bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with Physician Interventions to Address Adolescent Smoking
Authors: Sims Tammy H. , Meurer John R. , Sims Mario , Layde Peter M.
Published: May 2004

Objective. To determine the percent of adolescent Medicaid patients with medical record documentation about tobacco use status and cessation assistance; and factors associated with providers documenting and intervening with adolescent smokers.

Data Source. Secondary analysis of data collected in 1999 from medical records of Wisconsin Medicaid health maintenance organization (HMO) recipients 11 to 21 years old.

Study Design. Random reviews and data collection were related to visits from January 1997 to January 1999. Data collected included patient demographics, provider type, number of visits, and whether smoking status and cessation interventions were documented.

Data Extraction Methods. Medical charts were reviewed and a database was created using a data abstraction tool developed and approved by a committee to address tobacco use in Medicaid managed care participants.

Principal Findings. Among adolescents seen by a physician from 1997 to 1999, tobacco use status was documented in 55 percent of patient charts. Most often tobacco use status was documented on history and physical or prenatal forms. Of identified adolescent smokers, 50 percent were advised to quit, 42 percent assisted, and 16 percent followed for smoking cessation. Pregnant patients were more likely to have tobacco use documented than nonpregnant patients (OR=10.8, 95 percent CI=4.9 to 24). The odds of documentation increased 21 percent for every one‐year increase in patient age.

Conclusions. Providers miss opportunities to intervene with adolescents who may be using tobacco. Medical record prompts, similar to the tobacco use question on prenatal forms and the tobacco use vital sign stamp, are essential for reminding providers to consistently document and address tobacco use among adolescents.
The Lifetime Distribution of Health Care Costs
Authors: Alemayehu Berhanu , Warner Kenneth E.
Published: May 2004

Objective. To estimate the magnitude and age distribution of lifetime health care expenditures.

Data Sources. Claims data on 3.75 million Blue Cross Blue Shield of Michigan members, and data from the Medicare Current Beneficiary Survey, the Medical Expenditure Panel Survey, the Michigan Mortality Database, and Michigan nursing home patient counts.

Data Collection. Data were aggregated and summarized in year 2000 dollars by service, age, and gender.

Study Design. We use life table models to simulate a typical lifetime's distribution of expenditures, employing cross‐sectional data on age‐ and sex‐specific health care costs and the mortality experience of the population. We determine remaining lifetime expenditures at each age for all initial members of a birth cohort. Separately, we calculate remaining expenditures for survivors at all ages. Using cross‐sectional data, the analysis holds disease incidence, medical technology, and health care prices constant, thus permitting an exclusive focus on the role of age in health care costs.

Principal Findings. Per capita lifetime expenditure is $316,600, a third higher for females ($361,200) than males ($268,700). Two‐fifths of this difference owes to women's longer life expectancy. Nearly one‐third of lifetime expenditures is incurred during middle age, and nearly half during the senior years. For survivors to age 85, more than one‐third of their lifetime expenditures will accrue in their remaining years.

Conclusions. Given the essential demographic phenomenon of our time, the rapid aging of the population, our findings lend increased urgency to understanding and addressing the interaction between aging and health care spending.
Determining Personal Care Consumers' Preferences for a Consumer‐Directed Cash and Counseling Option: Survey Results from Arkansas, Florida, New Jersey, and New York Elders and Adults with Physical Disabilities
Authors: Mahoney Kevin J. , Simon‐Rusinowitz Lori , Loughlin Dawn M. , Desmond Sharon M. , Squillace Marie R.
Published: May 2004

Objective. To assess Medicaid consumers' interest in a consumer‐directed cash option for personal care and other services, in lieu of agency‐delivered services.

Data Sources/Study Setting. Telephone survey data were collected from four states from April to November 1997. Postsurvey focus groups were conducted in four states in 1998. Early implementation experiences are drawn from three states from 1999 to 2002.

Study Design. Participants (N=2,140) were selected for a structured telephone survey interview from a probability‐sampling frame of current Medicaid consumers in Arkansas, Florida, New Jersey, and New York. Key variables include interest in the cash option, demographic and background characteristics of consumers, as well as previous experience and training needed. Postsurvey focus groups were also conducted with current Medicaid consumers.

Data Collection/Extraction Methods. Interviewers read the telephone survey from computer screens and entered responses directly into the database of the Macintosh Computer Assisted Telephone Interview software. Data were analyzed using SPSS 10.0 (http://www.spss.com) for Windows.

Principal Findings. Cash option interest was positively associated with experience hiring and supervising workers, more severe levels of disability, having a live‐in caregiver, living in Florida, and minority status. Age of the client was also a significant factor.

Conclusions. There is significant interest in the cash option, although interest varies among subgroups of consumers. Future research should continue to evaluate interest in the cash option among different groups of consumers, as well as actual experience with the option when the Cash and Counseling Demonstration and Evaluation (CCDE) evaluation findings are completed.
Noncontact Mapping of the Left Ventricle:
Authors: THIAGALINGAM ARAVINDA , WALLACE ELISABETH M. , BOYD ANITA C. , EIPPER VICKI E. , CAMPBELL CRAIG R. , BYTH KAREN , ROSS DAVID L. , KOVOOR PRAMESH
Published: May 2004

It is not clear whether the noncontact electrograms obtained using the EnSite system in the left ventricle resemble most closely endocardial, intramural, or epicardial contact electrograms or a summation of transmural electrograms. This study compared unipolar virtual electrograms from the EnSite system with unipolar contact electrograms from transmural plunge needle electrodes using a 256‐channel mapping system. The study also evaluated the effects of differing activation sites (endocardial, intramural, or epicardial). A grid of 50–60 plunge needles was positioned in the left ventricles of eight male sheep. Each needle had four electrodes to record from the endocardium, two intramural sites, and the epicardium. Correlations between contact and noncontact electrograms were calculated on 32,242 electrograms. Noncontact electrograms correlated equally well in morphology and accuracy of timing with endocardial (0.88 ± 0.15), intramural (0.87 ± 0.15), epicardial (0.88 ± 0.15), and transmural summation contact electrograms (0.89 ± 0.14) during sinus rhythm, endocardial pacing, and epicardial pacing. There was a nonlinear relationship between noncontact electrogram accuracy as measured by correlation with the contact electrogram and distance from the multielectrode array (MEA): beyond 40 mm accuracy decreased rapidly. The accuracy of noncontact electrograms also decreased with increasing distance from the equator of the MEA. Virtual electrograms from noncontact mapping of normal left ventricles probably represent a summation of transmural activation. Noncontact mapping has similar accuracy with either endocardial or epicardial sites of origin of electrical activity provided the MEA is within 40 mm of the recording site. (PACE 2004; 27:570–578)
A Comparison of Biventricular and Conventional Transvenous Defibrillation:
Authors: MOCANU DANIEL , KETTENBACH JOACHIM , SWEENEY MICHAEL O. , KIKINIS RON , KENKNIGHT BRUCE H. , EISENBERG SOLOMON R.
Published: May 2004

Conventional transvenous defibrillation is performed with an ICD using a dual current pathway. The defibrillation energy is delivered from the RV electrode to the superior vena cava (SVC) electrode and the metallic case (CAN) of the ICD. Biventricular defibrillation uses an additional electrode placed in the LV free wall with sequential shocks to create an additional current vector. Clinical studies of biventricular defibrillation have reported a 45% reduction in mean defibrillation threshold (DFT) energy. The aim of the study was to use computational methods to examine the biventricular defibrillation fields together with their corresponding DFTs in a variety of patient derived models and to compare them to simulations of conventional defibrillation. A library of thoracic models derived from nine patients was used to solve for electric field distributions. The defibrillation waveform consisted of a LV → SVC + CAN monophasic shock followed by a biphasic shock delivered via the RV → SVC + CAN electrodes. When the initial voltage of the two shocks is the same, the simulations show that the biventricular configuration reduces the mean DFT by 46% (3.5 ± 1.3 vs 5.5 ± 2.7 J, P = 0.005). When the leading edge of the biphasic shock is equal to the trailing edge of the monophasic shock, there is no statistically significant difference in the mean DFT (4.9 ± 1.9 vs 5.5 ± 2.7 J, P > 0.05) with the DFT decreasing in some patients and increasing in others. These results suggest that patient‐specific computational models may be able to identify those patients who would most benefit from a biventricular configuration. (PACE 2004; 27:586–593)
Pacemaker Syndrome in the Young:
Authors: HORENSTEIN M. SILVANA , KARPAWICH PETER P.
Published: May 2004

The aim of this study was to determine if single chamber rate responsive ventricular pacing (VVIR) predisposes growing children to develop pacemaker syndrome (PS), and if so, what are determining factors and/or clinically useful predictors. PS is a constellation of symptoms that result from the lack of consistent AV sequential filling due to atrial contraction against closed AV valves. PS has not been commonly reported in the young. Data from all patients with pacemakers with congenital complete atrioventricular block (CAVB) with normal anatomy, and those with congenital heart disease (CHD), and surgically acquired CAVB were reviewed. Inclusion criteria were normal ventricular function by cardiac ultrasound and 100% VVIR pacing. Of 89 patients with VVIR pacemaker implants, 33 met these criteria. Of these, 19 developed PS. For statistical analysis, chi‐square and independent samples t‐test was used with significance defined at P ≤ 0.05. No consistent association was found between cardiac anatomy, type of CAVB, or age at implant with development of PS. However, PS did correlate with duration of pacing (P = 0.02). The exercise stress test showed significant differences between 100% VVIR‐paced patients with and without PS, in terms of work rate (P = 0.002) and measured oxygen consumption (P = 0.01). This study shows that PS appears to be a time related event in younger children with normal ventricular function who are 100% ventricular paced. Thus, this supports VVIR pacing as an adequate and cost‐effective initial therapy for symptomatic bradycardia due to CAVB. (PACE 2004; 27:600–605)
Sinus and Paced P Wave Duration and Dispersion as Predictors of Atrial Fibrillation After Pacemaker Implantation in Patients with Isolated Sick Sinus Syndrome
Authors: KRISTENSEN LENE , NIELSEN JENS COSEDIS , MORTENSEN PETER THOMAS , CHRISTENSEN PER DAHL , VESTERLUND THOMAS , PEDERSEN ANDERS KIRSTEIN , ANDERSEN HENNING RUD
Published: May 2004

The aim of this study was to prospectively evaluate the sinus and the paced P wave duration and dispersion as predictors of AF after pacemaker implantation in patients with isolated sick sinus syndrome (SSS). The study included 109 (69 women, mean age 72 ± 11 years) patients with SSS, 59 with bradycardia‐tachycardia syndrome (BTS). A 12‐lead ECG was recorded before pacemaker implantation and during high right atrial and septal right atrial pacing at 70 and 100 beats/min. The ECGs were scanned into a computer and analyzed on screen. The patients were treated with AAIR (n = 52) or DDDR pacing. The P wave duration was measured in each lead and mean P wave duration and P wave dispersion were calculated for each ECG. AF during follow‐up was defined as: AF in an ECG at or between follow‐up visits; an atrial high rate episode with a rate of ≥220 beats/min for ≥5 minutes, atrial sensing with a rate of ≥170 beats/min in ≥5% of total counted beats, mode‐switching in ≥5% of total time recorded, or a mode switching episode of ≥5 minutes recorded by the pacemaker telemetry. The ECG parameters were correlated to AF during follow‐up. Mean follow‐up was 1.5 ± 0.9 years. None of the ECG parameters differed between patients with AF and patients without AF during follow‐up, nor was there any difference between groups after correction for BTS and age. BTS was the strongest predictor of AF during follow‐up (P < 0.001). P wave duration and dispersion measured before and during pacemaker implantation were not predictive of AF after pacemaker implantation in patients with isolated SSS. (PACE 2004; 27:606–614)
Detection of Acute Myocardial Ischemia During Percutaneous Transluminal Coronary Angioplasty by Endocardial Acceleration
Authors: THERES HEINZ P. , KAISER DANIEL R. , NELSON SHANNON D. , GLOS MARTIN , LEUTHOLD THOMAS , BAUMANN GERT , SOWELAM SAMEH , SHELDON TODD J. , STYLOS LEE
Published: May 2004

The first heart sound is generated by vibrations from the myocardium during isovolumic contraction. Peak endocardial acceleration (PEA) has been used previously to measure these vibrations in humans and correlates with myocardial contractility during inotropic interventions. It is unknown if changes in PEA can be used to characterize a reduction in contractility during ischemic episodes. This study was designed to evaluate the use of an endocardial accelerometer for the detection of acute myocardial ischemia. Thirteen patients undergoing routine percutaneous transluminal coronary angioplasty (PTCA) consented to having a single‐axis, lead‐based accelerometer positioned in the right ventricular apex. PEA was defined as the maximum peak‐to‐peak amplitude during a window 50 ms before to 200 ms following the peak R wave. Time of endocardial acceleration (TEA) was defined as the time from the peak R wave to the maximum accelerometer signal within this window. To obtain a more robust estimate of the strength of vibrations, a 100‐beat template of the accelerometer signal was constructed at baseline and applied as a matched filter during ischemia. The peak magnitude of the filtered endocardial accelerometer signal (Max Filtered EA) was used as an index of signal intensity. Median baseline PEA, TEA, and Max Filtered EA were 0.91 ± 0.35 g, 75.2 ± 16.2 ms, and 0.40 ± 0.20 g, respectively. PEA and Max Filtered EA significantly decreased by 7% during ischemia (0.91 to 0.85 g and 0.40 to 0.37 g, both P < 0.05, respectively). TEA did not significantly change from baseline (77.0 ms, P = ns). The results of this study suggest that acute ischemia can be detected with an endocardial accelerometer in humans. (PACE 2004; 27:621–625)
Performance of Left Ventricular Versus Biventricular Pacing in Chronic Heart Failure Assessed by Stress Echocardiography
Authors: RIEDLBAUCHOVÁ LUCIE , FRÍDL PETR , KAUTZNER JOSEF , PEICHL PETR
Published: May 2004

Acute hemodynamic studies suggest that resynchronization therapy using single‐site left ventricular pacing (LVP) is equivalent to biventricular pacing (BIVP). The aim of this study was to assess the performance of LVP versus BIVP during exercise by means of stress echocardiography. A total of 28 patients (25 men and 3 women, mean age 60.9 ± 8 years) with advanced chronic heart failure and impaired ventricular conduction (QRS > 150 ms) were studied. Patients were randomly allocated to either BIVP or LVP mode with a crossover on the next day and cardiac output was estimated at rest and during each stage of bicycle ergometry in supine position by means of velocity time integral formula. Maximum exercise level was comparable for both pacing modes (up to 100 W) and no significant differences were revealed either in heart rate or in blood pressure at rest and during any step of exercise. LVP was associated with significantly higher cardiac output at rest (3.2 ± 0.5 vs 2.8 ± 0.6 l/min, P < 0.01) and during low level exercise (4.4 ± 0.8 vs 3.9 ± 0.8 l/min at 25 W, P < 0.05) as compared with BIVP. There was a trend towards higher cardiac output for LVP even at higher levels of exercise. These effects were predominantly confined to patients with idiopathic dilated cardiomyopathy. It is concluded that cardiac resynchronization therapy using single‐site LVP results in better hemodynamic response as compared with BIVP, both at rest and during physical exercise. (PACE 2004; 27:626–631)
Abnormal Right Atrial Electrograms Predict the Transition to Chronic Atrial Fibrillation in Paced Patients with Sick Sinus Syndrome
Authors: MIYAMOTO KOJI , NAKAO KOJIRO , SETO SHINJI , SHIBATA RIYAKO , DOI YOSHIYUKI , FUKAE SATOKI , MATSUO KIYOTAKA , KOMIYA NORIHIRO , YANO KATSUSUKE
Published: May 2004

Although pacing therapy for sick sinus syndrome (SSS) is established, the risk of developing chronic atrial fibrillation (CAF) makes pacing therapy infeasible in some patients. We evaluated whether electrophysiological characteristics of atrial muscle can serve as predictors of the transition to CAF after pacemaker implantation in patients with SSS. Eighty‐nine patients with SSS underwent electrophysiological study before pacing therapy. Catheter mapping of 12 right atrial sites was performed during sinus rhythm during electrophysiological. An abnormal atrial electrogram was defined as having a duration of 100 ms or longer, or eight or more fragmented deflections, or both. Right atrial extrastimulation was also performed for atrial vulnerability. After electrophysiological study, all patients underwent pacemaker implantation and were followed up. During the follow‐up period of 85 ± 50 months, development of CAF was observed in 12 patients (group A). The remaining 77 patients remained in sinus rhythm (group B). There were significantly more abnormal atrial electrograms in group A than group B (2.7 ± 2.3 vs 0.8 ± 1.2; P < 0.001). The distribution of abnormal atrial electrograms was also greater in group A; patients in group A had more abnormal atrial electrograms than patients in group B in both the high and middle right atrium (P < 0.005 and P < 0.01, respectively). Kaplan‐Meier analysis showed that almost 50% of the paced patients with abnormal atrial electrograms (n = 42) developed CAF (P < 0.005). Our data suggest that the existence of abnormal atrial electrograms is predictive of the transition to CAF in paced patients with SSS. (PACE 2004; 27:644–650)
Pacing in High Field Cardiac Magnetic Resonance Imaging:
Authors: NAHRENDORF MATTHIAS , HILLER KARL‐HEINZ , HU KAI , ZEIJLEMAKER VOLKERT , GRISWOLD MARK , BAUER WOLFGANG R.
Published: May 2004

Currently, cardiac MRI is contraindicated in patients with an implanted pacemaker or ICD due to safety hazards. However, MRI is promising to play a key role in cardiac diagnostics in near future. This study examined a rat with an implanted pacemaker pacing at a rate of 460/min with high field cardiac MRI. This study showed that pacing during cardiac imaging at 7 Tesla was possible. The pacemaker program was not disturbed by the high field or the strong gradients (maximum dB/dt 400 mT/s). The only noticeable effect on the MRI signal was a signal void of 2 cm around the device. (PACE 2004; 27:671–674)
Ventricular Fibrillation Without Overt Cardiomyopathy as First Presentation of Organic Cation Transporter 2‐Deficiency in Adolescence
Authors: RIJLAARSDAM RENSKE S. , SPRONSEN FRANCJAN J. VAN , BINK‐BOELKENS MARGREET TH.E. , REIJNGOUD DIRK‐JAN , WANDERS RONALD J.A. , NIEZEN‐KONING KLARY E. , VAN DER SLUIJS FJODOR H. , DORLAND BERT , BEAUFORT‐KROL GERTIE C.M.
Published: May 2004

This case report describes ventricular fibrillation without overt cardiomyopathy as the presenting symptom of primary carnitine deficiency due to organic cation transporter 2 (OCTN2)‐deficiency in a 15‐year‐old girl. Normally this disease presents early in life with hypoketotic hypoglycemia, muscle weakness, and/or cardiomyopathy. The patient fully recovered after carnitine suppletion. Recognition of this disease is important because its treatment is easy and effective. (PACE 2004; 27:675–676)
Inappropriate Therapy From a Defibrillator Complicating Transcoronary Ablation of Septal Hypertrophy in a Patient with Hypertrophic Obstructive Cardiomyopathy
Authors: SHAH PRASAD , HARRIS LOUISE , HILL ANN , SCHWARTZ LEONARD , CAMERON DOUGLAS
Published: May 2004

This case report describes a patient with obstructive hypertrophic cardiomyopathy who received therapy inappropriately from his implanted defibrillator, subsequent to transcoronary alcohol ablation for septal hypertrophy (TASH). Widening of the intracardiac electrogram postablation resulted in “double counting” of the intrinsic ventricular electrogram by the device and inappropriate tachycardia detection. (PACE 2004; 27:677–680)
Implantation of an Epicardial Dual Chamber ICD Following Unsuccessful Percutaneous Extraction of a Failed Ventricular Shocking Electrode
Authors: ADLAM DAVID , CUBBON RICHARD M. , SKEHAN DOUGLAS
Published: May 2004

This report describes the case of a 22‐year‐old patient presenting with ICD electrode failure where attempted percutaneous electrode extraction was unsuccessful. In view of the patient's young age, an operative approach was considered most appropriate. The failed electrode was surgically extracted and a new epicardial pacing/defibrillator system inserted. (PACE 2004; 27:686–687)
Inappropriate Sensing of Pectoral Myopotentials by an Implantable Cardioverter Defibrillator System
Authors: KARANAM and SREE , JOHN ROY M.
Published: May 2004

A case of inappropriate detection of pectoral myopotentials by an implantable cardioverter defibrillator (ICD) system due to inadvertent reversal of the high voltage pins in the ICD header is reported. Inappropriate high voltage connections can result in malfunction of both sensing and defibrillation functions of some ICDs. (PACE 2004; 27:688–689)
Shock Coil Failure Secondary to External Irradiation in a Patient with Implantable Cardioverter Defibrillator
Authors: JOHN and JOSEPH , KAYE GERALD C.
Published: May 2004

The use of implantable cardioverter defibrillator (ICD) in the management of malignant ventricular arrhythmia is well established. Radiation treatment is common in malignant neoplasms, but the direct effect of irradiation in ICD is largely not well understood. We describe a case where radiation treatment probably led to shock coil failure. (PACE 2004; 27:690–691)
Unsuccessful Rescrewing of a Dislodged Screw‐In Atrial Lead
Authors: ANTONELLI DANTE , FREEDBERG NAHUM ADAM , ROSENFELD TIBERIO
Published: May 2004

We report a case of unsuccessful rescrewing of an atrial lead after its early dislodgment in a 64 years old patient because of entrapped endocardial tissue in the screw‐in system. (PACE 2004; 27:692)
Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression
Authors: Panteli K. , Zagorianakou N. , Bai M. , Katsaraki A. , Agnantis N. J. , Bourantas K.
Published: May 2004

Increased bone marrow angiogenesis estimated as bone marrow microvessel density (MVD), or as serum angiogenic factor levels and/or immunohistochemical expression of these factors in bone marrow biopsy has been demonstrated in a variety of hematological disorders including chronic myeloproliferative diseases (MPDs). The aim of this study was to investigate the MVD in 25 cases of myelofibrosis with myeloid metaplasia (MMM). MVD was estimated by CD34 immunohistochemical expression in bone marrow biopsies. A control group of 27 patients without bone marrow disease, eight cases of polycythemia vera (PV), 41 cases of essential thrombocythemia (ET) and nine cases of chronic myeloid leukemia (CML) were also studied. Moreover, in cases with MMM, MVD was correlated with clinical, laboratory, histological parameters and the outcome of the patients. Our study confirmed a significantly higher degree of angiogenesis in MMM, PV, ET and CML compared with controls (P < 0.001, P = 0.0007, P < 0.001 and P = 0.0008, respectively). Angiogenesis was higher in MMM than PV, ET and CML cases (P < 0.001, P < 0.001 and P = 0.008). Increased angiogenesis was correlated with hypercatabolic symptoms in MMM patients (P = 0.009). No correlation with other clinicopathological parameters or clinical outcome was found. However, definitive conclusions regarding the prognostic value of increased angiogenesis may require additional follow‐up and a larger group of patients.
The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells
Authors: Baśkiewicz‐Masiuk Magdalena , Machaliński Bogusław
Published: May 2004

Objectives:  The STAT5 proteins are activated by many haematological cytokines and growth factors. They regulate cell cycle, apoptosis and proliferation of different cells via the influence on gene transcription. Because STAT5s are constitutively activated in certain haematooncologic diseases, they are suggested to play an important role in leukaemogenesis. However, the real function of these proteins in haematopoietic cell transformation and proliferation is not clear enough. The aim of this study was to evaluate the influence of suppression of STAT5A and STAT5B expression on the clonogenicity and apoptosis of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells.

Material and methods:  Blast cells from 34 newly diagnosed patients with CML and AML were used in our experiments. Antisense oligodeoxynucleotides (ODNs) were applied to block STAT5A and STAT5B at the mRNA level and the RT‐PCR method was used to study STAT5 mRNA expression in the cells after incubation with ODNs. Moreover, Western blot analysis of the STAT5 proteins was performed. The effect of ODN pretreatment on cell clonogenicity in methylocellulose cultures was examined according to the type of oligodeoxynucleotide and the time of exposure. The induction of apoptosis in cells was also estimated by the Annexin V/PI staining and the TUNEL method using flow cytometry.

Results:  Perturbation of STAT5 expression decreased proliferative potential of the CML and the AML blasts as well as enhanced their apoptosis (P < 0.05).

Conclusions:  Our studies showed that the STAT5 proteins may be critical in the regulation of growth and apoptosis of the CML and AML leukaemic cells.
A narrow deletion of 7q is common to HCL, and SMZL, but not CLL
Authors: Andersen Claus Lindbjerg , Gruszka‐Westwood Alicja , Østergaard Mette , Koch Jørn , Jacobsen Elisa , Kjeldsen Eigil , Nielsen Bendt
Published: May 2004

To further characterise the genetic background of the two closely related B‐lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase‐fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13‐31 (19%) and loss of 7q22‐q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unsual for low‐malignant B‐cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)‐markers SHGC‐3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase‐FISH investigation we showed the minimal lost 7q‐region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase‐FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL.
Outcome of allogeneic peripheral blood stem cell transplantation using matched sibling donors in patients with high‐risk hematological diseases
Authors: Sohn Sang Kyun , Kim Dong Hwan , Kim Jong Gwang , Sung Woo Jin , Baek Jin Ho , Lee Nan‐Young , Won Dong Il , Suh Jang‐Soo , Lee Kun Soo , Lee Kyu Bo
Published: May 2004

Although the use of peripheral blood stem cells instead of bone marrow is still a matter of debate in transplantation from HLA‐identical sibling donors, allogeneic peripheral blood stem cell transplantation (PBSCT), with a stronger graft‐versus‐leukemia (GVL) effect, may be preferable as a source of stem cells, especially in the case of advanced hematologic diseases. As such, the current paper reports on the outcomes of 27 consecutive patients with high‐risk hematologic diseases treated with allogeneic PBSCT. The median dose of CD34+, CD3+ cells, and MNC infused was 8.18 × 106/kg (range: 2.78–14.93), 1.50 × 108/kg (range: 0.06–4.25), and 7.17 × 108/kg (range: 0.95–15.85), respectively. The median time taken for the ANC and platelets to reach 500 and 20 000 × 106/μL was 15 (range: 9–25) and 16 d (range: 10–56), respectively. Three patients (11.1%) experienced transplant‐related mortality within 90 d of transplantation, and 15 (62.5%) of 24 evaluated patients developed chronic graft‐versus‐host disease (GVHD; six limited, nine extensive). There was a significant difference in overall survival (OS) between the group with chronic GVHD and the group without chronic GVHD (P = 0.0253). The causes of death included relapse (six cases) and non‐relapse mortality (infection: four cases, chronic GVHD‐related death: three cases). The 4‐yr OS rate and disease‐free survival rate was 43.3 ± 10.9% and 35.8 ± 10.2%, respectively. Accordingly, chronic GVHD was found to have a positive role in patients with high‐risk hematologic diseases that received allogeneic PBSCT.
The C→G transition in the α2‐globin gene of a normal αα‐chromosome is responsible for the Hb G‐Philadelphia variant in Sardinians
Authors: Masala B. , Musino L. , Pirastru M. , Manca L.
Published: May 2004

Sequencing of α‐globin genes of 18 Sardinian heterozygotes for the Hb G‐Philadelphia [α68(E17)Asn→Lys] variant, with four active α genes and circulating level of the variant of about 27%, showed the AAC→AAG change at codon 68 of the α2‐globin gene (αGα/αα). Two heterozygotes with level of about 37% were the carriers of the same mutation on the same α2 gene, and of the α2α1 hybrid gene, because of the 3.7‐kb deletion, in trans (αGα/−α3.7). In Black people, the same C→G mutation occurs on the hybrid gene (−αG3.7), whereas in Caucasians the Lys for Asn change is because of the C→A transversion occurring on the α2 gene of a normal αα arrangement. The identification of the C→G mutation on the normal αα chromosome points to an undescribed genotype for this rather common variant, which is probably because of the high rate of recombination between the duplicated α‐globin genes.
Levels of soluble angiogenin in chronic myeloid malignancies: clinical implications
Authors: Musolino Caterina , Alonci Andrea , Bellomo Giacomo , Loteta Barbara , Quartarone Eugenia , Gangemi Domenica , Massara Elisabetta , Calabrò Luana
Published: May 2004

Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodisplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor‐beta1 (sTGFβ1). Enzyme‐linked immunosorbent assay detected (P < 0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 ± 464.60 pg/mL and 196.00 ± 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 ± 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P < 0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 ± 267.66 pg/mL) and sTGFβ1 (76.69 ±6.08 pg/mL) were higher (P < 0.05) compared with healthy controls (57.93 ± 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGFβ1 or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.
Fatal Evans’ syndrome after matched unrelated donor transplantation for hyper‐IgM syndrome
Authors: Urban Christan , Benesch Martin , Sovinz Petra , Schwinger Wolfgang , Lackner Herwig
Published: May 2004

A 3½‐yr‐old boy underwent matched unrelated stem cell transplantation (SCT) for hyper‐IgM syndrome. He developed acute and chronic skin graft‐vs.‐host disease (GVHD). Ten months following SCT he presented with severe hemolytic anemia and thrombocytopenia (Evans’ syndrome). Treatment included high‐dose steroids, intravenous immunoglobulins, cyclosporine, mycophenolate mofetil, chemotherapeutic agents (cyclophosphamide, vincristine, VP‐16), immunoadsorption, and anti‐CD20 and anti‐CD52 monoclonal antibodies without response. The patient died 16 months after SCT.
The effects of birth weight and postnatal growth patterns on fat depth and plasma leptin concentrations in juvenile and adult pigs
Authors: Poore K. R. , Fowden A. L.
Published: May 2004

Low birth weight is associated with altered adipose tissue deposition and regulation of leptin production. This study determined the effects of naturally occurring variations in birth weight in pigs on postnatal growth patterns, body fat depth and plasma leptin and other hormone concentrations. Low (< 1.47 kg) and high (> 1.53 kg) birth weight piglets were studied at 3 months (juvenile; n= 47) and 12 months of age (young adult; n= 17). At each age, arterial and venous catheters were inserted under general anaesthesia. Plasma leptin, cortisol, glucose, insulin and catecholamine concentrations were determined in basal blood samples. Body fat depth was measured by ultrasound at 12 months of age. Overall, adult fat depth was greater in low compared to high birth weight pigs and increased fat depth was associated with thinness at birth and poor early growth rates. These effects were strongest in females. Fat depth was related to current weight only in males. Compared to high birth weight pigs, plasma leptin concentrations were reduced in low birth weight females at 3 months and in low birth weight males at 12 months of age. This study demonstrates sex‐specific effects of low birth weight on postnatal growth and body fatness and on plasma leptin concentrations in pigs.
Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise
Authors: Crameri Regina M. , Langberg Henning , Magnusson Peter , Jensen Charlotte H. , Schrøder Henrik Daa , Olesen Jens L. , Suetta Charlotte , Teisner Børge , Kjaer Michael
Published: May 2004

No studies to date have reported activation of satellite cells in vivo in human muscle after a single bout of high intensity exercise. In this investigation, eight individuals performed a single bout of high intensity exercise with one leg, the contralateral leg being the control. A significant increase in mononuclear cells staining for the neural cell adhesion molecule (N‐CAM) and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle on days 4 and 8 post exercise. In addition, a significant increase in the concentration of the FA1 protein was determined in intramuscular dialysate samples taken from the vastus lateralis muscle of the exercising leg (day 0: 1.89 ± 0.82 ng ml−1; day 2: 1.68 ± 0.37 ng ml−1; day 4: 3.26 ± 1.29 ng ml−1, P < 0.05 versus basal; day 8: 4.68 ± 2.06 ng ml−1, P < 0.05 versus basal and control). No change was noted in the control leg. Despite this increase in N‐CAM‐ and FA1‐positive mononuclear cells, an increased expression of myogenin and the neonatal isoform of the myosin heavy chain (MHCn) was not observed. Interestingly, myofibre lesions resulting from extensive damage to the proteins within the myofibre, particularly desmin or dystrophin, were not observed, and hence did not appear to induce the expression of either N‐CAM or FA1. We therefore propose that satellite cells can be induced to re‐enter the cell growth cycle after a single bout of unaccustomed high intensity exercise. However, a single bout of exercise is not sufficient for the satellite cell to undergo terminal differentiation.
Functional characterization of a Ca2+‐activated non‐selective cation channel in human atrial cardiomyocytes
Authors: Guinamard Romain , Chatelier Aurélien , Demion Marie , Potreau Daniel , Patri Sylvie , Rahmati Mohammad , Bois Patrick
Published: May 2004

Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current (Iti). Iti is the result of three different [Ca]i‐sensitive currents: the Na+–Ca2+ exchange current, a Ca2+‐activated chloride current and a Ca2+‐activated non‐selective cationic current. Using the cell‐free configuration of the patch‐clamp technique, we have characterized the properties of a Ca2+‐activated non‐selective cation channel (NSCCa) in freshly dissociated human atrial cardiomyocytes. In excised inside‐out patches, the channel presented a linear I–V relationship with a conductance of 19 ± 0.4 pS. It discriminated poorly among monovalent cations (Na+ and K+) and was slightly permeable to Ca2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the Kd for [Ca2+]i was 20.8 μm. Channel activity was reduced in the presence of 0.5 mm ATP or 10 μm glibenclamide on the cytoplasmic side to 22.1 ± 16.8 and 28.5 ± 8.6%, respectively, of control. It was also inhibited by 0.1 mm flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the ‘TRP melastatin’ subfamily. In conclusion, the NSCCa channel is a serious candidate to support the delayed after‐depolarizations observed in [Ca2+] overload and thus may be implicated in the genesis of arrhythmias.
The excitability of lumbar motoneurones in the neonatal rat is increased by a hyperpolarization of their voltage threshold for activation by descending serotonergic fibres
Authors: Gilmore Jonathan , Fedirchuk Brent
Published: May 2004

Previous work has shown there is an increase in motoneurone excitability produced by hyperpolarization of the threshold potential at which an action potential is elicited (Vth) at the onset, and throughout brainstem‐induced fictive locomotion in the decerebrate cat. This represents a transient facilitation in the membrane potential for activation dependent on the presence of fictive locomotion. The present study tests the hypothesis that a similar neuromodulatory mechanism facilitating neuronal recruitment also exists in the neonatal rat, and the endogenous pathway mediating the Vth hyperpolarization can be activated by electrical stimulation of the neonatal brainstem. Isolated brainstem–spinal cord preparations from 1‐ to 5‐day‐old neonatal rats, and whole‐cell recording techniques were used to examine the patterns of ventral root (VR) activity produced, and the effect of electrical stimulation of the ventromedial medulla on lumbar spinal neurones. Hyperpolarization of Vth was seen in 10/11 (range –2 to –18 mV) neurones recorded during locomotor‐like VR activity, and appeared analogous to the locomotor‐dependent Vth hyperpolarization previously described in the cat. However, in the present study, Vth hyperpolarization was also seen during electrical brainstem stimulation that evoked alternating, rhythmic, or tonic VR activity, or failed to evoke VR activity. Thirty‐six of 71 neurones were antidromically identified as lumbar motoneurones and 33/36 showed a hyperpolarization of Vth (–2 to –14 mV) during electrical brainstem stimulation. Of the unidentified lumbar ventral horn neurones, 31/35 also showed hyperpolarization of Vth (–2 to –20 mV) during brainstem stimulation. The hyperpolarization of Vth and VR activity induced by brainstem stimulation was reversibly blocked by cooling of the cervical cord, indicating it is mediated by descending fibres, and application of the serotonergic antagonist ketanserin to the spinal cord was effectively able to block the brainstem‐evoked hyperpolarization of Vth. These results demonstrate a previously unknown action of the endogenous descending serotonergic system to facilitate spinal motoneuronal recruitment and firing by inducing a hyperpolarization of Vth. This modulatory process can be examined in the neonatal rat brainstem–spinal cord preparation without the requirement for ongoing locomotor activity.
A role for SNAP‐25 but not VAMPs in store‐mediated Ca2+ entry in human platelets
Authors: Redondo Pedro C. , Harper Alan G. S. , Salido Ginés M. , Pariente Jose A. , Sage Stewart O. , Rosado Juan A.
Published: May 2004

Store‐mediated Ca2+ entry (SMCE) is a major mechanism for Ca2+ influx in non‐excitable cells. Recently, a conformational coupling mechanism allowing coupling between transient receptor potential channels (TRPCs) and IP3 receptors has been proposed to activate SMCE. Here we have investigated the role of two soluble N‐ethylmaleimide‐sensitive‐factor attachment protein receptors (SNAREs), which are involved in membrane trafficking and docking, in SMCE in human platelets. We found that the synaptosome‐associated protein (SNAP‐25) and the vesicle‐associated membrane proteins (VAMP) coimmunoprecipitate with hTRPC1 in platelets. Treatment with botulinum toxin (BoNT) E or with tetanus toxin (TeTx), induced cleavage and inactivation of SNAP‐25 and VAMPs, respectively. BoNTs significantly reduced thapsigargin‐ (TG) and agonist‐evoked SMCE. Treatment with BoNTs once SMCE had been activated decreased Ca2+ entry, indicating that SNAP‐25 is required for the activation and maintenance of SMCE. In contrast, treatment with TeTx had no effect on either the activation or the maintenance of SMCE in platelets. Finally, treatment with BoNT E impaired the coupling between naturally expressed hTRPC1 and IP3 receptor type II in platelets. From these findings we suggest SNAP‐25 has a role in SMCE in human platelets.
A Numerical Study of NOx Reduction for a DI Diesel Engine With Complex Geometry
Authors: Liu Renshan , Zhang Chao
Published: May 2004

A numerical study of NOx reduction for a Direct Injection (DI) Diesel engine with complex geometry, which includes intake/exhaust ports and moving valves, was carried out using the commercial computational fluid dynamics software KIVA-3v. The numerical simulations were conducted to investigate the effects of engine operating and geometrical parameters, including fuel injection timing, fuel injection duration, and piston bowl depth, on the NOx formation and the thermal efficiency of the DI Diesel engine. The tradeoff relationships between the reduction in NOx and the decrease in thermal efficiency were established.
Radiative Exchange Within a Two-Cavity Configuration With a Spectrally Selective Window
Authors: Z’Graggen A. , Steinfeld A.
Published: May 2004

Radiation heat transfer within a high-temperature solar thermochemical reactor that features two cavities in series is considered. The inner cavity is subjected to concentrated solar radiative power entering through a spectrally selective window positioned at its aperture. The outer cavity is a well-insulated enclosure containing the inner cavity. It serves as the reaction chamber and is subjected to thermal radiation emitted from the inner cavity. A radiation heat transfer analysis based on the radiosity enclosure theory is formulated and solved using the gray-band approximation for the selective (quartz) window. Energy absorption efficiencies and temperatures are determined and compared to the windowless case.
Semiactive Isolator With Liquid-Crystal Type ER Fluid for Momentum-Wheel Vibration Isolation
Authors: Oh Hyun-Ung , Onoda Junjiro , Minesugi Kenji
Published: May 2004

A semiactive isolator filled with liquid-crystal type electro-rheological (ER) fluid was developed to attenuate the disturbances generated by a momentum-wheel and to improve pointing performance. The principal characteristics of an ER isolator were measured in dynamic tests, and a mathematical model of the isolator was proposed. Two control laws for a semiactive approach were proposed. Numerical simulation results indicated that the proposed semiactive control system produced much better isolation performance than a passive system.
Development of Thermodynamic, Geometric, and Economic Models for Use in the Optimal Synthesis/Design of a PEM Fuel Cell Cogeneration System for Multi-Unit Residential Applications
Authors: Oyarza´bal Borja , Ellis Michael W. , von Spakovsky Michael R.
Published: May 2004

Thermodynamic, geometric, and economic models are developed for a proton exchange membrane (PEM) fuel cell system for use in cogeneration applications in multi-unit residential buildings. The models describe the operation and cost of the fuel processing sub-system and the fuel cell stack sub-system. The thermodynamic model reflects the operation of the chemical reactors, heat exchangers, mixers, compressors, expanders, and stack that comprise the PEMFC system. Geometric models describe the performance of a system component based on its size (e.g., heat exchanger surface area), and, thus, relate the performance at off-design conditions to the component sizes chosen at the design condition. Economic models are based on data from the literature and address the cost of system components including the fuel processor, the fuel cell materials, the stack assembly cost, the fuel cost, etc. As demonstrated in a forthcoming paper, these models can be used in conjunction with optimization techniques based on decomposition to determine the optimal synthesis and design of a fuel cell system. Results obtained using the models show that a PEMFC cogeneration system is most economical for a relatively large cluster of residences (i.e. 50) and for manufacturing volumes in excess of 1500 units per year. The analysis also determines the various system performance parameters including an electrical efficiency of 39% and a cogeneration efficiency of 72% at the synthesis/design point.