Coronary flow and flow reserve in canines using MR phase difference and complex difference processing

Coronary artery disease continues to be the leading cause of death for adults in the United States. Magnetic resonance imaging (MR) has the potential to dramatically impact the diagnosis of heart disease by noninvasively providing a wide range of anatomic and physiologic information. Previous research has shown that coronary flow, one component of a complete examination, can be accurately measured in the left anterior descending artery in vivo. The current work validates MR flow measurements in canine circumflex arteries using transit time ultrasound as a standard. The circumflex artery experiences greater in-plane motion and is a more stringent test for flow measurement accuracy. This work also compares two methods of processing MR velocity data, phase difference and complex difference techniques, and examines the sources of error present in the animal validation model. Phase difference processing with a 30% magnitude threshold best matched the mean ultrasound flow values (30% PD = 1.04 x US + 1.49, r = 0.94), but it was very sensitive to vessel boundary identification. The complex difference process was less sensitive to vessel boundary identification and correlated well with the transit time ultrasound despite systematic underestimations. The reasons for the discrepancies are shown to stem from a number of possible sources including variability of the ultrasound standard, low signal-to-noise ratios in the MR images, sensitivity of the MR technique to vessel boundary identification, and motion artifacts in the images.     

The troublesome submerged tooth: a diagnostic dilemma

Facial swelling caused by a periapical abscess is commonly encountered by dental practitioners. It requires prompt treatment, usually by removal of the infective foci and administration of appropriate antibiotics. However, diagnosis can be difficult, and may be complicated by the presence of retained deciduous teeth. This case report demonstrates a diagnostic dilemma and highlights the importance of looking beyond the obvious.     

Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain

OBJECTIVES: This study sought to determine the ability of early perfusion imaging using technetium-99m sestamibi to predict adverse cardiac outcomes in patients who present to the emergency department with possible cardiac ischemia and nondiagnostic electrocardiograms (ECGs). BACKGROUND: Evaluation of patients presenting to the emergency department with possible acute coronary syndromes and nondiagnostic ECGs is problematic. Accurate risk stratification is necessary to prevent serious adverse outcomes. Initial results suggest that early perfusion imaging using technetium-99m sestamibi enables reliable risk stratification. METHODS: Patients presenting to the emergency department with a low to moderate probability of acute coronary syndromes underwent rapid sestamibi injection with gated single-photon emission computed tomographic imaging. Studies showing perfusion defects with associated wall motion abnormalities were considered positive. RESULTS: A total of 532 consecutive patients underwent serial myocardial marker analysis and rest perfusion imaging. Of these patients, perfusion imaging was positive in 171 (32%). Positive perfusion imaging was the only multivariate predictor of myocardial infarction (MI) (p < 0.0001, odds ratio [OR] 33, 95% confidence interval [CI] 7.7 to 141) and was the most important independent predictor of MI or revascularization (p < 0.0001, OR 14, 95% CI 7.3 to 25), followed by diabetes (p < 0.01, OR 2.8, 95% CI 1.5 to 5.1), typical angina (p = 0.01, OR 2.1, 95% CI 1.2 to 3.7) and male gender (p = 0.03, OR 1.9, 95% CI 1.1 to 3.5). The sensitivity of positive perfusion imaging for MI was 93% (95% CI 77% to 98%), and for MI or revascularization it was 81% (95% CI 71% to 88%), with negative predictive values of 99% (95% CI 98% to 100%) and 95% (95% CI 92% to 97%), respectively. CONCLUSIONS: Positive rest perfusion imaging accurately identified patients at high risk for adverse cardiac outcomes, whereas negative perfusion imaging identified a low risk patient group. Early perfusion imaging allows for rapid and accurate risk stratification of emergency department patients with possible cardiac ischemia and nondiagnostic ECGs.     

An unusual effect of application of the amino acid L-arginine on cat visual cortical cells

Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17 of the anaesthetized/paralysed cat. Duration was long, and cells did not recover pre-application activity levels, indicating permanent decline. This effect was obtained without change in the extracellularly recorded wave-form, demonstrating that this did not result from depolarization block. In the remaining 55 cells, application of L-Arg alone, at levels capable of eliciting inhibition as described above, was without effect. In 29 cells, L-Arg application was able to reverse the effect of inhibition of nitric oxide (NO) production. Populations of cells showing the depressive effect described above and those affected by NO modulation levels were mutually exclusive.     

Substance P blockade with the potent and centrally acting antagonist GR205171 does not effect central trigeminal activity with superior sagittal sinus stimulation

The development and use of serotonin-1B/1D agonists to treat the acute attack of migraine has been a significant advance, but their vasoconstrictor effects have lead to a search for non-vasoconstrictor approaches to the management of the acute attack of migraine. One such suggested approach has been substance P (neurokinin-1) antagonists, since substance P is involved in mediating neurogenic plasma protein extravasation and has long been held to have a role in pain transmission. In this study, one such candidate compound, GR205171, a highly lipophilic potent neurokinin-1 antagonist, has been tested in a model of trigeminovascular nociception with considerable predictive value for anti-migraine activity. The superior sagittal sinus was isolated in the alpha-chloralose (60 mg/kg, i.p., and 20 mg/kg, i.v., supplemented every 2 h)-anaesthetized cat. The sinus was stimulated electrically (100 V, 250 micros duration, 0.3 Hz) and neurons in the dorsal C2 spinal cord monitored using electrophysiological methods. In separate experiments, the animals were prepared for stimulation and then maintained for 24 h before stimulation and perfusion for Fos immunohistochemistry. Stimulation of the superior sagittal sinus resulted in activation of cells in the dorsal horn of C2. Cells fired with a probability of 0.7 +/- 0.1 at a latency of 10.7 +/- 0.2 ms. Administration of GR205171 (100 microg/kg, i.v.) had no effect on probability of firing or latency. Stimulation of the sinus in separate cats resulted in increased expression over control levels in the superficial laminae of the trigeminal nucleus caudalis and C1/2 dorsal horns. GR205171 in the same dose had no effect upon Fos expression. Inhibition of substance P by the potent, selective and brain penetrant neurokinin-1 antagonist GR205171 had no effect upon either cell firing or Fos expression in the central trigeminal cells activated by stimulation of the superior sagittal sinus. These data and the published clinical data for other compounds suggest that neurokinin-1 blockade alone will not be an effective anti-migraine strategy. Further data will be required to assess whether neurokinin-1 antagonists will have any more general value in pain.     

Distribution, abundance, and seasonal activities of ticks collected from rodents and vegetation in South Carolina

Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter thus preventing the further synthesis of thyroid hormone but has no effect on the iodination process itself. It is concentrated by thyroid tissue in a manner similar to iodide but is not significantly metabolized in the gland or peripherally. What is not settled is whether there are additional perchlorate effects on iodide transport. Perchlorate has a fast turnover in the body and requires frequent daily doses for therapy of thyrotoxicosis. Perchlorate appears to be substantially more effective against large iodide loads than the thionamides, and, with long-term iodide contamination, combined therapy of perchlorate (with < or = 1 g/day) and thionamides is recommended for the more severe cases of thyrotoxicosis that may result from excess iodide or iodide-generating organic compounds, as for example with amiodarone. After approximately 30 days, the perchlorate dosage can be tapered or stopped, continuing with thionamides alone. This markedly increases its safe use. Despite serious side effects during its early use, lower dosages and shorter treatment periods appear to have prevented such reactions in its recent reintroduction, mostly for amiodarone-induced thyroid dysfunction. Perchlorate can also protect against inhibition of thyroid function and the resulting hypothyroidism caused by excess iodide, presumably by reducing the formation of an iodinated inhibitor. The reduction of the iodide pool by perchlorate thus has dual effects--reduction of excess hormone synthesis and hyperthyroidism, on the one hand, and reduction of thyroid inhibitor synthesis and hypothyroidism on the other. Perchlorate remains very useful also as a single dose application in tests measuring the discharge of radioiodide accumulated in the thyroid as a result of many different disruptions in the further metabolism of iodide in the thyroid gland.     

Monoclonal antibody-resistant mutants selected with a respiratory syncytial virus-neutralizing human antibody fab fragment (Fab 19) define a unique epitope on the fusion (F) glycoprotein

A recombinant human antibody fragment, designated RSV Fab 19, efficiently neutralizes respiratory syncytial virus (RSV). Here we report the results of our sequence analysis of antibody escape mutants that identified F glycoprotein amino acids critical for binding of human or murine RSV F-neutralizing antibodies.     

The immune response to Haemophilus ducreyi resembles a delayed-type hypersensitivity reaction throughout experimental infection of human subjects

Previous work in 3 subjects infected for 2 weeks indicated that experimental infection with Haemophilus ducreyi recruits CD4 cells to the skin at the pustular stage of disease. In order to describe the kinetics of the host response, 23 subjects were infected at 2 sites with a standardized dose of H. ducreyi. Subjects were biopsied 1 or 4 days after inoculation or when they developed a painful pustular lesion (days 7-14). Papules and pustules contained a predominant T cell infiltrate that consisted of CD45RO and CD4 cells of the alpha beta lineage. Both papules and pustules contained mixed or T helper 1 type cytokine mRNA and interleukin-8 and tumor necrosis factor-alpha mRNA. Although the subjects had no history of chancroid, their immune responses resembled delayed-type hypersensitivity reactions that occurred within 24 h of inoculation and persisted throughout the course of experimental infection.