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C Schmitt

Publications and source records attributed to C Schmitt.

At least 73 records · Page 4Linked to original sources

Incidence of electromagnetic interference in implantable cardioverter defibrillators.

Electromagnetic interference (EMI) with ICDs can lead to temporary inhibition of the device or to inappropriate delivery of antitachycardia pacing and shocks. The incidence of interactions between electronic devices and the current generation of ICDs is not known. In a retrospective study of 341 patients (665 patient-years) who underwent a regular follow-up every 3 months, five episodes of EMI were detected in four different patients. The risk for receiving inappropriate shocks due to EMI is < 1% per year and patient. In conclusion, although inappropriate delivery of shocks by ICDs due to EMI rarely occurs, patient information should emphasize the avoidance of situations of possible interference. Further efforts concerning lead technology and detection algorithms are necessary to minimize the risk of EMI.

Aged↗

Internal low energy cardioversion of atrial fibrillation using a single lead system: comparison of a left and right pulmonary artery catheter approach.

Internal cardioversion (ICV) has been demonstrated as an effective and safe method for restoring sinus rhythm in patients with AF. Recently, a new single lead system with a balloon-guided cardioversion catheter was introduced. ICV was performed after advancing a 7.5 Fr catheter flow-directed into the left or right pulmonary artery (PA, distal array, cathode). The proximal array (anode) was placed at the lateral RA wall. Synchronized shocks (3/3 ms biphasic impulse) were applied using a stepwise protocol (0.5, 3, 6, 9, 12, 15 J) until sinus rhythm was restored or maximum energy (15 J) was reached. Sixty-five patients (mean age 58 +/- 13 years) with acute and chronic AF were included. Sinus rhythm could be restored in 59 (91%) patients. Cardioversion success was 93% in the left PA compared to 86% in right PA. DFTs for the left and right PA approaches were 7.1 +/- 4.0 J and 10.2 +/- 4.0 J, respectively (P < 0.0001). It was significantly higher in patients with an AF history > 7 days (7.2 +/- 4.1 J) than for those with a recent onset of AF (5.6 +/- 4.1 J), P = 0.0012. Shock impedance differed for the left and right PA lead configuration (53 +/- 11 vs 49 +/- 13 omega, P < 0.05). A right PA lead configuration is as effective compared to a left PA catheter approach when performing ICV for AF. ICV with a single lead system is safe and cardioversion success is comparable to other internal and external cardioversion techniques. In combination with hemodynamic monitoring, flow-directed nonfluoroscopic catheter positioning is feasible and may serve as a valuable therapeutic and diagnostic tool in intensive care units.

Adult↗

Inappropriate shock delivery due to ventricular double detection with a biventricular pacing implantable cardioverter defibrillator.

This report describes a patient with advanced heart failure, pronounced intraventricular conduction delay, and ventricular tachycardias who underwent implantation of a multisite pacing ICD. Pacing leads were placed in the right atrium, right ventricular apex, and to the left ventricular posterior wall via a coronary sinus vein. The system proved to have correct sensing and pacing function in an atrial synchronized biventricular pacing mode and an appropriate detection of ventricular fibrillation. However, 1 month after implantation the patient received an inappropriate shock delivery due to double detection of ventricular premature beats. The inherent detection problem of dual ventricular sensing is discussed.

Defibrillators, Implantable↗

Internal atrial defibrillation during electrophysiological studies and focal atrial fibrillation ablation procedures.

Induction of sustained AF during electrophysiological studies requires electrical cardioversion to restore sinus rhythm for continuation of the electrophysiological study and mapping procedure. The study included 104 consecutive patients (age 59 +/- 12 years, 74 men), who were in stable sinus rhythm at the beginning of the electrophysiological study, underwent internal atrial defibrillation (IAD) of AF (> 15 minutes) that was induced during electrophysiological study. In 21 patients, AF was regarded to be the clinical problem (group I), and in the remaining 83 patients other arrhythmias represented the primary target of the electrophysiological study (group II). A 7.5 Fr cardioversion catheter (EP Medical) equipped with a distal array was used and placed in the left pulmonary artery and a proximal array of the same size was located along the lateral right atrial wall. All patients were successfully cardioverted with a mean energy of 6.2 +/- 4.0 1. In 18 (78%) of 21 group I patients and in 12 (14%) of 81 group II patients, AF recurred 3.7 +/- 3.4 and 2.4 +/- 1.4 times during electrophysiological study, respectively. The IAD shock did not suppress focal activity, thus the mapping of atrial foci responsible for AF could be continued even after several IADs. No IAD related complications occurred during the study. In conclusion, (1) IAD can be safely and successfully performed during electrophysiological study without using narcotic drugs or high electric energies; (2) IAD does not suppress focal activity; and (3) even if AF recurs frequently during the electrophysiological study, IAD can be performed several times without significant time delay.

Atrial Fibrillation↗

Noncontact mapping-guided ablation of atrial flutter and enhanced-density mapping of the inferior vena caval-tricuspid annulus isthmus.

Three-dimensional visualization of cardiac activation has become important in providing further insights into pathophysiological mechanisms of arrhythmias and to increase the efficacy of catheter ablation. The noncontact mapping enables a single beat analysis in a reconstructed geometry of the cardiac chamber. The aim of the study was to describe three-dimensional activation patterns and inferior vena caval-tricuspid annulus (IVC-TA) isthmus conduction characteristics in patients with atrial flutter and the noncontact guidance of the radiofrequency ablation of this arrhythmia. In 34 patients with atrial flutter, the noncontact probe was deployed in the RA. The global three-dimensional activation and the isthmus conduction (enhanced density mapping) were delineated during ongoing a trial flutter and paced rhythms. Ablation was performed nonfluoroscopically based on reconstructed anatomy and conduction patterns. Noncontact mapping was compared and validated with conventional multielectrode technique. IVC-TA isthmus ablation was completed successfully in 33 (97%) of 34 patients. In one patient a lower loop reentry around the inferior vena cava was depicted as a mechanism of atrial flutter. In another patient with positive flutter waves in inferior leads, an activation pattern typical of counterclockwise flutter was demonstrated in propagation maps. During a follow-up of 15.9 +/- 5.9 months, two atrial flutter recurrences occurred (5.8%). A gap of the resumed conduction through the IVC-TA isthmus was delineated as a mechanism of recurrence and ablated with one and three radiofrequency applications. Noncontact mapping allows construction of the global activation patterns in typical and atypical atrial flutter. It enables the nonfluoroscopic guidance of atrial flutter ablation and a comprehensive evaluation of the ablation results.

Atrial Flutter↗

Pseudotermination of intermittent atrial fibrillation by a pacemaker algorithm: antitachycardia pacing without capture miscounted as successful termination of fibrillation episodes.

A patient is described with intermittent AF and an implanted pacemaker which provides preventive pacing and overdrive stimulation designated to terminate atrial arrhythmias. The case highlights the possibility of false estimation of therapeutic efficacy and possible proarrhythmic effect of this therapeutic modality.

Algorithms↗

Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter defibrillators in reducing inappropriate therapies? A randomized, prospective study.

INTRODUCTION: Supraventricular tachyarrhythmias are the main cause of inappropriate therapies in patients with conventional single chamber implantable cardioverter defibrillators (VVI-ICD). It was anticipated that dual chamber cardioverter defibrillators (DDD-ICD), with their capacity to analyze atrial and ventricular rhythm, could substantially reduce inappropriate therapies. METHODS AND RESULTS: Our prospective study included 92 patients (87 men; mean age 61 +/- 12.7 years) who were randomly assigned to a VVI-ICD (45 patients) or a DDD-ICD (47 patients). Both groups were followed for 7.5 +/- 3.5 and 7.6 +/- 4.1 months, respectively. During the follow-up period, overall 725 ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes were recorded in 45 (49%) of 92 patients. Of these episodes, 404 (56%) occurred in the VVI-ICD group and 321 (44%) episodes occurred in the DDD-ICD group. Twenty-three (51%) patients in the VVI-ICD group and 22 (47%) patients in the DDD-ICD group (P = 0.8) developed VT/VF. Overall, 73 (10%) of 725 treated episodes were inappropriate in 6 (13%) patients in the VVI group and in 10 (21%) patients in the DDD-ICD group (P = 0.2). There were 22 (31%) inappropriately treated episodes in the VVI-ICD group and 51 (69%) in the DDD-ICD group. Thirty-two of the 51 inappropriate episodes in the DDD-ICD patients resulted from intermittent atrial sensing problems that led to failure of the respective dual chamber algorithms. Nonfatal complications occurred in 6 (13%) patients in the VVI-ICD group and in 3 (6%) patients in the DDD-ICD group (P = 0.7). CONCLUSION: We conclude that the implanted DDD-ICD and conventional VVI-ICD are equally safe and effective for therapy of life-threatening ventricular tachyarrhythmias. Although DDD-ICDs allow better rhythm classification, the applied detection algorithms do not offer benefits in avoiding inappropriate therapies during supraventricular tachyarrhythmias.

Aged↗

Dissociation between coronary sinus and left atrial conduction in patients with atrial fibrillation and flutter.

INTRODUCTION: Coronary sinus (CS) recordings are routinely used during electrophysiologic studies for various supraventricular and ventricular arrhythmias with the understanding that they represent left atrial (LA) activity. However, the behavior of CS electrical activity during atrial arrhythmias has not drawn any special attention beyond standard considerations. METHODS AND RESULTS: The study population consisted of 9 patients (3 women; mean age 59 +/- 11 years) with atrial fibrillation (AF) and atrial flutter (AFL) who developed dissociation of conduction between the CS and posterior LA during spontaneous AF and AFL. In all patients, the LA and the CS were mapped using a 64-electrode basket catheter and a multipolar electrode catheter, respectively. The right atrium (RA) was mapped simultaneously using a 24-polar electrode catheter (7 patients) or a 64-electrode basket catheter (2 patients). Eight patients showed stable double potentials in CS recordings during AF (9 episodes) and AFL (3 episodes). During ongoing arrhythmias, the first row of potentials maintained a constant relationship with the RA activity, whereas the second row of potentials was discordant with the posterior wall of the LA in 7 patients and concordant in 2 patients. In 1 patient with counterclockwise AFL, CS activation was isolated from the posterior wall of the RA until it reached the distal portion of the CS, after which it entered the lateral region of the LA. In 1 patient, a macroreentrant LA tachycardia involving CS muscle was observed. Rapid atrial pacing from the proximal CS and extrastimuli produced longitudinal dissociation of CS activation in all patients. CONCLUSION: Conduction between the CS and posterior LA can be dissociated during spontaneous atrial arrhythmias and provocative proximal CS pacing.

Arrhythmias, Cardiac↗

Activation patterns in the left atrium during counterclockwise and clockwise atrial flutter.

INTRODUCTION: Activation of the left atrium (LA) in patients with isthmus-dependent right atrial flutter (AFL) has not yet been studied. The aim of this study was to analyze the activation patterns in the LA in patients with counterclockwise and clockwise AFL. METHODS AND RESULTS: The study population consisted of 12 patients (10 men and 2 women; mean age 61+/-13 years) with documented AFL and atrial fibrillation referred for ablation. The LA was mapped with a 64-electrode basket catheter inserted through a transseptal approach (10 patients) or an open foramen ovale (2 patients). In patients with counterclockwise AFL (10 episodes), the LA was activated for a mean of 133+/-28 msec. Two endocardial breakthroughs of earliest activity on the left side of the interatrial septum, separated in time by an interval of 38+/-15 msec, were observed in 9 episodes (90%). Two wavefronts originated from these breakthroughs, which activated the posterior and the anterior LA walls, respectively. In one patient, the entire LA was activated from the inferior breakthrough. In patients with clockwise AFL (five episodes), the LA activation time was 130+/-13 msec. During ongoing episodes, two early electrical breakthroughs, separated in time by an interval of 41+/-15 msec, appeared in the high anteroseptal and low posteroseptal LA regions. The superior wavefront that emerged from the high anterolateral LA region was the dominant activation pathway in 4 (80%) of 5 episodes. CONCLUSION: In patients with AFL, the LA is activated by two wavefronts originating from the high anterior and the low posterior regions of the interatrial septum. The sequence of activation of these interatrial connections in counterclockwise or clockwise AFL and the conductive properties of the LA conduction pathways determine the activation patterns in the LA.

Activation Analysis↗

Maintenance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation; sotalol vs bisoprolol.

AIMS: The purpose of the study was to compare the efficacy and safety of sotalol and bisoprolol in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. METHODS: Patients (n=128) were randomized to sotalol (80 mg b.i.d.) or bisoprolol (5 mg x day(-1)). Patients with contraindications to beta-blockers, class III antiarrhythmic drugs or prior treatment with use of study medication for prevention of atrial fibrillation were excluded. Follow-up clinical evaluation was performed 1 day and 1 month after cardioversion and thereafter at 3-month intervals. RESULTS: There were no group differences in baseline clinical characteristics. After a follow-up of 12 months, 59% of all patients were still in sinus rhythm. The fraction remaining in sinus rhythm was calculated for the two groups by Kaplan--Meier analysis. During follow-up, 41% of patients on sotalol and 42% on bisoprolol developed atrial fibrillation (ns). In two patients (3.1%) on sotalol, life-threatening proarrhythmias (torsade de pointes tachycardias) occurred, whereas none were found in the bisoprolol group. Symptomatic bradycardias occurred in two patients on sotalol and three on bisoprolol. CONCLUSION: This study demonstrates that sotalol (160 mg x day(-1)) and bisoprolol (5 mg x day(-1)) are equally effective in maintaining sinus rhythm. Because of the side effects of sotalol, bisoprolol seems to be advantageous for maintenance of sinus rhythm after cardioversion of atrial fibrillation.

Adrenergic beta-Antagonists↗

Interobserver agreement for EUS in the evaluation and diagnosis of submucosal masses.

INTRODUCTION: EUS is an accurate means of evaluating and diagnosing submucosal lesions of the GI tract. The aim of this study was to prospectively determine interobserver agreement for the EUS classification of submucosal masses among endosonographers with different levels of training and experience from multiple centers. METHODS: Twenty patients with submucosal mass lesions diagnosed by upper endoscopy underwent EUS. Surgical findings were available for 16 patients. In 4 patients with obvious cystic/vascular structures (i.e., varices) no surgical specimen was necessary. A blinded observer developed a study videotape of critical endoscopic and EUS real-time imaging for each lesion. The videotape was distributed to 10 endosonographers, each with at least 1 year of experience, who independently reviewed the videotape and recorded their diagnosis based on EUS features. These endosonographers used previously agreed-upon standardized EUS diagnostic criteria for each category of lesion. A kappa (kappa) statistic, used to evaluate agreement, was calculated for each lesion category for the 10 endosonographers as a group and individually. An overall kappa statistic was also calculated. Significance was analyzed with a two-tailed t test. RESULTS: Agreement was excellent for cystic lesions (kappa = 0.80) and extrinsic compressions (kappa = 0.94), good for lipoma (kappa = 0.65), fair for leiomyoma and vascular lesions (kappa = 0.53 and 0.54, respectively), and poor for other submucosal lesions (kappa = 0.34). Overall agreement among observers was good (kappa = 0.63). Furthermore, a significant association was noted between total years of EUS experience and the number of correct answers (p = 0.01). CONCLUSIONS: Interobserver agreement is good for characterizing submucosal masses by EUS. However, it appears to be better for some lesions than others. The overall length of experience with EUS appears to play an important role in the accuracy of this modality in the evaluation of submucosal lesions.

Endosonography↗

Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain associated with chronic pancreatitis: a prospective single center experience.

OBJECTIVE: In our previous randomized trial, we suggested a possible role for endoscopic ultrasound (EUS) guided celiac plexus block in the treatment of abdominal pain associated with chronic pancreatitis. The purpose of this study was to evaluate our prospective experience with EUS-guided celiac plexus block for controlling pain attributed to chronic pancreatitis, including follow-up on response rates and complications. METHODS: All subjects enrolled had documented chronic pancreatitis by ERCP and EUS criteria and presented with chronic abdominal pain unresponsive to current treatment options. All were treated with EUS-guided celiac plexus block under the guidance of linear array endosonography using a 22-gauge FNA needle (GIP, Mediglobe Inc., Tempe, AZ) inserted on each side of the celiac area, followed by injection of 10 cc bupivacaine (0.25%) and 3 cc (40 mg) triamcinolone on each side of the celiac plexus. Individual pain scores, based on a visual analog scale (0-10), were determined preblock and postblock by a nurse at 2, 7, 14 days and monthly thereafter. Subjects also rated their overall comfort level during the EUS procedure. RESULTS: EUS-guided celiac plexus block was performed in 90 subjects (40 males, 50 females) having a mean age of 45 yr (range 17-76 yr) between July 1, 1995 and December 30, 1996. A significant improvement in overall pain scores occurred in 55% (50/90) of patients. The mean pain score decreased from 8 to 2 post EUS celiac block at both 4 and 8 wk follow-up (p < 0.05). In 26% of patients there was persistent benefit beyond 12 wk, and 10% still had persistent benefit at 24 wk, including three patients who were pain-free between 35 and 48 wk. Younger patients (<45 yr of age) and those having previous pancreatic surgery for chronic pancreatitis were unlikely to respond to the EUS-guided celiac block. Three patients experienced diarrhea post EUS celiac block, which resolved in 7-10 days; however, it is unclear whether this diarrhea was due to the block or to refractory disease. A cost comparison between the EUS ($1200) and CT ($1400) techniques shows the EUS celiac block to be less costly and perhaps more cost efficient in a subset of subjects. CONCLUSIONS: EUS-guided celiac plexus block appears to be safe, effective, and economical for controlling pain in some patients with chronic pancreatitis. Younger patients (<45 yr) and those having prior pancreatic surgery for chronic pancreatitis do not appear to benefit from this technique. Prophylactic antibiotics should be considered if acid suppressing agents are being taken.

Abdominal Pain↗

Diagnosis of acute myocardial infarction in angiographically documented occluded infarct vessel : limitations of ST-segment elevation in standard and extended ECG leads.

STUDY OBJECTIVES: The majority of thrombolysis studies require defined ST-segment elevations as an inclusion criterion for the diagnosis of acute myocardial infarction (AMI). However, depending on the occluded infarct vessel and the criteria applied, the ECG diagnosis of AMI can be difficult to establish. Accordingly, this study was performed to evaluate the sensitivity of ST-segment elevation of standard and extended ECG leads in a cohort of patients with angiographically confirmed diagnosis of AMI. PATIENTS AND METHODS: In 418 patients (mean +/- SD age, 60 +/- 13 years) with AMI (pain onset, 4.8 +/- 3.0 h), coronary angiography with percutaneous transluminal coronary angioplasty/stenting of the culprit lesion was performed. The diagnosis of AMI was confirmed by emergency coronary angiography and laboratory analyses. ST-segment elevation (in two contiguous leads) of 1 mm in standard lead I through aVF and ST-segment elevations of 2 mm (or 1 mm, corresponding values presented in parentheses) in V(1) through V(6) were considered significant. In a subset of 102 AMI patients, additional right precordial leads V(3)R through V(6)R for evaluation of right ventricular infarction and additional chest leads V(7) through V(9) for evaluation of posterior infarction were recorded. ST-segment elevations of 1 mm in the right precordial leads and 1 mm or 0.5 mm in the posterior leads were considered significant. RESULTS: Standard leads I through V(6) showed ST-segment elevation in 85% (96%) of patients with left anterior descending artery occlusion, in 46% (61%) of patients with left circumflex coronary artery (CX) occlusion, and in 85% (90%) of patients with right coronary artery occlusion. On consideration of additional ECG tracings in the subgroup of 102 patients (V(3)R through V(6)R and V(7) through V(9)), the respective numbers increased by 2 to 8% depending on different criteria for ST-segment elevation; in patients with CX occlusion, the increase amounted to 6 to 14%. There was a trend toward an extended infarct size (maximum creatine kinase [CK] values) with concomitant ST-segment elevation in additional ECG leads as assessed by maximum CK levels. CONCLUSIONS: The sensitivity of the ECG diagnosis of AMI is only marginally increased by extended precordial chest leads. There is a trend toward an extended infarct size in those patients with concomitant ST-segment elevation in additional ECG leads.

Angioplasty, Balloon, Coronary↗

Quantitation of hepatitis C virus RNA in saliva and serum of patients coinfected with HCV and human immunodeficiency virus.

The presence and the quantity of hepatitis C virus (HCV) RNA were investigated in saliva and serum of patients infected with both HCV and human immunodeficiency virus (HIV). Paired serum and saliva samples were collected from 59 HIV-HCV coinfected patients. HCV RNA was detected by nested-PCR, using primers derived from the 5' non-coding region of HCV, and positive results were quantified using the b-DNA method. HCV RNA was detected in the saliva of 22/59 (37.3%) patients, with a mean level of 1.15 x 10(6) genome equivalents/ml; there was no correlation of salivary positivity with immune status (CD4 cell count), age or HIV risk group, but there was with gender (19/38 [50%] positive results in male, compared to 3/21 [14.3%] in female, P = 0.007). HCV RNA was detected in the serum of 45/59 (76.3%) patients at a higher level (mean of 2.52 x 10(7) genome equivalents/ml) compared to saliva. Positivity was not correlated with age, gender or CD4 + cell count. There was a correlation between qualitative saliva and serum results (P = 0.003), but not between quantifications (P = 0.57). This first study reporting significant amounts of HCV RNA in saliva could have important implications for HCV epidemiology.

Adult↗

Characterization of dendritic cell differentiation pathways from cord blood CD34(+)CD7(+)CD45RA(+) hematopoietic progenitor cells.

To better characterize human dendritic cells (DCs) that originate from lymphoid progenitors, the authors examined the DC differentiation pathways from a novel CD7(+)CD45RA(+) progenitor population found among cord blood CD34(+) cells. Unlike CD7(-)CD45RA(+) and CD7(+)CD45RA(-) progenitors, this population displayed high natural killer (NK) cell differentiation capacity when cultured with stem cell factor (SCF), interleukin (IL)-2, IL-7, and IL-15, attesting to its lymphoid potential. In cultures with SCF, Flt3 ligand (FL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha (standard condition), CD7(+)CD45RA(+) progenitors expanded less (37- vs 155-fold) but yielded 2-fold higher CD1a(+) DC percentages than CD7(-)CD45RA(+) or CD7(+)CD45RA(-) progenitors. As reported for CD34(+)CD1a(-) thymocytes, cloning experiments demonstrated that CD7(+)CD45RA(+) cells comprised bipotent NK/DC progenitors. DCs differentiated from CD7(-)CD45RA(+) and CD7(+)CD45RA(+) progenitors differed as to E-cadherin CD123, CD116, and CD127 expression, but none of these was really discriminant. Only CD7(+)CD45RA(+) or thymic progenitors differentiated into Lag(+)S100(+) Langerhans cells in the absence of exogenous transforming growth factor (TGF)-beta 1. Analysis of the DC differentiation pathways showed that CD7(+)CD45RA(+) progenitors generated CD1a(+)CD14(-) precursors that were macrophage-colony stimulating factor (M-CSF) resistant and CD1a(-)CD14(+) precursors that readily differentiated into DCs under the standard condition. Accordingly, CD7(+)CD45RA(+) progenitor-derived mature DCs produced 2- to 4-fold more IL-6, IL-12, and TNF-alpha on CD40 ligation and elicited 3- to 6-fold higher allogeneic T-lymphocyte reactivity than CD7(-)CD45RA(+) progenitor-derived DCs. Altogether, these findings provide evidence that the DCs that differentiate from cord blood CD34(+)CD7(+)CD45RA(+) progenitors represent an original population for their developmental pathways and function. (Blood. 2000;96:3748-3756)

Adult↗

A new method for the evaluation of matches in non-recombining genomes: application to Y-chromosomal short tandem repeat (STR) haplotypes in European males.

A 9-locus microsatellite framework (minimal haplotype), previously developed for forensic purposes so as to facilitate stain analysis, personal identification and kinship testing, has been adopted for the establishment of a large reference database of male European Y-chromosomal haplotypes. The extent of population stratification pertaining to this database, an issue crucial for its practical forensic application, was assessed through analysis of molecular variance (AMOVA) of the 20 regional samples included. Despite the notion of some significant haplotype frequency differences, which were found to correlate with known demographic and historic features of Europeans, AMOVA generally revealed a high level of genetic homogeneity among the populations analyzed. Owing to their high diversity, however, accurate frequency estimation is difficult for Y-STR haplotypes when realistic (i.e. moderately sized) datasets are being used. As expected, strong pair-wise and higher order allelic associations were found to exist between all markers studied, implying that haplotype frequencies cannot be estimated as products of allele frequencies. A new extrapolation method was therefore developed which treats haplotype frequencies as random variables and generates estimates of the underlying distribution functions on the basis of closely related haplotypes. This approach, termed frequency 'surveying', is based upon standard population genetics theory and can in principle be applied to any combination of markers located on the Y-chromosome or in the mitochondrial genome. Application of the method to the quality assured reference Y-STR haplotype database described herein will prove very useful for the evaluation of positive trace-donor matches in forensic casework.

Alleles↗