Biomedical subjects
Publications and source records attributed to C D Morgan.
Investigation of a cardiac murmur and thrill in an asymptomatic 35-year-old man revealed a foreign body lying within the left ventricular cavity. Upon questioning, the man revealed that he had been shot in the chest years earlier. This is the first reported adult case of a retained intracardiac bullet causing a ventricular septal defect.
Numerous natural and synthetic quinone compounds possess significant antitumor properties. Various mechanisms have been proposed to account for these properties, including scission and degradation of tumor cell DNA, intracellular "redox cycling" to cogenerate semiquinone free radicals and reactive oxygen intermediates, and the interaction of semiquinone radicals with tumor cell surface flavoenzymes. However, no evidence has been presented to explain adequately the preferential attack on tumor cells by semiquinone radicals, as opposed to normal cells. To address this question, a synergistic interaction was examined. A therapy consisting of a mixture of L-ascorbate and 2,6-dimethoxy-p-benzoquinone, was used for in vivo evaluation. BALB/c mice were depleted of functional T-lymphocytes by xenogeneic monoclonal antibody pretreatment, challenged with Ehrlich ascites tumor, and administered the semiquinone radical-generating therapy. Mice depleted of CD4+ T-lymphocytes responded with rapidly fatal tumor progression, with significantly decreased mean survival times over controls, whereas less severe responses were observed in mice devoid of CD8+ T-lymphocytes. Mice depleted of both T-lymphocyte subpopulations responded with uninhibited tumor growth and rapid mortalities. When tumor challenge occurred after therapy, tumor growth was significantly delayed in mice enriched for CD4+ T-lymphocytes, with demonstrable increases in mean survival time over controls. This reagent combination had no significant effect on T-lymphocyte profiles in secondary lymphoid organs. These data suggest a synergistic phenomenon of semiquinone radical-induced cytostasis coupled with T-lymphocyte helper activity for optimal tumor suppression.
OBJECTIVES: To assess death rates among patients waiting for cardiac valve surgery or isolated coronary artery bypass surgery (CABG), and to determine independent risk factors for death while waiting for isolated CABG. DESIGN: Prospective cohort analysis based on an inclusive registry. SETTING: Nine cardiac surgical units in Ontario, Canada. PATIENTS: 29,293 consecutive patients scheduled for cardiac surgery between October 1991 and June 1995. MAIN OUTCOME MEASURES: Death rates while waiting for surgery were determined among patients scheduled for isolated CABG, isolated valve surgery, or combined procedures. Predictors of death among patients with isolated CABG were determined from multivariate analysis. RESULTS: There were 141 deaths (0.48%) among 29,293 patients. Adjusting for age, sex, and waiting time, patients waiting for valve surgery had a significantly increased risk of death compared with patients waiting for CABG alone (adjusted odds ratio 1.88, 95% confidence interval (CI) 1.23 to 2.88, p = 0.004). Results were similar for patients waiting for combined valve and CABG procedures compared with those who were waiting for isolated CABG. Independent risk factors for death while waiting for isolated CABG included: impaired left ventricular function (odds ratio 2.47, 95% CI 1.59 to 3.84, p < 0.001); advancing age (for each decade, odds ratio 1.41, 95% CI 1.10 to 1.80, p = 0.007); male sex (odds ratio 1.95, 95% CI 1.00 to 3.81, p = 0.05); and waiting longer than the maximum time recommended in Canadian guidelines for a patient's clinical profile (odds ratio 1.59, 95% CI 1.01 to 2.51, p = 0.044). After scaling waiting time to surgery or death continuously in days, the same predictors emerged. CONCLUSIONS: Patients waiting for valve surgery have a higher risk of death than patients waiting for isolated CABG. Guidelines to promote safer and fairer queuing for non-CABG cardiac surgery are needed. Shorter waiting lists, better compliance with existing guidelines, and guideline revisions to upgrade patients with left ventricular dysfunction could generate additional reductions in the already low risk of death for patients waiting for isolated CABG.
BACKGROUND: The Toronto stentless porcine valve (SPV) was designed to improve hemodynamics after aortic valve replacement by maximizing available flow area in comparison to stented valves (STD). METHODS: To assess possible hemodynamic differences between STD and SPV, 59 patients undergoing isolated aortic valve replacement (+/-coronary artery bypass graft) were prospectively evaluated by preoperative and 3- to 6-month postoperative echocardiography. Among these, 23 patients received a STD, whereas 36 received the Toronto SPV. RESULTS: The mean size (mm) of SPV implanted was larger (SPV, 26.6+/-2.1; STD, 24.0+/-2.9; P=0.0002). Patients receiving STD valves were older and had a higher prevalence of coronary artery disease and congestive heart failure. There were no preoperative differences in left ventricular mass index (g/mo2), peak or mean pressure gradients (mmHg), effective orifice area (cm2), extent of fractional shortening (%), or velocity of circumferential shortening (cf/sec). ANOVA demonstrated a significant reduction in left ventricular mass index at 3 to 6 months (P=.0001) but no differences in left ventricular mass index regression between groups (STD, -28.8+/-37.5; SPV, -31.2+/-32.4; P=.36). Effective orafice area was increased postoperatively (P=.0001), particularly among SPV cases (STD, 1.5+/-0.4; SPV, 1.9+/-0.7; P=.01). Postoperative left ventricular mass index and mean pressure gradient were reduced (P=.0001) but did not differ between groups. Fractional shortening and velocity of circumferential shortening were greater in the SPV patients at 3 to 6 months after aortic valve replacement (P=.0004 and .0001, respectively), and an interactive effect was seen between time and prosthetic group (P=.0028 and .032, respectively). CONCLUSIONS: In a consecutive series of patients, we identified no hemodynamic differences between STD and SPV, although ventricular function improved after SPV. Because of the nonrandomized nature of the study, selection bias may have accounted for some of the observed results. A prospective, randomized trial is necessary to determine the hemodynamic advantages, if any, of the SPV valve.
OBJECTIVE: Recently, a good deal of attention has been focused on alcoholism and eating disorders as comorbid conditions. Early identification of biologic, psychologic, and sociocultural factors that contribute to comorbid alcoholism and eating disorders may improve the outcome for such patients. METHOD: The following case report is of a 26-year-old woman who developed a severe eating disorder in her early teens that was followed by alcoholism. RESULTS: The combination of eating disorder and alcoholism in this patient led to approximately 70 hospitalizations for medical complications of her alcoholism. This paper chronicles her last few living months including her death due to alcoholic complications.
Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults (8M/8F) and 16 older adults (8M/8F) with inter-stimulus intervals (ISI) of 45, 60 and 90 s using amyl acetate as the odorant stimulus. N1, P2, and N2 peak amplitudes and latencies were measured. Young participants demonstrated significantly shorter peak latencies than older participants. Older males demonstrated significantly smaller peak amplitudes than the other participant groups. Peak amplitudes also increased with longer ISIs for older males. The OERP is compared to traditional olfactory psychophysical testing.
Neuropsychological assessment plays an important role in the process of diagnosing DAT. Whereas the brief screens are sensitive to the cognitive deficits associated with DAT, full battery measures should be used to rule out early dementia or to differentiate among the various dementing illnesses. Following diagnosis, there are numerous assessment measures that facilitate management and placement decisions. These measures include instruments that help stage the illness to determine severity, instruments that evaluate the patient's capacity to perform activities of daily living, and measures that evaluate for the behavior symptoms common in later-stage dementia.
There is a lack of defined reference points for reproducible femoral tunnel placement during posterior cruciate ligament (PCL) reconstruction. The PCL, consisting of two major bands, anterolateral (AL) and posteromedial (PM), has a femoral origin that spans 3 cm, which cannot be covered by a substitute graft positioned in one femoral tunnel to reconstruct the PCL. The purpose of this study was to define the location of the anatomic origin of both bands of the PCL in reference to local anatomy to develop landmarks that can be used to reproducibly position two femoral tunnels (one to each band's origin) during PCL reconstruction. The anatomy of the PCL origin was dissected and studied in 20 knees at the time of total knee replacement. The central origin point for each band was marked, and its distance was measured in reference to three axes. The AL band centrally originated 13 +/- 0.5 mm posterior to the medial articular cartilage-intercondylar wall interface and 13 +/- 0.5 mm inferior to the articular cartilage-intercondylar roof interface. The PM band centrally originated 8 +/- 0.5 mm posterior to the medial articular cartilage-intercondylar wall interface and 20 +/- 0.5 mm inferior to the articular cartilage-intercondylar roof interface. These distances were noted to be relatively constant despite varying knee morphologies and size. For this reason, referencing the articular cartilage-intercondylar roof, and wall interfaces may be used as a method to facilitate more reproducible anatomic femoral tunnel placements during PCL reconstruction.
The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cells are terminally differentiated melanoma cells, not monocyte-derived macrophages. Swine melanoma explants with no regression were transplanted into severe combined immunodeficient (SCID) mice. Harvested transplant sites were examined by routine light and electron microscopy techniques. Paraffin sections were also stained with Hoeschst dye and examined by fluorescence microscopy. All but one site had completely regressed and were replaced by PLM-like cells. Hoeschst staining indicated they were of swine, not mouse, origin. The ultrastructural features of the single, partially regressed lesion demonstrated many premelanosomes in these cells. We conclude that tumour differentiation is an important mechanism of regression in the Sinclair swine melanoma model.
OBJECTIVE: To establish whether clinically significant aortic and mitral valvular regurgitation can be excluded in adult patients undergoing transthoracic echocardiography without using colour flow imaging. SETTING: Sunnybrook Health Science Centre, a tertiary referral centre with full cardiovascular services affiliated with the University of Toronto, Toronto, Ontario. DESIGN: Logistic regression models were developed from a retrospective review of 14,051 unselected consecutive echocardiograms from 1991 through 1994. The dependent variable was more than mild aortic or mitral valvular regurgitation. Independent variables included age, sex and various functional and structural measures obtained during routine two-dimensional echocardiography. The negative predictive values and sensitivity of the models were estimated. INTERVENTION: The number of patients correctly classified by these models, as well as the proportion for whom the colour flow imaging did not add to the baseline echocardiogram, was determined. Nonparametric bootsrapping was used to obtain confidence intervals for these statistics. MAIN RESULTS: Ten models were developed, with negative predictive values ranging from 96.2% to 100%. Incorporation of such decision aids into the software of echocardiographic machinery would help echocardiographers to rule out significant aortic or mitral regurgitant lesions. In practices where colour flow imaging is routinely employed, 40% fewer procedures could be performed. CONCLUSIONS: Models based on simple demographic and two-dimensional echocardiographic variables can reliably exclude significant valvular regurgitation and could potentially reduce the volumes and costs of colour flow imaging. Given the widespread diffusion of colour Doppler imaging, the models may also be helpful to avoid misinterpretation of flow imaging results, by defining subgroups in whom the prior probability of significant aortic or mitral regurgitation is extremely low.
BACKGROUND: Various strategies exist for the use of cardiac catheterization in unstable angina or non-Q wave myocardial infarction. At the authors' institution, the overall volume of cardiac catheterization has increased in recent years. OBJECTIVE: To investigate whether this increased volume of cardiac catheterization was due to adoption of a more invasive approach to the management of patients with acute ischemic syndromes. DESIGN: A retrospective cohort study was conducted using detailed chart review of coronary care unit admissions during 1990/91 and 1993/94. SETTING: A university-affiliated tertiary care referral centre with facilities for cardiac catheterization. PATIENTS: One hundred patients randomly selected from among those with unstable angina, non-Q wave myocardial infarction or chest pain not yet diagnosed in each of the study years. Detailed follow-up was complete for all patients. OUTCOME MEASURE: The use of cardiac catheterization during the index admission was documented. MAIN RESULTS: There was a trend towards more frequent use of same admission cardiac catheterization in the later period (21% [CI 14% to 31%] versus 12% [CI 7% to 20%], P = 0.09). However, after controlling for baseline characteristics and in-hospital events, the year of admission did not independently predict the use of catheterization (P = 0.60). By multivariate logistic regression, recurrence of chest pain and evidence of myocardial necrosis were most closely associated with same-admission cardiac catheterization. CONCLUSIONS: Although clinical factors partially explain the increased use of catheterization over time, there may have also been shift towards a more aggressive practice style at the authors' institution. Further study is needed to address this possibility.
OBJECTIVE: Women with bulimia nervosa generally have reported greater sexual activity and experience relative to women with anorexia nervosa. However, past research has been based on small samples and has not controlled for potential confounding variables or symptom severity. We further investigated sexual experience among women diagnosed with an eating disorder. METHODS: Women evaluated in an outpatient eating disorders program, and subsequently diagnosed with either anorexia nervosa (n = 131) or bulimia nervosa (n = 319), completed the Diagnostic Survey for Eating Disorders-Revised (DSED-R) at intake. Sexual experience variables (masturbation, coitus, sexual satisfaction), as well as control variables (age, weight, and menarche) and measures of symptom severity, were derived from the DSED-R. Logistic regression analyses were used to predict sexual experience. RESULTS: After controlling for relevant covariates, bulimics were more likely than anorexics to have engaged in sexual intercourse. Masturbation experience, as well as self-ratings of current sexual satisfaction, were inversely related to degree of restriction of caloric intake, particularly among women with anorexia nervosa. When compared to anorexics, bulimics reported greater sexual interest and earlier age of first coitus. DISCUSSION: Coitus (sexual activity involving a partner) was related to eating disorder diagnosis independent of symptoms, whereas masturbation (self-focused sexual activity) was related to caloric restriction for the sample as a whole and anorexia nervosa patients in particular. These relationships between sexual experience and eating disorder symptoms and diagnosis may illuminate the personality features of women with anorexia nervosa versus bulimia nervosa as well as the functional role of caloric restriction.
BACKGROUND: Regression of left ventricular hypertrophy is an important and well-recognized salutary effect of aortic valve replacement. The earliest evidence of left ventricular mass regression after aortic valve replacement and the influence of prosthesis type are not well known, and were the focus of this study. METHODS: Transthoracic echocardiography was used to measure left ventricular mass index preoperatively and before discharge in 57 consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting). RESULTS: Three patients were excluded from the study because of inability to obtain accurate M-mode echocardiographic images for left ventricular mass measurement preoperatively (1) or postoperatively (2). Of the remaining 54 patients, mechanical bileaflet valves were used in 19, stented tissue bioprostheses were implanted in 15, and a stentless porcine bioprosthesis was chosen for 20. Postoperative echocardiograms were obtained 4.9 +/- 2.3 days after aortic valve replacement (range, 2 to 9 days). A two-way repeated-measures analysis of variance demonstrated a significant reduction of left ventricular mass index before discharge (preoperative 141.4 +/- 45.2 g/m2, postoperative 127.5 +/- 32.8 g/m2; p = 0.0005) but no differences between prostheses. CONCLUSIONS: Left ventricular mass regression begins early after aortic valve replacement, probably because of reduction of transvalvular gradients and left ventricular wall stress. At least in the very early postoperative period, the type of prosthesis does not influence the extent of mass regression.
Selectively-bred Sinclair miniature swine exhibit a high incidence of congenital malignant melanoma which either proves fatal (10-15% of tumor-bearing piglets) or spontaneously regresses with a biphasic immunological phenomenon (85-90%) and no recurrence of malignancy. Mononuclear leukocytes were isolated from cutaneous melanomas and peripheral blood specimens collected from melanomatous (tumor-bearing) Sinclair swine during second-phase regression, and from peripheral blood specimens collected from non-melanomatous (tumor-free) Sinclair swine and control Hanford swine. Leukocyte identities were determined with single- and dual-parameter indirect immunofluorescence assays via flow cytometry. Assays for the specific surface antigens CD45, CD2, CD4, CD8, CD1, MHC class II, and N1 were employed to develop immunophenotypic profiles within the gated lymphocyte clusters from each TIL and PBL suspension. Significantly more CD8+ T-lymphocytes were identified in TIL suspensions than in peripheral blood leukocyte (PBL) suspensions (P < and = 0.05), regardless of breed or tumor status. Conversely, PBL suspensions contained significantly higher percentages of CD4+ T-lymphocytes than the levels found in TIL suspensions (P < and = 0.05). Virtually all TIL were MHC class II+, whereas the percentages of PBL expressing this antigen were markedly lower (P < and = 0.05). The percentages of T-lymphocytes co-expressing CD4 and CD8, a normal subset unique to swine, were generally consistent in all TIL and PBL suspensions examined. The results of this study have firmly established the immunophenotypic identities of cells associated with the second-phase regression phenomenon of this melanoma and have identified specific variations in the leukocyte profiles of the respective TIL and PBL suspensions.
Thirty-four ankle arthrodeses performed using an arthroscopic technique were followed for an average of 8 years. The fusion rate was 97% and the average time to fusion was 9 weeks; 86% of patients had good or excellent functional results. There were no wound infections or neurological injuries. There was one malunion and one additional minor complication. The arthroscopic method uses an abrader to denude the joint surfaces of cartilage, followed by screw fixation. The average time to fusion is significantly less than other ankle arthrodesis techniques, which hastens the recovery period. The shorter time to fusion is likely a result of the minimal soft tissue stripping that is performed during the procedure. The low morbidity of this technique eliminates the need for hospitalization in most cases. There were no long-term adverse sequelae. This is the largest reported series of arthroscopic ankle arthrodeses.
The all-inside arthroscopic meniscal repair technique allows placement of vertically oriented sutures, which have the strongest pullout strength, across difficult-to-access posterior horn tears. These sutures are placed perpendicular to the tear, rather than obliquely, and without entrapment of the posterior capsule, resulting in a balanced anatomic repair. The posterior cannula allows excellent tear preparation and minimizes dissection. This may improve postoperative pain management and permit outpatient surgery. The all-inside technique minimizes neurovascular injury. This method has limited application and, therefore, requires that the surgeon learn more than one repair technique to repair tears anterior to the posterior horn. The main disadvantage is that advanced instruments (suture hooks and 70-deg lens) are required, as well as the surgical expertise to use them.
OBJECTIVE: To examine the sex-specific prevalence of referral to a cardiologist for noninvasive ischemic testing (NIIT) or angiography among outpatients with clinical suspicion of new coronary artery disease (CAD). DESIGN: Retrospective records-based cohort study. SETTING: Group cardiology referral practice in a tertiary care teaching hospital in Toronto. PATIENTS: Of 1212 new patients referred between Mar. 1, 1991, and Mar. 31, 1993, 339 (232 men and 107 women) had symptoms of CAD and had initiation or modification of antianginal therapy, or were prescribed NIIT or angiography by their cardiologist. OUTCOME MEASURES: Rates of prior NIIT and of subsequent diagnostic procedures for women and men. RESULTS: Women were less likely than men to have had prior NIIT (51 [47.7%] v. 162 [69.8%]) (p < 0.001). Women with class I or II angina were less likely than their male counterparts to have had prior NIIT (20/40 [50.0%] v. 84/109 [77.1%]) (p = 0.001); a similar difference was found between women and men with class III or IV angina (5/15 [33.3%] v. 43/60 [71.7%]) (p = 0.006). Men and women with atypical angina were equally likely to have had prior NIIT. Among patients with a positive initial NIIT result a higher proportion of women than of men did not have any further testing done by the cardiologist (53.5% v. 33.7%) (p = 0.02). Cardiologists referred a higher proportion of women (40.2%) than of men (25.4%) for NIIT (p = 0.006) and, for patients with a positive prior NIIT result, were also more likely to refer women (25.7% [9/43]) than men (12.0% [16/133]) for further NIIT (p = 0.04). Women with a positive prior NIIT result were more likely than their male counterparts to have a negative retest result (42.8% v. 18.2%). After adjustment for age, anginal class and overall result of NIIT, women were less likely than men to be referred for angiography (odds ratio 1.4), although the difference was not significant. CONCLUSIONS: In this exploratory study sex-related differences in patterns of use of NIIT by cardiologists seem largely based on differences in testing before referral by family physicians and general internists.
Silent ischemia is a frequent finding in patients with unstable angina and portends a poor prognosis. We compared the efficacy of sustained-release (SR) verapamil and metoprolol in reducing silent ischemia in patients with unstable angina and assessed whether detection of silent ischemia was related to unfavorable outcomes in the contemporary setting of concurrent therapy with heparin and aspirin. Holter monitoring (leads a VF, V2, V5) for the first 72 h was used to assess the frequency and duration of ST-shift episodes. There were 37 patients in the verapamil-SR group and 40 patients in the metoprolol group, with both groups having similar baseline characteristics. There were more episodes of angina in the verampamil-SR group (29 vs. 12, p = 0.05). There was no difference between the two groups in the frequency (51 vs. 49 episodes, p = 0.9) or duration (23 +/- 48 vs. 18 +/- 50 min, p = 0.6) of ST-shift episodes. There were 20 unfavorable in-hospital outcomes distributed equally between the two groups (p = 0.9). Patients with unfavorable outcomes had ST shift more often (50 vs. 28%, p = 0.07) and for a longer duration (40 +/- 69 vs. 13 +/- 38 min, p = 0.03). Patients with ST shift > or = 60 min had a 60% probability of unfavorable outcome compared with 33% for ST shift of 1-59 min duration and 20% for no ST shift (p = 0.04). We conclude that metoprolol appears to reduce symptoms better than verapamil-SR, but no difference in silent ischemia or unfavorable outcomes was seen. Silent ischemia remains a common occurrence in these patients despite heparin and aspirin therapy and its detection continues to have prognostic value.