Dynamic loading of immature epiphyseal cartilage pumps nutrients out of vascular canals.

The potential influence of mechanical loading on transvascular transport in vascularized soft tissues has not been explored extensively. This experimental investigation introduced and explored the hypothesis that dynamic mechanical loading can pump solutes out of blood vessels and into the surrounding tissue, leading to faster uptake and higher solute concentrations than could otherwise be achieved under unloaded conditions. Immature epiphyseal cartilage was used as a model tissue system, with fluorescein (332 Da), dextran (3, 10, and 70 kDa) and transferrin (80 kDa) as model solutes. Cartilage disks were either dynamically loaded (± 10% compression over a 10% static offset strain, at 0.2 Hz) or maintained unloaded in solution for up to 20 h. Results demonstrated statistically significant solute uptake in dynamically loaded (DL) explants relative to passive diffusion (PD) controls for all solutes except unbound fluorescein, as evidenced by the DL:PD concentration ratios after 20 h (1.0 ± 0.2, 2.4 ± 1.1, 6.1 ± 3.3, 9.0 ± 4.0, and 5.5 ± 1.6 for fluorescein, 3, 10, and 70 kDa dextran, and transferrin). Significant uptake enhancements were also observed within the first 30s of loading. Termination of dynamic loading produced dissipation of enhanced solute uptake back to PD control values. Confocal images confirmed that solute uptake occurred from cartilage canals into their surrounding extracellular matrix. The incidence of this loading-induced transvascular solute pumping mechanism may significantly alter our understanding of the interaction of mechanical loading and tissue metabolism.

Validation of theoretical framework explaining active solute uptake in dynamically loaded porous media.

Solute transport in biological tissues is a fundamental process necessary for cell metabolism. In connective soft tissues, such as articular cartilage, cells are embedded within a dense extracellular matrix that hinders the transport of solutes. However, according to a recent theoretical study (Mauck et al., 2003, J. Biomech. Eng. 125, 602-614), the convective motion of a dynamically loaded porous solid matrix can also impart momentum to solutes, pumping them into the tissue and giving rise to concentrations which exceed those achived under passive diffusion alone. In this study, the theoretical predictions of this model are verified against experimental measurements. The mechanical and transport properties of an agarose-dextran model system were characterized from independent measurements and substituted into the theory to predict solute uptake or desorption under dynamic mechanical loading for various agarose concentrations and dextran molecular weights, as well as different boundary and initial conditions. In every tested case, agreement was observed between experiments and theoretical predictions as assessed by coefficients of determination ranging from R(2)=0.61 to 0.95. These results provide strong support for the hypothesis that dynamic loading of a deformable porous tissue can produce active transport of solutes via a pumping mechanisms mediated by momentum exchange between the solute and solid matrix.

Frequency of visualization of presumed celiac ganglia by endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Celiac ganglia can be visualized by endoscopic ultrasound (EUS). It is unknown how often ganglia are visualized during EUS, and what clinical factors are associated with ganglion visualization. The aim of this study was to prospectively evaluate the frequency of visualization of presumed celiac ganglia by EUS and to identify factors that predict their visualization. PATIENTS AND METHODS: Clinical, demographic, EUS, and cytologic data were collected prospectively from 200 unselected patients who were undergoing EUS in a tertiary referral centre. When presumed celiac ganglia were visualized, their size, number, location, and echo features were noted. When presumed ganglia were aspirated, the results of cytology were recorded. RESULTS: The most common indication for EUS was investigation of a pancreatic mass or cyst (25 %). Presumed celiac ganglia were identified in 81 % of patients overall. Logistic regression analysis determined that female sex and having no prior history of gastrointestinal surgery were independently associated with ganglion visualization. Among patients whose ganglia were visualized, more ganglia were seen per patient with linear echo endoscopes (2, range 0 - 5) than with radial echo endoscopes (1, range 0 - 4) ( P = 0.001). Presumed celiac ganglia were aspirated in 10 patients; and cytologic examination revealed neural ganglia in all of these. CONCLUSIONS: Celiac ganglia can be visualized by EUS in most patients who undergo upper gastrointestinal EUS examinations, and are best seen with linear-array echo endoscopes. Ganglia can usually be differentiated from lymph nodes on the basis of their endosonographic appearance.

Widespread endoscopic mucosal resection of the esophagus with strategies for stricture prevention: a preclinical study.

BACKGROUND AND STUDY AIMS: Circumferential endoscopic mucosal resection of the esophagus is complicated by stricture formation. Prophylactic measures for avoiding such strictures have not been well studied. The aim of this preclinical study was to assess strategies for prevention of esophageal strictures in a porcine model following widespread endoscopic mucosal resection (EMR). METHODS: A total of 18 60-kg pigs were included in the study. The roles of strip width (group 1), prophylactic steroids (group 2), and prophylactic stents (group 3) in the prevention of post-mucosectomy strictures were studied. Six animals were included in each group. Esophageal mucosal resection was achieved using a novel widespread EMR technique previously described by our group. Animals in group 1 underwent partial (50% circumference) mucosal resection without prophylactic measures, while animals in the other two groups underwent circumferential mucosal resection. Animals in group 2 received 80 mg of triamcinolone injected directly into the exposed submucosal tissue (20 mg injection in four quadrants). Animals in group 3 received esophageal metal stents coated with small-intestine submucosa (SIS) that were deployed immediately post-resection. Animals were kept alive for 1 month. RESULTS: Partial and circumferential widespread EMRs were achieved in all animals. There were no procedural complications. Repeat endoscopy at 1 month showed no strictures in group 1. Only four animals were studied in group 2, owing to the high complication rate (periesophageal abscess in all animals) with one early death. Three of the surviving animals developed mild to tight strictures. In group 3, all animals developed tight strictures; however, there was early stent migration in four animals and premature stent removal in two animals because of persistent vomiting. CONCLUSIONS: Partial widespread EMR of the esophagus heals without stricture formation and does not require prophylactic intervention. The use of deep mural steroid injection following a circumferential resection does not appear to prevent strictures and may result in serious adverse events. Short-term use of esophageal stents is inadequate for stricture prevention. However, better results may be anticipated with longer term (at least 6 weeks) stent use.

Endoscopic and histologic diagnosis of Barrett esophagus.

Endoscopy plays an important role in the identification, diagnosis, and treatment of Barrett esophagus. Short-segment (<2-3 cm) and traditional long-segment (>2-3 cm) Barrett esophagus are distinguished solely on the length of metaplastic tissue above the esophagogastric junction. The histologic hallmark of intestinal metaplasia is required to confirm diagnosis. Biopsy specimens obtained from tissue of presumed Barrett esophagus or an irregular Z line confirm metaplastic glandular mucosa and permit evaluation of dysplastic or neoplastic changes. In the appropriate clinical setting, the use of adjunctive diagnostic techniques may facilitate the diagnosis of Barrett esophagus and sequelae such as dysplasia. Chromoendoscopy with high-resolution or magnified endoscopy is simple, safe, and desirable for surveillance but requires additional procedural time. The use of light-induced fluorescence endoscopy and light-scattering spectroscopy (i.e., optical biopsy) is appealing for the diagnosis and characterization of suspicious lesions. Adjunctive endoscopic techniques and adherence to a protocol for performing biopsies facilitate the early detection and subsequent surveillance of Barrett esophagus.

Widespread endoscopic mucosal resection.

The concept of widespread endoscopic mucosal resection is an alternative treatment for large surface area mucosal lesions. The need for such a technique is addressed by examining piecemeal mucosal resections. Early preclinical experience on esophageal widespread mucosectomy is presented.

Cost-effective analysis of hepatitis A prevention in Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective prevention strategy against hepatitis A virus (HAV) infection for healthcare workers and the general population at risk in Ireland. METHODS: Four prevention strategies were compared: active immunization with Havrix Monodose (1440E.U); screening for anti-HAV antibody and then vaccinating; passive immunization; screening for anti-HAV antibody and then passive immunization. The cost-effective ratio was calculated for each prevention strategy. Threshold analysis, sensitivity analysis, and model extension to include indirect cost from work days lost and secondary attack rates through horizontal transmission were also derived. RESULTS: The medical costs were lowest and the infection rate highest when no preventive action was taken. Vaccination was most cost effective when the prevalence of immunity was 45% or less, reducing the infection rate by 98% when compared to nonprevention. Screening before vaccination was most cost effective when the prevalence of immunity was greater than 45%. Passive immunization and screening before passive immunization were not comparable to the other strategies in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio for vaccination was dependent on vaccine price, incidence of HAV, and prevalence of immunity in the target group. Extending the model to include indirect costs further increased the cost effectiveness of vaccination. CONCLUSION: The best cost-effective strategy relates to target group immunity. Where HAV immunity is 45% or less, vaccination is the strategy of choice and when immunity is greater than 45%, then screening followed by vaccination should be used. This study can be used to provide a framework within which choices can be made to achieve better health for less cost.

Hepatitis A in urban Ireland.

AIMS: To determine the prevalence of immunity to hepatitis A virus (HAV) infection in urban Ireland and to categorize the region into low, intermediate or high HAV endemicity, and to analyse the significance of certain commonly associated risk factors. METHODS: Two hundred and thirty three volunteers were recruited from 6 general practices in Dublin, Ireland. There were 44 volunteers in the 10 to 19 yr age group, 40 in the 20 to 29, 42 in the 30 to 39, 43 in the 40 to 49 and 64 in the over 50 age groups. Each participant completed a detailed questionnaire and was tested for anti-HAV total antibody (primarily IgG) using a competitive ELISA assay. Urban Ireland was classified into the appropriate area of HAV endemicity according to the prevalence of immunity by age group. Risk factor differences were analysed for significance using the chi square test and Fisher's exact test. RESULTS: One hundred and fifty seven (67 per cent) volunteers were immune, of whom 20 (45 per cent) were in the 10 to 19 yr age group, 17 (43 per cent) in the 20 to 29, 30 (71 per cent) in the 30 to 39, 34 (79 per cent) in the 40 to 49 and 59 (92 per cent) in the over 50 age groups. Fifty-five per cent of the individuals studied below the age of 20 yr were non-immune. The immune rates over the age of 30 were significantly greater (p < 0.01) than those in the 10 to 29 age groups. Socioeconomic pattern in the total and 10 to 19 yr age group was a significant (p < 0.0002, p < 0.004 respectively) risk factor for infection. CONCLUSION: This study concludes that urban Ireland is an area of low HAV endemicity with age and socioeconomic status as the significant influences on seropositivity. This survey provides an insight into the changing epidemiology of HAV infection in Ireland and serves as a guide for immunisation of at risk population groups.

Small cell carcinoma of the lung presenting as chylous ascites: a unique case.

A 67-year-old female presenting with a history of weight loss and abdominal distension was noted on examination to have ascites. Paracentesis revealed a chylous ascites and chest radiography showed a right hilar enlargement with mid-zone infiltration. Abdominal computed tomography demonstrated retroperitoneal lymphadenopathy and biopsy of this showed small cell undifferentiated carcinoma. This appears to be the first documented association between metastatic small cell carcinoma of the lung and chylous ascites.

The reliability of saliva as a sample for the detection of hepatitis A immunoglobulins under various sampling conditions.

BACKGROUND: Saliva is increasingly being investigated as an alternative to serum for diagnostic and epidemiological testing even though antibody levels are substantially lower in buccal cavity fluids. However, there has been little study on whether buccal cavity activity and/or the timing of saliva sampling affects the diagnostic outcome, particularly in seropositive subjects. The absence of influence by these factors may be critical to the use of saliva for pre-vaccination screening for example. OBJECTIVES: The effects of eating, brushing of teeth and circadian rhythm on the measureable salivary immune status of 42 healthy individuals known to be serum and saliva anti-HAV positive were examined. STUDY DESIGN: A total of 141 saliva samples obtained from the 42 healthy subjects, before and after meals, before and after brushing of teeth and at various timepoints throughout the day, were assayed for total anti-HAV using an in-house saliva based enzyme-immunoassay, previously shown to have a 100% correlation in terms of sensitivity and specificity with a serum based assay. RESULTS: The results indicated that total anti-HAV titres varied according to the time of day and that eating had no significant effect on the total anti-HAV titre, but brushing of teeth did. Titres never varied to the extent that a result was falsely negative at any timepoint. CONCLUSION: These results confirm the usefulness of saliva as a diagnostic sample for the detection of hepatitis A antibody, regardless of sampling times, eating or tooth-brushing.

Two year old hepatitis A vaccine is as good as new.

This was a randomized, controlled, double-blind study assessing the reactogenicity and immunogenicity of newly produced vs 2 year old hepatitis A vaccine. Overall 215 non-immune volunteers, 18-39 years old were divided into four groups and administered vaccine at months 0, 1 and 6. Three groups each received a different vaccine lot which had been stored at 4 degrees C for 2 years, and one group received recently produced vaccine as control. The mean local and general adverse reaction rates were 59.1% and 17.4%, respectively, and all vaccinees had seroconverted by month 2. There were no significant differences in geometric mean anti-hepatitis A virus (HAV) antibody titres between the four groups. In conclusion 2 year old HAV vaccine is safe and equally immunogenic as newly produced vaccine.

Percutaneous endoscopic gastrostomy--results of an Irish single unit series.

The technique of percutaneous endoscopic gastrostomy (PEG) was first described in 1980, as an alternative to traditional surgical methods. The main indication for PEG is the need for longterm nutritional support. It is reported to have many advantages over surgical gastrostomy, being safer and cheaper. We reviewed our experience with the first 44 patients referred to our unit for PEG. The most common indications for referral were stroke, head injury and post brain surgery. There was a success rate of 97.6% and a complication rate of 13.8%. One patient (2.3%) suffered major complications as a result of early tube displacement. There were no procedure related deaths in our series and no deaths as a result of an underlying disease process within 30 days, reflecting appropriate patient selection. All patients benefited nutritionally from PEG placement. Two patients recovered sufficiently to no longer require a gastrostomy and the tube was easily removed in both cases.