bluuebunny/crossref_metadata_2025 huggingface dataset:
The Peopling of Modern Bosnia‐Herzegovina: Y‐chromosome Haplogroups in the Three Main Ethnic Groups
Authors: Marjanovic D. , Fornarino S. , Montagna S. , Primorac D. , Hadziselimovic R. , Vidovic S. , Pojskic N. , Battaglia V. , Achilli A. , Drobnic K. , Andjelinovic S. , Torroni A. , Santachiara‐Benerecetti A. S. , Semino O.
Published: October 2005

The variation at 28 Y‐chromosome biallelic markers was analysed in 256 males (90 Croats, 81 Serbs and 85 Bosniacs) from Bosnia‐Herzegovina. An important shared feature between the three ethnic groups is the high frequency of the “Palaeolithic” European‐specific haplogroup (Hg) I, a likely signature of a Balkan population re‐expansion after the Last Glacial Maximum. This haplogroup is almost completely represented by the sub‐haplogroup I‐P37 whose frequency is, however, higher in the Croats (∼71%) than in Bosniacs (∼44%) and Serbs (∼31%). Other rather frequent haplogroups are E (∼15%) and J (∼7%), which are considered to have arrived from the Middle East in Neolithic and post‐Neolithic times, and R‐M17 (∼14%), which probably marked several arrivals, at different times, from eastern Eurasia. Hg E, almost exclusively represented by its subclade E‐M78, is more common in the Serbs (∼20%) than in Bosniacs (∼13%) and Croats (∼9%), and Hg J, observed in only one Croat, encompasses ∼9% of the Serbs and ∼12% of the Bosniacs, where it shows its highest diversification. By contrast, Hg R‐M17 displays similar frequencies in all three groups. On the whole, the three main groups of Bosnia‐Herzegovina, in spite of some quantitative differences, share a large fraction of the same ancient gene pool distinctive for the Balkan area.
Multiple Testing in the Context of Haplotype Analysis Revisited: Application to Case‐Control Data
Authors: Becker T. , Cichon S. , Jönson E. , Knapp M.
Published: October 2005

We have lately presented a testing procedure for family data which accounts for the multiple testing problem that is induced by the enormous number of different marker combinations that can be analyzed in a set of tightly linked markers. Most methods of haplotype based association analysis already require simulations to obtain an uncorrected P value for a specific marker combination. As shown before, it is nevertheless not necessary to carry out nested simulations to obtain a global P value that properly corrects for the multiple testing of different marker combinations without neglecting the dependency of the tests. We have now implemented this approach for case‐control data in our program FAMHAP, as this data structure currently plays a dominant role in the field. We consider different ways to deal with phase ambiguities and two different statistical tests for the underlying single marker combinations to obtain uncorrected P values. One test statistic is chi‐square based, the other is a haplotype trend regression. The performance of these different tests in the multiple testing situation is investigated in a large simulation study. We obtain a considerable gain in power with our global P values as opposed to Bonferroni corrected P values for all suggested test statistics. Good power was obtained both with the haplotype trend regression approach as well as with the simpler chi‐square based test. Furthermore, we conclude that the better strategy to deal with phase ambiguities is to assign to each individual its list of weighted haplotype explanations, rather than to assign to each individual its most likely haplotype explanation. Finally, we demonstrate the usefulness of our approach by a real data example.
ATM Gene Founder Haplotypes and Associated Mutations in Polish Families with Ataxia‐Telangiectasia
Authors: Mitui M. , Bernatowska E. , Pietrucha B. , Piotrowska‐Jastrzebska J. , Eng L. , Nahas S. , Teraoka S. , Sholty G. , Purayidom A. , Concannon P. , Gatti R. A.
Published: October 2005

Ataxia‐telangiectasia (A‐T) is an early onset autosomal recessive ataxia associated with characteristic chromosomal aberrations, cell cycle checkpoint defects, cancer susceptibility, and sensitivity to ionizing radiation. We utilized the protein truncation test (PTT), and single strand conformation polymorphism (SSCP) on cDNA, as well as denaturing high performance liquid chromatography (dHPLC) on genomic DNA (gDNA) to screen for mutations in 24 Polish A‐T families. Twenty‐six distinct Short Tandem Repeat (STR) haplotypes were identified. Three founder mutations accounted for 58% of the alleles. Three‐quarters of the families had at least one recurring (shared) mutation, which was somewhat surprising given the low frequency of consanguinity in Poland. STR haplotyping greatly improved the efficiency of mutation detection. We identified 44 of the expected 48 mutations (92%): sixty‐nine percent were nonsense mutations, 23% caused aberrant splicing, and 5% were missense mutations. Four mutations have not been previously described. Two of the Polish mutations have been observed previously in Amish and Mennonite A‐T patients; this is compatible with historical records. Shared mutations shared the same Single Nucleotide Polymorphism (SNP) and STR haplotypes, indicating common ancestries. The Mennonite mutation, 5932 G>T, is common in Russian A‐T families, and the STR haplovariants are the same in both Poland and Russia. Attempts to correlate phenotypes with genotypes were inconclusive due to the limited numbers of patients with identical mutations.
Association of Common CRP Gene Variants with CRP Levels and Cardiovascular Events
Authors: Miller D. T. , Zee R. Y. L. , Suk Danik J. , Kozlowski P. , Chasman D. I. , Lazarus R. , Cook N. R. , Ridker P. M. , Kwiatkowski D. J.
Published: October 2005

C‐reactive protein (CRP) is a well‐documented marker of atherosclerotic cardiovascular disease risk. We resequenced CRP to identify a comprehensive set of common SNP variants, then studied and replicated their association with baseline CRP level among apparently healthy subjects in the Women's Health Study (WHS; n = 717), Pravastatin Inflammation/CRP Evaluation trial (PRINCE; n = 1,110) and Physicians' Health Study (PHS; n = 509) cohorts. The minor alleles of four SNPs were consistently associated in all three cohorts with higher CRP, while the minor alleles of two SNPs were associated with lower CRP (p < 0.05 for each). Single marker and haplotype analysis in all three cohorts were consistent with functional roles for the 5′‐flanking triallelic SNP −286C>T>A and the 3′‐UTR SNP 1846G>A. None of the SNPs associated with higher CRP were associated with risk of incident myocardial infarction (MI) or ischemic stroke in a prospective, nested case‐control study design from the PHS cohort (610 case‐control pairs). One SNP, −717A>G, was unrelated to CRP levels but associated with decreased risk of MI (p = 0.001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies.
The Relationship Between Older Adults' Knowledge of Their Drug Coverage and Medication Cost Problems
Authors: Piette John D. , Heisler Michele
Published: October 2005

Objectives: To determine whether chronically ill patients have gaps in knowledge about their prescription drug coverage and establish the relationship between gaps and medication cost problems.

Design: Nationwide, cross‐sectional survey.

Setting: Nationwide survey conducted via the Internet.

Participants: Three thousand one hundred nineteen adults aged 50 and older (1,400 of whom were aged ≥65) who had prescription drug coverage and at least one chronic illness.

Measurements: Patients were asked about features of their drug benefits and whether they had experienced problems due to medication costs in the prior year.

Results: Twenty‐five percent of respondents reported not knowing their usual prescription copayments, and 41% did not know whether there were caps on their drug coverage. Nonwhite race and lower income were independent risk factors for lack of knowledge about these aspects of pharmacy benefits. Lack of knowledge regarding the limits of coverage was associated with a greater likelihood of cutting back on medication use because of cost pressures, forgoing basic needs because of medication costs, borrowing money to pay for prescriptions, and worrying about medication costs (all P<.05).

Conclusion: Many older adults with prescription drug coverage do not know important features of their pharmacy benefits. Racial minorities and those with low incomes may have the greatest difficulty understanding coverage and as a result may be at greatest risk for underusing their benefits. Education about Medicare reforms and other efforts to increase prescription coverage should accompany these policies.
Two Outbreaks of Severe Respiratory Disease in Nursing Homes Associated with Rhinovirus
Authors: Hicks Lauri A. , Shepard Colin W. , Britz Phyllis H. , Erdman Dean D. , Fischer Marc , Flannery Brendan L. , Peck Angela J. , Lu Xiaoyan , Thacker W. Lanier , Benson Robert F. , Tondella Maria L. , Moll Mària E. , Whitney Cynthia G. , Anderson Larry J. , Feikin Daniel R.
Published: October 2005

Objectives: To characterize illness and identify the etiology for two nursing home outbreaks of respiratory illness.

Design: Multisite outbreak investigations; cohort.

Setting: Two nursing homes in Pennsylvania.

Participants: Facility A residents (n=170), Facility B residents (n=124), and employees (n=91).

Measurements: Medical records for Facility A and B residents were reviewed, and employees from Facility B self‐administered a questionnaire to identify risk factors for illness. Serological, oropharyngeal, and nasopharyngeal specimens were collected for both outbreaks, and testing for respiratory pathogens was performed.

Results: In Facility A, 40 (24%) of 170 residents were identified with respiratory illness; 13 (33%) case‐patients had radiographically confirmed pneumonia, 15 (38%) were taken to a hospital, and two (5%) died. Of 10 specimens collected from symptomatic Facility A case‐patients, four (40%) tested positive using reverse transcription polymerase chain reaction for rhinovirus. In Facility B, 77 (62%) of 124 residents had respiratory illness, and 40 (52%) had radiographically confirmed pneumonia; 12 (16%) case‐patients were hospitalized, and five (6%) died. Of 19 respiratory specimens collected from symptomatic Facility B case‐patients, six (32%) were positive for rhinovirus; one was from an employee. Five (50%) of 10 rhinovirus‐positive cases in both outbreaks had clinical and radiographic evidence of pneumonia.

Conclusion: These investigations suggest that rhinoviruses may be an underrecognized cause of respiratory outbreaks in nursing homes, capable of causing pneumonia and perhaps death.
Ten Years' Experience Conducting the Aging Game Workshop: Was It Worth It?
Authors: Pacala James T. , Boult Chad , Hepburn Ken
Published: October 2005

In the Aging Game, medical students experience simulated physical, sensory, and cognitive deficits that are associated with disability from chronic diseases. Since 1994, the University of Minnesota has presented an innovative version of the Aging Game as part of the curriculum in a required clinical clerkship. The experiences conducting the Aging Game over the past decade were reviewed, focusing on the resources necessary to produce it and on its worth as an educational tool. Because many of the reusable props were obtained free as donations, start‐up material costs were calculated at $530. Personnel necessary for each half‐day presentation of the Aging Game included two faculty and a minimum of five nonfaculty serving as facilitators; a staff coordinator was also essential. Quantitative student evaluations (N=673) exhibited mean ratings of 1.41, 1.35, and 1.40 (1=excellent) for overall value, teaching effectiveness, and quality of a postsimulation discussion. Written student comments regarding the strengths of the Aging Game centered on three major themes: mode of learning, especially using role playing and simulating deficits (total of 192 comments); attitudinal change, specifically raising awareness and stimulating reflection on the experiences of disabled older adults (121 comments); and educational value, particularly the Aging Game's capacity for creating a memorable impression (56 comments). Despite consuming significant personnel resources, the Minnesota version of the Aging Game is an effective tool for stimulating long‐lasting awareness and understanding of key issues related to aging and geriatrics.
Epicardial Idiopathic Ventricular Tachycardia Originating Within the Left Main Coronary Artery Ostium Area: Identification Using the LocaLisa Nonfluoroscopic Catheter Navigation System
Authors: ATIENZA FELIPE , ARENAL ANGEL , ORMAETXE JOSÉ , ALMENDRAL JESÚS
Published: October 2005

Idiopathic ventricular tachycardia (IVT) in patients without structural heart disease commonly arises from the right or left outflow tracts, but there remain arrhythmias that can only be ablated by an epicardial approach. We report a case of an epicardial ventricular tachycardia originating within the left main coronary artery ostium area, as identified using the LocaLisa nonfluoroscopic catheter navigation system. Due to the high risk of coronary artery thrombosis, ventricular tachycardia was successfully ablated by a transthoracic surgical approach using cryoenergy. Ventricular ectopy disappeared and ventricular tachycardia did not recur during long‐term follow‐up.
Human Histopathology of Electroanatomic Mapping After Cooled‐Tip Radiofrequency Ablation to Treat Ventricular Tachycardia in Remote Myocardial Infarction
Authors: DENEKE THOMAS , MÜLLER KLAUS‐MICHAEL , LEMKE BERND , LAWO THOMAS , CALCUM BERND , HELWING MARLENE , MÜGGE ANDREAS , GREWE PETER H.
Published: October 2005

Introduction: Catheter ablation of ventricular tachycardia (VT) in remote myocardial infarction (MI) often requires excessive mapping procedures. Documentation of the electrical substrate via electrogram amplitude may help to identify regions of altered myocardium resembling exit areas of reentrant VTs.

Methods and Results: A patient with multiple symptomatic monomorphic VTs (biventricular ICD, remote MI) underwent electroanatomic substrate mapping (CARTO™) for VT ablation. Regions of scar (bipolar electrogram amplitudes ≤0.5 mV), normal myocardium (≥1.5 mV), and “altered” myocardium (0.5–1.5 mV) were identified. Ablation was directed to regions with “altered” myocardium based on pace map correlation. After ablation the clinical VT did not reoccur. The patient died due to worsening of heart failure 7 days afterward. During postmortal evaluation specified sites of electroanatomic mapping were correlated to histopathological findings. Annotated scar areas were documented to consist of areas with massive fibrosis (≥80% of mural composition). Ablations were found to span through regions with intermediate fibrosis (21–79%) mapped as “altered” myocardium. Ablation produced transmural coagulation necrosis of mesh‐like fibrotic tissue with interspersed remnants of myocardial cells up to a maximum depth of 7.0 mm. Subendocardial intramural bleedings were universal findings 7 days after ablation.

Conclusions: Electroanatomic substrate mapping for VT ablation sufficiently identified regions of scar and normal myocardium. Regions with bipolar electrogram amplitudes between 0.5 and 1.5 mV were found to correlate to areas of “intermediate” fibrosis (21–79%) with only remnant strands of myocardial cells and were identified as target region for ablation. Cooled‐tip endocardial radiofrequency ablation lead to transmural coagulation necrosis up to a depth of 7.0 mm.
Dietary Fish Oil Protects Against Stretch‐Induced Vulnerability to Atrial Fibrillation in a Rabbit Model
Authors: NINIO DANIEL M. , MURPHY KAREN J. , HOWE PETER R. , SAINT DAVID A.
Published: October 2005

Introduction: Dietary fish oil is thought to reduce sudden cardiac death by suppressing ventricular arrhythmias but little is known about its impact on atrial arrhythmias. We examined the effect of dietary fish oil on the rabbit model of stretch‐induced vulnerability to atrial fibrillation (AF).

Methods and Results: Six‐week‐old rabbits were fed standard rabbit pellets supplemented with 5% tuna fish oil (n = 6) or supplemented with 5% sunflower oil (n = 6) for 12 weeks. Six rabbits raised on the standard diet were used as controls. In Langendorff‐perfused hearts intraatrial pressures were increased in a stepwise manner and rapid burst pacing applied to induce AF at increasing intraatrial pressures until AF was sustained (>1 minute). Atrial refractory periods were recorded at each pressure. Increased atrial pressure resulted in a reduction in atrial refractory period and a propensity for induction of sustained AF. Higher pressures were needed to induce and sustain AF in the fish oil group compared with the sunflower oil and control groups. The stretch‐induced drop in refractory period was also less marked in the fish oil group. Red blood cell, atrial, and ventricular omega‐3 fatty acid levels were significantly higher in the fish oil group. The ratio of atrial n‐6/n‐3 polyunsaturated fatty acids was 13 ± 0.9 with sunflower oil and 1.5 ± 0.01 with fish oil (P < 0.001).

Conclusions: Incorporation of dietary omega‐3 fatty acids into atrial tissue reduces stretch‐induced susceptibility to AF.
Left Ventricular‐Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (The PAVE Study)
Authors: DOSHI RAHUL N. , DAOUD EMILE G. , FELLOWS CHRISTOPHER , TURK KYONG , DURAN AURELIO , HAMDAN MOHAMED H. , PIRES LUIS A. ,   for the PAVE Study Group
Published: October 2005

Background: Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates.

Methods and Results: One hundred and eighty‐four patients requiring AV node ablation were randomized to receive a biventricular pacing system (n = 103) or a right ventricular pacing system (n = 81). The study endpoints were change in the 6‐minute hallway walk test, quality of life, and left ventricular ejection fraction. Patient characteristics were similar (64% male; age: 69 ± 10 years, ejection fraction: 0.46 ± 0.16; 83%, NYHA Class II or III). At 6 months postablation, patients treated with cardiac resynchronization had a significant improvement in 6‐minute walk distance, (31%) above baseline (82.9 ± 94.7 m), compared to patients receiving right ventricular pacing, (24%) above baseline (61.2 ± 90.0 m) (P = 0.04). There were no significant differences in the quality‐of‐life parameters. At 6 months postablation, the ejection fraction in the biventricular group (0.46 ± 0.13) was significantly greater in comparison to patients receiving right ventricular pacing (0.41 ± 0.13, P = 0.03). Patients with an ejection fraction ≤45% or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6‐minute walk distance compared to patients with normal systolic function or Class I symptoms.

Conclusion: For patients undergoing AV node ablation for atrial fibrillation, biventricular pacing provides a significant improvement in the 6‐minute hallway walk test and ejection fraction compared to right ventricular pacing. These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure.
Percutaneous Pulmonary Vein Stenting for the Treatment of Severe Stenosis After Pulmonary Vein Isolation
Authors: NEUMANN THOMAS , SPERZEL JOHANNES , DILL THORSTEN , KLUGE ALEXANDER , ERDOGAN ALI , GREIS HARALD , HANSEL JOCHEN , BERKOWITSCH ALEXANDER , KURZIDIM KLAUS , KUNISS MALTE , HAMM CHRISTIAN W. , PITSCHNER HEINZ‐F.
Published: October 2005

Introduction: Pulmonary vein stenosis (PVS) is a potential complication of pulmonary vein isolation (PVI) using radiofrequency energy. The aim of our study was the evaluation of the severity and long‐term outcome of primary angioplasty and angioplasty with pulmonary vein stenting for PVS.

Methods and Results: Twelve patients with 15 PVS (greater than 70% stenosis) were prospectively evaluated. Primary dilation of the stenosis was performed because of clinical symptoms (10 patients) and/or the lung perfusion scans showed a significant perfusion defect (11 patients). Magnetic resonance imaging and lung perfusion scans performed before, directly after, during 3‐month, and 6‐month follow‐up. In the stenting group additional multislice CT‐scans directly after, during 6‐month, and 12‐month follow‐up were performed.

Within 2 months after primary balloon angioplasty, the PV size parameters were significantly reduced (P < 0.001) with recurrence of PVS in 11 of 15 PVs (73%). Pulmonary vein stenting in 8 patients and 11 PVs resulted in no vein stenosis during 12‐month follow‐up. Normalization of lung perfusion was noted in 8 of 12 patients. We observed 2 patients with hemoptysis during PV dilation, as severe complications with potential life‐threatening character.

Conclusion: PVS stenting seems to be superior to balloon angioplasty and effective at least over a period of 12 months in treating acquired PVS after pulmonary vein isolation.
Enalapril Preserves Sinus Node Function in a Canine Atrial Fibrillation Model Induced by Rapid Atrial Pacing
Authors: SAKABE MASAO , FUJIKI AKIRA , NISHIDA KUNIHIRO , SUGAO MASATAKA , NAGASAWA HIDEHIKO , TSUNEDA TAKAYUKI , MIZUMAKI KOICHI , INOUE HIROSHI
Published: October 2005

Effects of enalapril on canine sinus node (SN) dysfunction induced by long‐term rapid atrial pacing were investigated.

Methods and Results: Seventeen beagles were pretreated with either placebo (group I, n = 9) or enalapril 1 mg/kg/day (group II, n = 8) and paced at 500/min from the right atrial appendage for 4 weeks. Every week, corrected sinus node recovery time (CSNRT) and sinus cycle length (SCL) were measured. Quantitative analysis of interstitial fibrosis (IF) and adipose tissue (AT) in the SN was performed with Masson's trichrome stain, and apoptosis of the sinus nodal cells were detected with terminal deoxynucleotidyl transferase nick end‐labeling. In group I, rapid atrial pacing prolonged both CSNRT and SCL. After 4 weeks of pacing, CSNRT and SCL were significantly shorter in group II (CSNRT, 410 ± 37 msec; SCL, 426 ± 34 msec) than in group I (CSNRT, 717 ± 52 msec, P < 0.005; SCL, 568 ± 73 msec, P < 0.05). Both IF and AT of the SN were greater in group I (IF, 9.7 ± 1.9%; AT, 32.6 ± 5.9%) than in seven sham dogs (IF, 2.4 ± 0.9%, P < 0.05; AT, 4.0 ± 1.7%, P < 0.05) and in group II dogs (IF, 4.0 ± 2.0%, P < 0.05; AT, 4.0 ± 1.7%, P < 0.05). End‐labeling assay was positive in three of nine dogs in group I, but negative in group II and sham dogs.

Conclusions: Rapid atrial pacing impaired SN function through IF and AT of the SN. Enalapril prevented these pacing‐induced degenerative changes and improved SN function.
Comparison of Cryothermia and Radiofrequency Current in Safety and Efficacy of Catheter Ablation within the Canine Coronary Sinus Close to the Left Circumflex Coronary Artery
Authors: AOYAMA HIROSHI , NAKAGAWA HIROSHI , PITHA JAN V. , KHAMMAR GEORGE S. , CHANDRASEKARAN KRISHNASWAMY , MATSUDAIRA KAGARI , YAGI TETSUO , YOKOYAMA KATSUAKI , LAZZARA RALPH , JACKMAN WARREN M.
Published: October 2005

Introduction: A canine model was used to compare cryoablation and radiofrequency ablation (RFA) within the coronary sinus (CS) in the ability to create a transmural CS myocardial (Trans‐CSM) lesion and risk of coronary artery stenosis.

Methods: After CS and left circumflex (LCx) coronary angiography, an intravascular ultrasound (IVUS) probe was placed in LCx in 29 dogs. An irrigated RFA catheter (8 dogs) or N2O cryoablation catheter (21 dogs) was inserted into the CS and positioned within 2 mm of LCx, confirmed by IVUS. RF (30–50W) was applied for 60 seconds at 10 CS sites. Cryoablation (−75°C) was performed with one (n = 7) or two (n = 14) 4‐minute applications. Dogs were sacrificed at 1 week (8 RFA and 13 cryoablation) or 3 months (8 cryoablation).

Results: During RFA, IVUS showed wall thickening and LCx narrowing in 9 of 10 sites. Angiography at 5‐minute post‐RFA identified LCx narrowing (25–90%) at 6 of 10 sites and 25–75% narrowing at 4 of 9 sites at 1‐week post‐RFA. During cryoablation, IVUS showed reversible ice ball compression of LCx, and no LCx narrowing by angiography at 5 minutes, 1 week, or 3 months. Histology showed Trans‐CSM lesion at 10 of 10 RFA sites and 20 of 21 cryoablation sites. RFA produced LCx medial necrosis at 7 of 10 sites, involving 20–50%(median 32.5%) of LCx circumference with loss of intima at 5 of 7 sites. Single and twice 4‐minute cryoablation produced LCx medial necrosis at 2 of 7 and 8 of 14 sites (5–40%, median 25% circumference). Intima was preserved at 1 week (13/13) with minor proliferation (without narrowing) at 2 of 8 sites at 3 months.

Conclusions: Cryoablation in CS within 2 mm of LCx produces Trans‐CSM lesions similar to RFA with lower risk of LCx stenosis than RFA.
Outcomes After Cardiac Perforation During Radiofrequency Ablation of the Atrium
Authors: BUNCH T. JARED , ASIRVATHAM SAMUEL J. , FRIEDMAN PAUL A. , MONAHAN KRISTI H. , MUNGER THOMAS M. , REA ROBERT F. , SINAK LAWRENCE J. , PACKER DOUGLAS L.
Published: October 2005

Background: Perforation during catheter procedures in either the atrium or ventricle is relatively uncommon, but potentially fatal if tamponade ensues. This study analyzes the occurrence and outcomes of cardiac perforation during catheter‐based radiofrequency ablation procedures in the left atrium.

Methods: All patients with a periprocedure perforation who have undergone radiofrequency ablation for atrial fibrillation (AF) or tachycardia were included.

Results: Of 632 procedures performed from January 1999 to October 2004, 15 (2.4%) were complicated by perforation requiring pericardiocentesis. The perforation site was left atrium in 9 (60.0%), right atrium in 1 (6.7%), and right ventricle in 5 (33.3%). Intracardiac echocardiography was used in 13 (86.7%) and revealed an effusion before overt instability in 11 (73.3%). Thirteen (86.7%) patients developed a blood pressure <60 mmHg. The pressure stabilized in all patients after pericardiocentesis (hypotension to intervention: 10.1 ± 5.1 minutes). The total blood volume removed was 848 ± 880 mL (left atrium/right atrium: 1,074 ± 1,002 vs right ventricle: 396 ± 266, P = 0.168). Two patients required surgery to close left atrium dome perforations. The ablation was completed in 7 (46.7%) patients. Ten (66.7%) later developed early reoccurrence of AF. All patients were neurologically intact at hospital discharge. During a 1.5 ± 1.1 year follow‐up, AF was eliminated (n = 4) or controlled (n = 1) in 5 (71.4%) patients with complete procedures, and 2 (20.0%) patients underwent successful repeat ablation.

Conclusion: The incidence of perforation during ablation of the left atrium is low. Most perforations occur in the left atrium; however, few require surgical closure. Although less than with uncomplicated procedures, the majority of patients with complete ablations achieve long‐term elimination of AF.
Is Wolff‐Parkinson‐White Syndrome a Genetic Disease?
Authors: EHTISHAM JAVED , WATKINS HUGH
Published: October 2005

Family studies, and more recent molecular genetic investigations, indicate that the Wolff‐Parkinson‐White (WPW) syndrome and associated preexcitation disorders can have a substantial genetic component. Because preexcitation disorders are sometimes inherited as single gene disorders, key mechanistic insights can be gained that are expected to be relevant also to the more common multifactorial forms of these traits. Potentially, such insights will inform the future management of these conditions. Where WPW is inherited as a familial trait, with or without associated cardiac defects or a systemic syndrome, there are clinical genetic ramifications that are already of practical importance.
Association of matrix metalloproteinase‐1 promoter polymorphism with generalized aggressive periodontitis in a Chinese population
Authors: Cao Zhengguo , Li Chengzhang , Jin Lijian , Corbet Esmonde F.
Published: October 2005

Background:  A single nucleotide polymorphism in the promoter region of −1607 bp of the human matrix metalloproteinase‐1 (MMP‐1) gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis.

Objectives:  The present study aimed to examine the distribution of MMP‐1 genotypes in a group of Chinese subjects with generalized aggressive periodontitis and a group of periodontally healthy subjects, and to evaluate the possible association of the MMP‐1 promoter polymorphism with aggressive periodontitis.

Methods:  Genomic DNA was obtained from whole blood samples in 40 Chinese subjects with generalized aggressive periodontitis and 52 periodontally healthy subjects as controls. MMP‐1 promoter fragment was amplified by polymerase chain reaction, and the polymorphisms were analyzed by restriction endonuclease cleavage. The alleles were detected by polyacrylamide gel electrophoresis and visualized with ethidium bromide.

Results:  The detection frequency of 2G allele was significantly higher in the subjects with generalized aggressive periodontitis (68.7%) than in the control subjects (49%) (p < 0.01). The genotype of 2G/2G was found in 52.5% of the patients, which was significantly greater than that of control subjects (23.1%) (p < 0.05).

Conclusion:  The present study suggests that a single nucleotide polymorphism in the MMP‐1 promoter region of −1607 bp may be associated with generalized aggressive periodontitis in Chinese population.
Genetic relatedness of oral yeasts within and between patients with marginal periodontitis and subjects with oral health
Authors: Song Xiaobo , Eribe Emenike R. K. , Sun Jinglu , Hansen B. Frode , Olsen Ingar
Published: October 2005

Background:  Yeasts are found in periodontal pockets at a frequency of 15–21%. However, the genetic relatedness of oral yeasts within and between patients with marginal periodontitis is not clear.

Objectives:  Assay genetic relatedness of oral yeasts from marginal periodontitis patients and oral health subjects, as well as genetic relatedness of yeasts from different oral sites in these two groups of participants.

Material and methods:  Yeast isolates were collected from 23 marginal periodontitis patients and 19 oral health subjects. Random amplified polymorphic DNA (RAPD) fingerprinting and the Dendron computer‐assisted program for gel analyses were applied for estimation of genetic relatedness of yeasts.

Results:  The similarity coefficient (SAB) of the marginal periodontitis group ranged from 0.49 to 1.00 with an average of 0.64 ± 0.11, whereas the SAB of the oral health group ranged from 0.62 to 1.00 with an average of 0.72 ± 0.07. Three genetic clusters and 73 genotypes were obtained from the marginal periodontitis group, whereas three genetic clusters and 55 genotypes were found in the oral health group. In the pooled dendrogram, 57% of the yeast isolates and the type strain of Candida albicans fell in a major cluster V. There were no significant differences between the frequencies of clusters from the different oral sites within the two participant groups.

Conclusions:  Genetically heterogeneous yeasts were found in the oral cavities of marginal periodontitis patients and oral health subjects. Similar genetic clustering patterns were obtained from the yeasts of the two groups, with cluster V being most predominant. Yeasts of the marginal periodontitis group were more genetically diverse than yeasts of the oral health group, and some yeasts of the marginal periodontitis group exhibited unique genetic patterns. There was no clear association between yeast genetic clusters and oral sites in the two participant groups.
Suppression of lipopolysaccharide‐induced cytokine production of gingival fibroblasts by a soybean, Kunitz trypsin inhibitor
Authors: Kobayashi Hiroshi , Yoshida Ryuji , Kanada Yasufumi , Fukuda Yoichi , Yagyu Tatsuo , Inagaki Kiyokazu , Kondo Toshiharu , Kurita Noriyuki , Suzuki Mika , Kanayama Naohiro , Terao Toshihiko
Published: October 2005

Background:  Human bikunin, a Kunitz‐type trypsin inhibitor, inhibits inflammation by down‐regulating the expression of proinflammatory cytokines such as tumor necrosis factor‐alpha (TNF‐α) in tumor cells and inflammatory cells.

Objectives:  We analyzed the effect of a soybean‐derived Kunitz trypsin inhibitor (KTI) on TNF‐α production in human gingival fibroblasts stimulated by lipopolysaccharide (LPS), an inflammatory inducer.

Material and methods:  Mitogen‐activated protein kinase (MAPK) activation and cytokine levels were monitored using western blot and a specific enzyme‐linked immunosorbent assay (ELISA).

Results:  Here, we show (i) a soybean KTI abrogates LPS‐induced up‐regulation of TNF‐α mRNA and protein expression in a dose‐dependent manner in gingival fibroblasts, (ii) KTI also blocks the induction of TNF‐α target molecules interleukin‐1β (IL‐1β) and IL‐6 proteins, (iii) inhibition by KTI of TNF‐α induction correlates with the suppressive capacity of extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38 signaling pathways, implicating repressed ERK1/2 and p38 signalings in the inhibition, and (iv) pretreatment of cells with KTI blocked LPS‐induced nuclear factor κB (NFκB) activation.

Conclusion:  Our results indicate that KTI inhibits LPS‐induced up‐regulation of cytokine expression possibly through suppression of ERK1/2 and p38 kinase‐mediated NFκB activation. These findings may identify anti‐inflammatory properties of KTI at the level of gingival fibroblasts and may be relevant to the use of KTI in modulating inflammation, including periodontal disease.
The correlation between the bone probing, radiographic and histometric measurements of bone level after regenerative surgery
Authors: Yun Jeong‐Ho , Hwang Sung‐Joon , Kim Chang‐Sung , Cho Kyoo‐Sung , Chai Jung‐Kiu , Kim Chong‐Kwan , Choi Seong‐Ho
Published: October 2005

Background and objective:  The most accurate method of assessing bone level is to elevate the flap and measure the bone level directly. However, this method causes discomfort to the patient and can damage the tissues. Therefore, many studies have been conducted to find an alternative method that can be used to assess the bone level clinically with accuracy and reliability. In the present study, we evaluated the clinical reliability and accuracy of bone probing and radiographic measurements, by comparing the bone levels obtained by both of these measurement techniques with the histometrically confirmed bone levels, after four different kinds of regenerative therapy.

Methods:  Twenty‐four intrabony defects (4 × 4 mm one‐wall intrabony defects) were surgically created bilaterally in the mandibular second and fourth premolars of six beagle dogs. The control group underwent a conventional flap operation. The graft group was treated with calcium phosphate glass only, the guided tissue regeneration group was treated with guided tissue regeneration only, and the graft + guided tissue regeneration group was treated with calcium phosphate glass and guided tissue regeneration. Bone probing and radiographic measurements were performed to assess the bone level 8 weeks after the operation and then the subjects were killed to perform the histometric measurements. The correlation between the bone probing depths and the histometric bone levels, and that between the radiographic bone levels and the histometric bone levels were analyzed by Spearman's rank correlation analysis. The statistical significance with respect to the type of regenerative therapy was analyzed by the Kruskal–Wallis test.

Results:  The difference between the bone probing depth and the histometric bone level measurements was 0.14, and that between the radiographic bone level and histometric bone level was 0.6. The coefficient of correlation between the bone probing depth and the histometric bone level was 0.90, and that between the radiographic bone level and the histometric bone level was 0.73. The type of regenerative therapy had no significant effect on the difference between the histometric bone level and the other measurements.

Conclusion:  The results of the present study suggest that the bone probing measurement may be a reliable method for the assessment of the actual bone level following any type of periodontal regenerative therapy.
In vivo Selective Cytoskeleton Dynamics Quantification in Interphase Cells Induced by Pulsed Ultraviolet Laser Nanosurgery
Authors: Colombelli Julien , Reynaud Emmanuel G. , Rietdorf Jens , Pepperkok Rainer , Stelzer Ernst H.K.
Published: October 2005

We report on the manipulation of intracellular filaments using a nanosurgery system based on a subnanosecond pulsed UV laser optimized for the localized severing of biological polymers. By inducing artificial catastrophe of selected microtubules (MTs), we perform shrinkage‐rate measurements in interphase Ptk‐2 cells throughout the entire cell. We quantify the impact of two labeling methods and three fluorescent markers, showing a 25% faster depolymerization with Alexa‐488 tubulin compared with Rhodamine and yellow fluorescent protein (YFP) tubulins and a 20% higher variability induced by microinjection compared with stable transfection. Using EB3‐GFP as a tip marker, we establish a new protocol to measure shrinkage rate, growth rate and rescue frequency simultaneously with high temporal and spatial specificity in live cells. As our analysis shows, laser‐induced MT dynamics are physiologically relevant. The high statistical efficiency that the method offers in terms of numbers of measured events and therefore reduced standard deviations represents an important quantitative improvement in the measurement of dynamic instability parameters in vivo. We extend the application of the method by demonstrating induced dynamic behavior of actin‐stress fibers after severing. This new method enables the quantitative investigation of cytoskeleton dynamics in a local confinement.
Avulsion of primary teeth and sequelae on the permanent successors
Authors: Christophersen Pia , Freund Mette , Harild Liselotte
Published: October 2005

Abstract –  The purpose of the present study was to determine the frequency of avulsion of primary teeth and the location of the avulsed tooth in a representative population of Danish children. Also, the frequency and the type of developmental disturbances in the permanent successors were assessed and related to age at the time of injury. The material included dental records of 4238 children from three clinics in Municipal Dental Health Services near Copenhagen, Denmark. The children were born between 1 January 1983 and 31 December 2000. Thirty‐five children (0.8%) were identified as having avulsed in all 44 primary teeth most frequently the maxillary incisors (89%). Thirty‐three fully erupted permanent successors were included in the study, the prevalence of developmental disturbances was 30% (10 teeth). The results showed the risk of developmental disturbances in the permanent successors to be more frequent the younger the age at the time of injury (P = 0.04). Discolouration affected all 10 permanent teeth, but also hypoplasia and horizontal enamel hypoplasia were found.
Primary tooth injuries in Norwegian children (1–8 years)
Authors: Skaare Anne Berit , Jacobsen Ingeborg
Published: October 2005

Abstract –  This prospective study examined the yearly incidence of traumatic injuries to primary teeth. The aim of the study was to find out more about dental injuries to primary teeth in Norwegian children. The study was performed in one county of Norway involving approximately 20 000 children in the age group 1–8 years. Twenty‐seven public dental clinics and 42 dentists participated. The dentists attended information and calibration meetings and received illustrations of the classification of dental trauma as well as examples of how to fill in the forms correctly. Two hundred and sixty‐six children were involved, including 447 primary teeth, recorded during a 1‐year registration period (2003). The dental trauma incidence was 1.3% with 3.5‐year old being the most accident‐prone. Boys were significantly more often injured than girls, 164 versus 102 (P < 0.001). The upper central incisors were most involved (92%), with a non‐significant difference between the right and left side. The minor periodontal injuries dominated (59%). Hard tissue injuries were far less frequent (13%). Avulsions were observed in 6.5% and intrusions in 7.5% of the injured children, being 5.5% and 5% of the injured teeth. Most of the injuries occurred either at home (38%) or at kindergarten (32%). Sixty‐two percentage were falling accidents often sustained during children's play, and 25% were pure playing accidents.

Conclusion:  In Norwegian children aged 1–8 years, with a predominance of boys, the most common primary tooth injuries were minor luxations of the maxillary central incisors, sustained at an age of 3.5 years. As the traumas often occurred during children's play and/or were the consequence of falls, these are difficult to prevent. However, follow ups should be carried out to disclose pulpal or periodontal complications and/or developmental disturbances of the permanent successors.
Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. A pilot study
Authors: Moreira Maria Stella , Katayama Emilio , Bombana Antonio Carlos , Marques Márcia Martins
Published: October 2005

Abstract –  The use of alendronate, a bisphosphonate which is able to inhibit bone resorption, in order to prevent dental root resorption after tooth replantation would be of clinical relevance. However, this drug must be biocompatible to the periapical tissues. The aim of this study was to analyze the effect of an alendronate paste in polyethyleneglycol (2 g ml−1) on endothelial cells in culture (in vitro) and on rat subcutaneous tissue (in vivo). For the in vitro study the paste was applied on round glass coverslips that were immersed into confluent cell cultures (clone Cips). The cell viability percentages of these cultures were obtained 0, 6 and 12 h after contact with the substance. As control, cultures that received plain coverslips were used. This analysis was carried out in triplicate using the Trypan blue dye exclusion assay. For the in vivo study the paste was introduced into polyethylene tubes that were placed into the rat subcutaneous tissue. The rats were killed 7 and 14 days later; then, the tissue sections stained with hematoxylin–eosin were analyzed. In vitro, the alendronate caused a significant decrease in the cell viability in 6 h (P < 0.05) and 12 h (P < 0.01), when compared with the control cultures. In vivo the tissue response was exuberant and similar at the two experimental times. There was a necrosis in a comprehensive area in contact with the open end of the tube. Presence of micro‐abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo.
The use of enamel matrix derivative (Emdogain®) for improvement of probing attachment level of the autotransplanted teeth
Authors: Hamamoto Yoshioki , Takahashi Kouji , Sakurai Hiromasa , Akiba Katsumi , Izumi Naoya , Kanoh Hiroyuki , Yoshizawa Michiko , Saito Chikara
Published: October 2005

Abstract –  The enamel matrix derivative (EMD, Emdogain®) was used for the purpose to obtain the periodontal regeneration on the denuded root‐surfaces of the donor teeth in two cases of the immediate tooth‐transplantation. The root‐surfaces at the cervical portion of the teeth were denuded because of extrusion. The healthy periodontium of each tooth remained at the apical portion of the roots. The denuded root‐surfaces were cleansed before extraction. Then, the donor teeth were gently extracted with forceps, administered EMD, and transplanted so that the denuded surfaces were covered by gingival flaps. After the transplantation, the mean probing attachment level (PAL) improved 3.2 mm and 1.5 mm, respectively. The mean probing pocket depth was within normal level. The actual supporting areas of the roots of the transplanted teeth increased and the teeth worked as the abutments of prosthetic bridges.
Oral and dental complications of intra‐oral piercing
Authors: Levin Liran , Zadik Yehuda , Becker Tal
Published: October 2005

Abstract –  The present study assessed the prevalence of oral piercing among young adults and revealed the types and rate of complications following oral piecing, as well as the awareness of the complications. The study included 400 consecutive patients, who randomly arrived at a military dental office. Before dental examination, patients were requested to fill out a questionnaire regarding oral piercing, their awareness of its complications, and the occurrence of complications related to piercing. Intra‐oral examination included special attention to piercing‐related complications, such as tooth fractures, gingivitis, bleeding, infections, gingival recessions, etc. A total of 389 patients, 210 (54%) males and 179 (46%) females agreed to participate (97.3% response rate), with an average age of 20.08 ± 1.1 years. Of the participants, 79 (20.3%) reported having at least one type of oral piercing; lingual piercing was the most common. Swelling and bleeding after piercing were reported by 41 (51.9%) and 36 (45.7%) participants, respectively. Among the participants, 225 (57.8%) were unaware of the dangers of intra‐oral piercing. Clinical examination revealed 15 fractured teeth in 11 (13.9%) participants with piercing. Gingival recessions were observed in 21 (26.6%), mostly in the mandibular incisor area. Dentists should be aware of the increasing number of patients with pierced intra‐ and peri‐oral sites and to provide appropriate guidance to patients who contemplate body piercing involving oral sites.
Investigating fragmentation conditions in self-gravitating accretion discs
Authors: Rice W. K. M. , Lodato G. , Armitage P. J.
Published: October 2005

The issue of fragmentation in self-gravitating gaseous accretion discs has implications both for the formation of stars in discs in the nuclei of active galaxies, and for the formation of gaseous planets or brown dwarfs in circumstellar discs. It is now well established that fragmentation occurs if the disc is cooled on a time-scale smaller than the local dynamical time-scale, while for longer cooling times the disc reaches a quasi-steady state in thermal equilibrium, with the cooling rate balanced by the heating due to gravitational stresses. We investigate here how the fragmentation boundary depends on the assumed equation of state. We find that the cooling time required for fragmentation increases as the specific heat ratio γ decreases, exceeding the local dynamical time-scale for γ= 7/5. This result can be easily interpreted as a consequence of there being a maximum stress (in units of the local disc pressure) that can be sustained by a self-gravitating disc in quasi-equilibrium. Fragmentation occurs if the cooling time is such that the stress required to reach thermal equilibrium exceeds this value, independent of γ. This result suggests that a quasi-steady, self-gravitating disc can never produce a stress that results in the viscous α parameter exceeding ∼0.06.