Biomedical subjects
D A Harrison
Publications and source records attributed to D A Harrison.
Deterministic models for breast cancer progression: application to the association between mammographic parenchymal pattern and histologic grade of breast cancers.
Dense mammographic patterns are a risk factor for breast cancer. In a recent case-control study, dense patterns were observed to be associated with a higher relative risk estimate for the more aggressive grade 3 tumors than for grade 1 or 2 tumors. The present study was designed to ascertain, by reference to odds ratio estimates of relative risk by tumor size and histologic grade, whether this was more likely to be due to increased innate predisposition of dense parenchymal patterns to grade 3 tumors, or to dedifferentiation of cases missed at screening due to dense patterns. If the observation were due entirely to dedifferentiation, then for a given size the relative risk of grade 3 tumors would be the same as for grades 1-2. Size-specific relative risks of grade 3 tumors were higher than those of grade 1-2 tumors. It is concluded that the majority of the enhanced risk of grade 3 tumors is due to enhanced innate predisposition to grade 3 tumors in dense breasts.
Concomitant sensitivity to sodium metabisulfite and clobetasone butyrate in Trimovate cream.
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Sustained atrial arrhythmias in adults late after repair of tetralogy of fallot.
We determined the prevalence of sustained atrial tachyarrhythmia (AT) in adults late after repair of tetralogy of Fallot (ToF) and examined its impact on subsequent heart failure, reoperation, and mortality. Ventricular arrhythmias are associated with increased morbidity and mortality in patients with repair of ToF. The clinical impact of AT in this population has not been established. A retrospective cohort study of 242 patients with repaired ToF identified 29 patients (prevalence of 12%) with sustained episodes of AT. Patients with repaired ToF but without sustained arrhythmia (n = 213) constituted a comparison group. Baseline characteristics and clinical outcomes in the 2 groups were compared. An echocardiographic analysis compared 15 patients with AT and 15 matched for age at operation and timing of echocardiography. The development of AT was associated with substantial morbidity including congestive heart failure, reoperation, subsequent ventricular tachycardia, stroke, and death (combined events, 20 of 29 patients [69%]). The rate of combined events (congestive heart failure, stroke, and deaths) in the 213 "arrhythmia-free" patients was 30% (64 of 213 patients). Event-free survival after repair was 18 +/- 2 years for the AT group and 28 +/- 1 years for the arrhythmia-free group (p < 0.001). Patients with AT were older at surgical repair (25 +/- 16 vs 10 +/- 9 years, p = 0.001), and at most recent assessment were aged 48 +/- 12 vs 32 +/- 10 years (p = 0.001). The AT group had a higher mean right atrial volume and proportion of significant pulmonary regurgitation than matched controls. The development of AT in the adult late after ToF repair identifies patients at risk and is associated with older age at repair, a higher frequency of hemodynamic abnormalities, and increased morbidity.
Effects of cataract extraction with intraocular lens placement on scanning laser polarimetry of the peripapillary nerve fiber layer.
PURPOSE: To determine the effects of cataract extraction with intraocular lens placement on scanning laser polarimetry of the peripapillary nerve fiber layer. DESIGN: Cohort study. METHODS: Thirty-four eyes of 33 patients undergoing phacoemulsification cataract surgery with intraocular lens were imaged using the GDx Nerve Fiber Analyzer within 4 weeks before and at least 4 weeks after cataract surgery. Preoperative and postoperative mean images were compared. The effects of cataract severity and type, and intraocular lens material, were also examined. RESULTS: Comparison of preoperative and postoperative mean scanning laser polarimetry measurements revealed that eyes in which acrylic intraocular lenses (n = 11) were placed had a significant increase in scanning laser polarimetry for the total band circumference, and superior, inferior, and nasal quadrants (P < or =.041). Placement of silicone (n = 15) and polymethylmethacrylate (n = 8) intraocular lenses did not result in statistically significant changes in scanning laser polarimetry measurements. However, eight of 34 eyes (23.5%) had changes of 15% or more postoperatively in the total circumference measurement, including eyes with acrylic, silicone, and polymethylmethacrylate intraocular lenses. CONCLUSIONS: Cataract extraction with intraocular lens was associated with a statistically significant change in mean scanning laser polarimetry values in eyes that received an acrylic intraocular lens. In individual patients, clinically important changes (15% or greater) in scanning laser polarimetry measurements were not uncommon irrespective of intraocular lens type. New baseline scanning laser polarimetry measurements may be warranted in eyes that undergo cataract extraction with intraocular lens.
Outcomes of late atrial tachyarrhythmias in adults after the Fontan operation.
OBJECTIVES: The purpose of this study was to compare the clinical and echocardiographic features of adults who developed atrial tachyarrhythmias (ATs) late after a Fontan procedure with those who have remained free of arrhythmias. BACKGROUND: Atrial tachyarrhythmias are a frequent complication of the Fontan operation. However, the outcomes in adult patients with AT who have had the Fontan operation have not been well defined. METHODS: We reviewed the outcomes of 94 consecutive patients who underwent the Fontan operation between 1977 and 1994 and were followed as adults at the University of Toronto Congenital Cardiac Centre for Adults. Sixty patients had an atriopulmonary connection, 21 patients had an atrioventricular connection, and 13 patients received a lateral tunnel connection. RESULTS: Thirty-nine patients (41%) had sustained AT (atrial fibrillation, atrial flutter or supraventricular tachycardia) after their Fontan procedure. Compared with patients who did not develop AT, those who did were more likely to develop heart failure (46% vs. 13%, p = 0.003) and right atrial thrombus (31% vs. 4%, p = 0.006), exhibit left atrial enlargement (mean [+/-SD] diameter: 44 +/- 10 vs. 37 +/- 9 mm, p = 0.002), exhibit right atrial enlargement (mean [+/-SD] volume: 139 +/- 149 vs. 76 +/- 54 ml, p = 0.040) and have moderate-to-severe systemic valve regurgitation (31% vs. 7%, p = 0.010). The mean survival time was not significantly different between the arrhythmia group and the arrhythmia-free group (21.2 +/- 1.3 and 18.0 +/- 0.7 years, respectively; p = 0.900). CONCLUSIONS: Systemic atrioventricular valvular regurgitation and biatrial enlargement are commonly observed in patients who develop AT after the Fontan procedure. These patients are more likely to develop right atrial thrombus and heart failure.
Forgotten partners of international assignments: development and test of a model of spouse adjustment.
The authors developed and tested a model of spouse adjustment to international assignments in a sequence of qualitative and quantitative investigations. From in-depth interviews with expatriate spouses, half of whom had either positive or negative experiences living abroad, the authors identified several potentially important sources of adjustment. These constructs were integrated with others from identity theory and earlier research on expatriates to develop a conceptual model of spouse adjustment. The model was tested by collecting multisource questionnaire data from 221 international assignee couples working in 37 countries. Correlation and regression analyses revealed several important relationships between individual, interpersonal relationship, and environmental sources of identity, and the adjustment of expatriate spouses.
Endovascular stents in the management of coarctation of the aorta in the adolescent and adult: one year follow up.
OBJECTIVES: To test the hypothesis that endovascular stents used with dilation of coarctation of the aorta (CoA) improve late outcomes. Balloon dilation for CoA has been limited by concerns over the risk for acute dissection, late restenosis, or aneurysm formation. DESIGN: All patients seen with CoA between November 1994 and September 1997 underwent attempted stent implantation. Follow up was obtained for all patients and a subgroup (n = 18) had repeat catheterisation at a mean (SD) of 1.3 (0.5) years to assess residual gradient and stent-CoA morphology. RESULTS: Stents were placed in 27 patients (15 male and 12 female patients, mean age 30.1 (13.1) years), of whom seven had prior surgical coarctectomy and one had a prior balloon dilation. Hypertension was present in 26 patients (mean pressure 164 (26)/86 (13) mm Hg), of whom 16 were on antihypertension drugs. CoA gradients were 46 (20) mm Hg (range 18-106 mm Hg) at baseline and 3 (5) mm Hg after the procedure. One patient had a stroke following the procedure; another patient had incomplete dilation and underwent a second procedure. At 1.8 (1) years after the procedure the mean pressure was 130 (14)/74 (11) mm Hg with seven patients on antihypertension treatment. The clinical gradient was 4 (8) mm Hg (range 0-32 mm Hg). At follow up angiography, the mean gradient was 4(6) mm Hg, and two patients had a gradient over 10 mm Hg. Aneurysms formed in three patients at the dilation site; one patient was referred for surgery. CONCLUSION: In this age group stent management for CoA appears to be an effective technique and results in sustained reduction in CoA gradients at early term follow up, but aortic aneurysm was detected in 17% of patients who had repeat angiography.
Mode of death in adults with congenital heart disease.
An increasing number of patients with congenital heart disease (CHD) are entering adulthood. Although prior studies have focused on the causes of death in the pediatric population, the modes of death for adults with CHD have not been well defined. In a cross-sectional study performed on a population of 2,609 consecutive adults assessed at a CHD specialty clinic, there were adequate information available in 197 of 199 deceased patients. Mean age at death was 37 +/- 15 years. Mortality was highest in patients with congenitally corrected transposition of the great arteries (26%), tricuspid atresia (25%), and univentricular connection (23%). Youngest mean age at death was observed in patients with tricuspid atresia (27 +/- 5 years), complete transposition of the great arteries (27 +/- 7 years), pulmonary atresia (27 +/- 6 years), and aortic coarctation (29 +/- 6 years). Sudden death (26%) was the most common cause of death followed by progressive heart failure (21%) and perioperative death (18%). Postmortem examinations were performed in 77 of 197 deceased patients (39%) and provided incremental data on the mechanism of death in 22% of autopsies. Thus, the 3 major causes of death in the growing population of adults with CHD are sudden, perioperative, and progressive heart failure.
Clinical effects of oleoresin capsicum (pepper spray) on the human cornea and conjunctiva.
OBJECTIVE: To evaluate the effects of oleoresin capsicum (OC) on the human cornea and conjunctiva and to test the effectiveness of topical anesthetics for relief of pain. DESIGN: Prospective, randomized clinical trial. METHODS: Forty-seven subjects were examined before and at 10 minutes and 1 hour after exposure to pepper spray during a training exercise. Eleven subjects were reexamined at 1 week after exposure. A short, subjective questionnaire was given asking subjects to rate their pain, blurring of vision, and tearing. After exposure, subjects were randomly given a placebo, a topical nonsteroidal antiinflammatory agent, or a topical anesthetic. MAIN OUTCOME MEASURES: Visual acuity and corneal sensitivity with a Cochet-Bonnet aesthesiometer (scale of 1-6 cm) was measured and the eyes were examined with a portable slit lamp using fluorescein. Symptoms of pain, blurring of vision, and tearing were recorded in a ranking of 0 to 10. RESULTS: Visual acuity was unaffected by exposure to pepper spray. Corneal sensitivity was reduced from a pretest mean of 5.7 cm to a posttest mean of 0.6 cm 10 minutes after exposure. At 1 hour, the mean corneal sensitivity had recovered to 2.9 cm. Twenty-one percent of eyes had evidence of punctate epithelial erosions, but no corneal abrasions were found. All subjects reported significant pain, blurring of vision, and tearing at 10 minutes that was much improved by 1 hour. Topical flurbiprofen 0.03% improved symptoms in two of 11 subjects, whereas topical proparacaine hydrochloride 0.5% improved symptoms in 16 of 29 eyes. At 1 week after exposure, corneal sensation returned to baseline, and no corneal abnormalities were noted. CONCLUSIONS: The predominant symptom after exposure to OC was pain. Topical flurbiprofen was not helpful in reducing symptoms of exposure, whereas topical proparacaine was effective in relieving pain in most subjects. Corneal sensitivity was dramatically reduced at 10 minutes after exposure and was improved after 1 hour. At 1 week, corneal sensation had returned to normal, as had slit-lamp appearance on all subjects examined.
Forming, changing, and acting on attitude toward affirmative action programs in employment: a theory-driven approach.
A model of attitude toward affirmative action programs (AAPs) was applied in 4 studies involving 1,622 participants. In Study 1, attributes people tacitly associate with AAPs were identified by open-ended elicitation. Using those attributes, an instrument was developed and administered in Studies 2, 3, and 4. In those studies, a multiplicative composite of beliefs and evaluations about the AAP attributes predicted AAP attitude, consistent with M. Fishbein and I. Ajzen's (1975) theory of reasoned action. Demographic effects on AAP attitude were partially mediated by this composite. In Studies 3 and 4, an experimental manipulation of AAP information was successful in changing AAP attitude, but in a way that polarized existing demographic differences. Study 4 also showed that AAP attitude and subjective norm jointly and uniquely predicted intentions to perform AAP-related behaviors. Intentions predicted the actual behavior of mailing postcards to political representatives reflecting participants' support for AAPs.
Involvement of protein kinase A and A kinase anchoring protein in the progesterone-initiated human sperm acrosome reaction.
The signal transduction pathways involved in the progesterone (P(4))-initiated mammalian sperm acrosome reaction (AR) are not fully understood. To investigate the role of the protein kinase A (PKA) pathway in the P(4)-initiated AR, we probed this pathway by pretreating capacitated human sperm with reagents designed to either inhibit PKA activation or disrupt PKA/A kinase anchoring protein (AKAP) interactions. Preincubation with the stearated (membrane permeable) PKA inhibitor, PKI alpha 5-24 (S-PKI alpha 5-24), significantly inhibited the P(4)-initiated AR at 10 microM as compared to stearated control peptide. In contrast, preincubation with 100 microM nonstearated PKI alpha 5-24 did not significantly inhibit versus solvent control. Preincubation with the PKA inhibitor Rp-8-Br-cAMP at 500 microM and 150 microM significantly inhibited the P(4)-initiated AR versus 8-Br-cAMP and versus solvent. Preincubation with the anchoring inhibitory peptide S-Ht-31 significantly stimulated the P(4)-initiated AR at 10, 3, and 1 microM versus inactive control peptide. The stimulation of the P(4)-initiated AR by 3 microM S-Ht31 was significantly inhibited by the addition of 30 microM S-PKI alpha 5-24 prior to the addition of S-Ht31. Preincubation with S-PKI alpha 5-24 (30 microM) partially inhibited the ionomycin (50 microM)-initiated AR. A role for PKA in the P(4)-initiated AR may exist both upstream and downstream of Ca(2+) entry. Our studies present the first evidence for the participation of PKA in the P(4)-initiated AR and also suggest that AKAPs are involved in the PKA-mediated events.
Tegument-specific, virus-reactive CD4 T cells localize to the cornea in herpes simplex virus interstitial keratitis in humans.
Herpes stromal keratitis (HSK) is a prevalent and frequently vision-threatening disease associated with herpes simplex virus type 1 (HSV-1) infection. In mice, HSK progression occurs after viral clearance and requires T cells and neutrophils. One model implicates Th1-like CD4 T cells with cross-reactivity between the HSV-1 protein UL6 and a corneal autoantigen. HSK can be prevented by establishing specific immunological tolerance. However, HSK can also occur in T-cell receptor-transgenic X SCID mice lacking HSV-specific T cells. To study the pathogenesis of HSK in the natural host species, we measured local HSV-specific T-cell responses in HSK corneas removed at transplant surgery (n = 5) or control corneas (n = 2). HSV-1 DNA was detected by PCR in two specimens. HSV-specific CD4 T cells were enriched in three of the five HSK specimens and were not detectable in the control specimens. Reactivity with peptide epitopes within the tegument proteins UL21 and UL49 was documented. Responses to HSV-1 UL6 were not detected. Diverse HLA DR and DP alleles restricted these local responses. Most clones secreted gamma interferon, but not interleukin-5, in response to antigen. HSV-specific CD8 cells were also recovered. Some clones had cytotoxic-T-lymphocyte activity. The diverse specificities and HLA-restricting alleles of local virus-specific T cells in HSK are consistent with their contribution to HSK by a proinflammatory effect.
Transcatheter closure of atrial septal defects using the Cardio-Seal implant.
OBJECTIVE: To review the outcomes of transcatheter closure of atrial septal defects using the Cardio-Seal implant. DESIGN: A prospective interventional study. SETTING: Tertiary referral centre. PATIENTS: The first 50 patients (median age 9.7 years) who underwent attempted percutaneous occlusion. INTERVENTIONS: Procedures were done under general anaesthesia and transoesophageal guidance between December 1996 and July 1998. MAIN OUTCOME MEASURES: Success of deployment, complications, and assessment of right ventricular end diastolic diameter, septal wall motion, and occlusion status by echocardiography. RESULTS: The median balloon stretched diameter was 14 mm. Multiple atrial septal defects were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19 (38%). In four patients (8%), a second device was implanted after removal of an initially malpositioned first implant. There were no significant immediate complications. All patients except one were discharged within 24 hours. At the latest follow up (mean 9.9 months) a small shunt was present in 23 patients (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion abnormalities normalised in all but one patient. No predictors for a residual shunt were identified. Supporting arm fractures were detected in seven patients (14%) and protrusion of one arm through the defect in 16 (32%), the latter being more common in those with smaller anterosuperior rims. No untoward effects resulted from arm fractures or protrusion. There were no complications during follow up, although five patients (10%) experienced transient headaches. CONCLUSIONS: The implantation of the Cardio-Seal device corrects the haemodynamic disturbances secondary to the right ventricular volume overload, with good early outcome.
Determinants of survival and length of survival in adults with Eisenmenger syndrome.
A retrospective study of adults with Eisenmenger syndrome assessed at a tertiary referral center was performed to identify clinical characteristics and establish prognostic determinants. Mortality and cause of death are reported with baseline clinical data correlated with mortality to identify predictors of death. Clinical events during follow-up, including heart failure, atrial arrhythmia, hemoptysis, and syncope were also reviewed. A total of 109 adults with Eisenmenger syndrome (mean +/- SD age 29 +/- 11 years, 43% men) were followed for a median of 6.3 years. Sixty-six patients (61%) had simple cardiac anatomy (13 atrial septal defect, 43 ventricular septal defect, 10 patent ductus arteriosus). The remainder (43 patients) had complex cardiac anatomy (including atrioventricular septal defect, truncus arteriosus, univentricular heart, and transposition of the great arteries). There were 33 deaths and 9 transplantations during follow-up. Median survival was 53 years. Multivariate Cox regression analysis identified age at presentation (hazard ratio [HR] 0.90), supraventricular arrhythmia (HR 3.44), precordial electrocardiogram voltage (HR 1.61/mV increase), and poor New York Heart Association functional class (HR 2.60) as independent predictors of mortality. There is a large variation in the life expectancy for adults with Eisenmenger syndrome. Baseline characteristics associated with increased mortality include younger age at presentation (associated with complex anatomy), functional class, supraventricular arrhythmia, and an electrocardiogram index for right ventricular hypertrophy.
Layer perfection in ultrathin MOVPE-grown InAs layers buried in GaAs(001) studied by X-ray standing waves and photoluminescence spectroscopy.
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Outcome of previous tricuspid valve operation and arrhythmias in adult patients with congenital heart disease.
BACKGROUND: Tricuspid valve operation or replacement has been associated with high perioperative mortality and poor long-term results. The prevalence of atrial arrhythmias before and after operation in these patients is undefined. METHODS: We retrospectively examined the outcome and frequency of atrial arrhythmias in 85 adult patients (46% men) with congenital heart defects who underwent tricuspid valve operation between 1961 and 1995. RESULTS: The majority had either Ebstein's anomaly (22%), congenitally corrected transposition (19%), tetralogy of Fallot (15%), atrial (13%), or ventricular (11%) septal defects. Forty-two (49%) patients had sustained arrhythmias within 1 year before operation. After tricuspid valve operation, 21 patients (50%) had recurrence of atrial arrhythmias, and 7 in preoperative sinus rhythm developed late rhythm disturbances. Multivariate analysis identified age at operation and preoperative arrhythmias as independent predictors of late arrhythmias. Perioperative mortality was 5%, and there were seven late deaths. Survival was 91% at 5 years, and 83% at 10 years. CONCLUSIONS: Surgical intervention does not prevent recurrence of atrial arrhythmias. Tricuspid valve operation in patients with congenital heart disease can be performed with a low risk of perioperative mortality and good long-term outcome.
Reoperation in adults with repair of tetralogy of fallot: indications and outcomes.
OBJECTIVE: The purpose of this study is to review indications, surgical procedures, and outcomes in adults with repaired tetralogy of Fallot referred for reoperation. METHOD: Sixty consecutive adults (age >/= 18 years) who underwent reoperation between 1975 and 1997 after previous repair of tetralogy of Fallot were reviewed. Mean age at corrective repair was 13.3 +/- 9.6 years and at reoperation 33.3 +/- 9.6 years. Mean follow-up after reoperation is 5.0 +/- 4.9 years. RESULTS: Long-term complications of the right ventricular outflow tract (n = 45, 75%) were the most common indications for reoperation: severe pulmonary regurgitation (n = 23, 38%) and conduit failure (n = 13, 22%) were most frequent. Less common indications were ventricular septal patch leak (n = 6) and severe tricuspid regurgitation (n = 3). A history of sustained ventricular tachycardia was present in 20 patients (33%) and supraventricular tachycardia occurred in 9 patients (15%). A bioprosthetic valve to reconstruct the right ventricular outflow tract was used in 42 patients. Additional procedures (n = 115) to correct other residual lesions were required in 46 patients (77%). There was no perioperative mortality. Actuarial 10-year survival is 92% +/- 6%. At most recent follow-up, 93% of the patients are in New York Heart Association classification I or II. Sustained ventricular tachycardia occurred in 4 patients (7%) during follow-up. CONCLUSIONS: Long-term complications of the right ventricular outflow tract were the main reason for reoperation. Mid-term survival and functional improvement after reoperation are excellent.