bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced nursing practitioners in primary care settings: an exploration of the developing roles
Authors: Carnwell Ros , Daly William M. 
Published: August 2003

Summary• Recent health care policies have resulted in patients having access to an integrated system of care that is quick and reliable. In concert with these changes, opportunities for professional development in nursing have increased, together with a reduction in the numbers of doctors. Advanced Nurse Practitioners (ANPs) have, therefore, developed to meet the complex demands of health care systems.• This paper reports on a study that aimed to explore the current role of ANPs in primary care in the West Midlands region of the UK and how ANPs within three different nursing disciplines in primary care developed their roles over time.• The study utilized a qualitative exploratory design incorporating a longitudinal element. Twenty‐one ANPs were interviewed during phase one, 15 of whom were interviewed again during phase two, approximately 15 months later. Their managers (where appropriate) were also interviewed during phase one.• The findings reveal that the nature and focus of practice varies between disciplines. At the extreme practice end of the practice‐strategic continuum, Practice Nurse ANPs’ expertise lies in their advanced practical assessment and diagnosis of individual patients, with little opportunity for strategic development. Health Visitor and District Nurse ANPs operate at the strategic end of the practice‐strategic continuum, but operate differently at this level. Health Visitors, being community and public health focused are involved in multi‐agency work, practice development and policy formulation. District Nurses work with individual patients/carers and the nursing team, thus their involvement in strategic developments tends to focus at the patient care level, such as protocol and practice developments, although their work also involves work in all three other domains. Overall, the findings reveal a unique role for all three with a potential career pathway for ANPs to become Nurse Consultants in the future.
Male sterility in transgenic tobacco plants induced by tapetum‐specific deacetylation of the externally applied non‐toxic compound N‐acetyl‐l‐phosphinothricin
Authors: Kriete G. , Niehaus K. , Perlick A.M. , Pühler A. , Broer I. 
Published: August 2003

SummaryA system for the inducible destruction of plant tissues based on the deacetylation of the non‐toxic compound N‐acetyl‐l‐phosphinothricin (N‐ac‐Pt) has been developed. The argE gene product of Escherichia coli, representing a N‐acetyl‐l‐ornithine deacetylase was identified to remove the acetyl‐group from N‐ac‐Pt giving the cytotoxic compound l‐phosphinothricin (Pt, glufosinate). Transgenic Nicotiana tabacum plants constitutively expressing the argE gene were constructed. No effect of the bacterial N‐acetyl‐l‐ornithine deacetylase on plant growth and reproduction could be traced. However, application of N‐ac‐Pt on leaves of the transgenic plants led to the formation of necrotic areas due to the release of Pt. Additionally, due to the uptake of the N‐ac‐Pt by roots, transgenic shoots grown on medium containing N‐ac‐Pt bleached within 6–7 days and finally died. Untransformed controls showed no reaction to high amounts of N‐ac‐Pt applied, either under sterile or under unsterile conditions.In order to construct inducible male‐sterile plants, the argE coding region was fused to a DNA fragment carrying sequences homologous to the tobacco TA29 promoter, known to function exclusively in the tapetum. Owing to the tapetum‐specific expression of the chimeric gene the application of N‐ac‐Pt led to empty anthers resulting in male‐sterile plants. The sanity of the female reproductive part of the male‐sterile flowers could be demonstrated by cross‐pollination. Without N‐ac‐Pt treatment the plants turned out to be completely fertile making fertility restoration in the F1 generation superflous. The system presented is easy to handle and might be applicable to a wide range of crop plants.
Different mechanisms influencing permeation of PDGF‐AA and PDGF‐BB across the blood–brain barrier
Authors: Kastin Abba J. , Akerstrom Victoria , Hackler Laszlo , Pan Weihong 
Published: September 2003

AbstractPlatelet‐derived growth factor (PDGF) exerts neurotrophic and neuromodulatory effects on the CNS. To determine the permeability of the blood–brain barrier (BBB) to PDGF, we examined the blood‐to‐brain influx of radioactively labeled PDGF isoforms (PDGF‐AA and PDGF‐BB) by multiple‐time regression analysis after intravenous (i.v.) injection and by in‐situ perfusion, and also determined the physicochemical characteristics which affect their permeation across the BBB, including lipophilicity (measured by octanol:buffer partition coefficient), hydrogen bonding (measured by differences in octanol : buffer and isooctane : buffer partition coefficients), serum protein binding (measured by capillary electrophoresis), and stability of PDGF in blood 10 min after i.v. injection (measured by HPLC). After i.v. bolus injection, neither 125I‐PDGF‐AA nor 125I‐PDGF‐BB crossed the BBB, their influx rates being similar to that of the vascular marker 99mTc‐albumin. 125I‐PDGF‐AA degraded significantly faster in blood than 125I‐PDGF‐BB. PDGF‐BB, however, was completely bound to a large protein in serum whereas PDGF‐AA showed no binding. Thus, degradation might explain the poor blood‐to‐brain influx of PDGF‐AA, whereas protein binding could explain the poor influx of circulating PDGF‐BB. Despite their lack of permeation in the intact mouse, both 125I‐PDGF‐AA and 125I‐PDGF‐BB entered the brain by perfusion in blood‐free buffer, and the significantly faster rate of 125I‐PDGF‐AA than 125I‐PDGF‐BB may be explained by the lower hydrogen bonding potential of 125I‐PDGF‐AA. Thus, the lack of significant distribution of PDGF from blood to brain is not because of the intrinsic barrier function of the BBB but probably because of degradation and protein binding. Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent.
Altered distribution of mitochondria impairs calcium homeostasis in rat hippocampal neurons in culture
Authors: Wang Guang Jian , Jackson Joshua G. , Thayer Stanley A. 
Published: September 2003

AbstractThe specificity of Ca2+ signals is conferred in part by limiting changes in cytosolic Ca2+ to subcellular domains. Mitochondria play a major role in regulating Ca2+ in neurons and may participate in its spatial localization. We examined the effects of changes in the distribution of mitochondria on NMDA‐induced Ca2+ increases. Hippocampal cultures were treated with the microtubule‐destabilizing agent vinblastine, which caused the mitochondria to aggregate and migrate towards one side of the neuron. This treatment did not appear to decrease the energy status of mitochondria, as indicated by a normal membrane potential and pH gradient across the inner membrane. Moreover, electron microscopy showed that vinblastine treatment altered the distribution but not the ultrastructure of mitochondria. NMDA (200 µm, 1 min) evoked a greater increase in cytosolic Ca2+ in vinblastine‐treated cells than in untreated cells. This increase did not result from impaired Ca2+ efflux, enhanced Ca2+ influx, opening of the mitochondrial permeability transition pore or altered function of endoplasmic reticulum Ca2+ stores. Ca2+ uptake into mitochondria was reduced by 53% in vinblastine‐treated cells, as reported by mitochondrially targeted aequorin. Thus, the distribution of mitochondria maintained by microtubules is critical for buffering Ca2+ influx. A subset of mitochondria close to a Ca2+ source may preferentially regulate Ca2+ microdomains, set the threshold for Ca2+‐induced toxicity and participate in local ATP production.
Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein
Authors: Hoshino Masataka , Tagawa Kazuhiko , Okuda Tomohiro , Murata Miho , Oyanagi Kiyomitsu , Arai Nobutaka , Mizutani Toshio , Kanazawa Ichiro , Wanker Erich E. , Okazawa Hitoshi 
Published: September 2003

AbstractPerturbation of histone acetyl‐transferase (HAT) activity is implicated in the pathology of polyglutamine diseases, and suppression of the counteracting histone deacetylase (HDAC) proteins has been proposed as a therapeutic candidate for these intractable disorders. Meanwhile, it is not known whether mutant polyglutamine disease protein affects the HDAC activity in declining neurons, though the answer is essential for application of anti‐HDAC drugs for polyglutamine diseases. Here, we show the effect of mutant huntingtin (htt) protein on the expression and activity of HDAC proteins in rat primary cortical neurons as well as in human Huntington's disease (HD) brains. Our findings indicate that expression and activity of HDAC proteins are not repressed by mutant htt protein. Furthermore, expression of normal and mutant htt protein slightly increased HDAC activity although the effects of normal and mutant htt were not remarkably different. In human HD cerebral cortex, HDAC5 immunoreactivity was increased in the nucleus of striatal and cortical neurons, suggesting accelerated nuclear import of this class II HDAC. Meanwhile, western blot and immunohistochemical analyses showed no remarkable change in the expression of class I HDAC proteins such as HDAC1 and HDCA8. Collectively, retained activity in affected neurons supports application of anti‐HDAC drugs to the therapy of HD.
Inclusion formation in Huntington's disease R6/2 mouse muscle cultures
Authors: Orth M. , Cooper J. M. , Bates G. P. , Schapira A. H. V. 
Published: September 2003

AbstractHuntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the number of glutamine repeats in the N‐terminal region of the huntingtin protein. Nuclear and cytoplasmic aggregates of the N‐terminal portion of huntingtin have been found in the brains of HD patients and the brains and non‐neuronal tissues of the R6/2 HD transgenic mouse. We have cultured myoblasts and myotubes from transgenic R6/2 mice and littermate controls to investigate the formation of these inclusions in post mitotic cells. Huntingtin immunoreactivity was intense in differentiating, desmin positive myoblasts and myotubes from both control and R6/2 mice suggesting that it may play a role in myotube differentiation. Following differentiation huntingtin and ubiquitin positive aggregates were observed in R6/2 but not control cultures. After 3 weeks in differentiation medium cytoplasmic huntingtin and ubiquitin immunoreactive aggregates were observed in non‐myotube cells, while nuclear huntingtin aggregates were seen in a proportion of myotubes after 6 weeks. Growth in the absence of serum resulted in a marked increase in the number of R6/2 myotubes containing nuclear inclusions after 6 weeks demonstrating that environmental factors influenced huntingtin aggregate formation in these cells. Consequently, cultured myotubes from R6/2 mice may be a useful post mitotic cell culture model to study both the biochemical consequences of huntingtin aggregates and the factors that may influence aggregate formation.
Pronounced Effect of Procainamide on Clockwise Right Atrial Isthmus Conduction Compared with Counterclockwise Conduction: Possible Mechanism of the Greater Incidence of Common Atrial Flutter During Antiarrhythmic Therapy
Authors: MORITA NORISHIGE , KOBAYASHI YOSHINORI , IWASAKI YU‐KI , HAYASHI MEISO , ATARASHI HIROTSUGU , KATOH TAKAO , TAKANO TERUO 
Published: August 2003

Bidirectional Conduction Property of Low RA Isthmus.
Introduction: It has been shown that the induction rates of common and reversed common atrial flutter are comparable during baseline control study, whereas the rate is significantly greater for common flutter than reversed common flutter during administration of antiarrhythmic agents. The mechanism of this discrepancy is not known. Methods and Results: The study consisted of 15 patients (group 1) with clinically documented common atrial flutter either with (n = 10) or without (n = 5) Class I antiarrhythmic therapy, and 15 patients with paroxysmal supraventricular tachycardia (group 2). Bidirectional conduction velocity and minimal pacing cycle length of 1:1 conduction during incremental pacing from both the low lateral right atrium and coronary sinus were assessed. The response of these variables to procainamide was analyzed in correlation with the induction rate of each type of flutter during the pacing protocol. Conduction velocity in the clockwise (CW) direction was significantly slower for all pacing cycle lengths than conduction velocity in the counterclockwise (CCW) direction in group 1 but was similar in group 2. Minimal pacing cycle length of 1:1 conduction did not differ between CW and CCW conduction in either group. However, in group 1, minimal pacing cycle length of 1:1 conduction of CW conduction was prolonged to a greater degree after procainamide than that of CCW conduction. There also was a significant increase in the induction rate of common flutter. This preferential effect of procainamide on CW conduction was not observed in group 2. Conclusion: CW conduction over the isthmus is preferentially influenced by procainamide compared with CCW conduction, which may explain the greater incidence and induction probability of common flutter during antiarrhythmic therapy.
Prognostic Significance of Nonsustained Ventricular Tachycardia After Revascularization
Authors: MITTAL SUNEET , LOMNITZ DAVID J. , MIRCHANDANI SUNIL , STEIN KENNETH M. , MARKOWITZ STEVEN M. , SLOTWINER DAVID J. , IWAI SEI , DAS MITHILESH K. , LERMAN BRUCE B. 
Published: August 2003

Ventricular Tachycardia After Revascularization.
Introduction: Two randomized trials (Multicenter Automatic Defibrillator Implantation Trial [MADIT] and Multicenter Unsustained Tachycardia Trial [MUSTT]) suggest that implantable cardioverter defibrillator (ICD) placement is associated with improved survival in patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia (VT) who also have inducible sustained VT. However, neither study directly addresses the management of such patients who develop nonsustained VT early after revascularization. Methods and Results: We evaluated 109 consecutive patients who underwent electrophysiologic testing to evaluate nonsustained VT, which occurred 5 ± 4 days following revascularization. Sustained monomorphic VT was inducible in 46 (42%) patients; these patients received an ICD. The remaining 63 (58%) noninducible patients received neither antiarrhythmic drug therapy nor an ICD. During 27 ± 12 months of follow‐up, 15 (33%) of 45 patients with an implanted ICD received at least one appropriate therapy from the device and 26 (24%) of the 109 study patients died. The 1‐ and 2‐year freedom from ventricular tachycardia/fibrillation or sudden death in noninducible patients (97% and 93%) was significantly greater than that of inducible patients (84% and 71%; P = 0.001). However, no difference was observed in total mortality. Conclusion: Patients with nonsustained VT during the early postrevascularization period who have inducible VT have a high incidence of arrhythmic events. Although this study was not designed to assess the impact of ICD placement on the total mortality of inducible patients, the finding that one third of these patients received appropriate ICD therapy suggests that the device may have a protective effect in these patients.
Long‐Term Follow‐Up After Radiofrequency Catheter Ablation of Ventricular Tachycardia: A Successful Approach?
Authors: VAN DER BURG ALIDA E. BORGER , DE GROOT NATASJA M.S. , VAN ERVEN LIESELOT , BOOTSMA MARIANNE , VAN DER WALL ERNST E. , SCHALIJ MARTIN J. 
Published: August 2003

RF Catheter Ablation of VT.
Introduction: Radiofrequency ablation (RFCA) of ventricular tachycardia (VT) is a potential curative treatment modality. We evaluated the results of RFCA in patients with VT. Methods and Results: One hundred fifty‐one consecutive patients (122 men and 29 women; age 57 ± 16 years) with drug‐refractory VT were treated. Underlying heart disease was ischemic heart disease in 89 (59%), arrhythmogenic right ventricular cardiomyopathy (ARVC) in 32 (21%), and idiopathic VT in 30 (20%; left ventricle in 9 [30%]; right ventricle in 21 [70%]). Ablation was performed using standard ablation techniques. Three hundred six different VTs were treated (cycle length 334 ± 87 msec, 2.0 ± 1.4 VTs per patient). Procedural success (noninducibility of VT after RFCA) was achieved in 126 (83%) patients (70 ischemic heart disease [79%]; 28 ARVC [88%]; 27 idiopathic VT [93%]). Procedure‐related complications (< 48 hours) occurred in 11 (7%) patients: death 3 (2.0%), cerebrovascular accident 2 (1.3%), complete heart block 4 (2.6%), and pericardial effusion 3 (2.0%). Thirty‐three (22%) patients received an implantable cardioverter defibrillator (because of hemodynamic unstable VT, failure of the procedure, or aborted sudden death). During follow‐up (34 ± 11 months), VT recurrences occurred in 38 (26%) patients (recurrence rate: 19% in successfully ablated patients and 64% in nonsuccessfully ablated patients; P < 0.001). During follow‐up, 12 (8%) patients died (heart failure 8, unknown cause 1, noncardiac cause 3). Conclusion: RFCA of VT can be performed with a high degree of success (83%). The long‐term outcome of successfully ablated patients is promising, with a 75% relative risk reduction compared with nonsuccessfully ablated patients. During follow‐up, only one patient died suddenly, supporting a selective ICD placement approach in patients with hemodynamically stable VT.
Beta‐Adrenergic Stimulation of Pig Myocytes with Decreased Cytosolic Free Magnesium Prolongs the Action Potential and Enhances Triggered Activity
Authors: WEI SHAO‐KUI , HANLON STEPHEN U. , HAIGNEY MARK C.P. 
Published: August 2003

Beta‐Adrenergic Stimulation and Repolarization.
Introduction: Heart failure results in chronic beta‐adrenergic stimulation, repolarization lability, and arrhythmias associated with early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs). Having described a significant reduction in intracellular free magnesium ([Mg2+]i) in experimental heart failure, we asked whether a reduction in [Mg2+]i would delay repolarization or facilitate EADs and/or DADs. Methods and Results: Left ventricular myocytes were isolated from Yorkshire swine. Cytosolic free [Mg2+] was set at 0.12 mM (LoMg) or 1.2 mM (HiMg) through pipette dialysis. Action potentials (AP), Ca current (ICa), and sodium/calcium exchange current (INCX) were measured in the presence or absence of isoproterenol (2 μM) at 37°C. Under basal conditions (0.1‐Hz stimulation, 2 mM external [Ca2+]), reducing [Mg2+]i had no effect on AP duration and ICa but did significantly enhance INCX. In contrast, during superfusion with isoproterenol, reduced [Mg2+]i caused a significant increase in AP duration at both 50% and 90% repolarization (APD50 and APD90) compared with HiMg (P < 0.05). LoMg cells manifested a high incidence of triggered activities, including spontaneous AP, EADs, and DADs (83.3% in LoMg, n = 12 vs 38.3% in HiMg, n = 13; P < 0.05). ICa and INCX were significantly increased in LoMg cells compared with HiMg cells (P < 0.05). Conclusion: Decreased cytosolic free magnesium prolongs AP duration and increases the incidence of triggered activity during beta‐adrenergic stimulation. These effects may be due to increased ICa and INCX in the presence of reduced intracellular [Mg2+]. A magnesium‐dependent increase in triggered activity coupled with delayed repolarization during beta‐adrenergic stimulation could contribute to the arrhythmogenic substrate in heart failure.
Usefulness of Paced Activation Sequence Mapping in Catheter Ablation of Accessory Pathways
Authors: PÉREZ‐CASTELLANO NICASIO , ALMENDRAL JESÚS , VILLACASTÍN JULIÁN , ARENAL ANGEL , GONZÁLEZ SERGIO , MORENO JAVIER , ORTIZ MERCEDES , TORRECILLA ESTEBAN , MACAYA CARLOS 
Published: August 2003

Pace Mapping for Accessory Pathways.
Introduction: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time‐consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs. Methods and Results: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia ≤5 msec (P < 0.001), a local AV ratio ≥1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria. Conclusion: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs.
Prognostic Significance of Nonsustained Ventricular Tachycardia Identified Postoperatively After Coronary Artery Bypass Surgery in Patients with Left Ventricular Dysfunction
Authors: PIRES LUIS A. , HAFLEY GAIL E. , LEE KERRY L. , FISHER JOHN D. , JOSEPHSON MARK E. , PRYSTOWSKY ERIC N. , BUXTON ALFRED E. 
Published: August 2003

Post‐CABG Nonsustained VT.
Introduction: Nonsustained ventricular tachycardia (NSVT) occurs frequently in the postoperative period (≤30 days) after coronary artery bypass graft (CABG) surgery, a setting where many factors may play a role in its genesis. The prognosis of NSVT in this setting in patients with left ventricular (LV) dysfunction is unknown. This study was designed to assess its significance. Methods and Results: We compared the outcome of untreated patients enrolled in the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD), LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age 67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66 years, 85% males). Sustained monomorphic ventricular tachycardia was induced in 27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT, respectively. The 2‐ and 5‐year rates of arrhythmic events were 6% and 16%, respectively, in postoperative patients versus 15% and 29% in nonpostoperative patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2‐ and 5‐year overall mortality rates were 15% and 36%, respectively, for postoperative patients versus 24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P = 0.027). Patients whose NSVT was identified early (<10 days) versus late (10–30 days) after CABG had significantly lower 2‐ (13% vs 23%) and 5‐year (30% vs 52%) mortality rates (unadjusted P = 0.024, adjusted P = 0.018). Conclusion: In this population of patients with CAD and LV dysfunction, the occurrence of postoperative NSVT, especially within 10 days after CABG, portends a far better outcome than when it occurs in nonpostoperative settings. This suggests that in a such setting, NSVT represents a less specific risk factor for future events and should be considered when assigning risk and treatment of similar patients.