aids: values clarification and reduction of decisional conflict. First, they argue that although clarifying values is central to decision making under uncertainty, it is not clear that decision aids—as they have been conceived and operationalized so far—can and should be used to achieve this goal. The pursuit of clarifying values, particularly values clarification exercises, raises a number of ethical, methodological, and conceptual issues, and the authors suggest research questions that should be addressed before values clarification is routinely endorsed. Second, the authors argue that the goal of reducing decisional conflict is conceptually untenable and propose that it be eliminated as an objective of decision aids.
Can Computerized Decision Support Help Patients Make Complex Treatment Decisions? A Randomized Controlled Trial of an Individualized Menopause Decision Aid
Authors: Col Nananda F. , Ngo Long , Fortin Jennifer M. , Goldberg Robert J. , O'Connor Annette M.
Published: September 2007

Purpose. To compare the effectiveness of an individualized decision aid (DA) with standard educational materials on decisions about menopausal treatments and to assess the feasibility of integrating this DA into clinical practice, with and without coaching. Methods. We conducted a 3-armed randomized controlled trial in 3 clinics, enrolling menopausal women between the ages of 45 and 65 years with primary care appointments. Of the 145 women included, 99 completed a 2-week follow-up. The control group received generic educational materials, 1 intervention group received an individualized computer-generated DA mailed to patients and their clinicians before clinic appointment, and the 2nd intervention group received the same DA along with coached care before clinic appointment (DA + CC). Decisional conflict, satisfaction, and knowledge were measured 2 weeks after clinic appointment. Results. Participants' mean age was 52 years, and 97% were white. Most women (98%) read all or most of the documents. Decisional conflict was significantly lower in both intervention groups but not in the control group. DA reduced decisional conflict from preintervention to postintervention (pre—post change) by 0.70 (SD = 0.56) points (on a 1—5 scale), compared to reductions of 0.51 (SD = 0.51) and 0.09 (SD = 0.44) for the DA + CC group and the control group, respectively. Satisfaction with the decision made was significantly higher at 2 weeks in the DA v. control group. Self-reported knowledge significantly improved in DA + CC compared to controls. Conclusion. Our decision aid lowered decisional conflict and improved patient satisfaction; adding coaching provided little additional benefit.
``It's My Body'': Does Patient Involvement in Decision Making Reduce Decisional Conflict?
Authors: Kremer Heidemarie , Ironson Gail , Schneiderman Neil , Hautzinger Martin
Published: September 2007

Objective. This study explores how much people with HIV/AIDS wanted and how much they actually perceived being involved in the decision to take or not to take antiretroviral treatment (ART). The congruence between desired and perceived decisional involvement was also related to decisional conflict. Method. Cross-sectional (N = 79), the Control Preferences Scale assessed patients' preferred versus perceived role in treatment decision making. The Decisional Conflict Scale measured patients' perceived difficulties in decision making. Results. Although a minority of patients (32%) perceived their role as shared decision making, the majority (59%) preferred shared decision making. Some did not desire shared decision making, with 28% preferring to decide on their own versus 13% wanting their physicians to decide for them. Overall, 58% did not feel they had achieved their desired role in decision making (half of whom perceived more control and the other half less control than preferred). Participants declining ART felt more pressure to decide alone compared with those taking ART (P < 0.01). Decisional conflict was expressed by 53% and was highest when physicians unilaterally made decisions about ART for patients who preferred shared decision making (P < 0.001). Conclusions. In this study, most physicians do not meet their patients' desired roles in decision making. One-third of people taking ART feel less involved than they desire. More critically, half of those declining ART feel pressured to decide alone, suggesting that physicians should remain involved in the decision to reject treatment, as this requires careful monitoring and periodical revisiting. Because lack of shared decision making is related to decisional conflict, physicians may reduce decisional conflict by meeting patients' desires for shared decision making.
A Meta-analysis of the Effects of Presenting Treatment Benefits in Different Formats
Authors: Covey Judith
Published: September 2007

Purpose. The purpose of this article is to examine the effects of presenting treatment benefits in different formats on the decisions of both patients and health professionals. Three formats were investigated: relative risk reductions, absolute risk reductions, and number needed to treat or screen. Methods. A systematic review of the published literature was conducted. Articles were retrieved by searching a variety of databases and screened for inclusion by 2 reviewers. Data were extracted on characteristics of the subjects and methodologies used. Log-odds ratios were calculated to estimate effect sizes. Results. A total of 24 articles were retrieved that reported on 31 unique experiments. The meta-analysis showed that treatments were evaluated more favorably when the relative risk format was used rather than the absolute risk or number needed to treat format. However, a significant amount of heterogeneity was found between studies, the sources of which were explored using subgroup analyses and metaregression. Although the subgroup analyses revealed smaller effect sizes in the studies conducted on physicians, the metaregression showed that these differences were largely accounted for by other features of the study design. Most notably, variations in effect sizes were explained by the particular wordings that the studies had chosen to use for the relative risk and absolute risk reductions. Conclusions. The published literature has consistently demonstrated that relative risk formats produce more favorable evaluations of treatments than absolute risk or number needed to treat formats. However, the effects are heterogeneous and seem to be moderated by key differences between the methodologies used.