Post-hypoxic animal model of myoclonus

Post-hypoxic myoclonus is a form of myoclonus frequently caused by cardiac arrest. Development of an animal model may facilitate understanding of the condition and its treatments. We describe an animal model of post-hypoxic myoclonus developed in our laboratory through cardiac arrest, initially induced by chemical and later by mechanical obstruction of major cardiac vessels. These animals respond to valproate, clonazepam and 5-hydroxytrytophan reminiscent of its human counterpart. We review their behavioral, pharmacological and neuropathological features. Therapy developed for myoclonus in this model may be helpful for myoclonus from other etiologies such as corticobasal degeneration, Lewy-body disorders, Creutzfeld-Jacob disease, Alzheimer's disease.     

Integrated CT-PET imaging of esophageal cancer: unexpected and unusual distribution of distant organ metastases

CT-PET imaging is being increasingly used for the initial staging, assessment of treatment response, and follow-up of patients with esophageal carcinoma, primarily because of its superior detection of distant metastases compared to conventional methods. Our recent experience has shown that metastases from esophageal cancer can occur in unusual locations and have an unexpected presentation. Recognition of the distribution and appearance of esophageal metastases is important for optimal image interpretation in order to avoid confusion with more benign disease. This article reviews the location and appearance of metastases detected by CT-PET imaging in patients with esophageal cancer either at presentation or after preoperative or definitive chemoradiation therapy.     

Studies of the cellular uptake of hydrogel nanospheres and microspheres by phagocytes, vascular endothelial cells, and smooth muscle cells

Intensive research efforts have been placed on the development of nanospheres for targeted drug delivery for treating a variety of diseases, including coronary restenosis, cancer, and inflammatory reactions. Although most of these drug-bearing spheres are delivered via intravenous administration, little is known about the effect of sphere physical characteristics on the responses of vascular and blood cells. To find the answer, this work was aimed to investigate the cellular uptake of nanosized (100 nm) and microsized hydrogel spheres (1 microm) made of poly(N-isopropylacrylamide) by vascular cells and phagocytes under various flow conditions in vitro. We found that the cellular uptake of nanospheres depended on incubation times and sphere concentrations as well as on the introduced shear stress levels of the medium. Measurements of the intracellular-released fluorescence and confocal fluorescence microscopy revealed that nanospheres were internalized by endothelial cells and smooth muscle cells more than microspheres, whereas microspheres were rapidly taken up by phagocytes, especially at high concentration. Our results strongly suggest that hydrogel nanospheres are more effective as an intravascular delivery system compared to microspheres in the terms of vascular cellular uptake and biocompatibility.     

Human Immune Proteome in Experimental Colonization with Staphylococcus aureus

More than 20% of adults are persistently colonized with Staphylococcus aureus. When hospitalized, these carriers have increased risks of infection with their own strains. However, a recent study demonstrated a lower incidence of bacteremia-related death among carriers than among noncarriers, raising the question whether the adaptive immune system plays a protective role. In fact, S. aureus carriers mount a highly specific neutralizing antibody response against superantigens of their colonizing strains. We now used 2-dimensional immunoblotting to investigate the profiles of antibodies from healthy individuals against S. aureus extracellular proteins. Moreover, we tested whether symptom-free experimental colonization of these individuals with an S. aureus strain of low virulence, 8325-4, is sufficient to induce an antibody response. Sera obtained before and 4 weeks after colonization were screened for immunoglobulin G (IgG) antibody binding to extracellular staphylococcal proteins. At baseline, most volunteers harbored IgG directed against conserved virulence factors, including alpha-hemolysin (Hla), beta-hemolysin (Hlb), phospholipase C (Plc), staphylococcal serine protease (SspA), and cysteine protease (SspB). However, the variability of spot patterns and intensities was striking and could be important in case of infection. Experimental nasal colonization with S. aureus 8325-4 did not elicit new antibodies or boost the humoral response. Thus, the high antibody prevalence in humans is likely not induced by short-term nasal colonization, and presumably minor infections are required to trigger anti-S. aureus antibody responses.Staphylococcus aureus is one of the most common causes of nosocomial infection, and the species is becoming increasingly resistant to antibiotics (2). Apart from being a major human pathogen, S. aureus is also a frequent colonizer of human skin and mucosa (34). The bacteria find their primary ecological niche in the human nose but are also able to colonize the throat, the intestines, and the perineal region, sometimes exclusively (1, 17). Approximately 20% of the adult population carry S. aureus in the nose persistently, and another 30% carry it intermittently, frequently only for a few days, whereas 50% are noncarriers (NC) (29, 30, 34). Nasal carriers stand an increased risk of developing severe S. aureus infections caused by their autologous strains, especially upon hospitalization or immune suppression (32, 35). This underlines the fact that host and environmental factors play a decisive role in determining the outcome of S. aureus host interactions.In a recent large prospective study, carriers acquired S. aureus bacteremia more frequently than NC but, surprisingly, had a better survival rate than NC (35). This observation raises the question whether the adaptive immune system establishes immunity to the colonizing S. aureus strain, which could be of advantage in autologous infections. In support of this hypothesis, our group recently showed that S. aureus carriers raise a strong and strain-specific antibody response against the superantigen cocktail produced by their colonizing strain (12). However, S. aureus produces a broad repertoire of virulence factors, and the antibody response against superantigens is likely only the tip of an iceberg (8). In fact, anti-S. aureus antibodies against staphylococcal toxins, immune evasion molecules, and adhesins have been detected in healthy individuals as well as in patients (6, 7, 11, 31).Virulence factor expression is strictly regulated in S. aureus. While adhesins are expressed by bacterial cells in logarithmic growth, the majority of known virulence factors, including most superantigens but also cytolytic toxins, proteases, lipases, and several immune evasion molecules, are secreted in the post-exponential-growth phase (23, 38). In contrast to intracellular and cell wall-associated proteins, secreted virulence factors can act systemically while bacteria remain localized. Consequently, these factors are the most likely stimuli of the adaptive immune system during epithelial colonization with S. aureus (28).To date, a comprehensive investigation of anti-S. aureus antibody profiles from healthy individuals and their variability is still lacking. Moreover, it remains unknown which conditions (e.g., nasal colonization, minor or major infections) are required to trigger an antibody response against S. aureus. Therefore, we experimentally colonized the nares of 16 healthy human volunteers with S. aureus (36) and compared the anti-S. aureus antibody profiles before and 28 days after colonization. Our aims were to analyze the variability of the anti-S. aureus antibody profiles and to test whether experimental nasal colonization elicits or boosts an antibody response.     

Oral health status of adults in Southern Vietnam - a cross-sectional epidemiological study

Background

Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited.

Methods/Design

The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered.

Discussion

This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States.

Trial Registration Number

NCT00357877     

Can Daytime Use of Bed Nets Not Treated with Insecticide Reduce the Risk of Dengue Hemorrhagic Fever Among Children in Vietnam?

The purpose of this study was to investigate the prevalence of bed net use and elucidate the effect of daytime bed net use on preventing dengue hemorrhagic fever (DHF) among children in Vietnam. We conducted a population-based cross-sectional survey and a matched case–control study in Khanh Hoa Province where not only some pre-schoolchildren but also some school children, who take a nap during lunch break prior to returning to school, used bed nets during the day. Among 36,901 children 2–10 years of age, most used untreated bed nets during the night (98.3%) compared with 8.4% during the day. The results of the case–control study, which defined 151 cases who were hospitalized with DHF in the provincial hospitals and 604 age-matched neighborhood controls, did not support our hypothesis that children using untreated bed nets during the day are less likely to be hospitalized with DHF (adjusted odds ratio = 0.56, 95% confidence interval = 0.23–1.39).Dengue hemorrhagic fever (DHF), a life-threatening syndrome caused by any one of four dengue virus (DENV) infections, is a rapidly increasing public health problem in the tropical and subtropical regions of the world.¹ The pathogenesis of DHF has been hypothesized to involve a complex interaction of several factors including the host immune response, virus virulence, and host genetic background.^2,3 However, antibody-dependent enhancement caused by secondary heterologous DENV infections is widely accepted as a principal risk factor for DHF, except in infants who acquire maternal dengue antibodies.⁴ Dengue infection is highly endemic in the urban/peri-urban areas of Vietnam, and all four serotypes of DENV (DEN-1 to DEN-4) have been identified.⁵ The breeding sites of dengue vector mosquitoes (i.e., Aedes aegypti) are located in and around households and may include indoor water jars, basins, and vases.^6–9 Because such containers are often indispensable, it is difficult to limit their use.⁹ As a result, household residents are highly susceptible to Ae. aegypti bites and subsequent dengue infection.Insecticide-treated bed nets, promoted for malaria control in the rural areas of Vietnam,¹⁰ are usually not used in urban/peri-urban areas, where malaria is not endemic. However, residents of urban/peri-urban areas commonly use untreated bed nets (not treated with insecticides) for protection against Culex mosquitoes and other nuisance insects during the night. If daytime bed net use for children could decrease the frequency of Ae. aegypti bites, the incidence of dengue may be reduced. To investigate the prevalence of bed net use and elucidate the effect of daytime bed net use on preventing DHF among children, we conducted a population-based cross-sectional study and a matched case–control study in Khanh Hoa Province in central Vietnam.The province has a hot-dry season from May through October and a cool-wet season from November through April. Although the province includes suburban communes surrounded by rice fields, most residents in the province live in urban communes. The study area covered 33 communes in this province. A population-based cross-sectional survey was conducted in July 2006 to collect information on the demography and socioeconomic statuses of all residents. The detailed study methods and the characteristics of this population have been described.¹¹ The study was reviewed and approved by the Institutional Review Board of the National Institute of Hygiene and Epidemiology, Hanoi, Vietnam, and the Institutional Review Board of the Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.All houses were geo-referenced using a handheld global positioning system unit with a resolution of 2–5 meters. We obtained admission records of two principal hospitals (provincial-level hospitals) in Khanh Hoa Province that provide medical care exclusively to patients with severe illnesses such as DHF. Patients with DHF were diagnosed by well-experienced local clinicians as part of routine procedures in the hospitals; diagnosis was based on the World Health Organization classification criteria.¹² Hospital records during the 16-month period preceding the census and population census data were linked by using the individual''s name, sex, age, contact person, and address.Among the identification-confirmed DHF patients, children 2–10 years (24–119 months) of age at the time of the interview were included in our case-control study. For each patient, four age-matched neighbor controls (the first- to fourth-nearest age-matched neighbors living in different households) were selected from the study population by using the census database and data from a geographic information system (ArcGIS version 9.3; Environmental Systems Research Institute, Redlands, CA). Information on child bed net practices was collected during household interviews with mothers. To evaluate the effect of daytime bed net use on DHF, we performed a case–control analysis by using a conditional logistic-regression model.A total of 52,671 children 2–10 years of age were enumerated in the census. Among these children, we excluded 4,028 preschool children (2–5 years of age) who attended kindergarten, 2,304 school age children (6–10 years of age) who had not attended primary school, and 9,438 for whom we had no information on bed net use or other socioeconomic variables. Thus, we included 36,901 children (70.1%) in the analysis. Almost all mothers of the children mentioned that their children used bed nets during the previous night of the household interview (36,259 of 36,901, 98.3%). However, few mothers of the children mentioned that their children used bed nets during the day on the previous day of the interview (3,107 of 36,901, 8.4%). Because insecticide treatment of bed nets and long-lasting insecticide-treated bed-nets were not available, all bed nets in the study area were not treated with insecticide.We identified 251 patients 2–10 years of age who were hospitalized with DHF from our study area within the 16-month period preceding the census. Among these patients, we obtained matched census data for 212 (47.6%). Among the matched 212 DHF patients, we included 151 (71.2%) patients in the case–control study except the minorities (i.e., attending kindergarten among preschool children and not attending primary school among school age children) and patients without complete information about bed net use or other variables. Among the 151 DHF patients and 604 age-matched neighbor controls, the mean age of persons in each group was 7.0 years. Children (cases and controls) had similar demographic and bed net use patterns (

Prevalence of risk factors for non-communicable diseases in the Mekong Delta, Vietnam: results from a STEPS survey

Background  

Despite the increasing burden of non-communicable diseases (NCD) in Vietnam, information on the prevalence of preventable risk factors for NCD is restricted to the main urban centres of Ha Noi, and Ho Chi Minh City (HCMC). This population-based survey aimed to describe the prevalence of risk factors for NCD in a rural Vietnamese sample.     

The impact of hospital volume on the number of nodes retrieved and outcome in colorectal cancer

We sought to examine the impact of hospital surgical volume on the number of nodes harvested and survival in colorectal cancer (CRC). Between January 1994 and December 2004, a total of 8567 patients with T1, 2, 3, and 4 primary tumors and N0, N1, or N2 disease were studied. Hospitals were stratified into very low volume (VLV) (<33 cases/year), low volume (LV) (33-56 cases/year), and medium volume (MV) (57-84 cases/year). Surgery for CRC was performed most commonly at VLV hospitals: 3488 (40.7%) VLV centers versus 2359 (27.5%) LV centers versus 2720 (31.7%) MV centers. The mean number of nodes retrieved for VLV centers was 8.6, for LV centers 9.4, and MV centers 10.2 (P < 0.0002). Actuarial 5-year survival for VLV centers was 71.4 per cent, for LV centers 75.6 per cent, and for MV 77.0 per cent (P < 0.00001). By Cox proportional hazards analysis, hospital volumes (P < 0.0011) and the number of lymph nodes harvested (P < 0.0034) remain significant predictors of disease specific survival. The number of nodes retrieved is impacted by hospital volumes. Hospital volumes impact survival in CRC. These findings cannot be attributed solely to improved staging due to increased node retrieval in VLV, LV, and MV hospitals.