Coronary artery fistula presenting as bacterial endocarditis

Coronary artery fistula is often considered to be a benign and rare congenital anomaly. It is usually an incidental finding encountered during routine cardiac catheterization. We report a case of a patient presenting with endocarditis involving a large coronary artery fistula connecting an aneurysmal circumflex coronary artery to the coronary sinus. The diagnosis was initially made by echocardiography and confirmed by cardiac catheterization. In addition, we briefly discuss the literature on management of this coronary anomaly.     

The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure.

It has been reported that growth hormone (GH) deficiency induced cardiomyopathy responds to growth hormone replacement therapy. We describe the case of a middle-aged male with cardiomyopathic heart failure and growth hormone deficiency of the adult secondary to surgical panhypopituitarism. We demonstrate clinical and hemodynamic improvement of cardiac function with growth hormone replacement therapy despite underlying structural heart disease.     

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.     

Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment.

Three years of daily alendronate treatment increases microdamage in vertebral bone but does not significantly increase it beyond levels of microdamage found after 1 yr of treatment. This suggests microdamage accumulation peaks during the early period of bisphosphonate treatment and does not continue to accumulate with longer periods of treatment. INTRODUCTION: Clinically relevant doses of alendronate increase vertebral microdamage by 4- to 5-fold in skeletally mature beagles after 1 yr of treatment. The goal of this study was to determine whether microdamage would continue to accumulate with 3 yr of alendronate treatment in an intact beagle dog model. MATERIALS AND METHODS: One-year-old female beagles were treated with daily oral doses of vehicle (VEH, 1 ml/kg/d) or alendronate (ALN, 0.2 or 1.0 mg/kg/d) for 3 yr. These ALN doses were chosen to approximate, on a milligram per kilogram basis, those used to treat osteoporosis (ALN0.2) and Paget's disease (ALN1.0). Microdamage accumulation, static and dynamic histomorphometry, densitometry, and mechanical properties of lumbar vertebrae were assessed. Comparisons were made among the three groups treated for 3 yr and also within each treatment group to animals treated under the same conditions for 1 yr. RESULTS: Overall microdamage accumulation (crack surface density) was not significantly higher in animals treated for 3 yr with either dose of ALN, whereas crack density increased significantly (100%; p < 0.05) with the higher dose of ALN compared with VEH. Both ALN doses significantly suppressed the rate of bone turnover (-60% versus VEH). There was no difference among groups for any of the structural biomechanical properties-ultimate load, stiffness, or energy absorption. However, when adjusted for areal BMD, ALN-treated animals had significantly lower energy absorption (-20%) compared with VEH. Toughness, the energy absorption capacity of the bone tissue, was significantly lower than VEH for both ALN0.2 (-27%) and ALN1.0 (-33%). Compared with animals treated for 1 yr, there was no significant difference in microdamage accumulation for either ALN dose. VEH-treated animals had significantly lower bone turnover (-58%) and significantly higher levels of microdamage (+300%) compared with values in 1-yr animals. Toughness was significantly lower in animals treated for 3 yr with ALN1.0 (-18%) compared with animals treated for 1 yr, whereas there was no difference in toughness between the two treatment durations for either VEH or ALN0.2. CONCLUSIONS: Although 3 yr of ALN treatment resulted in higher microcrack density in vertebral trabecular bone compared with control dogs, the amount of microdamage was not significantly higher than animals treated for 1 yr with similar doses. This suggests that bisphosphonate-associated increases in microdamage occur early in treatment. Because toughness continued to decline significantly over 3 yr of treatment at the higher ALN dose, decreases in toughness are probably not dependent on damage accumulation.     

Outcomes of Project Wall Talk: an HIV/AIDS peer education program implemented within the Texas State Prison system.

We report select outcomes from an evaluation of Project Wall Talk, a community-based, peer-led HIV prevention education program implemented in 36 Texas State prison units. Peer educators completed questionnaires prior to receipt of a 40-hour intensive training (N = 590) and at 9-month follow-up (N = 257). Students (N = 2506) completed questionnaires pre- and post-receipt of peer educator-led HIV education sessions. Peer educators and their students showed significant increases in HIV-related knowledge. Peer educators showed significant increases in assessment of their skills as educators. For both peer educators and students, significant differences in HIV-related knowledge were indicated across categories of prior educational level attained and race/ethnicity; no such differences were indicated at follow-up. Compared with baseline, a significantly greater proportion of peer educators reported ever having had an HIV test. After receiving peer-led education, a significantly smaller proportion of students reported they knew their HIV status and more indicated plans to take an HIV test. Additionally, in months 12 and 18 following program implementation, the numbers of HIV tests at the five units that implemented the peer education program were roughly twice that of five, matched comparison units without the peer education program. Based on peer educator reports, we projected that peer educators (N = 257) may have as many as 84,000 or more annual opportunities to share HIV-related knowledge with other prisoners outside the classroom.     

Screening for type 2 diabetes mellitus in children and adolescents: attitudes, barriers, and practices among pediatric clinicians.

OBJECTIVE: The American Diabetes Association (ADA) recommends screening children at risk for type 2 diabetes with a fasting plasma glucose test or an oral glucose tolerance test. The purpose of this study was to describe attitudes, barriers, and practices related to type 2 diabetes screening in children among pediatric clinicians. METHODS: Pediatricians, nurse practitioners and physician assistants from a multispecialty, group practice in Eastern Massachusetts completed a mailed survey. To assess screening practice, three vignettes were presented representing pediatric patients with low, moderately high, and high risk for type 2 diabetes. The moderately high-risk and high-risk patients met ADA criteria for screening. ADA-consistent practice was defined as only screening the moderately high-risk and high-risk patients; lower-threshold practice was defined as also screening the low-risk patient; and higher threshold practice was screening only the high-risk patient. RESULTS: Sixty-two of 90 clinicians responded (69%). Based on intent to screen in the 3 vignettes, 21% of respondents reported ADA-consistent screening practice, 39% lower-threshold, and 35% higher-threshold screening practice. Five percent had incomplete or nonclassifiable responses. Many clinicians ordered screening tests other than those recommended by the ADA; few (< or =8% in any vignette) ordered only an ADA-recommended test. Preferences for nonfasting tests were influenced by nonmedical factors such as access to or cost of transportation. Inadequate patient education materials and unclear recommendations for appropriate screening methods were the most frequently reported moderate/strong barriers to screening. CONCLUSIONS: Most respondents reported type 2 diabetes screening practices that differed from current ADA recommendations. Our findings suggest that type 2 diabetes screening tests must be practical for clinicians and patients if they are to be used in pediatric practice. Further study of the benefits and cost-effectiveness of type 2 diabetes screening in children is warranted to clarify the role and optimal methods for screening in pediatric primary care.     

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.