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Introduction: The lack of underrepresented individuals in the vast fields of scientific cancer research underlines the need for effective training programs to encourage aspiring trainees. There is a dire need to expand the number of underrepresented scientists to decrease the number of mortality rates and cancer incidences in minority populations. Training initiatives demand creativity, flexibility, commitment and a sincere desire to produce change in the system. Description: Project LINK (Leaders in New Knowledge) is a solution to this problem. Its primary goal is to create a cadre of culturally competent, well-trained cancer research scientists to ultimately contribute to improved health among ethnic and racial minority populations. With funding from the National Cancer Institute, Continuing Umbrella of Research Experiences- CURE, Project LINK is a year-round training program that provides trainees with hands-on research opportunities spanning the continuum of basic science to behavioral sciences under the direct mentorship of Moffitt scientists. Methods: Trainees’ educational and research activities include attendance at grand rounds, special lectures, lab meetings, annual dinner with the Moffitt's center director, and monthly Fireside Chats where trainees relate their different research experiences. Research skills learned include: viral production, proliferation assays, microarray analysis, flow cytometry, cell culture, PCR, mouse injections, genotype analysis, survey development, mixed research methods, literature searches. Outside the lab, trainees are exposed to a number of community outreach activities in efforts to tackle health disparities. Through the Tampa Bay Community Cancer Network (TBCCN), a community network program funded by NCI, LINK trainees witness firsthand how their laboratory research benefits their communities. With an annual research presentation day and research paper requirement, LINK trainees also have the opportunity to sharpen their presentation and scientific paper writing skills. To date, Project LINK has trained 37 aspiring scientists at the high school/early college level [Hispanics (n=13); African Americans (n=19); Native Americans (n=1); White (n=1); and Mixed Race (n=2); Other (n=1)]. Currently, there are 5 LINK trainees, and recruitment is underway to add 5 more. As LINK trainees, they are given insights into personal development and scientific thinking that they would not otherwise have received. Additionally, placing them in team-oriented research environments instills in the trainees key lessons such as collaboration, team work, and responsibility. Evaluations indicated that trainees felt Project LINK “has the potential to open many doors” in the future, that it “increases knowledge” in the field of research, and that it “allows opportunities to explore cancer research in a way that many undergraduates don't have a chance to explore.” Conclusion: With a well-established infrastructure, outstanding project team leadership, and a plethora of laboratory and community resources to learn from, training programs such as Project LINK are key to bolstering underrepresented researchers in cancer research and thereby impacting cancer disparities. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B33.

• We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks.

Summary Twenty-four hour outpatient monitoring was compared with maximum multi-stage Treadmill exercise testing for the detection of dysrhythmias producing syncope or near syncope in 119 patients. All patients had cardiovascular disorders; only 21% had coronary artery disease. Patients with obvious cause of syncope and/or significant dysrhythmias by resting electrocardiograms (ECGs) were excluded. A significant dysrhythmia was found which was considered the probable cause of syncope or pre-syncope in 76 patients (64%). A non-cardiac cause was found in 16 (13%), and in 27 (23%) no cause was identified. Except for one patient with supraventricular tachycardia, exercise testing identified only patients with complex ventricular dysrhythmias and missed 64% of these. Overall, dysrhythmias were found by ambulatory monitoring alone in 63 patients, by exercise testing alone in only three, and by both in 10. It is concluded that: 1) in the majority of patients with syncope or pre-syncope suspected to be of a cardiac origin, a dysrhythmia can be found; 2) ambulatory monitoring is far superior to exercise testing for detection of dysrhythmias; 3) exercise testing increases the yield for complex ventricular dysrhythmias.

Two patients presented with severe left heart failure and large secundum atrial septal defects without severe pulmonary hypertension. The acute hemodynamic effects of two commonly used vasodilator agents, isosorbide dinitrate and hydralazine, are described. Although isosorbide dinitrate improved systemic forward cardiac output, it also increased left-to-right intracardiac shunting in both patients. On the other hand, hydralazine dramatically improved systemic forward output and concomitantly diminished left-to-right shunt flow in each patient (43 and 21 percent). The complexities of combined severe left ventricular failure and a large atrial septal defect with left-to-right shunting, and the importance of extensive hemodynamic monitoring at the time of pharmacologic intervention, are discussed.

Hemodynamic data and systolic time intervals were obtained at resting heart rate and during atrial pacing in 10 patients with heart disease, eight with left ventricular dysfunction, and two with mitral stenosis. The mean increase in heart rate was 44 beats/min. During atrial pacing there was no significant alteration in cardiac output, minute work, left atrial or pulmonary wedge mean pressure, or duration of left ventricular pre-ejection period. When the pressure events which determine the duration of the isovolumic time and the left ventricular pre-ejection period were examined, aortic diastolic pressure rose while left ventricular end-diastolic pressure fell. The rate of pressure rise (dp/dt) determined from high-fidelity left ventricular pressure pulses in three patients increased out of proportion to the increased pressure developed throughout isovolumic contraction. The augmentation in dp/dt from lower end-diastolic pressure indicates improved mechanical performance of the left ventricle, which is not necessarily translated into hemodynamic improvement.

Schwartz and Dameshek1,2 have reported the apparent production of immunological tolerance in rabbits by the administration of a purine analogue, 6-mercaptopurine. Rabbits receiving concomitantly human serum albumin and 6-mercaptopurine failed to develop an immune response to the protein antigen, and weeks later, when antigen alone was administered, the animals remained tolerant. In an effort to confirm this finding and to explore the possible effects of 6-mercaptopurine on homografts in rabbits, two groups of rabbits received injections of ovalbumin in Freund's adjuvant and were grafted with skin from a common donor rabbit. One of these groups received 6-mercaptopurine in the maximum dose employed by Schwartz and Dameshek, the other group serving as controls. The 6-mercaptopurine did not produce immunological tolerance for ovalbumin nor did it result in successful homografts.

Excerpt Since its discovery, penicillin has remained the antibiotic of choice for the treatment of bacterial endocarditis. This disorder requires therapy with bacteriocidal agents, for the literatu...

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Hereditary diffuse leukoencephalopathy with spheroids (HDLS) presents with a variety of clinical phenotypes including motor impairments such as gait dysfunction, rigidity, tremor and bradykinesia as well as cognitive deficits including personality changes and dementia. In recent years, colony stimulating factor 1 receptor gene (CSF1R) has been identified as the primary genetic cause of HDLS. We describe the clinical and neuropathological features in three siblings with HDLS and the CSF1R p.Arg782His (c.2345G > A) pathogenic mutation. Each case had varied motor symptoms and clinical features, but all included slowed movements, poor balance, memory impairment and frontal deficits. Neuroimaging with magnetic resonance imaging revealed atrophy and increased signal in the deep white matter. Abundant white matter spheroids and CD68-positive macrophages were the predominant pathologies in these cases. Similar to other cases reported in the literature, the three cases described here had varied clinical phenotypes with a pronounced, but heterogeneous distribution of axonal spheroids and distinct microglia morphology. Our findings underscore the critical importance of genetic testing for establishing a clinical and pathological diagnosis of HDLS.

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433–0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457–0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37–0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341–0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534–0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

Excerpt Five normotensive patients developed severe brain dysfunction during cardiac angiography. Four had angiography because of recurrent, severe angina pectoris, and one patient had valvular aor...

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