bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Requirements of Human Ether-a-go-go– related Gene Channels for Block by Bupivacaine
Authors: Siebrands Cornelia C. , Friederich Patrick
Published: February 2007

Background

Local anesthetics interact with human ether-a-go-go-related gene (HERG) channels via the aromatic amino acids Y652 and F656 in the S6 region. This study aimed to establish whether the residues T623, S624, and V625 residing deeper within the pore are also involved in HERG channel block by bupivacaine. In addition, the study aimed to further define the role of the aromatic residues Y652 and F656 in bupivacaine inhibition by mutating these residues to threonine.

Methods

Alanine and threonine mutants were generated by site-directed mutagenesis. Electrophysiologic and pharmacologic properties of wild-type and mutant HERG channels were established using two-electrode voltage-clamp recordings of Xenopus laevis oocytes expressing HERG channels.

Results

Tail currents at -120 mV through HERG wild-type channels were inhibited with an IC50 value of 132 +/- 22 microm (n = 33). Bupivacaine (300 microm) inhibited wild-type tail currents by 62 +/- 12% (n = 7). Inhibition of HERG tail currents by bupivacaine (300 microm) was reduced by all mutations (P < 0.001). The effect was largest for F656A (inhibition 5 +/- 2%, n = 6) in the lower S6 region and for T623A (inhibition 13 +/- 4%, n = 9) near the selectivity filter. Introducing threonine at positions 656 and 652 significantly reduced inhibition by bupivacaine compared with HERG wild type (P < 0.001).

Conclusions

The authors' results indicate that not only the aromatic residues Y652 and F656 but also residues residing deeper within the pore and close to the selectivity filter of HERG channels are involved in inhibition of HERG channels by the low-affinity blocker bupivacaine.
Postoperative Cognitive Dysfunction after Noncardiac Surgery
Authors: Newman Stanton , Stygall Jan , Hirani Shashivadan , Shaefi Shahzad , Maze Mervyn , Warltier David C.
Published: February 2007

This article describes a systematic review on the research into postoperative cognitive dysfunction (POCD) in noncardiac surgery to ascertain the status of the evidence and to examine the methodologies used in studies. The review demonstrated that in the early weeks after major noncardiac surgery, a significant proportion of people show POCD, with the elderly being more at risk. Minimal evidence was found that patients continue to show POCD up to 6 months and beyond. Studies on regional versus general anesthesia have not found differences in POCD. Many studies were found to be underpowered, and a number of other methodologic difficulties were identified. These include the different types of surgery in studies and variations in the number and range of neuropsychological tests used. A particular issue is the variety of definitions used to classify individuals as having POCD.
Pathogenesis, Diagnosis, and Treatment of Lumbar Zygapophysial (Facet) Joint Pain
Authors: Cohen Steven P. , Raja Srinivasa N.
Published: February 2007

Lumbar zygapophysial joint arthropathy is a challenging condition affecting up to 15% of patients with chronic low back pain. The onset of lumbar facet joint pain is usually insidious, with predisposing factors including spondylolisthesis, degenerative disc pathology, and old age. Despite previous reports of a "facet syndrome," the existing literature does not support the use of historic or physical examination findings to diagnose lumbar zygapophysial joint pain. The most accepted method for diagnosing pain arising from the lumbar facet joints is with low-volume intraarticular or medial branch blocks, both of which are associated with high false-positive rates. Standard treatment modalities for lumbar zygapophysial joint pain include intraarticular steroid injections and radiofrequency denervation of the medial branches innervating the joints, but the evidence supporting both of these is conflicting. In this article, the authors provide a comprehensive review of the anatomy, biomechanics, and function of the lumbar zygapophysial joints, along with a systematic analysis of the diagnosis and treatment of facet joint pain.
Long‐term Outcome of Children Receiving Home Parenteral Nutrition: A 20‐year Single‐center Experience in 302 Patients
Authors: Colomb Virginie , Dabbas‐Tyan Myriam , Taupin Pierre , Talbotec Cécile , Révillon Y , Jan D , De Potter Sophie , Gorski‐Colin Anne‐Marie , Lamor Michèle , Herreman Karen , Corriol Odile , Landais Paul , Ricour Claude , Goulet Olivier
Published: February 2007

Background:

More information is needed regarding the prognosis of children receiving home parenteral nutrition (HPN). This article describes 20‐year outcome data in children receiving HPN and provides separate profiles for the major pediatric diagnostic subgroups.

Patients and Methods:

This retrospective study included children who started receiving HPN between January 1, 1980, and December 31, 1999, in a single pediatric HPN center.

Results:

A total of 302 children were recruited, 230 (76%) with primary digestive disorders and 72 (24%) with nonprimary digestive disorders. Median age at HPN onset was 1.5 years. Median duration of HPN was 1.3 years. By January 1, 2000, 54% had weaned from HPN, 26% were still receiving HPN, 16% had died, and 4% had undergone intestinal transplantation. The survival probabilities at 2, 5, 10, and 15 years were 97%, 89%, 81%, and 72%, respectively. The likelihood and cause of death depended on the underlying diagnosis. Nine percent of children with primary digestive disorders died, 24% from their primary disease and 48% from liver disease or sepsis. Children with intractable diarrhea of infancy had the highest mortality rate (25%) and the highest incidence of liver disease (48%; P = 0.0002). Thirty‐eight percent of children with primary nondigestive diseases died, 94% from their primary disease and 6% from liver disease or sepsis.

Conclusions:

Outcome and survival of children receiving HPN are mainly determined by their underlying diagnosis. Nearly all children with primary digestive disease survive if referred early to an expert center.
Pediatric Crohn Disease: Clinical and Genetic Characteristics in Taiwan
Authors: Hsiao Cheng‐Hui , Wei Shu‐Chen , Wong Jau‐Min , Lai Hong‐Shiee , Chang Mei‐Hwei , Ni Yen‐Hsuan
Published: February 2007

Objectives:

Crohn disease (CD) is a heterogeneous disorder. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 (NOD2/CARD15) gene located at 16q12 is strongly associated with susceptibility to CD in white people but is absent in adult Asian patients, whereas the role of Toll‐like receptor 4 (TLR4) polymorphisms has also been reported. Because clinical and genetic data in Asian children with CD are lacking, the aim of this study was to elucidate the clinical and genetic characteristics of Taiwanese children with CD.

Patients and Methods:

All of the children hospitalized at the National Taiwan University Hospital between January 2000 and July 2005 who fulfilled the diagnostic criteria for CD were enrolled. Their clinical characteristics were recorded, and genomic DNA was extracted from their white blood cells. After polymerase chain reaction was performed, direct sequencing was done to detect the 4 NOD2 hotspot mutations (P268S, R702W, G908R, 1007fs) and TLR4 polymorphisms (Asp299Gly, Thr399Ile).

Results:

CD was diagnosed in 10 children (6 boys and 4 girls; age range at diagnosis, 14 months to 13 years; median age, 11.1 years). There were 5 children with ileocolonic region involvement, 3 with colonic region involvement, 2 with ileal region involvement, 4 with additional upper gastrointestinal tract involvement, and 2 with additional perianal fistula. Half of the children had growth retardation at diagnosis. Neither NOD2/CARD15 mutations nor TLR4 polymorphisms were found in the 10 patients.

Conclusions:

Ileocolonic location and inflammatory behavior constitute the most frequent phenotype of CD in Taiwan. Mutations in the NOD2/CARD15 and TLR4 genes that are common in the West are not associated with CD in Taiwanese children.
Wasting and Intestinal Barrier Function in Children Taking Alanyl‐Glutamine–Supplemented Enteral Formula
Authors: Lima Noélia L , Soares Alberto M , Mota Rosa MS , Monteiro Helena SA , Guerrant Richard L , Lima Aldo AM
Published: February 2007

Objective:

We examined the effect of a diet supplemented with alanyl‐glutamine (AG) or placebo glycine (G) on intestinal barrier function and growth in children in northeastern Brazil.

Patients and Methods:

One hundred seven children ages 7.9 to 82.2 months with a weight‐for‐age (WAZ), height‐for‐age (HAZ), or weight‐for‐height (WHZ) z‐score less than −1 were studied. From July 2003 to November 2004, 51 study patients received AG (24 g/d) and 56 received G (25 g/d; isonitrogenic concentration) control for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed on days 1 and 10 of nutritional supplementation. Weight and height were measured on days 1, 10, 30, and 120 of the protocol.

Results:

The patients were similar on admission with regard to age, sex, birth weight, nutritional status, lactulose/mannitol ratio, and serum concentrations of glutamine and arginine. The percentage of lactulose urinary excretion significantly improved (decreased) in children receiving AG for 10 days but not in those receiving glycine controls. AG significantly increased cumulative change over 120 days in WHZ and WAZ scores but not HAZ scores after adjustment for age and season in comparison with the placebo glycine group.

Conclusions:

Children tolerated AG‐supplemented enteral formula well, and it significantly improved cumulative WHZ and WAZ over 120 days in comparison with children in the placebo glycine group. The data also suggested a beneficial effect of AG in the barrier function paracellular pathway, albeit with reduced mannitol excretion. Thus, although the effect of AG on reduced mannitol concentration requires clarification, AG appears to improve nutrition and barrier function.
Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast‐fed Infants
Authors: Ziegler Ekhard , Vanderhoof Jon A , Petschow Bryon , Mitmesser Susan Hazels , Stolz Suzanne I , Harris Cheryl L , Berseth Carol Lynn
Published: February 2007

Objectives:

The present study was designed to evaluate the effect of 2 different combinations of prebiotic ingredients, polydextrose (PDX), galactooligosaccharides (GOS), and lactulose (LOS), at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age.

Patients and Methods:

Healthy, formula‐fed, term infants (n = 226) were randomly assigned to 1 of 3 study formula groups: control group (n = 76), PG4 group (control formula supplemented with 4 g/L of a prebiotic blend, n = 74), or PGL8 group (control formula supplemented with 8 g/L of a prebiotic blend, n = 76). Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age, and 24‐hour dietary recall and 24‐hour tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study.

Results:

There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point. Significant differences in stool consistency were detected among the 3 formula groups at 30, 60, and 90 days of age (P < 0.001, P = 0.025, P = 0.004, respectively), with the supplemented formula groups having looser stools than the control group. The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age (P = 0.021 and P = 0.017, respectively), but all of the groups were similar at 60, 90, and 120 days of age. A statistical difference was detected among the formula groups in 3 categories of adverse events: diarrhea (control vs PG4, 4% vs 18%, P = 0.008), eczema (PG4 vs control, 18% vs 7%, P = 0.046; PG4 vs PGL8, 18% vs 4%, P = 0.008), and irritability (control vs PGL8, 4% vs 16%, P = 0.027).

Conclusions:

Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast‐fed infants in comparison with infants fed an unsupplemented formula. A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics.
The topography of steady sandpiles on arbitrary domains
Authors: Pauli Nathan Stephen , Gioia Gustavo
Published: February 2007

If sand is continually and slowly added onto a table, a pile will grow and reach some steady state, whereupon any further sand added to the pile will fall off the table, leaving the surface of the pile unchanged. A construction that gives the surface of a unique steady pile for a table of any given shape was proposed by Arpad L. Nadai. Here, we show that Nadai's construction can be justified mathematically on the basis of a few plausible assumptions on the mechanical behaviour of sand. We also show that the surface of the steady pile given by the construction is the maximal topography supported on the domain of the table; that the surface may contain smooth patches, valleys, peaks and ridges; that any smooth patch is developable; that any valley is smooth, straight and without tributaries, and has a slope equal to the angle of repose of the sand; that any peak is sharp; and that any ridge is sharp and has a slope less than the angle of repose of the sand. Lastly, we perform simple experiments and verify that actual steady piles look similar to those given by the construction, with a precision that depends on the type of sand and how carefully the sand is poured to form a pile.
Integral criteria for closed surfaces with constant mean curvature
Authors: Guzzardi Luca , Virga Epifanio G
Published: February 2007

We propose three integral criteria that must be satisfied by all closed surfaces with constant mean curvature immersed in the three-dimensional Euclidean space. These criteria are integral identities that follow from requiring the second variation of the area functional to be invariant under rigid displacements. We obtain from them a new proof of the old result by Delaunay, to the effect that the sphere is the only closed axis-symmetric surface.
Compositional controls on melting and dissolving a salt into a ternary melt
Authors: Hatton D.C , Woods A.W
Published: February 2007

We explore theoretically the controls on dissolution of salt A, in an undersaturated brine of salts A and B. We show that, as the concentration of B increases, the dissolution rate of A decreases, for brine of given temperature. We also show that there is a sharper decrease in dissolution rate with increasing concentration, for concentrations of B above a critical value, where B limits the equilibrium concentration. We explore the implications of the predictions for dissolution of KCl or NaCl, by a mixed brine of NaCl and KCl, a common reaction that may arise in dissolution of evaporites. We predict that, with mixed-composition brine, KCl crystals dissolve more rapidly than NaCl crystals, unless the (far-field) brine is nearly saturated in KCl. We also predict that the dissolution rate of these salts is largely independent of fluid temperature and is controlled by compositional diffusion.
Geometric phases and critical phenomena in a chain of interacting spins
Authors: Reuter Moritz E , Hartmann Michael J , Plenio Martin B
Published: February 2007

The geometric phase can act as a signature for critical regions of interacting spin chains in the limit where the corresponding circuit in parameter space is shrunk to a point and the number of spins is extended to infinity; for finite circuit radii or finite spin chain lengths, the geometric phase is always trivial (a multiple of 2
π
). In this work, two related signatures of criticality are proposed which obey finite-size scaling and which circumvent the need for assuming any unphysical limits. They are based on the notion of the Bargmann invariant, whose phase may be regarded as a discretized version of the Berry phase. As circuits are considered which are composed of a discrete finite set of vertices in parameter space, they are able to pass directly
through
a critical point, rather than having to circumnavigate it. The proposed mechanism is shown to provide a diagnostic tool for criticality in the case of a given non-solvable one-dimensional spin chain with nearest-neighbour interactions in the presence of an external magnetic field.
The nested structure of a scavenger community
Authors: Selva Nuria , Fortuna Miguel A
Published: February 2007

Scavenging is a widespread phenomenon in vertebrate communities which has rarely been accounted for, in spite of playing an essential role in food webs by enhancing nutrient recycling and community stability. Most studies on scavenger assemblages have often presented an oversimplified view of carrion foraging. Here, we applied for the first time the concept of nestedness to the study of a species-rich scavenger community in a forest ecosystem (Białowieża Primeval Forest, Poland) following a network approach. By analysing one of the most complete datasets existing up to now in a pristine environment, we have shown that the community of facultative scavengers is not randomly assembled but highly nested. A nested pattern means that species-poor carcasses support a subset of the scavenger assemblage occurring at progressively species-rich carcasses. This result contradicts the conventional view of facultative scavenging as random and opportunistic and supports recent findings in scavenging ecology. It also suggests that factors other than competition play a major role in determining community structure. Nested patterns in scavenger communities appear to be promoted by the high diversity in carrion resources and consumers, the differential predictability of the ungulate carcass types and stressful environmental conditions.
Genetic polymorphism in leaf-cutting ants is phenotypically plastic
Authors: Hughes William O.H , Boomsma Jacobus J
Published: February 2007

Advanced societies owe their success to an efficient division of labour that, in some social insects, is based on specialized worker phenotypes. The system of caste determination in such species is therefore critical. Here, we examine in a leaf-cutting ant (
Acromyrmex echinatior
) how a recently discovered genetic influence on caste determination interacts with the social environment. By removing most of one phenotype (large workers; LW) from test colonies, we increased the stimulus for larvae to develop into this caste, while for control colonies we removed a representative sample of all workers so that the stimulus was unchanged. We established the relative tendencies of genotypes to develop into LW by genotyping workers before and after the manipulation. In the control colonies, genotypes were similarly represented in the large worker caste before and after worker removal. In the test colonies, however, this relationship was significantly weaker, demonstrating that the change in environmental stimuli had altered the caste propensity of at least some genotypes. The results indicate that the genetic influence on worker caste determination acts via genotypes differing in their response thresholds to environmental cues and can be conceptualized as a set of overlapping reaction norms. A plastic genetic influence on division of labour has thus evolved convergently in two distantly related polyandrous taxa, the leaf-cutting ants and the honeybees, suggesting that it may be a common, potentially adaptive, property of complex, genetically diverse societies.
Evidence that pigeons orient to geomagnetic intensity during homing
Authors: Dennis Todd E , Rayner Matt J , Walker Michael M
Published: February 2007

The influence of the Earth's magnetic field on locomotory orientation has been studied in many taxa but is best understood for homing pigeons (Columba livia). Effects of experimentally induced and naturally occurring perturbations in the geomagnetic field suggest that pigeons are sensitive to changes in geomagnetic parameters. However, whether pigeons use the Earth's magnetic field for position determination remains unknown. Here we report an apparent orientation to theintensitygradient of the geomagnetic field observed in pigeons homing from sites in and around a magnetic anomaly. From flight trajectories recorded by GPS-based tracking devices, we noted that many pigeons released at unfamiliar sites initially flew, in some cases up to several kilometres, in directions parallel and/or perpendicular to the bearing of the local intensity field. This behaviour occurred irrespective of the homeward direction and significantly more often than what was expected by random chance. Our study describes a novel behaviour which provides strong evidence that pigeons when homing detect and respond to spatial variation in the Earth's magnetic field—information of potential use for navigation.
Getting back to the rough ground: deception and ‘social living’
Authors: Reddy Vasudevi
Published: February 2007

At the heart of the social intelligence hypothesis is the central role of ‘social living’. But living is messy and psychologists generally seek to avoid this mess in the interests of getting clean data and cleaner logical explanations. The study of deception as intelligent action is a good example of the dangers of such avoidance. We still do not have a full picture of the development of deceptive actions in human infants and toddlers or an explanation of why it emerges. This paper applies Byrne & Whiten's functional taxonomy of tactical deception to the social behaviour of human infants and toddlers using data from three previous studies. The data include a variety of acts, such as teasing, pretending, distracting and concealing, which are not typically considered in relation to human deception. This functional analysis shows the onset of non-verbal deceptive acts to be surprisingly early. Infants and toddlers seem to be able to communicate false information (about themselves, about shared meanings and about events) as early as true information. It is argued that the development of deception must be a fundamentally social and communicative process and that if we are to understand why deception emerges at all, the scientist needs to get ‘back to the rough ground’ as Wittgenstein called it and explore the messy social lives in which it develops.
Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells
Authors: Dirks Peter B
Published: February 2007

Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence points towards the brain's known proliferative zones. The identification of brain tumour stem cells has important implications for understanding brain tumour biology and these cells may be critical cellular targets for curative therapy.
Clinical Correlates of Isolated Left Ventricular Diastolic Dysfunction Among Hospitalized Older Heart Failure Patients
Authors: Ahmed Ali , Nanda Navin C. , Weaver Michael T. , Allman Richard M. , DeLong James F.
Published: February 2007

Heart failure due to isolated left ventricular diastolic dysfunction (LVDD) is common among older adults. The purpose of this study was to develop a model based on admission clinical features to predict isolated LVDD in older adults hospitalized with heart failure. The authors studied 394 Alabama Medicare beneficiaries discharged with a primary discharge diagnosis of heart failure. All patients had data on LV function determined by echocardiography performed during the index hospitalization. Isolated LVDD was defined by LV ejection fraction ≥45% or LV function described as normal. The authors used all subsets multiple logistic regression analyses to examine various models predicting isolated LVDD. Patients had a mean (±SD) age of 78 (±7) years and 58% were women. One hundred thirty nine (35%) patients had isolated LVDD. More women (47%) than men (21%) had isolated LVDD (p<0.001). Variables independently associated with isolated LVDD in the selected 12‐predictor model were female sex (odds ratio [OR]=3.10; 95% confidence interval [CI]=1.86–5.15), pulse 100 beats/min or greater (OR=0.43; 95% CI=0.25–0.72), systolic blood pressure (OR=1.01; 95% CI=1.00–1.02), diastolic blood pressure (OR=0.98; 95% CI=0.96–0.99), pulmonary vascular congestion by chest x‐ray (OR=0.51; 95% CI=0.30–0.88), coronary artery disease (OR=0.54; 95% CI=0.32–0.92), cardiomyopathy (OR=0.21; 95% CI=0.10–0.47), and admission to a teaching hospital (OR=0.36; 95% CI=0.15–0.88). The authors concluded that the proportion of patients with isolated LVDD among this cohort of elderly hospitalized heart failure patients was low and was associated with few clinical characteristics. Except for female sex and systolic blood pressure, all model variables were negatively associated with isolated LVDD.
“You Aren't Going to Get Better by Just Sitting Around”: Physical Activity Perceptions, Motivations, and Barriers in Adults 75 Years of Age or Older
Authors: Grossman Melanie D. , Stewart Anita L.
Published: February 2007

Despite accumulating evidence of cardiovascular benefits associated with physical activity in older people, sedentary behavior increases with age. Few physical activity research studies focus on underactive adults 75 years and older. In‐depth qualitative interviews using open‐ended questions explored perceptions, motivations, and barriers to physical activity in 33 previously sedentary or underactive adults age ≥75. Data were analyzed using the NUD*IST (Non‐numerical, Unstructured Data Indexing, Searching, and Theorizing) qualitative analysis program. Participants saw sedentary behavior as harmful, considered themselves relatively active, were unsure of amounts of physical activity to do, and welcomed more physical activity information from their doctors. Motivations included health, independence, family, and appearances. Barriers were poor health, lack of time, aging, and adverse environments. Results suggest that people continue to be interested in physical activity as they age, but some misperceptions about physical activity exist. Even with health problems and age, physical activity counseling by doctors is valued and considered helpful by this age group.
Atrial Fibrillation in the Elderly
Authors: Yadav Anil , Scheinman Melvin
Published: February 2007

Atrial fibrillation is the most common arrhythmia in the United States, whose incidence is greatest in the elderly population. This rhythm disorder can be paroxysmal or chronic and is associated with a range of clinical conditions from palpitations and dyspnea to stroke and death. In the elderly the mainstay of treatment of atrial fibrillation should utilize drug therapy. The main goals of drug therapy should be effective rate control to avoid tachycardia‐induced cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism, and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those patients in whom effective rate control cannot be achieved, catheter ablation of the atrioventricular node and implantation of a permanent pacemaker should be considered. Catheter ablation of atrial fibrillation by targeting pulmonary venous foci or pulmonary venous isolation currently remains investigational and we advocate its use be limited to symptomatic patients who have failed traditional therapy.
Sexual Activity and the Cardiac Patient
Authors: Thorson Anne I.
Published: February 2007

Coronary heart disease is the major cause of morbidity and mortality in the elderly population in the United States, affecting both men and women. Advances in cardiac therapies have enabled cardiac patients to remain both physically and sexually active even into their eighties and nineties. However, both patients and physicians are reluctant to discuss sexual issues. A significant number of patients will have sexual dysfunction following a diagnosis of cardiovascular disease. It is therefore imperative that physicians initiate discussions regarding sexual activity and potential risks to the patient such as myocardial infarction, sudden death, and arrhythmia. Risk stratification based on objective criteria and in particular cases, functional testing, may be useful in counseling patients regarding individual risk. Newly available pharmacologic therapies such as sildenafil may be useful, but must be used with caution in patients with known cardiovascular disease.
Elderly Patients With Acute Coronary Syndromes: Higher Risk and Greater Benefit From Antiplatelet Therapy and/or Interventional Therapy
Authors: Cannon Christopher P.
Published: February 2007

Outcomes in elderly patients with acute coronary syndromes are worse than in younger patients, and disappointingly, some therapies, such as thrombolysis for ST elevation myocardial infarction, appear to have less relative benefit than in younger patients. However, in unstable angina and non‐ST elevation myocardial infarction, the elderly appear to derive greater relative and absolute benefit from the newer more potent antithrombotic therapies. With the glycoprotein IIb/IIIa inhibitors, an equivalent relative benefit has been observed, which translated into a greater absolute benefit in older vs. younger patients. Similarly, when comparing clopidogrel plus aspirin to aspirin alone, there was a consistent 20% reduction in cardiovascular death, myocardial infarction, or stroke in both elderly and younger patients. An emerging area of focus, however, is that of the appropriate dose in the elderly. Because the elderly on average have worse renal function, many drugs will not be cleared as well, and thus higher plasma levels will exist, which can translate into higher bleeding complications. Future studies are evaluating downward dose‐adjustment of new therapies in the elderly as a means of improving the efficacy/safety profile. Thus, in unstable angina and non‐ST elevation myocardial infarction, elderly patients are at higher risk and appear to derive particular benefit from more aggressive antithrombotic and interventional therapies.
Drug Therapy Of Heart Failure in the Elderly
Authors: Rich Michael W.
Published: February 2007

Heart failure is a disorder that predominantly affects older adults, with more than 50% of heart failure hospitalizations occurring in persons over 75 years of age. Unfortunately, most of the major heart failure clinical trials have targeted middle‐aged patients with systolic heart failure, and the applicability of these studies to elderly patients, particularly those with preserved left ventricular systolic function, remains uncertain. In this paper, current data on the pharmacotherapy of heart failure in older adults are reviewed, recommended approaches to managing systolic and diastolic heart failure are outlined, and the importance of preventive measures is emphasized.
Cost‐Savings Analysis of Using a Portable Coagulometer for Monitoring Homebound Elderly Patients Taking Warfarin
Authors: Cheung Dorothy S. , Heizer Diane , Wilson Janice , Gage Brian F.
Published: February 2007

The authors present a prospective cost‐savings analysis to determine how the use of portable coagulometers in the home health setting affects medical expenditure. Thirty‐five elderly patients (mean age 67 years) receiving cardiac home health care and long‐term oral anticoagulation were evaluated with paired measurements of the international normalized ratio by both a traditional, laboratory‐based prothrombin time and a point‐of‐care coagulometer (CoaguChek, Roche Diagnostics, Basel, Switzerland). Costs for materials, procedures, transportation, and labor were summed for both methods, and it was found that cost of international normalized ratio determination by the portable coagulometer was significantly less than the traditional method ($6.85 vs. $17.30; p<0.001). The authors conclude that by saving on the costs of transporting and processing traditional international normalized ratio specimens, use of point‐of‐care coagulometers by home health nurses could reduce medical expenditure. The cost savings and potential improvement in quality of care argue for equipping home health nurses with portable coagulometers.
Management of the Elderly Aortic Stenosis Patient With Low Gradient and Low Ejection Fraction
Authors: Carabello Blase A.
Published: February 2007

The incidence of aortic stenosis increases with age and thus it occurs frequently in elderly patients. Once severe obstruction has developed, death occurs within 3 years unless the aortic valve is replaced. The results of aortic valve surgery, even in octogenarians, are usually excellent in the absence of comorbidity. The exception to this rule is for the aortic stenosis patient who has low ejection fraction, a low cardiac output and a transvalvular gradient of <30 mm Hg. Such patients have far advanced left ventricular dysfunction and increased operative mortality. However, even these patients may benefit from surgery if they have truly severe aortic stenosis. Because valve area is unreliable at low cardiac outputs, output should be increased pharmacologically in such patients and the valve area recalculated. If the transvalvular gradient increases with output, severe aortic stenosis is present and valve replacement may be beneficial. However, if output increases but gradient does not, only mild stenosis is present and surgery is unlikely to prolong life.
Prophylactic Aortic Valve Replacement in Older Patients for Mild Aortic Stenosis During Coronary Bypass Surgery
Authors: Eslami Mahmoud , Rahimtoola Shahbudin H.
Published: February 2007

Coronary bypass surgery (CBS) is performed in many older patients who frequently also have mild calcific aortic stenosis. It is important that a correct assessment of the severity of aortic stenosis is done by calculating the aortic valve area. Mild aortic stenosis is aortic valve area >1.5 cm2, >0.9 cm2/m2; severe aortic stenosis is aortic valve area = 1.0 cm2, = 0.6 cm2/m2. Patients who have severe aortic stenosis should have aortic valve replacement (AVR) at the time of CBS. Patients with mild aortic stenosis should not have AVR simultaneously with CBS because: 1) patients having AVR+CBS have a higher operative and 10‐year mortality; 2) prosthetic heart valves are associated with a complication rate of 2%‐6% per year; and 3) only about 12% of patients with mild aortic stenosis will have developed severe aortic stenosis in 10 years. Performing AVR for mild aortic stenosis at the time of CBS will probably result in 91 unnecessary AVRs and 29 excess deaths in 10 years.
Treating Hypertension in the Elderly Protagonist Viewpoint
Authors: Weber Michael A.
Published: February 2007

Cardiovascular disease is the main cause of serious illness and death in the United States. Increasing age is a strong predictor of cardiovascular events, driven largely by such major conditions as hypertension and diabetes mellitus. Systolic hypertension probably reflects progressive stiffening of large and small arteries; close to 90% of all Americans will have this diagnosis by their 80s. Regardless of age, systolic hypertension is a powerful risk factor for stroke, heart failure, and other cardiovascular outcomes. Treating hypertension in the elderly sharply decreases the probability of these events. Clinical trial evidence does not include patients with stage 1 systolic hypertension (140–159 mm Hg), although the results in stage 2 are so convincing that it is very reasonable (as concluded by national guidelines committees) to extrapolate benefits and recommend treatment to patients in the less‐severe group. Whereas evidence of treatment benefits in patients aged 80 years and older is limited, sufficient octogenarians have been studied to confidently assert that strokes, at least, can be prevented. Another potentially important benefit that is yet to be fully confirmed is that treating hypertension in older people may also reduce the incidence of dementia.
Routine Implantation of Cardioverter/Defibrillator Devices in Patients Aged 75 Years and Older With Prior Myocardial Infarction and Left Ventricular Ejection Fraction <30: Antagonist Viewpoint
Authors: Basta Lofty L.
Published: February 2007

The Multicenter Automatic Defibrillator Implantation Trial (MADIT II) investigators assert that their results justify the placement of artificial implantable defibrillator cardioverter devices in patients aged 75 years and older with prior myocardial infarction and left ventricular dysfunction (ejection fraction of 30 or less). The authors claim that the results of the trial do not justify this conclusion. The majority of patients were male (84%) and aged 64±10 years. Also, 2.8% of patients assigned to the defibrillator group and 1.5% had their device removed. Of the latter subgroup, nine patients (1.3%) received a heart transplant. Twelve had their artificial implantable defibrillator cardioverter device deactivated mostly because of terminal illness. Although the study results show a significant reduction in mortality over the control group (absolute reduction=5.6%), almost the same percentage required hospitalization because of manifestation of congestive heart failure (absolute value 5%; p=0.09). Also, 1.8% had lead problems, 0.7% had infections, and the benefits were only seen after the first year. Caution is needed before the results of this study are applied to a much older cohort comprised mainly of women in whom heart transplant is contraindicated and who have multiple health problems, including cognitive impairment. Artificial implantable cardioverter/defibrillator devices are expensive and this study's results need to be duplicated in other comparable cohorts.
Diastolic Dysfunction in the Elderly—The Interstitial Issue
Authors: Burlew Brad S.
Published: February 2007

Diastolic dysfunction is increasingly recognized as a cause of congestive heart failure. Meta‐analyses of earlier studies of this disorder suggest that 40%–50% of patients with the congestive heart failure syndrome have preserved left ventricular systolic function, with current estimates ranging up to 74%. Among patients ≥65 years of age with congestive heart failure, 55% of all subjects and 67% of women had normal systolic function. Histopathologic evaluation reveals a maladaptive remodeling of the interstitium associated with aging, resulting in an increase in interstitial collagen content. The interstitium normally plays a critical role in the generation of early diastolic suction. When there is a significant enough increase in myocardial collagen volume fraction, with its increased viscoelastic burden, this normal early diastolic suction is compromised and diastolic pressures increase. Left ventricular diastolic dysfunction ensues. Neurohumoral abnormalities associated with diastolic dysfunction include activation of the renin‐angiotensin‐aldosterone system, including increased elaboration of myocardial aldosterone. This excess of aldosterone appears to play a major role in the development of myocardial fibrosis. Recent observations in animal models and humans have demonstrated regression of interstitial collagen volume fraction in response to inhibition of the renin‐angiotensin‐aldosterone system by angiotensin‐converting enzyme inhibitors and aldosterone inhibition, with improvement in diastolic function. Therapeutic implications of these observations suggest targeting the maladaptive remodeling of the interstitium via inhibition of the renin‐angiotensin‐aldosterone system.
Seasonal Variations in Blood Pressure
Authors: Rosenthal Talma
Published: February 2007

The influence of temperature changes on risk factors like hypertension is often disregarded despite extensive literature on the phenomenon. Numerous surveys and studies have documented the correlation between temperature and blood pressure in various countries among adults, the elderly, and children. Twenty‐four‐hour blood pressure studies also generally show higher blood pressure in the winter. The suggested etiology is that cold increases sympathetic tone, evidenced by elevated blood pressure and plasma and urinary noradrenaline concentrations. The lower blood pressure in warm temperatures is attributed to cutaneous vasodilatation and loss of water and salt from sweating. Taking seasonal variations in blood pressure into account will increase the meaningful information collected in population surveys and mass screenings. It will also result in more personalized management of antihypertensive medications tailored to the individual.
Chronic Renal Insufficiency and Cardiovascular Events in the Elderly: Findings From the Cardiovascular Health Study
Authors: Shlipak Michael G. , Fried Linda F. , Stehman‐Breen Catherine , Siscovick David , Newman Anne B.
Published: February 2007

In the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community‐dwelling elderly adults. Defined as a serum creatinine level ≥1.3 mg/dL in women and ≥1.5 mg/dL in men, CRI was present in 647 (11%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64% in participants with CRI and 43% in those without CRI (odds ratio, 2.34; 95% confidence interval, 1.96–2.80). The incidence of cardiovascular disease events during follow‐up was 3% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7% per year in those with creatinine ≥1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C‐reactive protein, fibrinogen, and interleukin‐6) and hemostatic (factor VII, factor VIII, plasmin‐antiplasmin product, and D‐dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.
Delay discounting and the alcohol Stroop in heavy drinking adolescents
Authors: Field Matt , Christiansen Paul , Cole Jon , Goudie Andrew
Published: February 2007

Aims  To investigate whether adolescent heavy drinkers exhibit biased cognitive processing of alcohol‐related cues and impulsive decision making.

Design  A between‐subjects design was employed.

Setting  Classrooms in a single sixth‐form college in Merseyside, UK.

Participants  Ninety adolescent students (mean age 16.83 years), of whom 38% were identified as heavy drinkers and 36% were identified as light drinkers, based on a tertile split of their weekly alcohol consumption.

Measurements  Participants provided information about alcohol consumption before completing measures of alcohol craving, delay discounting and an ‘alcohol Stroop’ in which they were required to name the colour in which alcohol‐related and matched control words were printed.

Findings  Compared to light drinkers, heavy drinkers showed more pronounced discounting of delayed hypothetical monetary and alcohol rewards, which is indicative of a more short‐term focus in decision making in heavy drinkers. Heavy drinkers were also slower to colour‐name alcohol‐related words, which indicates an attentional bias for alcohol‐related cues. In all participants, measures of delay discounting and attentional bias were correlated moderately with each other, and also with the level of alcohol consumption and with alcohol craving.

Conclusions  In adolescents, heavy alcohol use is associated with biased attentional processing of alcohol‐related cues and a shorter‐term focus in decision making.
A novel substitution I381V in the sterol 14α‐demethylase (CYP51) of Mycosphaerella graminicola is differentially selected by azole fungicides
Authors: FRAAIJE B. A. , COOLS H. J. , KIM S‐H. , MOTTERAM J. , CLARK W. S. , LUCAS J. A.
Published: February 2007

The recent reduction in the efficacy of azole fungicides in controlling Septoria leaf blotch of wheat, caused by Mycosphaerella graminicola, has prompted concerns over possible development of resistance, particularly in light of the recent emergence of widespread resistance to quinone outside inhibitors (QoIs). We have recently implicated alterations in the target‐encoding sterol 14α‐demethylase protein (CYP51), and over‐expression of genes encoding efflux pumps, in reducing sensitivity to the azole class of sterol demethylation inhibitors (DMIs) in M. graminicola. Here we report on the prevalence and selection of two CYP51 alterations, substitution I381V and deletion of codons 459 and 460 (ΔY459/G460), in populations of M. graminicola. Neither alteration has previously been identified in human or plant pathogenic fungi resistant to azoles. The presence of ΔY459/G460 showed a continuous distribution of EC50 values across isolates with either I381 or V381, and had no measurable effect on azole sensitivity. Data linking fungicide sensitivity with the presence of I381V in M. graminicola show for the first time that a particular CYP51 alteration is differentially selected by different azoles in field populations of a plant pathogen. Substitution I381V although not an absolute requirement for reduced azole sensitivity, is selected by tebuconazole and difenoconazole treatment, suggesting an adaptive advantage in the presence of these two compounds. Prochloraz treatments appeared to select negatively for I381V, whereas other azole treatments did not or only weakly impacted on the prevalence of this substitution. These findings suggest treatments with different members of the azole class of fungicides could offer a resistance management strategy.
Increased mite parasitism as a cost of testosterone in male striped plateau lizards Sceloporus virgatus
Authors: COX ROBERT M. , JOHN‐ALDER HENRY B.
Published: February 2007

Testosterone (T) co‐ordinates the seasonal and sex‐specific expression of numerous physiological, behavioural and morphological traits that contribute to male reproductive success. However, increased susceptibility to parasitism has been proposed as a potential cost of elevated plasma T.

During the spring breeding season, male striped plateau lizards Sceloporus virgatus harbour significantly more ectoparasitic mite larvae (Acari: Trombiculidae) than females. Plasma T levels are also elevated in males at this time, suggesting that sex differences in mite parasitism may be driven by underlying sex differences in circulating T.

We tested this hypothesis experimentally by manipulating plasma T levels of yearling males via surgical castration and exogenous T implants. Upon recapture of free‐living animals, we found significantly fewer mites on castrated males relative to either intact controls or castrated males that received T implants.

After removing variance attributable to treatment effects, we observed (1) a positive correlation between residual measures of plasma T and mite load, and (2) a negative correlation between residual measures of mite load and growth rate. These correlations suggest a growth cost associated with mite parasitism.

Previous studies have shown that exogenous T increases parasitism, but ours is one of the few to show that castration also reduces parasitism. This result, coupled with the fact that our induced plasma T levels remain within physiological limits, makes this one of the clearest demonstrations of a functional relationship between T and parasitism in any free‐living vertebrate.