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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Driveway injuries in children: risk factors, morbidity, and mortality.

BACKGROUND/PURPOSE: Injuries that occur around the driveway are not typically regarded as reportable to the police and thus are often underrecognized. The aim of this study was to characterize the pattern and consequences of motor vehicle collisions that occur in the driveway. METHODS: Over the past 13 years, 64 patients admitted to the Children's Hospital of Pittsburgh sustained motor vehicle-related injuries in a driveway. These injuries resulted from a vehicle driven by an adult driver striking a child (group 1) or a child shifting an idle vehicle out of gear (group 2). We compared demographic variables and outcome measures between the 2 groups. RESULTS: There was no difference in gender, injury pattern, Injury Severity Score, length of stay, or operations performed between the groups. Patients in group 1 were younger, smaller, had a lower Glasgow Coma Scale, and had poorer outcomes. The majority of collisions (~65%) in group 1 resulted from a truck or sport-utility vehicle going in reverse. CONCLUSIONS: Younger children are more severely injured in driveway-related crashes, which are most likely to be caused by a truck or sport-utility vehicle going in reverse. These vehicles should be equipped with additional safety features such as extended mirrors to visualize small children.

Accidents, Home↗
PubMed2000

Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular junction ablation for prevention of atrial fibrillation. The atrial pacing peri-ablation for paroxysmal atrial fibrillation (PA (3)) study investigators.

BACKGROUND: Some clinical data suggest that atrial-based pacing prevents paroxysmal atrial fibrillation (AF). This study tested the hypothesis that DDDR pacing compared with VDD pacing prevents AF after atrioventricular (AV) junction ablation. METHODS AND RESULTS: Patients were randomized to DDDR pacing (n=33) or to VDD pacing (n=34) after AV junction ablation and followed every 2 months for 6 months. Patients then crossed over to the alternate pacing mode and were followed for an additional 6 months. Primary analysis included the time to first recurrence of sustained AF (duration >5 minutes), total AF burden, and the development of permanent AF. The time to first episode of AF was similar in the DDDR group (0.37 days, 95% CI 0.1 to 1.3 days) and the VDD pacing group (0.5 days, 95% CI 0.2 to 1.7 days, P=NS). AF burden increased over time in both groups (P<0.01). At the 6-month follow-up, AF burden was 6.93 h/d (95% CI 4. 37 to 10.96 h/d) in the DDDR group and 6.30 h/d (95% CI 3.99 to 9.94 h/d) in the VDD group (P=NS). Twelve (35%) patients in the DDDR group and 11 (32%) patients in the VDD group had permanent AF within 6 months of ablation. Within 1 year of follow-up, 43% of patients had permanent AF. CONCLUSIONS: DDDR pacing compared with VDD pacing does not prevent paroxysmal AF over the long term in patients in the absence of antiarrhythmic drug therapy after total AV junction ablation. Many patients have permanent AF within the first year after ablation.

Aged↗
PubMed2000

Theileria parva genomics reveals an atypical apicomplexan genome.

The discipline of genomics is setting new paradigms in research approaches to resolving problems in human and animal health. We propose to determine the genome sequence of Theileria parva, a pathogen of cattle, using the random shotgun approach pioneered at The Institute for Genomic Research (TIGR). A number of features of the T. parva genome make it particularly suitable for this approach. The G+C content of genomic DNA is about 31%, non-coding repetitive DNA constitutes less than 1% of total DNA and a framework for the 10-12 Mbp genome is available in the form of a physical map for all four chromosomes. Minisatellite sequences are the only dispersed repetitive sequences identified so far, but they are limited in distribution to 13 of 33 SfiI fragments. Telomere and sub-telomeric non-coding sequences occupy less than 10 kbp at each chromosomal end and there are only two units encoding cytoplasmic rRNAs. Three sets of distinct multicopy sequences encoding ORFs have been identified but it is not known if these are associated with expression of parasite antigenic diversity. Protein coding genes exhibit a bias in codon usage and introns when present are unusually short. Like other apicomplexan organisms, T. parva contains two extrachromosomal DNAs, a mitochondrial DNA and a plastid DNA molecule. By annotating the genome sequence, in combination with the use of microarray technology and comparative genomics, we expect to gain significant insights into unique aspects of the biology of T. parva. We believe that the data will underpin future research to aid in the identification of targets of protective CD8+ cell mediated immune responses, and parasite molecules involved in inducing reversible host leukocyte transformation and tumour-like behaviour of transformed parasitised cells.

Animals↗
PubMed2000

The locus of a novel gene responsible for arrhythmogenic right-ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14.

Arrhythmogenic right-ventricular dysplasia (ARVD), a cardiomyopathy inherited as an autosomal-dominant disease, is characterized by fibro-fatty infiltration of the right-ventricular myocardium. Four loci for ARVD have been mapped in the Italian population, and recently the first locus was mapped in inhabitants of North America. None of the genes have been identified. We have now identified another North American family with early onset of ARVD and high penetrance. All of the children with the disease haplotype had pathological or clinical evidence of the disease at age <10 years. The family spans five generations, having 10 living and 2 dead affected individuals, with ARVD segregating as an autosomal-dominant disorder. Genetic linkage analysis excluded known loci, and a novel locus was identified on chromosome 10p12-p14. A peak two-point LOD score of 3.92 was obtained with marker D10S1664, at a recombination fraction of 0. Additional genotyping and haplotype analysis identified a shared region of 10.6 cM between marker D10S547 and D10S1653. Thus, a novel gene responsible for ARVD resides on the short arm of chromosome 10. This disease is intriguing, since it initiates exclusively in the right ventricle and exhibits pathological features of apoptosis. Chromosomal localization of the ARVD gene is the first step in identification of the genetic defect and the unraveling of the molecular basis responsible for the pathogenesis of the disease.

Adult↗
PubMed2000

Impact of pediatric trauma centers on mortality in a statewide system.

BACKGROUND: Regional pediatric trauma centers (PTC) were established to optimize the care of injured children. However, because of the relative shortage of PTC, many injured children continue to be treated at adult trauma centers (ATC). As a result, a growing controversy has evolved regarding the impact of PTC and ATC on outcome for injured children. METHODS: A retrospective analysis of 13,351 injured children entered in the Pennsylvania Trauma Outcome Study between 1993 and 1997 was conducted. Patients were stratified according to mechanism of injury, injury severity, specific organ injury, and type of trauma center: PTC; Level I ATC (ATC I); Level II ATC (ATC II); or ATC with added qualifications to treat children (ATC AQ). Mortality was the major outcome variable measured. RESULTS: Most injured children were treated at a PTC or ATC AQ. The majority of children below 10 years of age were admitted to PTC. Patients treated at PTC and ATC had similar injury severity as determined by median Injury Severity Score, mean Revised Trauma Score, and Glasgow Coma Scale. Overall survival was significantly better at PTC and ATC AQ compared with ATC I and ATC II. Survival for head, spleen, and liver injuries was significantly better at PTC compared with ATC AQ, ATC I, or ATC II. Children who sustained moderate or severe head injuries were more likely to undergo neurosurgical intervention and have a better outcome when treated at a PTC. Despite similar mean Abbreviated Injury Scores for spleen and liver, significantly more children underwent surgical exploration (especially splenectomy) for spleen and liver injuries at ATC compared with PTC. CONCLUSION: Children treated at PTC or ATC AQ have significantly better outcome compared with those treated at ATC. Severely injured children (Injury Severity Score > 15) with head, spleen, or liver injuries had the best overall outcome when treated at PTC. This difference in outcome may be attributable to the approach to operative and nonoperative management of head, liver, and spleen injuries at PTC.

Adolescent↗
PubMed1999

Interpolated Markov models for eukaryotic gene finding.

Computational gene finding research has emphasized the development of gene finders for bacterial and human DNA. This has left genome projects for some small eukaryotes without a system that addresses their needs. This paper reports on a new system, GlimmerM, that was developed to find genes in the malaria parasite Plasmodium falciparum. Because the gene density in P. falciparum is relatively high, the system design was based on a successful bacterial gene finder, Glimmer. The system was augmented with specially trained modules to find splice sites and was trained on all available data from the P. falciparum genome. Although a precise evaluation of its accuracy is impossible at this time, laboratory tests (using RT-PCR) on a small selection of predicted genes confirmed all of those predictions. With the rapid progress in sequencing the genome of P. falciparum, the availability of this new gene finder will greatly facilitate the annotation process.

Algorithms↗
PubMed1999

The genome of the malaria parasite.

The genome of the human malaria parasite Plasmodium falciparum is being sequenced by an international consortium. Two of the parasite's 14 chromosomes have been completed and several other chromosomes are nearly finished. Even at this early stage of the project, analysis of the genome sequence has provided promising new leads for drug and vaccine development.

Animals↗
PubMed1999

A shotgun optical map of the entire Plasmodium falciparum genome.

The unicellular parasite Plasmodium falciparum is the cause of human malaria, resulting in 1.7-2.5 million deaths each year. To develop new means to treat or prevent malaria, the Malaria Genome Consortium was formed to sequence and annotate the entire 24.6-Mb genome. The plan, already underway, is to sequence libraries created from chromosomal DNA separated by pulsed-field gel electrophoresis (PFGE). The AT-rich genome of P. falciparum presents problems in terms of reliable library construction and the relative paucity of dense physical markers or extensive genetic resources. To deal with these problems, we reasoned that a high-resolution, ordered restriction map covering the entire genome could serve as a scaffold for the alignment and verification of sequence contigs developed by members of the consortium. Thus optical mapping was advanced to use simply extracted, unfractionated genomic DNA as its principal substrate. Ordered restriction maps (BamHI and NheI) derived from single molecules were assembled into 14 deep contigs corresponding to the molecular karyotype determined by PFGE (ref. 3).

Animals↗
PubMed1999

Low-frequency component of body surface potential maps identifies patients at risk for ventricular tachycardia.

AIMS: To investigate the ability of spectral features of signal-averaged body-surface potential maps in identifying post-infarction patients who are at risk of developing ventricular tachycardia. METHODS AND RESULTS: We recorded 120 lead body surface potential maps during sinus rhythm in 135 subjects (45 patients with healed myocardial infarction but no history of ventricular tachycardia, 45 patients with both healed myocardial infarction and at least one episode of sustained ventricular tachycardia, and 45 normal subjects) and analysed spectral features of body surface potential maps selected on the basis of isoharmonic maps for given bands of the frequency spectrum. We found that in the low-frequency band (1-11 Hertz), the group-mean power spectra of leads located at isoharmonic map maxima were significantly different (P<0.0001) between the two groups of myocardial infarction patients. We estimated that this single feature alone can prospectively identify myocardial infarction patients at risk for ventricular tachycardia with a predictive accuracy of 74+/-6%. CONCLUSION: Our results suggest that the bulk of diagnostic information associated with arrhythmogenicity resides in the low-frequency band of the power spectrum. This finding is at variance with the established notion that only the high-frequency component of signal-averaged electrocardiograms carries such information.

Adult↗
PubMed1999

Arrhythmia vulnerability assessment using magnetic field maps and body surface potential maps.

Magnetic field maps and body surface potential maps can be used to measure cardiac activity. The ability of magnetic and potential body surface maps to identify patients' vulnerable to recurrent sustained ventricular arrhythmia (VA) were compared. Magnetic field maps (MFM) and body surface potential mapping (BSPM) were obtained from 76 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 VA patients. QRST integral maps were calculated for each subject and nondipolar content was determined using Karhunen-Loeve transform eigen-maps. Although differences in nondipolar content were significant between the normal and patient groups (P = 2.4 x 10(-5) for BSPM and P = 6.0 x 10(-8) for MFM), differences in nondipolar content between MI and VA patients using QRST integral BSPM and MFM maps were not significant. The trajectory of the location of the maxima and minima on the map area during the QRS and ST-T intervals were also constructed. Discrimination between MI and VA patients was based on intergroup differences in the amount of fragmentation of the trajectory plots. The ST-T trajectory plots were significantly more fragmented (P < 0.0001 and P < 0.05 for MFM and BSPM, respectively) for VA than for MI patients. The ST-T interval MFM and BSPM trajectory plots enabled separation of MI and VA patients with accuracies of 83% and 73%, respectively. These results suggest that repolarization MFM and BSPM extrema trajectory plots can be used effectively as a means of identifying patients at risk for VA.

Adult↗
PubMed1999

Optical mapping of Plasmodium falciparum chromosome 2.

Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of genomic DNA enables large stretches of the genome to be mapped and circumvents library construction and associated cloning artifacts. We used pulsed-field gel electrophoresis purified Plasmodium falciparum chromosome 2 DNA as the starting material for optical mapping, a system for making ordered restriction maps from ensembles of individual DNA molecules. DNA molecules were bound to derivatized glass surfaces, cleaved with NheI or BamHI, and imaged by digital fluorescence microscopy. Large pieces of the chromosome containing ordered DNA restriction fragments were mapped. Maps were assembled from 50 molecules producing an average contig depth of 15 molecules and high-resolution restriction maps covering the entire chromosome. Chromosome 2 was found to be 976 kb by optical mapping with NheI, and 946 kb with BamHI, which compares closely to the published size of 947 kb from large-scale sequencing. The maps were used to further verify assemblies from the plasmid library used for sequencing. Maps generated in silico from the sequence data were compared to the optical mapping data, and good correspondence was found. Such high-resolution restriction maps may become an indispensable resource for large-scale genome sequencing projects.

Animals↗
PubMed1999

The malaria genome sequencing project: complete sequence of Plasmodium falciparum chromosome 2.

An international consortium has been formed to sequence the entire genome of the human malaria parasite Plasmodium falciparum. We sequenced chromosome 2 of clone 3D7 using a shotgun sequencing strategy. Chromosome 2 is 947 kb in length, has a base composition of 80.2% A + T, and contains 210 predicted genes. In comparison to the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, a greater proportion of genes containing introns, and nearly twice as many proteins containing predicted non-globular domains. A group of putative surface proteins was identified, rifins, which are encoded by a gene family comprising up to 7% of the protein-encoding gene in the genome. The rifins exhibit considerable sequence diversity and may play an important role in antigenic variation. Sixteen genes encoded on chromosome 2 showed signs of a plastid or mitochondrial origin, including several genes involved in fatty acid biosynthesis. Completion of the chromosome 2 sequence demonstrated that the A + T-rich genome of P. falciparum can be sequenced by the shotgun approach. Within 2-3 years, the sequence of almost all P. falciparum genes will have been determined, paving the way for genetic, biochemical, and immunological research aimed at developing new drugs and vaccines against malaria.

Animals↗
PubMed1998

Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum.

Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A+T-rich P. falciparum genome is technically feasible.

Amino Acid Sequence↗
PubMed1998

The malaria genome sequencing project.

An international consortium of genome centres, advanced development teams and funding agencies has begun the task of sequencing the genome of the parasite Plasmodium falciparum, the most important cause of human malaria. Sequencing is proceeding chromosome by chromosome, and the annotated sequence of chromosome 2 is nearly finished. With the continual release of sequence data as they are generated, malaria researchers have access to a steady stream of genomic sequences and will soon have the complete annotation of all of the estimated 5000-7000 P. falciparum genes. The task will then be how to best apply these data to the development of new anti-malarial drugs, vaccines and diagnostic tests. This review provides a brief overview of the Malaria Genome Sequencing Project and suggests potential directions for future malaria research.

Journal Article↗