bluuebunny/crossref_metadata_2025 huggingface dataset:
Ankle–branch index and HIV: the role of antiretrovirals
Authors: Olalla J , Salas D , Del Arco A , De la Torre J , Prada JL , Machín‐Hamalainen S , García‐Alegría J
Published: September 2008

Objective

To study the relationship between antiretroviral (ARV) treatment and abnormal ankle–branch index (ABI) and to compare the risk factors for altered ABI.

Methods

Patients coming to the office from April 2007 until July 2007 were offered the chance to take part in the study. ABI was obtained by the standard technique. Those ≤0.9 or ≥1.3 were considered altered ABI. Clinical reports were reviewed to examine traditional vascular risk factors, coinfection with hepatitis C virus and/or hepatitis B virus, tobacco use, highly active antiretroviral therapy use and its components and length of use of each ARV drug.

Results

ABI was measured in 147 patients, 82.3% males. Thirty‐three patients (22.45%) had an altered ABI, and it was related to CD4 cell nadir, dyslipidaemia and protease inhibitor (PI) use. When logistic regression was carried out, only dyslipidaemia (OR 2.68, CI 95%: 1.06–6.91) and PI use (OR 2.79, CI 95%: 1.15–6.54) remained in the model.

Conclusions

Altered ABI is associated with PI use independently of dyslipidaemia. Probably, it marks patients with high vascular risk not identified with traditional scales.
Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum
Authors: Read JS , Best BM , Stek AM , Hu C , Capparelli EV , Holland DT , Burchett SK , Smith ME , Sheeran EC , Shearer WT , Febo I , Mirochnick M
Published: September 2008

Objectives

Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum.

Methods

The participants were HIV‐1‐infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady‐state 12‐h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration–time curve (AUC0–12) was ≥10th percentile NFV AUC0–12 in non‐pregnant historical controls (18.5 μg h/mL).

Results

Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (Cmax), 12‐h post‐dose concentration (C12) and AUC0–12 were significantly lower during the third trimester compared to postpartum (P≤0.03). The metabolite hydroxyl‐tert‐butylamide (M8) AUC0–12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P<0.01). The NFV AUC0–12 exceeded the AUC0–12 target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (Cmin) was above the suggested minimum trough concentration (0.8 μg/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was <400 HIV‐1 RNA copies/mL in 81% of patients at delivery.

Conclusions

These results suggest that higher doses of NFV should be considered during pregnancy.
Antiretroviral effects on HIV‐1 RNA, CD4 cell count and progression to AIDS or death: a meta‐regression analysis
Authors: Mills EJ , Kelly S , Bradley M , Mollon P , Cooper C , Nachega J
Published: September 2008

Objective

Governments, clinicians and drug‐licensing bodies have adopted changes in CD4 cell counts and HIV‐1 RNA levels as evidence of effectiveness for new therapeutic interventions. We aimed to determine the strength of the association between the magnitude of the effect of changes in CD4 cell count and HIV‐1 RNA and progression to AIDS or death in the highly active antiretroviral therapy (HAART) era.

Methods

We identified all randomized clinical trials (RCTs) evaluating the effect of HAART on both clinical and surrogate endpoints (1994 to September 2006). We performed a meta‐regression and weighted linear regression. We additionally estimated potential RCT sample sizes that would be required to assess the effectiveness of new interventions in terms of clinical endpoints.

Results

We included data from 178 RCTs. We were unable to demonstrate a strong relationship at any time‐point. Specifically, this was the case when CD4 T‐cell change and clinical outcomes were examined at week 24 [coefficient −0.01, 95% confidence interval (CI) −0.03 to 0.001, P=0.54], week 48 (coefficient −0.01, 95% CI −0.02 to 0.001, P=0.83) and week 96 (coefficient 0.00, 95% CI −0.03 to 0.04, P=0.76). This was also the case when viral load was examined as a surrogate marker. Given the small number of clinical events occurring in new interventional RCTs, any RCT aiming to evaluate clinical endpoints within these time‐points would require an exceptionally large sample size.

Conclusions

Our findings indicate that, within short‐term clinical trial settings, it is not possible to estimate the proportion of treatment effect associated with surrogate endpoints.
Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor‐naïve, nonnucleoside reverse transcriptase inhibitor‐experienced patients: study TMC125‐C227*
Authors: Ruxrungtham K , Pedro RJ , Latiff GH , Conradie F , Domingo P , Lupo S , Pumpradit W , Vingerhoets JH , Peeters M , Peeters I , Kakuda TN , De Smedt G , Woodfall B ,   on behalf of the TMC125‐C227 study group
Published: September 2008

Objectives

TMC125‐C227, an exploratory phase II, randomized, controlled, open‐label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator‐selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)‐resistant, protease inhibitor‐naïve, HIV‐1‐infected patients.

Methods

Patients were randomized to TMC125 800 mg twice a day (bid) (phase II formulation; n=59) or the control PI (n=57), plus two nucleoside reverse transcriptase inhibitors (NRTIs).

Results

In an unplanned interim analysis, patients receiving TMC125 demonstrated suboptimal virological responses relative to the control PI. Therefore, trial enrolment was stopped prematurely and TMC125 treatment discontinued after a median of 14.3 weeks. In this first‐line NNRTI‐failure population, baseline NRTI and NNRTI resistance was high and reduced virological responses were observed relative to the control PI. No statistically significant relationship was observed between TMC125 exposure and virological response at week 12. TMC125 was better tolerated than a boosted PI for gastrointestinal‐, lipid‐ and liver‐related events.

Conclusions

In a PI‐naïve population, with baseline NRTI and NNRTI resistance and NRTI recycling, TMC125 was not as effective as first use of a PI. Therefore the use of TMC125 plus NRTIs alone may not be optimal in PI‐naïve patients with first‐line virological failure on an NNRTI‐based regimen. Baseline two‐class resistance, rather than pharmacokinetics or other factors, was the most likely reason for suboptimal responses.
Liver enzyme elevation after lamivudine withdrawal in HIV–hepatitis B virus co‐infected patients: the Swiss HIV Cohort Study
Authors: Bellini C , Keiser O , Chave J‐P , Evison JM , Fehr J , Kaiser L , Weber R , Vernazza P , Bernasconi E , Telenti A , Cavassini M ,   the Swiss HIV Cohort Study
Published: September 2008

Background

The principal causes of liver enzyme elevation among HIV–hepatitis B virus (HBV) co‐infected patients are the hepatotoxic effects of antiretroviral therapy (ART), alcohol abuse, ART‐induced immune reconstitution and the exacerbation of chronic HBV infection.

Objectives

To investigate the incidence and severity of liver enzyme elevation, liver failure and death following lamivudine (3TC) withdrawal in HIV–HBV co‐infected patients.

Methods

Retrospective analysis of the Swiss HIV Cohort Study database to assess the clinical and biological consequences of the discontinuation of 3TC. Variables considered for analysis included liver enzyme, HIV virological and immunological parameters, and medication prescribed during a 6‐month period following 3TC withdrawal.

Results

3TC was discontinued in 255 patients on 363 occasions. On 147 occasions (109 patients), a follow‐up visit within 6 months following 3TC withdrawal was recorded. Among these patients, liver enzyme elevation occurred on 42 occasions (29%), three of them (2%) with severity grade III and five of them (3.4%) with severity grade IV elevations (as defined by the AIDS Clinical Trials Group). Three patients presented with fulminant hepatitis. One death (0.7%) was recorded.

Conclusions

HBV reactivation leading to liver dysfunction may be an under‐reported consequence of 3TC withdrawal in HIV–HBV co‐infected patients. Regular monitoring of HBV markers is warranted if active therapy against HBV is discontinued.
Thermal pain thresholds are decreased in the migraine preattack phase
Authors: Sand T. , Zhitniy N. , Nilsen K. B. , Helde G. , Hagen K. , Stovner L. J.
Published: September 2008

Background and purpose:  Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls.

Methods:  A thermode was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup of 11 migraine patients had been tested within 24 h before their next attack and in the interictal phase.

Results:  In the preattack phase, HPT was lower compared with the paired interictal recording for the hand (44.8°C vs. 45.9°C, P = 0.009), neck (46.8°C vs. 48.2°C, P = 0.02), and forehead (45.1°C vs. 46.3°C, P = 0.02). Neck and hand CPT were higher in the preattack phase than interictally (10°C vs. 7.3°C, P = 0.01 and 11.6°C vs. 9.4°C, P = 0.06, respectively). Preattack forehead changes were most apparent on the headache side of the subsequent attack.

Discussion:  Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack.
Acute headache: a prospective diagnostic work‐up of patients admitted to a general hospital
Authors: Bø S. H. , Davidsen E. M. , Gulbrandsen P. , Dietrichs E.
Published: September 2008

Background and purpose:  To find a specified diagnosis for every patient investigated in the hospital emergency room for acute headache suspicious of subarachnoid haemorrhage (SAH), and to describe similarities and differences between the diagnostic groups.

Methods:  We used a standardized set of questionnaires and supplementary tests, including cerebral computed tomography (CT) and if needed lumbar puncture, in the investigation of the patients. Two neurologists diagnosed the same cases independently.

Results:  We found 30 different diagnoses as the cause of acute headache. Sixteen per cent had a SAH, and 57% had a primary headache. Patient characteristics, conditions at headache onset and accompanying symptoms were surprisingly similar in the diagnostic groups. For three SAH patients, it took 30 min to reach maximum pain intensity. In all diagnostic groups, a large proportion of the patients reached maximum pain within 60 s.

Conclusions:  To distinguish between benign and malignant causes of acute headache is difficult based on clinical features. The consistent use of CT and lumbar puncture is valuable when investigating sudden onset ‘first or worst headache ever’. This can reduce the risk of missing a SAH diagnosis, and make it possible to give more exact diagnoses to patients suffering from both primary and secondary headaches.
Influence of cephalosporins on the coagulation time of yogurt made from ewes’ milk
Authors: BERRUGA MARIA ISABEL , NOVÉS BEATRIZ , MOLINA MARIA PILAR , ROMÁN MARIO , MOLINA ANA
Published: September 2008

Ceftiofur and cephalexin were independently added to ewes’ milk at three different concentrations 50, 100 and 150 µg/kg. Spiked milk was used to produce yogurt and the acidification of the yogurt during incubation was then studied. Ceftiofur showed significant delays in the pH decrease rate at all concentrations assayed, but no significant delays occurred with cephalexin. When these antibiotics were administered intramuscularly to lactating ewes, from which the milk was used to make yogurt immediately after the corresponding withdrawal periods, absence of residues and pH delays were not observed during the yogurt fermentation in the presence of any antibiotic.
Effect of somatic cell counts on lipolysis, proteolysis and apparent viscosity of UHT milk during storage
Authors: FERNANDES ANDREZZA M , MORETTI THAIS S , BOVO FERNANDA , LIMA CÉSAR G , OLIVEIRA CARLOS A F
Published: September 2008

In this work, lipolysis, proteolysis and viscosity of ultra‐high temperature (UHT) milk containing different somatic cell counts (SCC) were investigated. UHT milks were analysed on days 8, 30, 60, 90 and 120 of storage. Lipolysis as measured by free fatty acids increase, casein degradation and viscosity of UHT milk were not affected by SCC but increased during storage. A negative relationship was observed between SCC and casein as a percentage of true protein on the 120th day of storage, hence indicating that high SCC increases the proteolysis of UHT milk by the end of its shelf life.
Acute ethanol suppresses glutamatergic neurotransmission through endocannabinoids in hippocampal neurons
Authors: Basavarajappa Balapal S. , Ninan Ipe , Arancio Ottavio
Published: September 2008

Ethanol exposure during fetal development is a leading cause of long‐term cognitive impairments. Studies suggest that ethanol exposure have deleterious effects on the hippocampus, a brain region that is important for learning and memory. Ethanol exerts its effects, in part, via alterations in glutamatergic neurotransmission, which is critical for the maturation of neuronal circuits during development. The current literature strongly supports the growing evidence that ethanol inhibits glutamate release in the neonatal CA1 hippocampal region. However, the exact molecular mechanism responsible for this effect is not well understood. In this study, we show that ethanol enhances endocannabinoid (EC) levels in cultured hippocampal neurons, possibly through calcium pathways. Acute ethanol depresses miniature post‐synaptic current (mEPSC) frequencies without affecting their amplitude. This suggests that ethanol inhibits glutamate release. The CB1 receptors (CB1Rs) present on pre‐synaptic neurons are not altered by acute ethanol. The CB1R antagonist SR 141716A reverses ethanol‐induced depression of mEPSC frequency. Drugs that are known to enhance thein vivofunction of ECs occlude ethanol effects on mEPSC frequency. Chelation of post‐synaptic calcium by EGTA antagonizes ethanol‐induced depression of mEPSC frequency. The activation of CB1R with the selective agonist WIN55,212‐2 also suppresses the mEPSC frequency. This WIN55,212‐2 effect is similar to the ethanol effects and is reversed by SR141716A. In addition, tetani‐induced excitatory post‐synaptic currents (EPSCs) are depressed by acute ethanol. SR141716A significantly reverses ethanol effects on evoked EPSC amplitude in a dual recording preparation. These observations, taken together, suggest the participation of ECs as retrograde messengers in the ethanol‐induced depression of synaptic activities.
Tissue‐type plasminogen activator requires a co‐receptor to enhance NMDA receptor function
Authors: Samson Andre L. , Nevin Simon T. , Croucher David , Niego Be’eri , Daniel Philip B. , Weiss Thomas W. , Moreno Eliza , Monard Denis , Lawrence Daniel A. , Medcalf Robert L.
Published: September 2008

Glutamate is the main excitatory neurotransmitter of the CNS. Tissue‐type plasminogen activator (tPA) is recognized as a modulator of glutamatergic neurotransmission. This attribute is exemplified by its ability to potentiate calcium signaling following activation of the glutamate‐binding NMDA receptor (NMDAR). It has been hypothesized that tPA can directly cleave the NR1 subunit of the NMDAR and thereby potentiate NMDA‐induced calcium influx. In contrast, here we show that this increase in NMDAR signaling requires tPA to be proteolytically active, but does not involve cleavage of the NR1 subunit or plasminogen. Rather, we demonstrate that enhancement of NMDAR function by tPA is mediated by a member of the low‐density lipoprotein receptor (LDLR) family. Hence, this study proposes a novel functional relationship between tPA, the NMDAR, a LDLR and an unknown substrate which we suspect to be a serpin. Interestingly, whilst tPA alone failed to cleave NR1, cell‐surface NMDARs did serve as an efficient and discrete proteolytic target for plasmin. Hence, plasmin and tPA can affect the NMDAR via distinct avenues. Altogether, we find that plasmin directly proteolyses the NMDAR whilst tPA functions as an indirect modulator of NMDA‐induced events via LDLR engagement.
ProNGF inhibits NGF‐mediated TrkA activation in PC12 cells
Authors: Sobottka Bettina , Reinhardt Dieter , Brockhaus Manfred , Jacobsen Helmut , Metzger Friedrich
Published: September 2008

Degeneration of cholinergic basal forebrain neurons (CBFN) is a hallmark in the pathology of Alzheimer’s disease (AD). Critically depending upon the neurotrophic support through nerve growth factor (NGF), CBFN in the AD brain face elevated concentrations of the pro‐form of NGF (proNGF) and suffer from an imbalance between TrkA and p75NTR expression. Research for the underlying mechanisms of CBFN death suggested a pro‐apoptotic activity of proNGF. However, this finding could not be confirmed by all investigators and other studies even observed a neurotrophic function of proNGF. In the presence of these controversial findings we investigated the activity of proNGF in PC12 cells with specific emphasis on its neurotoxic versus neurotrophic action. In this study, we show that proNGF can mediate TrkA receptor signaling directly, yet in the manner of a partial agonist with a lower maximum activity than NGF. A pro‐apoptotic activity of proNGF could not be confirmed in our cellular system. Interestingly and surprisingly, pre‐incubation with proNGF at low, sub‐active concentrations inhibited TrkA‐mediated neurotrophic NGF signaling in PC12 cells. Our data support a novel hypothesis for the role of elevated proNGF levels in CBFN pathology in AD. Thus, proNGF can indirectly contribute to the slow neurodegeneration in AD by reducing NGF‐mediated trophic support.
A Systematic Review of the Preventive Effect of Oral Hygiene on Pneumonia and Respiratory Tract Infection in Elderly People in Hospitals and Nursing Homes: Effect Estimates and Methodological Quality of Randomized Controlled Trials
Authors: Sjögren Petteri , Nilsson Erika , Forsell Marianne , Johansson Olle , Hoogstraate Janet
Published: September 2008

The objective of this study was to investigate the preventive effect of oral hygiene on pneumonia and respiratory tract infection, focusing on elderly people in hospitals and nursing homes, by systematically reviewing effect estimates and methodological quality of randomized controlled trials (RCTs) and to provide an overview of additional clinical studies in this area. Literature searches were conducted in the Medline database, the Cochrane library databases, and by hand‐searching reference lists. Included publications were analyzed for intervention (or topic) studied, main conclusions, strength of evidence, and study design. RCTs were further analyzed for effect magnitudes and methodological details. Absolute risk reductions (ARRs) and numbers needed to treat (NNTs) were calculated. Fifteen publications fulfilled the inclusion criteria. There was a wide variation in the design and quality of the studies included. The RCTs revealed positive preventive effects of oral hygiene on pneumonia and respiratory tract infection in hospitalized elderly people and elderly nursing home residents, with ARRs from 6.6% to 11.7% and NNTs from 8.6 to 15.3 individuals. The non‐RCT studies contributed to inconclusive evidence on the association and correlation between oral hygiene and pneumonia or respiratory tract infection in elderly people. Mechanical oral hygiene has a preventive effect on mortality from pneumonia, and non‐fatal pneumonia in hospitalized elderly people and elderly nursing home residents. Approximately one in 10 cases of death from pneumonia in elderly nursing home residents may be prevented by improving oral hygiene. Future research in this area should be focused on high‐quality RCTs with appropriate sample size calculations.
Changes in Muscle Mass, Muscle Strength, and Power but Not Physical Function Are Related to Testosterone Dose in Healthy Older Men
Authors: Storer Thomas W. , Woodhouse Linda , Magliano Lynne , Singh Atam B. , Dzekov Connie , Dzekov Jeanne , Bhasin Shalender
Published: September 2008

OBJECTIVES: To examine the effect of graded doses of testosterone on physical function and muscle performance in healthy, older men.

DESIGN: Randomized, double‐blind, placebo‐controlled clinical trial.

SETTING: General clinical research center.

PARTICIPANTS: Community‐dwelling healthy men aged 60 to 75 (N=44).

INTERVENTION: Monthly treatment with a gonadotropin‐releasing hormone agonist plus 25, 50, 125, or 300 mg/wk of intramuscular injections of testosterone enanthate for 20 weeks.

MEASUREMENTS: Skeletal muscle mass (SMM) was estimated using dual‐energy X‐ray absorptiometry. Leg press strength was measured by one repetition maximum, leg power by Nottingham Leg Rig, and muscle fatigability by repetitions to failure in the leg press exercise. Stair climbing, 6‐meter and 400‐meter walking speed, and a timed‐up‐and‐go (TUG) test were used to assess physical function.

RESULTS: Significant testosterone dose‐ and concentration‐dependent increases were observed in SMM (P<.001) and maximal strength (P=.001) but not muscle fatigability. Leg power also increased dose‐dependently (P=.048). In contrast, changes in self‐selected normal and fast walking speed over 6 or 400 meters, stair climbing power, and time for the TUG were not significantly related to testosterone dose, testosterone concentrations, or changes in muscle strength or power, or SMM.

CONCLUSION: Testosterone administration was associated with dose‐dependent increases in SMM, leg strength, and power but did not improve muscle fatigability or physical function. The observation that physical function scores did not improve linearly with strength suggests that these high‐functioning older men were already in the asymptotic region of the curve describing the relationship between physical function and strength.
Defining the Domain of Geriatric Medicine in an Urban Public Health System Affiliated with an Academic Medical Center
Authors: Callahan Christopher M. , Weiner Michael , Counsell Steven R.
Published: September 2008

The American Geriatrics Society has recommended a reexamination of the roles and deployment of providers with expertise in geriatric medicine. Healthcare systems use a variety of strategies to maximize their geriatric expertise. In general, these health systems tend to focus geriatric medicine resources on a group of older adults that are locally defined as the most in need. This article describes a model of care within an academic urban public health system and describes how local characteristics interact to define the domain of geriatric medicine. This domain is defined using 4 years of data from an electronic medical record combined with data collected from clinical trials.

From January 2002 to December 2005, 31,443 adults aged 65 and older were seen at any clinical site within this healthcare system. The mean age was 75 (range 65–105); 61% were women; 35% African American, and 2% Hispanic. The payer mix was 80% Medicare and 17% Medicaid. The local geriatric medicine program includes sites of care in inpatient, ambulatory, nursing home, and home‐based settings.

By design, this geriatric medicine clinical practice complements the care provided to older adults by the primary care practice. Primary care physicians tend to cede care to geriatric medicine for older adults with advanced disability or geriatric syndromes. This is most apparent for older adults in nursing facilities or those requiring home‐based care. There is a dynamic interplay between design features, reputation, and capacity that modulates volume, location, and type of patients seen by geriatrics.
Orthostatic Hypotension and Risk of Cardiovascular Disease in Elderly People: The Rotterdam Study
Authors: Verwoert Germaine C. , Mattace‐Raso Francesco U. S. , Hofman Albert , Heeringa Jan , Stricker Bruno H. C. , Breteler Monique M. B. , Witteman Jacqueline C. M.
Published: September 2008

OBJECTIVES: To determine the prognostic role of orthostatic hypotension for cardiovascular disease (CVD) and all‐cause mortality in elderly people.

DESIGN: Prospective study.

SETTING: Community based.

PARTICIPANTS: Five thousand sixty‐four subjects from the Rotterdam study aged 55 and older.

MEASUREMENTS: Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder. Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to standing position at any of three measurements taken 1, 2, and 3 minutes after standing.

RESULTS: At baseline, 901 subjects had orthostatic hypotension. During follow‐up, 668 subjects had coronary heart disease (CHD) (mean follow‐up 6.0 ± 3.5 years), and 1,835 subjects died (mean follow‐up period 7.8 ± 3.8 years). Orthostatic hypotension increased the risk of CHD (hazard ratio (HR)=1.31, 95% confidence interval (CI)=1.08–1.57) and all‐cause mortality (HR=1.22, 95% CI=1.09–1.36), in models adjusted for age and sex. The risk was slightly lower after additional adjustment for cardiovascular risk factors. In analyses stratified for age, the HRs for all‐cause mortality were 1.80 (95% CI 1.25–2.60), 1.13 (0.89–1.42), and 1.27 (95% CI=1.11–1.44), in the first, second, and third tertile of age, respectively.

CONCLUSION: Orthostatic hypotension increases the risk of CHD and all‐cause mortality in elderly people. The risk of CVD and mortality is strongest in younger and very old subjects.
The Constitution of Risk Communication in Advanced Liberal Societies
Authors: Wardman Jamie K.
Published: September 2008

This article aims to bring to the fore some of the underlying rationales that inform common conceptions of the constitution of risk communication in academic and policy communities. “Normative,”“instrumental,” and “substantive” imperatives typically employed in the utilization of risk communication are first outlined. In light of these considerations, a theoretical scheme is subsequently devised leading to the articulation of four fundamental “idealized” models of risk communication termed the “risk message” model, the “risk dialogue” model, the “risk field” model, and the “risk government” model, respectively. It is contended that the diverse conceptual foundations underlying the orientation of each model suggest a further need for a more contextualized view of risk communication that takes account not only of the strengths and limitations of different formulations and functions of risk communication, but also the underlying knowledge/power dynamics that underlie its constitution. In particular, it is hoped that the reflexive theoretical understanding presented here will help to bring some much needed conceptual clarity to academic and policy discourses about the use and utility of risk communication in advanced liberal societies.
Analyzing Complicity in Risk
Authors: Busby Jerry
Published: September 2008

When risks generate anger rather than fear, there is at least someone who regards the imposition of those risks as wrongdoing; and it then makes sense to speak of the involvement in producing those risks as complicity. It is particularly relevant to examine the complicity of risk bearers, because this is likely to have a strong influence on how far other actors should go in providing them with protection. This article makes a case for analyzing complicity explicitly, in parallel with normal processes of risk assessment, and proposes a framework for this analysis. It shows how it can be applied in a case study of maritime transportation, and examines the practical and theoretical difficulties of this kind of analysis. The conclusion is that the analysis has to be formative rather than summative, but that it could provide a useful way of exposing differences in the assumptions of different actors about agency and responsibility.
The Symmetry Rule: A Seven‐Year Study of Symptoms and Explanatory Labels Among Gulf War Veterans
Authors: Brewer Noel T. , Hallman William K. , Kipen Howard M.
Published: September 2008

Noticing medical symptoms can cause one to search for explanatory labels such as “ate bad food” or even “exposed to anthrax,” and perhaps these labels may cause new symptom reports. The present study examined whether there is empirical support for this symptom‐label “symmetry rule.” We interviewed veterans (N= 362) from the Gulf War Registry in 1995 and 2002 about their medical symptoms and about their exposure to war‐related hazards and stressors. Health symptom reports were strongly correlated between the two time periods and showed relatively stable mean levels, whereas recall of war‐related exposures was notably unstable. Veterans starting with fewer medical symptoms recalled fewer war‐related exposures seven years later. Initial recollection of chemical and biological warfare exposure (but not other exposures) longitudinally predicted novel medical symptoms. The findings generally support the symmetry rule hypotheses, although the evidence for the label to symptom link was less strong. The findings account for some variability in symptoms and exposure recall over time, but they do not, on their own, account for the Gulf War veterans' elevated number of unexplained medical symptoms.
Ventricular Arrhythmias after Left Ventricular Assist Device Implantation
Authors: REFAAT MARWAN , CHEMALY ELIE , LEBECHE DJAMEL , GWATHMEY JUDITH K. , HAJJAR ROGER J.
Published: September 2008

Background:

Left ventricular assist devices (LVADs) have been used as a bridge to cardiac transplantation and as destination therapy in patients with advanced heart failure. The period after LVAD support is associated with ventricular arrhythmias (VAs) despite ventricular unloading and such VAs can have a detrimental effect on survival. Despite the increasing use of LVAD, little is known regarding post‐LVAD VAs at the molecular level and in vivo.

Methods:

Forty‐two patients who received LVAD over a 24‐month period were evaluated and grouped on the basis of the presence or absence of VAs during LVAD support. We completed a comparative microarray analyses between six patients who developed ventricular tachycardia (VT) or ventricular fibrillation (VF) after LVAD support and six patients who did not develop VAs after LVAD.

Results:

VAs occurred in 15 patients (35.7%) during LVAD support at a median post‐LVAD day of 25.2. VAs were strongly associated with nonusage of a β‐blocker post‐LVAD (odds ratio of 7.04, P‐value = 0.001). Analysis of a subset of patients who had VT or VF after LVAD placement showed a decrease in the expression of connexin 43 (0.48 ± 0.07), Na+/K+–ATPase (0.60 ± 0.05), and voltage‐gated K+ channel Kv4.3 (0.42 ± 0.04), and an increase in Na+/Ca2+ exchanger (2.2 ± 0.4) and the structural genes: Titin (2.1 ± 0.2), laminin (1.7 ± 0.4), calsequestrin (1.8 ± 0.5), skeletal muscle isoform of troponin T (5.1 ± 0.9), and skeletal muscle isoform of troponin I (3.9 ± 0.7).

Conclusion:

After LVAD, the increased risk of VAs is strongly associated with nonusage of β‐blocker postoperatively.
Remote Monitoring of CRT‐ICD: The Multicenter Italian CareLink Evaluation—Ease of Use, Acceptance, and Organizational Implications
Authors: MARZEGALLI MAURIZIO , LUNATI MAURIZIO , LANDOLINA MAURIZIO , PEREGO GIOVANNI B. , RICCI RENATO P. , GUENZATI GIUSEPPE , SCHIRRU MILENA , BELVITO CHIARA , BRAMBILLA ROBERTO , MASELLA CRISTINA , DI STASI FRANCESCA , VALSECCHI SERGIO , SANTINI MASSIMO
Published: September 2008

Purpose:

The Medtronic CareLink allows remote implantable device follow‐up. In this first European experience with CareLink, we assessed the ease of use of the system, the acceptance, and satisfaction of patients and clinicians.

Methods:

Patients implanted with biventricular defibrillators for more than 6 months received the CareLink monitor and were trained to perform home device interrogation and transmission. Patient and clinician experience and preference were evaluated through specific questionnaires.

Results:

Sixty‐seven patients were enrolled and were able to perform data transmissions during the 3‐month study duration. The overall duration of interrogation procedure was 7 ± 5 minutes, and frequently the procedure did not require the assistance of a caregiver. Patients reported a general preference for remote versus in‐clinic follow‐up and described a sense of reassurance created by the remote monitoring capability.
In the centers, the review procedure was successful; its mean duration was 5 ± 2 minutes per transmission and the users indicated that the access and navigation of the review website were easy. At the end of the evaluation, the data available for remote review were judged complete and adequate to provide almost the same standard of care as that offered in traditional in‐clinic visit. In general, the remote monitoring was seen as a potential tool to improve the clinical management of patients with device.

Conclusions:

The ease of use, satisfaction, and acceptance of the CareLink Network in European clinical practice appears elevated both for patients and for clinicians.
Hemodynamics and Prognosis after Primary Cardiac Resynchronization System Implantation Compared to “Upgrade” Procedures
Authors: NÄGELE HERBERT , DODECK JULIA , BEHRENS STEFAN , AZIZI MOJGAN , HASHAGEN SANDRA , EISERMANN CHRISTINE , CASTEL MARIA A.
Published: September 2008

Introduction:

Left bundle brunch block (LBBB) and right ventricular stimulation (RVS) may be associated with asynchrony and heart failure. Differences between these two entities and their response to cardiac resynchronization therapy (CRT) are not well defined.

Methods:

Patients receiving CRT from 1999 to 2006 were analyzed for cardiac events and prognosis separated between primary implants for LBBB (n = 221) and upgrades from RVS (n = 107). A subgroup of 105 patients (LBBB = 69; RVS = 36) was studied in more detail (New York Heart Association [NYHA], quality of life, brain natriuretic peptide, peakVO2, left ventricular ejection fraction [LVEF], wedge pressure, Cardiac Index, QRS, left‐right preejection period using pulsed wave doppler, septum‐lateral wall motion delay using tissue doppler imaging) at baseline and after 1 year.

Results:

Age (68.4 ± 11 years vs 68.7 ± 15 years, n. s.), NYHA class (3.1 vs 3.1, n. s.), LVEF (26.4 vs 28.1, n. s.), and clinical parameters were comparable between LBBB and RVS. The latter group consisted of more patients with chronic atrial fibrillation (14% vs 37%, P = 0.03). After 1 year, NYHA class (−0.8 ± 0.8 vs −0.6 ± 0.8, n. s.), LVEF (+13.7 ± 14% vs +8.7 ± 10%, n. s.), and clinical parameters improved similarly. After a median follow‐up of 2.33 ± 1.8 years in the LBBB versus 2.43 ± 1.9 years in the RVS group, there was no difference in long‐term prognosis or cardiac events in the total cohort (5‐year event rate, 53% vs 55%, P = n. s.).

Conclusion:

Upgrade patients showed similar baseline parameters and response to CRT as to primary implants. No difference in events or long‐term prognosis could be observed.
Long‐Term Prognostic Value of Baseline C‐Reactive Protein in Predicting Recurrence of Atrial Fibrillation after Electrical Cardioversion
Authors: KORANTZOPOULOS PANAGIOTIS , KALANTZI KALLIRROI , SIOGAS KONSTANTINOS , GOUDEVENOS JOHN A.
Published: September 2008

Background:

An increasing body of evidence links atrial fibrillation (AF) to the inflammatory state. It has been suggested that increased C‐reactive protein (CRP) levels are associated with greater risk of AF recurrence at short‐ and mid‐term.

Objective:

We sought to investigate the association between CRP and long‐term risk of AF recurrence.

Methods:

This was a prospective observational study. We investigated the association between baseline CRP levels and recurrence of AF over a 3‐year follow‐up period after successful electrical cardioversion (EC). A total of 60 patients were studied (mean age: 68.4 ± 7.2 years, 60% men). All patients were receiving amiodarone for sinus rhythm maintenance. We further divided the study population into three tertiles according to the values of baseline CRP (tertile 1: <0.43 mg/dL; tertile 2: 0.43–0.8 mg/dL; tertile 3: >0.8 mg/dL).

Results:

Overall, 75% of patients relapsed into AF during the 3‐year study period. AF recurrence was significantly lower in the 1st CRP tertile group (P = 0.039). The Kaplan‐Meier survival analysis showed that the rate of AF recurrence was significantly lower in the lowest CRP tertile (log rank; P < 0.001). In a multivariable Cox regression model adjusted for other potential covariates, only CRP (upper two tertiles) was an independent predictor of AF recurrence (heart rate: 6.3, 95% confidence interval: 3.1–12.7, P < 0.001).

Conclusions:

Our findings suggest that baseline CRP levels before EC have an independent prognostic value in predicting the long‐term risk of AF recurrence.
Arrhythmic Risk Evaluation during Exercise at High Altitude in Healthy Subjects: Role of Microvolt T‐Wave Alternans
Authors: GIBELLI GIUSEPPE , FANTONI CECILIA , ANZÀ CLAUDIO , CATTANEO PAOLO , ROSSI ANDREA , MONTENERO ANNIBALE S. , BARAVELLI MASSIMO
Published: September 2008

Background:

Altitude‐induced sympathetic hyperactivity can elicit rhythm disturbances in healthy subjects, in particular during exercise.

Aim:

To asses the real susceptibility of healthy myocardium to malignant ventricular arrhythmias during exercise at high altitude using microvolt T‐wave alternans (MTWA).

Methods:

We evaluated eight healthy trained participants (one female, 42 ± 9 years) during a mountain climbing expedition on Gashembrum II (Pakistan, 8,150 m). MTWA and heart rate variability (HRV) were measured in each subject at sea level and at high altitude, both under rest conditions and during exercise. MTWA was determined with the modified moving average method. HRV was expressed as root mean square of successive differences.

Results:

Rest HRV at high altitude was significantly lower compared to rest HRV at sea level (36 ± 5 vs 56 ± 9 ms, P = 0.003). HRV during exercise was significantly lower with respect to rest condition both in normoxia (46 ± 7 vs 56 ± 9 ms, P = 0.0001) and hypoxia (27 ± 4 vs 36 ± 5 ms, P = 0.005). Moreover, HRV was significantly lower during exercise at high altitude compared to exercise at sea level (27 ± 4 vs 46 ± 7 ms, P = 0.0002) and arrhythmias were more frequent during exercise in hypoxia. Nevertheless, MTWA was absent under rest conditions both at sea level and at high altitude and minimally evoked during exercise in both conditions (22 ± 3 μV and 23 ± 3 μV, respectively, P = 0.2).

Conclusions:

In spite of an enhanced sympathetic activity, MTWA testing during exercise at high altitude was negative in all participants. Healthy trained subjects during exercise under hypoxia seem to be at low risk for dangerous arrhythmias.
Increased Myocardial Collagen Turnover in Patients with Progressive Cardiac Conduction Disease
Authors: BOZKAYA YASEMIN T. , AYDIN HIKMET H. , CELIK HANDAN A. , KAYIKCIOGLU MERAL , PAYZIN SERDAR , KULTURSAY HAKAN , AYDIN MEHMET , YESIL MURAT , CAN LEVENT H. , HASDEMIR CAN
Published: September 2008

Background:

Histopathologically, progressive cardiac conduction disease (PCCD) is characterized by progressive fibrosis and sclerodegenerative changes in the proximal and distal conduction system of the heart. Therefore, we sought to determine the serum levels of myocardial collagen turnover markers, extracellular matrix components, transforming growth factor β1 (TGFβ1), and bone morphogenic protein‐7 (BMP‐7) in this population.

Methods:

Study population included 20 patients (6 M/14 F, mean age 76 ± 8 years) with acquired, permanent 2:1, or complete atrioventricular block and compared with age‐ and sex‐matched, asymptomatic, healthy control subjects (n = 18, 6 M/12 F, mean age 75 ± 7 years). Serum myocardial collagen turnover markers:matrix metalloproteinases (MMP‐1, 2, 9), tissue inhibitor of matrix metalloproteinase (TIMP‐1), amino‐terminal propeptide of procollagen type I (PINP) and type III (PIIINP), carboxy‐terminal telopeptide of collagen type I (CITP), and carboxy‐terminal propeptide of procollagen type I (PICP), serum extracellular matrix components (laminin and fibronectin), TGFβ1, and BMP‐7 levels were measured in both groups.

Results:

Serum PICP (849 ± 396 vs 631 ± 294 ng/mL, P = 0.04), PIIINP (3.7 ± 1.3 vs 3 ± 1 μg/L, P = 0.03), CITP (0.68 ± 0.35 vs 0.48 ± 0.25 ng/mL, P = 0.037), and plasma MMP‐9 (58.8 ± 56 vs 25.9 ± 17.3 ng/mL, P = 0.006) levels were higher in patient population compared to control subjects. Serum MMP‐1 (24.1 ± 20.5 vs 13.6 ± 7.5 ng/mL, P = 0.045) and MMP‐2 (1310 ± 139 vs 1186 ± 163 ng/mL, P = 0.01) levels were higher in control subjects compared to patient population. There was no difference in serum TIMP‐1, PINP, laminin, fibronectin, TGFβ1, and BMP‐7 levels between two groups.

Conclusion:

Our findings demonstrate the presence of increased myocardial collagen turnover and active fibrotic process in patients with PCCD compared to control subjects.
Performance of an Autonomous Telemonitoring System in Children and Young Adults with Congenital Heart Diseases
Authors: ZARTNER PETER , HANDKE RONALD , PHOTIADIS JOACHIM , BRECHER ANNE M. , SCHNEIDER MARTIN B.
Published: September 2008

Background:

Integrated telemonitoring systems controlling circulatory and electrical parameters in adults with an implanted pacemaker have shown to be advantageous during follow‐up of this patient group. In children and young adults with a congenital heart disease (CHD), these systems have to cope with a diversity of varying arrhythmias and a broad range of intrinsic cardiac parameters. Additional problems arise from the patients' growth and anatomic anomalies.

Methods:

Since 2005, eight young patients (age 4.1– 37 years, mean 15.5 years) with a CHD received a pacemaker or implantable cardioverter defibrillator with an autonomous telemonitoring system at our clinic. The mean follow‐up time was 395 days (range 106–834 days, 8.7 patient years).

Results:

In seven of eight patients the system transmitted information, which led to beneficial modifications of the current antiarrhythmic therapy. In three patients the reported events were of a critical nature. One patient remained event‐free for 192 days after implantation. During follow‐up, 96% of the days were covered. The system also transferred additional information on the effectiveness of antiarrhythmic medication and the impact of physical activity.

Conclusions:

Young patients with an insufficient intrinsic heart rate or progressing arrhythmia, in addition to the conventional indications for pacemaker or defibrillator implantation, seem to profit to a high percentage from a telemetric surveillance system. The fully automated procedure of device interrogation and information transmission gives a daily overview on system function and specific arrhythmic events, especially in children who are unaware of any symptoms.
Remote Magnetic Versus Manual Catheter Navigation for Ablation of Supraventricular Tachycardias: A Randomized, Multicenter Trial
Authors: WOOD MARK A. , ORLOV MICHAEL , RAMASWAMY KARTHIK , HAFFAJEE CHARLES , ELLENBOGEN KENNETH ,   The Stereotaxis Heart Study Investigators
Published: September 2008

Introduction:

The potential benefits of remote robotic navigation for catheter ablation procedures have not been demonstrated in controlled clinical trials. The purpose of this study was to compare remote magnetic catheter navigation to manual navigation for the ablation of common supraventricular arrhythmias.

Methods and Results:

Patients with supraventricular arrhythmias due to atrioventricular (AV) nodal reentry, accessory pathways, or undergoing AV junctional ablation for complete heart block were randomized in a 3:1 ratio between magnetic (Niobe system and Helios II catheter, Stereotaxis, Inc., St. Louis, MO) and manual navigation for radiofrequency ablation at 13 centers. The primary endpoint of the study was total fluoroscopic time. Fifty‐six patients were randomized to magnetic navigation and 15 to manual navigation. AV nodal reentry was the most common arrhythmia in both groups. Total fluoroscopy time was reduced in the magnetic navigation group (median 17.8 minutes, interquartile (IQ) range 9.9,27.8 minutes) compared to manual navigation (27.1, IQ 19.0,48.0, P < 0.05). The acute success rates (91% for magnetic and 87% for manual navigation, P > 0.05) did not differ between groups. The number of lesions delivered was less for magnetic navigation (6, IQ 4,9 vs 10, IQ 7, 26, P < 0.05). Total procedure time (median 151, IQ 111, 221 minutes magnetic and 151, IQ 110, 221 minutes manual) and complication rates (5.4% patients magnetic and 6.7% patients manual) were similar between the groups (both P > 0.05).

Conclusions:

Remote magnetic catheter navigation reduces fluoroscopic time and radiofrequency lesion deliveries for the ablation of common supraventricular arrhythmias compared to manual catheter navigation.
Focal and Linear Endocardial and Epicardial Catheter‐Based Cryoablation of Normal and Infarcted Ventricular Tissue
Authors: D'AVILA ANDRÉ , ARYANA ARASH , THIAGALINGAM ARAVINDA , HOLMVANG GODTFRED , SCHMIDT EHUD , GUTIERREZ PAULO , RUSKIN JEREMY N. , REDDY VIVEK Y.
Published: September 2008

Background:

This study of a chronic porcine postinfarction model examined whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium including scarred ventricle. Endocardial and epicardial focal cryolesions were also compared to determine if there were significant differences in lesion characteristics.

Methods:

Eighty focal endocardial and 28 focal epicardial cryoapplications were delivered to eight normal caprine and four normal porcine ventricular myocardium, and 21 linear cryolesions were applied along the border of infarcted epicardial tissue in a chronic porcine infarct model in six swines.

Results:

Focal endocardial cryolesions in normal animals measured 9.7±0.4 mm (length) by 7.3±1.4 mm (width) by 4.8±0.2 mm (depth), while epicardial lesions measured 10.2±1.4 mm (length) by 7.7±2 mm (width) by 4.6±0.9 mm (depth); P > 0.05. Linear epicardial cryolesions in the chronic porcine infarct model measured 36.5±7.8 mm (length) by 8.2±1.3 mm (width) by 6.0±1.2 mm (depth). The mean depth of linear cryolesions applied to the border of the infarct scar was 7±0.7 mm, as measured by magnetic resonance imaging.

Conclusions:

Cryoablation can create deep lesions when delivered to the ventricular epicardium. Endocardial and epicardial cryolesions created by a focal cryoablation catheter are similar in size and depth. The ability to rapidly create deep linear cryolesions may prove to be beneficial in substrate‐based catheter ablation of ventricular arrhythmias.
Biventricular ICD Implantation Using the Iliofemoral Approach: Providing CRT to Patients with Occluded Superior Venous Access
Authors: ALLRED JAMES D. , McELDERRY HUGH T. , DOPPALAPUDI HARISH , YAMADA TAKUMI , KAY G. NEAL
Published: September 2008

A 32‐year‐old woman with a history of nonischemic dilated cardiomyopathy, left bundle branch block, left ventricular ejection fraction of 0.15, and New York Heart Association Class III congestive heart failure, despite optimal medical treatment, was referred for cardiac resynchronization therapy with implantation of an implantable cardioverter defibrillator. The patient had prior chemotherapy for non‐Hodgkin's lymphoma and was shown to have chronic total occlusion of the superior vena cava (SVC) by magnetic resonance imaging. Cardiac resynchronization was accomplished with an iliofemoral approach without complications resulting in marked clinical improvement. We conclude that the iliofemoral approach allows transvenous implantation of cardiac resynchronization therapy in patients with superior vena cava occlusion.