JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer.
PLoS ONE
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
In this study a microRNA (miRNA) signature was identified in a gemcitabine resistant pancreatic ductal adenocarcinoma (PDAC) cell line model (BxPC3-GZR) and this signature was further examined in advanced PDAC tumor specimens from The Cancer Genome Atlas (TCGA) database. BxPC3-GZR showed a mesenchymal phenotype, expressed high levels of CD44 and showed a highly significant deregulation of 17 miRNAs. Based on relevance to cancer, a seven-miRNA signature (miR-100, miR-125b, miR-155, miR-21, miR-205, miR-27b and miR-455-3p) was selected for further studies. A strong correlation was observed for six of the seven miRNAs in 43 advanced tumor specimens compared to normal pancreas tissue. To assess the functional relevance we initially focused on miRNA-125b, which is over-expressed in both the BxPC3-GZR model and advanced PDAC tumor specimens. Knockdown of miRNA-125b in BxPC3-GZR and Panc-1 cells caused a partial reversal of the mesenchymal phenotype and enhanced response to gemcitabine. Moreover, RNA-seq data from each of 40 advanced PDAC tumor specimens from the TCGA data base indicate a negative correlation between expression of miRNA-125b and five of six potential target genes (BAP1, BBC3, NEU1, BCL2, STARD13). Thus far, two of these target genes, BBC3 and NEU1, that are tumor suppressor genes but not yet studied in PDAC, appear to be functional targets of miR-125b since knockdown of miR125b caused their up regulation. These miRNAs and their molecular targets may serve as targets to enhance sensitivity to chemotherapy and reduce metastatic spread.
Related JoVE Video
Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay.
Int J Endocrinol
PUBLISHED: 04-07-2014
Show Abstract
Hide Abstract
Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2]. This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various populations with different levels of vitamin D binding protein (DBP). Total serum 25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA measured DBP levels. The mean serum DBP concentrations were higher for pregnancy (415??g/mL) and lower for hemodialysis subjects (198??g/mL) than for healthy subjects and were highest for spiked serum (545??g/mL). The average bias between the ADVIA Centaur assay and the LC-MS/MS method was -1.4% (healthy), -6.1% (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from some pregnancy and hemodialysis subjects with serum DBP levels outside of the normal healthy range fell within a clinically acceptable range-reflected by analysis of their low-range (?136??g/mL), medium-range (137-559??g/mL), and high-range (?560??g/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total assay demonstrates acceptable performance compared with an LC-MS/MS method for populations containing different amounts of DBP.
Related JoVE Video
Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma.
BMC Cancer
PUBLISHED: 03-21-2014
Show Abstract
Hide Abstract
New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.
Related JoVE Video
Combined targeting of STAT3/NF-?B/COX-2/EP4 for effective management of pancreatic cancer.
Clin. Cancer Res.
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
Near equal rates of incidence and mortality emphasize the need for novel targeted approaches for better management of patients with pancreatic cancer. Inflammatory molecules NF-?B and STAT3 are overexpressed in pancreatic tumors. Inhibition of one protein allows cancer cells to survive using the other. The goal of this study is to determine whether targeting STAT3/NF-?B crosstalk with a natural product Nexrutine can inhibit inflammatory signaling in pancreatic cancer.
Related JoVE Video
Spontaneous free perforation of the small intestine in adults.
World J. Gastroenterol.
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn's disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn's disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair.
Related JoVE Video
Natural history and long-term clinical course of Crohn's disease.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Crohn's disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues. Genetic, epigenetic and environmental factors appear to play a role. Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance. The disorder occurs over a broad age spectrum, from early childhood to late adulthood. More than 80% are diagnosed before age 40 years usually with terminal ileal and colonic involvement. Pediatric-onset disease is more severe and more extensive, usually with a higher chance of upper gastrointestinal tract disease, compared to adult-onset disease. Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications (i.e., fistula, abscess). Although prolonged remission may occur, discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process. Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis. Until now, treatment has focused on removing risk factors, particularly cigarette smoking, and improving symptoms. In clinical trials, clinical remission is largely defined as improved numerical and endoscopic indices for "mucosal healing". "Deep remission" is a conceptual, more "extended" goal that may or may not alter the long-term natural history of the disease in selected patients, albeit at a significant risk for treatment complications, including serious and unusual opportunistic infections.
Related JoVE Video
Cooperativity of oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Activation of K-ras and inactivation of p16 are the most frequently identified genetic alterations in human pancreatic epithelial adenocarcinoma (PDAC). Mouse models engineered with mutant K-ras and deleted p16 recapitulate key pathological features of PDAC. However, a human cell culture transformation model that recapitulates the human pancreatic molecular carcinogenesis is lacking. In this study, we investigated the role of p16 in hTERT-immortalized human pancreatic epithelial nestin-expressing (HPNE) cells expressing mutant K-ras (K-rasG12V). We found that expression of p16 was induced by oncogenic K-ras in these HPNE cells and that silencing of this induced p16 expression resulted in tumorigenic transformation and development of metastatic PDAC in an orthotopic xenograft mouse model. Our results revealed that PI3K/Akt, ERK1/2 pathways and TGF? signaling were activated by K-ras and involved in the malignant transformation of human pancreatic cells. Also, p38/MAPK pathway was involved in p16 up-regulation. Thus, our findings establish an experimental cell-based model for dissecting signaling pathways in the development of human PDAC. This model provides an important tool for studying the molecular basis of PDAC development and gaining insight into signaling mechanisms and potential new therapeutic targets for altered oncogenic signaling pathways in PDAC.
Related JoVE Video
Bioequivalence of oxycodone hydrochoride extended release tablets to marketed reference products OxyContin® in Canada and US.
Int J Clin Pharmacol Ther
PUBLISHED: 10-24-2013
Show Abstract
Hide Abstract
Oxycodone is a semisynthetic opioid agonist used for the relief of moderate to severe pain. A new generic oxycodone hydrochloride (HCl) extended release (ER) tablet is currently being developed by Ranbaxy Pharmaceutical Inc., New Brunswick, NJ, USA.
Related JoVE Video
Early stage colon cancer.
World J. Gastroenterol.
PUBLISHED: 09-29-2013
Show Abstract
Hide Abstract
Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.
Related JoVE Video
Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure.
Circ Cardiovasc Qual Outcomes
PUBLISHED: 09-10-2013
Show Abstract
Hide Abstract
Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF.
Related JoVE Video
Natural history and long-term outcomes of patients treated for early stage colorectal cancer.
Can. J. Gastroenterol.
PUBLISHED: 07-18-2013
Show Abstract
Hide Abstract
The long-term natural history of early stage colon cancer and the outcome of long-term colonoscopic surveillance in routine specialist clinical practice after removal of the incident cancers have not been fully defined. In the present long-term evaluation up to 25 years, metachronous neoplasia, including both advanced adenomas and carcinomas, was defined.
Related JoVE Video
Detection of adult celiac disease with duodenal screening biopsies over a 30-year period.
Can. J. Gastroenterol.
PUBLISHED: 07-18-2013
Show Abstract
Hide Abstract
Serological studies suggest that celiac disease may be present in approximately 0.5% to 1% of the North American population. Screening data based on small intestinal biopsy performed during routine endoscopic evaluations are not available.
Related JoVE Video
A GHS-consistent approach to health hazard classification of petroleum substances, a class of UVCB substances.
Regul. Toxicol. Pharmacol.
PUBLISHED: 06-18-2013
Show Abstract
Hide Abstract
The process streams refined from petroleum crude oil for use in petroleum products are among those designated by USEPA as UVCB substances (unknown or variable composition, complex reaction products and biological materials). They are identified on global chemical inventories with unique Chemical Abstract Services (CAS) numbers and names. The chemical complexity of most petroleum substances presents challenges when evaluating their hazards and can result in differing evaluations due to the varying level of hazardous constituents and differences in national chemical control regulations. Global efforts to harmonize the identification of chemical hazards are aimed at promoting the use of consistent hazard evaluation criteria. This paper discusses a systematic approach for the health hazard evaluation of petroleum substances using chemical categories and the United Nations (UN) Globally Harmonized System (GHS) of classification and labeling. Also described are historical efforts to characterize the hazard of these substances and how they led to the development of categories, the identification of potentially hazardous constituents which should be considered, and a summary of the toxicology of the major petroleum product groups. The use of these categories can increase the utility of existing data, provide better informed hazard evaluations, and reduce the amount of animal testing required.
Related JoVE Video
Non-dietary forms of treatment for adult celiac disease.
World J Gastrointest Pharmacol Ther
PUBLISHED: 06-12-2013
Show Abstract
Hide Abstract
At present, treatment for celiac disease includes a strict gluten-free diet. Compliance, however, is difficult and gluten-free food products are costly, and, sometimes very inconvenient. A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy. In the past, non-dietary forms of treatment were used (e.g., corticosteroids) by some clinicians, often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet. Some of new and novel non-dietary measures have already advanced to a clinical trial phase. There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment. In particular, precise monitoring of the response to these agents will become critical. Symptom or laboratory improvement may be important, but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present. Therapeutic trials will be made more difficult because there is already an effective treatment regimen.
Related JoVE Video
Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer.
Mol. Cancer
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
Among the solid tumors, human pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis. Gemcitabine is the standard first line of therapy for pancreatic cancer but has limited efficacy due to inherent or rapid development of resistance and combining EGFR inhibitors with this regimen results in only a modest clinical benefit. The goal of this study was to identify molecular targets that are activated during gemcitabine therapy alone or in combination with an EGFR inhibitor.
Related JoVE Video
Risky driving behavior among university students and staff in the Sultanate of Oman.
Accid Anal Prev
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
There is a well developed literature on research investigating the relationship between various driving behaviors and road crash involvement. However, this research has predominantly been conducted in developed economies dominated by western types of cultural environments. To date no research has been published that has empirically investigated this relationship within the context of the emerging economies such as Oman.
Related JoVE Video
Long-term follow-up of patients with malignant pedunculated colon polyps after colonoscopic polypectomy.
Can. J. Gastroenterol.
PUBLISHED: 02-05-2013
Show Abstract
Hide Abstract
Previously published studies have suggested that patients with resected colon cancer have an increased risk for early metachronous colon cancer. Current screening guidelines recommend intense surveillance by colonoscopy for the initial five years after the initial colon cancer has been resected. Information regarding endoscopically removed malignant polyps is limited.
Related JoVE Video
Design and validation of a dynamic cell-culture system for bone biology research and exogenous tissue-engineering applications.
J Tissue Eng Regen Med
PUBLISHED: 01-20-2013
Show Abstract
Hide Abstract
Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd.
Related JoVE Video
Use of evidence-based cardiac prevention therapy among outpatients with atrial fibrillation.
Am. J. Med.
PUBLISHED: 01-11-2013
Show Abstract
Hide Abstract
Patients with atrial fibrillation often have cardiovascular risk factors or known comorbid disease, yet the use of evidence-based primary and secondary prevention cardiac therapy among atrial fibrillation outpatients is unknown.
Related JoVE Video
Effectiveness of ?-blockers in heart failure with left ventricular systolic dysfunction and chronic kidney disease.
J. Card. Fail.
PUBLISHED: 01-10-2013
Show Abstract
Hide Abstract
Establishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of ?-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We examined whether initiation of ?-blocker therapy was associated with better outcomes among patients with chronic kidney disease and newly diagnosed heart failure with left ventricular systolic dysfunction.
Related JoVE Video
Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-?B Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). To further study the individual and combinatorial roles of these two mutations in the pathogenesis of PDAC, immortalized human pancreas nestin postive cells (HPNE) were genetically modified by either expressing oncogenic K-Ras (HPNE/K-Ras), by shRNA knock down of Smad4 (HPNE/ShSmad4) or by creating both alterations in the same cell line (HPNE/K-Ras/ShSmad4). We previously found that expression of oncogenic K-Ras caused an increase in expression of EGFR and loss of Smad4 further enhanced the up regulation in expression of EGFR and that this increase in EGFR was sufficient to induce invasion. Here we further investigated the mechanism that links mutational alterations and EGFR expression with invasion. The increase in EGFR signaling was associated with up regulation of MMP9 and uPA protein and activity. Moreover, the increase in EGFR signaling promoted a nuclear translocation and binding of RelA (p65), a subunit of NF-?B, to the promoters of both MMP-9 and uPA. Treatment of HPNE/K-Ras/ShSmad4 cells with an inhibitor of EGFR reduced EGF-mediated NF-?B nuclear translocation and inhibitors of either EGFR or NF-?B reduced the increase in MMP-9 or uPA expression. In conclusion, this study provides the mechanism of how a combination of oncogenic K-Ras and loss of Smad4 causes invasion and provides the basis for new strategies to inhibit metastases.
Related JoVE Video
Physician procedure volume and complications of cardioverter-defibrillator implantation.
Circulation
PUBLISHED: 11-17-2011
Show Abstract
Hide Abstract
The outcomes of procedures are often better when they are performed by more experienced physicians. We assessed whether the rate of complications after implantable cardioverter-defibrillator (ICD) placement varied with the volume of procedures a physician performed.
Related JoVE Video
The impact of ST elevation on athletic screening.
Clin J Sport Med
PUBLISHED: 09-06-2011
Show Abstract
Hide Abstract
To demonstrate the prevalence and patterns of ST elevation (STE) in ambulatory individuals and athletes and compare the clinical outcomes.
Related JoVE Video
Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.
Int. J. Toxicol.
PUBLISHED: 08-30-2011
Show Abstract
Hide Abstract
A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.
Related JoVE Video
Novel function of transcription factor Nrf2 as an inhibitor of RON tyrosine kinase receptor-mediated cancer cell invasion.
J. Biol. Chem.
PUBLISHED: 07-28-2011
Show Abstract
Hide Abstract
Recepteur d origine nantais (RON), a tyrosine kinase receptor, is aberrantly expressed in human tumors and promotes cancer cell invasion. RON receptor activation is also associated with resistance to tamoxifen treatment in breast cancer cells. Nrf2 is a positive regulator of cytoprotective genes. Using chromatin immunoprecipitation (ChIP) and site-directed mutagenesis studies of the RON promoter, we identified Nrf2 as a negative regulator of RON gene expression. High Nrf2 and low RON expression was observed in normal mammary tissue whereas high RON and low or undetectable expression of Nrf2 was observed in breast tumors. The Nrf2 inducer sulforaphane (SFN) as well as ectopic Nrf2 expression or knock-down of the Nrf2 negative regulator keap1, which stabilizes Nrf2, inhibited RON expression and invasion of carcinoma cells. Consequently, our studies identified a novel functional role for Nrf2 as a "repressor" and RON kinase as a molecular target of SFN, which mediates the anti-tumor effects of SFN. These results are not limited to breast cancer cells since the Nrf2 inducer SFN stabilized Nrf2 and inhibited RON expression in carcinoma cells from various tumor types.
Related JoVE Video
The use of recreation planning tools in U.S. Forest Service NEPA assessments.
Environ Manage
PUBLISHED: 05-18-2011
Show Abstract
Hide Abstract
U.S. Forest Service managers are required to incorporate social and biophysical science information in planning and environmental analysis. The use of science is mandated by the National Environmental Policy Act, the National Forest Management Act, and U.S. Forest Service planning rules. Despite the agencys emphasis on science-based decision-making, little is known about how science is actually used in recreation planning and management. This study investigated the perceptions of Forest Service interdisciplinary (ID) team leaders for 106 NEPA projects dealing with recreation and travel management between 2005 and 2008. Our survey data show how managers rate the importance of social and biophysical science compared to other potential success factors in NEPA assessments. We also explore how team leaders value and use multi-disciplinary tools for recreation-related assessments. Results suggest that managers employ a variety of recreation planning tools in NEPA projects, but there appears to be no common understanding or approach for how or when these tools are incorporated. The Recreation Opportunity Spectrum (ROS) was the most frequently used planning tool, but the Visitor Experience and Resource Protection (VERP) framework was the most consistently valued tool by those who used it. We recommend further evaluation of the strengths and weaknesses of each planning tool and future development of procedures to select appropriate planning tools for use in recreation-related NEPA assessments.
Related JoVE Video
Collagenous sprue.
Can. J. Gastroenterol.
PUBLISHED: 04-28-2011
Show Abstract
Hide Abstract
Collagenous sprue is a small bowel mucosal lesion that has been historically associated with persistent diarrhea, progressive weight loss and severe malabsorption causing multiple nutrient deficiencies. A severe to variably severe mucosal lesion with distinct subepithelial collagen deposits occurs. Celiac disease has been intimately linked to collagenous sprue and, similar to celiac disease, small bowel ulceration, perforation and lymphoma may complicate the clinical course of collagenous sprue. In collagenous sprue, concomitant collagen deposits may also occur in gastric or colonic mucosal sites (or both), indicating that this unusual mucosal process may be very heterogeneous and far more extensive in the intestinal tract than previously appreciated. Moreover, reports of diagnosis during infancy suggest that the natural history of the disorder could be more prolonged than is currently appreciated. Finally, the collagen deposits, per se, may be due to different causes and, in some, even represent a novel paraneoplastic histopathological marker. Future studies are needed to more precisely define molecular and genetic biomarkers that identify homogeneous groups and permit the development of improved treatment strategies for this increasingly recognized disorder.
Related JoVE Video
Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.
Regul. Toxicol. Pharmacol.
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.
Related JoVE Video
Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt.
Regul. Toxicol. Pharmacol.
PUBLISHED: 03-23-2011
Show Abstract
Hide Abstract
Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 ?g applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 ?g, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.
Related JoVE Video
Improving Road Safety through Deterrence-Based Initiatives: A review of research.
Sultan Qaboos Univ Med J
PUBLISHED: 02-12-2011
Show Abstract
Hide Abstract
The efficacy of road safety countermeasures to deter motorists from engaging in illegal behaviours is extremely important when considering the personal and economic impact of road accidents on the community. In many countries, deterrence theory has remained a cornerstone of criminology and criminal justice policy, particularly within the field of road safety, as policy makers and enforcement agencies attempt to increase perceptions regarding the certainty, severity and swiftness of sanctions for those who engage in illegal motoring behaviours. Using the Australian experience (particularly the tremendous amount of research into drink driving), the current paper reviews the principles underpinning deterrence theory, the utilisation of the approach within some contemporary road safety initiatives (e.g., random breath testing) as well as highlighting some methods to enhance a deterrent effect. The paper also provides direction for future deterrence-based research, in particular, considering the powerful impact of non-legal sanctions, punishment avoidance as well as creating culturally embedded behavioural change.
Related JoVE Video
Intestinal lymphangiectasia in adults.
World J Gastrointest Oncol
PUBLISHED: 01-31-2011
Show Abstract
Hide Abstract
Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipples disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohns disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.
Related JoVE Video
Recent advances in celiac disease.
World J. Gastroenterol.
PUBLISHED: 01-06-2011
Show Abstract
Hide Abstract
Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.
Related JoVE Video
Recurrent myopericarditis with extensive ulcerative colitis.
Can J Cardiol
PUBLISHED: 12-18-2010
Show Abstract
Hide Abstract
A 26-year-old man with ulcerative colitis was independently evaluated in different emergency rooms on two occasions, separated by six years, for episodes of severe chest pain consistent with myopericarditis. Cardiac enzyme and electrocardiographic changes were accompanied by extensive colonic inflammatory changes. Treatment with corticosteroids led to resolution. While his cardiac findings were initially believed to be caused by a previously reported drug hypersensitivity to mesalamine (5-aminosalicylate), sulphasalazine was tolerated. Recurrent myopericarditis with ulcerative colitis appears to be rare, but responsive to steroids. It may occur more often than is currently appreciated and may lead to fatal arrhythmias or cardiac failure.
Related JoVE Video
Perivascular epithelioid cell neoplasm of the colon.
World J Gastrointest Oncol
PUBLISHED: 12-17-2010
Show Abstract
Hide Abstract
A 17-year-old female presented with rectal bleeding from an ulcerated sigmoid mass in 1994. Initial pathological evaluation revealed a rare clear cell neoplasm of the colon, possibly originating from kidneys, adrenals, lung or a gynecologic source as a metastatic lesion. Extensive imaging studies were negative, and over the next 15 years, she remained well with no recurrence. The original resected neoplasm was reviewed and re-classified as a perivascular epithelioid cell neoplasm (PEComa). Although the long-term natural history of PEComas requires definition, increased clinical and pathological awareness should lead to increased recognition of an apparently rare type of colonic neoplasm that likely occurs more often than is currently appreciated.
Related JoVE Video
Reproductive changes associated with celiac disease.
World J. Gastroenterol.
PUBLISHED: 12-15-2010
Show Abstract
Hide Abstract
Celiac disease is a mucosal disorder of the small intestine that may be triggered by dietary exposure to gluten in genetically-susceptible individuals. The disorder is often associated with diarrhea, malabsorption and weight loss along with other extra-intestinal complications. Reproductive changes have been described, including impaired fertility and adverse pregnancy outcomes possibly related to immune-mediated mechanisms or nutrient deficiency. Other possible pathogenetic factors that may alter placental function include maternal celiac disease autoantibodies binding to placental transglutaminase, and genetic mutations that may facilitate microthrombus formation. Reports noting activation during pregnancy or the puerperium may be important, and suggest that celiac disease may also be hypothetically precipitated by maternal exposure to one or more fetal antigens.
Related JoVE Video
Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation.
Ann. Intern. Med.
PUBLISHED: 11-01-2010
Show Abstract
Hide Abstract
Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin.
Related JoVE Video
Surveillance for colitis-associated colon neoplasia.
World J. Gastroenterol.
PUBLISHED: 09-28-2010
Show Abstract
Hide Abstract
The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accurate assessment of the surveillance effectiveness of colonoscopy and multi-site biopsy protocols. Although the clinical challenge posed to even the most experienced clinicians remains significant, evolving methods of endoscopic imaging may facilitate better evaluation of this highly select group of patients.
Related JoVE Video
Effect of whole-body vibration on bone properties in aging mice.
Bone
PUBLISHED: 06-29-2010
Show Abstract
Hide Abstract
Recent studies suggest that whole-body vibration (WBV) can improve measures of bone health for certain clinical conditions and ages. In the elderly, there also is particular interest in assessing the ability of physical interventions such as WBV to improve coordination, strength, and movement speed, which help prevent falls and fractures and maintain ambulation for independent living. The current study evaluated the efficacy of WBV in an aging mouse model. Two levels of vibration--0.5 and 1.5g--were applied at 32Hz to CB57BL/6 male mice (n=9 each) beginning at age 18 months and continuing for 12 weeks, 30 min/day, in a novel pivoting vibration device. Previous reports indicate that bone parameters in these mice begin to decrease substantially at 18 months, equivalent to mid-fifties for humans. Micro-computed tomography (micro-CT) and biomechanical assessments were made in the femur, radius, and lumbar vertebra to determine the effect of these WBV magnitudes and durations in the aging model. Sera also were collected for analysis of bone formation and breakdown markers. Mineralizing surface and cell counts were determined histologically. Bone volume in four regions of the femur did not change significantly, but there was a consistent shift toward higher mean density in the bone density spectrum (BDS), with the two vibration levels producing similar results. This new parameter represents an integral of the conventional density histogram. The amount of high density bone statistically improved in the head, neck, and diaphysis. Biomechanically, there was a trend toward greater stiffness in the 1.5 g group (p=0.139 vs. controls in the radius), and no change in strength. In the lumbar spine, no differences were seen due to vibration. Both vibration groups significantly reduced pyridinoline crosslinks, a collagen breakdown marker. They also significantly increased dynamic mineralization, MS/BS. Furthermore, osteoclasts were most numerous in the 1.5 g group (p? 0.05). These findings suggest that some benefits of WBV found in previous studies of young and mature rodent models may extend to an aging population. Density parameters indicated 0.5 g was more effective than 1.5 g. Serological markers, by contrast, favored 1.5 g, while biomechanically and histologically the results were mixed. Although the purported anabolic effect of WBV on bone homeostasis may depend on location and the parameter of interest, this emerging therapy at a minimum does not appear to compromise bone health by the measures studied here.
Related JoVE Video
Mesenteric lymph node cavitation syndrome.
World J. Gastroenterol.
PUBLISHED: 06-24-2010
Show Abstract
Hide Abstract
The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal disease that fails to respond to a gluten-free diet. Splenic hypofunction may also be present. The cause is not known but its development during the clinical course of celiac disease is usually indicative of a poor prognosis for the intestinal disorder, a potential for significant complications including sepsis and malignancy, particularly T-cell lymphoma, and significant mortality. Modern abdominal imaging modalities may permit earlier detection in celiac disease so that earlier diagnosis and improved understanding of its pathogenesis may result.
Related JoVE Video
Biotransformation of quinazoline and phthalazine by Aspergillus niger.
J. Biosci. Bioeng.
PUBLISHED: 06-14-2010
Show Abstract
Hide Abstract
Cultures of Aspergillus niger NRRL-599 in fluid Sabouraud medium were grown with quinazoline and phthalazine for 7 days. Metabolites were purified by high-performance liquid chromatography and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Quinazoline was oxidized to 4-quinazolinone and 2,4-quinazolinedione, and phthalazine was oxidized to 1-phthalazinone.
Related JoVE Video
"Porcelain heart" cardiomyopathy secondary to hyperparathyroidism: radiographic, echocardiographic, and cardiac CT appearances.
J Cardiovasc Comput Tomogr
PUBLISHED: 06-10-2010
Show Abstract
Hide Abstract
We report the radiographic, echocardiographic and cardiac CT appearances of porcelain heart in an 85-year-old woman who presented with progressive heart failure. The extensive myocardial calcification was secondary to hyperparathyroidism with renal failure.
Related JoVE Video
Expression of oncogenic K-ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cells.
Int. J. Cancer
PUBLISHED: 05-18-2010
Show Abstract
Hide Abstract
Activating mutation of K-ras and inactivation of DPC4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). A separate common event in PDAC progression is increased expression of phosphotyrosine kinase receptors (PTKRs). In our study, we examined whether activating mutations of K-ras and loss of Smad4 play a role in causing the aberrant expression of PTKRs. Immortalized human pancreas ductal cells (HPNE) were genetically modified by expressing oncogenic K-ras and/or by shRNA knockdown of Smad4. EGFR and erbB2 protein levels but not Ron or IGF-1R were substantially upregulated in HPNE cells that express K-ras((GD12)). The increased expression of EGFR in HPNE cells that expressed K-ras((GD12)) was mediated by both stabilizing EGFR protein and by increasing EGFR transcription. TGF-beta signaling partially suppressed K-ras((GD12)) induced EGFR transcription in Smad4 intact HPNE cells; whereas knockdown of Smad4 in cells expressing K-ras((GD12)) further enhanced expression of EGFR and erbB2. The upregulation of EGFR and erbB2 was associated with an increase of invasion, which was blocked by a kinase inhibitor of EGFR. Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion.
Related JoVE Video
Substrate specificity and structural characteristics of the novel Rieske nonheme iron aromatic ring-hydroxylating oxygenases NidAB and NidA3B3 from Mycobacterium vanbaalenii PYR-1.
MBio
PUBLISHED: 04-29-2010
Show Abstract
Hide Abstract
The Rieske nonheme iron aromatic ring-hydroxylating oxygenases (RHOs) NidAB and NidA3B3 from Mycobacterium vanbaalenii PYR-1 have been implicated in the initial oxidation of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs), forming cis-dihydrodiols. To clarify how these two RHOs are functionally different with respect to the degradation of HMW PAHs, we investigated their substrate specificities to 13 representative aromatic substrates (toluene, m-xylene, phthalate, biphenyl, naphthalene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, benzo[a]pyrene, carbazole, and dibenzothiophene) by enzyme reconstitution studies of Escherichia coli. Both Nid systems were identified to be compatible with type V electron transport chain (ETC) components, consisting of a [3Fe-4S]-type ferredoxin and a glutathione reductase (GR)-type reductase. Metabolite profiles indicated that the Nid systems oxidize a wide range of aromatic hydrocarbon compounds, producing various isomeric dihydrodiol and phenolic compounds. NidAB and NidA3B3 showed the highest conversion rates for pyrene and fluoranthene, respectively, with high product regiospecificity, whereas other aromatic substrates were converted at relatively low regiospecificity. Structural characteristics of the active sites of the Nid systems were investigated and compared to those of other RHOs. The NidAB and NidA3B3 systems showed the largest substrate-binding pockets in the active sites, which satisfies spatial requirements for accepting HMW PAHs. Spatially conserved aromatic amino acids, Phe-Phe-Phe, in the substrate-binding pockets of the Nid systems appeared to play an important role in keeping aromatic substrates within the reactive distance from the iron atom, which allows each oxygen to attack the neighboring carbons.
Related JoVE Video
Risk factors in familial forms of celiac disease.
World J. Gastroenterol.
PUBLISHED: 04-17-2010
Show Abstract
Hide Abstract
Celiac disease has been reported in up to 2% of some European populations. A similar risk has been identified in the America and Australia where immigration of Europeans has occurred. Moreover, an increasing number of celiac disease patients are being identified in many Asian countries, including China and India. Finally, celiac disease has also been detected in Asian immigrants and their descendants to other countries, such as Canada. Within these so-called "general" celiac populations, however, there are specific high risk groups that have an even higher prevalence of celiac disease. Indeed, the single most important risk factor for celiac disease is having a first-degree relative with already-defined celiac disease, particularly a sibling. A rate up to 20% or more has been noted. Risk is even greater if a specific family has 2 siblings affected, particularly if a male carries the human leukocyte antigen-DQ2. Both structural changes in the small bowel architecture occur along with functional changes in permeability, even in asymptomatic first-degree relatives. Even if celiac disease is not evident, the risk of other autoimmune disorders seems significantly increased in first-degree relatives as well as intestinal lymphoma. Identification of celiac disease is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated.
Related JoVE Video
The relation between hospital procedure volume and complications of cardioverter-defibrillator implantation from the implantable cardioverter-defibrillator registry.
J. Am. Coll. Cardiol.
PUBLISHED: 04-10-2010
Show Abstract
Hide Abstract
We sought to examine the relationship between hospital implantable cardioverter-defibrillator (ICD) implantation volume and procedural complications in a contemporary, representative population.
Related JoVE Video
Unraveling the complexity of driving while intoxicated: a study into the prevalence of psychiatric and substance abuse comorbidity.
Accid Anal Prev
PUBLISHED: 03-17-2010
Show Abstract
Hide Abstract
Research is beginning to provide an indication of the co-occurring substance abuse and mental health needs for the driving under the influence (DUI) population. This study aimed to examine the extent of such psychiatric problems among a large sample size of DUI offenders entering treatment in Texas.
Related JoVE Video
Performance evaluation of the ADVIA Centaur(®) HIV Ag/Ab Combo assay.
J. Virol. Methods
PUBLISHED: 02-18-2010
Show Abstract
Hide Abstract
Early diagnosis of HIV infection and appropriate care reduces morbidity and mortality. As a result, recent guidelines recommend that HIV screening be routinely included in patient care. Routine screening will likely result in more patients being tested prior to seroconversion; fourth-generation assays can facilitate diagnosis in these patients. This study evaluated the performance of the automated fourth-generation ADVIA Centaur(®) HIV Ag/Ab Combo assay. Samples from three sites were tested using the HIV Ag/Ab Combo assay and a CE-marked predicate assay. The HIV Ag/Ab Combo assays relative sensitivity was 98.36% (599/609; 95% confidence interval: 97.00-99.21%), and the relative specificity was 99.74% (7743/7763; 95% confidence interval: 99.60-99.84%). The HIV Ag/Ab Combo assay detected seroconversion at the same bleed or at least one bleed earlier in 34/37 panels compared to the CE-marked predicate assay. Compared to the final result, the HIV Ag/Ab Combo assays sensitivity was 100% (598/598; 95% confidence interval: 99.39-100.00%), and the specificity was 99.74% (7753/7773; 95% confidence interval: 99.60-99.84%). Sensitivity was 100% for the HIV genotypes tested. The HIV Ag/Ab Combo assay is a sensitive and specific assay that can assist clinicians in the early diagnosis of HIV infection.
Related JoVE Video
Update on collagenous sprue.
World J. Gastroenterol.
PUBLISHED: 01-19-2010
Show Abstract
Hide Abstract
Collagenous sprue has traditionally been defined as a small intestinal mucosal disorder characterized by persistent diarrhea, severe malabsorption with multiple nutrient deficiencies and progressive weight loss. Pathologically, a severe to variably severe "flattened" mucosal biopsy lesion with distinctive sub-epithelial deposits in the lamina propria region is detected. Histochemical stains and ultrastructural studies have confirmed that these deposits contain collagens. Often, an initial diagnosis of celiac disease is considered but no continued response to treatment with a gluten-free diet occurs. Recent reports indicate an intimate relationship between collagenous sprue and celiac disease, sometimes with concomitant T-cell enteropathy. In addition, permanent disappearance of these deposits after resection of a localized colon cancer suggested that this disorder could actually represent a paraneoplastic morphologic marker of an occult malignancy. Studies showing either gastric or colonic involvement (or both) with this unusual collagenous inflammatory mucosal process may also reflect a far more extensive and heterogeneous process than previously appreciated.
Related JoVE Video
Adding an electrocardiogram to the pre-participation examination in competitive athletes: a systematic review.
Curr Probl Cardiol
PUBLISHED: 11-06-2009
Show Abstract
Hide Abstract
No matter how rare, the death of young athletes is a tragedy. Can it be prevented? The European experience suggests that adding the electrocardiogram (ECG) to the standard medical and family history and physical examination can decrease cardiac deaths by 90%. However, there has not been a randomized trial to demonstrate such a reduction. While there are obvious differences between the European and American experiences with athletes including very differing causes of athletic deaths, some would highlight the European emphasis on public welfare vs the protection of personal rights in the USA. Even the authors of this systematic review have differing interpretation of the data: some of us view screening as a hopeless battle against Bayes, while others feel that the ECG can save lives. What we all agree on is that the USA should implement the American Heart Association 12-point screening recommendations and that, before ECG screening is mandated, we need to gather more data and optimize ECG criteria for screening young athletes.
Related JoVE Video
Multifocal stenosing ulceration of the small intestine.
World J. Gastroenterol.
PUBLISHED: 10-21-2009
Show Abstract
Hide Abstract
Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration. Compared to Crohns disease, the ulcers are not transmural and typically remain shallow, and involve only the mucosa and submucosa. The disorder seems to be localized in the jejunum and proximal ileum only, and not the distal ileum or colon. Only nonspecific inflammatory changes are present without giant cells or other typical features of granulomatous inflammation. Most patients present clinically with recurrent obstructive events that usually respond to steroids, surgical resection, or both. With the development of newer imaging modalities to visualize the small-intestinal mucosa, such as double-balloon enteroscopy, improved understanding of the long-term natural history of this apparently distinctive disorder should emerge.
Related JoVE Video
Applying Stafford and Warrs reconceptualization of deterrence theory to drug driving: can it predict those likely to offend?
Accid Anal Prev
PUBLISHED: 05-28-2009
Show Abstract
Hide Abstract
In December 2007, random roadside drug testing commenced in Queensland, Australia. Subsequently, the aim of this study was to explore the preliminary impact of Queenslands drug driving legislation and enforcement techniques by applying Stafford and Warrs [Stafford, M.C., Warr, M., 1993. A reconceptualization of general and specific deterrence. Journal of Research in Crime and Delinquency, 30, 123-135] reconceptualization of deterrence theory. Completing a comprehensive drug driving questionnaire were 899 members of the public, university students, and individuals referred to a drug diversion program. Of note was that approximately a fifth of participants reported drug driving in the past six months. Additionally, the analysis indicated that punishment avoidance and vicarious punishment avoidance were predictors of the propensity to drug drive in the future. In contrast, there were indications that knowing of others apprehended for drug driving was not a sufficient deterrent. Sustained testing and publicity of the legislation and countermeasure appears needed to increase the deterrent impact for drug driving.
Related JoVE Video
Screening for drugs in oral fluid: drug driving and illicit drug use in a sample of Queensland motorists.
Traffic Inj Prev
PUBLISHED: 05-20-2009
Show Abstract
Hide Abstract
Random roadside oral fluid testing is becoming increasingly popular as an apprehension and deterrence-based countermeasure to reduce drug driving. This article outlines research conducted to provide an estimate of the extent of drug driving in a sample of drivers in Brisbane, Queensland.
Related JoVE Video
Statin use and ventricular arrhythmias during clinical treadmill testing.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 05-12-2009
Show Abstract
Hide Abstract
Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise-induced ventricular arrhythmias has not been investigated.
Related JoVE Video
Biotransformation of acridine by Mycobacterium vanbaalenii.
Environ. Toxicol. Chem.
PUBLISHED: 05-09-2009
Show Abstract
Hide Abstract
Cultures of Mycobacterium vanbaalenii strain PYR-1 in a liquid medium were exposed to the toxic environmental contaminant acridine (260 microM). After incubation for 7 d, the cultures were extracted with ethyl acetate. Metabolites were purified using high-performance liquid chromatography and analyzed by mass spectrometry and 1H nuclear magnetic resonance spectroscopy. Four metabolites, 9,10-dihydroacridine, 4-hydroxyacridine, acridine cis-1 ,2-dihydrodiol, and acridin-9(10H)-one, were identified.
Related JoVE Video
Tropheryma whipplei infection.
World J. Gastroenterol.
PUBLISHED: 05-07-2009
Show Abstract
Hide Abstract
Whipples disease was initially described in 1907. Over the next century, the clinical and pathological features of this disorder have been better appreciated. Most often, weight loss, diarrhea, abdominal and joint pain occur. Occasionally, other sites of involvement have been documented, including isolated neurological disease, changes in the eyes and culture-negative endocarditis. In the past decade, the responsible organism Tropheryma whipplei has been cultivated, its genome sequenced and its antibiotic susceptibility defined. Although rare, it is a systemic infection that may mimic a wide spectrum of clinical disorders and may have a fatal outcome. If recognized, prolonged antibiotic therapy may be a very successful form of treatment.
Related JoVE Video
Too young to drink but old enough to drive under the influence: a study of underage offenders as seen in substance abuse treatment in Texas.
Drug Alcohol Depend
PUBLISHED: 04-06-2009
Show Abstract
Hide Abstract
Driving under the influence (DUI) is a major road safety problem. Historically, alcohol has been assumed to play a larger role in crashes and DUI education programs have reflected this assumption, although recent evidence suggests that younger drivers are becoming more likely to drive drugged than to drive drunk. This is a study of 7096 Texas clients under age 21 who were admitted to state-funded treatment programs between 1997 and 2007 with a past-year DUI arrest, DUI probation, or DUI referral. Data were obtained from the States administrative dataset. Multivariate logistic regressions models were used to understand the differences between those minors entering treatment as a DUI as compared to a non-DUI as well as the risks for completing treatment and for being abstinent in the month prior to follow-up. A major finding was that over time, the primary problem for underage DUI drivers changed from alcohol to marijuana. Being abstinent in the month prior to discharge, having a primary problem with alcohol rather than another drug, and having more family involved were the strongest predictors of treatment completion. Living in a household where the client was exposed to alcohol abuse or drug use, having been in residential treatment, and having more drug and alcohol and family problems were the strongest predictors of not being abstinent at follow-up. As a result, there is a need to direct more attention towards meeting the needs of the young DUI population through programs that address drug as well as alcohol consumption problems.
Related JoVE Video
Malignancy in adult celiac disease.
World J. Gastroenterol.
PUBLISHED: 04-03-2009
Show Abstract
Hide Abstract
Prior studies have suggested that the incidence of some neoplastic disorders, particularly malignant lymphoma and small intestinal adenocarcinoma, are increased in celiac disease. Earlier studies from the United Kingdom have also suggested a link between celiac disease and esophageal carcinoma, although this has not been confirmed in North America. The risk of other gastrointestinal cancers seems to be limited. Gastric cancer does not appear to be detected more frequently, although direct endoscopic visualization of the upper gastrointestinal tract is now very common in patients with celiac disease. Colon cancer also appears to be limited in celiac disease, even in patients first diagnosed with celiac disease late in life. This has led to the hypothesis that untreated celiac disease may be protective, possibly owing to impaired absorption of fat or fat-soluble agents, including hydrocarbons and putative co-carcinogens implicated in the pathogenesis of colon cancer, which may be poorly absorbed and rapidly excreted.
Related JoVE Video
Long-term natural history of Crohns disease.
World J. Gastroenterol.
PUBLISHED: 03-19-2009
Show Abstract
Hide Abstract
Crohns disease is a chronic inflammatory granulomatous process that usually involves different sites in the intestinal tract. Genetic and environmental factors are thought to play a role in its etiology and pathogenesis. The disorder has a heterogeneous clinical expression and data from tertiary care settings have documented its female predominance, occasional familial nature, and high rate of stricture formation and penetrating disease. It may appear from early childhood to late adulthood, although over 80% are currently diagnosed before age 40 years, usually with terminal ileal and colonic involvement. Several studies have now shown differences in phenotypic clinical expression depending on the initial age at diagnosis, with pediatric-onset disease being more severe and more extensive with more involvement of the upper gastrointestinal tract compared to adult-onset disease. In addition, long-term studies from these tertiary care settings have documented that the disorder may evolve with time into a more complex disease with stricture formation and penetrating disease complications (i.e. fistula and abscess). Although prolonged remission with no evidence of inflammatory disease may occur, discrete periods of symptomatic and active granulomatous inflammatory disease may re-appear over many decades. Long-term studies on the natural history have also suggested that discrete events (or agents) may precipitate this granulomatous inflammatory process.
Related JoVE Video
Targeted therapy of human osteosarcoma with 17AAG or rapamycin: characterization of induced apoptosis and inhibition of mTOR and Akt/MAPK/Wnt pathways.
Int. J. Oncol.
PUBLISHED: 01-17-2009
Show Abstract
Hide Abstract
Osteosarcoma is highly resistant to current chemotherapy regimens. Novel therapeutic approaches, potentially involving targeting of specific survival pathways, are needed. We used 17-AAG to inhibit Hsp90 and rapamycin to inhibit mTOR, in the osteosarcoma cell lines, HOS and KHOS/NP. HOS and KHOS cells were treated for 24 and 48 h with 17-AAG or rapamycin and studied drug-induced apoptosis, cell cycle, mitochondrial membrane potential and levels of reduced glutathione (GSH), dephosphorylation of signal transduction proteins in the Akt/MAP kinase pathway and mTOR signaling. 17-AAG was a potent inducer of apoptosis, involving effective depletion of GSH and mitochondrial membrane (MM) depolarization, strong activation of caspase-8 and -9 and release of AIF from mitochondria to the cytosol. Furthermore, 17-AAG down-regulated pAkt, p44Erk, p-mTOR, p70S6, TSC1/2 and pGSK-3beta. Treatment with 17-AAG also caused down-regulation of cyclin D1, GADD45a, GADD34 and pCdc2 and upregulation of cyclin B1 and mitotic block. A decrease in Hsp90 and increase in Hsp70 and Hsp70 C-terminal fragments were also observed. Rapamycin was a less potent inducer of apoptosis, involving a small decrease in GSH and MM potential with no activation of caspases or release of AIF. Rapamycin strongly inhibited cell growth with an increase in G1 and a decrease in S-phase of the cell cycle concomitant with down-regulation of cyclin D1. Rapamycin also down-regulated the activity of p70S6, pAkt and p-mTOR, but had no effect on pGSK-3beta, p44Erk, pCdc2, TSC1/2 or Hsp70 or Hsp90. We conclude that Hsp90 inhibition merits further study in the therapy of osteosarcoma.
Related JoVE Video
Appearance of attenuated intestinal polyposis during chronic non-steroidal anti-inflammatory drugs use.
World J Gastrointest Pharmacol Ther
Show Abstract
Hide Abstract
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.
Related JoVE Video
Effectiveness of implantable cardioverter defibrillators and cardiac resynchronization therapy in heart failure.
Heart Fail Clin
Show Abstract
Hide Abstract
Randomized trials and observational data have consistently demonstrated the benefit of ICDs for primary prevention of SCD in patients with HF and LVSD or secondary prevention in patients with a history of prior ventricular arrhythmias or aborted SCD, most of whom have HF. Secondary and post hoc analyses of trial data, as well as observational data, generally suggest that ICD therapy is effective in most selected subpopulations, such as the elderly and patients with NYHA class IV HF symptoms, but some studies suggest that ICDs may not be as effective in women and those with severe comorbidities, such as ESRD. Although there is limited evidence for an incremental benefit achieved with dual-chamber compared with single-chamber ICDs, the former devices are placed almost twice as frequently in the United States. Finally, observational data have recently shown that ICD procedural outcomes are improved when the device is placed by an electrophysiologist and at a high-volume hospital. More recently, clinical trials have demonstrated that cardiac resynchronization therapy improves quality of life and lowers rates of HF hospitalization in patients with symptomatic HF, LVSD, and a prolonged QRS complex already receiving optimal medical management; recent trial results have also suggested a mortality benefit with CRT in this population. In addition, recent trial data suggest that CRT reduces nonfatal events among mildly symptomatic patients (NYHA class I-II); however, the cost-effectiveness of CRT in this population remains unclear. As with ICDs, secondary and post hoc analyses of trial data as well as observational data suggest that CRT remains effective in most selected subpopulations, including stable NYHA class IV patients, the very elderly, and women. Recent observational work has suggested that CRT may not benefit patients with an RBBB QRS morphology to the same extent as those with an LBBB pattern, although because more conclusive studies are currently lacking, the guidelines do not tailor the recommendations based on QRS morphology. In summary, ICDs, CRT-P, and CRT-D represent important and effective treatment modalities for select patients with HF. Additional investigation is required to better determine which patient populations most benefit from these cardiac devices and which device, implanting physician, and hospital characteristics optimize outcomes with these cardiac devices.
Related JoVE Video
Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells.
J Transl Med
Show Abstract
Hide Abstract
Circulating melanoma cells (CMCs) are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage.
Related JoVE Video
Colitis associated with biological agents.
World J. Gastroenterol.
Show Abstract
Hide Abstract
In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohns disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.
Related JoVE Video
Light white oils exhibit low tissue accumulation potential and minimal toxicity in F344 rats.
Int. J. Toxicol.
Show Abstract
Hide Abstract
Female F344 rats were fed diets containing 0.02%, 0.2%, or 2.0% white mineral oil for 90 days. There were no gross or microscopic differences in target organs at the 0.02% level. In the higher-dose groups, relative liver and mesenteric lymph node (MLN) weights were increased, and MLN inflammation was observed. At the 2% level, there was very limited evidence of microgranuloma formation in the liver but at a lower incidence and at lesser severity than has been reported in studies of C??-C?? oils. Analysis of liver extracts from treated rats revealed that C??-C?? constituents were underrepresented by comparison to their corresponding concentrations in the test oil. These results provide evidence that although hydrocarbons with carbon numbers < C?? are absorbed, they are not preferentially retained and do not contribute to inflammatory processes in liver.
Related JoVE Video
Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation.
J. Am. Coll. Cardiol.
Show Abstract
Hide Abstract
The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.