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PubMed2004

Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence.

INTRODUCTION: Recurrence of atrial fibrillation (AF) may be related to AF-induced electrical remodeling characterized by shortening of the atrial action potential duration (APD) and loss of its rate adaptation. We investigated the effects of pretreatment with oral d,l-sotalol on rate-dependent changes in atrial monophasic action potential (MAP) duration after cardioversion of chronic AF with reference to the efficacy in preventing the arrhythmia recurrence. METHODS AND RESULTS: MAPs were recorded from the right atrium at six pacing cycle lengths (CLs) from 300 to 750 ms in 19 chronic AF patients after electrical cardioversion; 9 had been pretreated with oral d,l-sotalol (196 +/- 42 mg/day) for 7 days and 10 were untreated. MAP duration at 90% repolarization (MAPD90) in 11 control patients increased progressively with increases in CLs from 209 +/- 19 ms at CL = 300 ms to 264 +/- 28 ms at CL = 750 ms. In AF patients without sotalol, the CL-MAPD relation was shifted downward and flattened at longer CLs; MAPD90 values were 206 +/- 11 ms and 227 +/- 16 ms at CLs of 300 and 750 ms, respectively. MAPD90 values at CLs > or =500 ms in AF were significantly shorter than controls. In AF patients with sotalol, the normal CL-MAPD relation was preserved; MAPD90 increased from 226 +/- 19 ms to 282 +/- 46 ms in the CL range. AF recurred within 2 weeks after cardioversion in 14 of 24 patients pretreated with d,l-sotalol (216 +/- 51 mg/day) despite of continuation of sotalol treatment. CONCLUSION: Sotalol reverses AF-induced decrease in MAPD adaptation to rate in the atria of chronic AF patients, but this effect does not lead to prevention of AF recurrence.

Action Potentials↗
PubMed1996

A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms.

The ultimate informativeness of the zebrafish mutations described in this issue will rest in part on the ability to clone these genes. However, the genetic infrastructure required for the positional cloning in zebrafish is still in its infancy. Here we report a reference cross panel of DNA, consisting of 520 F2 progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map by 102 simple sequence length polymorphisms. This reference cross DNA provides: (1) a panel of DNA from the cross that was used to construct the genetic linkage map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for the development of a physical map (an ordered array of clones each containing a known portion of the genome). This reference cross DNA will serve as a resource enabling investigators to relate genes or genetic markers directly to a single genetic linkage map and avoid the problem of integrating different maps with different genetic markers, as must be currently done when using randomly amplified polymorphic DNA markers, or as has occurred with human genetic linkage maps.

Alleles↗
PubMed2000

Body surface mapping of counterclockwise and clockwise typical atrial flutter: a comparative analysis with endocardial activation sequence mapping.

OBJECTIVES: This study was directed at developing spatial 62-lead electrocardiogram (ECG) criteria for classification of counterclockwise (CCW) and clockwise (CW) typical atrial flutter (Fl) in patients with and without structural heart disease. BACKGROUND: Electrocardiographic classification of CCW and CW typical atrial Fl is frequently hampered by inaccurate and inconclusive scalar waveform analysis of the 12-lead ECG. METHODS: Electrocardiogram signals from 62 torso sites and multisite endocardial recordings were obtained during CCW typical atrial Fl (12 patients), CW typical Fl (3 patients), both forms of typical Fl (4 patients) and CCW typical and atypical atrial Fl (1 patient). All the Fl wave episodes were divided into two or three successive time periods showing stable potential distributions from which integral maps were computed. RESULTS: The initial, intermediate and terminal CCW Fl wave map patterns coincided with: 1) caudocranial activation of the right atrial septum and proximal-to-distal coronary sinus activation, 2) craniocaudal activation of the right atrial free wall, and 3) activation of the lateral part of the subeustachian isthmus, respectively. The initial, intermediate and terminal CW Fl wave map patterns corresponded with : 1) craniocaudal right atrial septal activation, 2) activation of the subeustachian isthmus and proximal-to-distal coronary sinus activation, and 3) caudocranial right atrial free wall activation, respectively. A reference set of typical CCW and CW mean integral maps of the three successive Fl wave periods was computed after establishing a high degree of quantitative interpatient integral map pattern correspondence irrespective of the presence or absence of organic heart disease. CONCLUSIONS: The 62-lead ECG of CCW and CW typical atrial Fl in man is characterized by a stereotypical spatial voltage distribution that can be directly related to the underlying activation sequence and is highly specific to the direction of Fl wave rotation. The mean CCW and CW Fl wave integral maps present a unique reference set for improved clinical detection and classification of typical atrial Fl.

Aged↗
PubMed2005

The lumbar multifidus muscle and patterns of pain.

This paper describes the patterns of pain induced by injecting hypertonic saline into the lumbar multifidus muscle opposite the L5 spinous process in 15 healthy adult volunteers. All subjects experienced local pain while referred pain was reported by 13 subjects in one of two regions of the thigh; anterior (n=5) or posterior (n=8). These results confirm that the multifidus muscle may be a source of local and referred pain. Comparison of these maps with pain maps following stimulation of the L4 medial dorsal rami and L4-5 interspinous ligaments shows that pain arising from the band of multifidus innervated by the L4 dorsal ramus has a segmental distribution. In addition patterns of pain arising from multifidus clearly overlap those reported for other lumbar structures. These findings highlight the difficulty of using pain distribution to accurately identify specific lumbar structures as the source of pain.

Adult↗
PubMed2001

The effects of the lurcher mutation on object localization, T-maze discrimination, and radial arm maze tasks.

The Lurcher mutation is characterized by degeneration of the cerebellar cortex and cerebellar ataxia. The mutants were compared to littermate controls of the same background strain in three spatial tasks: 1) left-right discrimination in a water-filled T-maze, a reference memory task requiring a win-stay strategy; 2) the radial arm maze, a working memory task requiring a win-shift strategy; 3) object localization, a reference memory task requiring the use of cognitive mapping. Lurcher mutants were impaired in the object localization and radial arm maze tasks but not in the left-right discrimination task. These results indicate that trial-independent tasks and reference memory tasks using cognitive mapping may be particularly vulnerable to cerebellar degeneration.

Animals↗
PubMed1999

Experimental human muscle pain induced by intramuscular injections of bradykinin, serotonin, and substance P.

After intramuscular (m. tibialis anterior) injection of three different algogenic substances, the pain intensity was continuously scored on a visual analogue scale (VAS) in eight volunteers. The subject drew the distribution of the local and referred pain areas on a map. Four times within the first hour after injection, the pressure pain-thresholds (PPTs) and supra pressure-pain thresholds were assessed at the injection point, 2 cm distal from the injection site, at the arm, and at the contralateral leg. Measurements were done before and after injection of 0.5 ml of the algogenic substance [bradykinin (BKN), serotonin (5-HT), substance P (SP)], and isotonic saline as control. Cutaneous sensitivity to mechanical stimuli was assessed with a Von Frey hair at the same location as PPT determinations.The pain intensity (VAS-peak) after BKN (2, 4, and 10 nmol) and 5-HT (2, 4, and 20 nmol) was significantly higher (p< 0.05) than after SP (0.2, 0.4, and 0.8 nmol) and isotonic saline. The VAS-peak after infusions of hypertonic saline was significantly higher (p< 0.05) compared with VAS-peaks after all other substances. A significantly larger (p< 0.05) local pain area was found after BKN compared with isotonic saline. After injections of hypertonic saline, the offsets of evoked pain were significantly longer (p< 0.05) and the local and referred pain areas were significantly larger (p< 0.05) compared with all other substances. There was no dose-response relation between the pain intensity and the different doses of BKN, 5-HT, and SP. PPTs and skin sensitivity were not affected by any of the injections.We conclude that under the present experimental conditions, BKN and 5-HT can produce low levels of muscle pain after intramuscular injection. In the used concentrations, however, BKN, 5-HT, and SP did not generate cutaneous or muscular hyperalgesia. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed2006

A high-density consensus map of barley to compare the distribution of QTLs for partial resistance to Puccinia hordei and of defence gene homologues.

A consensus map of barley was constructed based on three reference doubled haploid (DH) populations and three recombinant inbred line (RIL) populations. Several sets of microsatellites were used as bridge markers in the integration of those populations previously genotyped with RFLP or with AFLP markers. Another set of 61 genic microsatellites was mapped for the first time using a newly developed fluorescent labelling strategy, referred to as A/T labelling. The final map contains 3,258 markers spanning 1,081 centiMorgans (cM) with an average distance between two adjacent loci of 0.33 cM. This is the highest density of markers reported for a barley genetic map to date. The consensus map was divided into 210 BINs of about 5 cM each in which were placed 19 quantitative trait loci (QTL) contributing to the partial resistance to barley leaf rust (Puccinia hordei Otth) in five of the integrated populations. Each parental barley combination segregated for different sets of QTLs, with only few QTLs shared by any pair of cultivars. Defence gene homologues (DGH) were identified by tBlastx homology to known genes involved in the defence of plants against microbial pathogens. Sixty-three DGHs were located into the 210 BINs in order to identify candidate genes responsible for the QTL effects. Eight BINs were co-occupied by a QTL and DGH(s). The positional candidates identified are receptor-like kinase, WIR1 homologues and several defence response genes like peroxidases, superoxide dismutase and thaumatin.

Basidiomycota↗
PubMed1994

Value of body surface mapping in localizing the site of origin of ventricular tachycardia in patients with previous myocardial infarction.

OBJECTIVES: This study examined the performance of the 62-lead body surface electrocardiogram (ECG) in identifying the site of origin of ventricular tachycardia in patients with a previous myocardial infarction. BACKGROUND: Because the accuracy of ECG localization of ventricular tachycardia using standard 12-lead recordings is restricted to the identification of rather large ventricular areas, application of multiple torso lead recordings may augment the resolving power of the surface ECG and result in more discrete localization of arrhythmogenic foci. METHODS: Thirty-two patients were selected for electrophysiologically guided ablative therapy for drug-resistant postinfarction ventricular tachycardia. In these patients, QRS integral maps of distinct monomorphic ventricular tachycardia configurations were correlated with a previously generated infarct-specific reference data base of paced QRS integral maps. Each paced pattern in the data base corresponded with ectopic endocardial impulse formation at 1 of 18 or 22 discrete segments of the left ventricle with a previous anterior or inferior myocardial infarction, respectively. Electrocardiographic localization was compared with the results obtained during intraoperative or catheter endocardial activation sequence mapping. RESULTS: Body surface mapping was performed during 101 distinct ventricular tachycardia configurations. Compared with the activation mapping data that were acquired in 64 of 101 ventricular tachycardias, body surface mapping identified the correct segment of origin in 40 (62%) of 64 tachycardias, a segment adjacent to the segment where the arrhythmia actually originated in 19 (30%) of 64 tachycardias and a segment disparate from the actual segment of origin in 5 (8%) of 64 tachycardias. With respect to infarct location, the segment of origin was correctly identified in 28 (60%) of 47 ventricular tachycardias in patients with anterior, 7 (70%) of 10 tachycardias in patients with inferior and 5 (71%) of 7 tachycardias in patients with combined anterior and inferior myocardial infarction. CONCLUSIONS: This study shows that body surface mapping enables precise localization of the origin of postinfarction ventricular tachycardia in 62% and regional approximation in 30% of tachycardias. The multiple-lead ECG may be used to guide and shorten catheter-based mapping procedures during ventricular tachycardia and to provide relevant information on the origin of tachycardias that cannot be mapped with conventional single-site mapping techniques because of unfavorable characteristics.

Body Surface Potential Mapping↗
PubMed1998

Symptom provocation of fluoroscopically guided cervical nerve root stimulation. Are dynatomal maps identical to dermatomal maps?

STUDY DESIGN: This prospective study consisted of mechanical stimulation of cervical nerve roots C4 to C8 in patients with cervical radicular symptoms undergoing diagnostic selective nerve root block. OBJECTIVES: To document the distribution of pain and paresthesias that result from stimulation of specific cervical nerve roots and compare that distribution to documented sensory dermatomal maps. SUMMARY OF BACKGROUND DATA: Cervical dermatomes were first studied in the late 19th century. The results of those studies underpin current clinical decision making for patients with neck and arm pain. However, it has been observed that patients with radicular symptoms may have cervical pathology by radiographic imaging that is not corroborative, or have imaging studies that suggest a lesion at a level other than the one suggested by the patient's dermatomal symptoms. These observations may suggest that cervical dermatomal mapping is inaccurate or the distribution of referred symptoms (dynatome) from cervical root irritation is different than the sensory deficit outlined by dermatomal maps. METHODS: Inclusion criteria consisted of consecutive patients undergoing fluoroscopically guided diagnostic cervical selective nerve root blocks from C4 to C8. Immediately preceding contrast injection, mechanical stimulation of the root was performed. An independent observer interviewed and recorded the location of provoked symptoms on a pain diagram. Visual data was subsequently compiled using a 793 body sector bit map. Forty-three clinically relevant body regions were defined on this bit map. Frequencies of symptom provocation and likelihood of symptom location from C4 to C8 stimulation of each nerve root were generated. RESULTS: One hundred thirty-four cervical nerve root stimulations were performed on 87 subjects. There were 4 nerve root stimulations at C4, 14 at C5, 43 at C6, 52 at C7, and 21 at C8. Analyzing the frequency of involvement of the predetermined clinically relevant body regions either individually or in various combinations yielded more than 1,000 bits of data. Although the distribution of symptom provocation resembled the classic dermatomal maps for cervical nerve roots, symptoms were frequently provoked outside of the distribution of classic dermatomal maps. CONCLUSION: The current study demonstrates a distinct difference between dynatomal and dermatomal maps.

Cervical Vertebrae↗
PubMed1990

Pvt-1 transcripts are found in normal tissues and are altered by reciprocal(6;15) translocations in mouse plasmacytomas.

The mouse Pvt-1 (for plasmacytoma variant translocation) region maps to a chromosome 15 breakpoint region that is frequently interrupted by "variant" reciprocal chromosome translocations, rcpt(6;15), in plasmacytomas. This region lies several hundred kilobases (kb) 3' of the mouse c-myc gene (Myc) which is deregulated in both rcpt(6;15) and rcpt(12;15) plasmacytomas. rcpt(12;15) translocations apparently activate c-myc directly by interrupting the gene itself, but the mechanism causing c-myc deregulation in tumors bearing rcpt(6;15) translocations remains unknown. The indirect activation of c-myc by Pvt-1 interruption has remained an appealing possibility, but heretofore it has not been possible to establish such a connection. Furthermore, no genes from the Pvt-1 locus have been shown to be transcribed in normal tissues or in tumors with rcpt(6;15) translocations. We report the isolation of a cDNA clone, Pvt-1-1, from mouse spleen mRNA that is specific to the Pvt-1 region. This cDNA probe detects low levels of large (ca. 14 kb) RNA transcripts in normal mouse tissues. In plasmacytomas with rcpt(6;15) translocations, the Pvt-1 transcripts are elevated in abundance and truncated in size. Both changes are apparently induced by the chromosomal translocation. Expression of 14-kb Pvt-1 RNA is elevated in B-cell tumor lines that express immunoglobulin light chain genes; thus, we postulate that these translocations are facilitated by the increased DNA accessibility of immunoglobulin kappa light chain and Pvt-1 genes when they are simultaneously expressed at certain times during B-cell ontogeny.

Amino Acid Sequence↗
PubMed1991

The substitution of arginine for glycine 85 of the alpha 1(I) procollagen chain results in mild osteogenesis imperfecta. The mutation provides direct evidence for three discrete domains of cooperative melting of intact type I collagen.

We report a case of mild osteogenesis imperfecta in a 56-year-old male undergoing aortic valve replacement surgery. The primary defect in this patient was the substitution of arginine for glycine 85 in one of the two chains of alpha 1(I) procollagen. The thermal stability of the type I collagen synthesized by the patient's cultured skin fibroblasts was examined by enzymatic digestion. Digestion of the mutant type I collagen with trypsin and chymotrypsin at increasing temperatures sequentially generated three discrete collagenous fragments, approximately 90, 170, and 230 amino acids shorter than normal type I collagen. This incremental thermal denaturation is indicative of cooperative melting blocks within the type I collagen. This is the first demonstration of such cooperative blocks of melting in intact, essentially normal post-translationally modified type I collagen. This direct evidence for cooperative melting domains of uncut type I collagen suggests that discrete blocks of amino acids function as core sites stabilizing the collagen helix. The location of mutations of the alpha chains of type I collagen relative to these discrete blocks of amino acids may influence the severity of the disease phenotype.

Amino Acid Sequence↗
PubMed2003

Influence of the normalization template on the outcome of statistical parametric mapping of PET scans.

Spatial normalization is an essential preprocessing step in statistical parametric mapping (SPM)-based analysis of PET scans. The standard template provided with the SPM99 software package was originally constructed using (15)O-H(2)O PET scans and is commonly applied regardless of the tracer actually used in the scans being analyzed. This work studies the effect of using three different normalization templates in the outcome of the statistical analysis of PET scans: (1) the standard SPM99 PET template; (2) an (18)F-FDG PET template, constructed by averaging PET scans previously normalized to the standard template; and (3) an MRI-aided (18)F-FDG PET template, constructed by averaging PET scans normalized according to the deformation parameters obtained from MRI scans. A strictly anatomical MRI normalization of each PET was used as a reference, under the rationale that a normalization based only upon MRI should provide higher spatial accuracy. The potential bias involved in the normalization process was estimated in a clinical SPM study comparing schizophrenic patients with control subjects. For each between-group comparison, three SPM maps were obtained, one for each template. To evaluate the influence of the template, these SPM maps were compared to the reference SPM map achieved using the anatomical normalization. SPMs obtained by MRI-aided normalization showed the highest spatial specificity, and also higher sensitivity when compared to the standard normalization using the SPM99 (15)O-H(2)O template. These results show that the use of the standard template under inappropriate conditions (different tracer or mental state) may lead to inconsistent interpretations of the statistical analysis.

Acute Disease↗
PubMed1995

On the potential of the Wilson central terminal with respect to an ideal reference for unipolar electrocardiography.

Body surface potential mapping was performed in 60 clinical cases and an ideal 0 potential was calculated in each case at 2msec intervals, which corresponds to the potential at infinity. Maximal deviation of the Wilson terminal voltage the ideal potential was 0.14mv on the average. Time course of potential variations of the central terminal was in proportion to the measured surface potentials. The lead vector of Wilson terminal was determined for each case, with a method to make a minimal difference between calculate and observed Wilson terminal voltage. The lead vector was directed superiorly and posteriorly with the magnitude of 24% of that of lead I on the average.

Body Surface Potential Mapping↗
PubMed1994

Systematic sextant biopsies in 651 patients referred for prostate evaluation.

In 651 patients mapping of the prostate by 6 systematic sextant ultrasonography guided biopsies was performed without major side effects using the automatic biopsy gun. The histological findings provided data on patients with normal and abnormal prostates as determined by digital rectal examination. Only 3 of 72 nonurological patients (4%) with normal prostate specific antigen (PSA) levels of less than 4 ng./ml. had prostate cancer. Of the 259 patients with a firm prostate on digital rectal examination 105 (41%) had prostate cancer. For those with a PSA level of less than 4 and 4 ng./ml. or greater the positive biopsy rates were 13% and 58%, respectively. Of 56 patients with clinical stage B or C disease and a PSA level of less than 4 ng./ml. 20 (36%) had prostate cancer, compared to 155 of 187 (83%) with a PSA level of 4 ng./ml. or greater. Transrectal ultrasound was not helpful in screening for prostate cancer due to the low positive biopsy rate for hypoechoic lesions. However, among 175 patients with clinical stage B or C disease transrectal ultrasound identified 157 (90%) with prostate cancer.

Adult↗
PubMed2002

Cold and warmth perception mapped for age, gender, and body area.

Reference data on cold and warmth perception at three different body areas are provided based on 24 young (20-30 years) and 24 elderly (55-65 years) healthy women and men. Perception thresholds (method of limits), perceived intensity (free-number magnitude estimation), and perceived quality (verbal descriptors) were assessed for cold and for warmth at thenar, the upper arm, the knee, and the foot. Inter-individual comparison of perceived-intensity scales for cold and warmth was achieved by a Master Scaling procedure utilizing thenar as a reference area. Perception thresholds showed gender difference for cold at thenar, and interaction effect of age and gender for heat-pain tolerance at the upper arm. In contrast, perceived intensity of cold and warmth showed multiple effects of age, gender, and specific body area (also for the nociceptive channels). For instance, at the knee, elderly women's perceived intensity for stimulation in the nociceptive range was elevated for both cold and warmth, as compared to young women and men, and to elderly men. Conversely, at the upper arm, elderly women's perceived intensity for the corresponding nociceptive range was lowered, as compared to young women and young men, and to elderly men. At the foot, both elderly women's and men's perceived intensity of cold and warmth was lowered, as compared to young women and men. Overall, the perceived quality of perceptions did not differ between groups. The present findings on age differences in perceived intensity of cold and warmth at the upper arm, knee and foot in healthy women and men provide reference data hitherto lacking for diagnostic work in patients with somatosensory dysfunctions and ongoing pain.

Adult↗
PubMed1994

Low, but strongly structured mitochondrial DNA diversity in root knot nematodes (Meloidogyne).

Root-knot nematodes (genus Meloidogyne) have been the subject of recent and numerous studies of genetic variation because of the need to develop molecular diagnostics for the four globally distributed, parthenogenetic species that are significant agricultural pests. Our analysis of Meloidogyne mtDNA improves on previous studies: (i) by examining restriction site polymorphism among a large number of isolates also characterized for standard morphological, host range and allozyme phenotypes; (ii) by using higher resolution electrophoretic techniques; and (iii) by mapping variable restriction sites with reference to the complete nucleotide sequence. This revealed fivefold less sequence divergence (< 0.6%) between variants than estimated in previous restriction fragment length polymorphism (RFLP) studies, but perfect correspondence between mtDNA haplotype and allozyme (esterase) phenotypes. The mtDNA variation, although limited, is strongly structured with as much divergence between two lineages of Meloidogyne arenaria as between either of these and Meloidogyne javanica. The low diversity of mtDNAs suggests that these parthenogenetic lineages arose from distinct but closely related sexual females, a pattern seen in other parthenogenetic complexes. In contrast to the concordance between mtDNA and allozyme markers, there were several discrepancies between the traditional methods of identification. We suggest that further studies of these nematodes should focus on well defined genetic groups, whether or not these coincide with existing taxonomic units.

Animals↗
PubMed2005

Magnetocardiogram recordings in a nonshielded environment--reproducibility and ischemia detection.

BACKGROUND: Magnetocardiography (MCG) is a noninvasive technology that measures the magnetic field of the heart by superconducting quantum interference devices (SQUID) sensors. The novelty of the present system is that the sensors can be operated without electromagnetic shielding of the examination room, thus allowing the system to be easily installed in the emergency department or chest pain unit. Studies in shielded rooms, found that this imaging modality may have better sensitivity as compared to ECG in detecting ischemia. We aimed (1) to assess the reproducibility, intra-observer, and interobserver interpretation variability and (2) to assess the MCG maps in the presence of coronary narrowings. METHODS AND RESULTS: All measurements were performed in a nonshielded room. For the first part of the study, two MCG maps were recorded in 24 otherwise healthy volunteers (age 20-44 years, median 24, 16 male) in an interval ranging from 2 to 48 hours. The maps were interpreted using the CardioMag software for contour maps, averaged MCG time traces, and waveform morphology of repolarization by two observers blinded to each other. The parameters tested had low disagreement between repeated measurements. The correlations of the intra-observer and interobserver interpretation were excellent. Secondly, MCG maps were obtained in 29 patients referred for angiography due to suspected coronary artery disease. Nineteen of them had coronary narrowings defined as more than 50%. In this group, 16 (84.2%) had abnormal MCG maps as compared to only 5 (26.3%) who had abnormal ECGs (P < 0.01). CONCLUSIONS: MCG maps can be successfully obtained in a nonshielded room and allow feasible, accurate, and reproducible measurements with little intra-observer and interobserver variability. Ischemic changes in the heart's magnetic field may occur before electrical changes. Our pilot data suggests that this imaging modality may potentially offer better sensitivity as compared to rest ECG in detecting ischemia in a cohort of patients who had coronary narrowings identified by angiography.

Algorithms↗