Some gonad-infecting species of Philometra (Nematoda, Philometridae) from offshore fishes of South Carolina and Georgia, USA, including Philometra charlestonensis sp. nov. from the scamp Mycteroperca phenax

Three gonad-infecting species of Philometra Costa, 1845 were, for the first time, recorded from perciform fishes from estuarine and marine waters in South Carolina and Georgia, USA: Philometra charlestonensis sp. nov. from the scamp Mycteroperca phenax (Jordan et Swain) (Serranidae), P. saltatrix Ramachandran, 1973 from the bluefish Pomatomus saltatrix (Linnaeus) (Pomatomidae), and Philometra sp. from the Atlantic croaker Micropogonias undulatus (Linnaeus) (Sciaenidae). The new species is characterized mainly by males (body length 2.65–3.14 mm) with equally long, needle-like spicules (length 132–141 μm) and the gubernaculum (81–93 μm) bearing dorsal transverse lamella-like structures on its distal portion, the body length of gravid females (168–247 mm), the presence of a well-developed anterior bulbous inflation on the female oesophagus, and by the length of the first-stage larvae (544–597 μm). A key to gonad-infecting species of Philometra parasitizing marine and brackish-water fishes is provided.     

Effects of exercise training on resting metabolic rate in postmenopausal African American and Caucasian women

Ambiguous findings have been reported in previous studies concerning the relationships between resting metabolic rate (RMR), effects of exercise, and race in postmenopausal women. The purposes of this study were (1) to determine the effect of exercise training on RMR in postmenopausal women and (2) to determine whether this effect is different by race. We analyzed data from 24 African American (AA) (age, 56.3 +/- 5.0 years) and 23 Caucasian (CA) (age, 58.6 +/- 6.1 years) women. RMR was measured by indirect calorimetry after an overnight fast. Subjects completed tests of maximal exercise with metabolic measurements, waist to hip ratio, and body composition. At the completion of all tests, each subject was randomly assigned to either the exercise training or the control group. Aerobic exercise was performed 3 to 4 days per week for 6 months. Intensity was set at 70% to 85% maximal heart rate for 45 to 60 minutes per session. Both AA and CA exercise groups had a significant decrease (P < .05) in body weight (kilograms), percent body fat, and body mass index (BMI) and an increase in aerobic capacity, whereas the control groups did not change. There were no race effects. AA women exhibited significantly lower values than CA women for measured RMR (P < .05). The RMR (kilojoules) of the AA women (both control and exercise groups) decreased over time (P < .05), whereas the RMR of the CA women did not change. Adjusting RMR for BMI or for changes in lean body mass and fat mass did not alter these results. In conclusion, this 6-month endurance-training program did not affect RMR in these postmenopausal women, as RMR did not change in CA women, but decreased significantly over time in both groups of AA women. The factors that contribute to these findings should be the focus of future studies.     

Race, ethnicity, socioeconomic position, and quality of care for adults with diabetes enrolled in managed care: the Translating Research Into Action for Diabetes (TRIAD) study

OBJECTIVE: To examine racial/ethnic and socioeconomic variation in diabetes care in managed-care settings. RESEARCH DESIGN AND METHODS: We studied 7,456 adults enrolled in health plans participating in the Translating Research Into Action for Diabetes study, a six-center cohort study of diabetes in managed care. Cross-sectional analyses using hierarchical regression models assessed processes of care (HbA(1c) [A1C], lipid, and proteinuria assessment; foot and dilated eye examinations; use or advice to use aspirin; and influenza vaccination) and intermediate health outcomes (A1C, LDL, and blood pressure control). RESULTS: Most quality indicators and intermediate outcomes were comparable across race/ethnicity and socioeconomic position (SEP). Latinos and Asians/Pacific Islanders had similar or better processes and intermediate outcomes than whites with the exception of slightly higher A1C levels. Compared with whites, African Americans had lower rates of A1C and LDL measurement and influenza vaccination, higher rates of foot and dilated eye examinations, and the poorest blood pressure and lipid control. The main SEP difference was lower rates of dilated eye examinations among poorer and less educated individuals. In almost all instances, racial/ethnic minorities or low SEP participants with poor glycemic, blood pressure, and lipid control received similar or more appropriate intensification of therapy relative to whites or those with higher SEP. CONCLUSIONS: In these managed-care settings, minority race/ethnicity was not consistently associated with worse processes or outcomes, and not all differences favored whites. The only notable SEP disparity was in rates of dilated eye examinations. Social disparities in health may be reduced in managed-care settings.     

Detection of Molecular Markers of Drug Resistance in 2009 Pandemic Influenza A (H1N1) Viruses by Pyrosequencing

The M2 blockers amantadine and rimantadine and the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir are approved by the FDA for use for the control of influenza A virus infections. The 2009 pandemic influenza A (H1N1) viruses (H1N1pdm) are reassortants that acquired M and NA gene segments from a Eurasian adamantane-resistant swine influenza virus. NAI resistance in the H1N1pdm viruses has been rare, and its occurrence is mainly limited to oseltamivir-exposed patients. The pyrosequencing assay has been proven to be a useful tool in surveillance for drug resistance in seasonal influenza A viruses. We provide a protocol which allows the detection of adamantane resistance markers as well as the I43T change, which is unique to the H1N1pdm M2 protein. The protocol also allows the detection of changes at residues V116, I117, E119, Q136, K150, D151, D199, I223, H275, and N295 in the NA, known to alter NAI drug susceptibility. We report on the detection of the first cases of the oseltamivir resistance-conferring mutation H275Y and the I223V change in viruses from the United States using the approach described in this study. Moreover, the assay permits the quick identification of the major NA group (V106/N248, I106/D248, or I106/N248) to which a pandemic virus belongs. Pyrosequencing is well suited for the detection of drug resistance markers and signature mutations in the M and NA gene segments of the pandemic H1N1 influenza viruses.In the spring of 2009, an antigenically novel influenza A virus (H1N1) was detected in North America (7). The rapid widespread transmission of the virus resulted in the declaration of an influenza pandemic by the World Health Organization (WHO) (42). The 2009 pandemic influenza A (H1N1) virus (H1N1pdm) was determined to be a reassortant with a combination of gene segments that had not been previously described (12, 21). Phylogenetic analysis of the full genome sequences revealed that in the late 1990s, reassortment between seasonal influenza A virus (H3N2), classical swine influenza virus, and North American avian influenza viruses led to the appearance of triple-reassortant H3N2 and H1N2 swine influenza viruses that have since circulated in pigs in North America (40). The pandemic virus was a result of further reassortment between a triple-reassortant swine influenza virus and a Eurasian avian influenza virus-like swine influenza virus, resulting in the acquisition of two gene segments, coding for the M protein and neuraminidase (NA), from the Eurasian avian influenza virus-like swine influenza virus lineage. Recent genome sequence analysis performed with pandemic viruses collected in different regions found variants with characteristic amino acid changes, including 2 amino acid changes in the NA (21, 29). The reports identified three NA variants among the H1N1pdm viruses: one variant group has V106 and N248 (referred to as the A/California/04/2009 group); the second variant, named the A/Osaka/164/2009 group, is characterized by I106 and N248; and the third NA variant group contains I106 and D248, such as the A/New York/18/2009 strain.Currently circulating triple-reassortant swine influenza viruses in the United States do not contain any known markers of adamantane resistance (L26F, V27A, A30V, A30T, S31N, and G34E) (10, 25), whereas the Eurasian avian-like influenza viruses as well as the pandemic virus contain the adamantane resistance-conferring change S31N in the M2 protein. Currently, two classes of antiviral drugs are approved for use by the FDA for the control of influenza virus infections: adamantanes (M2 blockers) and neuraminidase inhibitors (NAIs). Resistance to adamantanes makes the NAIs oseltamivir and zanamivir the only pharmaceutical options available for use for the control of infections caused by the pandemic virus. Monitoring of resistance to NAIs is mainly based on the NA inhibition assay (23, 39, 41), which allows the detection of resistance conferred by known and novel mutations. However, the NA inhibition assay requires virus isolation and propagation, and the detection of resistance by the NA inhibition assay requires confirmation by sequencing of the NA gene segment to identify the markers of resistance and their presence in the original clinical material.Prior to the 2007-2008 influenza season, the frequency of resistance to NAIs had been very low (<0.5%) among field isolates (28, 35, 36). During the 2007-2008 influenza season, seasonal H1N1 viruses resistant to oseltamivir emerged and spread globally (3, 17, 31, 39), and by April of 2009, the majority of the H1N1 viruses were resistant to oseltamivir but sensitive to zanamivir. Of note, nearly all of the 2009 pandemic H1N1 viruses were sensitive to NAIs (8); only sporadic cases of oseltamivir-resistant viruses with the H275Y mutation in the NA gene segment were reported to the WHO, and they were mainly detected following antiviral drug treatment (5, 6, 42). The H275Y mutation is equivalent to the H274Y mutation in the N2 subtype amino acid numbering. Throughout the text, amino acids are described with the N1 numbering, and the corresponding N2 amino acid numbering is shown in parentheses, when it differs from the N1 numbering. Recent reports on the emergence of oseltamivir resistance highlight the need for close monitoring of the susceptibility of the pandemic H1N1 virus to the available drugs (5, 6, 42). Such information is needed to make informed decisions on measures aimed at managing pandemic virus infections.The molecular markers of NAI resistance are type and subtype specific and are also drug specific (1, 23). The H275Y (H274Y) change is the most commonly reported mutation conferring resistance to oseltamivir in the N1 subtype of NA. This change has been reported not only in seasonal H1N1 viruses but also in highly pathogenic H5N1 viruses (13, 22, 23, 31, 33). The H275Y (H274Y) mutation is also known to reduce susceptibility to the investigational NAI peramivir (23). The amino acid replacement N295S (N294S) in N1 has also been shown to reduce susceptibility to oseltamivir and zanamivir (33, 43). In addition, recent studies have demonstrated that mutations in other residues located in and around the NA active site can alter the susceptibilities of viruses to NAIs. For instance, changes at residues V116, I117, E119, Q136, D199 (D198), and I223 (I222) were associated with reduced susceptibility to NAIs in both seasonal and H5N1 viruses (26-28, 30, 32, 39). Moreover, crystal structure studies with the NAs of H1N1 and H5N1 viruses (9, 37) suggested that mutations at amino acids Q136, K150, and D151 (37) may affect susceptibility to oseltamivir and zanamivir, presumably by interfering with the binding of the drug to the NA. Changes at these residues were reported to reduce the susceptibilities to NAIs of viruses with the N1 enzyme (34; CDC, Atlanta, GA, unpublished data).It is important to develop the tools necessary for the rapid detection of NA markers known or suspected of affecting susceptibility to NAIs. Pyrosequencing has previously been shown to provide a rapid and high-throughput method for the detection of molecular markers of drug resistance in seasonal as well as highly pathogenic avian influenza viruses (4, 8, 15, 16, 19, 30, 31, 38).Here we report on the design and validation of pyrosequencing assays for the detection of signature markers in the M2 and NA gene segments of the pandemic H1N1 viruses.     

Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension

Introduction

TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex® ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.

Methods

A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.

Results

Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.

Conclusion

TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.     

Differential diagnosis of cardiac masses using contrast echocardiographic perfusion imaging

OBJECTIVES: We investigated the usefulness of echocardiographic contrast perfusion imaging in differentiating cardiac masses. BACKGROUND: Two-dimensional echocardiography is the primary diagnostic modality for cardiac masses. However, differentiation between the different types of cardiac masses may be difficult at times. We hypothesized that echocardiographic contrast perfusion imaging would differentiate the neo-vascularization of malignancies from the avascularity of thrombi and the sparse vascularity of stromal tumors. METHODS: Sixteen patients with cardiac masses underwent power-modulation imaging after echocardiographic intravenous contrast administration. Pixel intensities in the mass and an adjacent section of myocardium were analyzed visually and by dedicated software. All masses had a pathologic diagnosis or resolved after anticoagulation. In a subset of patients, video-intensity curves of contrast replenishment in the mass and myocardium over time were generated. The post-impulse steady-state pixel intensity (A) and initial rate of contrast replenishment after impulse (beta) were compared with an index of blood vessel area on pathology. RESULTS: In seven of 16 patients, contrast enhancement resulted in greater pixel intensity in the mass than in the adjacent myocardium. All of these masses were classified pathologically as malignant (n = 6) or benign and vascular (n = 1). Nine masses demonstrated decreased pixel intensity, compared with the myocardium, and were diagnosed pathologically as myxomas (n = 2) or thrombi (n = 5), or they resolved with anticoagulation (n = 2). For the subset of patients, beta correlated with the vessel area index (r = 0.60). CONCLUSIONS: Echocardiographic contrast perfusion imaging aids in the differentiation of cardiac masses. Compared with the adjacent myocardium, malignant and vascular tumors hyper-enhanced, whereas stromal tumors and thrombi hypo-enhanced.