Cardiac imaging in the evaluation of patients presenting to the emergency department with chest pain

Conclusions  Despite the utility and benefits that each imaging modality has to offer, it is easy to see why there is still no perfect choice for a noninvasive cardiac imaging modality to assist in the management of chest pain patients. All of the current imaging techniques have their own significant strengths and weaknesses when compared with other modalities. SPECT and echocardiography are wellestablished technologies that can directly assess the presence of myocardial ischemia and its functional consequence on RF; newer and more expensive techniques such as MDCT and CMR can directly assess coronary anatomy and have just started to be evaluated in the acute chest pain setting. There are no studies that directly compare these technologies, and more data are clearly needed before the question of whether anatomic imaging versus perfusion/function imaging is the better approach can be answered. Other comparisons such as relative safety, availability, logistics, and cost-effectiveness between the various technologies are also lacking. Of all of the imaging modalities discussed, MCE is the only portable technology. The images do not require expensive software or other technology for offline processing before interpretation, and any trained cardiologist can read the study at the bedside or, potentially, over the Internet, providing near-instantaneous results in the acute cardiac setting, where time is of the essence. MCE is also relatively cheap compared with other technologies, a potential advantage for payors but not necessarily for payees. How reimbursement rates and fee structures eventually affect clinical practice is also unknown. Despite these and other questions that need to be answered before any one technique will be used exclusively, the future of noninvasive cardiac imaging remains an exciting and ever-changing field. The adaptation of any one of these techniques into its proper role in the ED Journal of Nuclear Cardiology Wyrick and Wei 753 Volume 13, Number 6;749-55 Cardiac imaging in patients with chest pain will take considerably more time and effort in terms of research, money, and time-tested clinical experience.     

Cytoskeletal requirements in Chlamydia trachomatis infection of host cells.

Infection of genital epithelial cells by the closely related sexually transmitted pathogens Chlamydia trachomatis serovars E and L2 results in different clinical disease manifestations. Following entry into target host cells, individual vesicles containing chlamydiae fuse with one another to form one large inclusion. At the cellular level, the only obvious difference between these serovars is the time until inclusion maturation, which is 48 h for the invasive serovar L2 and 72 h for serovar E. To begin to define the intracellular events of these pathogens, the effect of cytoskeletal disruption on early endosome fusion and inclusion development in epithelial (HEC-1B) and fibroblast (McCoy) cells was analyzed by fluorescence microscopy. Disruption of microfilaments with cytochalasin D markedly reduced serovar E, but not serovar L2, infection of both cell lines. Conversely, microfilament as well as microtubule disruption, with colchicine or nocodazole, had no effect on serovar E inclusion development but resulted in the formation of multiple serovar L2 inclusions per cell during early and mid-development. Later in serovar L2 inclusion development (> 36 h postinfection), vesicles containing chlamydiae fused to form one large inclusion in the absence of an intact cytoskeleton. These results imply that (i) C. trachomatis serovar E may utilize a different pathway for uptake and development from serovar L2; (ii) these differences are consistent in both epithelial cells and fibroblasts; and (iii) the cytoskeleton plays a unique role in the infection of host cells by these two genital pathogens.     

Conformational analysis and molecular modeling of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as D1 dopamine receptor ligands

Conformational studies on a series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines that possess an identical substituent pattern to the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (1)] were performed with use of molecular mechanics calculations [MM2(85), with newly developed aromatic halide bending and torsional parameters that are now incorporated into MM2(87)], single-crystal X-ray analysis, and high-field NMR spectroscopy. The synthesis and biological testing of compounds 2-7 has been previously reported. The test compounds were compared both quantitatively and graphically to compound 1. Calculations on both the free-base and protonated forms of each compound were carried out. To insure that conformation space was adequately sampled, the test compounds were energy minimized from different starting geometries; ring inversion of the heterocycle was employed, as were dihedral driver calculations on the phenyl or benzyl rings. For N-methyl-6-chloro-7-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (2), it was determined that the torsion angle tau(C8a-C1-C12-C17) had energy minima at approximately 60 degrees and 240 degrees. This finding was corroborated by NMR studies that indicated a dramatic upfield chemical shift of ArH8 after ring cyclization. The nitrogen lone pair or hydrogen vector was approximately orthogonal to the plane of the substituted aromatic ring in the tetrahydroisoquinolines; this explained the upfield chemical shift of the vicinal chiral proton (H1). In all instances, the 6-membered heterocyclic ring in the energy-minimized structures preferred the half-chair conformation with the phenyl rings pseudo-equatorial. Distance comparisons of the proposed pharmacophoric atoms (Cl, N, O, centroid of the phenyl or benzyl ring) showed that the phenyl or benzyl centroid to ammonium H distance, Cl to N distance, and distance of the nitrogen above or below the plane of the isoquinoline aromatic ring are the distances most highly correlated with biological activity (r = 0.82, 0.75, 0.81, respectively). Resolution and single-crystal X-ray analysis of compound 2 showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-1. Least-squares fitting of the energy-minimized structures with SYBYL molecular modeling software showed (S)-(+)-2, rather than (R)-(-)-2, gave a better fit to (R)-1. Volume determinations derived from SYBYL multifit analyses aided in receptor mapping to qualitatively describe areas of "active" pharmacophore space as well as areas of "inactive" substituent space.(ABSTRACT TRUNCATED AT 400 WORDS)     

Response of C3H/HeJ and C3H/HeN mice and their peritoneal macrophages to the toxicity of Chlamydia psittaci elementary bodies.

Intravenous injection of toxic doses of Chlamydia psittaci elementary bodies into endotoxin-responsive C3H/HeN mice or endotoxin-nonresponsive C3H/HeJ mice resulted in essentially identical time intervals to death. Inoculation of monolayer cultures of thioglycolate-stimulated peritoneal macrophages from the two strains of mice with 250 elementary bodies per macrophage resulted in immediate host cell toxicity, although the C3H/HeJ macrophages were somewhat less sensitive to elementary body toxicity than were the C3H/HeN macrophages.     

Entry of genital Chlamydia trachomatis into polarized human epithelial cells.

To study the initial invasion process(es) of genital chlamydiae, a model system consisting of hormonally maintained primary cultures of human endometrial gland epithelial cells (HEGEC), grown in a polarized orientation on collagen-coated filters, was utilized. After Chlamydia trachomatis inoculation of the apical surface of polarized HEGEC, chlamydiae were readily visualized, by transmission electron microscopy, in coated pits and coated vesicles. This was true for HEGEC maintained in physiologic concentrations of estrogen (proliferative phase) and of estrogen plus progesterone (secretory phase), despite the finding that association of chlamydiae with secretory-phase HEGEC is significantly reduced (P = 0.025; A.S. Maslow, C.H. Davis, J. Choong, and P.B. Wyrick, Am. J. Obstet. Gynecol. 159:1006-1014, 1988). In contrast, chlamydiae were rarely observed in the clathrin-associated structures if the HEGEC were cultured on plastic surfaces. The same pattern of coated pit versus noncoated pit entry was reproducible in HeLa cells. The quantity of coated pits associated with isolated membrane sheets derived from HeLa cells, grown on poly-L-lysine-coated cover slips in medium containing the female hormones, was not significantly different as monitored by radiolabeling studies and by laser scanning microscopy. These data suggest that culture conditions which mimic in vivo cellular organization may enhance entry into coated pits for some obligate intracellular pathogens.     

Hypolipidemic Agents of Phthalimide Derivatives 6. Effects of Aromatic vs. Non-Aromatic Imides

A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % and serum cholesterol 47 % after 16 days dosing in mice. For the N-substituted derivatives, i. e., n-butyl, butanone, and propionic acid, of these four cyclic imides, there appeared to be no obvious trend in ability to reduce serum lipid levels. In general, the 1,8-naphthalimide and glutarimide derivatives appeared to be less active than phthalimide and succinimide. However, the -phenylsuccinimide afforded less activity than the -phenylglutarimide. Most of the derivatives at 20mg/kg/day demonstrated improved activity over clofibrate at 150mg/kg/day.     

A Novel Telemedicine System for Care of Statewide Hand Trauma

Background: Telemedicine is an evolving tool to increase patients’ access to subspecialty care. Since 2014, Arkansas has been utilizing telemedicine in the evaluation of patients with hand injuries. The purpose of this study is to assess the effect of this novel telemedicine system for the management of hand trauma on patient transfer. Methods: We reviewed data from the first year of the telemedicine program (2014) and compared it to data from the year prior (2013). Data collection from both years included number of hand consults and need for transfer. From the 2014 data, we also recorded the use of telemedicine, type of transfer, distance of transfer, and time to disposition. Results: During 2013 (pre-telemedicine), there were 263 hand traumas identified. In all, 191 (73%) injuries required transfer to a higher level of care, while 72 (23%) were managed locally. In the first year of the telemedicine program (2014), a total of 331 hand injuries were identified. A total of 298 (90%) resulted in telemedicine consultation with 65% (195) utilizing video encounters. After telemedicine consultation, local management was recommended for 164 injuries (55%) while transfer was recommended for 134 (45%). Using telemedicine, there was a significant decrease in the percentage of transfer for hand injuries (P < .001). Conclusions: The telemedicine program was well utilized and provided patients throughout the state with continuous access to fellowship trained hand surgeons including regions where hand subspecialty care is not available. The program resulted in a significant decrease in the number of hospital transfers for the management of acute hand trauma.