bluuebunny/crossref_metadata_2025 huggingface dataset:
The Intestinal Absorption of Biliary and Dietary Cholesterol as a Drug Target for Lowering the Plasma Cholesterol Level
Authors: Turley Stephen D. , Dietschy John M.
Published: June 2007

Elevated plasma low‐density lipoprotein cholesterol levels constitute a major risk factor for coronary heart disease. The plasma low‐density lipoprotein cholesterol concentration is dictated partly by the efficiency of intestinal cholesterol absorption. The efficacy of treatments designed to block cholesterol absorption is partially offset to the extent that the liver compensates for the interruption to the enterohepatic movement of cholesterol by increasing the rate at which it synthesizes cholesterol. Currently, the most widely‐used treatment for hypercholesterolemia is based on a class of agents (statins) that partially inhibit cholesterol synthesis within the body. Recent clinical trials with a unique, potent, and selective cholesterol absorption inhibitor (ezetimibe) used in combination with lower doses of various statins showed an additive reduction in plasma low‐density lipoprotein cholesterol levels which equaled the reduction achieved with maximal doses of statins given alone. Combination therapy using a statin and this novel cholesterol absorption inhibitor represents an efficacious new approach to the treatment of hypercholesterolemia in the general population.
Effectiveness of Statin‐Gemfibrozil Combination Therapy in Patients With Mixed Hyperlipidemia: Experience of a Community Lipid Clinic and Safety Review From the Literature
Authors: Shammas Nicolas W. , Kapalis Matthew J. , Deckert Judi , Dippel Eric J. , Labroo Ajay , McKinney Dawn
Published: June 2007

This retrospective study was carried out to assess the effectiveness of statin‐gemfibrozil combination therapy in a community practice lipid clinic and to review safety data from published literature. Forty‐six consecutive patients received a statin and gemfibrozil combination for resistant hyperlipidemia to either agent therapy. Fasting total cholesterol (mg/dL), high‐density lipoprotein cholesterol (mg/dL), and triglycerides (mg/dL) were measured. Low‐density lipoprotein cholesterol (mg/dL) was calculated using the Friedewald formula if triglycerides were <400 mg/dL. Combination therapy reduced total cholesterol, low‐density lipoprotein cholesterol, and triglycerides by 11% (p=0.02), 22% (p=0.049), and 39% (p=0.0002), respectively, and raised high‐density lipoprotein cholesterol by 5% (p=0.3). A pooled analysis of 838 patients from the literature on statin‐gemfibrozil combination therapy revealed an incidence of myositis and severe myopathy of 0.7% and 0.6%, respectively (excluding cerivastatin). We conclude that statin‐gemfibrozil combination therapy is effective in significantly reducing total cholesterol, low‐density lipoprotein cholesterol, and triglycerides with a trend toward raising high‐density lipoprotein cholesterol in patients with hyperlipidemia resistant to either agent alone. Myositis and severe myopathy are infrequent, but not rare side effects which may be statin‐specific regarding the incidence of occurrence.
Once‐Daily Niacin Extended Release/Lovastatin Combination Tablet Has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Than Atorvastatin and Simvastatin
Authors: Bays Harold E. , McGovern Mark E. , Kopin Laurie
Published: June 2007

Standard lipoprotein measurements may not adequately reflect the increased atherogenic risk found in patients with abnormalities in lipoprotein particle size and subfraction distribution such as disproportionate amounts of small, dense low‐density lipoprotein particles, small high‐density lipoprotein particles, or large very‐low‐density lipoprotein particles. Measurement or anticipation of patients most susceptible to lipoprotein subfraction abnormalities may influence therapeutic choices for the optimal management of dyslipidemia. Previously, the ADvicor Vs. Other Cholesterol‐modulating Agents Trial Evaluation demonstrated that niacin extended release/lovastatin provided greater global improvement in lipid parameters such as low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, and apolipoprotein A‐I blood levels compared with atorvastatin and simvastatin monotherapies. In this report, niacin extended release/lovastatin was also more effective than atorvastatin and simvastatin monotherapies in reducing small, dense low‐density lipoprotein particles and improving low‐density lipoprotein phenotype pattern at relative starting doses, and was more effective in increasing the proportion of high‐density lipoprotein in the potentially cardioprotective 2b subclass at all doses.
Psychologic Treatment for Hypertension Can Be Efficacious
Authors: Linden Wolfgang
Published: June 2007

The traditional view of psychologic treatments and their efficacy for treating primary hypertension is that they may be of some benefit for borderline hypertension and that they can be potentially useful adjuncts to medical treatment. This review challenges such cautious conclusions by critically analyzing previous reviews and by also considering innovative, newer clinical trials. One reason for cautious conclusions has been selective reviewing and a lack of well‐designed trials. Measurement and study protocol differences as well as differences in treatment modality have all been shown to have major effects on observed outcomes. Studies that promise better results have the following characteristics: 1) use of 24‐hour ambulatory monitoring as an end point to rule out white coat hypertension that does not need treatment in the first place; 2) inclusion of patients with truly elevated blood pressure at pretreatment; and 3) multicomponent treatments that are tailored to individual patient needs.
Physical Activity and Markers of Inflammation and Thrombosis Related to Coronary Heart Disease
Authors: Panagiotakos Demosthenes B. , Kokkinos Peter , Manios Yannis , Pitsavos Christos
Published: June 2007

Epidemiologic studies have provided strong evidence of the beneficial effects of physical activity in patients with coronary heart disease; however, the mechanisms for the cardioprotective effect of physical activity are not fully understood. The more favorable changes in coronary risk profiles of physically active individuals and the favorable changes observed on several of the established coronary risk factors in exercise intervention studies must play a partial role in that protection. In more recent years, inflammatory and thrombotic factors have been implicated in the development and progression of atherosclerosis. Physical activity has been associated with lower levels of several inflammatory markers; however, the effect of physical activity on coagulation markers remains controversial. The authors summarize the studies on the effect of physical activity on several inflammatory and thrombotic variables. The importance of physical activity in the prevention of cardiovascular disease through modification of the inflammatory and thrombogenic processes is also addressed.
Atorvastatin Reduces Remnant Lipoproteins and Small, Dense Low‐Density Lipoproteins Regardless of the Baseline Lipid Pattern
Authors: O'Keefe James H. , Captain Becky K. , Jones Philip G. , Harris William S.
Published: June 2007

Elevated plasma levels of remnant lipoproteins and small, dense low‐density lipoprotein (LDL) particles increase the risk of atherosclerosis. This prospective, placebo‐controlled, crossover trial evaluated the effect of atorvastatin on various lipid parameters including remnant lipoproteins and small, dense‐LDL cholesterol levels. Forty‐five subjects were enrolled in the study. These subjects fell into three distinct lipid patterns: atherogenic dyslipidemia, isolated hypercholesterolemia, and mixed dyslipidemia. Regardless of the baseline lipid profile, atorvastatin (10 mg q.d.) reduced levels of remnant lipoproteins by 25%, LDL‐cholesterol by 27%, and the three LDL subfractions by 23%–28% (p<0.0001 for all). Combining all patients, atorvastatin did not significantly alter the overall LDL subfraction pattern; however, in the isolated hypercholesterolemia group, the proportion of LDL present as the small, dense fraction increased by 23% (p=0.01) with treatment, whereas it did not change significantly in the other two groups. Overall, atorvastatin reduced triglycerides by 18% and apolipoprotein‐B100 by 23% and increased high‐density lipoproteins by 6.2% (p<0.001 all). Since atorvastatin is known to reduce the risk for coronary heart disease events and these data suggest that it does not appear to alter the LDL subfraction pattern, it is unclear whether or not the latter is an important risk predictor independent of LDL‐cholesterol concentrations. Increased attention should be paid to absolute concentrations of LDL subfraction cholesterol, which may be a more sensitive indicator of coronary heart disease risk than total LDL or an LDL pattern.
BOOK REVIEW
Authors: Pignone Michael , Sheridan Stacey L. , Lee Yueh Z. , Kuo Johnny , Phillips Christopher , Mulrow Cynthia , Zeiger Roni
Published: June 2007

Heart to Heart is a computer‐based decision aid for patients and providers that provides personalized, evidence‐based information about coronary heart disease (CHD) risk and potential risk‐reducing interventions. To develop Heart to Heart, the authors used Framingham risk equations and systematic reviews of risk‐reducing interventions. The Web version was programmed using PHP: Hypertext Processor, a Web‐based programming language, and has separate interfaces for providers and patients. The authors subsequently developed a modified version for personal digital assistants. Heart to Heart uses information about a patient's CHD risk factors (age, gender, total and high‐density lipoprotein cholesterol levels, diabetes, smoking, systolic blood pressure, and left ventricular hypertrophy) to calculate risk of total CHD events over 5 or 10 years. Patients and providers can then examine the effect of introducing one or more risk‐reducing interventions (aspirin, lipid‐lowering drug therapy, antihypertensive medication, or smoking cessation) on the patient's CHD risk. Future research will be directed to determining whether Heart to Heart can improve utilization of effective CHD risk‐reducing interventions.
Heart to Heart: A Computerized Decision Aid for Assessment of Coronary Heart Disease Risk and the Impact of Risk‐Reduction Interventions for Primary Prevention
Authors: Michael Pignone , Sheridan Stacey L. , Lee Yueh Z. , Kuo Johnny , Phillips Christopher , Mulrow Cynthia , Zeiger Roni
Published: June 2007

Heart to Heart is a computer‐based decision aid for patients and providers that provides personalized, evidence‐based information about coronary heart disease (CHD) risk and potential risk‐reducing interventions. To develop Heart to Heart, the authors used Framingham risk equations and systematic reviews of risk‐reducing interventions. The Web version was programmed using PHP: Hypertext Processor, a Web‐based programming language, and has separate interfaces for providers and patients. The authors subsequently developed a modified version for personal digital assistants. Heart to Heart uses information about a patient's CHD risk factors (age, gender, total and high‐density lipoprotein cholesterol levels, diabetes, smoking, systolic blood pressure, and left ventricular hypertrophy) to calculate risk of total CHD events over 5 or 10 years. Patients and providers can then examine the effect of introducing one or more risk‐reducing interventions (aspirin, lipid‐lowering drug therapy, antihypertensive medication, or smoking cessation) on the patient's CHD risk. Future research will be directed to determining whether Heart to Heart can improve utilization of effective CHD risk‐reducing interventions.
Relaxation Response for Veterans Affairs Patients With Congestive Heart Failure: Results From a Qualitative Study Within a Clinical Trial
Authors: Chang Bei‐Hung , Jones Debra , Hendricks Ann , Boehmer Ulrike , Locastro Joseph S. , Slawsky Mara
Published: June 2007

Fifty‐seven veterans with congestive heart failure were interviewed about their experiences and changes after participating in a three‐armed randomized trial: relaxation response (RR) training, cardiac education, and usual care. The interviews were tape‐recorded, transcribed, and analyzed. Half of the 20 RR group interviewees reported physical improvements, and 13 reported emotional improvements. These improvements went beyond disease management to lifestyle changes and improved family/friends relationships. Five of 16 cardiac education group interviewees reported physical improvements, and eight reported emotional improvements. These improvements consisted of a better understanding of the disease and resulted in feeling more at ease. None of the usual care group interviewees reported any improvement from study participation. Although group support contributed to the benefits reported by RR and cardiac education groups, the use of the RR techniques seems to be the factor that distinguished the improvements. The value of the RR in congestive heart failure health care is suggested by the results.
Rosuvastatin Alone or With Extended‐Release Niacin: A New Therapeutic Option for Patients With Combined Hyperlipidemia
Authors: Capuzzi David M. , Morgan John M. , Carey Christina M. , Intenzo Charles , Thomas Tulenko , Dana Kearney , Kalen Walker , Cressman Michael D.
Published: June 2007

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of highdensity lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended‐release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24‐week, open‐label, multicenter trial, men and women aged ≥18 years with fasting levels of total cholesterol ≥200 mg/dL, HDL cholesterol ≤45 mg/dL, triglycerides 200–800 mg/dL, and apolipoprotein B ≥110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10–40 mg, ER niacin 0.5–2 g, rosuvastatin 40 mg plus ER niacin 0.5–1 g, or rosuvastatin 10 mg plus ER niacin 0.5–2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low‐density lipoprotein (LDL) cholesterol and non‐HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non‐HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono‐ and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A‐1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoproteinlipid abnormalities of combined hyperlipidemia.
Body Composition Profiles Derived From Dual‐Energy X‐Ray Absorptiometry, Total Body Scan, and Mortality
Authors: Krakauer Jesse C. , Franklin Barry , Kleerekoper Michael , Karlsson Magnus , Levine James A.
Published: June 2007

Little has been reported on the association of derived body composition data and cardiovascular mortality. The authors defined body composition profiles based on one‐ and two‐variable measures from dual‐energy x‐ray absorptiometry (DXA) total body scans. Scan results are labeled “apple” if Z score for percent of total fat in trunk is >0 and “pear” if Z score for height‐corrected limb fat is ≥0. The fat measures were combined to define four body composition profiles: “pickle,”“avocado,”“mango,” and “barrel.” A third axis, the Z score of height‐corrected limb lean tissue, is an index of skeletal muscle mass and was used to label subjects as “hard” or “soft.” Subjects (n=324) who were in good health from Malmö, Sweden, underwent body composition analysis using DXA and were followed for 10 years. The distribution of body composition profiles was similar for both genders and across age groups. Among subjects aged 50–74 years at baseline (n=116), there were 21 deaths. Barrel had the highest mortality rate: 13/39 (33.3%) mortality for barrels, compared with 8/77 (10.4%) mortality for non‐barrels; mortality odds ratio, 3.2; 95% confidence interval, 1.45–7.08. The increased mortality was principally attributable to cardiovascular cause‐related deaths. Soft (sarcopenia) was also associated with increased mortality (25.9%; p=0.05), but not cardiovascular cause‐related deaths, whereas the total mortality among apples was not significantly increased but cardiovascular cause‐related deaths were predominant (75%; p=0.02). The authors propose that DXA‐body composition profiles can identify increased mortality risk of magnitude similar to major cardiovascular risk factors and may prove useful in health assessment.
Intensive Lifestyle Modification: Impact on Cardiovascular Disease Risk Factors in Subjects With and Without Clinical Cardiovascular Disease
Authors: Ellsworth Darrell L. , O'Dowd Sean C. , Salami Barbara , Hochberg Alan , Vernalis Marina N. , Marshall Debra , Morris Jonathan A. , Somiari Richard I.
Published: June 2007

Intensive lifestyle modification programs are intended to stabilize or promote regression of coronary artery disease; however, clinical response is often nonuniform, complicating appropriate utilization of resources and prediction of outcome. This study assessed physiological and psychological benefits to 72 persons participating in a prospective, nonrandomized, fourcomponent lifestyle change program and compared response between patients with clinical cardiovascular disease (CVD) and patients with elevated risk factors for CVD but without clinical manifestations of disease. Subjects entering the program due to elevated risk factor levels alone demonstrated equal or greater benefit, in terms of improvement in primary CVD risk factors and reduction in measures of coronary disease risk developed in the Framingham Heart Study, than those with clinical CVD. These findings suggest that intensive lifestyle change programs may be important for primary prevention in individuals at increased risk of CVD.
Cardiovascular Actions of Selective Estrogen Receptor Modulators and Phytoestrogens
Authors: Nandur Radhika , Kumar Kavita , Villablanca Amparo C.
Published: June 2007

Cardiovascular disease is the leading cause of death among men and women in Western societies. Over the past decade, interest in a better understanding of gender differences in cardiovascular disease has heightened. Concomitantly, the use of hormone therapy for cardiovascular risk reduction in postmenopausal women has come into question in light of recent landmark clinical studies casting doubt on the benefits of this therapy. As a consequence, alternatives to conventional hormone replacement, including selective estrogen receptor modulators and phytoestrogens, have attracted considerable attention. The authors provide an up‐to‐date review of the clinical actions of selective estrogen receptor modulators on cardiovascular disease. The actions of tamoxifen, raloxifene, droloxifene, and soy phytoestrogens are discussed in the context of cardiovascular disease epidemiology, coronary events, clinical markers of cardiovascular risk, and vascular function. In addition, the authors' current understanding of the mechanism of action of these agents is discussed and recommendations for clinical practice are reviewed.
Beyond Traditional Risk Factor Analysis for Coronary Artery Disease: The Case for Coronary Artery Calcium Assessment With Electron Beam Computed Tomography
Authors: Arad Yadon
Published: June 2007

Coronary artery disease is often asymptomatic, leading to inefficient detection. Although coronary artery disease is associated with multiple risk factors, better methods for detection are needed. The quantity of coronary artery calcium as detected with electron beam computed tomography is indicative of plaque mass, and the likelihood of coronary obstruction and future coronary events is independent of other risk factors. Screening for coronary artery disease with electron beam computed tomography offers a complimentary way of detecting early atherosclerosis in asymptomatic patients.
A Controlled Pilot Study of Stress Management Training of Elderly Patients With Congestive Heart Failure
Authors: Luskin Frederic , Reitz Megan , Newell Kathryn , Quinn Thomas Gregory , Haskell William
Published: June 2007

The purpose of this study was to evaluate the effect of stress management training on quality of life, functional capacity, and heart rate variability in elderly patients with New York Heart Association class I‐III congestive heart failure (CHF). While substantial research exists on stress management training for patients with coronary heart disease, there are few data on the value of psychosocial training on patients with CHF. Thirty‐three multiethnic patients (mean age, 66±9 years) were assigned through incomplete randomization to one of two treatment groups or a wait‐listed control group. The 14 participants who completed the treatment attended eight training sessions during a 10‐week period. The training consisted of 75‐minute sessions adapted from the Freeze‐Frame stress management program developed by the Institute of HeartMath. Subjects were assessed at baseline and again at the completion of the training. Depression, stress management, optimism, anxiety, emotional distress, and functional capacity were evaluated, as well as heart rate variability. Significant improvements (p<0.05) were noted in perceived stress, emotional distress, 6‐minute walk, and depression, and positive trends were noted in each of the other psychosocial measures. The 24‐hour heart rate variability showed no significant changes in autonomic tone. The authors noted that CHF patients were willing study participants and their emotional coping and functional capacity were enhanced. This program offers a simple and cost‐effective way to augment medical management of CHF. Given the incompleteness of CHF medical management and the exploding interest in complementary medical intervention, it seems imperative that further work in psychosocial treatment be undertaken.
A Treatise on the “Mammogram of the Heart”
Authors: Detrano Robert
Published: June 2007

The enormous toll that coronary heart disease takes on our population merits serious consideration of all possible approaches toward early detection and prevention. It is pedestrian to the knowledgeable epidemiologist to state that coronary disease will kill more than twice as many women this year than will breast cancer. Coronary disease kills men at an even greater rate. If we had an effective preventive strategy involving early screening for one disease, why not find and apply a similar strategy for the other? Its vocal proponents have touted the coronary computed tomographic scan for calcification as the mammogram of the heart. However, unlike the breast mammogram, there are no studies showing that those tested fare any better than those who forego testing, in other words, that the test actually improves prognosis. Furthermore, the results regarding the prognostic value of computed tomographic screening are far from completely conclusive and will not be until the ongoing Multi‐Ethnic Study of Atherosclerosis (MESA) trial (available at: http://140.142.220.3/mesa/) is completed.
Statins and C‐Reactive Protein: Considering a Novel Marker of Cardiovascular Risk
Authors: Gotto Antonio M.
Published: June 2007

Landmark intervention trials have validated the importance of lipid control in reducing the incidence of coronary ischemic events, over a range of baseline lipid levels. With the release of the third iteration of the National Cholesterol Education Program's Adult Treatment Panel guidelines, there is renewed debate about the appropriate use of pharmacologic therapies in individual patients, especially in primary prevention. Markers of low‐grade inflammation may capture the inflammatory aspect of atherosclerosis and may prove to be useful clinical predictors of excess coronary risk. C‐reactive protein, an acute‐phase reactant protein, appears to be one such promising measurement and may have important implications for the optimal targeting of statin therapy.
Cardiovascular Medications Taken by Patients Aged ≥70 Years Hospitalized for Acute Coronary Syndromes Before Hospitalization and at Hospital Discharge
Authors: Woodworth Stephen , Nayak Devraj , Aronow Wilbert S. , Pucillo Anthony L. , Koneru Srinivas
Published: June 2007

A prospective study was performed in 177 patients, mean age 78±6 years, hospitalized with acute coronary syndromes. Obstructive coronary artery disease was documented by coronary angiography in 154 of 177 patients (87%). Coronary revascularization was performed in 96 of 177 patients (54%). Five of 177 patients (3%) died during hospitalization. Compared to use before hospitalization, at hospital discharge the use of aspirin increased from 43% to 84% (p<0.001), the use of clopidogrel increased from 21% to 54% (p<0.001), the use of β blockers increased from 38% to 76% (p<0.001), the use of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers increased from 42% to 70% (p<0.001), the use of long‐acting nitrates increased from 15% to 31% (p<0.001), and the use of calcium channel blockers decreased from 28% to 23% (p=NS). Dyslipidemia was present in 62% of the 177 patients. The use of statins increased from 34% before hospitalization to 63% at hospital discharge (p<0.001).
Association Between a Polymorphism in the Lymphotoxin−a Promoter Region and Migraine
Authors: Lee Kyung‐A , Jang Soo Yeon , Sohn Kwang‐Min , Won Hong Hee , Kim Min Ji , Kim Jong‐Won , Chung Chin‐Sang
Published: June 2007

Objective.—The aim of this study was to determine whether polymorphisms in the lymphotoxin (LTA)‐tumor necrosis factor (TNF) region are associated with the risk of migraine.

Background.—Previous studies concerning the role of TNFα in migraine have provided conflicting results. It has been reported that LTA could be a susceptibility gene in migraine. It is possible that the TNFα polymorphism associated with migraine is in linkage disequilibrium with other functional polymorphisms that influence migraine risk. Moreover, there are significant differences among the allele frequencies of TNF gene variants among populations from different ethnic groups.

Methods.—In a case‐control study, including 439 migraine patients and 382 controls, we examined the association between 15 single nucleotide polymorphisms in the coding and promoter regions of LTA and TNFα genes, which are located within the 22 kb around TNF and the risk of migraine. We performed a chromatin immunoprecipitation (ChIP) assay and an electrophoretic mobility shift assay (EMSA) to identify differential protein‐DNA binding of LTA‐294.

Results.—Homozygosity for the LTA‐294C allele was significantly associated with an increased risk of migraine compared with CT/TT carriers (corrected P= .005, odds ratio [OR]= 1.7, 95% confidence interval [CI] 1.3‐2.3). Haplotype TGAAC was found to be significantly associated with a protective effect against migraine (P= .0005, Bonferroni corrected P= .003, OR = 0.7, 95% CI 0.5‐0.8). There was no differential protein‐DNA binding pattern in both EMSA and ChIP assays.

Conclusions.—We found that the LTA haplotypes were associated with migraine among Koreans and that the best marker for this is the LTA‐294 T/C polymorphism. Our results indicate that these associations should be defined in the context of the involvement of other genetically linked region, such as human leukocyte antigen (HLA) loci.
Disability in Chronic Migraine With Medication Overuse: Treatment Effects at 3 Years
Authors: Andrasik Frank , Grazzi Licia , Usai Susanna , D'Amico Domenico , Kass Steven , Bussone Gennaro
Published: June 2007

Objectives.—To determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated 3 years previously.

Background.—Patients who have chronic migraine accompanied by medication overuse are particularly difficult to treat. Investigations are limited in number, few have included follow‐up beyond 6 months, and almost none have examined whether treatment leads to concurrent improvements in disability and functional impairment. In a prior report, we described the clinical course of 84 such patients followed for 1 full year after treatment.

Methods.—These same 84 patients were followed for 2 additional years to assess longer term maintenance of effects, using measurement procedures identical to those in the original investigation.

Results.—Both endpoint and completer analyses revealed significant improvement on all measures studied—headache days per month, analgesic consumption, and MIDAS scores (Total, Headache Frequency, and Headache Intensity)—with some loss of benefits over time for the pain indices. MIDAS total scores, however, were lower at 36 months than at 6 months. Comparisons of those who completed the 3‐year follow‐up to those who did not revealed few differences at baseline. All of this suggests attrition did not have a bearing on outcome.

Discussion.—High levels of maintenance were revealed at 3 years. Even though reports of pain revealed some lessening of effects, this was not accompanied by reports of deterioration in functioning. This suggests that patients have learned to adapt and adjust to headaches in their daily lives.
A Double‐Blind, Dose Comparison Study of Topiramate for Prophylaxis of Basilar‐Type Migraine in Children: A Pilot Study
Authors: Lewis Donald , Paradiso Erika
Published: June 2007

Background.— Basilar‐type migraine (BM) is the most common migraine “variant,” representing 3‐19% of migraine in children.BMis characterized by attacks of dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by migraine headache.

Objective.— The objective of this study is to assess the efficacy and safety of topiramate for prophylaxis of BM in children and adolescents (6‐18 years).

Design.— Outpatient, double‐blind, parallel‐group, dose comparison study with 2 phases: prerandomization (screening/washout and 4‐week prospective baseline) and 12‐week double blind (titration and maintenance).

Methods.— Following consent and assent, subjects with BMs, as defined by the International Classification of Headache Disorders (second edition), and ≥4 migraines/month were randomized to receive either 25 mg per day or 100 mg per day of topiramate in a 1 : 1 ratio.

Results.— Fourteen children (4 boys, 10 girls) completed the double‐blind phase (7 in the 25‐mg group and 7 in the 100‐mg group). During the prospective baseline, the mean headache frequency of the combined group “all migraines” per month was 4.5/month (25 mg) and 4.8/month (100 mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg) and average mean pain (5‐point faces scale) was 3.3 for both (25 mg 100 mg).

The reduction in median monthly migraine rate during the double‐blind treatment phase relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25‐mg and 100‐mg topiramate‐treated groups, respectively (P < .001).

The reduction in median monthly BM rate during the double‐blind treatment phase relative to baseline was 2.5 (74.24%) and 2.3 (82.8%) for the 25‐mg and 100‐mg topiramate‐treated groups, respectively. The overall reduction in BM attacks reduced from 2.84/month to 0.59/month (79.2%; P < .0042).

Overall, 86% of patients responded with a greater than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg). There was no significant difference in migraine severity between the 2 groups. Parent Global Assessment was “very much” or “much improved” in 6 of 7 (25 mg) and 3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas© reduced from moderate to no disability (P < .001). There were no serious adverse events.

Conclusions.— Preventive therapy with topiramate resulted in reducing the overall migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg doses relative to the historical baseline and prospective baseline periods. The 2 treatment groups resulted in comparable outcomes.
Supraorbital Nerve Electric Stimulation for the Treatment of Intractable Chronic Cluster Headache: A Case Report
Authors: Narouze Samer N. , Kapural Leonardo
Published: June 2007

We describe a patient with intractable chronic cluster headache that responded well to supraorbital nerve electric stimulation.
Vigabatrin and Epilepsy: Lessons Learned
Authors: Wild John M. , Ahn Hyo‐sook , Baulac Michel , Bursztyn Joseph , Chiron Catherine , Gandolfo Enrico , Safran Avinoam B. , Schiefer Ulrich , Perucca Emilio
Published: June 2007

Summary:  Purpose: The risk factors for visual field loss attributable to vigabatrin (VAVFL) are equivocal. This multinational, prospective, observational study aimed to clarify the principal/major factors for VAVFL.

Methods: Interim analysis of three groups with refractory partial epilepsy, stratified by age (8–12 years; >12 years) and exposure to vigabatrin (VGB). Group I comprised participants treated with VGB for ≥6 months, Group II participants previously treated with VGB for ≥6 months who had discontinued the drug for ≥6 months and Group III those never treated with VGB. Perimetry was undertaken at least every six months, for up to 36 months; results were evaluated masked to drug exposure.

Results: Based upon 563 participants in the locked data set, 432 yielded one or more Conclusive visual field examinations. For Group I, the frequency of VAVFL at the last Conclusive examination was 10/32 (31.2%) for those aged 8–12 years and 52/125 (41.6%) for those aged >12 years. For Group II, the proportions were 4/39 (10.3%) and 31/129 (24.0%). No cases resembling VAVFL manifested in Group III. VAVFL was associated with duration of VGB therapy (Odds ratio [OR] 14.2; 95% CI 5.0 to 40.5); mean dose of VGB (OR 8.5; 95% CI 2.2 to 33.2); and male gender (OR 2.1; 95% CI 1.2 to 3.7). VAVFL was more common with static than kinetic perimetry (OR 2.3, 95% CI 1.3 to 4.2).

Conclusions: The therapeutic benefit of VGB is counteracted by the progressive accrual of the risk of VAVFL with continued exposure and with increase in mean dose.
Subepidermal Moisture Predicts Erythema and Stage 1 Pressure Ulcers in Nursing Home Residents: A Pilot Study
Authors: Bates‐Jensen Barbara M. , McCreath Heather E. , Kono Ayumi , Apeles Neil Christopher R. , Alessi Cathy
Published: June 2007

OBJECTIVES: To examine the relationship between a measure of subepidermal moisture (SEM) and visual skin assessment (VSA) of erythema and Stage 1 pressure ulcers (PUs) performed a week later in nursing home (NH) residents.

DESIGN: Descriptive, cohort study.

SETTING: Two NHs.

PARTICIPANTS: Thirty‐five residents.

METHODS: Concurrent VSAs and SEM readings were obtained at the sacrum, right and left trochanters, buttocks, and ischial tuberosities weekly for 52 weeks. SEM was measured using a handheld dermal phase meter, with higher readings indicating greater SEM (range 0–999 dermal phase units [DPUs]). VSA was rated as normal, erythema/Stage 1 PU, or Stage 2+PU. SEM was modeled as a predictor of VSA of erythema and PUs 1 week later (controlling for clustering), with concurrent moisture, Braden Scale PU risk status, anatomic site, and ethnicity as covariates.

RESULTS: Participants had a mean age of 84.7, 83% were female, and 80% were non‐Hispanic white. SEM measures were lowest for normal skin (97±122 DPU), higher for erythema/Stage 1 PUs (192±188 DPU), and highest for Stage 2+PUs (569±320 DPU) across all sites (all P<.001). SEM was responsive to changes in VSA, and higher SEM predicted greater likelihood of erythema/Stage 1 PU the next week (odds ratio=1.26 for every 100‐DPU increase in SEM, P=.04).

CONCLUSION: SEM measures are associated with concurrent erythema and PUs and future (1 week later) development of erythema/Stage 1 PUs. SEM may assist in predicting early PU damage, allowing for earlier intervention to prevent skin damage.
Blood group genotyping in Germany
Authors: Flegel Willy A.
Published: June 2007

BACKGROUND: Molecular methods for blood group genotyping became available more than 10 years ago as one major aspect of immunogenetics. Since then, the clinical applications have been expanded and refined. Their implementation varies considerably among different health‐care systems, notably between North America and Europe.

STUDY DESIGN: This summary is based on studies published mostly during the last 3 years and on workshop reports from the German and Swiss transfusion societies. It represents an edited transcript of the author's presentation given at the Workshop on Molecular Methods in Immunohematology organized by the Food and Drug Administration (FDA) in Bethesda on September 25, 2006.

RESULTS: Current applications of blood group genotyping in Germany, Switzerland, and Austria are detailed: weak D testing in patients and pregnant women; blood group genotyping in perinatal care, in patients who received a transfusion, and in patients with immunohematologic problems; RHD genotyping in donors for DEL and D+/– chimera; and RHD zygosity testing.

CONCLUSION: Since around 2000, molecular tests for blood groups have been widely offered as a routine service. Many samples are shipped to reference laboratories in the German‐speaking countries with the specific request for such testing. The advent of Conformité Européenne (CE)‐labeled test kits renders it technically and legally possible, within the specifications of the CE‐certification process for in vitro diagnostic devices in the European Union, to replace several blood group serology tasks by genotyping.
Molecular genetic blood group typing by the use of PCR‐SSP technique
Authors: Prager Martina
Published: June 2007

BACKGROUND:DNA‐based methods are useful for enhancing immunohematology typings. Ready‐to‐use Conformité Européenne (CE)‐marked test kits based on polymerase chain reaction with sequence‐specific priming (PCR‐SSP) have been developed, which enable the examination of weak, unexpected, or unclear serologic findings.

DEVELOPMENT AND VALIDATION:Primers were designed according to established mutation databases. Proficiency testing for CE marking was performed in accordance with Directive 98/79EC of the European Parliament and of the Council of October 27, 1998 on in vitro diagnostic medical devices using pretyped in‐house and external samples.

INTENDED USE:BAGene PCR‐SSP kits are in vitro diagnostic devices. Genotyping ofABOandRHD/RHCEas well asHPAandKEL,JK, andFYspecificities has to be performed after the conclusion of the serologic determination.

APPLICATION:Ready‐to‐use PCR‐SSP typing kits allow the determination of common, rare, or weak alleles of the ABO blood group, Rhesus, and Kell/Kidd/Duffy systems as well as alleles of the human platelet antigens.

RESULTS:The investigations showed clear‐cut results in accordance with serology or molecular genetic pretyping.

CONCLUSION:PCR‐SSP is a helpful supplementary technique for resolving most of the common problems caused by discrepant or doubtful serologic results, and it is an easy‐to‐handle robust method. Questionable cases in donor, recipient, and patient typing can be examined with acceptable cost.
Technical Considerations for Dominant Frequency Analysis
Authors: NG JASON , KADISH ALAN H. , GOLDBERGER JEFFREY J.
Published: June 2007

Introduction: Dominant frequency (DF) analysis of atrial electrograms has been used to characterize atrial fibrillation (AF). The aim of this study was to explore technical issues that may affect the estimation of local activation rate during AF using DF analysis.

Methods and Results: Epicardial atrial electrograms recorded during AF from 10 dogs were used to evaluate the effects of unipolar versus bipolar recordings, bipolar electrode spacing, postrecording processing, far field ventricular depolarizations, ventricular template subtraction, and signal duration on DF analysis. Simulated electrograms were used to evaluate the effect of far field ventricular depolarizations and signal‐to‐noise ratio. DFs were compared with activation rates obtained by manual marking and the reproducibility of the DFs was evaluated. Bipolar electrograms were found to be preferable to unipolar electrograms. Preprocessing was a necessary step for bipolar signals, but also aided analysis of unipolar recordings. Ventricular far field depolarizations significantly affected DFs. Ventricular template subtraction helped DF analysis in signals with both minimal and significant ventricular components. A recording duration above 2 seconds was required for reliable DF measurements. Signal‐to‐noise ratios below 13 dB could also affect DF, particularly for signals with significant amplitude and frequency variation.

Conclusions: Various factors affect DF analysis. Proper interpretation of DF analysis requires careful evaluation of the AF signals and robust processing techniques.
Ventricular Tachycardia With Participation of the Left Bundle‐Purkinje System in Patients With Structural Heart Disease: Identification of Slow Conduction During Sinus Rhythm
Authors: REITHMANN CHRISTOPHER , HAHNEFELD ANTON , REMP THOMAS , STEINBECK GERHARD
Published: June 2007

Introduction: Idiopathic left ventricular tachycardia (VT) originating from the left posterior fascicle can be eliminated by ablation at sites with abnormal diastolic potentials (DPs) during sinus rhythm. We investigated whether such DPs can also be recorded in patients with structural heart disease and VT involving the left bundle‐Purkinje system.

Methods and Results: Eight patients (mean age 67 ± 11 years) with nonischemic cardiomyopathy (n = 5) or prior myocardial infarction (n = 3) presented with VT involving the left bundle‐Purkinje system (cycle length 376 ± 45 ms). Three types of VT were observed: macroreentrant VT with participation of both left bundle fascicles in three patients, fascicular VT involving the left posterior fascicle in two patients, and scar‐related VT with Purkinje fibers as part of the reentrant circuit in three patients. In all patients, abnormal isolated DPs of low amplitude with a QRS—earliest DP interval of 374 ± 86 ms were found during sinus rhythm in the mid‐ or inferior left ventricular septum in areas with Purkinje potentials. The abnormal DPs during sinus rhythm coincided or were in proximity to DPs during the VT in six patients. VT ablation targeting the sites with the earliest abnormal DPs during sinus eliminated the VT in 7 of 8 patients with freedom from VT recurrence in six patients during the follow‐up of 11 ± 5 months.

Conclusions: Isolated DPs during sinus rhythm were found in proximity to the posterior Purkinje network in patients with VT involving the left bundle‐Purkinje system associated with heart disease and can be used to guide successful catheter ablation.
Hybrid Epicardial and Endocardial Ablation of Persistent or Permanent Atrial Fibrillation: A New Approach for Difficult Cases
Authors: PAK HUI‐NAM , HWANG CHUN , LIM HONG EUY , KIM JIN SEOK , KIM YOUNG‐HOON
Published: June 2007

Background: Although percutaneous epicardial catheter ablation (PECA) has been used for the management of epicardial ventricular tachycardia, the use of PECA for atrial fibrillation (AF) has not yet been reported.

Objective: To evaluate the efficacy and feasibility of a hybrid PECA and endocardial ablation for AF.

Methods: We performed PECA for AF in five patients (48.6 ± 8.1 years old, all male, four redo ablation procedures of persistent AF with a risk of pulmonary vein (PV) stenosis, one de novo ablation of permanent [AF]) after an endocardial AF ablation guided by PV potentials and 3D mapping (NavX). Utilizing an open irrigation tip catheter, a left atrial (LA) linear ablation from the roof to the perimitral isthmus or localized ablation at the junction between the LA appendage and left‐sided PVs or ligament of Marshall (LOM) was performed.

Results: PECA of AF was successful in all patients with an ablation time of <15 minutes. The left‐sided PV potentials were eliminated by PECA in all patients. Bidirectional block of the perimitral line was achieved in two of two patients and a left inferior PV tachycardia with conduction block to the LA was observed during the ablation in the area of the LOM in one patient. A hemopericardium developed in one patient, but was controlled successfully. During 8.0 ± 6.3 months of follow‐up, all patients have remained in sinus rhythm (four patients without antiarrhythmic drugs).

Conclusion: A hybrid PECA of AF is feasible and effective in patients with redo‐AF ablation procedures and at risk for left‐sided PV stenosis or who are resistant to endocardial linear ablation.
Knockin Animal Models of Inherited Arrhythmogenic Diseases: What Have We Learned From Them?
Authors: NILLES KATHY M , LONDON BARRY
Published: June 2007

Mouse models are becoming an increasingly accepted method of studying human diseases. Knockin and knockout techniques have several advantages over traditional transgenic overexpression, and the versatility of the knockin mouse allows the study of both gain of function mutations through targeted mutagenesis, as well as the replacement of one gene by another functional gene. Here, we will review the methods available to generate knockin mice; provide an overview of the techniques used to study electrophysiology in the mice at the cellular, organ, and whole animal level; and highlight knockin mice that have implications for inherited arrhythmias. Specifically, we will focus on models that used knockin mice to clarify gene expression, identify similarities and differences between related genes, and model human arrhythmia syndromes. Our goal is to provide the reader with a general understanding of studies done on knockin mouse models of inherited arrhythmias as well as ideas for future directions.
Causal Assessment in Small‐N Policy Studies
Authors: Steinberg Paul F.
Published: June 2007

The identification of cause‐and‐effect relationships plays an indispensable role in policy research, both for applied problem solving and for building theories of policy processes. Historical process tracing has emerged as a promising method for revealing causal mechanisms at a level of precision unattainable through statistical techniques. Yet historical analyses often produce dauntingly complex causal explanations, with numerous factors emerging as necessary but insufficient causes of an outcome. This article describes an approach that renders complex causal narratives more analytically tractable by establishing measurement criteria for ranking the relative importance of component causes. By focusing on subjectively useful measurement attributes, the approach is well suited to the policy sciences' unique combination of explicitly normative aspirations and a commitment to the systematic assessment of causal claims.
Disaster Management in the United States: Examining Key Political and Policy Challenges
Authors: Gerber Brian J.
Published: June 2007

The failures associated with the Hurricane Katrina response call attention to the challenges of, and the need to better understand disaster management practices in the United States. This article reviews several recent contributions to the field of disaster research and considers four key issues: the concept of disaster vulnerability, how individuals respond to hazard risks, challenges associated with effective hazard mitigation, and the idea of policy learning in the area of disasters. Beyond a review of these aspects of disaster management, future directions in disaster research is discussed.