bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and genomic characterization of a novel human torque teno virus of 3.2 kb
Authors: Ninomiya Masashi , Nishizawa Tsutomu , Takahashi Masaharu , Lorenzo Felipe R. , Shimosegawa Tooru , Okamoto Hiroaki
Published: June 2007

In the process of searching for the recently described small anelloviruses 1 and 2 (SAVs) with the genomic DNA length of 2.2 or 2.6 kb in human sera, we isolated a novel virus with its genomic organization resembling those of torque teno virus (TTV) of 3.8–3.9 kb and torque teno mini virus (TTMV) of 2.8–2.9 kb. The entire genomic sequence of three isolates (MD1-032, MD1-073 and MD2-013), which comprised 3242–3253 bases and exhibited 76–99 % identities with the SAVs within the overlapping sequence, was determined. Although the MD1-032, MD1-073 and MD2-013 isolates differed by 10–28 % from each other over the entire genome, they segregated into the same cluster and were phylogenetically distinguishable from all reported TTVs and TTMVs. These results suggest that SAVs are deletion mutants of the novel virus with intermediate genomic length between those of TTV and TTMV and that the novel virus can be classified into a third group of the genus Anellovirus.
Rescue of a chimeric rinderpest virus with the nucleocapsid protein derived from peste-des-petits-ruminants virus: use as a marker vaccine
Authors: Parida Satya , Mahapatra Madhuchhanda , Kumar Sai , Das Subash C. , Baron Michael D. , Anderson John , Barrett Thomas
Published: June 2007

The nucleocapsid (N) protein of all morbilliviruses has a highly conserved central region that is thought to interact with and encapsidate the viral RNA. The C-terminal third of the N protein is highly variable among morbilliviruses and is thought to be located on the outer surface and to be available to interact with other viral proteins such as the phosphoprotein, the polymerase protein and the matrix protein. Using reverse genetics, a chimeric rinderpest virus (RPV)/peste-des-petits-ruminants virus (PPRV) was rescued in which the RPV N gene open reading frame had been replaced with that of PPRV (RPV–PPRN). The chimeric virus maintained efficient replication in cell culture. Cattle vaccinated with this chimeric vaccine showed no adverse reaction and were protected from subsequent challenge with wild-type RPV, indicating it to be a safe and efficacious vaccine. The carboxyl-terminal variable region of the rinderpest N protein was cloned and expressed inEscherichia coli. The expressed protein was used to develop an indirect ELISA that could clearly differentiate between RPV- and PPRV-infected animals. The possibility of using this virus as a marker vaccine in association with a new diagnostic ELISA in the rinderpest eradication programme is discussed.
Metaplastic effect of apamin on LTP and paired-pulse facilitation
Authors: Ris Laurence , Capron Brigitte , Sclavons Coralie , Liégeois Jean-François , Seutin Vincent , Godaux Emile
Published: June 2007

In area CA1 of hippocampal slices, a single 1-sec train of 100-Hz stimulation generally triggers a short-lasting long-term potentiation (S-LTP) of 1–2 h. Here, we found that when such a train was applied 45 min after application of the small conductance Ca2+-activated K+ (SK) channel blocker apamin, it induced a long-lasting LTP (L-LTP) of several hours, instead of an S-LTP. Apamin-induced SK channel blockage is known to resist washing. Nevertheless, the aforementioned effect is not a mere delayed effect; it is metaplastic. Indeed, when a single train was delivered to the Schaffer’s collaterals during apamin application, it induced an S-LTP, like in the control situation. At the moment of this LTP induction (15th min of apamin application), the SK channel blockage was nevertheless complete. Indeed, at that time, under the influence of apamin, the amplitude of the series of field excitatory postsynaptic potentials (fEPSPs) triggered by a stimulation train was increased. We found that the metaplastic effect of apamin on LTP was crucially dependent on the NO-synthase pathway, whereas the efficacy of the NMDA receptors was not modified at the time of its occurrence. We also found that apamin produced an increase in paired-pulse facilitation not during, but after, the application of the drug. Finally, we found that the induction of each of these two metaplastic phenomena was mediated by NMDA receptors. A speculative unitary hypothesis to explain these phenomena is proposed.
Hormone Replacement Therapy for Prevention or Treatment of Atherosclerosis in Postmenopausal Women: Promises, Controversies, and Clinical Trials
Authors: Blum Arnon , Koh Kwang , Cannon Richard O.
Published: June 2007

Cardiovascular disease is the leading cause of death among men and women in the U.S. and other developed societies. However, myocardial infarction and stroke are uncommon in women until their sixth decade and beyond. Clinicians have long suspected that the delay of a decade or more in cardiovascular disease expression in women relative to men is due to the protective effects of estrogen prior to menopause. Reports from population based observational studies of the favorable effects of hormone replacement therapy on cardiovascular morbidity and mortality have led to enthusiasm for widespread use of estrogen by postmenopausal women for the prevention of cardiovascular disease. In support of the antiatherogenic potential of estrogen are studies in postmenopausal women showing favorable effects on lipoprotein levels, fibrinolysis, and vascular function. However, a secondary prevention trial in postmenopausal women with coronary artery disease showed no cardiovascular benefit of hormone replacement therapy. Ongoing clinical trials and options to conventional hormone replacement therapy for cardiovascular protection will be discussed in this review.
Cardiovascular Drug Use in the Elderly
Authors: Nolan Paul E. , Marcus Frank
Published: June 2007

The elderly patient is at increased risk for adverse drug effects because of altered pharmacokinetic and pharmacodynamic changes that occur with aging. In addition, the potential for adverse drug interactions are increased because the elderly take a disproportionate number of drugs relative to younger patients. Cardiovascular drugs are frequently implicated in the occurrence of adverse drug interactions. Recommendations are provided to minimize or avoid adverse drug reactions in the elderly.
Acute Myocardial Infarction in the Elderly
Authors: Reardon Michael , Camm John A.
Published: June 2007

Up to half of admissions with myocardial infarction are over 70 years of age. Mortality in this age group is higher than in younger age groups. However, elderly patients are less likely to be managed in an acute coronary care setting. Low dose aspirin should be given to all elderly patients with myocardial infarction. Thrombolytic agents have the greatest effect in the elderly even though they give an increased risk of hemorrhagic stroke. They are underused in the elderly with myocardial infarction for a number of reasons. β‐Blockers reduce mortality post infarction and ACE inhibitors improve morbidity and mortality rates in those with evidence of heart failure post infarction. Amiodarone may also be of use as an antiarrhythmic in the post infarction period.
The Management of Chronic Ischemic Heart Disease in the Elderly
Authors: Kaski Juan C. , Smith David A.
Published: June 2007

Despite advances in medical and surgical therapy, ischemic heart disease remains the most important cause of death and disability in an ever growing population. The management of elderly patients with ischemic heart disease is made more difficult by the presence of comorbid medical conditions, which can both further aggravate ischemic heart disease and interfere with pharmacological and interventional therapy. Despite the difficulties in the management of ischemic heart disease in the elderly, there is substantial evidence that older patients can benefit greatly from aggressive, rational treatment of this condition and, therefore, such treatment should not be denied solely on the grounds of age.
Homocysteine: The New Risk Factor for Cardiovascular Disease in the Elderly
Authors: Wilson Peter W.F.
Published: June 2007

Higher levels of plasma homocysteine are associated with a variety of atherosclerotic conditions that are particularly pertinent to elderly persons. Cross sectional data have suggested that the lower deciles of plasma and dietary folate are highly associated with the presence of carotid stenosis in the elderly. Recent prospective studies have demonstrated strong associations between elevated concentrations of homocysteine and the incidence of cardiovascular mortality, total mortality, and stroke in elderly men and women. The impact of folate fortification on homocysteine levels has been assessed in middle‐aged adults, but the clinical impact of fortification or supplementation of the diet with folate on clinical end points of cardiovascular disease is presently unknown, although clinical trials with folate supplementation are underway.
Hormonal and Nonhormonal Therapies for the Postmenopausal Woman: What is the Evidence for Cardioprotection?
Authors: Wenger Nanette K.
Published: June 2007

Despite biologically plausible mechanisms whereby estrogen may confer cardioprotection as well as observational data suggesting cardiovascular benefit, data from the sole randomized controlled clinical outcomes trial reported on the benefit of hormone use. A trend was observed in the Heart and Estrogen/progestin Replacement Study (HERS) of an early increase in coronary events with possible late benefit, and in a recent angiographic trial, the Estrogen Replacement and Atherosclerosis trial (ERA) where no benefit was seen. Furthermore, selective estrogen receptor modulators may enable dissociation of estrogen risks and benefits; the selective estrogen replacement modulator raloxifene is under study in a large randomized clinical outcomes trial entitled the Raloxifene Use for the Heart trial (RUTH).
Research Agenda for Cardiovascular Aging: Humans to Molecules
Authors: Lakatta Edward G.
Published: June 2007

Clinical manifestations of specific cardiovascular diseases, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke likely become altered in older persons of advanced age because interactions occur between age‐associated cardiovascular changes in health and specific pathophysiologic mechanisms that underlie cardiovascular diseases. The interactions result in a lower threshold for clinical symptoms, and greater severity and poorer prognosis of these diseases in older vs. younger persons. In this regard, cardiovascular changes that occur during aging in health ought not to be considered to reflect a “normal process”; rather these specific age‐associated changes must be construed as specific “risk factors” for the aforementioned cardiovascular diseases and ought to become targets of interventions designed to prevent the epidemic of cardiovascular disease in later life. Such a strategy would thus advocate preventive treatment for what is now considered to be “normal cardiovascular aging.” Effective and efficient prevention of the “risks” associated with cardiovascular aging in apparent health requires a fundamental understanding of these changes ranging in scope from humans to molecules. An opinion regarding specific directions for research aimed toward the achievement of this understanding is provided.
Orthostatic Hypotension in the Elderly: Contributions of Impaired LV Filling and Altered Sympathovagal Balance
Authors: Gottdiener John S. , Yanez David , Rautaharju Penttii , Gardin Julius M. , Bild Diane E. , Lima Joao , Newman Anne B.
Published: June 2007

Orthostatic hypotension, which occurs in 5%–18% of the elderly, may contribute to age‐related disability. While autonomic dysfunction and alterations of cardiac structure and function likely to impair postural maintenance of blood pressure are common in the elderly, these have not been jointly studied in large cohorts. The authors evaluated the association of orthostatic hypotension with echocardiographic measures of cardiac structure and function, and with autonomic function determined by analysis of heart rate variability, in a large population of community‐dwelling elderly. A total of 5201 men and women, aged 65–100 years and living in four geographically separate communities, were recruited from Medicare eligibility lists. In this prospective, observational cohort study, measurements included clinical questionnaires, standing and supine blood pressures, mini‐glucose tolerance testing, echocardiography, and 24‐hour Holter recording for assessment of heart rate variability. Orthostatic hypotension, defined as a decrease in standing systolic blood pressure of 20 mm Hg or more, was positively associated in bivariate analyses with left ventricular wall thickness, peak velocity of late diastolic filling, vagal tone on heart rate variability analysis, supine systolic pressure, supine diastolic pressure, age, and diabetes, and inversely associated with body weight. After statistical adjustment for the presence of myocardial infarction, stroke, and use of antihypertensive medication, the associations were maintained, and a previous trend toward an association with decreased left ventricular cavity size became statistically significant. The data suggest that in elderly, community‐based individuals, orthostatic hypotension is associated with increased blood pressure and decreased weight; it possibly acts mechanistically via altered sympathovagal balance, increased left ventricular wall thickness, decreased left ventricular preload, and alterations of left ventricular diastolic filling.
Lipid Lowering Therapy is Safe in the Elderly: The LifeHelp 80‐80 Analysis
Authors: McIvor Michael E. , Witt Jeffrey R. , King Helen M. , Young Lanette D.
Published: June 2007

Little information is available regarding the safety and efficacy of lipid lowering therapy in the elderly. Records of 80 octogenarians, taken from the database of the LifeHelp Lipid Clinic of the Heart Institute of St. Petersburg, FL, were examined, representing 1863 patient months of treatment. Therapy was effective, lowering low density lipoprotein cholesterol (from 140±4 to 92±3 mg/dL), raising high density lipoprotein cholesterol (from 44±1 to 50±1 mg/dL), and lowering triglycerides (from 199±21 to 146±9 mg/dL). Six patients developed myalgias (without significant creatine phosphokinase rise) or gastrointestinal disturbances. Three of these patients restarted therapy without difficulty. No patient developed rhabdomyolysis (including the 11% of patients on combination therapy). One patient developed an elevation of liver (>3 times upper limits of normal), but later restarted therapy without sequelae. We conclude that lipid lowering therapy was effective at modifying hyperlipidemia in the elderly without significant adverse effects.
Ventricular Rate Control in the Elderly: Is Digoxin Enough?
Authors: Falk Rodney H.
Published: June 2007

The ventricular response in untreated patients with atrial fibrillation often exceeds 120 beats/min at rest. Digoxin can slow this rate, but its efficacy during exertion may be limited. Alternatives, or additions, to digoxin therapy include the β blockers and diltiazem or verapamil. This review discusses the role of digoxin in relation to these other drugs, with particular reference to the elderly population.
Optimal Investigation of the Elderly and Very Elderly Patient With Atrial Fibrillation—What Must Be Done?
Authors: Vlietstra Ronald E.
Published: June 2007

The investigation of atrial fibrillation should be tailored to match the needs of the patient. Those needs may differ between younger and older patients. While many different investigations might be used, the emphasis in this review will be on what must be done. It should be remembered that rigid protocols cannot be presented, however, because many of these important issues have not been subjected to critical scrutiny in elderly cohorts.
Aortic Pulse Wave Velocity: An Independent Marker of Cardiovascular Risk
Authors: Safar Michel E. , Henry Olivier , Meaume Sylvie
Published: June 2007

Aortic pulse wave velocity, a classic index of aortic stiffness, may be easily measured in humans using noninvasive ultrasound methods of high reproducibility. Recent epidemiologic studies have shown that, independently of confounding factors such as age, blood pressure and cardiac mass, aortic pulse wave velocity is a predictor of cardiovascular mortality in populations of hypertensive subjects, whether they have end‐stage renal disease or not. Since aortic pulse wave velocity is dominantly influenced by age, this finding may be of major importance for the evaluation of cardiovascular risk in geriatric populations.
Pharmacologic Therapy of Lipid Disorders in the Elderly
Authors: Aronow Wilbert S.
Published: June 2007

Older men and women with coronary artery disease, prior stroke, peripheral arterial disease, and extracranial carotid arterial disease with a serum low‐density lipoprotein (LDL) cholesterol >125 mg/dL despite diet should be treated with lipid‐lowering drug therapy, preferably with statins, to reduce the serum LDL cholesterol to <100 mg/dL. If statin drug therapy does not lower the serum LDL cholesterol to <100 mg/dL in older persons with coronary artery disease, a bile acid binding resin, such as cholestyramine, should be added, since this drug does not increase the incidence of myositis in persons taking statins. The physician should use statins to treat older persons without atherosclerotic cardiovascular disease with a serum LDL cholesterol=160 mg/dL plus one major risk factor, or a serum LDL cholesterol=130 mg/dL plus a serum high‐density lipoprotein (HDL) cholesterol <50 mg/dL. Gemfibrozil may be useful in reducing the incidence of coronary events in persons with coronary artery disease whose primary lipid abnormality is a low serum HDL cholesterol level. There are no good data supporting treatment of hypertriglyceridemia unassociated with increased LDL cholesterol or decreased HDL cholesterol for prevention of cardiovascular disease.
Coronary Heart Disease Risk Factors in the Elderly
Authors: Kannel William B.
Published: June 2007

Hypertension, dyslipidemia, impaired glucose tolerance, and obesity remain the major modifiable risk factors for most of the coronary disease afflicting the elderly. The relative risk associated with these established risk factors diminishes with advancing age, but this is offset by a greater absolute and attributable risk. Diabetes is increasing alarmingly in prevalence and operates more powerfully in women, eliminating their coronary disease resistance (relative to men). Interest in this entity now focuses on the insulin resistance syndrome promoted by abdominal obesity that has become so common in the elderly. The isolated systolic hypertension and large pulse pressure that predominate in the elderly is now recognized as a coronary disease hazard.

Dyslipidemia, characterized by a high total to high‐density lipoprotein cholesterol ratio, is the most predictive lipid profile for coronary disease in the elderly. High triglycerides, accompanied by low high‐density lipoprotein cholesterol usually signifies insulin resistance and more atherogenic, small, dense low‐density lipoprotein. Left ventricular hypertrophy is an ominous harbinger of coronary disease. Fibrinogen and the leukocyte count are correlated coronary disease risk factors that may indicate unstable lesions. Novel risk factors, such as hemostatic factors, homocysteine, lipoprotein(a), C‐reactive protein, and hyperinsulinemia, are worthy of attention, but the efficacy of correcting them in the elderly has not yet been demonstrated. Nor has the efficacy of hormone replacement therapy in women.

All the coronary risk factors tend to cluster, and the hazard posed by each is greatly influenced by the burden of coexisting risk factors. High‐risk elderly candidates for coronary disease can be efficiently targeted for treatment by global risk assessment, using only the major established risk factors. The distinction between primary and secondary prevention in the elderly is less clear than in the middle‐aged because they often have advanced presymptomatic vascular pathology that imposes a coronary event rate comparable to that of the middle‐aged who have already sustained a clinical event. Declines in coronary mortality rates in the United States have included the elderly, justifying optimism about the efficacy of preventive measures. Most of the elderly have sufficient remaining life expectancy to warrant vigorous preventive management. Trials of risk factor modification in the elderly indicate that decades of exposure to modifiable risk factors can be countered by measures implemented late in life.
Epidemiologic Appraisal of Hypertension as a Coronary Risk Factor in the Elderly
Authors: O'Donnell Christopher J. , Kannel William B.
Published: June 2007

Five decades of epidemiologic research has established elevated blood pressure as a major contributor to atherosclerotic cardiovascular diseases in the elderly, including coronary heart disease. Clinicians formerly favored the diagnosis and treatment of hypertension in terms of the diastolic blood pressure and categorical “hypertension.” Epidemiologic data now emphasize the essential role of systolic blood pressure, pulse pressure, and a graded influence of blood pressure, even within the high‐normal range. The risk of coronary heart disease, the most common lethal sequela of hypertension, increases with the extent of risk factor clustering. Among hypertensive persons, about 39% of coronary events in men and 68% in women are attributable to the presence of two or more additional risk factors. When risk factor clustering is associated with glucose intolerance, obesity, and dyslipidemia, it may be attributed to insulin resistance promoted by abdominal obesity. Other hazardous influences often accompanying hypertension in the elderly are the presence of an elevated heart rate, elevated levels of fibrinogen, and left ventricular hypertrophy. Because clustering with other risk factors is characteristic of hypertension in the elderly, it is essential to screen for them and for the presence of comorbid cardiovascular diseases, target organ disease, and subclinical vascular disease likely to be present. Multivariate risk assessment profiles enable global estimation of hypertensive risk of developing coronary heart disease. Hypertensive elderly patients are more appropriately targeted for antihypertensive therapy by such risk stratification than by relying solely on the severity of the blood pressure elevation. The goal of therapy should be to improve the multivariate risk profile as well as the level of the blood pressure.
Obesity, Diabetes, and Risk of Cardiovascular Disease in the Elderly
Authors: Wilson Peter W.F. , Kannel William B.
Published: June 2007

There is an age‐related increase in total body fat and visceral adiposity until age 65 years that often is accompanied by diabetes or impaired glucose tolerance. The prevalence of type 2 diabetes increases progressively with age, peaking at 16.5% in men and 12.8% in women at age 75–84 years. Over age 65, diabetes or glucose intolerance was present in 30%–40% of Framingham Study subjects. There has been an alarming increase, of epidemic proportions, in both obesity and diabetes in the general population. Type 2 diabetes and obesity are both associated with a clustering of atherogenic risk factors, and when three or more are present it generally signifies an insulin resistance syndrome. This is promoted by weight gain and visceral adiposity. The risk of macrovascular disease is increased before glucose levels reach the diagnostic threshold for “diabetes,” and 25% of newly diagnosed diabetics already have overt cardiovascular disease. In the Framingham Study, increased risk of cardiovascular disease was two‐fold in men and three‐fold in women, eliminating the female advantage over men for all outcomes except stroke. Coronary disease is the most common and lethal sequela, and unrecognized myocardial infarctions are three times more common in diabetic than nondiabetic men. Following a myocardial infarction, diabetes imposes a high rate of recurrence, heart failure, and death, more so in women than men. The risk of cardiovascular sequelae in diabetics is variable, the majority of events occurring in those with two or more additional risk factors. Because of the variable risk of cardiovascular disease in either the diabetic or obese person, risk stratification is necessary to determine the hazard of impending cardiovascular disease. This is readily accomplished with Framingham cardiovascular risk formulations. For persons with diabetes or obesity, the chief goal is to avoid the common cardiovascular sequelae. Comprehensive care should include not only normalization of the blood sugar, but also weight reduction, dietary fat restriction, strict blood pressure and lipid control, exercise, and avoidance of tobacco. Trial data indicate that preventive measures benefit obese diabetics even more than nondiabetics.
Patterns of ACE Inhibitor Use in Elderly Medicaid Patients With Heart Failure
Authors: Howard Patricia A. , Shireman Theresa I. , Dhingra Ashish , Ellerbeck Edward F. , Fincham Jack E.
Published: June 2007

The authors identified 321 elderly Kansas Medicaid patients with congestive heart failure and examined angiotensin‐converting enzyme (ACE) inhibitor use. Using retrospective claims data, ACE inhibitor use was quantified and daily doses compared to a target enalapril‐equivalent dose of 20 mg. The cohort patients averaged 80 years of age, 84% were female, and 70% resided primarily in a nursing home. Only 37.8% received an ACE inhibitor. Users were younger than nonusers (t=2.00; p=0.046), but there was no gender difference (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.73, 2.6). ACE inhibitor users averaged eight prescriptions annually, providing approximately 257 medication days (70% of the study period). The average enalapril‐equivalent daily dose was 10.6 mg, and only 22% received the target dose. Nursing home residents were less likely to receive an ACE inhibitor than ambulatory patients (OR, 0.55; 95% CI, 0.34, 0.89) but equally likely to receive target doses (OR, 1.3; 95% CI, 0.34, 4.9). ACE inhibitor use in the Kansas Medicaid congestive heart failure population is not consistent with practice guidelines, particularly among older and/or nursing home patients.
Reversal of Heart Failure Remodeling With Age
Authors: Levine T. Barry , Levine Arlene B. , Bolenbaugh Janet , Green Pamela R.
Published: June 2007

Since heart failure is a major cause of morbidity in the elderly, we studied the effect of up‐titrated heart failure therapy in older vs. younger individuals on symptoms and left ventricular (LV) function over 1 year. Seventy‐one patients with heart failure and an LV ejection fraction ≤35% were enrolled and were followed with echocardiography at baseline and at 1 year. “Young” patients were born in or after 1935 (n=48; 51.7±9.1 years); “middle‐aged” were born between 1925–1934 (n=14; 69.7±2.8 years); and “older” patients in or prior to 1924 (n=9; 80.5±3.3 years). Baseline LV ejection fraction was 18%±7%, LV end‐diastolic diameter 6.9±0.9 cm, and New York Heart Association class was 2.6±1.0, equivalent for all groups. On medical therapy, at 12 months, LV ejection fraction improved only for the young and middle‐aged (36%±14% and 37%±17%; p=0.002), but not for the older patients (22%±7%; p=NS). Reductions in LV end‐diastolic diameter and mitral regurgitation were significant only for the young. However, New York Heart Association status improved similarly for all groups (1.6±0.8; p<0.001), as did heart failure hospitalizations (p<0.0001). Although all groups tolerated intensified heart failure therapy, only the young and middle‐aged improved LV remodeling. However, older patients experienced equivalent significant improvements in heart failure symptoms and hospitalizations.
Atrial Pacing Stress Echocardiography: An Alternative Diagnostic Test for Chest Pain in the Elderly
Authors: Shenoy Mohandas M. , Sengupta Ranjita , Khanna Ashok
Published: June 2007

The authors utilized rapid right atrial pacing and handgrip exercise to provoke myocardial ischemia in 20 participants (age >65 years) who, for reasons of disability, were not candidates for exercise and pharmacologic stress testing. Echocardiographic left ventricular ejection fraction and left ventricular wall motions were obtained during pacing at baseline and at maximal pacing rates and were compared with coronary angiography. Using the failure of left ventricular ejection fraction to increase with pacing as an indicator of myocardial ischemia, the test yielded a sensitivity of 75%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 71%. When a pacing‐induced decrease of wall‐motion index was taken as an ischemia indicator, the sensitivity was 63%, specificity 100%, positive predictive value 100%, and negative predictive value 80%. Rapid atrial pacing echocardiography is a safe test. It may be considered in a select group of elderly patients as an alternative to exercise or pharmacologic tests before resorting to coronary angiography.
Is the Presence of Interatrial Septal Hypertrophy a Marker for Atrial Fibrillation in the Elderly?
Authors: López‐Candales Angel
Published: June 2007

Interatrial septal thickness (IST) appears to increase with heart weight, body surface area, and the presence of vacuolated fat cells within the atrial septum. The increased thickness of the atrial septum is an infrequently observed but readily recognized entity by echocardiography. Several reports have suggested that some cardiac arrhythmias, particularly those of atrial origin, may be a consequence of this fatty deposition. However, to date, no study has correlated the presence of atrial fibrillation with IST in the elderly. This is of particular importance as this rhythm is so prevalent in this population. Accordingly, a retrospective analysis was conducted in a group of 40 patients, age 65 and older, to measure IST using transthoracic echocardiography. Furthermore, measurements of right and left atrial size, body surface area, left ventricular wall thickness, and left ventricular ejection fraction were recorded. Group I consisted of 20 patients with known atrial fibrillation (eight males and 12 females; mean age 78±8 years) and group II consisted of 20 patients in normal sinus rhythm (three males and 17 females; mean age 74±6 years). There was no difference between the two groups in terms of body surface area (1.83 vs. 1.79 m2; p<0.78); left ventricular wall thickness (1.16 vs. 1.12 cm; p<0.58); and left ventricular ejection fraction (48% vs. 55%; p<0.17). Group I had somewhat larger right atrial (4.2 vs. 3.4 cm; p<0.001) and left atrial (4.7 vs. 4.1 cm; p<0.02) dimensions than group II. Furthermore, IST was found to be the most significant variable that differentiated patients with atrial fibrillation from patients with normal sinus rhythm (1.39 vs. 0.85 cm; p<0.0001). Even after adjusting for all the covariables, IST remained statistically significant (p<0.0001). The findings of this pilot study show a strong correlation between IST and atrial fibrillation. Although the stimulus for the increased thickness of the atrial septum remains elusive, IST may identify a structural cause for atrial fibrillation in elderly patients that is easily identified by transthoracic echocardiography.
Controls on sediment export from the Waipaoa River basin, New Zealand
Authors: Phillips Jonathan D. , Gomez Basil
Published: June 2007

A stability model of drainage basin mass balance is used to interpret historic and prehistoric patterns of sediment production, storage and output from the Waipaoa River basin, New Zealand and assess the sensitivity of basin sediment yield to land use change in the historic period. Climate and vegetation cover changed during the late Holocene, but the drainage basin mass balance system was stable before the basin was deforested by European colonists in the late 19th and early 20th centuries. In this meso‐scale dispersal system sediment sources and sinks are closely linked, and before that time there was also little variability in the rate of terrigenous mass accumulation on the adjacent continental shelf. However, despite strong first‐order geologic controls on erosion and extensive alluvial storage, sediment delivery to the continental shelf is sensitive and highly responsive to historic hillslope destabilization driven by land use change. Alluvial buffering can mask the effects of variations in sediment production within a basin on sediment yield at the outlet, but this is most likely to occur in basins where alluvial storage is large relative to yield and where the residence time of alluvial sediment is long relative to the time scale of environmental change. At present, neither situation applies to the Waipaoa River basin. Thus, the strength of the contemporary depositional signal may not only be due to the intensity of the erosion processes involved, but also to the fact that land use change in the historic period destabilized the drainage basin mass balance system.
The influence of continuous venovenous haemodialysis on the pharmacokinetics of multiple oral moxifloxacin administration to patients with severe renal dysfunction
Authors: Stass H. , Bührmann S. , Mitchell A. , Kubitza D. , Möller J.‐G. , Kribben A. , Wenzel R. R. , Schäfers R. F.
Published: June 2007

What is already known about this subject

• Although renal excretion is one important route of excretion of moxifloxacin and its metabolites, moxifloxacin pharmacokinetics are similar in patients with varying degrees of renal impairment (but not on dialysis) and in healthy subjects.

What this study adds

• This study showed that moxifloxacin pharmacokinetics are comparable in patients with severe renal failure requiring haemodialysis and in healthy subjects and patients with impaired renal function not on dialysis.

• No dose adjustments are required for haemodialysis patients on oral moxifloxacin therapy.

Aim

We investigated single dose and steady‐state pharmacokinetics of moxifloxacin in eight venovenous haemodialysis patients.

Methods

Plasma, dialysate and urine pharmacokinetic parameters for moxifloxacin and its main metabolites were calculated after single and multiple (7 days) dosing with 400 mg day−1.

Results

Moxifloxacin pharmacokinetics after a single dose and at steady state (multidose day 7) were comparable in patients with impaired renal function and healthy subjects (geometric mean/%CV AUC mg l−1 h single dose 37.0/24.3 in haemodialysis patients vs. 29.8/22.6 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 99.34%, 154.60%; steady state 40.4/29.1 haemodialysis patients vs. 33.9/20.1 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 90/39%, 156.93%). In haemodialysis patients plasma concentrations of moxifloxacin at steady‐state were elevated compared with those after a single 400 mg dose (AUC mg l−1 h, geometric mean/%CV, 40.4/29.1) compared with 37.0/24.3; 95% CI for ratio of steady‐state to single dose 87.29%, 136.52%, as were concentrations of metabolite M1 3.21/34.6 compared with 2.02/45.3, 95% CI for ratio of steady state to single dose 14.21%, 175.07%. Haemodialysis cleared about 9% of the dose as unchanged moxifloxacin.

Conclusions

No dose adjustments are required for venovenous haemodialysis patients on oral moxifloxacin therapy.
National underuse of anti‐thrombotic therapy in chronic atrial fibrillation identified from digoxin prescribing
Authors: Mahmud Azra , Bennett Kathleen , Okechukwu Ifeanyi , Feely John
Published: June 2007

What is already known about this subject

• Underuse of antithrombotic therapy in atrial fibrillation has been identified in hospital base and community surveys.

• Whether this applies nationally and whether underuse is age or gender related is not established.

What this study adds

• Using a pharmacoepidemiological database with digoxin as a surrogate for atrial fibrillation, its prevalence and the concomitant use of antithrombotic therapy nationally mirrors that seen in smaller studies.

• In addition, both prescribers' views and practice show that, based on age, those at highest risk and women are least likely to receive warfarin, which is predominantly used in the low‐risk population.

• Such databases may be used nationally to examine adherence to guidelines.

Aims

To examine if appropriate antithrombotic therapy in atrial fibrillation is implemented nationally.

Methods

Using prescriptions for digoxin as a surrogate for atrial fibrillation, we identified its coprescription with antithrombotic therapy, aspirin or warfarin in a national prescribing database in 27 571 patients over 45 years old.

Results

Proportionately significantly more men were on warfarin, and use in those >75 years old was three times less than in those <65 years. Reluctance to use antithrombotics was confirmed in a postal survey.

Conclusion

Data suggest a missed opportunity to prevent stroke with women and those >75 years old least likely to receive warfarin.
Mast cell infiltration is a favourable prognostic factor in diffuse large B‐cell lymphoma
Authors: Hedström Gustaf , Berglund Mattias , Molin Daniel , Fischer Marie , Nilsson Gunnar , Thunberg Ulf , Book Majlis , Sundström Christer , Rosenquist Richard , Roos Göran , Erlanson Martin , Amini Rose‐Marie , Enblad Gunilla
Published: June 2007

Previous studies indicate that the inflammatory response in diffuse large B‐cell lymphomas (DLBCL) is important for the clinical outcome. Mast cells are key regulators in this response; we investigated whether the number of tryptase‐positive mast cells is correlated with clinical outcome. Patients with many mast cells had a significantly better event‐free survival (EFS) compared to those with few mast cells (P < 0·03 in both germinal centre (GC) and non‐GC DLBCL. This supports the idea that the infiltration of mast cells is a reflection of the host inflammatory response and is related to a favourable outcome.
A practical strategy for the routine use of BIOMED‐2 PCR assays for detection of B‐ and T‐cell clonality in diagnostic haematopathology
Authors: Liu Hongxiang , Bench Anthony J. , Bacon Chris M. , Payne Karen , Huang Yuanxue , Scott Mike A. , Erber Wendy N. , Grant John W. , Du Ming‐Qing
Published: June 2007

BIOMED‐2 polymerase chain reaction (PCR) assays for clonality analysis of immunoglobulin (IG) and T‐cell receptor (TCR) gene rearrangements were evaluated in routine haematopathological practice where paraffin‐embedded tissues constitute the majority of specimens. One hundred and twenty‐five fresh/frozen and 316 paraffin specimens were analysed for DNA quality and clonality. Seventy‐nine per cent of paraffin specimens yielded PCR products of over 300 bp. These specimens and all fresh/frozen specimens were analysed with the complete set of BIOMED‐2 reactions for IG (8 reactions) and/or TCR (6 reactions) gene rearrangements. The rate of detection of clonality was 96% in mature B‐cell neoplasms and 98% in mature T‐cell neoplasms and there were no significant differences in these rates between paraffin and fresh/frozen specimens. As the value of sole use of any individual BIOMED‐2 reaction in clonality detection was limited, we assessed combinations of reactions that gave the greatest sensitivity with fewest reactions and were applicable for both fresh/frozen and paraffin specimens. For IG gene rearrangements, three reactions combining one targeting the IG heavy chain framework‐2 region and two targeting the IG kappa locus achieved a 91% detection rate. For TCR gene rearrangements, the two TCR gamma reactions gave a 94% detection rate. We therefore recommend this strategy as the first‐line assays for routine B‐ and T‐cell clonality analysis in diagnostic haematopathology.
Two novel imatinib‐responsive PDGFRA fusion genes in chronic eosinophilic leukaemia
Authors: Curtis Claire E. , Grand Francis H. , Musto Pellegrino , Clark Andrew , Murphy John , Perla Gianni , Minervini Maria M. , Stewart Janet , Reiter Andreas , Cross Nicholas C. P.
Published: June 2007

We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2), respectively, in association with BCR‐ABL and FIP1L1‐PDGFRA negative chronic eosinophilic leukaemia. Molecular analysis revealed a novel STRN‐PDGFRA fusion for the t(2;4) and ETV6‐PDGFRA for the t(4;12). The fusions were confirmed by specific amplification of the genomic breakpoints, reverse transcription polymerase chain reaction and fluorescence in situ hybridisation. Both patients were treated with imatinib and, following a rapid haematological response, achieved cytogenetic remission and a major molecular response. In conclusion, PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of these fusions is important as they are particularly sensitive to imatinib.
Intensity of HLA class I expression and KIR‐mismatch determine NK‐cell mediated lysis of leukaemic blasts from children with acute lymphatic leukaemia
Authors: Pfeiffer Matthias , Schumm Michael , Feuchtinger Tobias , Dietz Klaus , Handgretinger Rupert , Lang Peter
Published: June 2007

The impact of human leucocyte antigen (HLA) class I expression intensity and killer‐cell immunoglobulin‐like receptor (KIR)‐mismatch was investigated on natural killer (NK)‐cell mediated lysis of B‐lineage leukaemic blasts from 21 paediatric patients in vitro. Blast susceptibility to standardised NK‐activity and HLA‐expression differed widely. A clear association between HLA‐molecules/cell (range 442 000–13 000) and specific lysis (mean 59%, range 13–98%) was observed (r2 = 0·68). A compound model incorporating HLA‐expression and KIR‐ligand‐mismatch provided an even stronger association (r2 = 0·87), whereas KIR‐ligand‐mismatch alone was not significant. Assessment of these factors might identify patients who could benefit from NK‐mediated graft‐versus‐leukaemia effects after mismatched stem cell transplantation.
Early childhood wheezing symptoms in relation to plasma selenium in pregnant mothers and neonates
Authors: Devereux G. , McNeill G. , Newman G. , Turner S. , Craig L. , Martindale S. , Helms P. , Seaton A.
Published: June 2007

Objective
Reduced dietary selenium intake has been linked to the development of asthma. We have investigated whether childhood wheezing symptoms, and asthma up to the age of 5 years are associated with plasma selenium and erythrocyte glutathione peroxidase (GPx) concentrations in pregnant mothers and neonates.

Methods
Two thousand pregnant women were recruited and their 1924 singleton children followed up. Plasma selenium and erythrocyte GPx concentrations were measured in maternal blood during early pregnancy (12 weeks gestation) and in neonatal cord blood. Cohort children were followed up at 1, 2 and 5 years using a respiratory symptom questionnaire and at 5 years children were also invited for spirometry and skin‐prick test (SPT). Maternal and neonatal plasma selenium and erythrocyte GPx were related to the childhood outcomes of wheezing, and asthma.

Results
At 2 years 1282 children were followed up. At 5 years symptom data were available for 1167 children, 700 children were SPT tested, and forced expiratory volume in 1 s (FEV1) was measured in 478. Maternal plasma selenium concentration during early pregnancy was inversely associated with wheezing (odds ratio per 10 μg/kg plasma selenium 0.86, 95% confidence interval 0.76–0.97), and consulting a doctor because of wheeze (0.79, 0.69–0.93) in the second year of life. Cord plasma selenium was also inversely associated with wheezing (0.67, 0.47–0.96), and consulting a doctor because of wheeze (0.62, 0.41–0.93) in the second year of life. By age 5 these associations had disappeared. Maternal and neonatal erythrocyte GPx concentrations were not associated with any childhood outcomes at 2 or 5 years.

Conclusion
The selenium status of mothers during early pregnancy, and neonates is associated with early childhood wheezing but not asthma or atopic sensitization, furthermore, this association is absent by the age of 5 years.
The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women
Authors: Kuchuk Natalia O. , Van Schoor Natasja M. , Pluijm Saskia M. F. , Smit Johannes H. , De Ronde Willem , Lips Paul
Published: June 2007

Objective  Sex steroids play an important role in the maintenance of bone health. Association studies on sex steroids and fractures are not consistent. Our objective was to examine whether serum oestradiol (E2) and testosterone (T) are associated with quantitative ultrasound (QUS), bone mineral density (BMD), bone turnover markers and fracture incidence.

Design  The Longitudinal Ageing Study Amsterdam (LASA), an ongoing cohort study including 623 men and 634 women, aged 65–88 years.

Measurements  Serum levels of E2, T, SHBG, albumin, bone turnover markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD/Cr) were measured. QUS of the heel and BMD of the hip were assessed, and a 6‐year fracture follow‐up was performed.

Results  Men in the lowest quartile (Q1) of bioavailable E2 (bioE2) had higher levels of bone turnover and lower BMD (B = –0·09, P < 0·01) and QUS than men in the highest quartile (Q4). This also applied to Q1 of bioT. Women in Q1 of bioE2 had higher levels of bone turnover and lower BMD (B = –0·07, P < 0·01) and QUS than women in Q4. In men and women, levels of bioE2 below the median were associated with an increased risk of osteoporotic fractures after all adjustments [hazard ratio (HR) 1·53, 95% confidence interval (CI) 1·02–2·29]. In men, univariate analysis revealed that low bioT was associated with an increased fracture risk (HR 1·91, 95% CI 1·03–3·56), but after adjustment for age, this association was no longer significant.

Conclusions  Low levels of bioE2 and bioT were found to be associated with high bone turnover, low QUS and BMD and high risk of osteoporotic fractures in both men and women.