Condom effectiveness for prevention of C trachomatis infection.
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Chlamydia Infections↗
Biomedical subjects
D Newman
Publications and source records attributed to D Newman.
Methods for injury surveillance in international cricket.
BACKGROUND: The varying methods of cricket injury surveillance projects have made direct comparison of published studies in this field impossible. METHODS: A consensus regarding definitions and methods to calculate injury rates in cricket was sought between researchers in this field. This was arrived at through a variety of face-to-face meetings, email communication and draft reviews between researchers from six of the major cricket-playing nations. RESULTS: It is recommended that a cricket injury is defined as any injury or other medical condition that either: (a) prevents a player from being fully available for selection for a major match or (b) during a major match, causes a player to be unable to bat, bowl or keep wicket when required by either the rules or the team's captain. Recommended definitions for injury incidence (for matches, training sessions and seasons) and injury prevalence are also provided. It is proposed that match injury incidence is calculated using a denominator based on a standard time estimated for player exposure in matches, for the purposes of simplicity. This will allow all injury surveillance systems, including those with limited resources, to make calculations according to a standard definition. CONCLUSION: The consensus statement presented provides a standard which, if followed, allows meaningful comparison of injury surveillance data from different countries and time periods, which will assist in the possible identification of risk factors for injury in cricket.
Athletic Injuries↗
Respiratory infections during air travel.
An increasing number of individuals undertake air travel annually. Issues regarding cabin air quality and the potential risks of transmission of respiratory infections during flight have been investigated and debated previously, but, with the advent of severe acute respiratory syndrome and influenza outbreaks, these issues have recently taken on heightened importance. Anecdotally, many people complain of respiratory symptoms following air travel. However, studies of ventilation systems and patient outcomes indicate the spread of pathogens during flight occurs rarely. In the present review, aspects of the aircraft cabin environment that affect the likelihood of transmission of respiratory pathogens on airplanes are outlined briefly and evidence for the occurrence of outbreaks of respiratory illness among airline passengers are reviewed.
Aerospace Medicine↗
Methods for injury surveillance in international cricket.
BACKGROUND: The varying methods of cricket injury surveillance have made direct comparison of published studies in this field impossible. METHODS: A consensus regarding definitions and methods to calculate injury rates in cricket was sought between researchers in this field. This was arrived at through a variety of face to face meetings, email communication, and draft reviews between researchers from six of the major cricket playing nations. RESULTS: It is recommended that a cricket injury is defined as any injury or other medical condition that either (a) prevents a player from being fully available for selection for a major match or (b) during a major match, causes a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team's captain. Recommended definitions for injury incidence (for matches, training sessions, and seasons) and injury prevalence are also provided. It is proposed that match injury incidence is calculated using a denominator based on a standard time estimated for player exposure in matches, for the purposes of simplicity. This will allow all injury surveillance systems, including those with limited resources, to make calculations according to a standard definition. CONCLUSION: The consensus statement presented provides a standard which, if followed, allows meaningful comparison of injury surveillance data from different countries and time periods, which will assist in the possible identification of risk factors for injury in cricket.
Athletic Injuries↗
Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini.
The human NBC1 (SLC4A4) gene encodes the electrogenic sodium bicarbonate cotransporters kNBC1 and pNBC1, which are highly expressed in the kidney and pancreas, respectively. The HCO3-:Na+ stoichiometry of these cotransporters is an important determinant of the direction of ion flux. Recently we showed in a mouse proximal tubule (mPCT) cell line expressing kNBC1, that 8-Br-cAMP shifts the stoichiometry of the cotransporter from 3:1 to 2:1 via protein kinase A (PKA)-dependent phosphorylation of Ser982. pNBC1 has the identical carboxy-terminal consensus phosphorylation PKA site (KKGS1026), and an additional site in its amino-terminus (KRKT49). In this study we determined the potential role of these sites in regulating the function of pNBC1. The results demonstrated that in mPCT cells expressing pNBC1, PKA-dependent phosphorylation of Ser1026 following 8-Br-cAMP treatment shifted the stoichiometry from 3:1 to 2:1. The effect was electrostatic in nature as replacing Ser1026 with Asp resulted in a similar stoichiometry shift. In addition to shifting the stoichiometry, 8-Br-cAMP caused a significant increase in the 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS)-sensitive basolateral membrane conductance (GDS) of cells expressing pNBC1, but not kNBC1. Although, the effect did not involve phosphorylation of Thr49, which was endogenously phosphorylated, replacing this residue with Asp or Ala abolished the 8-Br-cAMP-induced increase in GDS. In the mPEC pancreatic duct cell line, where endogenous pNBC1 functions with a HCO3-:Na+ stoichiometry of 2:1, 8-Br-cAMP increased GDS by ~90 % without altering the stoichiometry or inducing phosphorylation of the cotransporter. The results demonstrate that phosphorylation of Ser1026 mediates the cAMP-dependent shift in the stoichiometry of pNBC1, whereas Thr49 plays an essential role in the cAMP-induced increase in GDS.
8-Bromo Cyclic Adenosine Monophosphate↗
Gap junction blockers decrease defibrillation thresholds without changes in ventricular refractoriness in isolated rabbit hearts.
BACKGROUND: The maintenance and termination of reentry arrhythmias are determined by tissue properties such as refractoriness and conduction velocity. Although the effects of Na(+) and K(+) channel block on electrophysiological properties and defibrillation threshold (DFT) have been studied, little is known about the effect of gap junction blockers on defibrillation and tissue electrophysiological properties. METHODS AND RESULTS: Triplicate DFTs (volts) were obtained before and 15 minutes after 4 micromol/L 16-doxyl-stearic acid (16-DSA, n=8), 1 mmol/L 1-heptanol (n=12) (both gap junction blockers), 3 microg/mL lidocaine (a sodium channel blocker) (n=8), and respective controls (n=27) in isolated perfused rabbit hearts. DFT decreased after 16-DSA (23+/-14%, P<0.01) and 1-heptanol (21+/-16%, P<0.01) but increased after lidocaine (26+/-28%, P<0.05). Ventricular fibrillation cycle length (VFCL) and QRS duration increased after all 3 agents, by 36+/-19% and 44+/-16% (16-DSA), 87+/-42% and 49+/-15% (heptanol), and 57+/-20% and 43+/-26% (lidocaine), respectively (all P<0.01). Spatially averaged temporal VFCL dispersion decreased significantly after all 3 agents, by 47+/-42% (16-DSA, P<0.05), 74+/-19% (1-heptanol, P<0.01), and 82+/-13% (lidocaine, P<0.01), respectively. Ventricular effective refractory period and monophasic action potential duration at 90% repolarization were unchanged after 16-DSA and 1-heptanol (P=NS) but increased after lidocaine (16+/-13%, P<0.01, and 6+/-5%, P=NS, respectively). There were no significant changes in DFT or any other electrophysiological variable in control hearts. CONCLUSIONS: Electrical uncoupling by 16-DSA and 1-heptanol significantly lowers DFT and dispersion of VFCL without altering refractoriness; lidocaine, at doses resulting in similar slowing of conduction, increases DFT.
Animals↗
New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome.
BACKGROUND: Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF. METHODS AND RESULTS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients' physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.14+/-1.39 years. Compared with men, women were older at the time of presentation, more likely to seek medical advice because of symptoms, and experienced significantly higher heart rates during AF. Compared with older men, older women were half as likely to receive warfarin and twice as likely to receive acetylsalicylic acid. Compared with men on warfarin, women on warfarin were 3.35 times more likely to experience a major bleed. CONCLUSIONS: Anticoagulants are underused in older women with AF relative to older men with AF, despite comparable risk profiles. Women receiving warfarin have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.
Anticoagulants↗
Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial.
The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.
Amiodarone↗
Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued).
In eukaryotes, it is rare for a single gene to encode two functionally unrelated proteins. p150(Glued) is a component of the dynactin heteromultimeric complex of proteins which is required for dynein-mediated vesicle and organelle transport by microtubules. NBC4 is an electrogenic sodium bicarbonate cotransporter, which regulates intracellular pH. Here we report that NBC4 and p150(Glued) are encoded by the same locus, DCTN1-SLC4A5. We have characterized the genomic organization of the human DCTN1-SLC4A5 locus which spans approximately 230 kilobases on chromosome 2p13 and contains 66 exons. This information should allow the study of potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping to this genomic region.
5' Untranslated Regions↗
Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation.
OBJECTIVES: To assess the relative contributions of rate control and rhythm regularization to left ventricular function in atrial fibrillation (AF) patients undergoing atrioventricular nodal ablation. This was performed by assessing the effect of ventricular rhythm regularization on left ventricular function during AF, and the effect of varying heart rate on left ventricular function after ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R pacemakers undergoing therapeutic atrioventricular nodal ablation were studied. Preablation patients underwent two 30 min observation periods in a randomized, blinded fashion during which they were either in baseline AF (pacer set to default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA) designed to regularize rhythm without changing baseline ventricular rate. Six weeks after ablation, patients were again observed during the two following 30 min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and pacing at the rapid, mean preablation rate. During all observation periods, left ventricular function was measured continuously using a nuclear vest that provided validated measures of heart rate, ejection fraction, and normalized end-systolic volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA successfully regularized rhythm, decreasing the coefficient of variation of interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/-19 beats/min) was not significantly different from the baseline AF rate (102+/-21 beats/min). Increased rhythm regularity achieved by RSA significantly improved left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11% (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9 beats/min, a much greater improvement in ejection fraction was observed, increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm regularity achieved by a regularizing pacing algorithm can significantly, albeit modestly, improve left ventricular function in AF. However, more marked improvements in left ventricular function seen after ablation are primarily due to rate reduction alone.
Aged↗
Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation.
Patients with atrial fibrillation (AF) report impaired health-related quality of life (QOL). Differences between men and women with AF have not been described and personality attributes such as somatization (tendency to amplify benign bodily sensations) may mediate potential gender differences in QOL. Patients with AF (n = 264, 59% men) who participated in the Canadian Trial of Atrial Fibrillation (n = 403) completed validated QOL questionnaires at baseline, 3 months, and 12 months after antiarrhythmic drug treatment. Women were significantly older than men and a greater proportion had hypertension, but other cardiac variables did not differ between women and men. At baseline, after controlling for significant clinical and demographic factors, women reported worse physical health (p = 0.002) and functional capacity (p < 0.001), but not mental health or general well-being. Women also had more frequent and severe cardiac symptoms than men (both p < 0.001). Physical health improved significantly from baseline to 3 months for women (p = 0.002), but not for men (p = 0.066). Conversely, mental health improved for men (p = 0.007), but not for women. Cardiac symptom frequency and severity improved over time for women and men (all p < 0.001). Tendency to somatize predicted poor QOL, and women had higher scores than men (p = 0.023). However, after controlling for somatization, women still had worse physical function, functional capacity, and symptom burden than men. Independent of cardiac disease severity and age, women with AF had significantly more impaired QOL than men, specifically on domains related to physical rather than emotional functioning. Personality attributes may have a role in influencing QOL outcomes.
Age Factors↗
Cloning, characterization and chromosomal assignment of NBC4, a new member of the sodium bicarbonate cotransporter family.
We report the cloning, characterization and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4, from human heart. NBC4 maps to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. NBC4 encodes a 1074-residue polypeptide with 12 putative membrane-spanning domains. Unlike other members of the NBC family, NBC4 has a unique glycine-rich region (amino acids 438-485). In addition, NBC4 lacks the lysine-rich C-terminus of NBC1 with which it is most homologous. The first of two putative stilbene binding motifs (K(M/L)(X)K) is lacking in NBC4 (amino acids 655-658). The approximately 6 kb NBC4 transcript is moderately expressed in heart, with the highest expression in liver, testes and spleen.
Amino Acid Sequence↗
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↗
A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms.
A first-generation genetic linkage map of the baboon (Papio hamadryas) genome was developed for use in biomedical and evolutionary genetics. Pedigreed baboons (n = 694) were selected from the breeding colony maintained by the Southwest Foundation for Biomedical Research. To facilitate comparison with the human genome, the baboon linkage map consists primarily of human microsatellite loci amplified using published human PCR primers. Genotypes for 325 human microsatellites and 6 novel baboon microsatellites were used in linkage analyses performed with the MultiMap expert system. The resulting sex-averaged meiotic recombination map covers all 20 baboon autosomes, with average spacing among loci of 7.2 cM. Direct comparison among homologous (orthologous) loci reveals that, for 7 human autosomes, locus order is conserved between humans and baboons. For the other 15 autosomes, one or more rearrangements distinguish the two genomes. The total centimorgan distances among homologous markers are 28.0% longer in the human genome than in the baboon, suggesting that rates of recombination may be higher in humans. This baboon linkage map is the first reported for any nonhuman primate species and creates opportunities for mapping quantitative trait loci in baboons, as well as for comparative evolutionary analyses of genome structure.
Animals↗
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
Several electrogenic sodium bicarbonate cotransporters have been cloned from different human organs. In the renal proximal tubule, the electrogenic sodium bicarbonate cotransporter kNBC1 (1035aa) mediates the majority of basolateral sodium bicarbonate absorption. In pancreatic ducts, the electrogenic sodium bicarbonate cotransporter pNBC1 (1079aa) mediates basolateral sodium bicarbonate influx. hNBC1 (hhNBC), cloned from human heart, is identical to pNBC1 at the amino acid level. We have demonstrated that kNBC1 and pNBC1 are highly homologous proteins that have different N-termini. In kNBC1, 41 amino acids replace the initial 85 amino acids of pNBC1. Whether these proteins are coded by one or more genes is unknown. In order to determine the genetic basis for these transcripts, we first characterized the genomic organization of the NBC1 gene (SLC4A4). NBC1 spans approximately 450 kilobases containing 26 exons that are flanked by typical splice donor and acceptor sequences at the intron-exon boundaries. Exon 1 is specific for the pNBC1 transcript. The first alternative exon of the hNBC1 transcript, containing the 5'-untranslated region, is derived from the last 43 nucleotides of intron 1 in the NBC1 gene coupled to exon 2. kNBC1 is transcribed from an alternative promoter in intron 3. In the first alternative exon of kNBC1, the last 313 nucleotides of intron 3 are coupled to exon 4, which is common to pNBC1 and hNBC1. The major transcription initiation site in kNBC1 is located 192 nucleotides upstream from the translation initiation codon. A minor start site is located 182 nucleotides upstream from the translation initiation codon. Structural analysis of the proximal kNBC1 promoter revealed an atypical TATA sequence (-33) and several potentially important transcription factor binding sites. Functional studies showed that the 5'-flanking region of the alternative kNBC1 promoter (-159 to+43) is sufficient for promoter activity. This work is the first demonstration that the three N-terminal transcripts of the human electrogenic sodium bicarbonate cotransporter NBC1 are encoded by the SLC4A4 gene. Furthermore, knowledge of the genomic organization and alternative promoter usage in the NBC1 gene provides a molecular basis for understanding disorders involving electrogenic sodium bicarbonate cotransporters and facilitates the elucidation of transcriptional control of NBC1 expression.
Amino Acid Sequence↗
Effect of physiological mechanical perturbations on intact human myocardial repolarization.
OBJECTIVE: The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS: Patients implanted with a stimulus to T wave (Stim-T) sensing pacemaker specially adapted to output a validate measure of beat to beat local repolarization (n = 9) performed Valsalva manoeuvers (40 mmHg for 15 s) while paced at a cycle length of 500 ms. Stim-T intervals were measured before and after autonomic blockade (Block: 0.03 mg/kg i.v. atropine +/- 0.15 mg/kg propranolol). Right ventricular end diastolic volume was estimated by simultaneous 2D-echocardiography. RESULTS: Without autonomic blockade, compared to baseline, repolarization significantly prolonged during Valsalva strain (1.1 +/- 0.7%) and shortened during release (-1.4 +/- 1.0%). After block, strain related repolarization prolongation was also observed (1.0 +/- 0.6%), with significantly less release related repolarization shortening (-0.8 +/- 0.8%) compared to pre-block (P < 0.05). Right ventricular end diastolic volume decreased during strain by 11 +/- 10 and 9 +/- 16% from baseline, pre- and post-block respectively (P < 0.05). CONCLUSION: In a chronically instrumented human model, an acute physiologic volume reduction modestly prolongs right ventricular repolarization independent of changes in rate or autonomic tone.
Action Potentials↗
Inappropriate therapy from atrial fibrillation and sinus tachycardia in automated implantable cardioverter defibrillators.
BACKGROUND: Inappropriate therapy from supraventricular tachyarrhythmias (atrial fibrillation [AF] and sinus tachycardia [ST]) in patients with implanted cardioverter defibrillators is a major challenge. We tested the performance of stability algorithms from 3 manufacturers for episodes of inappropriate therapy delivered because of AF and an onset algorithm for all episodes of inappropriate therapy caused by ST. METHODS: Therapy was classified as caused by ventricular tachycardia (VT), ST, or AF from review of stored intracardiac electrograms, history, clinical information, and R-R data before study inception. By using 30 to 60 R-R intervals before therapy, sensitivity and specificity for a family of stability values and percentage of onset values were calculated for each manufacturer and receiver operating characteristic curves generated. RESULTS: Of the 217 patients monitored, 62 (29%) received inappropriate therapy, and 40 had complete R-R information available. Of the 40 patients, 21 patients received therapy for AF, 19 for ST, and 1 patient for noise; 15 (38%) also received appropriate therapy for VT. We analyzed 83 episodes of VT from 18 patients, 94 episodes of AF from 21 patients, and 56 episodes of ST from 19 patients. Specificity, in the clinically relevant sensitivity range of >/=95%, was comparable across manufacturers at about 40%. An onset value of 80% was associated with 91% sensitivity and 95% specificity for the specific algorithm tested. CONCLUSIONS: Inappropriate therapy is a common problem in implantable cardiac defibrillators. The performance of the stability algorithms used to differentiate AF from VT was less than ideal, though comparable across manufacturers. The onset algorithm accurately differentiates ST from VT.
Aged↗
The application of psychosomatic research to clinical cardiology
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Journal Article↗