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Biomedical subjects

R McBride

Publications and source records attributed to R McBride.

At least 19 recordsLinked to original sources

Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin.

Distant metastases are the major cause of morbidity and mortality in women with breast cancer. The ability to predict the metastatic proclivity is essential in choosing the optimal treatment. Tumor size and grade, which are frequently used markers in node-negative breast cancer patients, are inadequate markers for prognosis and individualized treatment design. The steps in metastatic progression include angiogenesis, invasion, and changes in adhesion characteristics. We developed a strategy for choosing biomarkers representing these steps in malignant progression to identify patients with occult metastases who will need chemotherapy and spare those women whose tumors have not developed the capacity to spread. To evaluate the added significance of E-cadherin to that of nm23-H1 and angiogenesis in determining metastatic proclivity, we used archival material from 168 node-negative breast cancer patients who were treated with mastectomy without any adjuvant chemotherapy or hormone therapy. Immunohistochemistry was used to detect E-cadherin and nm23-H1 expression, whereas angiogenesis was determined by microvessel count (MVC) after immunohistochemical staining. The median follow-up is 14 years. We found that E-cadherin is better in identifying the poor prognosis patients. The 14-year disease-free survival (DFS) is 84%, 80%, and 56% in patients with high, intermediate, and low E-cadherin. The worst prognosis group using nm23-H1 and MVC as biomarkers has a 14-year DFS of 62%. In this group, if E-cadherin is low, the 14-year DFS is further decreased to 44%. Nm23-H1 and MVC are better in identifying the good prognosis patients. The long-term DFS is >90% if MVC is low or if nm23-H1 is high. Multivariate analysis shows that E-cadherin, nm23-H1, and MVC are more significant prognostic biomarkers than tumor size or grade. Loss of E-cadherin appears to be a latter step in the metastatic progression compared to angiogenesis and the loss of nm23-H1 expression.

Adult

Expression of fos and jun proto-oncogenes in benign versus malignant human uterine tissue.

OBJECTIVE: The objective of this study was to evaluate expression of fos and jun proto-oncogenes in benign human uterine tissue compared with malignant uterine tissue. METHODS: Forty-two endometrial tissue specimens were obtained at the time of hysterectomy. Tissue samples from different phases of the menstrual cycle and from postmenopausal patients were stained using immunohistochemical methods to detect Fos and Jun proteins, estrogen and progesterone receptor status, and Ki67 (detects a nuclear antigen associated with proliferating cells). Tissue was examined microscopically for nuclear staining in endometrial epithelium and stroma. The endometrium was based on the patient's last menstrual period, pathologic dating, and proliferative versus nonproliferative status as determined by Ki67. Benign and malignant specimens were subjected to Northern blot analysis to evaluate levels of expression of c-fos, c-jun, and jun-B mRNA. The pattern of c-fos mRNA expression in malignant samples was further evaluated using in situ hybridization. RESULTS: In proliferative, secretory, postmenopausal, and progesterone-influenced, uterine specimens immunohistochemically stained and examined, the endometrial and stromal nuclei stained for both Fos and Jun in varying intensities. However, no pattern was found in the variation of intensity according to the phase of the endometrium. Similarly, in malignant and benign endometrial tissue examined by Northern blot and in situ hybridization analyses, expression of proto-oncogene mRNAs was readily detectable, but no statistical correlation between type of tissue examined, grade of adenocarcinoma, and stage of endometrial cancer was found in this study. CONCLUSIONS: In rodent models, control of uterine cell proliferation is related to change in expression of fos and jun proto-oncogenes. Our results indicate that hormonal control is likely to be different in human endometrium and probably involves genes other than the proto-oncogenes under study. Expression of Fos and Jun do not correlate with endometrial cancer stage and grade.

Adenocarcinoma

Sex and other predictors of intra-aortic balloon counterpulsation-related complications: prospective study of 1119 consecutive patients.

BACKGROUND AND OBJECTIVE: Intra-aortic balloon counterpulsation (IABC) complication rates remain significant despite technical advances that have simplified and expanded its use. Previous reports implicated patient height, diabetes, or peripheral vascular disease as risk factors. However, these studies were small and not prospective. Therefore a prospective study at one high-volume center was conducted examining the complications associated with IABC and the role of sex and other risk factors in the current era. METHODS: The study prospectively evaluated 1174 consecutive percutaneous IAB insertions in 1119 patients between 1993 and 1997. Major complications were defined as embolism or limb ischemia requiring surgery; bleeding requiring transfusion or surgery; systemic infection; balloon rupture; or death from one of these causes. Minor complications were defined as limb ischemia or pulse loss resolving without surgery or after IAB removal or bleeding not requiring transfusion or surgical intervention. All variables were analyzed with univariate and stepwise multivariate analysis. RESULTS: Data were collected on 1119 patients (727 men and 392 women) with a mean age of 65 +/- 11 years. The prevalence of diabetes, hypertension, and peripheral vascular disease was 27%, 52%, and 8%, respectively. Complications occurred in 166 patients (15%) and a major complication occurred in 126 (11%) of the 1119 patients. Multivariate logistic regression analysis was done with demographic, clinical, and procedural variables in a cohort of 1106 patients. The analysis identified peripheral vascular disease (relative risk [RR] 4.1), female sex (RR 2.3), and body surface area (RR 0.26 per m(2)) as independent predictors of a major complication. In addition, cardiac index (RR 0.7) was also identified as an independent predictor of any or major complications in a subset of 915 patients. In 754 high-risk patients (women or patients with peripheral vascular disease, diabetes, cardiac index <2.2 L/min/m(2), or body surface area <1.8 m(2)), 114 major complications occurred (15%) compared with 8 (3%) among 278 non-high-risk patients (P <.0001). CONCLUSIONS: The current complication rate associated with IABC remains significant. Advances in IAB technology need to focus on the high-risk subset of patients that includes women, smaller patients, and those with peripheral vascular disease.

Aged

Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.

PURPOSE: To characterize the efficacy and safety of anticoagulants and antiplatelet agents for prevention of stroke in patients with atrial fibrillation. DATA SOURCES: Randomized trials identified by using the search strategy developed by the Cochrane Collaboration Stroke Review Group. STUDY SELECTION: All published randomized trials testing antithrombotic agents to prevent stroke in patients with atrial fibrillation. DATA EXTRACTION: Data on interventions, number of participants, duration of exposure and occurrence of all stroke (ischemic and hemorrhagic), major extracranial bleeding, and death were extracted independently by two investigators. DATA SYNTHESIS: Sixteen trials included a total of 9874 participants (mean follow-up, 1.7 years). Adjusted-dose warfarin (six trials, 2900 participants) reduced stroke by 62% (95% CI, 48% to 72%); absolute risk reductions were 2.7% per year for primary prevention and 8.4% per year for secondary prevention. Major extracranial bleeding was increased by warfarin therapy (absolute risk increase, 0.3% per year). Aspirin (six trials, 3119 participants) reduced stroke by 22% (CI, 2% to 38%); absolute risk reductions were 1.5% per year for primary prevention and 2.5% per year for secondary prevention. Adjusted-dose warfarin (five trials, 2837 participants) was more efficacious than aspirin (relative risk reduction, 36% [CI, 14% to 52%]). Other randomized comparisons yielded inconclusive results. CONCLUSIONS: Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more efficacious than aspirin. The benefit of antithrombotic therapy was not offset by the occurrence of major hemorrhage among participants in randomized trials. Judicious use of antithrombotic therapy, tailored according to the inherent risk for stroke, importantly reduces stroke in patients with atrial fibrillation.

Anticoagulants

Reduction in ischemic vascular complications with a hydrophilic-coated intra-aortic balloon catheter.

Hydrophilic coatings improve the handling characteristics of angioplasty equipment, but until recently this technology has not been available for intra-aortic balloon (IAB) catheters. To determine whether a new hydrophilic coating is associated with a reduction in IAB-related complications, we prospectively evaluated 188 patients undergoing insertion of this new IAB catheter. Complications related to IAB insertion were recorded and compared to data from 682 patients previously treated with an uncoated IAB catheter of the same shaft diameter and balloon size. By multivariate analysis the hydrophilic-coated IAB catheter was associated with a 72% reduction in ischemic vascular complications (relative risk 0.28, 95% CI 0.08-0.96, P= 0.04). There were also trends toward reductions in IAB rupture and the need for vascular surgical repair for bleeding or ischemia. While further investigation is warranted, hydrophilic coatings that reduce the coefficient of friction during IAB catheter insertion may also reduce subsequent ischemic vascular complications.

Aged

Left atrial diameter in nonvalvular atrial fibrillation: An echocardiographic study. Stroke Prevention in Atrial Fibrillation Investigators.

BACKGROUND: The left atrium (LA) is usually enlarged in patients with nonvalvular atrial fibrillation (AF), but factors associated with LA diameter are incompletely defined. METHODS AND RESULTS: This transthoracic echocardiographic cohort study includes 3465 participants with nonvalvular AF in 3 multicenter clinical trials. LA diameter determined by M-mode echocardiography was correlated with clinical and echocardiographic features by cross-sectional multivariate regression analyses. The mean LA diameter was 47 +/- 8 mm, on average 6 mm larger in those with AF at the time of echocardiography than in those with sinus rhythm (48 vs 42 mm, P <. 001). Patient age and body weight were independently predictive of LA diameter (P <.0001), but sex, body surface area, and body mass index were not. The estimated independent contribution of atrial rhythm to LA diameter was approximately 2.5 mm. Prolonged duration of AF, left ventricular dilatation and increased muscle mass, mitral regurgitation, annular calcification, and hypertension were additional independent predictors of LA diameter. CONCLUSIONS: Multiple factors appear to contribute to LA enlargement in patients with nonvalvular AF, including the presence and persistence of the dysrhythmia.

Age Factors

Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators.

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin. METHODS: We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed. RESULTS: Age (relative risk [RR]=1.8 per decade, P<0.001), female sex (RR=1.6, P=0.01), history of hypertension (RR=2.0, P<0.001), systolic blood pressure >160 mm Hg (RR=2.3, P<0.001), and prior stroke or transient ischemic attack (RR=2.9, P<0.001) were independently associated with increased stroke risk. Regular consumption of >/=14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4, P=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2, P=0.007). With the use of these variables, a risk stratification scheme for primary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants were less often disabling (P<0.001). CONCLUSIONS: Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.

Aged

Acute coronary syndromes in the United States and United Kingdom: a comparison of approaches. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: Patients with coronary artery disease are managed differently in different countries. HYPOTHESIS: These variations in patient management may affect clinical outcome, a possibility that should be taken into consideration in multicenter studies. METHODS: In a binational, 3 months study of antithrombotic treatment of patients with unstable angina and non-Q-wave infarction (ATACS), we compared the experience in the four enrollment centers in the United States (US) with the three centers in the United Kingdom (UK). The 59 US patients and the 299 UK patients were similar with regard to age, rates of prior revascularization, prior positive exercise tests, medication use, and aspirin use. RESULTS: US patients were more commonly women (45 vs. 28%), diabetic (30 vs. 4%), or hypertensive (52 vs. 31%), and had a prior coronary angiogram (30 vs. 18%). After enrollment, coronary angiography was performed more frequently in the US than in the UK (61 vs. 22%). Although the distribution of coronary disease was similar, revascularization without recurrent angina (19 vs. 4%, p < 0.001), or following recurrent angina (8 vs. 3%), was significantly more frequent in the US. Combined primary end points (recurrent angina, myocardial infarction, or death) did not differ between US (29%) and UK (25%) patients. CONCLUSION: Therefore, international studies of acute coronary disease need to account for different treatments in different countries. These differences, in the small ATACS study, did not have a major impact on the composite primary outcome variables.

Adult

Prospective Comparison of Patient Characteristics and Outcome of Non-prior Aspirin Users versus Aspirin Users with Unstable Angina or Non-Q-Wave Myocardial Infarction Treated with Combination Antithrombotic Therapy.

The objective of this study was to determine if aspirin users presenting with acute coronary syndromes are at higher risk for subsequent clinical events. In a trial evaluating combination antithrombotic therapy in resting angina or non-Q-wave myocardial infarction (MI), patients were prospectively dichotomized on admission into nonprior versus recent aspirin users. Then 105 nonprior users and 144 users were randomized to treatment with aspirin plus heparin/warfarin for 12 weeks. Recurrent myocardial ischemia occurring during the 12-week follow-up period was defined as recurrent angina (with electrocardiographic changes or prompting coronary revascularization), MI, or death. Prior aspirin users had a significantly higher incidence of previous MI, prior bypass grafting, beta-blocker use, or hypertension (p </= 0.003) and were more likely to present with unstable angina as opposed to non-Q-wave MI. (p </= 0.008). The cumulative probability of recurrent ischemic endpoints for nonprior versus recent users was 10% versus 21% at 14 days (log rank p = 0.03), and 19% versus 29%, at 12 weeks (p = 0.06). Using the Cox model, adjusting for variables significantly associated with outcome, aspirin use remained a significant predictor of 14-day outcome (p = 0.04) but not of 12-week outcome (p = 0.06). In conclusion, even after adjusting for significant differences in baseline variables, aspirin users presenting with rest angina or non-Q-infarction have a worse short-term prognosis in spite of maximal medical therapy.

Journal Article

Biochemical markers of alcohol abuse.

Excessive alcohol consumption is a major health problem in the UK leading to both serious morbidity and mortality. This study compared newer potential biochemical markers of excessive alcohol consumption [carbohydrate-deficient transferrin (CDT), mitochondrial AST (mAST) and alpha glutathione-s-transferase (alpha-GST)] with conventional markers (AST, ALT, GGT, MCV). Patients (n = 85) were enrolled in the study and subdivided into several groups on the basis of alcohol consumption. Patients with non-alcoholic liver disease (NALD) (n = 40) were also enrolled. All the markers, with the exception of the ratio mAST/total AST were significantly higher in heavy drinkers/alcoholics compared to teetotallers/social drinkers (p < 0.05). mAST and AST/ALT ratio were significantly higher in alcoholics compared to NALD (p < 0.01), whereas ALT was higher in the NALD group (p < 0.05). Multivariate discriminant function analysis (Wilks method) demonstrated that the logarithmic functions of AST/ALT ratio and mAST could correctly classify 87.9% of cases into either the alcoholic or NALD groups. ROC plot analysis showed that AST, mAST and GGT were the best markers at distinguishing heavy consumption of alcohol from lesser levels and that AST/ALT ratio and mAST were the best in distinguishing alcoholics from NALD. In conclusion, none of the newer biochemical markers, with the exception of mAST, offers any major advantage over the conventional markers.

Adult

The Cardiac Arrhythmia Suppression Trial: Implications for nursing practice.

BACKGROUND: Care of patients with ventricular arrhythmia after myocardial infarction requires careful nursing management, including assisting with arrhythmia monitoring and testing. Because ventricular premature depolarization is a known risk factor for sudden cardiac death, it was hypothesized that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarization would improve survival in these patients. OBJECTIVE: To review the Cardiac Arrhythmia Suppression Trial findings and provide implications for nursing practice for patients after myocardial infarction. METHODS: The Cardiac Arrhythmia Suppression Trial was a multicenter, randomized, placebo-controlled trial designed to determine whether the suppression of ventricular premature depolarizations in postmyocardial infarction patients would improve survival. Three class I antiarrhythmic drugs were used: encainide, flecainide, or moricizine. Patients for whom the drug suppressed their arrhythmia 80% or more were randomly assigned to that drug and dose or its matching placebo and were followed every 4 months (main study). Patients with 1% to 79% suppression were randomly assigned to the drug or its placebo that best treated their arrhythmia and followed every 4 months. RESULTS: Suppression of asymptomatic or mildly symptomatic ventricular premature depolarization in patients using encainide, flecainide, or moricizine failed to improve patient survival and was even harmful in some cases. CONCLUSIONS: Our results showed that in the absence of effective antiarrhythmic drug therapy, supportive nursing care and arrhythmia monitoring is important until appropriate therapy for the management of these arrhythmias in patients who have had a myocardial infarction can be found. Clinical trials are essential to provide an evaluation of therapies and direction for further studies, as well as a basis for practicing clinicians.

Aged

Prospective evaluation of complications associated with percutaneous intraaortic balloon counterpulsation.

In summary, current, prospective experience with 691 consecutive patients revealed that female gender, peripheral vascular disease, cardiac index, and diabetes were the only independent predictors of risk after percutaneous IAB insertion. Neither sheathless insertion nor smaller IAB catheter size was associated with a lower complication rate. There may be a threshold of catheter size associated with a dramatic reduction in complications. If that exists, it has not yet been reached.

Aged

Toward vital status sweeps: a case history in sequential monitoring.

We use data from the Cardiac Arrhythmia Suppression Trial (CAST) to demonstrate the sensitivity of sequential monitoring to the timeliness of survival data. In CAST vital status sweeps were not routinely performed prior to the times of sequential analysis. Examination of the delay between death and reporting of death shows that the change in the time of sequential analysis by even as few as several months can have dramatic impact on the results of the sequential analysis.

Anti-Arrhythmia Agents

Pilot prospective evaluation of counterpulsation with different intra-aortic balloon volumes on cardiac performance in humans.

UNLABELLED: Smaller intra-aortic balloons (IAB) may minimize peripheral vascular complications. To determine the influence of different IAB volumes on cardiac performance, we studied 20 hemodynamically stable patients on IAB counterpulsation. Variables were measured with either a 40cc or 32cc IAB displacement, at an assist ratio of 1:1 or 1:8: Heart rate, Ao and PA pressures, and Fick cardiac output. By echo-Doppler, the velocity time integral (VTI) across the LV outflow tract, a measure of stroke volume was also calculated. The mean age was 60 yr (range 18-77), height 5'6" (5'2"-5'11"), and body surface area 1.9M2 (1.5-2.3). Results presented as mean values were: [table: see text] *P < 0.005 1:1 vs 1:8 for both 40 and 32cc IAB. CONCLUSION: IAB pumping at 1:1 with either 40 cc or 32 cc volume displacement yields similar degrees of improvement in cardiac performance. A larger cohort is required to determine if smaller balloons may decrease complications without compromising efficacy.

Adolescent

Tympanic membrane thermometry in the care of out-of-hospital patients.

STUDY OBJECTIVES: To determine the effectiveness of tympanic membrane (TM) thermometry in the out-of-hospital setting and to characterize the patients with abnormal out-of-hospital temperatures. DESIGN: Prospective, randomized, single-month study. SETTING: Inner city. PARTICIPANTS: Subjects transported by ambulance for whom consent was obtainable. RESULTS: TM probes set to rectal equivalent were assigned to three of the ambulance units of the local health department on randomly selected shifts during August 1992, one half at night and one half during the day. Simultaneous left and right ear temperatures at the scene and at the hospital, ambient temperatures, and patient's hospital temperatures were recorded. Other data recorded included each patient's mental status, activity level, and environment temperature. Paramedics noted whether they suspected a temperature problem before using the probe and whether any treatment was directed toward the patient's temperature. Regression, bias analysis, and chi 2 testing were performed; P was considered significant if it was less than .05. Right and left ear TM temperatures were correlated both at the scene and at the hospital (r = .91 and .92, respectively). TM temperatures and hospital temperatures were also correlated (r = .83 for right ear and .78 for left ear). Evaluation of agreement indicated that TM and hospital methods were equal, with a bias of -0.55 degrees F for oral and +0.66 degrees F for rectal temperatures. Thirty-two subjects (17%) were hyperthermic at the scene; of these, 9 of 32 (28%) were suspected before use of the probe. The paramedics initially treated 5 of the 9 suspected to have a temperature-related problem before using the probe and none of the 23 who were not suspected before using the probe (chi 2, P < .001). CONCLUSION: The TM probe functioned well despite a month of vigorous handling. Temperature correlation with the gold standard and between ears was acceptable in this setting. Presence of the probe did not help with the management of hyperthermic patients in this study.

Adolescent

Prospective comparison of unstable angina versus non-Q wave myocardial infarction during antithrombotic therapy. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

OBJECTIVES: This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy. BACKGROUND: Antithrombotic therapy is beneficial in patients with these two coronary syndromes. METHODS: In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups. RESULTS: Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week. CONCLUSIONS: Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.

Adrenergic beta-Antagonists