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Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3'-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 µM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.

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BACKGROUND AND PURPOSE: We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves co-administration of QX-314 and a TRPV1 agonist to produce a long-lasting local analgesia. For potential clinical use we propose using lidocaine as the TRPV1 agonist, because it activates TRPV1 at clinical doses. EXPERIMENTAL APPROACH: We conducted experiments in rats to determine optimal concentrations and ratios of lidocaine and QX-314 that produce the greatest degree and duration of pain-selective block when administered nearby the sciatic nerve: reduction in the response to noxious mechanical (pinch) and to radiant heat stimuli, with minimal disruption in motor function (grip strength). KEY RESULTS: A combination of 0.5% QX-314 and 2% lidocaine produced 1 h of non-selective sensory and motor block followed by >9 h of pain-selective block, where grip strength was unimpaired. QX-314 at this concentration had no effect by itself, while 2% lidocaine by itself produced 1 h of non-selective block. The combination of 0.5% QX-314 and 2% lidocaine was the best of the many tested, in terms of the duration and selectivity of local analgesia. CONCLUSIONS AND IMPLICATIONS: Targeting charged sodium channel blockers into specific sets of axons via activation of differentially expressed large-pore channels provides an opportunity to produce prolonged local analgesia, and represents an example of how exploiting ion channels as a drug delivery port can be used to increase the specificity and efficacy of therapeutics.

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Robust findings show that categorical perception (CP) occurs in identification of familiar faces. CP has also been observed for unfamiliar morphed faces after sufficient learning of the original, unmorphed faces has taken place. We previously suggested that CP arises when the activation of inconsistent visual and verbal representations creates a conflict between perceptual and category information. In the present study, we conducted two experiments in which the endpoint faces of an unfamiliar morphed continuum were presented in either a covert training regime (famous vs. nonfamous judgments) or an overt training regime (previously seen vs. unseen judgments). In both experiments, participants' reaction times to repeated targets decreased relative to reaction times to control items during training. After overt training, CP was observed for the previously unfamiliar faces. No CP was observed for covertly trained faces. We conclude that individual faces must be explicitly categorized before CP can be established for the morphed continuum between them.

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The conditions under which categorical perception (CP) occurs for unfamiliar faces are unclear. Although CP is generally found only for familiar faces, it has been reported for unfamiliar faces after brief training (Levin & Beale, 2000) or even without any learning of the original faces (Campanella, Hanoteau, Seron, Joassin, & Bruyer, 2003). Three experiments investigated whether CP can be observed for an unfamiliar morphed face continuum without preexposure to the endpoints of the continuum (Experiment 1); with brief exposure to the endpoints (Experiment 2); or with exposure to named endpoints (Experiment 3). CP was always observed for matched pairs of famous faces. However, CP for unfamiliar faces was induced only when participants observed names paired with the endpoint faces before the start of the experiment. The results suggest that CP effects for unfamiliar faces can be observed extremely rapidly when clear category labels are presented.

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We report two patients who were found to have nearly identical, very peculiar atrial septal anatomy. The septum actually consisted of two distinct septa with discrete defects creating an interatrial chamber. The orifice from the left atrium was unrestrictive, but the orifice to the right atrium was restrictive. Overall, there was net left-to-right shunting. This finding represents a clinical dilemma: Left untreated, the interatrial chamber might be a nidus for thrombus formation, but attempting device closure might result in incomplete obliteration of the chamber, also resulting in potential locus for clot formation. Clot formation might lead to systemic embolization. Angiographic findings are correlated with echocardiographic findings. Embryology and treatment options are considered.

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OBJECTIVE: To study the perioperative management strategies in a large group of pediatric patients undergoing surgical therapy for suppurative adenitis of the parapharyngeal and retropharyngeal spaces. STUDY DESIGN: Retrospective analysis of all patients treated surgically from January 1, 1989, to December 31, 1998, in a tertiary care pediatric hospital. METHODS: Charts were reviewed for demographic data, duration and nature of symptoms, radiological workup, surgical approach, complications, duration of medical therapy and antibiotic choice, and bacteriological findings. Computed tomography (CT) results were correlated to surgical findings. RESULTS: A dramatic increase in the incidence of deep neck space infection was seen during the study period; this increase was congruent with the increase in culture-positive group A beta-hemolytic streptococcal abscesses. More than two-thirds of the patients were boys with the peak incidence being in the 3- to 5-year-old group. The duration of symptoms before presentation was less than might be expected, especially in the younger age groups. Seventy of 73 children were treated with a transoral approach. Sixty-eight of 73 were successfully treated with one operative intervention. Irregularity of the abscess wall was found to be a stronger predictor of the presence of pus than the presence of ring enhancement. CONCLUSIONS: The current study represents the largest series of pediatric retropharyngeal abscesses in the modern medical literature. Changes in the disease process and in management from the first half of the century to today are reviewed, and recommendations for optimal management presented. The data in this series support a transoral approach to these abscesses unless there is extension lateral to the great vessels.

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IMPLICATIONS: We conducted a randomized study in 147 pediatric patients undergoing cardiopulmonary bypass to determine when there are any differences in hemodynamic effects if CaCl(2) 20 mg/kg and protamine 5mg/kg are mixed together and infused over 10 min versus administering half of the calcium dose (10 mg/kg) as a bolus followed by a 10-min infusion of protamine 5 mg/kg and CaCl(2) 10mg/kg.

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The Louisiana Office of Public Health Tobacco Control and Prevention Program received funding from the Louisiana State Legislature to expand smoking cessation activities in the state. The Tobacco Control Program conducted a review of other states' current smoking cessation programs, cessation programs in Louisiana, and epidemiological evidence in planning the expansion of the Louisiana tobacco smoking cessation program. As a result, a smoking cessation helpline has been developed. Medical clinicians in Louisiana have a powerful impact on their patients' smoking cessation success. Simple discussion by physicians with their patients about how to quit smoking has improved successful quitting rates by 40%. Approximately 70% of smokers visit a physician each year and 60% visit a dentist, so there is clearly an opportunity to reach many persons at risk. The telephone smoking cessation helpline at 1-800-LUNG-USA is a tool for clinicians to use when advising their patients on ways to improve their health and prevent disease.

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OBJECTIVE: The purpose of this study was to investigate the association between deep dental overbite and eustachian tube dysfunction (ETD). DESIGN: Case-control study. SETTING: Tertiary care pediatric otolaryngology outpatient clinic at the Children's Hospital, Boston, Massachusetts. PATIENTS: 105 patients between the ages of 2 and 6 years. STUDY MEASUREMENTS: Dental overbite, overjet, and occlusal relationships were measured by an observer who was unaware of ETD status. ETD was defined as having ventilation tubes in place or having the recommendation for ventilation tube placement by an attending pediatric otolaryngologist. In addition, demographic information and medical and social histories were prospectively recorded. RESULTS: In a multivariate logistic regression model, children with deep bites were 2.8 times more likely to have ETD than those without deep bites (P = .03). Other independent risk factors for ETD identified in this model were family history of otitis media (OM) and age less than 3 years. CONCLUSIONS: Children with deep dental overbites are at a significantly increased risk for developing ETD.

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Organic acids have been shown to be effective in reducing the presence of pathogenic bacteria on hot beef carcass surfaces; however, application for decontaminating chilled carcasses has not been fully evaluated. In this study, a postchill, 30-s lactic acid spray (500 ml of 4% L-lactic acid, 55 degrees C) was applied onto outside rounds that had been contaminated with Escherichia coli O157:H7 and Salmonella Typhimurium, subsequent to prechill hot carcass treatments consisting of water wash alone or water wash followed by a 15-s lactic acid spray (250 ml of 2% L-lactic acid, 55 degrees C). The prechill treatments reduced both pathogens by 3.3 to 3.4 log cycles (water wash alone) to 5.2 log cycles (water wash and lactic acid). In all cases, the postchill acid treatment produced an additional reduction in E. coli O157:H7 of 2.0 to 2.4 log cycles and of 1.6 to 1.9 log cycles for Salmonella Typhimurium. The counts of both pathogens remained significantly lower in ground beef produced from the outside rounds that received prechill and postchill acid spray than from those that received a postchill spray only. These data indicate that organic acid sprays may be successfully applied for pathogen reduction in beef carcass processing after the cooler, especially when combined with prechill treatments.

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A series of five experiments examined the categorical perception previously found for color and facial expressions. Using a two-alternative forced-choice recognition memory paradigm, it was found that verbal interference selectively removed the defining feature of categorical perception. Under verbal interference, there was no longer the greater accuracy normally observed for cross-category judgments relative to within-category judgments. The advantage for cross-category comparisons in memory appeared to derive from verbal coding both at encoding and at storage. It thus appears that while both visual and verbal codes may be employed in the recognition memory for colors and facial expressions, subjects only made use of verbal coding when demonstrating categorical perception.

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The authors sought to replicate and extend the work of E. Rosch Heider (1972) on the Dani with a comparable group from Papua, New Guinea, who speak Berinmo, which has 5 basic color terms. Naming and memory for highly saturated focal, non-focal, and low-saturation stimuli from around the color space were investigated. Recognition of desaturated colors was affected by color vocabulary. When response bias was controlled, there was no recognition advantage for focal stimuli. Paired-associate learning also failed to show an advantage for focal stimuli. Categorical Perception effects for both English and Berinmo were found, but only at the boundaries of existing linguistic categories. It is concluded that possession of linguistic categories facilitates recognition and influences perceptual judgments.

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Models in which a single large systemic dose of gentamicin is used to cause near-synchronous hair cell (HC) loss in the basal end of the chick cochlea have proven increasingly useful in the study of HC regeneration. We quantified the amount of HC death, as a percentage of the length of the basilar papilla, following single doses of 200 mg/kg and 300 mg/kg of gentamicin in 23-day-old chicks. Following 200 mg/kg of gentamicin, there was total HC loss in the basal 18.0% of the sensory epithelium and partial HC loss in the basal 26.3%. Following 300 mg/kg of gentamicin, there was total HC loss in the basal 30.5% of the epithelium and partial HC loss in the basal 40.9%. The second goal of this study was to determine whether cannula implantation in the inner ear, and infusion of bromodeoxyuridine causes HC damage. We found that creation of a fistula in the labyrinth is not associated with HC damage, but that cannula implantation can cause HC death, and can also cause potentiation of gentamicin-induced HC death. Revision of the cannula and surgical technique to ensure minimal penetration into the labyrinth almost entirely eliminated these effects. We conclude that surgical technique is critical in experimental models in which the labyrinth is violated.

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Survival surgeries upon chicks are commonly used in auditory research. Appropriate anesthesia is usually obtained with intramuscular or intraperitoneal injections of systemic agents. These techniques have several drawbacks, including delayed onset of anesthesia, difficulty in adjusting the dosage to accomodate individual animals' different responses, prolonged recovery times, and in some cases substantial mortality. We present a technique of administering inhaled isoflurane via an endotracheal tube which we have used for over a year with excellent results. With this agent, onset of deep anesthesia is very rapid, dosage can be titrated readily, overdosage is survivable, complete recovery occurs within a few minutes and mortality is rare. This technique may be valuable for other auditory scientists performing survival surgery in avian species.

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A series of experiments are reported on a patient (LEW) with difficulties in naming. Initial findings indicated severe impairments in his ability to freesort colours and facial expressions. However, LEW's performance on other tasks revealed that he was able to show implicit understanding of some of the classic hallmarks of categorical perception; for example, in experiments requiring the choice of an odd-one-out, the patient chose alternatives dictated by category rather than by perceptual distance. Thus, underlying categories appeared normal and boundaries appeared intact. Furthermore, in a two-alternative forced-choice recognition memory task, performance was worse for within-category decisions than for cross-category decisions. In a replication of the study of Kay and Kempton [Kay, P., Kempton, W., 1984. What is the Sapir-Whorf hypothesis? American Anthropologist 86, 65-78], LEW showed that his similarity judgements for colours could be based on perceptual or categorical similarity according to task demands. The consequences for issues concerned with perceptual categories and the relationship between perceptual similarity and explicit categorisation are considered; we argue for a dissociation between these kinds of judgements in the freesort tasks. LEW's inability to make explicit use of his intact (implicit) knowledge is seen as related to his language impairment.

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Necrotizing fasciitis is a rare clinical entity in the head and neck region. We report a case of necrotizing fasciitis following adenotonsillectomy in a previously healthy 2-year-old girl. The child presented in a septic state with impending airway compromise. Computed tomography (CT) showed massive soft tissue widening with air in the retropharyngeal, parapharyngeal and retromandibular spaces. Intraoperative exploration showed necrosis of the posterior pharyngeal wall from the skull base to the cricoid, with extension into the parapharyngeal and retropharyngeal spaces. Cultures from the debrided tissues grew two aerobes and three anaerobes. Management involved airway support, surgical debridement, broad spectrum antibiotic coverage and nutritional support. The patient ultimately developed nasopharyngeal and oropharyngeal stenosis requiring tracheostomy and gastrostomy tube placement. This case report highlights an extremely rare complication of adenotonsillectomy.

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BACKGROUND: In recent years many health care providers, physicians, hospitals, and managed care organizations have undergone significant reorganization in both delivery and financing systems. This has created new organizations called integrated or organized delivery systems. Sentara Health System (Norfolk, Va), one of these new integrated entities, developed a unified strategy for clinical process improvement for the entire organization. This system-wide approach had unanticipated problems and benefits. METHODS: The Sentara Health System created a team responsible for coordinating clinical process improvement activities across its hospitals and ambulatory physician sites. A steering committee directed this team to improve the organization and delivery of care for specific high-cost, high-volume, or problem-prone disease for physicians to manage. A standardized approach aimed at coordinating care across sites was the cornerstone of these activities. RESULTS: Significant improvements in patient outcomes and a concomitant decrease in costs of care were accomplished for multiple diseases and procedures. These projects uncovered unanticipated barriers to implementing improvement projects in a complex health care system which make implementing these activities far more difficult than for an individual hospital with its medical staff. CONCLUSION: Coordinating clinical improvement activities across multiple hospitals and other sites of care in a complex integrated delivery system serves important purposes in addition to improving patient care. These projects were an important cultural change agent to transform the individual components of the system into one that is capable of delivering care continuously across multiple sites. Standardization of care practices, policies, and procedures is considerably enhanced by coordinating these activities across the entire system.

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