bluuebunny/crossref_metadata_2025 huggingface dataset:
Bovine leukemia virus protease: comparison with human T-lymphotropic virus and human immunodeficiency virus proteases
Authors: Sperka Tamás , Miklóssy Gabriella , Tie Yunfeng , Bagossi Péter , Zahuczky Gábor , Boross Péter , Matúz Krisztina , Harrison Robert W. , Weber Irene T. , Tözsér József
Published: June 2007

Bovine leukemia virus (BLV) is a valuable model system for understanding human T-lymphotropic virus 1 (HTLV-1); the availability of an infectious BLV clone, together with animal-model systems, will help to explore anti-HTLV-1 strategies. Nevertheless, the specificity and inhibitor sensitivity of the BLV protease (PR) have not been characterized in detail. To facilitate such studies, a molecular model for the enzyme was built. The specificity of the BLV PR was studied with a set of oligopeptides representing naturally occurring cleavage sites in various retroviruses. Unlike HTLV-1 PR, but similar to the human immunodeficiency virus 1 (HIV-1) enzyme, BLV PR was able to hydrolyse the majority of the peptides, mostly at the same position as did their respective host PRs, indicating a broad specificity. When amino acid residues of the BLV PR substrate-binding sites were replaced by equivalent ones of the HIV-1 PR, many substitutions resulted in inactive protein, indicating a great sensitivity to mutations, as observed previously for the HTLV-1 PR. The specificity of the enzyme was studied further by using a series of peptides containing amino acid substitutions in a sequence representing a naturally occurring HTLV-1 PR cleavage site. Also, inhibitors of HIV-1 PR, HTLV-1 PR and other retroviral proteases were tested on the BLV PR. Interestingly, the BLV PR was more susceptible than the HTLV-1 PR to the inhibitors tested. Therefore, despite the specificity differences, in terms of mutation intolerance and inhibitor susceptibility of the PR, BLV and the corresponding animal-model systems may provide good models for testing of PR inhibitors that target HTLV-1.
In vivo replication kinetics and transcription patterns of the nucleopolyhedrovirus (NeabNPV) of the balsam fir sawfly, Neodiprion abietis
Authors: Duffy Simon P. , Becker Elisa M. , Whittome Beatrixe H. , Lucarotti Christopher J. , Levin David B.
Published: June 2007

DNA replication and transcription of NeabNPV, the nucleopolyhedrovirus (NPV) of the balsam fir sawfly, Neodiprion abietis (Hymenoptera: Diprionidae), in host larvae were investigated. NPV DNA replication kinetics and gene-expression patterns have been resolved only in lepidopteran cell-culture systems and in limited in vivo experiments with lepidopteran larvae. Furthermore, there are significant differences in pathologies caused by lepidopteran NPVs, which replicate in many tissues, and hymenopteran NPVs, known to replicate in midgut epithelium only. Despite the differences in host specificity and pathology, NeabNPV DNA replication kinetics were similar to those reported for lepidopteran NPVs. Maximal NeabNPV DNA synthesis was observed between 4 and 24 h post-inoculation (p.i.) but, in contrast to lepidopteran NPVs, synthesis continued at a lower rate up to 72 h p.i. Selected NeabNPV genes exhibited a cascade pattern of transcription similar to that of lepidopteran NPVs. RT-PCR products of the NeabNPV lef-1, lef-2 and dnapol transcripts were observed as early as 2 h p.i., whilst lef-8 and lef-9, encoding putative viral RNA polymerase subunits, were detected at 1 and 6 h p.i., respectively. Two structural late transcripts (gp41 and p74) were observed from 6 h p.i. The very late factor 1 (vlf-1) transcript, a transactivator of very late genes, was observed from 12 h p.i., but the very late transcript polh, encoding the major occlusion protein, polyhedrin, was observed from 24 h p.i. This study provides the first insight into DNA replication and gene expression of a non-lepidopteran baculovirus.
Antigenic and genetic characterization of H9N2 swine influenza viruses in China
Authors: Cong Yan L. , Pu Juan , Liu Qin F. , Wang Shuai , Zhang Guo Z. , Zhang Xing L. , Fan Wei X. , Brown Earl G. , Liu Jin H.
Published: June 2007

As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the generation of pandemic virus through reassortment. Antigenic and genetic characterization was performed for five swine H9N2 influenza viruses isolated from diseased pigs from different farms. The haemagglutinin (HA) antigenicity of swine H9N2 viruses was different from that of chicken H9N2 viruses prevalent in northern China. Genetic analysis revealed that all five isolates had an RLSR motif at the cleavage site of HA, which was different from those of A/duck/Hong Kong/Y280/97 (Dk/HK/Y280/97)-like viruses established in chickens in China. Phylogenetic analyses indicated that the five swine H9N2 viruses formed novel HA and neuraminidase sublineages that were related closely to those of earlier chicken H9 viruses and were also consistent with the extent of the observed antigenic variation. The six internal genes of the isolates possessed H5N1-like sequences, indicating that they were reassortants of H9 and H5 viruses. The present results indicate that avian to porcine interspecies transmission of H9N2 viruses might have resulted in the generation of viruses with novel antigenic and genetic characteristics; therefore, surveillance of swine influenza should be given a high priority.
Vaccinia virus gene F3L encodes an intracellular protein that affects the innate immune response
Authors: Froggatt Graham C. , Smith Geoffrey L. , Beard Philippa M.
Published: June 2007

The Vaccinia virus BTB/kelch protein F3 has been characterized and its effects on virus replicationin vitroand virus virulencein vivohave been determined. The loss of theF3Lgene had no effect on virus growth, plaque phenotype or cytopathic effect in cell culture under the conditions tested. However, the virulence of a virus lackingF3Lin an intradermal model was reduced compared with controls, and this was demonstrated by a significantly smaller lesion and alterations to the innate immune response to infection. The predicted molecular mass of the F3 protein is 56 kDa; however, immunoblotting of infected cell lysates using an antibody directed against recombinant F3 revealed two proteins of estimated sizes 37 and 25 kDa.
Hypertension in the Aging Patient: New Imperatives, New Options
Authors: Weber Michael A.
Published: June 2007

Over half of all people over the age of 65 in the U.S. have hypertension. In most cases this is diagnosed because of increased systolic blood pressure. It is now recognized that systolic blood pressure is more predictive of cardiovascular events than diastolic blood pressure; since these events are the major cause of death and disability in this population, current hypertension guidelines now emphasize more aggressive blood pressure criteria for both diagnosing and treating systolic hypertension. This process has been stimulated by evidence from large clinical trials that reducing systolic blood pressure improves survival and prevents strokes, heart failure, and other cardiovascular outcomes. The guidelines of both the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and the World Health Organization‐International Society of Hypertension (WHO‐ISH) recommend that, regardless of age, hypertension can be diagnosed when the systolic blood pressure is >140 mm Hg. The treatment target is <140 mm Hg, though in the presence of concomitant conditions like diabetes mellitus or cardiac or renal impairment, which are common findings in the elderly, even lower target levels may be justified. For patients with systolic blood pressures in the range 140 mm Hg–159 mm Hg but who are without other cardiovascular risk factors, it is not yet certain that aggressive treatment is warranted. New clinical trials are now addressing this question. So far, most experience with treating systolic hypertension in older persons has been with diuretics and calcium channel blockers. But growing evidence indicates that most antihypertensive drug classes are effective and that agents should be selected to best match the needs of individual patients.
The Evidence for Lifestyle Modification in Lowering Blood Pressure in the Elderly
Authors: Stanton Judith A. , Lowenthal David T.
Published: June 2007

Lifestyle modifications are a safe, effective treatment option for hypertension, yet are widely underutilized by clinicians, particularly in the elderly population. This review outlines the nonpharmacologic approaches to the treatment and prevention of hypertension, and discusses their applicability to the elderly population. Accepted recommendations include weight loss, regular exercise, decreased alcohol consumption, and dietary modifications. Each of these changes has been shown to independently reduce blood pressure in elderly individuals, as well as reduce the incidence and severity of comorbid conditions which potentiate cardiovascular risk. The safety of these recommendations equals or exceeds that of pharmacologic therapy, and few contraindications to their implementation exist. A simple, safe, and effective plan appropriate and acceptable to the geriatric patient is described, offering primary care physicians a guideline to follow when prescribing lifestyle modifications to the elderly hypertensive patient.
The Growing Role of Calcium Antagonists in Treating Hypertension in the Elderly
Authors: Epstein Murray
Published: June 2007

Increasing attention has focused on the magnitude of hypertension in the elderly, with recent data indicating that it afflicts over 50% of people >65 years of age. Recent studies have clearly demonstrated that treatment of isolated systolic and diastolic hypertension in older patients confers substantive protection against hypertension induced morbidity and mortality, to an extent greater than previously appreciated. The results of the recent Systolic Hypertension in Europe (Syst‐Eur) trial have demonstrated a striking decrease in the occurrence of strokes, as well as heart failure and all cardiac events in the active treatment group. Because a long acting dihydropyridine calcium antagonist was used in the Syst‐Eur trial, it is reasonable and appropriate to recommend a long acting calcium antagonist as one of the preferred agents in the management of isolated systolic hypertensive (ISH) patients. Recent attention has also focused on the importance of formulation and pharmacokinetics as a determinant of cardiovascular risk. It is clear that the newer slow release formulations and intrinsically long acting calcium antagonists are to be preferred. By virtue of their ability to attain more gradual and sustained plasma levels, they do not evoke reactive sympathetic activation. Concomitantly, such formulations should promote increased patient compliance and thereby favorably influence hypertension related morbidity and mortality.
Acute Congestive Heart Failure and Tumor Necrosis Factor Alpha
Authors: Somasundaram Porur , Hee Sung Bong , Mousa Shaker A. , Wilson Michael F.
Published: June 2007

Congestive heart failure is prevalent in the elderly; recurrent hospital admissions for acute deterioration is a major health care problem. We examined tumor necrosis factor alpha levels in 31 congestive heart failure patients who were admitted to the hospital due to acute cardiogenic pulmonary edema. Blood samples were taken within 24 hours of admission and at the time of discharge after recovery. Tumor necrosis factor alpha levels were also measured in 10 stable congestive heart failure outpatients and 16 healthy controls. Tumor necrosis factor alpha level at admission was higher than at time of discharge (4.6±1.9 vs. 3.4±1.1 (rg/mL, p<0.02). Mean tumor necrosis factor alpha level of stable congestive heart failure outpatient was 2.6±0.7 rg/mL healthy controls had significantly lower tumor necrosis factor alpha levels (1.7±0.7 rg/mL) than congestive heart failure patients (p<0.01). tumor necrosis factor alpha levels were highest among acute congestive heart failure patients. Elevated tumor necrosis factor alpha appears to be related to the exacerbation of congestive heart failure and may be a marker for deterioration.
Ethical Issues in the Management of Geriatric Cardiac Patients
Authors: O'Neal Michael L. , Basta Lofty
Published: June 2007

Ethical Issue: An elderly mute and deaf patient with a known history of cardiac dysrrhythmia is evaluated in the absence of a sign interpreter and subsequently discovered to have been misinterpreted.
Arrhythmia Therapy in the Elderly
Authors: McAnulty John H.
Published: June 2007

As with other illnesses, the risks and benefits of diagnostic studies and treatments for arrhythmias are altered by age. In the elderly, the risks of treatment are often greater; drug metabolism varies and mechanical approaches (ablation procedures and insertion of electrical devices) are associated with greater complication rates. This paper reviews recommendations for diagnosis and treatment of arrhythmias in the elderly.
Nonpharmacologic Management of Supraventricular Tachycardia
Authors: Scheinman Melvin M.
Published: June 2007

This paper reviews three recent large scale studies on the use of catheter ablation for elderly patients with supraventricular tachycardia. These patients underwent catheter ablation of the atrioventricular junction for control of atrial fibrillation, ablation of the slow atrioventricular nodal pathway for those with atrioventricular nodal, reentry tachycardia, and ablation of the accessary pathway for those with atrioventricular reentry tachycardia. There was a higher incidence of atrioventricular junctional ablation and lesser incidence of junctional tachycardia compared to other series involving younger individuals. There was no significant difference in the incidence of successful procedures comparing the elderly with younger patients. In addition, there was no significant difference in the incidence of adverse effects between the two groups. In summary, catheter ablation appears to be safe and effective for elderly patients and the procedure should not be omitted solely on the basis of patient age.
Exercise Radionuclide Cineangiography for Predicting Long Term Prognosis in Elderly Post Coronary Artery Bypass Graft Patients
Authors: Shapira Itzhak , Isakov Aharon , Heller Israel , Topilsky Marcel , Villa Yael , Pines Amos
Published: June 2007

Issue. The immediate benefits of coronary artery bypass grafting may only be transient. Recent studies which showed that exercise radionuclide cineangiography studies may predict cardiac events and survival had evaluated post coronary artery bypass grafting patients of all ages. This prospective study was done on an elderly subgroup. Methods. The results of exercise radionuclide cineangiography performed early (4–8 months) post coronary artery bypass grafting were correlated over six years of follow up with mortality, major surgical and nonsurgical cardiac events, and cardiac event free survival in 87 consecutive patients ≥65 years. Results. The rest to peak exercise difference in left ventricular ejection fraction correlated with later cardiac death and the need for surgical interventions, while rest left ventricular ejection fraction correlated only with the latter parameter. Conclusions. Assessment of left ventricular ejection fraction at rest and at exercise has prognostic values after coronary artery bypass grafting in elderly patients. Exercise radionuclide cineangiography carried out soon after coronary artery bypass grafting might be considered an useful tool to assess patient prognosis. The efficacy of exercise radionuclide cineangiography carried out soon after coronary artery bypass grafting should be confirmed in larger and more varied patient subgroups.
Early Prognostic Assessment and Treatment of Acute Myocardial Infarction in the Elderly
Authors: Bueno Hé;ctor
Published: June 2007

The progressive aging of the population is associated with an increase in the proportion of very old patients (>75 years) hospitalized with acute myocardial infarction. The lack of evidence regarding the efficacy of most therapeutic interventions for acute myocardial infarction in these patients is leading to a significant degree of uncertainty in the cardiology community with respect to their optimal management. When aggressive treatment (defined as a therapeutic strategy designed to obtain and maintain a patent infarct‐related coronary artery at an early moment) of acute myocardial infarction is considered in very old patients, three main questions should be addressed: why should we treat? Whom should we treat? And how should we treat? To answer these questions, the authors reviewed the data available in the literature as well as new data from the PPRIMM75 (Pronóstico del PRimer Infarto de Miocardio en Mayores de 75 años) Registry, a large, prospective database of patients aged 75 years or older, admitted to a single coronary care unit in Madrid, Spain, for their first acute myocardial infarction during the last decade.
Ethical Issues in the Management of Geriatric Cardiac Patients
Authors: Morrow Michael F. , Basta Lofty L.
Published: June 2007

Ethical Issue: A medically impaired patient is determined to operate an automobile against his physicians’ advice.
The Role of Echocardiography in Hypertensive Heart Disease in the Elderly
Authors: Mensah George A.
Published: June 2007

The evaluation of target organ damage attributable to hypertension is a crucial component of risk stratification to determine the urgency and intensity of treatment as well as the assessment of overall prognosis. In the cardiovascular system, the spectrum of hypertensive damage includes left ventricular and vascular hypertrophy, heart failure secondary to decreased systolic function, impaired left ventricular diastolic relaxation, reduced left ventricular diastolic compliance, coronary microvascular disease, left atrial abnormality, and dilatation and dissection of the aorta. Echocardiography plays an important role and is frequently the diagnostic modality of choice in these conditions. It provides reliable measures of systolic performance, diastolic function, arterial compliance, atrial and ventricular chamber size, and ventricular mass—all of which may play important roles in decisions about treatment and prognosis. The versatility of echocardiography in these conditions, however, does not justify its routine use in all hypertensive patients. In selected patients and especially in the elderly, where the prevalence of hypertensive target organ damage is high, echocardiography is cost‐effective in the evaluation and management of hypertensive heart disease.
Issues of Hormone Replacement Therapy and Cardiovascular Disease for Elderly Women
Authors: Limacher Marian C.
Published: June 2007

Based on epidemiologic studies demonstrating mainly positive biologic effects of estrogen on cardiovascular risk factors and outcomes, earlier recommendations decreed that most, if not all women should be treated with long‐term postmenopausal hormone replacement. A review of recent controlled clinical trials demonstrates that previously held dictums might not prove accurate. For elderly women, the decision to begin hormone replacement therapy should not be based on an assumption of protection from cardiovascular diseases. A careful assessment of the risks and benefits, as well as acknowledgement of the outcomes for which hormone replacement therapy has unknown impact, is needed for any decision to begin, continue, or stop hormone replacement therapy.
High Blood Pressure in the Geriatric Population: Treatment Considerations
Authors: Sander Gary E.
Published: June 2007

Increases in blood pressure (BP), particularly systolic BP, have traditionally been considered to be a normal or “physiologic” component of the aging process. However, it is now clear that elevated BP, particularly systolic BP, represents a pathophysiologic manifestation of altered cardiovascular physiology and structure, ultimately manifesting as increased cardiovascular morbidity and mortality (myocardial infarction, stroke, and total cardiovascular death rates). More than one half of the population aged 65 or older have hypertension, defined as BP=140/90 mm Hg. Framingham data indicate that the risk of coronary heart disease increases with lower diastolic BP at any level of systolic BP=120 mm Hg, thus further stressing the importance of pressure‐induced arterial vascular compliance changes and introducing pulse pressure as an important predictor of cardiovascular risk. Geriatric hypertension is generally of a salt‐sensitive nature and often associated with impaired baroreflex function. Reduction in sodium intake is important and effective in older patients, and should be initiated before or together with drug therapy. Encouraging data from clinical trials now strongly support the aggressive anti‐hypertensive treatment of elderly patients. A recent meta‐analysis of eight outcome trials evaluating the risks of treated and untreated isolated systolic hypertension has demonstrated a 30% reduction in combined fatal and nonfatal stroke, a 26% reduction in fatal and nonfatal cardiovascular events, and a 13% reduction in total mortality. Those drugs effective in younger patients also appear effective in the elderly; low‐dose thiazides (alone or in combination with potassium sparing agents),β blockers, long‐acting dihydropyridine calcium antagonists, angiotensin‐converting enzyme inhibitors, and angiotensin receptor blockers all have demonstrated efficacy. In selecting an agent, it is important to consider comorbid disease states, and to recognize the potential of all nonsteroidal anti‐inflammatory drugs, whether conventional or cyclooxygenase‐2 specific, to increase BP or interfere with other antihypertensive agents. In general, the elderly should be treated to target BP levels identical to those suggested for younger patients, although a more gradual reduction to target, perhaps with an intermediate BP goal of <160 mm Hg, may be advisable.
Long‐Term Pharmacologic Management of Atrial Fibrillation in the Elderly
Authors: Waldo Albert L.
Published: June 2007

The first decision to be made in treating atrial fibrillation in the elderly is to determine whether to pursue a treatment strategy of rate control or rhythm control. Both strategies require use of anticoagulation therapy with warfarin (target international normalized ratio, 2.5; range 2–3). If a decision is made for rhythm control, the critical therapy is almost always with an antiarrhythmic drug. Before selecting an antiarrhythmic drug for use, it is first necessary to determine the presence or absence of underlying structural heart disease, as that will affect the available options for antiarrhythmic drug use. If there is no underlying structural heart disease, any of the available antiarrhythmic drugs may be used, although a clinically reasoned approach is suggested. If there is underlying structural heart disease, not all antiarrhythmic drugs are appropriate for use. A clinically reasoned approach is suggested in the presence of coronary artery disease, left ventricular dysfunction/congestive heart failure, or hypertension based largely on the risk/benefit profile of the drugs.
Clinical Profile of Chronic Heart Failure in Elderly Women
Authors: Tandon Suman , Hankins Shelley R. , Le Jemtel Thierry H.
Published: June 2007

The pathogenesis, clinical course, and treatment of chronic heart failure (HF) are different in elderly women from those of patients recruited in the landmark trials of chronic HF. Patients included in these landmark trials were predominantly men whose age was 10–15 years younger than the average age of patients with chronic HF in the United States. Diastolic dysfunction resulting in impaired left ventricular (LV) filling is the preponderant LV functional alteration that leads to chronic HF in elderly women. Gender differences in the LV remodeling process that accompanies chronic cardiac pressure are likely to be responsible for the preponderance of LV diastolic dysfunction over systolic dysfunction in elderly women. In response to chronic pressure overload, the LV wall becomes thicker in women than in men. Consequently, in response to chronic pressure overload, women are able to normalize LV wall stress and preserve LV systolic function to a greater extent than men. However, impaired LV filling is an undesirable consequence of the greater increase in LV wall thickness in women. Thus, clinical observations and therapeutic guidelines derived from data collected in the landmark trials of chronic HF may not apply to elderly women with chronic HF. In view of the lack of evidence‐based information needed to guide the management of elderly women with chronic HF, special attention should be given to include a substantial number of elderly women in future therapeutic trials recruiting patients with chronic HF.
Surgical Coronary Revascularization in Geriatric Patients
Authors: Subramanian Valavanur A. , Patel Nilesh U. , Maini Archana
Published: June 2007

Surgical coronary revascularization, especially in geriatric patients, is technically demanding and requires careful patient selection, selection of type of procedure, and postoperative care. Recent advances in coronary revascularization, especially in the variety of minimally invasive approaches and beating heart surgery, has enabled surgeons to operate upon elderly patients with improved results.
Doppler Echocardiographic Assessment of Left Ventricular Filling Pressures in Elderly Patients With Moderate/Severe Aortic Stenosis
Authors: D'Agate David J. , Smith Richard H. , Lazar Jason M.
Published: June 2007

Doppler‐derived mitral inflow indices reflect left ventricular (LV) filling pressures but often vary with age. Diastolic filling is impaired in LV pressure overload states. The objective of this study was to determine the influence of age on the relationship between mitral inflow indices and LV filling pressures in patients with aortic stenosis. The authors studied 57 consecutive patients (age, 77 years; 52% male) with moderate to severe aortic stenosis (aortic valve area ≤1.0 cm2) on cardiac catheterization and echocardiographic studies performed within 48 hours of catheterization. Patients with atrial fibrillation, aortic insufficiency, mitral stenosis, and paced rhythm were excluded. Echocardiographic variables obtained from five cardiac cycles were: E/A ratio and deceleration time (DT). Patients were sub‐classified by age (< and ≥75 years), ejection fraction ([EF] < and ≥50%), and coronary artery disease (CAD). Pulmonary capillary wedge pressure (PCWP) correlated with DT (r=−0.86; p=0.001) and with E/A (r=0.7; p=0.001) more strongly than did LV end‐diastolic pressure. Age did not alter the relationship between DT and PCWP (r=−0.92; p=0.001 for <75 years vs. r=−0.83; p=0.001 for ≥75 years). PCWP was predicted by the equation PCWP=−0.10DT+43, regardless of age. EF also had little influence on the correlation between PCWP and DT (r=−0.80; p=0.001 for EF ≥50% vs. r=−0.94; p=0.001 for EF ≥ 50%). Similarly, there were no significant differences between the regression equations and correlations between the CAD and no‐CAD groups: for CAD patients, PCWP=41.8–0.10DT; p<0.0001; r=−0.84 (p<0.0001). For no‐CAD subjects, PCWP=46.2–0.12DT; p<0.0001; r=−0.92 (p<0.0001). In patients with significant aortic stenosis, DT correlated strongly with PCWP but not with LV end‐diastolic pressure. This relationship was independent of age, CAD, or EF.
Epidemiology of Hypertension in the Elderly
Authors: Fagard Robert H.
Published: June 2007

In Western populations, mean systolic and diastolic blood pressures rise with advancing age up to the sixth decade of life, whereupon systolic blood pressure continues to increase and diastolic pressure starts to decline. The ensuing widening of pulse pressure is mainly ascribed to stiffening of the arterial vasculature. When hypertension is defined as systolic blood pressure of at least 140 mm Hg and/or diastolic pressure of at least 90 mm Hg, its prevalence amounts to 60%–70% of the population above 60 years of age. About 60% of these hypertensives have isolated systolic hypertension—that is, elevated systolic pressure and normal diastolic pressure. It should be realized, however, that approximately 25% of those labeled hypertensive on the basis of conventional blood pressure measurements have normal blood pressure on ambulatory blood pressure monitoring, or so‐called white‐coat, isolated clinic, or nonsustained hypertension. There is little doubt that elevated blood pressure leads to a number of cardiovascular complications. Whereas diastolic blood pressure has been emphasized for many years, the paradigm has shifted toward systolic blood pressure. In addition, pulse pressure has been shown to be an important predictor of cardiovascular events and death, above and beyond the predictive power of mean blood pressure.
Results of Antihypertensive Treatment Trials in the Elderly
Authors: Leonetti Gastone , Zanchetti Alberto
Published: June 2007

The prevalence of arterial hypertension is age‐dependent, and with the prolongation of life expectancy the number of elderly subjects with arterial hypertension is very relevant. Epidemiologic studies have shown that arterial hypertension is a risk factor in elderly patients and therefore the physician must know if the pharmacologic and nonpharmacologic reduction of blood pressure values is associated with a corresponding decrease in systolic‐diastolic or isolated systolic hypertension. Clinical trials have shown that the lowering of blood pressure values is commonly associated with a decrease in cardiovascular events. So far, the reduction of blood pressure per se appears more relevant to the cardiovascular benefit than does a particular class of antihypertensive agents. The benefit of antihypertensive treatment has been shown up to the age of 80 years, while there are no clear indications of a benefit in persons older than 80 years. While sufficient data suggest that a diastolic blood pressure between 80 and 90 mm Hg is associated with a clear benefit in elderly patients, the data in support of a systolic reduction below 140 mm Hg require further direct confirmation.
Ethical Issues in the Management of Geriatric Cardiac Patients
Authors: Le Tien V. , Basta Lofty L.
Published: June 2007

Ethical Issue: A neurosurgeon takes extraordinary measures to convince family members to act against a hospice patient's express wishes.
Ethical Issues in the Management of Geriatric Cardiac Patients
Authors: Basta Lofty L.
Published: June 2007

Ethical Issue: A competent patient on renal dialysis asks to go home to be under the care of her unqualified husband.
Ethical Issues in the Management of Geriatric Cardiac Patients
Authors: Basta Lofty L.
Published: June 2007

Ethical Issue: A woman executed a living will with provisions that impeded its implementation.
Hemostatic and Inflammatory Markers as Risk Factors for Coronary Disease in the Elderly
Authors: Tracy Russell P.
Published: June 2007

Inflammation has been recognized as an integral component of atherothrombotic disease, and inflammatory markers are strongly related to future cardiovascular disease risk in elderly men, and to a certain extent in elderly women. The association is complicated by the prevalence of hormone replacement therapy among older women, and the variety of the underlying vascular disease. For fatal events, inflammation markers exhibit a time‐to‐event dependency in the elderly that has not been noted to the same degree in younger people. Hemostatic markers that represent inflammatory processes or coagulation activation also predict future risk in older individuals, but there is little evidence for associations between cardiovascular disease risk and ambient levels of coagulation or fibrinolytic factors.
Rhabdomyolysis and Satin Therapy: Relevance to the Elderly
Authors: Sica Domenic A. , Gehr Todd W.B.
Published: June 2007

A recent debate has emerged as to the risk‐benefit ratio of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins). This debate has centered on the withdrawal of the HMG‐CoA reductase inhibitor cerivastatin (Baycol®). Its withdrawal was prompted by an unacceptably high rate of rhabdomyolysis associated with its use. The development of rhabdomyolysis in cerivastatin‐treated patients surprised few, since myotoxicity is a class effect with HMG‐CoA reductase inhibitors. What has sprung from the cerivastatin experience, though, is the concept of “guilt by association”; thus, other members of this class are now viewed in a similarly negative light. Such misgivings are understandable, but to a degree may be ill‐advised, since differences exist in the risk and therefore the rate of rhabdomyolysis occurrence among the various HMG‐CoA reductase inhibitors. In this regard, pravastatin and fluvastatin are least likely to provoke muscle cell damage, which, at least in part, relates to their not being metabolized by the cytochrome P‐450 (CYP) 3A4 pathway. When muscle damage does occur with HMG‐CoA reductase inhibitors, it is commonly the result of drug‐drug interactions rather than a specific adverse response to HMG‐CoA reductase inhibitor monotherapy. Such drug‐drug interactions inevitably result in higher plasma concentrations of an HMG‐CoA reductase inhibitor and thereby an increased risk of myotoxicity. A growing consensus supports an expanded use of HMG‐CoA reductase inhibitors in elderly patients. Polypharmacy and altered drug metabolism both put the elderly patient at increased risk of myotoxicity when drugs in the HMG‐CoA reductase inhibitor class are administered. Physicians must take many factors into account when selecting a member of the HMG‐CoA reductase inhibitor class, particularly as relates to their use in the multiply medicated elderly patient.
Resprouting enhances seedling persistence in a subtropical coastal dune forest
Authors: Nzunda Emmanuel F. , Griffiths Megan E. , Lawes Michael J.
Published: June 2007

In theory, resprouting enables species with low reproductive output (i.e., few seedlings) to persist. The advantage conferred by seedling sprouts on tree species persistence was evaluated in a subtropical coastal dune forest in South Africa. Species with a higher frequency of seedling sprouts demonstrated greater persistence as evidenced by a larger proportion of seedlings >1 year old and a larger seedling bank than species with few seedling sprouts. Resprouted seedlings had a larger basal diameter than true seedlings. Although resprouting resulted in the maintenance of multiple stems in some seedlings, the proportion of multi‐stemmed seedlings was low. Multi‐stemming was not a favoured form of seedling growth except in one species that occupied relatively open sites. Despite the apparent difference among species in resprouting ability, we found that seedling resprouting was not phylogenetically constrained. These results demonstrate that seedling sprouts form an important component of seedling banks in coastal dune forest.
Morphologic variability of exposed mass‐transport deposits on the eastern slope of Gela Basin (Sicily channel)
Authors: Minisini Daniel , Trincardi Fabio , Asioli Alessandra , Canu Marcello , Foglini Federica
Published: June 2007

The NE portion of Gela Basin in the Sicily Channel is affected by multiple slope failures originated during the late‐Quaternary. Basin sequences show evidence of stacked acoustically transparent and/or chaotic units, characterized by irregular upper surfaces, interpreted as mass‐transport deposits. The seafloor morphology also shows evidence of both old, partially buried, as well as recent slide products. Two recent slides exposed at seafloor, only 6 km apart (Twin Slides), are similar in geomorphological parameters, age and multistage evolution. Multistage failure of Twin Slides evolved from mud flows, derived from the extensive failure of less consolidated post‐glacial units, to localized slides (second stage of failure) affecting older and more consolidated materials. Although Twin Slides are very close to each other and have similar runout and fall height, they produced very dissimilar organization of the displaced masses, likely reflecting the distinct source units affected by failures. Integrating geophysical, sedimentological, structural and palaeontological data, a detailed investigation was conducted to determine the size and internal geometry of this mass‐transport complex, to explain the differentiated product and to shed light on its predisposing factors, triggers and timing.
What therapies have replaced rofecoxib in Ireland?
Authors: Teeling Mary , O'Connor Humphrey , Feely John , Bennett Kathleen
Published: June 2007

What is already known about this subject

• Prior to the worldwide withdrawal of rofecoxib in 2004, due to cardiovascular toxicity with its use, selective COX‐2 inhibitors had been shown to be preferentially prescribed to ‘at‐risk’ patients in Ireland, including older females or those receiving antiulcer medications or multiple concomitant medications.

What this study adds

• During the 12 months post rofecoxib withdrawal the majority of those previously receiving chronic rofecoxib therapy were prescribed either no further nonsteroidal anti inflammatory drug (NSAID) therapy or short‐term NSAID therapy only.

• Prescriptions for analgesic agents were initiated in half of the study group.

• These results suggest that the withdrawal of rofecoxib and the subsequent controversy may have led prescribers to question their use of NSAIDs in the first place and to adhere more closely to published guidelines on their use.

Aims

To examine prescription patterns of nonsteroidal anti‐inflammatory drugs (NSAIDs) or analgesics in patients prescribed chronic rofecoxib treatment prior to withdrawal from the Irish market, and to determine the impact on proton pump inhibitor (PPI) co‐prescription.

Methods

Using a national prescribing database, adults (≥16 years) prescribed rofecoxib for ≥3 months, but not analgesics, from January to September 2004 were identified. A longitudinal prescribing history was used to determine switching patterns to other cyclooxygenase (COX)‐2 inhibitors, NSAIDs or analgesics during 3 and 12 months after withdrawal. Concomitant PPI prescription was examined. Logistic regression was used to determine the likelihood of switching to a COX‐2 inhibitor vs. nonselective NSAID and factors influencing concomitant PPI prescription.

Results

After rofecoxib withdrawal, 30.2% (1558) and 17.9% (922) of the 5155 study subjects received no further NSAID prescription during 3 and 12 months, respectively. During the 12‐month period, approximately one‐third of NSAID prescriptions were for <3 months; 40.7% (2096) received sequential prescriptions for different NSAIDs. Co‐prescription of analgesics occurred in 49.3% (2539) of subjects. Neither age nor gender influenced the type of NSAID prescribed in the 12 months post rofecoxib withdrawal. PPI prescription increased by 5.5% during the study, associated with use of nonselective NSAIDs, prior use of PPIs and increasing age.

Conclusions

The majority of those receiving chronic rofecoxib therapy were prescribed either no further NSAID or short‐term NSAID therapy only during the 12 months post withdrawal, which suggests the subsequent controversy may have encouraged prescribers to adhere more closely to published guidelines.
Incorporation of fibrin molecules containing fibrinopeptide A alters clot ultrastructure and decreases permeability
Authors: Flood Veronica H. , Nagaswami Chandrasekaran , Chernysh Irina N. , Al‐Mondhiry Hamid A. , Weisel John W. , Farrell David H.
Published: June 2007

Previous studies have shown that a heterozygous mutation in the fibrinogen Aα chain gene, which results in an Aα R16C substitution, causes fibrinolytic resistance in the fibrin clot. This mutation prevents thrombin cleavage of fibrinopeptide A from mutant Aα R16C chains, but not from wild‐type Aα chains. However, the mechanism underlying the fibrinolytic resistance is unclear. Therefore, this study investigated the biophysical properties of the mutant fibrin that contribute to fibrinolytic resistance. Fibrin clots made from the mutant fibrinogen incorporated molecules containing fibrinopeptide A into the polymerised clot, which resulted in a ‘spiky’ clot ultrastructure with barbed fibrin strands. The clots were less stiff than normal fibrin and were cross‐linked slower by activated FXIII, but had an increased average fiber diameter, were more dense, had smaller pores and were less permeable. Protein sequencing showed that unclottable fibrinogen remaining in the supernatant consisted entirely of homodimeric Aα R16C fibrinogen, whereas both cleaved wild‐type α chains and uncleaved Aα R16C chains were in the fibrin clot. Therefore, fibrinolytic resistance of the mutant clots is probably a result of altered clot ultrastructure caused by the incorporation of fibrin molecules containing fibrinopeptide A, resulting in larger diameter fibers and decreased permeability to fibrinolytic enzymes.
Identification of MEN1 and HRPT2 somatic mutations in paraffin‐embedded (sporadic) parathyroid carcinomas
Authors: Haven C. J. , Van Puijenbroek M. , Tan M. H. , Teh B. T. , Fleuren G. J. , Van Wezel T. , Morreau H.
Published: June 2007

Objective  Parathyroid carcinoma remains difficult to diagnose. Recently, it has been shown that mutations in the HRPT2 gene (encoding parafibromin) are associated with the development of parathyroid carcinoma. Although MEN1 is not typically thought to be involved in carcinoma formation, parathyroid carcinoma may be an extremely rare feature of the multiple endocrine neoplasia type 1 (MEN1) syndrome. We recently concluded that loss of heterozygosity (LOH) of the MEN1 gene is present in a relatively large number of parathyroid carcinomas, often in combination with LOH at the HRPT2 locus. The aim of this study was to evaluate the role of MEN1 and HRPT2 mutations in sporadic parathyroid tumours fulfilling histological criteria for malignancy.

Patients and design  Formalin‐fixed, paraffin‐embedded (FFPE) parathyroid carcinoma tissue from 28 cases identified in the period 1985–2000 in the Netherlands was studied. HRPT2 (27/28 cases) and MEN1 (23/28 cases) were analysed by direct sequencing.

Results  Somatic MEN1 mutations were found in three of 23 (13%) sporadic parathyroid carcinoma cases; these consisted of one missense and two frameshift mutations. One of the latter two cases displayed lymph‐node and lung metastases during follow‐up. Six HRPT2 mutations were found in 4/27 cases (15%): five were truncating mutations and one was a missense mutation. Consistent with previously published reports, we found double mutations (2×) and germline mutations (2×) in apparently sporadic parathyroid carcinomas.

Conclusions  These results suggest that not only HRPT2 but also MEN1 mutations may play a role in sporadic parathyroid cancer formation.
Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1
Authors: Toledo Rodrigo A. , Lourenco Delmar M. , Coutinho Flavia L. , Quedas Elisangela , Mackowiack Ivone , Machado Marcel C. C. , Montenegro Fabio , Cunha‐Neto Malebranche B. C. , Liberman Bernardo , Pereira Maria A. A. , Correa Pedro H. S. , Toledo Sergio P. A.
Published: June 2007

Objective  To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1).

Settings  Non‐profit academic centre.

Patients  Fourteen Brazilian families with MEN1 and 141 at‐risk relatives.

Results  We identified 12 different MEN1 disease‐causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial‐DNA and Y‐chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC‐rich repetitive regions. Genetic screening of 141 at‐risk family members identified 38 MEN1 mutation carriers, 37 (97·4%) of whom had at least one major MEN1‐related tumour upon clinical investigation.

Conclusions  High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil.
Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer
Authors: Iervasi A. , Iervasi G. , Ferdeghini M. , Solimeo C. , Bottoni A. , Rossi L. , Colato C. , Zucchelli G. C.
Published: June 2007

Objective  Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/metastases after treatment for differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly sensitive Tg assay during routine follow‐up of DTC patients.

Design  Tg values were measured by a highly sensitive Tg assay during L‐T4 suppressive therapy and after recombinant human thyrotropin (rh‐TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay.

Patients  One hundred and sixty consecutive DTC‐treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied.

Measurements  Measured variables included neck ultrasonography, 131I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA).

Results  During L‐T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut‐off of 2 µg/l after rh‐TSH, a negative response was associated with undetectable Immulite Tg during L‐T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L‐T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively.

Conclusions  The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC‐treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh‐TSH test.
A technique for the orientation of endoscopically resected laryngeal lesions
Authors: Murray C.E. , Cooper L. , Handa K.K. , MacLeod T. , MacKenzie K.
Published: June 2007

Keypoints

• Endoscopic resection is a widely accepted method of treating early laryngeal malignancies.

• Accurate histological assessment of resected laryngeal specimens can be difficult due to their small size and potential damage and distortion caused by standard orientation and processing techniques.

• A new technique is described which employs dehydrated cucumber to mount laryngeal specimens for orientation and processing

• This technique is quick, easy, cheap and reliable, allowing accurate histological assessment of potentially malignant lesions.

• Better orientating and processing of laryngeal specimens can optimise treatment decisions based on histological results.