Coronary artery anomalies: assessment with free-breathing three-dimensional coronary MR angiography

PURPOSE: To evaluate a simplified protocol by using free-breathing three-dimensional (3D) coronary magnetic resonance (MR) angiography to determine the anatomy of anomalous coronary arteries, in particular the relationship of the vessels to the aortic root. MATERIALS AND METHODS: Twenty-six patients (18 men, eight women; mean age, 50 years; age range, 18-77 years) who had a history of chest pain, palpitations, or syncope and who were suspected of having coronary artery anomalies were examined with free-breathing MR angiography. Multiple 3D volume slabs were acquired at the level of the sinuses of Valsalva by using diaphragmatic navigators for respiratory artifact suppression. The proximal anatomy of the coronary arteries was determined. RESULTS: Six anomalous circumflex arteries originated from the right sinus of Valsalva and passed behind the aortic root. Six right coronary arteries arose from the left sinus of Valsalva and coursed between the aortic root and the right ventricular outflow tract (RVOT). Nine left coronary arteries arose from the right sinus of Valsalva; seven of nine coursed between the aortic root and the RVOT. Five patients had minor anomalies. Overall, in eight patients with anomalous arteries that coursed between the aortic root and the RVOT, conventional coronary angiography could not be used confidently to identify the proximal course. CONCLUSION: Free-breathing 3D coronary MR angiography can be used to identify the proximal anatomy of anomalous coronary arteries.     

Epstein-Barr virus as a marker of survival after Hodgkin's lymphoma: a population-based study.

PURPOSE: Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype. PATIENTS AND METHODS: Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3). CONCLUSION: In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.     

Characterization of new rat anti-mouse IgE monoclonals and their use along with chimeric IgE to further define the site that interacts with Fc epsilon RII and Fc epsilon RI.

Three rat monoclonal antibodies specific for mouse IgE (C12B9, 23G3, and B1E3) were established by using monoclonal anti-DNP mouse IgE (mIgE) as immunogen. These antibodies, as well as a fourth, (R1E4) were characterized. It was found that one antibody (C12B9) recognizes an allotypic determinant (Igh-7a) found on the C epsilon chain of mIgE. Antibody cross-blocking studies and epitope mapping studies using recombinant mIgE indicated that 3 antibodies (C12B9, R1E4 and 23G3) were directed against the C epsilon 3 domain while one (B1E3) was directed against the C epsilon 4 domain. A highly specific sandwich RIA for mIgE was developed using these antibodies. Use of these monoclonal anti-mIgE antibodies in conjunction with recombinant chimeric mIgE-human IgG1 molecules, demonstrated that the C epsilon 3 domain is important in the binding of mIgE to the murine B cell Fc epsilon RII as well as to the murine mast cell F epsilon RI. The presence of the C epsilon 4 domain influenced the binding of the recombinant IgE to the Fc epsilon RII; in contrast to the C epsilon 4 domain had no effect on binding to the Fc epsilon RI.     

In vitro and in vivo evaluation of cotton wool filtration of platelet concentrates obtained by automated and manual apheresis

The effect of cotton wool filtration of apheresis platelet concentrates (PCs) on platelet viability and complement activation was evaluated by two laboratories. PCs were prepared by automated (Lab A, n = 5) or manual (Lab B, n = 5) apheresis. After storage for 1 day, the PC was filtered through cotton wool before transfusion on one occasion and, on the other occasion, filtered through a standard screen filter before transfusion to the same donor. Five paired studies were performed by each laboratory. Except for a small, but significant reduction in mean platelet size, from 7.3 +/- 1.1 to 6.6 +/- 0.9 microns 3, after cotton wool filtration, no effect of filtration on various tests of in vitro platelet function and morphologic integrity was found. As demonstrated by autologous radiolabeled studies, no effect of cotton wool filtration on platelet viability was found by Laboratory B, while Laboratory A found a slight increase in the percentage of recovery from 59 +/- 4 to 68 +/- 13 percent, and a small reduction in survival, from 8.2 +/- 0.9 to 7.7 +/- 0.5 days after cotton wool filtration (p less than 0.05). Cotton wool filtration was associated with a slight increase in C3a levels found in manual apheresis PCs. Neither laboratory found any effect of cotton wool filtration per se on the recipients' white cell (WBC) counts or C3a and C5a levels after transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemia in the ambulatory setting--the total ischemic burden: relation to exercise testing and investigative and therapeutic implications

To establish the relation between treadmill exercise testing and ambulatory St segment monitoring in the detection of ischemia in patients with coronary artery disease, and to assess whether standard medical therapy affects any such relation, 277 patients with stable angina and angiographically documented coronary artery disease were studied with treadmill exercise testing and 48 h ambulatory ST segment monitoring. One hundred forty-six patients (52%) were studied while receiving no routine antianginal therapy, and 131 (48%) while receiving standard medical therapy. In 187 patients (67%) the exercise test was positive for ischemia. During 11,964 h of ambulatory monitoring, 881 episodes of ischemia (645 [73%] silent) were recorded, of which 809 (92%) occurred in patients with a positive exercise test. The mean heart rate at the onset of ischemic episodes during ambulatory monitoring was significantly less than that at the onset of 1 mm ST segment depression during exercise testing (94.5 versus 105.9 beats/min, p less than 0.0001). However, the frequency of ambulatory ischemic episodes was strongly related to a positive exercise test (p less than 0.001), and this relation was similar for both silent and painful ischemia (p less than 0.0001 for both) and in patients who were and were not receiving therapy (p less than 0.0001 for both). The total duration of ischemia was similarly related to a positive exercise test (p less than 0.0001). Only one patient with a negative exercise test had frequent (greater than 5/day) episodes of ischemia on ambulatory monitoring and had documented coronary artery spasm. Thus, exercise testing identifies the majority of patients likely to have significant ischemia during their daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Summary We examined the effect in rats of 2 months of streptozotocin-induced diabetes mellitus on relaxation and contraction of aortas in vitro. A further diabetic group was treated from time of diabetes induction with a 1% dietary supplement of vitamin E. Diabetes caused a 26.5% deficit (p<0.001) in maximum endothelium-dependent relaxation to acetylcholine in phenylephrine-precontracted aortas. This was 64.3% attenuated (p<0.01) by vitamin E treatment; maximum relaxation was not significantly altered compared to non-diabetic rats. Vitamin E treatment of non-diabetic rats did not significantly affect acetylcholine-induced relaxation. Diabetes or treatment did not significantly alter acetylcholine sensitivity. Endothelium-independent relaxation response to glyceryl trinitrate was not affected by diabetes or vitamin E treatment, indicating that vascular smooth muscle responses to nitric oxide remained unaltered. There was a 35.4% reduction in the maximum contractile response to phenylephrine with diabetes (p<0.05) which was unaffected by vitamin E treatment. The data suggest that the chronic deficit in nitric oxide-mediated endothelium-dependent relaxation in diabetes depends largely upon excess activity of reactive oxygen species. Treatment with vitamin E to increase free radical scavenging specifically protected vascular endothelium although it had no effect on deficits in vascular smooth muscle contractile responses.Abbreviations NO Nitric oxide - ARI aldose reductase inhibitor - ACH acetylcholine - GTN glyceryl trinitrate - GSH reduced form of glutathione - EC₅₀ effective concentration for 50% of the maximal response     

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients.

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.     

Fetal choroid plexus cysts: An independent risk factor for chromosomal anomalies

As a result of numerous conflicting reports, we designed a prospective controlled study to determine the inherent risk of aneuploidy with second-trimester fetal choroid plexus cysts. Our controls were patients who had ultrasonography and genetic amniocentesis, between 15 weeks and 22 weeks, menstrual age, by the same sonologist on the same day as a study subject with a choroid plexus cyst. Sixty-three cases of fetal choroid plexus cysts were detected in 3247 second-trimester examinations (1.9%). Six chromosomally abnormal fetuses [Trisomy 18 (3), Down syndrome (2), Klinefelter syndrome] were found in the cyst group (9.5%) with only one Trisomy 21 among the controls (0.5%) (p <.002). Of note, 5 of 21 (23.8%) fetuses with cysts greater than 5 mm in diameter had aneuploidy, as compared with only 1 of 42 (2.4%) chromosomal anomalies with smaller cysts (p <.02). We conclude that fetal choroid plexus cysts are an independent risk factor for chromosomal anomalies; genetic counseling and prenatal chromosomal analysis are indicated. © 1993 John Wiley & Sons, Inc.     

Racial/Ethnic and Socioeconomic Differences in Short-Term Breast Cancer Survival Among Women in an Integrated Health System

Objectives. We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment.Methods. Using electronic medical records data from Kaiser Permanente Northern California linked to data from the California Cancer Registry, we included 6262 women newly diagnosed with invasive breast cancer. We analyzed survival using multivariable Cox proportional hazards regression with follow-up through 2010.Results. After consideration of tumor stage, subtype, comorbidity, and type of treatment received, non-Hispanic White women living in low-SES neighborhoods (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.07, 1.52) and African Americans regardless of neighborhood SES (high SES: HR = 1.44; 95% CI = 1.01, 2.07; low SES: HR = 1.88; 95% CI = 1.42, 2.50) had worse overall survival than did non-Hispanic White women living in high-SES neighborhoods. Results were similar for breast cancer–specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival.Conclusions. Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients.Breast cancer is the most common cancer among women in the United States, and it is the second leading cause of cancer death.1 Despite significant improvements in breast cancer survival from 1992 to 2009,1,2 racial/ethnic and socioeconomic survival disparities have persisted.3,4 African American women have consistently been found to have worse survival after breast cancer,3,5–11 Hispanic women have worse or similar survival,3,9,11,12 and Asian women as an aggregated group have better or similar survival3,9,11,12 than do non-Hispanic White women. Underlying factors thought to contribute to these racial/ethnic disparities include differences in stage at diagnosis,8,12,13 distributions of breast cancer subtypes,14–16 comorbidities,12,13,17 access to and utilization of quality care,13,18 and treatment.12,13Numerous studies also have found poorer survival after breast cancer diagnosis among women residing in neighborhoods of lower socioeconomic status (SES).6,9,19,20 Research has shown that inadequate use of cancer screening services, and consequent late stage diagnosis and decreased survival, contribute to the SES disparities.21,22 Similar to racial/ethnic disparities, SES disparities have been attributed to inadequate treatment and follow-up care and comorbidities.18 Previous population-based studies have continued to observe racial/ethnic survival disparities after adjusting for neighborhood SES, but these studies have not considered the combined influence of neighborhood SES and race/ethnicity.3,9,11,12,23 These disparities may remain because information on individual-level SES, health insurance coverage, comorbidities, quality of care, and detailed treatment regimens have typically not been available.3,8,9,11,13 Even among studies using national Surveillance Epidemiology and End Results–Medicare linked data, in which more detailed information on treatment and comorbidities are available among some patients aged 65 years and older, survival disparities have remained.12,23,24 However, not all data on medical conditions and health care services are captured in Medicare claims, including data on Medicare beneficiaries enrolled in HMOs (health maintenance organizations).25,26Using electronic medical records data from Kaiser Permanente Northern California (KPNC) linked to data from the population-based California Cancer Registry (CCR), we recently reported that chemotherapy use followed practice guidelines but varied by race/ethnicity and neighborhood SES in this integrated health system.27 Therefore, to overcome the limitations of previous studies and address simultaneously the multiple social28 and clinical factors affecting survival after breast cancer diagnosis, we used the linked KPNC–CCR database to determine whether racial/ethnic and socioeconomic differences in short-term overall and breast cancer–specific survival persist in women in a membership-based health system. Our study is the first, to our knowledge, to consider the combined influence of neighborhood SES and race/ethnicity and numerous prognostic factors, including breast cancer subtypes and comorbidities, thought to underlie these long-standing survival disparities among women with uniform access to health care and treatment.