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Biomedical subjects

Christopher R Thompson

Publications and source records attributed to Christopher R Thompson.

29 records · Page 2Linked to original sources

Transesophageal echocardiography to guide pulmonary vein mapping and ablation for atrial fibrillation.

BACKGROUND: This study describes the use and outcomes of transesophageal echocardiography to guide atrial fibrillation (AF) ablation procedures. METHODS: Under general anesthesia, 25 patients with a history of AF underwent multiplane transesophageal echocardiography in conjunction with catheter placement under fluoroscopy. RESULTS: In this series, a combined fluoroscopic/echocardiographic approach obviated the need for angiographic imaging. Anatomic variation in pulmonary veins (PV) was common; the shortest distance between the ostia ranged from 2 to 11 mm. Individual PV diameters did not predict the presence of ectopic foci. The number of radiofrequency pulses delivered per vein was 2.6 +/- 2.3 (range: 0-10). Mean fluoroscopy time per procedure was 31 +/- 13 minutes and mean procedure time was 110 +/- 31 minutes. At follow-up, 68% of patients were free from AF. CONCLUSIONS: Transesophageal echocardiography enables identification and cannulation of the ostia and proximal branches of PV during AF ablation. Fluoroscopy, procedure times, and outcomes compare favorably with series using PV angiography and, as such, suggest that a controlled trial is warranted.

Adult↗

Novel development rescuing factors (DRFs) secreted by the developing Dictyostelium cells, that are involved in the restoration of a mutant lacking MAP-kinase ERK2.

We found novel development rescuing factors (DRFs) secreted from developing Dictyostelium cells, by using a mutant (erkB-) which is missing MAP-kinase ERK2 as a test strain for bioassay. The mutant erkB- fails to undergo multicellular morphogenesis due to impaired cAMP signaling. However, such developmental defect can be restored by the presence of low-molecular weight DRFs that are secreted from developing wild-type cells. We previously showed that DIF-1 (Differentiation-Inducing Factor 1 for stalk cells) possesses this activity, indicating a newly discovered role of DIF-1. Surprisingly, however, the mutant dmtA-, which is incapable of DIF-1 synthesis still exerts a strong inducing activity of the multicellular morphogenesis of erkB-. After analysis of HPLC fractions of conditioned media prepared from both wild type Ax2 and dmtA- strains revealed that both strains secrete at least two novel DRF activities with DIF-like mobility. However, these activities were not derived from other DIFs such as DIF-2 and DIF-3. Identification of these DRFs found in this study would provide insight into the mechanism by which the development of the erkB- mutant is restored and how these factors act in the normal development of Dictyostelium.

Animals↗

A case of factitious homicidal ideation.

Homicidal ideation is often fabricated or embellished by psychiatric patients in both the emergency room and inpatient settings. Typically, this symptom is malingered to achieve short-term hospital admission and temporary relief from complications of substance abuse, homelessness, and illicit activities. Very rarely, a patient may feign homicidal intent for the primary purpose of remaining in the role of patient (factitious disorder). Although factitious disorder with psychological symptoms has been described in a variety of circumstances, the psychiatric literature lacks any reports of factitious homicidal ideation. This is a report on the case of a patient who was civilly committed on numerous occasions for protracted periods based solely on his self-professed homicidal ideation. The case raises both forensic and clinical questions and reinforces the authors' belief that further investigation is needed to develop more sophisticated methods of detection, evaluation, and treatment of factitious disorder with psychological symptoms.

Bacterial Toxins↗

Revascularization use and survival outcomes after cardiac catheterization in British Columbia and Alberta.

BACKGROUND: Alberta and British Columbia have comprehensive cardiac databases that provide detailed demographic, clinical and procedural data, including coronary anatomy, on all patients undergoing cardiac catheterization. OBJECTIVES: To examine the baseline clinical characteristics of patients undergoing cardiac catheterization, describe the use of revascularization treatments (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) following catheterization, and describe survival after cardiac catheterization, stratified by treatment strategy received and proposed, using cardiac databases from Alberta and British Columbia. PATIENTS AND METHODS: All patients between 20 and 105 years of age, admitted to hospital for their first coronary angiography between April 1, 1995, and March 31, 2001, with angiographic evidence of coronary disease were included in the study. Procedure volumes, baseline characteristics and therapy received within one year of cardiac catheterization are described by province. Stepwise, multivariate logistic regression analysis was used to model determinants of the revascularization modality. Kaplan-Meier curves of one-year survival after index cardiac catheterization were estimated for the therapy received (Alberta and British Columbia) and the therapy proposed (British Columbia only). RESULTS: Patients were predominantly men (70%), commonly presented with two- or three-vessel disease, and frequently had hypertension, a history of myocardial infarction and dyslipidemia. Within one year of catheterization, 21% to 26% underwent CABG and 32% to 42% underwent PCI. Emergency or urgent status at the time of catheterization was associated with receiving PCI, while three-vessel and left main disease were associated with receiving CABG. Patients who did not undergo revascularization within one year (presumed medical therapy) had the lowest one-year survival rate (93.4%; 95% CI 92.1% to 94.7%); this group comprised patients receiving medical therapy as proposed (one-year survival rate of 95.7%, 95% CI 94.6% to 96.8%), as well as patients receiving medical therapy at variance with the proposal for revascularization (84.6%; 95% CI 80.5% to 88.9%). CONCLUSIONS: Between 53.1% and 67.5% of patients presenting for cardiac catheterization undergo revascularization within one year. Urgent status increased the probability of PCI, and anatomy (ie, three-vessel and left main) increased the probability of CABG. Patients not undergoing proposed revascularization by one year had poorer outcomes, in contrast with those proposed for medical therapy, who had excellent outcomes.

Adult↗

Outcome of mitral valve repair or replacement: a comparison by propensity score analysis.

BACKGROUND: There are no randomized trials comparing outcomes after mitral valve (MV) repair and replacement. Propensity scoring is a powerful tool that has the potential to reduce selection bias in nonrandomized studies. METHODS: From the BC Cardiac Registries, 2,060 patients presented for MV surgery, with or without CABG between 1991 and 2000. We then identified 322 MV repairs who were then matched by propensity score to an equal number of MV replacement patients. We compared survival and freedom from re-operation outcomes using Cox proportional hazards model analysis. Multivariable analysis was then used to compare outcomes in 358 MV repair patients with 352 MV replacement patients who had undergone chordal sparing surgery. RESULTS: The comparison groups generated using propensity scores were well balanced with respect to all collected baseline risk factors. Median follow-up time was 3.4 years. Patients undergoing MV repair had significantly improved survival (RR 0.46; 95% CI, 0.28 to 0.75) but a trend toward more re-operations (RR 2.11; 95% CI, 1.00 to 4.47) compared with patients undergoing replacement. Mitral valve repair patients still had better survival (RR 0.52; 95% CI, 0.32 to 0.85) compared with MV replacement patients who had undergone chordal sparing surgery. CONCLUSIONS: We used propensity score methods to reduce selection bias in a population-based cohort of patients undergoing MV repair/replacement. Repair was associated with better survival, but a trend to increased re-operation.

Disease-Free Survival↗

Contrasting activities of the aggregative and late PDSA promoters in Dictyostelium development.

Expression of the Dictyostelium PdsA gene from the aggregative (PdA) and late (PdL) promoter is essential for aggregation and slug morphogenesis, respectively. We studied the regulation of the PdA and PdL promoters in slugs using labile beta-galactosidase (gal) reporter enzymes. PdL was active in prestalk cells as was also found with stable gal. PdA activity decreased strongly in slugs from all cells, except those at the rear. This is almost opposite to PdA activity traced with stable gal, where slugs showed sustained activity with highest levels at the front. PdA was down-regulated after aggregation irrespective of stimulation with any of the factors known to control gene expression. PdL activity was induced in cell suspension by cAMP and DIF acting in synergy. However, a DIF-less mutant showed normal PdL activity during development, suggesting that DIF does not control PdL in vivo. Dissection of the PdL promoter showed that all sequences essential for correct spatiotemporal control of promoter activity are downstream of the transcription start site in a region between -383 and -19 nucleotides relative to the start codon. Removal of nucleotides to position -364 eliminated responsiveness to DIF and cAMP, but normal PdL activity in prestalk cells in slugs was retained. Further 5' deletions abolished all promoter activity. This result also indicates that the induction by DIF and cAMP as seen in cell suspensions is not essential for PdL activity in normal development.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase.

One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), and three million people die of tuberculosis each year. Following its ingestion by macrophages (MPs), Mtb inhibits the maturation of its phagosome, preventing progression to a bactericidal phagolysosome. Phagocytosis of Mtb is uncoupled from the elevation in MP cytosolic Ca(2+) that normally accompanies microbial ingestion, resulting in inhibition of phagosome-lysosome fusion and increased intracellular viability. This study demonstrates that the mechanism responsible for this failure of Ca(2+)-dependent phagosome maturation involves mycobacterial inhibition of MP sphingosine kinase. Thus, inhibition of sphingosine kinase directly contributes to survival of Mtb within human MPs and represents a novel molecular mechanism of pathogenesis.

Animals↗

Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock.

BACKGROUND: Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy. METHODS AND RESULTS: One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis. The 2 groups were similar in terms of clinical and early echocardiographic characteristics. Mean left ventricular ejection fraction (LVEF) was 31%, and moderate or greater mitral regurgitation (MR) was noted in 39.1%. On multivariate analysis, the only independent predictors of survival were MR severity and LVEF. A survival benefit for the ERV strategy was observed at all levels of LVEF and MR. CONCLUSIONS: A wide range of cardiac structural and functional abnormalities exists in patients presenting with acute cardiogenic shock. Both short- and long-term mortality appear to be associated with initial left ventricular systolic function and MR as assessed by echocardiography, and a benefit of ERV is noted regardless of baseline LVEF or MR.

Aged↗

Factors other than the Duke criteria associated with infective endocarditis among injection drug users.

BACKGROUND: Modified Duke criteria were applied to consecutive injection drug users (IDUs) who were admitted to an inner-city hospital with a clinical suspicion of infective endocarditis, and the presence of any other clinical variables that were predictive of the presence of infective endocarditis was determined. METHODS: Clinical data on consecutive IDUs who were hospitalized over 15 months in Vancouver were collected. Data included the admission history, and findings on physical examination and on initial laboratory investigations. Each subject's course in hospital was followed until discharge or death during the index hospitalization. Follow-up data collected included culture results, the interpretation of the echocardiogram and the discharge diagnosis. The modified Duke criteria were used for the diagnosis of infective endocarditis (definite, possible or rejected). Multiple logistic regression was used to determine what clinical variables (exclusive of the Duke criteria) available within 48 hours of presentation were independent predictors of infective endocarditis. RESULTS: One hundred IDUs were enrolled. Fifty-one were female, and 58 were HIV-positive. Twenty-three met the modified Duke criteria for definite infective endocarditis, and 25 had possible infective endocarditis. IDUs with definite infective endocarditis were more commonly noted to have evidence of vascular phenomena (arterial embolism, septic pulmonary infarction, mycotic aneurysm, intracranial hemorrhage or Janeway lesions) (6 [26%]) than those who had possible endocarditis (1 [4%]). Those with definite infective endocarditis more often had multiple opacities on chest radiography (56% v. < 12%), and fewer had an obvious source of infection (52% v. 72% and 81% of possible and rejected infective endocarditis, respectively). Among febrile IDUs, definite endocarditis was highly associated with having no obvious source of infection (odds ratio 3.1 [95% confidence interval 1.1-8.7]) compared with febrile IDUs with an obvious source of infection. In similarly compared groups, the presence of hematuria, proteinuria or pyuria was also predictive of definite endocarditis (odds ratio 2.9 [95% CI 1.1-8.6]). CONCLUSIONS: Among IDUs, the modified Duke criteria are useful for classifying cases with definite infective endocarditis and rejecting cases without infective endocarditis. The classification of possible infective endocarditis is suitable for this population.

British Columbia↗