Causes of failure with Szabo technique - an analysis of nine cases.

PubMed

Jain, Rajendra Kumar; Padmanabhan, T N C; Chitnis, Nishad

2013-01-01

The objective of this case series is to identify and define causes of failure of Szabo technique in rapid-exchange monorail system for ostial lesions. From March 2009 to March 2011, 42 patients with an ostial lesion were treated percutaneously at our institution using Szabo technique in a monorail stent system. All patients received unfractionated heparin during intervention. Loading dose of clopidogrel, followed by clopidogrel and aspirin was administered. In 57% of patients, drug-eluting stents were used and in 42.8% patients bare metal stents. The stent was advanced over both wires, the target wire and the anchor wire. The anchor wire, which was passed through the proximal trailing strut of the stent helps to achieve precise stenting. The procedure was considered to be successful if stent was placed precisely covering the lesion and without stent loss or anchor wire prolapsing. Of the total 42 patients, the procedure was successful in 33, while failed in 9. Majority of failures were due to wire entanglement, which was fixed successfully in 3 cases by removing and reinserting the anchor wire. Out of other three failures, in one stent dislodgment occurred, stent could not cross the lesion in one and in another anchor wire got looped and prolapsed into target vessel. This case series shows that the Szabo technique, in spite of some difficulties like wire entanglement, stent dislodgement and resistance during stent advancement, is a simple and feasible method for treating variety of ostial lesions precisely compared to conventional angioplasty. Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Trans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsies.

PubMed

Ukimura, Osamu; Marien, Arnaud; Palmer, Suzanne; Villers, Arnauld; Aron, Manju; de Castro Abreu, Andre Luis; Leslie, Scott; Shoji, Sunao; Matsugasumi, Toru; Gross, Mitchell; Dasgupta, Prokar; Gill, Inderbir S

2015-11-01

To compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS. Pre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010-09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason score ≥7 and/or maximum cancer core length ≥5 mm. Targeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41 %; p = 0.007), sPCa detection rate (43 vs. 23 %; p = 0.0013), cancer core length (7.5 vs. 3.9 mm; p = 0.0002), and cancer rate per core (56 vs. 12 %; p < 0.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate (p < 0.0001), higher Gleason score (p = 0.018), and greater cancer core length (p < 0.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield (p < 0.0001) and higher sPCa detection rate (p < 0.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate. MR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.

Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis.

PubMed

van Horssen, Jack; van der Pol, Susanne; Nijland, Philip; Amor, Sandra; Perron, Hervé

2016-07-01

Attempts to identify a causative agent of Multiple Sclerosis (MS) among environmental viruses have consistently failed suggesting that development of MS is a result from gene-environment interactions. A new pathogenic player within human genes, a human endogenous retrovirus (HERV) was identified from MS cells, named MS-associated retrovirus element (MSRV) and unveiled homologous multicopy HERVs (HERV-W). As independent studies revealed biological features of HERV-W on immune-mediated inflammation and on remyelinating cells, the present study characterized the presence of HERV-W envelope protein (MSRV-Env) at the cellular level, in different MS lesion stages to extend and validate previous studies. Immunohistological analysis of HERV-W envelope cellular expression in different lesion stages from a cohort of MS brains versus controls, using well-characterized and highly specific monoclonal antibodies. HERV-W envelope protein was detected in all MS brains and quite essentially in lesions. Immunohistochemistry showed dominant expression in macrophages and microglia, coinciding with areas of active demyelination, spread over the active lesions, or limited to the rim of active microglia in chronic active lesions or in few surviving astrocytes of inactive plaques. Weak expression was seen in MS normal appearing white matter. In active plaques, few lymphoid cells and astrocytes were also stained. This HERV-W expression was not observed in control brains. HERV-W was expressed in demyelinated lesions from MS brains, which were all positive for this endogenous pathogenic protein. Pronounced HERV-W immunoreactivity in active MS lesions was intimately associated with areas of active demyelination throughout the successive stages of lesion evolution in MS brains. Based on its pathogenic potential, this HERV-W (MSRV) endogenous toxin thus appears to be a novel therapeutic target in MS. It also has a unique positioning as an early and lifelong expressed pathogenic agonist, acting

Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions.

PubMed

Neesse, Albrecht; Hahnenkamp, Anke; Griesmann, Heidi; Buchholz, Malte; Hahn, Stefan A; Maghnouj, Abdelouahid; Fendrich, Volker; Ring, Janine; Sipos, Bence; Tuveson, David A; Bremer, Christoph; Gress, Thomas M; Michl, Patrick

2013-07-01

Novel imaging methods based on specific molecular targets to detect both established neoplasms and their precursor lesions are highly desirable in cancer medicine. Previously, we identified claudin-4, an integral constituent of tight junctions, as highly expressed in various gastrointestinal tumours including pancreatic cancer. Here, we investigate the potential of targeting claudin-4 with a naturally occurring ligand to visualise pancreatic cancer and its precursor lesions in vitro and in vivo by near-infrared imaging approaches. A non-toxic C-terminal fragment of the claudin-4 ligand Clostridium perfringens enterotoxin (C-CPE) was labelled with a cyanine dye (Cy5.5). Binding of the optical tracer was analysed on claudin-4 positive and negative cells in vitro, and tumour xenografts in vivo. In addition, two genetically engineered mouse models for pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancer were used for in vivo validation. Optical imaging studies were conducted using 2D planar fluorescence reflectance imaging (FRI) technology and 3D fluorescence-mediated tomography (FMT). In vitro, the peptide-dye conjugate showed high binding affinity to claudin-4 positive CAPAN1 cells, while claudin-4 negative HT1080 cells revealed little or no fluorescence. In vivo, claudin-4 positive tumour xenografts, endogenous pancreatic tumours, hepatic metastases, as well as preinvasive PanIN lesions, were visualised by FRI and FMT up to 48 h after injection showing a significantly higher average of fluorochrome concentration as compared with claudin-4 negative xenografts and normal pancreatic tissue. C-CPE-Cy5.5 combined with novel optical imaging methods enables non-invasive visualisation of claudin-4 positive murine pancreatic tumours and their precursor lesions, representing a promising modality for early diagnostic imaging.

Technology platform development for targeted plasma metabolites in human heart failure.

PubMed

Chan, Cy X'avia; Khan, Anjum A; Choi, Jh Howard; Ng, Cm Dominic; Cadeiras, Martin; Deng, Mario; Ping, Peipei

2013-01-01

Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic

MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

PubMed

Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio

2016-11-01

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.

Targeting Mitochondrial Calcium Handling and Reactive Oxygen Species in Heart Failure.

PubMed

Dietl, Alexander; Maack, Christoph

2017-08-01

In highly prevalent cardiac diseases, new therapeutic approaches are needed. Since the first description of oxidative stress in heart failure, reactive oxygen species (ROS) have been considered as attractive drug targets. Though clinical trials evaluating antioxidant vitamins as ROS-scavenging agents yielded neutral results in patients at cardiovascular risk, the knowledge of ROS as pathophysiological factors has considerably advanced in the past few years and led to novel treatment approaches. Here, we review recent new insights and current strategies in targeting mitochondrial calcium handling and ROS in heart failure. Mitochondria are an important ROS source, and more recently, drug development focused on targeting mitochondria (e.g. by SS-31 or MitoQ). Important advancement has also been made to decipher how the matching of energy supply and demand through calcium (Ca 2+ ) handling impacts on mitochondrial ROS production and elimination. This opens novel opportunities to ameliorate mitochondrial dysfunction in heart failure by targeting cytosolic and mitochondrial ion transporters to improve this matching process. According to this approach, highly specific substances as the preclinical CGP-37157, as well as the clinically used ranolazine and empagliflozin, provide promising results on different levels of evidence. Furthermore, the understanding of redox signalling relays, resembled by catalyst-mediated protein oxidation, is about to change former paradigms of ROS signalling. Novel methods, as redox proteomics, allow to precisely analyse key regulatory thiol switches, which may induce adaptive or maladaptive signalling. Additionally, the generation of genetically encoded probes increased the spatial and temporal resolution of ROS imaging and opened a new methodological window to subtle, formerly obscured processes. These novel insights may broaden our understanding of why previous attempts to target oxidative stress have failed, and at the same time provide us

Frequency of bacetrial content finding in persistant periapical lesions

PubMed Central

Grgurević, Joško; Tambić Andrašević, Arjana; Prpić Mehičić, Goranka; Kuzmac, Sania; Jukić, Silvana

2017-01-01

Objectives To determine the percentage of persistant apical lesions positive for bacterial nucleic acids, to detect microorganisms difficult to cultivate in persistant apical lesions by PCR and relate them to endodontic failure, clinical symptoms and diabetes mellitus. Materials and methods The samples of persistent apical lesions were collected during apicoectomy. Bacterial ubiquitous primer 16S rRNA was used to detect 16S ribosomal RNA in 36 samples. A species–specific PCR was performed with primers targeted to the bacterial 16S rRNA genes of Prevotella Nigrescens, Pseudoramibacter alactolyticus, and Propionobacterium propionicum. Results Six samples (16.67%) were positive for bacterial ribosomal RNA. Pseudoramibacter alactolyticus was detected in three samples. Propionibacterium propionicum and Prevotella nigrescens were detected in one sample each. The prevalence of infection of such lesions with P. intermedia, P. propionicum and P. alactolyticus is low. Conslusion The study we conducted gave insufficient data about extraradicular infection and its connection with diabetes mellitus and clinical symptoms. Conclusions Apical lesions persisting after endodontic treatment could harbor microorganisms other than Actinomyces and Propionicum species. PMID:29225362

Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure.

PubMed

Frey, Anna; Sell, Roxane; Homola, György A; Malsch, Carolin; Kraft, Peter; Gunreben, Ignaz; Morbach, Caroline; Alkonyi, Bálint; Schmid, Eric; Colonna, Isabella; Hofer, Edith; Müllges, Wolfgang; Ertl, Georg; Heuschmann, Peter; Solymosi, László; Schmidt, Reinhold; Störk, Stefan; Stoll, Guido

2018-05-31

This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment. Cognitive deficits have been reported in patients with HF. A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls. Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p < 0.001). The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls. Moreover, patients had a 2.7-fold increased risk for presence of clinically silent lacunes. HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

PubMed Central

Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

PubMed

Kimura, Takeshi; Morimoto, Takeshi; Nakagawa, Yoshihisa; Kawai, Kazuya; Miyazaki, Shunichi; Muramatsu, Toshiya; Shiode, Nobuo; Namura, Masanobu; Sone, Takahito; Oshima, Shigeru; Nishikawa, Hideo; Hiasa, Yoshikazu; Hayashi, Yasuhiko; Nobuyoshi, Masakiyo; Mitudo, Kazuaki

2012-01-31

There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.

The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic Lesions in a Mouse Model.

PubMed

Quattrone, Federica; Sanchez, Ana Maria; Pannese, Maria; Hemmerle, Teresa; Viganò, Paola; Candiani, Massimo; Petraglia, Felice; Neri, Dario; Panina-Bordignon, Paola

2015-09-01

Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P = .029 and P = .006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P = .02; metalloproteinase [MMP] 3: P = .02; MMP9: P = .04; vascular endothelial growth factor: P = .04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium. © The Author(s) 2015.

Lesion progression in post-treatment persistent endodontic lesions.

PubMed

Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

2012-10-01

Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

Laser fluorescence in monitoring the influence of targeted tooth brushing on remineralization of initial caries lesions on newly erupted molar teeth - RCT.

PubMed

Laitala, M-L; Jaanti, E; Vähänikkilä, H; Määttä, T; Heikka, H; Hausen, H; Anttonen, V

2017-11-01

This study aimed to monitor mineralization changes in initial caries lesions on newly erupted second molars using laser fluorescence (LF) scanning after a 1-month targeted tooth brushing intervention. Altogether, 124 13- to 14-year-old school children were invited to participate. Of those who fulfilled the clinical criteria (at least one initial lesion with LF value >10 in second molars), 51 gave their written consent to participate. Laser fluorescence values were registered at baseline and after 1-month follow-up period. All participants were individually taught targeted tooth brushing of their second molars and randomly provided tooth paste with 0 or 1500 ppm fluoride. Brushing frequency was investigated at baseline and after the follow-up. Change in LF values was compared considering the tooth, content of fluoride in the paste and brushing frequency. In lesions with LF values ≤30 at baseline, change in LF values demonstrated improvement. Improvement was detected especially in upper molars. In lesions with LF values >30 at baseline, improvement was least detected. Brushing frequency increased slightly during the intervention. Laser fluorescence is a simple method and useful in monitoring remineralization of incipient lesions even in weeks. Targeted tooth brushing seems to induce remineralization even in weeks. Laser fluorescence could be a valuable motivating tool in promoting patients' self-care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

PubMed

Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

2013-01-01

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

How to diagnose and treat focal therapy failure and recurrence?

PubMed

Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

2014-05-01

Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Association Study between Cervical Lesions and Single or Multiple Vaccine-Target and Non-Vaccine Target Human Papillomavirus (HPV) Types in Women from Northeastern Brazil

PubMed Central

Chagas, Bárbara Simas; Comar, Manola; Gurgel, Ana Pavla Almeida Diniz; Paiva, Sérgio; Seraceni, Silva; de Freitas, Antonio Carlos; Crovella, Sergio

2015-01-01

We performed an association between high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and single or multiple vaccine-target as well as non-vaccine target Human papillomavirus (HPV) types. Using bead-based HPV genotyping, 594 gynecological samples were genotyped. An association between squamous intraepithelial lesion (SIL) and presence of HPV16, 18, 31, 58 and 56 types were calculated. The risk was estimated by using odds ratio (OR) and 95% of confidence intervals (CI). A total of 370 (62.3%) women were HPV positive. Among these, 157 (42.7%) presented a single HPV infection, and 212 (57.3%) were infected by more than one HPV type. HPV31 was the most prevalent genotype, regardless single and multiple HPV infections. Single infection with HPV31 was associated with LSIL (OR=2.32; 95%CI: 1.01 to 5.32; p=0.04); HPV31 was also associated with LSIL (OR=3.28; 95%CI: 1.74 to 6.19; p= 0.0002) and HSIL (OR=3.82; 95%CI: 2.10 to 6.97; p<0.001) in multiple HPV infections. Risk to harbor cervical lesions was observed in multiple HPV infections with regard to the HPV56 (OR=5.39; 95%CI: 2.44 to 11.90; p<0.001for LSIL; OR=5.37; 95%CI: 2.71 to 10.69; p<0.001) and HPV58 (OR=3.29; 95%CI: 1.34 to 8.09; p=0.0091 for LSIL; OR=3.55; 95%CI: 1.56 to 8.11; p=0.0026) genotypes. In addition, women coinfected with HPV16/31/56 types had 6 and 5-fold increased risk of HSIL (OR=6.46; 95%CI: 1.89 to 22.09; p=0.002) and LSIL (OR=5.22; 95%CI: 1.10 to 24.70; p=0.03), respectively. Multiple HPV infections without HPV16/18 has 2-fold increased risk of HSIL (OR=2.57; 95%CI: 1.41 to 4.70; p=0.002) and LSIL OR=2.03; 95%CI: 1.08 to 3.79; p=0.02). The results of this study suggest that single and multiple vaccine target as well as non-vaccine target HPV types are associated with LSIL and HSIL. These finding should be taken into consideration in the design of HPV vaccination strategies. PMID:26176537

Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription

PubMed Central

Aydin, Özge Z.; Marteijn, Jurgen A.; Ribeiro-Silva, Cristina; Rodríguez López, Aida; Wijgers, Nils; Smeenk, Godelieve; van Attikum, Haico; Poot, Raymond A.; Vermeulen, Wim; Lans, Hannes

2014-01-01

Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA. PMID:24990377

Cardio-oncology Related to Heart Failure: Epidermal Growth Factor Receptor Target-Based Therapy.

PubMed

Kenigsberg, Benjamin; Jain, Varun; Barac, Ana

2017-04-01

Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology. The article discusses challenges in predicting, monitoring, and treating cardiac dysfunction and heart failure associated with ErbB-targeted cancer therapeutics and highlights opportunities for researchers and clinical investigators. Copyright © 2016 Elsevier Inc. All rights reserved.

Does the achievement of an intermediate glycemic target reduce organ failure and mortality? A post hoc analysis of the Glucontrol trial.

PubMed

Penning, Sophie; Chase, J Geoffrey; Preiser, Jean-Charles; Pretty, Christopher G; Signal, Matthew; Mélot, Christian; Desaive, Thomas

2014-06-01

This research evaluates the impact of the achievement of an intermediate target glycemic band on the severity of organ failure and mortality. Daily Sequential Organ Failure Assessment (SOFA) score and the cumulative time in a 4.0 to 7.0 mmol/L band (cTIB) were evaluated daily up to 14 days in 704 participants of the multicentre Glucontrol trial (16 centers) that randomized patients to intensive group A (blood glucose [BG] target: 4.4-6.1 mmol/L) or conventional group B (BG target: 7.8-10.0 mmol/L). Sequential Organ Failure Assessment evolution was measured by percentage of patients with SOFA less than or equal to 5 on each day, percentage of individual organ failures, and percentage of organ failure-free days. Conditional and joint probability analysis of SOFA and cTIB 0.5 or more assessed the impact of achieving 4.0 to 7.0 mmol/L target glycemic range on organ failure. Odds ratios (OR) compare the odds risk of death for cTIB 0.5 or more vs cTIB less than 0.5, where a ratio greater than 1.0 indicates an improvement for achieving cTIB 0.5 or more independent of SOFA or glycemic target. Groups A and B were matched for demographic and severity of illness data. Blood glucose differed between groups A and B (P<.05), as expected. There was no difference in the percentage of patients with SOFA less than or equal to 5, individual organ failures, and organ failure-free days between groups A and B over days 1 to 14. However, 20% to 30% of group A patients failed to achieve cTIB 0.5 or more for all days, and significant crossover confounds interpretation. Mortality OR was greater than 1.0 for patients with cTIB 0.5 or more in both groups but much higher for group A on all days. There was no difference in organ failure in the Glucontrol study based on intention to treat to different glycemic targets. Actual outcomes and significant crossover indicate that this result may not be due to the difference in target or treatment. Odds ratios-associated achieving an intermediate 4

Significance of Vertebral Endplate Failure in Symptomatic Lumbar Disc Herniation

PubMed Central

Sahoo, Madan Mohan; Kaur, Sheetal; Sarangi, Jitendra; Mohapatra, Manoranjan

2017-01-01

Study Design: Prospective cohort study. Objective: Endplate lesions though have been implicated in the genesis of lumbar disc herniation (LDH), very little is known regarding their clinical course. Thus, the present study is aimed to investigate the incidence and types of endplate failure (EPF) in LDH and its correlation with the clinical symptoms and prognosis. Methods: Clinical and magnetic resonance imaging (MRI) features of 66 patients with isolated single level LDH were studied. Three-dimensional fast spoiled gradient (3D FSPGR) MRI and computed tomography scans were used to identify the bony and cartilaginous EPF. Twenty-five patients were operated on and 41 patients were treated conservatively. Changes in the pain score, function and neurology were noted at 3, 6, 12, 24, and 36 weeks. Results: Endplate lesions were observed in 64 patients (96.9%), including bony endplate failure (bony failure) in 47 patients (71.2%) and isolated cartilaginous endplate lesions in 17 patients (25.7%). Bony failure group had similar pain and functional scores but more severe neurological deficit at the initial evaluation. Clinical parameters improved in all groups, but the recovery was lesser in conservatively treated bony failure patients. Conclusion: Endplate lesions are commonly associated with symptomatic LDH. Presence of bony failure can increase neurological deficit and reduce the chance of recovery with conservative management. The 3D FSPGR sequence of MRI can be successfully used for detection of the endplate lesions in the herniated disc. PMID:28660105

Significance of Vertebral Endplate Failure in Symptomatic Lumbar Disc Herniation.

PubMed

Sahoo, Madan Mohan; Mahapatra, Sudhir Kumar; Kaur, Sheetal; Sarangi, Jitendra; Mohapatra, Manoranjan

2017-05-01

Prospective cohort study. Endplate lesions though have been implicated in the genesis of lumbar disc herniation (LDH), very little is known regarding their clinical course. Thus, the present study is aimed to investigate the incidence and types of endplate failure (EPF) in LDH and its correlation with the clinical symptoms and prognosis. Clinical and magnetic resonance imaging (MRI) features of 66 patients with isolated single level LDH were studied. Three-dimensional fast spoiled gradient (3D FSPGR) MRI and computed tomography scans were used to identify the bony and cartilaginous EPF. Twenty-five patients were operated on and 41 patients were treated conservatively. Changes in the pain score, function and neurology were noted at 3, 6, 12, 24, and 36 weeks. Endplate lesions were observed in 64 patients (96.9%), including bony endplate failure (bony failure) in 47 patients (71.2%) and isolated cartilaginous endplate lesions in 17 patients (25.7%). Bony failure group had similar pain and functional scores but more severe neurological deficit at the initial evaluation. Clinical parameters improved in all groups, but the recovery was lesser in conservatively treated bony failure patients. Endplate lesions are commonly associated with symptomatic LDH. Presence of bony failure can increase neurological deficit and reduce the chance of recovery with conservative management. The 3D FSPGR sequence of MRI can be successfully used for detection of the endplate lesions in the herniated disc.

Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions

PubMed Central

Jotova, Iveta; Wu, T. C.; Wang, Chenguang; Desmarais, Cindy; Boyer, Jean D.; Tycko, Benjamin; Robins, Harlan S.; Clark, Rachael A.; Trimble, Cornelia L.

2014-01-01

About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral blood T cell responses to vaccine antigen. We report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting HPV16 E6/E7 antigens, in subjects with CIN2/3 who had modest detectable responses in circulating T lymphocytes. Histologic and molecular changes, including markedly (average threefold) increased intensity of CD8+ T cell infiltrates in both the stromal and epithelial compartments, suggest an effector response to vaccination. Postvaccination cervical tissue immune infiltrates included organized tertiary lymphoid-like structures in the stroma subjacent to residual intraepithelial lesions and, unlike infiltrates in unvaccinated lesions, showed evidence of proliferation induced by recognition of cognate antigen. At a molecular level, these histologic changes in the stroma were characterized by increased expression of genes associated with immune activation (CXCR3) and effector function (Tbet and IFNβ), and were also associated with an immunologic signature in the overlying dysplastic epithelium. High-throughput T cell receptor sequencing of unmanipulated specimens identified clonal expansions in the tissue that were not readily detectable in peripheral blood. Together, these findings indicate that peripheral therapeutic vaccination to HPV antigens can induce a robust tissue-localized effector immune response, and that analyses of immune responses at sites of antigen are likely to be much more informative than analyses of cells that remain in the circulation. PMID:24477000

Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure

PubMed Central

Brinks, Henriette; Koch, Walter J

2010-01-01

In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF. PMID:21218155

Double Kissing Crush Versus Provisional Stenting for Left Main Distal Bifurcation Lesions: DKCRUSH-V Randomized Trial.

PubMed

Chen, Shao-Liang; Zhang, Jue-Jie; Han, Yaling; Kan, Jing; Chen, Lianglong; Qiu, Chunguang; Jiang, Tiemin; Tao, Ling; Zeng, Hesong; Li, Li; Xia, Yong; Gao, Chuanyu; Santoso, Teguh; Paiboon, Chootopol; Wang, Yan; Kwan, Tak W; Ye, Fei; Tian, Nailiang; Liu, Zhizhong; Lin, Song; Lu, Chengzhi; Wen, Shangyu; Hong, Lang; Zhang, Qi; Sheiban, Imad; Xu, Yawei; Wang, Lefeng; Rab, Tanveer S; Li, Zhanquan; Cheng, Guanchang; Cui, Lianqun; Leon, Martin B; Stone, Gregg W

2017-11-28

Provisional stenting (PS) is the most common technique used to treat distal left main (LM) bifurcation lesions in patients with unprotected LM coronary artery disease undergoing percutaneous coronary intervention. The double kissing (DK) crush planned 2-stent technique has been shown to improve clinical outcomes in non-LM bifurcations compared with PS, and in LM bifurcations compared with culotte stenting, but has never been compared with PS in LM bifurcation lesions. The authors sought to determine whether a planned DK crush 2-stent technique is superior to PS for patients with true distal LM bifurcation lesions. The authors randomized 482 patients from 26 centers in 5 countries with true distal LM bifurcation lesions (Medina 1,1,1 or 0,1,1) to PS (n = 242) or DK crush stenting (n = 240). The primary endpoint was the 1-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Routine 13-month angiographic follow-up was scheduled after ascertainment of the primary endpoint. TLF within 1 year occurred in 26 patients (10.7%) assigned to PS, and in 12 patients (5.0%) assigned to DK crush (hazard ratio: 0.42; 95% confidence interval: 0.21 to 0.85; p = 0.02). Compared with PS, DK crush also resulted in lower rates of target vessel myocardial infarction I (2.9% vs. 0.4%; p = 0.03) and definite or probable stent thrombosis (3.3% vs. 0.4%; p = 0.02). Clinically driven target lesion revascularization (7.9% vs. 3.8%; p = 0.06) and angiographic restenosis within the LM complex (14.6% vs. 7.1%; p = 0.10) also tended to be less frequent with DK crush compared with PS. There was no significant difference in cardiac death between the groups. In the present multicenter randomized trial, percutaneous coronary intervention of true distal LM bifurcation lesions using a planned DK crush 2-stent strategy resulted in a lower rate of TLF at 1 year than a PS�

Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Whetsell, W. O.; Jobe, J.; Nadeau, J. H.

1994-01-01

Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).

Network pharmacology-based strategy for predicting active ingredients and potential targets of Yangxinshi tablet for treating heart failure.

PubMed

Chen, Langdong; Cao, Yan; Zhang, Hai; Lv, Diya; Zhao, Yahong; Liu, Yanjun; Ye, Guan; Chai, Yifeng

2018-01-31

Yangxinshi tablet (YXST) is an effective treatment for heart failure and myocardial infarction; it consists of 13 herbal medicines formulated according to traditional Chinese Medicine (TCM) practices. It has been used for the treatment of cardiovascular disease for many years in China. In this study, a network pharmacology-based strategy was used to elucidate the mechanism of action of YXST for the treatment of heart failure. Cardiovascular disease-related protein target and compound databases were constructed for YXST. A molecular docking platform was used to predict the protein targets of YXST. The affinity between proteins and ingredients was determined using surface plasmon resonance (SPR) assays. The action modes between targets and representative ingredients were calculated using Glide docking, and the related pathways were predicted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A protein target database containing 924 proteins was constructed; 179 compounds in YXST were identified, and 48 compounds with high relevance to the proteins were defined as representative ingredients. Thirty-four protein targets of the 48 representative ingredients were analyzed and classified into two categories: immune and cardiovascular systems. The SPR assay and molecular docking partly validated the interplay between protein targets and representative ingredients. Moreover, 28 pathways related to heart failure were identified, which provided directions for further research on YXST. This study demonstrated that the cardiovascular protective effect of YXST mainly involved the immune and cardiovascular systems. Through the research strategy based on network pharmacology, we analysis the complex system of YXST and found 48 representative compounds, 34 proteins and 28 related pathways of YXST, which could help us understand the underlying mechanism of YSXT's anti-heart failure effect. The network-based investigation could help researchers simplify the complex

Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure.

PubMed

Fox, Susan H; Lang, Anthony E; Brotchie, Jonathan M

2006-10-01

Studies in MPTP-lesioned nonhuman primates have demonstrated the potential of nondopaminergic drugs in reducing the problems of levodopa-induced dyskinesia (LID). Here we review the process of translating findings from the monkey to man. Agents targeting glutamate, adensosine, noradrenaline, 5-hydroxytryptamine, cannabinoid, and opioid transmitter systems have been assessed for antidyskinetic potential in human studies. Eleven nondopaminergic drugs with antidyskinetic efficacy in the MPTP primate have been advanced to proof-of-concept phase IIa trials in PD patients (amantadine, istradefylline, idazoxan, fipamezole, sarizotan, quetiapine, clozapine, nabilone, rimonabant, naloxone, and naltrexone). For all six nondopaminergic transmitter systems reviewed, the MPTP-lesioned primate correctly predicted phase II efficacy of at least one drug. Of the 11 specific molecules tested in both monkeys and humans, 8 showed clear antidyskinetic properties in both human and monkey. In the instances where the primate studies did not, or did not consistently, predict the outcome of the human studies, the discrepancy may reflect limitations in the validity of the model or limitations in the design of either the clinical or the preclinical studies. We find that the major determinant of success in predicting efficacy is to ensure that primate studies are conducted in a statistically rigorous way and incorporate designs and outcome measures with clinical applicability. On the other hand, phase IIa trials should strive to replicate the preclinical study, especially in terms of protocol, drug dose equivalence, and outcome measure, so as to test the same hypothesis. Failure to meet these criteria carries the risk of false negative conclusions in phase IIa trials.

Diagnostic power of diffuse reflectance spectroscopy for targeted detection of breast lesions with microcalcifications

PubMed Central

Soares, Jaqueline S.; Barman, Ishan; Dingari, Narahara Chari; Volynskaya, Zoya; Liu, Wendy; Klein, Nina; Plecha, Donna; Dasari, Ramachandra R.; Fitzmaurice, Maryann

2013-01-01

Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. Here, we introduce an approach based on diffuse reflectance spectroscopy for detection of microcalcifications that focuses on variations in optical absorption stemming from the calcified clusters and the associated cross-linking molecules. In this study, diffuse reflectance spectra are acquired ex vivo from 203 sites in fresh biopsy tissue cores from 23 patients undergoing stereotactic breast needle biopsies. By correlating the spectra with the corresponding radiographic and histologic assessment, we have developed a support vector machine-derived decision algorithm, which shows high diagnostic power (positive predictive value and negative predictive value of 97% and 88%, respectively) for diagnosis of lesions with microcalcifications. We further show that these results are robust and not due to any spurious correlations. We attribute our findings to the presence of proteins (such as elastin), and desmosine and isodesmosine cross-linkers in the microcalcifications. It is important to note that the performance of the diffuse reflectance decision algorithm is comparable to one derived from the corresponding Raman spectra, and the considerably higher intensity of the reflectance signal enables the detection of the targeted lesions in a fraction of the spectral acquisition time. Our findings create a unique landscape for spectroscopic validation of breast core needle biopsy for detection of microcalcifications that can substantially improve the likelihood of an adequate, diagnostic biopsy in the first attempt. PMID:23267090

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions.

PubMed

Eberle, Alex N; Rout, Bhimsen; Qi, Mei Bigliardi; Bigliardi, Paul L

2017-01-01

Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

CRISPR/Cas9 Technology Targeting Fas Gene Protects Mice From Concanavalin-A Induced Fulminant Hepatic Failure.

PubMed

Liang, Wei-Cheng; Liang, Pu-Ping; Wong, Cheuk-Wa; Ng, Tzi-Bun; Huang, Jun-Jiu; Zhang, Jin-Fang; Waye, Mary Miu-Yee; Fu, Wei-Ming

2017-03-01

Fulminant hepatic failure is a life-threatening disease which occurs in patients without preexisting liver disease. Nowadays, there is no ideal therapeutic tool in the treatment of fulminant hepatic failure. Recent studies suggested that a novel technology termed CRISPR/Cas9 may be a promising approach for the treatment of fulminant hepatic failure. In this project, we have designed single chimeric guide RNAs specifically targeting the genomic regions of mouse Fas gene. The in vitro and in vivo effects of sgRNAs on the production of Fas protein were examined in cultured mouse cells and in a hydrodynamic injection-based mouse model, respectively. The in vivo delivery of CRISPR/Cas9 could maintain liver homeostasis and protect hepatocytes from Fas-mediated cell apoptosis in the fulminant hepatic failure model. Our study indicates the clinical potential of developing the CRISPR/Cas9 system as a novel therapeutic strategy to rescue Concanavalin-A-induced fulminant hepatic failure in the mouse model. J. Cell. Biochem. 118: 530-536, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology.

PubMed

van Bilsen, Marc; Patel, Hitesh C; Bauersachs, Johann; Böhm, Michael; Borggrefe, Martin; Brutsaert, Dirk; Coats, Andrew J S; de Boer, Rudolf A; de Keulenaer, Gilles W; Filippatos, Gerasimos S; Floras, John; Grassi, Guido; Jankowska, Ewa A; Kornet, Lilian; Lunde, Ida G; Maack, Christoph; Mahfoud, Felix; Pollesello, Piero; Ponikowski, Piotr; Ruschitzka, Frank; Sabbah, Hani N; Schultz, Harold D; Seferovic, Petar; Slart, Riemer H J A; Taggart, Peter; Tocchetti, Carlo G; Van Laake, Linda W; Zannad, Faiez; Heymans, Stephane; Lyon, Alexander R

2017-11-01

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future? © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Social Brains in Context: Lesions Targeted to the Song Control System in Female Cowbirds Affect Their Social Network

PubMed Central

Maguire, Sarah E.; Schmidt, Marc F.; White, David J.

2013-01-01

Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system. PMID:23650558

Social brains in context: lesions targeted to the song control system in female cowbirds affect their social network.

PubMed

Maguire, Sarah E; Schmidt, Marc F; White, David J

2013-01-01

Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system.

Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Duplancic, B; Marovic, A; Zoricic, I; Prkacin, I; Lovric-Bencic, M; Aralica, G; Ziger, T; Perovic, D; Jelovac, N; Dodig, G; Rotkvic, I; Mise, S; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either

Acceleration of recovery in acute renal failure: from cellular mechanisms of tubular repair to innovative targeted therapies.

PubMed

Abbate, M; Remuzzi, G

1996-05-01

Kidney repair from injury is a major focus of interest for research, both clinical and basic, in the field of acute renal failure. This is so because very little progress has been made during the past several years to improve mortality in hospitalized patients with acute renal failure despite the unique potential of the kidney for complete structural and functional recovery. Novel therapeutic options have recently emerged from the knowledge of molecular mechanisms of tissue injury after ischemia, including pathways of endothelial-leukocyte interaction and epithelial cell aggregation mediated by integrin molecules. These strategies are promising because they may target early mechanisms of leukocyte infiltration and tubular obstruction. However, it seems clear that additional interventions should address the reparative program that potentially leads to the full restoration of kidney structure and function. Thus, acceleration of repair from acute renal failure is achieved experimentally by growth factors which besides different renal actions seem to have in common the ability to stimulate proliferation of surviving tubular epithelial cells. We direct attention to cellular processes which characterize, and possibly have role in, renal repair from acute tubular injury as potential targets of therapy. In addition to proliferation, they include epithelial differentiation and apoptosis. Further investigation in the biology of repair should set the stage for rational design of targeted therapies which may accelerate the pace of recovery and hopefully decrease mortality in such a dramatic and potentially reversible setting.

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

PubMed Central

Lemmens, Katrien; Vrints, Christiaan J.

2017-01-01

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF. PMID:28706575

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

PubMed Central

Senni, Michele; Paulus, Walter J.; Gavazzi, Antonello; Fraser, Alan G.; Díez, Javier; Solomon, Scott D.; Smiseth, Otto A.; Guazzi, Marco; Lam, Carolyn S. P.; Maggioni, Aldo P.; Tschöpe, Carsten; Metra, Marco; Hummel, Scott L.; Edelmann, Frank; Ambrosio, Giuseppe; Stewart Coats, Andrew J.; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Anker, Stefan D.; Levy, Daniel; Pfeffer, Marc A.; Stough, Wendy Gattis; Pieske, Burkert M.

2014-01-01

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed. PMID:25104786

Rethinking Skin Lesion Segmentation in a Convolutional Classifier.

PubMed

Burdick, Jack; Marques, Oge; Weinthal, Janet; Furht, Borko

2017-10-18

Melanoma is a fatal form of skin cancer when left undiagnosed. Computer-aided diagnosis systems powered by convolutional neural networks (CNNs) can improve diagnostic accuracy and save lives. CNNs have been successfully used in both skin lesion segmentation and classification. For reasons heretofore unclear, previous works have found image segmentation to be, conflictingly, both detrimental and beneficial to skin lesion classification. We investigate the effect of expanding the segmentation border to include pixels surrounding the target lesion. Ostensibly, segmenting a target skin lesion will remove inessential information, non-lesion skin, and artifacts to aid in classification. Our results indicate that segmentation border enlargement produces, to a certain degree, better results across all metrics of interest when using a convolutional based classifier built using the transfer learning paradigm. Consequently, preprocessing methods which produce borders larger than the actual lesion can potentially improve classifier performance, more than both perfect segmentation, using dermatologist created ground truth masks, and no segmentation altogether.

The gut-kidney axis in chronic renal failure: A new potential target for therapy.

PubMed

Khoury, Tawfik; Tzukert, Keren; Abel, Roy; Abu Rmeileh, Ayman; Levi, Ronen; Ilan, Yaron

2017-07-01

Evidence is accumulating to consider the gut microbiome as a central player in the gut-kidney axis. Microbiome products, such as advanced glycation end products, phenols, and indoles, are absorbed into the circulation but are cleared by normal-functioning kidneys. These products then become toxic and contribute to the uremic load and to the progression of chronic kidney failure. In this review, we discuss the gut-kidney interaction under the state of chronic kidney failure as well as the potential mechanisms by which a change in the gut flora (termed gut dysbiosis) in chronic kidney disease (CKD) exacerbates uremia and leads to further progression of CKD and inflammation. Finally, the potential therapeutic interventions to target the gut microbiome in CKD are discussed. © 2016 International Society for Hemodialysis.

Targeting Premalignant Lesions: Implications for Early Breast Cancer Detection and Intervention

DTIC Science & Technology

2016-04-01

prostate, lung, colon and pancreas and have been also reported in the premalignant lesions. This peptide could provide us with an opportunity to...including those of the breast, prostate, lung, colon and pancreas and have been also reported in the premalignant lesions (Erez N, et. al Cancer Cell

Pathological mechanisms of left main stent failure.

PubMed

Mori, Hiroyoshi; Torii, Sho; Harari, Emanuel; Jinnouchi, Hiroyuki; Brauman, Ryan; Smith, Samantha; Kutys, Robert; Fowler, David; Romero, Maria; Virmani, Renu; Finn, Aloke V

2018-07-15

Despite the increasing use of left main (LM) percutaneous coronary intervention (LM-PCI), there have been no pathological studies devoted to understanding the causes of LM stent failure. We aimed to systematically determine the pathological mechanisms of LM stent failure. From the CVPath Stent registry, a total of 46 lesions were identified to have LM-PCI. Pathologic stent failure (PSF) was defined as stent thrombosis, restenosis and in-stent chronic total occlusion (CTO). Failed and patent LM stented lesions were pathologically assessed to determine predictors of PSF. Malapposition and uncovered struts were numerically greater in the LM ostium, body, and bifurcation while neointimal thickness was relatively greater in bifurcation and proximal circumflex. In this study cohort, half of the lesions (n = 23) showed PSF. Stent thrombosis (ST, n = 18) was the major mode of PSF followed by in-stent CTO (n = 4) and restenosis (n = 1). Failed lesions showed significantly greater prevalence of malapposition >20% of struts/section (65% vs. 13%, P < 0.01), stent struts crossing an ostial side branch >30% of the circumference (48% vs. 13%, P < 0.01) and uncovered struts >30% (57% vs. 18%, P = 0.03). In multivariate analysis, the prevalence of malapposition >20% was the strongest risk factor for PSF (Odds ratio 8.0, 95% confidence interval 1.8-45.4, P < 0.01) followed by struts crossing an ostial side branch >30% (Odds ratio 4.2, 95% confidence interval 0.8-24.7, P = 0.09). Our data demonstrate the main pathological predictors for LM stent failure are malapposition and struts crossing an ostial side branch and suggest that imaging-guided PCI may be important. Copyright © 2018 Elsevier B.V. All rights reserved.

A Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

PubMed

Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M; Kjær, Andreas; Langer, Seppo W; Aznar, Marianne C; Persson, Gitte F; Bentzen, Søren M

2018-04-01

The aim of the study was to build a model of first failure site- and lesion-specific failure probability after definitive chemoradiotherapy for inoperable NSCLC. We retrospectively analyzed 251 patients receiving definitive chemoradiotherapy for NSCLC at a single institution between 2009 and 2015. All patients were scanned by fludeoxyglucose positron emission tomography/computed tomography for radiotherapy planning. Clinical patient data and fludeoxyglucose positron emission tomography standardized uptake values from primary tumor and nodal lesions were analyzed by using multivariate cause-specific Cox regression. In patients experiencing locoregional failure, multivariable logistic regression was applied to assess risk of each lesion being the first site of failure. The two models were used in combination to predict probability of lesion failure accounting for competing events. Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than squamous cell carcinoma (HR = 0.45, 95% confidence interval [CI]: 0.26-0.76, p = 0.003). Distant failures were more common in the adenocarcinoma group (HR = 2.21, 95% CI: 1.41-3.48, p < 0.001). Multivariable logistic regression of individual lesions at the time of first failure showed that primary tumors were more likely to fail than lymph nodes (OR = 12.8, 95% CI: 5.10-32.17, p < 0.001). Increasing peak standardized uptake value was significantly associated with lesion failure (OR = 1.26 per unit increase, 95% CI: 1.12-1.40, p < 0.001). The electronic model is available at http://bit.ly/LungModelFDG. We developed a failure site-specific competing risk model based on patient- and lesion-level characteristics. Failure patterns differed between adenocarcinoma and squamous cell carcinoma, illustrating the limitation of aggregating them into NSCLC. Failure site-specific models add complementary information to conventional prognostic models. Copyright © 2018 International Association for the Study of Lung Cancer

First Report of the Resolute Onyx 2.0-mm Zotarolimus-Eluting Stent for the Treatment of Coronary Lesions With Very Small Reference Vessel Diameter.

PubMed

Price, Matthew J; Saito, Shigeru; Shlofmitz, Richard A; Spriggs, Douglas J; Attubato, Michael; McLaurin, Brent; Popma Almonacid, Alexandra; Brar, Sandeep; Liu, Minglei; Moe, Elizabeth; Mehran, Roxana

2017-07-24

The aim of this study was to explore the safety and efficacy of a dedicated drug-eluting stent for the treatment of coronary lesions with very small reference vessel diameter (RVD). Smaller RVD is associated with increased risk for restenosis and target lesion failure (TLF) after stent implantation. This was a prospective, single-arm, multicenter trial of the Resolute Onyx 2.0-mm zotarolimus-eluting stent. The primary endpoint was 12-month TLF, which was compared with a pre-specified performance goal. Subjects with stable or unstable angina or ischemia, target lesions ≤27 mm in length, and RVD ≥2.0 and <2.25 mm were eligible for enrollment. A subset of subjects underwent follow-up angiography at 13 months post-procedure. A total of 101 subjects with 104 lesions were enrolled. The mean age was 67.3 ± 9.6 years, 47% of subjects had diabetes, the mean lesion length was 12.6 ± 6.3 mm, and the mean RVD was 1.91 ± 0.26 mm. The rate of TLF at 12 months was 5.0%, fulfilling the pre-specified performance goal of 19% (p < 0.001). The rates of target lesion revascularization and target vessel myocardial infarction were 2.0% and 3.0%, respectively. There were no episodes of stent thrombosis. In-stent late lumen loss was 0.26 ± 0.48 mm, and the rate of binary restenosis was 12.0%. In this first report of a drug-eluting stent with a dedicated size to treat lesions with RVD <2.25 mm, the Resolute Onyx 2.0-mm zotarolimus-eluting stent was associated with a low rate of TLF and late lumen loss, without a signal for stent thrombosis. This novel-sized drug-eluting stent appears to be a feasible option for the treatment of coronary lesions in extremely small vessels. (Medtronic Resolute Onyx 2.0 mm Clinical Study; NCT02412501). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure.

PubMed

Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

2018-03-24

acetyl-CoA and lactate. This results in histone H3 hyper-acetylation and expression of damage response genes. Inhibition of PDHC and LDH reduces liver damage and improves survival in mice with acute liver failure. Thus, PDHC and LDH are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive deterioration of liver function resulting in high mortality. In experimental mouse models of acute liver failure, we found that two metabolic enzymes, namely pyruvate dehydrogenase complex and lactic dehydrogenase, translocate to the nucleus resulting in detrimental gene expression. Treatment with an inhibitor of these two enzymes was found to reduce liver damage and to improve survival. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Independent predictors of retrograde failure in CTO-PCI after successful collateral channel crossing.

PubMed

Suzuki, Yoriyasu; Muto, Makoto; Yamane, Masahisa; Muramatsu, Toshiya; Okamura, Atsunori; Igarashi, Yasumi; Fujita, Tsutomu; Nakamura, Shigeru; Oida, Akitsugu; Tsuchikane, Etsuo

2017-07-01

To evaluate factors for predicting retrograde CTO-PCI failure after successful collateral channel crossing. Successful guidewire/catheter collateral channel crossing is important for the retrograde approach in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). A total of 5984 CTO-PCI procedures performed in 45 centers in Japan from 2009 to 2012 were studied. The retrograde approach was used in 1656 CTO-PCIs (27.7%). We investigated these retrograde procedures to evaluate factors for predicting retrograde CTO-PCI failure even after successful collateral channel crossing. Successful guidewire/catheter collateral crossing was achieved in 77.1% (n = 1,276) of 1656 retrograde CTO-PCI procedures. Retrograde procedural success after successful collateral crossing was achieved in 89.4% (n = 1,141). Univariate analysis showed that the predictors for retrograde CTO-PCI failure were in-stent occlusion (OR = 1.9829, 95%CI = 1.1783 - 3.3370 P = 0.0088), calcified lesions (OR = 1.9233, 95%CI = 1.2463 - 2.9679, P = 0.0027), and lesion tortuosity (OR = 1.5244, 95%CI = 1.0618 - 2.1883, P = 0.0216). On multivariate analysis, lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing (OR = 1.3472, 95%CI = 1.0614 - 1.7169, P = 0.0141). The success rate of retrograde CTO-PCI following successful guidewire/catheter collateral channel crossing was high in this registry. Lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing. Devices and techniques to overcome complex CTO lesion morphology, such as lesion calcification, are required to further improve the retrograde CTO-PCI success rate. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

PubMed

Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

Hybrid radioguided occult lesion localization (hybrid ROLL) of (18)F-FDG-avid lesions using the hybrid tracer indocyanine green-(99m)Tc-nanocolloid.

PubMed

KleinJan, G H; Brouwer, O R; Mathéron, H M; Rietbergen, D D D; Valdés Olmos, R A; Wouters, M W; van den Berg, N S; van Leeuwen, F W B

2016-01-01

To assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT. Four patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity. A total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology. The hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

[Colonic angiodysplasia in a chronic renal failure patient].

PubMed

Tudor, S; Dima, B; Herlea, V; Chiriac-Babei, Gh; Vasilescu, C

2006-01-01

An important cause of intestinal bleeding in patients with chronic renal failure is angiodysplasia. In retrospective reports up to 19-32% of patients had bleeding from angiodysplastic lesions. These are usually multiple, have a high tendency of rebleeding (25-47%) and are often located in the stomach and duodenum, but can affect the colon and the jejunum as well. Bleeding from angiodysplastic lesions is usually low grade and stops spontaneously in more than 90% of patients, but some times may be life threatening necessitate therapeutic interventions to achieve hemostasis. We report a case of an 18-year old female with renal failure on CAPD who presented a massive lower gastrointestinal bleeding and imposed emergency surgery.

Leakage detection on CT myelography for targeted epidural blood patch in spontaneous cerebrospinal fluid leaks: calcified or ossified spinal lesions ventral to the thecal sac.

PubMed

Yoshida, Hiroki; Takai, Keisuke; Taniguchi, Makoto

2014-09-01

The purpose of this study was to describe significant CT myelography findings for determination of the leak site and outcome of targeted epidural blood patch (EBP) in patients with spontaneous CSF leaks. During 2005-2013, spontaneous CSF leaks were diagnosed for 12 patients with orthostatic headaches. The patients received targeted EBP on the basis of CT myelography assessments. Computed tomography myelograms revealed ventral extradural collection of contrast medium distributed over multiple spinal levels (average 16 levels). Intraforaminal contrast medium extravasations were observed at multiple spinal levels (average 8.2 levels). For 8 (67%) of 12 patients, spinal lesions were noted around the thecal sac and included calcified discs with osteophytes, an ossified posterior longitudinal ligament, and an ossified yellow ligament; lesions were mostly located ventral to the thecal sac and were in close contact with the dura mater. The levels of these spinal lesions were considered potential leak sites and were targeted for EBP. For the remaining 4 patients who did not have definite spinal lesions around the thecal sac, leak site determination was based primarily on the contrast gradient hypothesis. The authors hypothesized that the concentration of extradural contrast medium would be the greatest and the same as that of intradural contrast medium at the leak site but that it would decrease with increased distance from the leak site according to the contrast gradient. Epidural blood patch was placed at the level of spinal lesions and/or of the greatest and same concentration of contrast medium between the intradural and extradural spaces. For 10 of the 12 patients, the orthostatic headaches decreased significantly within a week of EBP and disappeared within a month. For the remaining 2 patients, headaches persisted and medical treatment was required for several months. For 3 patients, thick chronic subdural hematomas caused severe headaches and/or disturbed

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

Finding lesion correspondences in different views of automated 3D breast ultrasound

NASA Astrophysics Data System (ADS)

Tan, Tao; Platel, Bram; Hicks, Michael; Mann, Ritse M.; Karssemeijer, Nico

2013-02-01

Screening with automated 3D breast ultrasound (ABUS) is gaining popularity. However, the acquisition of multiple views required to cover an entire breast makes radiologic reading time-consuming. Linking lesions across views can facilitate the reading process. In this paper, we propose a method to automatically predict the position of a lesion in the target ABUS views, given the location of the lesion in a source ABUS view. We combine features describing the lesion location with respect to the nipple, the transducer and the chestwall, with features describing lesion properties such as intensity, spiculation, blobness, contrast and lesion likelihood. By using a grid search strategy, the location of the lesion was predicted in the target view. Our method achieved an error of 15.64 mm+/-16.13 mm. The error is small enough to help locate the lesion with minor additional interaction.

Altered sarco(endo)plasmic reticulum calcium adenosine triphosphatase 2a content: Targets for heart failure therapy.

PubMed

Liu, Gang; Li, Si Qi; Hu, Ping Ping; Tong, Xiao Yong

2018-05-01

Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is responsible for transporting cytosolic calcium into the sarcoplasmic reticulum and endoplasmic reticulum to maintain calcium homeostasis. Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is the dominant isoform expressed in cardiac tissue, which is regulated by endogenous protein inhibitors, post-translational modifications, hormones as well as microRNAs. Dysfunction of sarco(endo)plasmic reticulum calcium adenosine triphosphatase is associated with heart failure, which makes sarco(endo)plasmic reticulum calcium adenosine triphosphatase a promising target for heart failure therapy. This review summarizes current approaches to ameliorate sarco(endo)plasmic reticulum calcium adenosine triphosphatase function and focuses on phospholamban, an endogenous inhibitor of sarco(endo)plasmic reticulum calcium adenosine triphosphatase, pharmacological tools and gene therapies.

CORRELATION OF LOCAL FAILURE WITH MEASURES OF DOSE INSUFFICIENCY IN THE HIGH-DOSE SINGLE-FRACTION TREATMENT OF BONY METASTASES

PubMed Central

Lovelock, D. Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya

2011-01-01

Purpose In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. Methods and Materials The minimum doses received by the hottest 100%, 98%, and 95% (Dmin, D98, and D95) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18–24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12–14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. Results With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV Dmin, D98, and D95 for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for Dmin, D98, and D95 were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. Conclusions The results indicate that Dmin, D98, and D95 may be important risk factors for local failure. No local failures in any histology were observed when Dmin was >15 Gy, suggesting that this metric may be an important predictor of local control. PMID:20350795

CT-guided transthoracic core needle biopsy for small pulmonary lesions: diagnostic performance and adequacy for molecular testing.

PubMed

Tian, Panwen; Wang, Ye; Li, Lei; Zhou, Yongzhao; Luo, Wenxin; Li, Weimin

2017-02-01

Computed tomography (CT)-guided transthoracic needle biopsy is a well-established, minimally invasive diagnostic tool for pulmonary lesions. Few large studies have been conducted on the diagnostic performance and adequacy for molecular testing of transthoracic core needle biopsy (TCNB) for small pulmonary lesions. This study included CT-guided TCNB with 18-gauge cutting needles in 560 consecutive patients with small (≤3 cm) pulmonary lesions from January 2012 to January 2015. There were 323 males and 237 females, aged 51.8±12.7 years. The size of the pulmonary lesions was 1.8±0.6 cm. The sensitivity, specificity, accuracy and complications of the biopsies were investigated. The risk factors of diagnostic failure were assessed using univariate and multivariate analyses. The sample's adequacy for molecular testing of non-small cell lung cancer (NSCLC) was analyzed. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy were 92.0% (311/338), 98.6% (219/222), and 94.6% (530/560), respectively. The incidence of bleeding complications was 22.9% (128/560), and the incidence of pneumothorax was 10.4% (58/560). Logistic multivariate regression analysis showed that the independent risk factors for diagnostic failure were a lesion size ≤1 cm [odds ratio (OR), 3.95; P=0.007], lower lobe lesions (OR, 2.83; P=0.001), and pneumothorax (OR, 1.98; P=0.004). Genetic analysis was successfully performed on 95.45% (168/176) of specimens diagnosed as NSCLC. At least 96.8% of samples with two or more passes from a lesion were sufficient for molecular testing. The diagnostic yield of small pulmonary lesions by CT-guided TCNB is high, and the procedure is relatively safe. A lesion size ≤1 cm, lower lobe lesions, and pneumothorax are independent risk factors for biopsy diagnostic failure. TCNB specimens could provide adequate tissues for molecular testing.

Automated segmentation of chronic stroke lesions using LINDA: Lesion Identification with Neighborhood Data Analysis

PubMed Central

Pustina, Dorian; Coslett, H. Branch; Turkeltaub, Peter E.; Tustison, Nicholas; Schwartz, Myrna F.; Avants, Brian

2015-01-01

The gold standard for identifying stroke lesions is manual tracing, a method that is known to be observer dependent and time consuming, thus impractical for big data studies. We propose LINDA (Lesion Identification with Neighborhood Data Analysis), an automated segmentation algorithm capable of learning the relationship between existing manual segmentations and a single T1-weighted MRI. A dataset of 60 left hemispheric chronic stroke patients is used to build the method and test it with k-fold and leave-one-out procedures. With respect to manual tracings, predicted lesion maps showed a mean dice overlap of 0.696±0.16, Hausdorff distance of 17.9±9.8mm, and average displacement of 2.54±1.38mm. The manual and predicted lesion volumes correlated at r=0.961. An additional dataset of 45 patients was utilized to test LINDA with independent data, achieving high accuracy rates and confirming its cross-institutional applicability. To investigate the cost of moving from manual tracings to automated segmentation, we performed comparative lesion-to-symptom mapping (LSM) on five behavioral scores. Predicted and manual lesions produced similar neuro-cognitive maps, albeit with some discussed discrepancies. Of note, region-wise LSM was more robust to the prediction error than voxel-wise LSM. Our results show that, while several limitations exist, our current results compete with or exceed the state-of-the-art, producing consistent predictions, very low failure rates, and transferable knowledge between labs. This work also establishes a new viewpoint on evaluating automated methods not only with segmentation accuracy but also with brain-behavior relationships. LINDA is made available online with trained models from over 100 patients. PMID:26756101

Reactive oral lesions associated with dental implants. A systematic review.

PubMed

Atarbashi-Moghadam, Fazele; Atarbashi-Moghadam, Saede; Namdari, Mahshid; Shahrabi-Farahani, Shokoufeh

2018-05-11

Reactive lesion formation around dental implants a complication that has been given much consideration. These lesions can lead to marginal bone loss, and consequently, implant failure. In the present systematic review, all reported reactive lesions associated with dental implants in the literature were assessed. An electronic search was performed using PubMed Central, Scopus, Google Scholar, and Science Direct. The search strategy was limited to human studies (case reports and case series), full-text English language articles, published until May 2017. A total of 19 articles reporting 27 lesions in 25 cases were included. Peripheral giant cell granuloma and pyogenic granuloma were the most reactive lesions found around dental implants. The mean age of the patients was 51.28 ± 14.48 years, with a slight female predilection. Posterior mandibular gingiva was the most common location for these lesions. The recurrence rate of lesions was 33.33%, and the chance of implant removal was 29.62%. Due to the clinical significance of these lesions, early histopathologic examination is recommended to exclude the presence of such pathological lesions. © 2018 John Wiley & Sons Australia, Ltd.

Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.

PubMed

Methner, Carmen; Chouchani, Edward T; Buonincontri, Guido; Pell, Victoria R; Sawiak, Stephen J; Murphy, Michael P; Krieg, Thomas

2014-07-01

Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure. Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis. MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Understanding chronic heart failure

PubMed Central

Fenton, Matthew; Burch, Michael

2007-01-01

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality. PMID:17715446

Lesion Size Does Not Predict Outcomes in Fresh Osteochondral Allograft Transplantation.

PubMed

Tírico, Luis E P; McCauley, Julie C; Pulido, Pamela A; Bugbee, William D

2018-03-01

Cartilage repair algorithms use lesion size to choose surgical techniques when selecting a cartilage repair procedure. The association of fresh osteochondral allograft (OCA) size with graft survivorship and subjective patient outcomes is still unknown. To determine if lesion size (absolute or relative) affects outcomes after OCA transplantation. Cohort study; Level of evidence, 3. The study included 156 knees in 143 patients who underwent OCA transplantation from 1998 to 2014 for isolated femoral condyle lesions. The mean age was 29.6 ± 11.4 years, and 62.9% were male. The majority of patients (62.2%) presented for cartilage repair because of osteochondritis dissecans. The mean graft area, used as a surrogate for absolute size of the lesion, was 6.4 cm 2 (range, 2.3-11.5 cm 2 ). The relative size of the lesion was calculated as the tibial width ratio (TWR; ratio of graft area to tibial width) and affected femoral condyle ratio (AFCR; ratio of graft area to affected femoral condyle width) using preoperative radiographs. All patients had a minimum follow-up of 2 years. Further surgical procedures were documented, and graft failure was defined as revision OCA transplantation or conversion to arthroplasty. International Knee Documentation Committee (IKDC) pain, function, and total scores were obtained. Satisfaction with OCA transplantation was assessed. The mean follow-up among patients with grafts remaining in situ was 6.0 years (range, 1.9-16.5 years). The OCA failure rate was 5.8%. Overall survivorship of the graft was 97.2% at 5 years and 93.5% at 10 years. No difference in postoperative outcomes between groups was found in absolute or relative size. Change in IKDC scores (from preoperative to latest follow-up) was greater for knees with large lesions compared to knees with small lesions, among all measurement methods. Overall satisfaction with the results of OCA transplantation was 89.8%. The size of the lesion, either absolute or relative, does not influence

Targeting SQSTM1/p62 Induces Cargo Loading Failure and Converts Autophagy to Apoptosis via NBK/Bik

PubMed Central

Chen, Shuang; Zhou, Liang; Zhang, Yu; Leng, Yun; Pei, Xin-Yan; Lin, Hui; Jones, Richard; Orlowski, Robert Z.

2014-01-01

In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cyclin T1 transcriptionally downregulated SQSTM1/p62 but did not affect autophagic flux. These interventions, or short hairpin RNA (shRNA) directly targeting SQSTM1/p62, resulted in cargo loading failure and inefficient autophagy, phenomena recently described for Huntington's disease neurons. These events led to the accumulation of the BH3-only protein NBK/Bik on endoplasmic reticulum (ER) membranes, most likely by blocking loading and autophagic degradation of NBK/Bik, culminating in apoptosis. Whereas NBK/Bik upregulation was further enhanced by disruption of distal autophagic events (e.g., autophagosome maturation) by chloroquine (CQ) or Lamp2 shRNA, it was substantially diminished by inhibition of autophagy initiation (e.g., genetically by shRNA targeting Ulk1, beclin-1, or Atg5 or pharmacologically by 3-methyladenine [3-MA] or spautin-1), arguing that NBK/Bik accumulation stems from inefficient autophagy. Finally, NBK/Bik knockdown markedly attenuated apoptosis in vitro and in vivo. Together, these findings identify novel cross talk between autophagy and apoptosis, wherein targeting SQSTM1/p62 converts cytoprotective autophagy to an inefficient form due to cargo loading failure, leading to NBK/Bik accumulation, which triggers apoptosis. PMID:25002530

Correlation of local failure with measures of dose insufficiency in the high-dose single-fraction treatment of bony metastases.

PubMed

Lovelock, D Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya

2010-07-15

In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. The minimum doses received by the hottest 100%, 98%, and 95% (D(min), D(98), and D(95)) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D(min), D(98), and D(95) for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D(min), D(98), and D(95) were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. The results indicate that D(min), D(98), and D(95) may be important risk factors for local failure. No local failures in any histology were observed when D(min) was >15 Gy, suggesting that this metric may be an important predictor of local control. Copyright 2010 Elsevier Inc. All rights reserved.

Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammel, Markus; Michel, Geert; Hoefer, Christina

2007-08-10

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies inmore » type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.« less

Extraoral sinus tract misdiagnosed as an endodontic lesion.

PubMed

Cohenca, Nestor; Karni, Sunil; Rotstein, Ilan

2003-12-01

The extraoral sinus tract may occur as a result of an inflammatory process associated with a necrotic pulp. However, several non-odontogenic disorders may also produce an extraoral sinus tract. Thus, the differential diagnosis of this clinical finding is of paramount importance in providing appropriate clinical care because misdiagnosis of this condition may result in healing failure or unnecessary treatment. This case report of a 19-yr-old male patient describes an extraoral cutaneous sinus tract misdiagnosed as an endodontic lesion. Consequently, the patient underwent unnecessary exploratory procedures and antibiotic therapy. Identification of the inflammatory source of the lesion and removal of the affected tissue led to tissue healing.

Electromagnetic navigation system for CT-guided biopsy of small lesions.

PubMed

Appelbaum, Liat; Sosna, Jacob; Nissenbaum, Yizhak; Benshtein, Alexander; Goldberg, S Nahum

2011-05-01

The purpose of this study was to evaluate an electromagnetic navigation system for CT-guided biopsy of small lesions. Standardized CT anthropomorphic phantoms were biopsied by two attending radiologists. CT scans of the phantom and surface electromagnetic fiducial markers were imported into the memory of the 3D electromagnetic navigation system. Each radiologist assessed the accuracy of biopsy using electromagnetic navigation alone by targeting sets of nine lesions (size range, 8-14 mm; skin to target distance, 5.7-12.8 cm) under eight different conditions of detector field strength and orientation (n = 117). As a control, each radiologist also biopsied two sets of five targets using conventional CT-guided technique. Biopsy accuracy, number of needle passes, procedure time, and radiation dose were compared. Under optimal conditions (phantom perpendicular to the electromagnetic receiver at highest possible field strength), phantom accuracy to the center of the lesion was 2.6 ± 1.1 mm. This translated into hitting 84.4% (38/45) of targets in a single pass (1.1 ± 0.4 CT confirmations), which was significantly fewer than the 3.6 ± 1.3 CT checks required for conventional technique (p < 0.001). The mean targeting time was 38.8 ± 18.2 seconds per lesion. Including procedural planning (∼5.5 minutes) and final CT confirmation of placement (∼3.5 minutes), the full electromagnetic tracking procedure required significantly less time (551.6 ± 87.4 seconds [∼9 minutes]) than conventional CT (833.3 ± 283.8 seconds [∼14 minutes]) for successful targeting (p < 0.001). Less favorable conditions, including nonperpendicular relation between the axis of the machine and weaker field strength, resulted in statistically significant lower accuracy (3.7 ± 1 mm, p < 0.001). Nevertheless, first-pass biopsy accuracy was 58.3% (21/36) and second-pass (35/36) accuracy was 97.2%. Lesions farther from the skin than 20-25 cm were out of range for successful electromagnetic tracking

Assessment of cerebral microbleeds by susceptibility-weighted imaging at 3T in patients with end-stage organ failure.

PubMed

Sparacia, Gianvincenzo; Cannella, Roberto; Lo Re, Vincenzina; Gambino, Angelo; Mamone, Giuseppe; Miraglia, Roberto

2018-02-17

Cerebral microbleeds (CMBs) are small rounded lesions representing cerebral hemosiderin deposits surrounded by macrophages that results from previous microhemorrhages. The aim of this study was to review the distribution of cerebral microbleeds in patients with end-stage organ failure and their association with specific end-stage organ failure risk factors. Between August 2015 and June 2017, we evaluated 15 patients, 9 males, and 6 females, (mean age 65.5 years). Patients population was subdivided into three groups according to the organ failure: (a) chronic kidney failure (n = 8), (b) restrictive cardiomyopathy undergoing heart transplantation (n = 1), and (c) end-stage liver failure undergoing liver transplantation (n = 6). The MR exams were performed on a 3T MR unit and the SWI sequence was used for the detection of CMBs. CMBs were subdivided in supratentorial lobar distributed, supratentorial non-lobar distributed, and infratentorial distributed. A total of 91 microbleeds were observed in 15 patients. Fifty-nine CMBs lesions (64.8%) had supratentorial lobar distribution, 17 CMBs lesions (18.8%) had supratentorial non-lobar distribution and the remaining 15 CMBs lesions (16.4%) were infratentorial distributed. An overall predominance of supratentorial multiple lobar localizations was found in all types of end-stage organ failure. The presence of CMBs was significantly correlated with age, hypertension, and specific end-stage organ failure risk factors (p < 0.001). CMBs are mostly founded in supratentorial lobar localization in end-stage organ failure. The improved detection of CMBs with SWI sequences may contribute to a more accurate identification of patients with cerebral risk factors to prevent complications during or after the organ transplantation.

Lesion search and recognition by thymine DNA glycosylase revealed by single molecule imaging

PubMed Central

Buechner, Claudia N.; Maiti, Atanu; Drohat, Alexander C.; Tessmer, Ingrid

2015-01-01

The ability of DNA glycosylases to rapidly and efficiently detect lesions among a vast excess of nondamaged DNA bases is vitally important in base excision repair (BER). Here, we use single molecule imaging by atomic force microscopy (AFM) supported by a 2-aminopurine fluorescence base flipping assay to study damage search by human thymine DNA glycosylase (hTDG), which initiates BER of mutagenic and cytotoxic G:T and G:U mispairs in DNA. Our data reveal an equilibrium between two conformational states of hTDG–DNA complexes, assigned as search complex (SC) and interrogation complex (IC), both at target lesions and undamaged DNA sites. Notably, for both hTDG and a second glycosylase, hOGG1, which recognizes structurally different 8-oxoguanine lesions, the conformation of the DNA in the SC mirrors innate structural properties of their respective target sites. In the IC, the DNA is sharply bent, as seen in crystal structures of hTDG lesion recognition complexes, which likely supports the base flipping required for lesion identification. Our results support a potentially general concept of sculpting of glycosylases to their targets, allowing them to exploit the energetic cost of DNA bending for initial lesion sensing, coupled with continuous (extrahelical) base interrogation during lesion search by DNA glycosylases. PMID:25712093

Combining clinical and angiographic variables for estimating risk of target lesion revascularization after drug eluting stent placement.

PubMed

Stolker, Joshua M; Cohen, David J; Kennedy, Kevin F; Pencina, Michael J; Arnold, Suzanne V; Kleiman, Neal S; Spertus, John A

Drug-eluting stents (DES) reduce restenosis but require prolonged antiplatelet therapy, when compared with bare metal stents. Ideally, the patient should be involved in this risk:benefit assessment prior to selecting DES, to maximize the benefits and cost-effectiveness of care, and to improve medication adherence. However, accurate estimation of restenosis risk may require angiographic factors identified at cardiac catheterization. In a large PCI registry, we used logistic regression to identify clinical and angiographic predictors of clinically-driven target lesion revascularization (TLR) over the first year after stent placement. Discrimination c-statistic and integrated discrimination improvement (IDI) were used to calculate the incremental utility of angiographic variables when added to clinical predictors. Of 8501 PCI patients, TLR occurred in 4.5%. After adjusting for DES use, clinical TLR predictors were younger age, female sex, diabetes, prior PCI, and prior bypass surgery (model c-statistic 0.630). Angiographic predictors were vein graft PCI, in-stent restenosis lesion, longer stent length, and smaller stent diameter (c-statistic 0.650). After adding angiographic factors to the clinical model, c-statistic improved to 0.680 and the average separation in TLR risk among patients with and without TLR improved by 1% (IDI=0.010, 95% CI 0.009-0.014), primarily driven by those experiencing TLR (from 5.9% to 6.9% absolute risk). Among unselected PCI patients, the incidence of clinically-indicated TLR is <5% at 1-year, and standard clinical variables only moderately discriminate who will and will not experience TLR. Angiographic variables significantly improve TLR risk assessment, suggesting that stent selection may be best performed after coronary anatomy has been delineated. Although several recent studies have challenged traditional expectations regarding the duration of dual antiplatelet therapy, current guidelines recommend at least 6 to 12months of treatment

[Acute kidney failure in infectious mononucleosis].

PubMed

Ramelli, G P; Marone, C; Truniger, B

1990-10-27

Overt renal disease is a rare complication of infectious mononucleosis (MI). In contrast, up to 16% of patients with MI have been shown to exhibit abnormalities in urinary sediment. Histological abnormalities--usually interstitial nephritis, and occasionally glomerular lesions--are rather common. Clinical symptoms include in rare cases isolated macrohematuria, occasionally a nephrotic or nephritic syndrome, and more commonly acute renal failure due to rhabdomyolysis, hepatorenal syndrome or acute interstitial nephritis. We report two observations of acute renal failure with a typically benign course and discuss these observations in the light of an updated literature survey of 34 patients.

SU-F-T-613: Multi-Lesion Cranial SRS VMAT Plan Quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballangrud, A; Kuo, L; Happersett, L

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs weremore » used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI < 5 can be achieved for lesions > 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes <0.1cc GI<9, 0.1–0.4cc GI<6, 0.4–0.1.0cc GI<5, and for volumes >1.0cc GI<4. CI is < 1.3 for all lesions except for targets < 0.1cc. Cranial SRS VMAT plans must be optimized to lower the GI to reduce the dose to normal brain tissue.« less

Primary Prevention of Heart Failure

PubMed Central

Butler, Javed

2012-01-01

Most heart failure research and quality improvement efforts are targeted at treatment and secondary prevention of patients with manifest heart failure. This is distinct from coronary disease where primary prevention has been a focus for over three decades. Given the current importance and the projected worsening of heart failure epidemiology, a more focused effort on prevention is urgently needed. PMID:22957272

Narrowing the scope of failure prediction using targeted fault load injection

NASA Astrophysics Data System (ADS)

Jordan, Paul L.; Peterson, Gilbert L.; Lin, Alan C.; Mendenhall, Michael J.; Sellers, Andrew J.

2018-05-01

As society becomes more dependent upon computer systems to perform increasingly critical tasks, ensuring that those systems do not fail becomes increasingly important. Many organizations depend heavily on desktop computers for day-to-day operations. Unfortunately, the software that runs on these computers is written by humans and, as such, is still subject to human error and consequent failure. A natural solution is to use statistical machine learning to predict failure. However, since failure is still a relatively rare event, obtaining labelled training data to train these models is not a trivial task. This work presents new simulated fault-inducing loads that extend the focus of traditional fault injection techniques to predict failure in the Microsoft enterprise authentication service and Apache web server. These new fault loads were successful in creating failure conditions that were identifiable using statistical learning methods, with fewer irrelevant faults being created.

Evaluation of Genetic Polymorphism of Leishmania (V.) braziliensis Isolates Obtained from the Same Patient before and after Therapeutic Failure or Reactivation of Cutaneous Lesions

PubMed Central

Baptista, Cibele; Schubach, Armando de Oliveira; Madeira, Maria de Fatima; de Freitas Campos Miranda, Luciana; Guimarães de Souza Pinto, Andressa; Helena da Silva Barros, Juliana; Conceição-Silva, Fatima; Fernandes Pimentel, Maria Ines; da Silva Pacheco, Raquel

2012-01-01

The aim of this study was to investigate genetic polymorphism in Leishmania braziliensis population previously typed through isoenzyme electrophoresis, isolated from the same patient in two different moments: (A) before the beginning of treatment and (B) after treatment failure to meglumine antimoniate or reactivation after successful initial treatment. Fifteen pairs of isolates were assessed using the polymorphic molecular marker LSSP-PCR and following the phenetic analysis. The genetic profiles of the 30 samples were grouped in four clusters. Only two patients presented total identity in the A and B isolates. Most isolates presented similarity coefficients varying from 0.63 to 0.91. In this group of patients genetic polymorphisms could be observed indicating low similarity between the pairs of isolates. The results demonstrate the existence of genetic polymorphism between the samples isolated before treatment and after reactivation or treatment failure, suggesting a possible differentiation of the structure of the original parasite population which could be involved in the mechanisms of resistance to treatment or reactivation of lesions in the ATL. This phenomenon is important, although other factors also could be involved in this context and are discussed in this paper. PMID:23304168

Sulfur-oxidizing bacterial populations within cyanobacterial dominated coral disease lesions.

PubMed

Bourne, David G; van der Zee, Marc J J; Botté, Emmanuelle S; Sato, Yui

2013-08-01

This study investigated the diversity and quantitative shifts of sulfur-oxidizing bacteria (SOB) during the onset of black band disease (BBD) in corals using quantitative PCR (qPCR) and cloning approaches targeting the soxB gene, involved in sulfur oxidation. Four Montipora sp. coral colonies identified with lesions previously termed cyanobacterial patches (CP) (comprising microbial communities different from those of BBD lesions), was monitored in situ as CP developed into BBD. The overall abundance of SOB in both CP and BBD lesions were very low and near the detection limit of the qPCR assay, although consistently indicated that SOB populations decreased as the lesions transitioned from CP to BBD. Phylogenetic assessment of retrieved soxB genes showed that SOB in both CP and BBD lesions were dominated by one sequence type, representing > 70% of all soxB gene sequences and affiliated with members of the Rhodobacteraceae within the α-Proteobacteria. This study represents the first assessment targeting SOB within BBD lesions and clearly shows that SOB are not highly diverse or abundant in this complex microbial mat. The lack of oxidation of reduced sulfur compounds by SOB likely aids the accumulation of high levels of sulfide at the base of the BBD mat, a compound contributing to the pathogenicity of BBD lesions. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Dialysis Arteriovenous Fistula Failure and Angioplasty: Intimal Hyperplasia and Other Causes of Access Failure.

PubMed

Duque, Juan C; Tabbara, Marwan; Martinez, Laisel; Cardona, Jose; Vazquez-Padron, Roberto I; Salman, Loay H

2017-01-01

The arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients' morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty continues to be the gold-standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a 2-stage brachiobasilic AVF that was complicated by failure 4 months after creation. An angiogram showed multiple juxta-anastomotic and midfistula stenotic lesions. Percutaneous transluminal angioplasty was successful in assisting maturation and subsequently cannulating the AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis because biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH and highlights the need for more therapeutic options to reduce AVF failure rate. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Heart Failure in Women

PubMed Central

Bozkurt, Biykem; Khalaf, Shaden

2017-01-01

Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women. PMID:29744014

Zebrafish heart failure models: opportunities and challenges.

PubMed

Shi, Xingjuan; Chen, Ru; Zhang, Yu; Yun, Junghwa; Brand-Arzamendi, Koroboshka; Liu, Xiangdong; Wen, Xiao-Yan

2018-05-03

Heart failure is a complex pathophysiological syndrome of pumping functional failure that results from injury, infection or toxin-induced damage on the myocardium, as well as genetic influence. Gene mutations associated with cardiomyopathies can lead to various pathologies of heart failure. In recent years, zebrafish, Danio rerio, has emerged as an excellent model to study human cardiovascular diseases such as congenital heart defects, cardiomyopathy, and preclinical development of drugs targeting these diseases. In this review, we will first summarize zebrafish genetic models of heart failure arose from cardiomyopathy, which is caused by mutations in sarcomere, calcium or mitochondrial-associated genes. Moreover, we outline zebrafish heart failure models triggered by chemical compounds. Elucidation of these models will improve the understanding of the mechanism of pathogenesis and provide potential targets for novel therapies.

The most common mistakes on dermatoscopy of melanocytic lesions

PubMed Central

Kamińska-Winciorek, Grażyna

2015-01-01

Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists. PMID:25821425

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

Restorations in abrasion/erosion cervical lesions: 8-year results of a triple blind randomized controlled trial.

PubMed

Dall'Orologio, Giovanni Dondi; Lorenzi, Roberta

2014-10-01

An equivalence randomized controlled trial within the subject was organized to evaluate the clinical long-term success of a new 2-step etch & rinse adhesive and a new nano-filled ormocer. 50 subjects, 21 males and 29 females aged between 21 and 65, were randomized to receive 150 restorations, 100 with the new restorative material, 50 with the composite as control, placed in non-carious cervical lesions with the same bonding system. The main outcome measure was the cause of failure at 8 years. Randomization was number table-generated, with allocation concealment by opaque sequentially numbered sealed and stapled envelopes. Subjects, examiner, and analyst were blinded to group assignment. Two interim analyses were performed. Data were analyzed by ANOVA and Cox test (P < 0.05). After 8 years, 40 subjects and 120 teeth were included in the analysis of the primary outcome. There were eight failures in the experimental group and four failures in the control group. The cumulative loss rate was 7% for both restorative materials, with the annual failure lower than 1%, without any statistically significant difference. There were two key elements of failure: the presence of sclerotic dentin and the relationship between lesion and gingival margin.

Culotte stenting for coronary bifurcation lesions with 2nd and 3rd generation everolimus-eluting stents: the CELTIC Bifurcation Study.

PubMed

Walsh, Simon J; Hanratty, Colm G; Watkins, Stuart; Oldroyd, Keith G; Mulvihill, Niall T; Hensey, Mark; Chase, Alex; Smith, Dave; Cruden, Nick; Spratt, James C; Mylotte, Darren; Johnson, Tom; Hill, Jonathan; Hussein, Hafiz M; Bogaerts, Kris; Morice, Marie-Claude; Foley, David P

2018-05-24

The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern-generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2-connector SYNERGY. Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES. A total of 170 patients were included. Technical success and final kissing balloon inflation occurred in >96% of cases. Major adverse cardiovascular or cerebrovascular events (MACCE: a composite of death, myocardial infarction [MI], cerebrovascular accident [CVA] and target vessel revascularisation [TVR]) occurred in 5.9% of patients by nine months. The primary endpoint was a composite of death, MI, CVA, target vessel failure (TVF), stent thrombosis and binary angiographic restenosis. At nine months, the primary endpoint occurred in 19% of XIENCE patients and 16% of SYNERGY patients (p=0.003 for non-inferiority for platform performance). MACCE rates for culotte stenting using contemporary everolimus-eluting DES are low at nine months. The XIENCE and SYNERGY stents demonstrated comparable performance for the primary endpoint.

Multi-institutional application of Failure Mode and Effects Analysis (FMEA) to CyberKnife Stereotactic Body Radiation Therapy (SBRT).

PubMed

Veronese, Ivan; De Martin, Elena; Martinotti, Anna Stefania; Fumagalli, Maria Luisa; Vite, Cristina; Redaelli, Irene; Malatesta, Tiziana; Mancosu, Pietro; Beltramo, Giancarlo; Fariselli, Laura; Cantone, Marie Claire

2015-06-13

A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife® Centres. The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered. The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value. The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety.

[Focusing on MRI-suspected lesions in targeted transrectal prostate biopsy guided by MRI-TRUS fusion imaging for the diagnosis of prostate cancer].

PubMed

Qu, Hua-Wei; Liu, Hui; Cui, Zi-Lian; Jin, Xun-Bo; Zhao, Yong; Wang, Mu-Wen; Song, Wei; Zhang, Xin-Juan

2016-09-01

To improve the accuracy of prostate cancer (PCa) detection by focusing biopsy on the suspected lesion manifested by MRI with the total number of biopsy cores relatively unchanged. A prospective randomized analysis was performed on 262 cases of suspected PCa detected by multi-parametric MRI (mp-MRI), each with a single suspected lesion with 10 μg/L≤ PSA <20 μg/L. All the patients underwent targeted transrectal prostate biopsy guided by fusion imaging of MRI with transrectal ultrasonography (TRUS), using the 6X+6 strategy (6 cores in the suspected region and another 6 in the systematic prostate) for 134 cases and the traditional 12+2X method (12 cores in the systematic prostate and 2 in the suspected region) for the other 128. Comparisons were made between the two methods in the PCa detection rate in the cases of suspected lesion, total PCa detection rate, incidence of post-biopsy complications, and Gleason scores. Analyses were performed on the prostate imaging reporting and data system (PI-RADS) score, location, transverse section, and diameter of the suspected lesion. Both the total PCa detection rate and that in the cases of suspected lesion were significantly higher in the 6X+6 (44.8% and 37.3%) than in the 12+2X group (37.5% and 27.3%) (P<0.05). MRI showed that the suspected lesions were mostly (45%) located in the middle part of the prostate, the mean area of the transverse section was (0.48±0.11) cm2, and the mean diameter of the tumor was (8.51±2.21) mm. The results of biopsy showed that low-grade tumors (Gleason 3+3=6) accounted for 68% in the 6X+6 group and 71% in the 12+2X group. No statistically significant differences were found between the two groups in the incidence rate of post-biopsy complications. Compared with the traditional 12+2X method, for the suspected lesion manifested by mp-MRI, focusing biopsy on the suspected region with the 6X+6 strategy can achieve a higher PCa detection rate without increasing the incidence of complications.

The effect of expert knowledge on medical search: medical experts have specialized abilities for detecting serious lesions.

PubMed

Nakashima, Ryoichi; Watanabe, Chisaki; Maeda, Eriko; Yoshikawa, Takeharu; Matsuda, Izuru; Miki, Soichiro; Yokosawa, Kazuhiko

2015-09-01

How does domain-specific knowledge influence the experts' performance in their domain of expertise? Specifically, can visual search experts find, with uniform efficiency, any type of target in their domain of expertise? We examined whether acquired knowledge of target importance influences an expert's visual search performance. In some professional searches (e.g., medical screenings), certain targets are rare; one aim of this study was to examine the extent to which experts miss such targets in their searches. In one experiment, radiologists (medical experts) engaged in a medical lesion search task in which both the importance (i.e., seriousness/gravity) and the prevalence of targets varied. Results showed decreased target detection rates in the low prevalence conditions (i.e., the prevalence effect). Also, experts were better at detecting important (versus unimportant) lesions. Results of an experiment using novices ruled out the possibility that decreased performance with unimportant targets was due to low target noticeability/visibility. Overall, the findings suggest that radiologists do not have a generalized ability to detect any type of lesion; instead, they have acquired a specialized ability to detect only those important lesions relevant for effective medical practices.

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

PubMed Central

Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

2012-01-01

Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting

Visual Search of Experts in Medical Image Reading: The Effect of Training, Target Prevalence, and Expert Knowledge

PubMed Central

Nakashima, Ryoichi; Kobayashi, Kazufumi; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

2013-01-01

The aims of this study are (a) To determine the effect of training on the multiple-target lesion search performance; and (b) To examine the effect of target prevalence on the performance of radiologists and novices. We conducted four sessions of 500 trials in a lesion search on a medical image task in which participants searched for three different target lesions. Participants were 10 radiologists and novices. In each session, the prevalence of the different target lesions varied from low (2%) to high (40%). The sensitivity of novices was higher in the later sessions than in the first session, whereas there were no differences among sessions in radiologists. The improvement on sensitivity of novices was largely due to attenuations of false alarm (FA) errors. In addition, miss rates of the three targets did not differ in data of novices, whereas radiologists produced a higher miss rate for the highest prevalence target lesion (non-serious lesion) than for the other two lesions (serious lesions). The conclusions are (a) The training for the multiple-target lesion search task can be effective to reduce FA errors; and (b) The prevalence effect on lesion search can be attenuated by the multiple-target identification and the knowledge about seriousness of lesions. This suggests that acquired knowledge about normal cases and serious lesions is an important aspect of a radiologists’ skill in searching for medical lesions and their high performance levels. PMID:23576997

Visual search of experts in medical image reading: the effect of training, target prevalence, and expert knowledge.

PubMed

Nakashima, Ryoichi; Kobayashi, Kazufumi; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

2013-01-01

The aims of this study are (a) To determine the effect of training on the multiple-target lesion search performance; and (b) To examine the effect of target prevalence on the performance of radiologists and novices. We conducted four sessions of 500 trials in a lesion search on a medical image task in which participants searched for three different target lesions. Participants were 10 radiologists and novices. In each session, the prevalence of the different target lesions varied from low (2%) to high (40%). The sensitivity of novices was higher in the later sessions than in the first session, whereas there were no differences among sessions in radiologists. The improvement on sensitivity of novices was largely due to attenuations of false alarm (FA) errors. In addition, miss rates of the three targets did not differ in data of novices, whereas radiologists produced a higher miss rate for the highest prevalence target lesion (non-serious lesion) than for the other two lesions (serious lesions). The conclusions are (a) The training for the multiple-target lesion search task can be effective to reduce FA errors; and (b) The prevalence effect on lesion search can be attenuated by the multiple-target identification and the knowledge about seriousness of lesions. This suggests that acquired knowledge about normal cases and serious lesions is an important aspect of a radiologists' skill in searching for medical lesions and their high performance levels.

Impact of stepwise ablation on the biatrial substrate in patients with persistent atrial fibrillation and heart failure.

PubMed

Jones, David G; Haldar, Shouvik K; Jarman, Julian W E; Johar, Sofian; Hussain, Wajid; Markides, Vias; Wong, Tom

2013-08-01

Ablation of persistent atrial fibrillation can be challenging, often involving not only pulmonary vein isolation (PVI) but also additional linear lesions and ablation of complex fractionated electrograms (CFE). We examined the impact of stepwise ablation on a human model of advanced atrial substrate of persistent atrial fibrillation in heart failure. In 30 patients with persistent atrial fibrillation and left ventricular ejection fraction ≤35%, high-density CFE maps were recorded biatrially at baseline, in the left atrium (LA) after PVI and linear lesions (roof and mitral isthmus), and biatrially after LA CFE ablation. Surface area of CFE (mean cycle length ≤120 ms) remote to PVI and linear lesions, defined as CFE area, was reduced after PVI (18.3±12.03 to 10.2±7.1 cm(2); P<0.001) and again after linear lesions (7.7±6.5 cm(2); P=0.006). Complete mitral isthmus block predicted greater CFE reduction (P=0.02). Right atrial CFE area was reduced by LA ablation, from 25.9±14.1 to 12.9±11.8 cm(2) (P<0.001). Estimated 1-year arrhythmia-free survival was 72% after a single procedure. Incomplete linear lesion block was an independent predictor of arrhythmia recurrence (hazard ratio, 4.69; 95% confidence interval, 1.05-21.06; P=0.04). Remote LA CFE area was progressively reduced following PVI and linear lesions, and LA ablation reduced right atrial CFE area. Reduction of CFE area at sites remote from ablation would suggest either regression of the advanced atrial substrate or that these CFE were functional phenomena. Nevertheless, in an advanced atrial fibrillation substrate, linear lesions after PVI diminished the target area for CFE ablation, and complete lesions resulted in a favorable clinical outcome.

Heart failure—potential new targets for therapy

PubMed Central

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

PubMed

Miller, Ross A; Mody, Dina R; Tams, Kimberlee C; Thrall, Michael J

2015-11-01

The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques. To evaluate the detection rate of glandular lesions with screening techniques currently used for cervical cancer screening and to provide insight as to which techniques are most efficacious in our study population. We retrospectively reviewed any available cytology, human papillomavirus (HPV), and histologic malignancy data in patients diagnosed with adenocarcinoma in situ and adenocarcinoma from 2 geographically and socioeconomically disparate hospital systems. Identified patients having had a negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or adenocarcinoma tissue diagnosis were considered Pap test screening failures. Patients with negative HPV tests on cytology samples were considered HPV screening failures. One hundred thirty cases were identified (age range, 22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining cases (8.8%) were screening failures. The detected sensitivity for identifying adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were 7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus 42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous cell of undetermined significance on cytology. Our results highlight the importance of combined Pap and HPV cotesting. Although the

Orion Burn Management, Nominal and Response to Failures

NASA Technical Reports Server (NTRS)

Odegard, Ryan; Goodman, John L.; Barrett, Charles P.; Pohlkamp, Kara; Robinson, Shane

2016-01-01

An approach for managing Orion on-orbit burn execution is described for nominal and failure response scenarios. The burn management strategy for Orion takes into account per-burn variations in targeting, timing, and execution; crew and ground operator intervention and overrides; defined burn failure triggers and responses; and corresponding on-board software sequencing functionality. Burn-to- burn variations are managed through the identification of specific parameters that may be updated for each progressive burn. Failure triggers and automatic responses during the burn timeframe are defined to provide safety for the crew in the case of vehicle failures, along with override capabilities to ensure operational control of the vehicle. On-board sequencing software provides the timeline coordination for performing the required activities related to targeting, burn execution, and responding to burn failures.

Dynamics of Leading-strand Lesion Skipping by the Replisome

PubMed Central

Yeeles, Joseph T.P.; Marians, Kenneth J.

2013-01-01

SUMMARY The E. coli replisome stalls transiently when it encounters a lesion in the leading-strand template, skipping over the damage by reinitiating replication at a new primer synthesized downstream by the primase. We report here that template unwinding and lagging-strand synthesis continue downstream of the lesion at a reduced rate after replisome stalling, that one replisome is capable of skipping multiple lesions, and that the rate limiting steps of replication restart involve the synthesis and activation of the new primer downstream. We also find little support for the concept that polymerase uncoupling, where extensive lagging-strand synthesis proceeds downstream in the absence of leading-strand synthesis, involves physical separation of the leading-strand polymerase from the replisome. Instead, our data indicate that extensive uncoupled replication likely results from a failure of the leading-strand polymerase still associated with the DNA helicase and the lagging-strand polymerase that are proceeding downstream to reinitiate synthesis. PMID:24268579

Metabolic support for the heart: complementary therapy for heart failure?

PubMed

Heggermont, Ward A; Papageorgiou, Anna-Pia; Heymans, Stephane; van Bilsen, Marc

2016-12-01

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Generation and Repair of AID-initiated DNA Lesions in B Lymphocytes

PubMed Central

Chen, Zhangguo; Wang, Jing H.

2014-01-01

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions. PMID:24748462

Beyond Wires and Seeds: Reflector-guided Breast Lesion Localization and Excision.

PubMed

Mango, Victoria L; Wynn, Ralph T; Feldman, Sheldon; Friedlander, Lauren; Desperito, Elise; Patel, Sejal N; Gomberawalla, Ameer; Ha, Richard

2017-08-01

Purpose To evaluate outcomes of Savi Scout (Cianna Medical, Aliso Viejo, Calif) reflector-guided localization and excision of breast lesions by analyzing reflector placement, localization, and removal, along with target excision and rates of repeat excision (referred to as re-excision). Materials and Methods A single-institution retrospective review of 100 women who underwent breast lesion localization and excision by using the Savi Scout surgical guidance system from June 2015 to May 2016 was performed. By using image guidance 0-8 days before surgery, 123 nonradioactive, infrared-activated, electromagnetic wave reflectors were percutaneously inserted adjacent to or within 111 breast targets. Twenty patients had two or three reflectors placed for bracketing or for localizing multiple lesions, and when ipsilateral, they were placed as close as 2.6 cm apart. Target and reflector were localized intraoperatively by one of two breast surgeons who used a handpiece that emitted infrared light and electromagnetic waves. Radiographs of the specimen and pathologic analysis helped verify target and reflector removal. Target to reflector distance was measured on the mammogram and radiograph of the specimen, and reflector depth was measured on the mammogram. Pathologic analysis was reviewed. Re-excision rates and complications were recorded. By using statistics software, descriptive statistics were generated with 95% confidence intervals (CIs) calculated. Results By using sonographic (40 of 123; 32.5%; 95% CI: 24.9%, 41.2%) or mammographic (83 of 123; 67.5%; 95% CI: 58.8% 75.1%) guidance, 123 (100%; 95% CI: 96.4%, 100%) reflectors were placed. Mean mammographic target to reflector distance was 0.3 cm. All 123 (100%; 95% CI: 96.4%, 100%) targets and reflectors were excised. Pathologic analysis yielded 54 of 110 malignancies (49.1%; 95% CI: 39.9%, 58.3%; average, 1.0 cm; range, 0.1-5 cm), 32 high-risk lesions (29.1%; 95% CI: 21.4%, 38.2%), and 24 benign lesions (21.8%; 95% CI

Advances in gene therapy for heart failure.

PubMed

Fish, Kenneth M; Ishikawa, Kiyotake

2015-04-01

Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.

Impaired threat prioritisation after selective bilateral amygdala lesions

PubMed Central

Bach, Dominik R.; Hurlemann, Rene; Dolan, Raymond J.

2015-01-01

The amygdala is proposed to process threat-related information in non-human animals. In humans, empirical evidence from lesion studies has provided the strongest evidence for a role in emotional face recognition and social judgement. Here we use a face-in-the-crowd (FITC) task which in healthy control individuals reveals prioritised threat processing, evident in faster serial search for angry compared to happy target faces. We investigate AM and BG, two individuals with bilateral amygdala lesions due to Urbach–Wiethe syndrome, and 16 control individuals. In lesion patients we show a reversal of a threat detection advantage indicating a profound impairment in prioritising threat information. This is the first direct demonstration that human amygdala lesions impair prioritisation of threatening faces, providing evidence that this structure has a causal role in responding to imminent danger. PMID:25282058

Cytokine analysis in lesions refractory to endodontic treatment.

PubMed

Henriques, Luiz Carlos Feitosa; de Brito, Luciana Carla Neves; Tavares, Warley Luciano Fonseca; Vieira, Leda Quércia; Ribeiro Sobrinho, Antônio Paulino

2011-12-01

Failure in endodontic treatment is often caused by the persistence of microorganisms in the root canal after therapy. When treatment fails, an immune response develops that is characterized by an extensive network of immunologic mechanisms that lead to the production of cytokines and chemokines. The objective of this study was to determine the relative messenger RNA (mRNA) expression of IFN-γ, TNF-α, IL-1β, IL-17A, IL-10, and MCP-1 in periapical dental lesions refractory to treatment. Clinical samples were taken from teeth presenting periapical lesions refractory to endodontic treatment (the experimental group) or from healthy teeth with pulp vitality (the control group). Three paper points passing through the root apex (2 mm) were used to collect the samples. The total RNA was extracted from each sample, complementary DNA was synthesized, and quantitative polymerase chain reaction analysis was performed. The Mann-Whitney U test was used to determine the statistical significance of our findings (P < .05). Significant differences in the levels of IFN-γ, TNF-α, IL-17A, and MCP-1 mRNA expression were observed in cases refractory to endodontic treatment as compared with the control group. The expression of IL-1β mRNA was not significantly different between the groups. The expression of IL-10 mRNA was insignificant in both the experimental and control groups. A significantly increased expression of TNF-α, IFN-γ, IL-17A, and MCP-1 mRNA was observed in the periapical immune response in cases of endodontic failure. These results suggest that a proinflammatory cytokine profile predominates in these types of dental lesions. Copyright © 2011 American Association of Endodontists. All rights reserved.

The impact of 18 F-FET PET-CT on target definition in image-guided stereotactic radiotherapy in patients with skull base lesions.

PubMed

Badakhshi, Harun; Graf, Reinhold; Prasad, Vikas; Budach, Volker

2014-06-25

18 F-fluoro-ethyl-tyrosine PET is gaining more indications in the field of oncology. We investigated the potentials of usage of FET-PET/CT in addition to MRI for definition of gross tumor volume (GTV) in stereotactic radiotherapy of lesions of skull base. We included in a prospective setting 21 cases. An MRI was performed, completed by FET PET/CT. Different GTV's were defined based on respective imaging tools: 1. GTVMRI, 2. GTV MRI /CT, 3. GTV composit (1 + 2), and GTVPET = GTV Boost. Lesions could be visualised by MRI and FET-PET/CT in all patients. FET tracer enhancement was found in all cases. Skull base infiltration by these lesions was observed by MRI, CT (PET/CT) and FET-PET (PET/CT) in all patients. Totally, brain tissue infiltration was seen in 10 patients. While, in 7 (out 10) cases, MRI and CT (from PET/CT) were indicating brain infiltration, FET-PET could add additional information regarding infiltrative behaviour: in 3 (out 10) patients, infiltration of the brain was displayed merely in FET-PET. An enlargement of GTVMRI/CT due to the FET-PET driven information, which revealed GTVcomposite , was necessary in 7 cases,. This enlargement was significant by definition (> 10% of GTVMRI/CT). The mean PET-effect on GTV counted for 1 ± 4 cm3. The restricted boost fields were based mainly on the GTVPET volume. In mean, about 8.5 cm3 of GTVMRI/CT, which showed no FET uptake, were excluded from target volume. GTV boost driven by only-PET-activity, was in mean by 33% smaller than the initial large treatment field, GTV composite, for those cases received boost treatment. FET-PET lead to significant (>10%) changes in the initial treatment fields in 11/21 patients and showed additional tumour volume relevant for radiation planning in 6/21 cases, and led to a subsequent decrease of more than 10% of the initial volumes for the boost fields. The implementation of FET PET into the planning procedures showed a benefit in terms of accurate definition of skull base lesions

Multiple lesion track structure model

NASA Technical Reports Server (NTRS)

Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

1992-01-01

A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plating, delaying plating, and fractionated exposure protocols employed by Yang. A study is made of the effects of target fragments in energetic proton exposures and of the repair-deficient target-fragment-induced lesions.

Long-Term Prognosis of Deferred Acute Coronary Syndrome Lesions Based on Nonischemic Fractional Flow Reserve.

PubMed

Hakeem, Abdul; Edupuganti, Mohan M; Almomani, Ahmed; Pothineni, Naga Venkata; Payne, Jason; Abualsuod, Amjad M; Bhatti, Sabha; Ahmed, Zubair; Uretsky, Barry F

2016-09-13

Deferring percutaneous coronary intervention in nonischemic lesions by fractional flow reserve (FFR) is associated with excellent long-term prognosis in patients with stable ischemic heart disease (SIHD). Although FFR is increasingly used for clinical decision making in acute coronary syndrome (ACS) patients with intermediate lesions, its effect on long-term prognosis has not been well established. This study investigated the clinical and prognostic utility of FFR in ACS patients with percutaneous coronary intervention deferred on the basis of nonischemic FFR. We studied 206 consecutive ACS patients with 262 intermediate lesions and 370 patients with SIHD (528 lesions) in whom revascularization was deferred on the basis of a nonischemic FFR (>0.75). The primary outcome measure was a composite of myocardial infarction and target vessel failure (major adverse cardiovascular events [MACE]). In the entire cohort, the long-term (3.4 ± 1.6 years) MACE rate was higher in the ACS group than in the SIHD group (23% vs. 11%, p < 0.0001). After propensity score matching (200 patients/group), MACE remained significantly higher (ACS 25% vs. SIHD 12%; p < 0.0001). On Cox proportional hazards analysis for MACE, ACS had a hazard ratio of 2.8 (95% confidence interval: 1.9 to 4.0; p < 0.0001). In both the matched and unmatched cohorts, across all FFR categories, ACS patients had a significantly higher annualized myocardial infarction/target vessel revascularization rate compared with SIHD (p < 0.05). Receiver-operating characteristic analysis identified FFR cutoffs (best predictive accuracy for MACE) of <0.84 for ACS (MACE 21% vs. 36%; p = 0.007) and <0.81 for SIHD (MACE 17% vs. 9%; p = 0.01). Deferring percutaneous coronary intervention on the basis of nonischemic FFR in patients with an initial presentation of ACS is associated with significantly worse outcomes than SIHD. Caution is warranted in using FFR values derived from patients with SIHD for clinical decision making

Molecular mechanisms and treatment targets of muscle wasting and cachexia in heart failure: an overview.

PubMed

Ebner, Nicole; Elsner, Sebastian; Springer, Jochen; von Haehling, Stephan

2014-03-01

This article aims to describe molecular pathways involved in the development of muscle wasting and cachexia, diagnostic possibilities, and potential treatments that have seen clinical testing in recent heart failure trials. An understanding of the specific changes that cause an anabolic-catabolic imbalance is an essential first step in the development of pharmaceutical intervention strategies aimed at blocking muscle wasting. Skeletal muscle mass and muscle strength are the most important determinants of exercise capacity in patients with heart failure. In contrast to cachexia, muscle wasting is not usually associated with weight loss, implying the need for sophisticated assessment methods to correctly diagnose muscle wasting, for example the use of computed tomography, magnetic resonance imaging, or dual energy X-ray absorptiometry. Simpler techniques such as handgrip strength, exercise testing, or even a biomarker may help in determining patients with a high pre-test probability of muscle wasting. Despite intensive research efforts in the field of muscle wasting during the last couple of decades, no effective treatment of muscle wasting currently exists other than exercise training. This situation remains true even though study of the molecular pathways involved in muscle wasting suggests many therapeutic targets. Easily applicable diagnostic tools may help to identify patients at risk of developing muscle wasting.

Posterior medial meniscus root ligament lesions: MRI classification and associated findings.

PubMed

Choi, Ja-Young; Chang, Eric Y; Cunha, Guilherme M; Tafur, Monica; Statum, Sheronda; Chung, Christine B

2014-12-01

The purposes of this study were to determine the prevalence of altered MRI appearances of "posterior medial meniscus root ligament (PMMRL)" lesions, introduce a classification of lesion types, and report associated findings. We retrospectively reviewed 419 knee MRI studies to identify the presence of PMMRL lesions. Classification was established on the basis of lesions encountered. The medial compartment was assessed for medial meniscal tears in the meniscus proper, medial meniscal extrusion, insertional PMMRL osseous changes, regional synovitis, osteoarthritis, insufficiency fracture, and cruciate ligament abnormality. PMMRL abnormalities occurred in 28.6% (120/419) of the studies: degeneration, 14.3% (60/419) and tear, 14.3% (60/419). Our classification system included degeneration and tearing. Tearing was categorized as partial or complete with delineation of the point of failure as entheseal, midsubstance, or junction to meniscus. Of all tears, 93.3% (56/60) occurred at the meniscal junction. Univariate analysis revealed significant differences between the knees with and without PMMRL lesions in age, medial meniscal tear, medial meniscal extrusion, insertional PMMRL osseous change, regional synovitis, osteoarthritis, insufficiency fracture (p=0.017), and cruciate ligament degeneration (p<0.001). PMMRL lesions are commonly detected in symptomatic patients. We have introduced an MRI classification system. PMMRL lesions are significantly associated with age, medial meniscal tears, medial meniscal extrusion, insertional PMMRL osseous change, regional synovitis, osteoarthritis, insufficiency fracture, and cruciate ligament degeneration.

Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease.

PubMed

Ellis, Stephen G; Kereiakes, Dean J; Metzger, D Christopher; Caputo, Ronald P; Rizik, David G; Teirstein, Paul S; Litt, Marc R; Kini, Annapoorna; Kabour, Ameer; Marx, Steven O; Popma, Jeffrey J; McGreevy, Robert; Zhang, Zhen; Simonton, Charles; Stone, Gregg W

2015-11-12

In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III Clinical

Adaptive lesion formation using dual mode ultrasound array system

NASA Astrophysics Data System (ADS)

Liu, Dalong; Casper, Andrew; Haritonova, Alyona; Ebbini, Emad S.

2017-03-01

events has been shown to produce precisely controlled lesions with no evidence of overexposure even when fast raster scan of volumetric HIFU lesion is attempted. We also show that the DMUA beamformed echo data is capable of detecting underexposure condition at the target location, e.g. due to the obstruction of the HIFU beam resulting from cavitation activity in the path of the beam. The results clearly demonstrate the advantage of adaptive lesion formation in reducing the treatment time while confining the tissue damage to the target volume.

[Arthroscopic Reconstruction of Intratendinous Lesions of the Supraspinatus Tendon - a Systematic Review].

PubMed

von Knoch, Marius; Frosch, Stephan; Lehmann, Wolfgang

2018-06-12

Intratendinous lesions of the rotator cuff of the shoulder are frequent and may be a distinct clinical entity. Nevertheless, there are only a few publications which deal specifically with this subject. This study analyses the existing literature for the arthroscopic reconstruction of the intratendinous lesion of the supraspinatus tendon, by means of a systematic review, and identifies relevant research questions for future studies. In January 2017, a systematic review of the U. S. National Library of Medicine/National Institutes of Health (PubMed) Database and the Cochrane Library was conducted using the PRISMA checklist. The search words were "supraspinatus" and "interstitial"; "supraspinatus", "tear" and "intratendinous"; "supraspinatus" and "concealed". In the course of the review, articles written in English with at least a partial arthroscopic case series dealing with the reconstruction of the supraspinatus tendon were identified and further analysed. Primarily 70 hits could be generated. Five articles met the inclusion criteria and were analysed in detail. The number of arthroscopic cases ranged between 6 and 33. Level of evidence was IV in all studies. The diagnosis of an intratendinous lesion was made by MR imaging when T2/fat-saturated sequences showed an intratendinous high intensity signal without disruption of the bursal or articular layer. Three different concepts were followed in surgical treatment: opening of the intratendinous lesion from the bursal or articular side or by complete resection of the lesion. The reconstruction was performed with suture anchors in all cases. In the majority of cases, an acromioplasty was also performed. The reported clinical results were mostly good. Healing of the tendon was shown by MR imaging in 81.5 to 100% of cases. After failure of conservative treatment, symptomatic intratendinous lesions of the supraspinatus tendon can be localised intraoperatively and reconstructed after failure of conservative treatment

Thermographic diagnostics to discriminate skin lesions: a clinical study

NASA Astrophysics Data System (ADS)

Stringasci, Mirian Denise; Moriyama, Lilian Tan; Salvio, Ana Gabriela; Bagnato, Vanderlei Salvador; Kurachi, Cristina

2015-06-01

Cancer is responsible for about 13% of all causes of death in the world. Over 7 million people die annually of this disease. In most cases, the survival rates are greater when diagnosed in early stages. It is known that tumor lesions present a different temperature compared with the normal tissues. Some studies have been performed in an attempt to establish new diagnosis methods, targeting this temperature difference. In this study, we aim to investigate the use of a handheld thermographic camera to discriminate skin lesions. The patients presenting Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis, Pigmented Seborrheic Keratosis, Melanoma or Intradermal Nevus lesions have been investigated at the Skin Departament of Amaral Carvalho Hospital. Patients are selected by a dermatologist, and the lesion images are recorded using an infrared camera. The images are evaluated taken into account the temperature level, and differences into lesion areas, borders, and between altered and normal skin. The present results show that thermography may be an important tool for aiding in the clinical diagnostics of superficial skin lesions.

Lesions of basal ganglia due to disulfiram neurotoxicity.

PubMed Central

Laplane, D; Attal, N; Sauron, B; de Billy, A; Dubois, B

1992-01-01

Three cases of disulfiram induced Parkinsonism and frontal lobe-like syndrome associated with bilateral lesions of the lentiform nuclei on CT scan are reported. Symptoms developed either after an acute high dose of disulfiram (one case) or after several days to weeks of disulfiram treatment (two cases) and persisted over several years in two patients. These observations suggest that basal ganglia are one of the major targets of disulfiram neurotoxicity. The mechanisms of the lesions of basal ganglia may involve carbon disulfide toxicity. Images PMID:1431956

Temporal Lobe Epilepsy Surgery Failures: A Review

PubMed Central

Harroud, Adil; Bouthillier, Alain; Weil, Alexander G.; Nguyen, Dang Khoa

2012-01-01

Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE. PMID:22934162

Automatic colonic lesion detection and tracking in endoscopic videos

NASA Astrophysics Data System (ADS)

Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

2011-03-01

The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

Management of Cyst-like Periapical Lesions by Orthograde Decompression and Long-term Calcium Hydroxide/Chlorhexidine Intracanal Dressing: A Case Series.

PubMed

Santos Soares, Suelleng Maria Cunha; Brito-Júnior, Manoel; de Souza, Flávia Kelly; Zastrow, Eduardo Von; Cunha, Carla Oliveira da; Silveira, Frank Ferreira; Nunes, Eduardo; César, Carlos Augusto Santos; Glória, José Cristiano Ramos; Soares, Janir Alves

2016-07-01

Cyst-like periapical lesions should be treated initially with conservative nonsurgical procedures. In this case series, we describe the clinical and radiographic outcomes of large cyst-like lesions that were treated by orthograde decompression and long-term intracanal use of calcium hydroxide [Ca(OH)2] mixed with 2% chlorhexidine digluconate. Ten cases of cyst-like periapical lesions involving 15 teeth from 10 patients were selected. Maximal radiographic diameters of the lesions ranged from 11 to 28 mm. Nonsurgical procedures were performed, including apical patency, orthograde puncture of cyst-like exudates, chemomechanical preparation, and placement of intracanal Ca(OH)2/CHX dressings, which were periodically replaced during 6-10 months. The root canals were then filled with gutta-percha and sealer. The follow-up periods ranged from 6 to 24 months, and the outcome was classified as healed, healing, or failure. Nine lesions drained copious exudates after canal patency. One lesion only drained bloody serous exudate after periapical overinstrumentation. In 9 patients, intracanal exudation ceased in the first follow-up visit. At the 24-month follow-up, 6 lesions (60.0%) had healed, and 3 lesions (30.0%) were healing, with the corresponding patients being without clinical signs or symptoms. The case of treatment failure was submitted to surgical treatment. Microscopically, the lesion appeared to be an apical cyst with exuberant extraradicular bacterial biofilms attached to the sectioned root apex. This case series supports the use of nonsurgical methods to resolve larger cyst-like periapical lesions. Published by Elsevier Inc.

The Pattern of Failure After Reirradiation of Recurrent Squamous Cell Head and Neck Cancer: Implications for Defining the Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popovtzer, Aron; Gluck, Iris; Chepeha, Douglas B.

2009-08-01

Purpose: Reirradiation (re-RT) of recurrent head and neck cancer (HNC) may achieve long-term disease control in some patients, at the expense of high rates of late sequelae. Limiting the re-RT targets to the recurrent gross tumor volume (rGTV) would reduce the volumes of reirradiated tissues; however, its effect on tumor recurrence pattern is unknown. Methods and Materials: This is a retrospective review of 66 patients who underwent curative-intent re-RT for nonresectable recurrent or second primary mucosal squamous cell HNC. Treatment was delivered with three-dimensional conformal (3D) RT or intensity-modulated RT (IMRT). The targets in all patients consisted of the rGTVsmore » with tight (0.5-cm) margins, with no intent to treat prophylactically lymph nodes or subclinical disease in the vicinity of the rGTVs. The sites of locoregional failures (LRFs) were determined using imaging at the time of failure and were compared with the rGTVs. Results: Median re-RT dose was 68 Gy. Forty-seven patients (71%) received concomitant chemotherapy, and 31 (47%) received hyperfractionated, accelerated RT. At a median follow-up of 42 months, 16 (23%) were alive and disease-free. Fifty patients (77%) had a third recurrence or persistent disease, including 47 LRFs. All LRFs occurred within the rGTVs except for two (4%) (95% confidence interval, 0-11%). Nineteen patients (29%) had Grade {>=} 3 late complications, mostly dysphagia (12 patients). Conclusions: Almost all LRFs occurred within the reirradiated rGTVs despite avoiding prophylactic RT of tissue at risk of subclinical disease. These results support confining the re-RT targets to the rGTVs to reduce reirradiated tissue volumes.« less

Magnetic Resonance Imaging-Guided Focused Laser Interstitial Thermal Therapy for Intracranial Lesions: Single-Institution Series

PubMed Central

Hawasli, Ammar H.; Bagade, Swapnil; Shimony, Joshua S.; Miller-Thomas, Michelle

2013-01-01

BACKGROUND: Surgical treatments for deep-seated intracranial lesions have been limited by morbidities associated with resection. Real-time magnetic resonance imaging–guided focused laser interstitial thermal therapy (LITT) offers a minimally invasive surgical treatment option for such lesions. OBJECTIVE: To review treatments and results of patients treated with LITT for intracranial lesions at Washington University School of Medicine. METHODS: In a review of 17 prospectively recruited LITT patients (34-78 years of age; mean, 59 years), we report demographics, treatment details, postoperative imaging characteristics, and peri- and postoperative clinical courses. RESULTS: Targets included 11 gliomas, 5 brain metastases, and 1 epilepsy focus. Lesions were lobar (n = 8), thalamic/basal ganglia (n = 5), insular (n = 3), and corpus callosum (n = 1). Mean target volume was 11.6 cm3, and LITT produced 93% target ablation. Patients with superficial lesions had shorter intensive care unit stays. Ten patients experienced no perioperative morbidities. Morbidities included transient aphasia, hemiparesis, hyponatremia, deep venous thrombosis, and fatal meningitis. Postoperative magnetic resonance imaging showed blood products within the lesion surrounded by new thin uniform rim of contrast enhancement and diffusion restriction. In conjunction with other therapies, LITT targets often showed stable or reduced local disease. Epilepsy focus LITT produced seizure freedom at 8 months. Preliminary overall median progression-free survival and survival from LITT in tumor patients were 7.6 and 10.9 months, respectively. However, this small cohort has not been followed for a sufficient length of time, necessitating future outcomes studies. CONCLUSION: Early peri- and postoperative clinical data demonstrate that LITT is a safe and viable ablative treatment option for intracranial lesions, and may be considered for select patients. ABBREVIATION: LITT, laser interstitial thermal therapy

Malpractice claims related to musculoskeletal imaging. Incidence and anatomical location of lesions.

PubMed

Fileni, Adriano; Fileni, Gaia; Mirk, Paoletta; Magnavita, Giulia; Nicoli, Marzia; Magnavita, Nicola

2013-12-01

Failure to detect lesions of the musculoskeletal system is a frequent cause of malpractice claims against radiologists. We examined all the malpractice claims related to alleged errors in musculoskeletal imaging filed against Italian radiologists over a period of 14 years (1993-2006). During the period considered, a total of 416 claims for alleged diagnostic errors relating to the musculoskeletal system were filed against radiologists; of these, 389 (93.5%) concerned failure to report fractures, and 15 (3.6%) failure to diagnose a tumour. Incorrect interpretation of bone pathology is among the most common causes of litigation against radiologists; alone, it accounts for 36.4% of all malpractice claims filed during the observation period. Awareness of this risk should encourage extreme caution and diligence.

Vitamin D and Heart Failure.

PubMed

Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J

2017-10-01

Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

Failure to use corollary discharge to remap visual target locations is associated with psychotic symptom severity in schizophrenia

PubMed Central

Rösler, Lara; Rolfs, Martin; van der Stigchel, Stefan; Neggers, Sebastiaan F. W.; Cahn, Wiepke; Kahn, René S.

2015-01-01

Corollary discharge (CD) refers to “copies” of motor signals sent to sensory areas, allowing prediction of future sensory states. They enable the putative mechanisms supporting the distinction between self-generated and externally generated sensations. Accordingly, many authors have suggested that disturbed CD engenders psychotic symptoms of schizophrenia, which are characterized by agency distortions. CD also supports perceived visual stability across saccadic eye movements and is used to predict the postsaccadic retinal coordinates of visual stimuli, a process called remapping. We tested whether schizophrenia patients (SZP) show remapping disturbances as evidenced by systematic transsaccadic mislocalizations of visual targets. SZP and healthy controls (HC) performed a task in which a saccadic target disappeared upon saccade initiation and, after a brief delay, reappeared at a horizontally displaced position. HC judged the direction of this displacement accurately, despite spatial errors in saccade landing site, indicating that their comparison of the actual to predicted postsaccadic target location relied on accurate CD. SZP performed worse and relied more on saccade landing site as a proxy for the presaccadic target, consistent with disturbed CD. This remapping failure was strongest in patients with more severe psychotic symptoms, consistent with the theoretical link between disturbed CD and phenomenological experiences in schizophrenia. PMID:26108951

Temporary Basolateral Amygdala Lesions Disrupt Acquisition of Socially Transmitted Food Preferences in Rats

ERIC Educational Resources Information Center

Fontanini, Alfredo; Katz, Donald B.; Wang, Yunyan

2006-01-01

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in…

Successful Nonsurgical Management of Periapical Lesions of Endodontic Origin: A Conservative Orthograde Approach

PubMed Central

Karunakaran, J. V.; Abraham, Chris Susan; Karthik, A. Kaneesh; Jayaprakash, N.

2017-01-01

Periapical lesions of endodontic origin are common pathological conditions affecting periradicular tissues. Microbial infection of pulpal tissues is primarily responsible for initiation and progression of apical periodontitis. The primary objective of endodontic therapy should be to restore involved teeth to a state of normalcy nonsurgically. Different nonsurgical management techniques, namely, conservative root canal therapy, decompression technique, method using calcium hydroxide, aspiration-irrigation technique, lesion sterilization and tissue repair therapy, active nonsurgical decompression technique, and the apexum procedure have been advocated. New techniques which use drug-loaded injectable scaffolds, simvastatin, and epigallocatechin-3-gallate have been tried. Surgical option should be considered when intra- or extra-radicular infections are persistent. Incidence of nonendodontic periapical lesions has also been reported. An accurate diagnosis of the periapical lesion whether it is of endodontic or nonendodontic origin has to be made. Surgical methods have many disadvantages, and hence should be considered as an option only in the case of failure of nonsurgical techniques. Assessment of healing of periapical lesions has to be done periodically which necessitates a long-term follow-up. Even large periapical lesions and retreatment cases where the lesion is of endodontic origin have been successfully managed nonsurgically with orthograde endodontic therapy. PMID:29284973

The association between sterilizing activity and drug distribution into tuberculosis lesions

PubMed Central

Prideaux, Brendan; Via, Laura E.; Zimmerman, Matthew D.; Eum, Seokyong; Sarathy, Jansy; O’Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M.; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, TaeSun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N.; Barry, Clifton E.; Dartois, Véronique

2015-01-01

Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a MALDI mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration contributes to treatment outcome has wide implications for TB. PMID:26343800

Broken or dislodged poly-L-lactic acid bioabsorbable tacks in patients after SLAP lesion surgery.

PubMed

Sassmannshausen, Greg; Sukay, Michael; Mair, Scott D

2006-06-01

To document the complication of bioabsorbable poly-L-lactic acid (PLLA) tack breakage and repair failure after arthroscopic stabilization of SLAP lesions. Six patients (average age, 38 years) were referred to the senior author because of persistent postoperative pain and disability after arthroscopic stabilization of an unstable SLAP lesion was performed with bioabsorbable PLLA tacks. A total of eight tacks were used in the six patients, and the time from index procedure to evaluation at our facility averaged 9.5 months (range, 8 to 12 months). Three patients experienced an identifiable reinjury an average of 4 months after the index procedure was performed. Magnetic resonance imaging (MRI) revealed a broken or dislodged tack in all cases. All patients were taken to the operating room for arthroscopic evaluation of the biceps anchor, tack fragment removal, and restabilization of the SLAP lesion as needed. At repeat arthroscopy, all shoulders were found to have minimal healing of the SLAP lesion with failure of the bioabsorbable tack. Chondral injury was noted in 2 cases. In all cases, revision SLAP repair was performed with the use of arthroscopic suture repair. At an average follow-up of 14 months (range, 8 to 17 months), all patients reported alleviation of symptoms. Five patients had returned to work with no or minimal symptoms. One patient experienced significant improvement in function and range of motion but did not return to work. Bioabsorbable PLLA tack breakage or dislodgement is a potential postoperative complication after SLAP lesions are arthroscopically stabilized. This event may result in postoperative reports of pain or mechanical symptoms. Surgeons who use these devices must be aware of the potential complications when they evaluate postoperative patients with persistent complaints. MRI may be helpful in identifying tack fragments. Subsequent arthroscopy to evaluate biceps anchor healing, remove tack fragments, and restabilize the labral lesion may

Altered sarcoplasmic reticulum calcium cycling—targets for heart failure therapy

PubMed Central

Kho, Changwon; Lee, Ahyoung; Hajjar, Roger J.

2013-01-01

Cardiac myocyte function is dependent on the synchronized movements of Ca2+ into and out of the cell, as well as between the cytosol and sarcoplasmic reticulum. These movements determine cardiac rhythm and regulate excitation–contraction coupling. Ca2+ cycling is mediated by a number of critical Ca2+-handling proteins and transporters, such as L-type Ca2+ channels (LTCCs) and sodium/calcium exchangers in the sarcolemma, and sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), ryanodine receptors, and cardiac phospholamban in the sarcoplasmic reticulum. The entry of Ca2+ into the cytosol through LTCCs activates the release of Ca2+ from the sarcoplasmic reticulum through ryanodine receptor channels and initiates myocyte contraction, whereas SERCA2a and cardiac phospholamban have a key role in sarcoplasmic reticulum Ca2+ sequesteration and myocyte relaxation. Excitation–contraction coupling is regulated by phosphorylation of Ca2+-handling proteins. Abnormalities in sarcoplasmic reticulum Ca2+ cycling are hallmarks of heart failure and contribute to the pathophysiology and progression of this disease. Correcting impaired intracellular Ca2+ cycling is a promising new approach for the treatment of heart failure. Novel therapeutic strategies that enhance myocyte Ca2+ homeostasis could prevent and reverse adverse cardiac remodeling and improve clinical outcomes in patients with heart failure. PMID:23090087

Herpesviruses in asymptomatic apical periodontitis lesions: an immunohistochemical approach.

PubMed

Saboia-Dantas, C J; Coutrin de Toledo, L F; Sampaio-Filho, H R; Siqueira, J F

2007-10-01

Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been recently detected in samples from apical periodontitis lesions by means of molecular biology techniques and a role in the pathogenesis of this disease has been suggested. The present study was designed to survey asymptomatic primary apical periodontitis lesions for the presence of HCMV- and/or EBV-infected cells by means of immunohistochemistry. Apical periodontitis lesions were obtained from 35 patients [26 human immunodeficiency virus (HIV) -seronegative patients and nine HIV-seropositive patients] after tooth extraction and subjected to immunohistochemical analysis using monoclonal antibodies specific for HCMV and EBV. Fifteen of the 35 apical periodontitis lesions were positive for the target herpesviruses. Overall, EBV was found in 31% of the samples and HCMV in 23%, with 14% of the lesions showing EBV and HCMV dual infection. No association was found between HCMV or EBV with any particular histopathological type of apical periodontitis (P > 0.05). HCMV was significantly more frequent in apical periodontitis lesions from HIV-positive patients (67%) than in lesions from HIV-negative patients (8%) (P = 0.001). EBV was detected in 44% of lesions from HIV-positive patients and in 27% of lesions from HIV-negative patients, but this difference was not significant (P = 0.91). Our results showed that cells infected by HCMV and EBV can be found in apical periodontitis lesions, with a higher prevalence in HIV-positive patients. The specific role that these viruses play in the pathogenesis of apical periodontitis remains to be described.

Temporal Characteristics of Radiologists' and Novices' Lesion Detection in Viewing Medical Images Presented Rapidly and Sequentially.

PubMed

Nakashima, Ryoichi; Komori, Yuya; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

2016-01-01

Although viewing multiple stacks of medical images presented on a display is a relatively new but useful medical task, little is known about this task. Particularly, it is unclear how radiologists search for lesions in this type of image reading. When viewing cluttered and dynamic displays, continuous motion itself does not capture attention. Thus, it is effective for the target detection that observers' attention is captured by the onset signal of a suddenly appearing target among the continuously moving distractors (i.e., a passive viewing strategy). This can be applied to stack viewing tasks, because lesions often show up as transient signals in medical images which are sequentially presented simulating a dynamic and smoothly transforming image progression of organs. However, it is unclear whether observers can detect a target when the target appears at the beginning of a sequential presentation where the global apparent motion onset signal (i.e., signal of the initiation of the apparent motion by sequential presentation) occurs. We investigated the ability of radiologists to detect lesions during such tasks by comparing the performances of radiologists and novices. Results show that overall performance of radiologists is better than novices. Furthermore, the temporal locations of lesions in CT image sequences, i.e., when a lesion appears in an image sequence, does not affect the performance of radiologists, whereas it does affect the performance of novices. Results indicate that novices have greater difficulty in detecting a lesion appearing early than late in the image sequence. We suggest that radiologists have other mechanisms to detect lesions in medical images with little attention which novices do not have. This ability is critically important when viewing rapid sequential presentations of multiple CT images, such as stack viewing tasks.

Temporal Characteristics of Radiologists' and Novices' Lesion Detection in Viewing Medical Images Presented Rapidly and Sequentially

PubMed Central

Nakashima, Ryoichi; Komori, Yuya; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

2016-01-01

Although viewing multiple stacks of medical images presented on a display is a relatively new but useful medical task, little is known about this task. Particularly, it is unclear how radiologists search for lesions in this type of image reading. When viewing cluttered and dynamic displays, continuous motion itself does not capture attention. Thus, it is effective for the target detection that observers' attention is captured by the onset signal of a suddenly appearing target among the continuously moving distractors (i.e., a passive viewing strategy). This can be applied to stack viewing tasks, because lesions often show up as transient signals in medical images which are sequentially presented simulating a dynamic and smoothly transforming image progression of organs. However, it is unclear whether observers can detect a target when the target appears at the beginning of a sequential presentation where the global apparent motion onset signal (i.e., signal of the initiation of the apparent motion by sequential presentation) occurs. We investigated the ability of radiologists to detect lesions during such tasks by comparing the performances of radiologists and novices. Results show that overall performance of radiologists is better than novices. Furthermore, the temporal locations of lesions in CT image sequences, i.e., when a lesion appears in an image sequence, does not affect the performance of radiologists, whereas it does affect the performance of novices. Results indicate that novices have greater difficulty in detecting a lesion appearing early than late in the image sequence. We suggest that radiologists have other mechanisms to detect lesions in medical images with little attention which novices do not have. This ability is critically important when viewing rapid sequential presentations of multiple CT images, such as stack viewing tasks. PMID:27774080

Comparison of Long-Term Clinical Outcomes of Lesions Exhibiting Focal and Segmental Peri-Stent Contrast Staining.

PubMed

Tokuda, Takahiro; Yamawaki, Masahiro; Takahara, Mitsuyohi; Mori, Shinsuke; Makino, Kenji; Honda, Yosuke; Takafuji, Hiroya; Takama, Takuro; Tsutsumi, Masakazu; Sakamoto, Yasunari; Takimura, Hideyuki; Kobayashi, Norihiro; Araki, Motoharu; Hirano, Keisuke; Ito, Yoshiaki

2016-03-18

Peri-stent contrast staining (PSS) after metallic drug-eluting stent deployment is associated with target lesion revascularization and very late stent thrombosis. However, the type of PSS that influences the clinical outcomes is unknown. Therefore, we aimed to reveal which PSS type was influencing clinical outcomes. This study included 5580 de novo lesions of 4405 patients who were implanted with a first- or second-generation drug-eluting stent and who were evaluated using follow-up angiography within 12 months after stent implantation. We compared the clinical outcomes of patients divided into focal PSS and segmental PSS groups for 6 years after stent implantation. Total PSS was observed in 97 lesions (2.2%), of which 42 and 55 lesions were focal and segmental PSS, respectively. Baseline characteristics were similar between groups, except for intraoperative chronic total occlusion (segmental PSS=47.3% versus focal PSS=11.9%, P=0.0001). The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent (83.6% versus 16.4%, P=0.05). The cumulative incidence of stent thrombosis in the 6 years of segmental PSS group was significantly higher than that of the focal PSS group (13.9% versus 0%, P=0.04). The cumulative incidence of overall target lesion revascularization for restenosis, excluding target lesion revascularization procedures for stent thrombosis, was significantly higher in the segmental PSS group (38.0% versus 0%, P=0.01). The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent and appeared to be significantly associated with target lesion revascularization and stent thrombosis. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Dichotic listening in patients with splenial and nonsplenial callosal lesions.

PubMed

Pollmann, Stefan; Maertens, Marianne; von Cramon, D Yves; Lepsien, Joeran; Hugdahl, Kenneth

2002-01-01

The authors found splenial lesions to be associated with left ear suppression in dichotic listening of consonant-vowel syllables. This was found in both a rapid presentation dichotic monitoring task and a standard dichotic listening task, ruling out attentional limitations in the processing of high stimulus loads as a confounding factor. Moreover, directed attention to the left ear did not improve left ear target detection in the patients, independent of callosal lesion location. The authors' data may indicate that auditory callosal fibers pass through the splenium more posterior than previously thought. However, further studies should investigate whether callosal fibers between primary and secondary auditory cortices, or between higher level multimodal cortices, are vital for the detection of left ear targets in dichotic listening.

Malnutrition and Cachexia in Heart Failure.

PubMed

Rahman, Adam; Jafry, Syed; Jeejeebhoy, Khursheed; Nagpal, A Dave; Pisani, Barbara; Agarwala, Ravi

2016-05-01

Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients. © 2015 American Society for Parenteral and Enteral Nutrition.

Complex coronary lesions and rotational atherectomy: one hospital’s experience*

PubMed Central

Jiang, Jun; Sun, Yong; Xiang, Mei-xiang; Dong, Liang; Liu, Xian-bao; Hu, Xin-yang; Feng, Yan; Wang, Jian-an

2012-01-01

Objective: To evaluate the safety and effectiveness of rotational atherectomy followed by drug eluting stent (DES) implantation in patients with complex coronary lesions. Methods: From August 2006 to August 2012, 253 consecutive patients with 289 lesions and who underwent rotational atherectomy in our center were enrolled in this study. Results: The overall procedure success rate was 98% with the cost of two (0.8%) coronary perforations, three (1.2%) dissections, five (2.0%) slow flows or no flows, three (1.2%) peri-procedure myocardial infarctions, and two (0.8%) in hospital deaths. During follow-up (mean three years), one (0.4%) patient died, two (0.8%) patients had acute myocardial infarction, 14 (5.5%) had restenosis, and target lesion revascularization occurred in eight patients (3.2%). Conclusions: Rotational atherectomy followed by DES implantation is a safe and effective technique for patients with complex coronary lesions, especially calcified and non-dilatable lesions. PMID:22843185

Dynamic Constitutive/Failure Models

DTIC Science & Technology

1988-12-01

compressive failure--microfracture versus microplasticity . Actual traces observed in plate impact tests on ceramic targets are hardly ever as simple as the...observa- tions for microfracture and microplasticity . Unfortunately, each team of investigators has used slightly different experimental techniques and

The Loss of GSTM1 Associates with Kidney Failure and Heart Failure.

PubMed

Tin, Adrienne; Scharpf, Robert; Estrella, Michelle M; Yu, Bing; Grove, Megan L; Chang, Patricia P; Matsushita, Kunihiro; Köttgen, Anna; Arking, Dan E; Boerwinkle, Eric; Le, Thu H; Coresh, Josef; Grams, Morgan E

2017-11-01

Glutathione S-transferase mu 1 ( GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1 , respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1 : kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 ( P >0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure. Copyright © 2017 by the American Society of Nephrology.

Characteristics of PI-RADS 4 lesions within the prostatic peripheral zone: a retrospective diagnostic accuracy study evaluating 170 lesions.

PubMed

Shankar, Prasad R; Curci, Nicole E; Davenport, Matthew S

2017-12-02

To determine whether peripheral zone PI-RADS 4 observations can be further risk-stratified. This was an IRB-approved HIPAA-compliant retrospective diagnostic accuracy study. Peripheral zone PI-RADS 4 observations prospectively identified at the study institution from 8/1/2015 to 12/31/2016 (n = 170 in 149 mpMRIs) were reviewed independently by two blinded genitourinary radiologists on the basis of (a) PI-RADS v2 shape, (b) pattern of peripheral zone sparing, and (c) rationale for PI-RADS 4 designation. Reference standard was targeted MR-ultrasound fusion biopsy and detection of Gleason 7+ prostate cancer. Positive predictive values (PPVs) were calculated. Predictors were assessed with binary logistic regression. PI-RADS 4 lesions with a DWI score of 4 were more likely to represent Gleason 7+ prostate cancer (p = 0.008-0.01; Reader 1 PPV: 53%; Reader 2 PPV: 48%). Pattern of peripheral zone sparing and most lesion shapes were not predictive (p > 0.05); however, oval lesions were predictive for Reader 1 (PPV = 59%, p = 0.03) and lentiform lesions were predictive for Reader 2 (PPV = 74%, p = 0.01). Lesions scored as "not meeting PI-RADS 4 criteria" had significantly lower PPV (p = 0.016-0.003; Reader 1 PPV: 14%, Reader 2 PPV: 16%). Peripheral zone PI-RADS 4 lesions with a DWI score of 4 are more likely Gleason 7+ cancer than those with a DWI score of 3. Lesions overcalled as PI-RADS 4 have PPV similar to published PI-RADS 3 data. Lesion shape and peripheral zone sparing in general do not predict Gleason 7+ cancer within PI-RADS 4 observations.

Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calvo-Ortega, J.F., E-mail: jfcdrr@yahoo.es; Pozo, M.; Moragues, S.

To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom onmore » the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application ( (www.radiochromic.com)) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm{sup 2} region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed.« less

Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions.

PubMed

Calvo-Ortega, J F; Pozo, M; Moragues, S; Casals, J

2017-01-01

To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom on the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application (www.radiochromic.com) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm 2 region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Conservative approach to preneoplastic cervical lesions in postmenopause.

PubMed

Vetrano, Giuseppe; Aleandri, Vincenzo; Ciolli, Paola; Scardamaglia, Paola; Pacchiarotti, Arianna; Verrico, Monica; Carboni, Simona; Corosu, Roberto

2008-01-01

To evaluate the recurrence rate of high-grade squamous intraepithelial lesions in postmenopausal women previously submitted to laser CO2 conization and the role of persistent oncogenic HPV types. Fifty-five patients with a cytological diagnosis of high-grade squamous intraepithelial lesions were triaged with a standard colposcopy. Hormonal replacement therapy was considered as significative in influencing cervical trophism. Vaginal smears for microbiological examination were obtained. H-R HPV test was performed by PCR. The follow-up checks including cytology, colposcopy and HVP test were performed for a minimum of 5 years. Histological analysis revealed 19 CIN2 (cervical intraepithelial lesions) and 36 CIN3 lesions. The cumulative failure rate at first treatment was 14%. HPV test was positive for HPV 16 type in all patients. Forty-two patients during the follow up checks resulted negative to cytology, colposcopy and HR HPV test. At the one-year follow-up check, 7 patients revealed normal cytological and abnormal colposcopical findings and persistent positive HR HPV test. At the five-year follow-up check, 14 patients with a normal cytological smear had a recurrence of CIN2/3 and positive HR HPV test. In postmenopause, the correct management of H-R squamous intraepithelial lesions is still debated. However, a satisfactory follow-up is the main requirement for the conservative management. HPV typing in the follow-up is important to detect persistent types to identify women at risk of developing cervical abnormalities. The incidence of cervical neoplasia does not decrease with increasing age. Since HPV positivity predicted subsequent infection, testing postmenopausal patients for the virus may be a cost-effective method of disease prevention.

Prefrontal Cortex Is Critical for Contextual Processing: Evidence from Brain Lesions

ERIC Educational Resources Information Center

Fogelson, Noa; Shah, Mona; Scabini, Donatella; Knight, Robert T.

2009-01-01

We investigated the role of prefrontal cortex (PFC) in local contextual processing using a combined event-related potentials and lesion approach. Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Targets were preceded by either randomized sequences of standards…

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste

PubMed Central

Al Khasawnah, Qusai; Hassan, Fathi; Malhan, Deeksha; Engelhardt, Markus; Daghma, Diaa Eldin S.; Obidat, Dima; Lips, Katrin S.; Heiss, Christian

2018-01-01

Background The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. Materials and Methods Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. Results No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. Conclusion CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase. PMID:29619378

Prospective Trial with Optical Molecular Imaging for Percutaneous Interventions in Focal Hepatic Lesions

PubMed Central

Sheth, Rahul A.; Arellano, Ronald S.; Uppot, Raul N.; Samir, Anthony E.; Goyal, Lipika; Zhu, Andrew X.; Gervais, Debra A.

2015-01-01

Purpose To demonstrate the clinical translation of optical molecular imaging (OMI) for the localization of focal hepatic lesions during percutaneous hepatic interventions. Materials and Methods Institutional review board approval was obtained for this prospective, single-center, HIPAA-compliant trial. Patients who were suspected of having hepatocellular carcinoma or liver metastases from colorectal cancer and were scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Patients (n = 5) received 0.5 mg per kilogram of body weight of indocyanine green (ICG) intravenously 24 hours prior to their scheduled procedure in this study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17-gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence in biopsy samples. Target-to-background ratios (TBRs) were calculated by dividing the mean fluorescence intensity in the lesion by the mean fluorescence intensity in the adjacent liver parenchyma. The reference standard for determination of proper needle positioning in patients undergoing biopsy was final pathologic analysis of biopsy specimens or follow-up imaging. Results Intraprocedural OMI was successfully performed in six lesions (two lesions in patient 3) in five patients. The median size of the targeted lesions was 16 mm (range, 10–21 mm). Four of five biopsies (80%) yielded an accurate pathologic diagnosis, and one biopsy specimen showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with TBRs greater than 2.0 (median, 7.9; range, 2.4–13.4) in all target lesions. No trial-related adverse events were reported. Conclusion The clinical translation of OMI to

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

NASA Astrophysics Data System (ADS)

Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

2012-11-01

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for

The PARAGON stent study: a randomized trial of a new martensitic nitinol stent versus the Palmaz-Schatz stent for treatment of complex native coronary arterial lesions.

PubMed

Holmes, D R; Lansky, A; Kuntz, R; Bell, M R; Buchbinder, M; Fortuna, R; O'Shaughnessy, C D; Popma, J

2000-11-15

A new martensitic nitinol stent with improved flexibility and radiopacity was tested to evaluate whether these differences improve initial or long-term outcome. Patients who underwent percutaneous revascularization of a discrete native coronary lesion were randomly assigned to the new stent (PARAGON, n = 349) or to the first-generation Palmaz-Schatz (PS) stent (n = 339). The primary end point was target vessel failure at 6 months (a composite of cardiac or noncardiac death, any infarction in the distribution of the treated vessel, or clinically indicated target vessel revascularization). Secondary end points were, among others, device and procedural success and angiographic restenosis. Mean age was 62 years; diabetes was present in 21% of patients, prior bypass surgery in 6%, and recent infarction in 22% (p = NS for comparison between the 2 randomized arms). The PARAGON stent group had smaller reference vessels (2.97 vs 3.05 mm, p = 0.05), more prior restenosis (8.0% vs 4.5%, p = 0.07), and a longer average stent length (21.3 vs 19.4 mm, p < 0.05). Device success was significantly higher in the PARAGON arm (99.1% vs 94.3%, p < 0.05). Death and infarction at 6-month follow-up were infrequent in both groups. There was no significant difference in death (2.0% vs 1.2%, p = 0.546), but a higher rate of infarction for the PARAGON cohort (9.2% vs 4.7%, p = 0.025). Although target vessel failure (20.3% vs 12.4%, p = 0.005) and target lesion revascularization (12.0% vs 5.9%, p = 0.005) were higher in the PARAGON group, there was no significant difference in 6-month follow-up in in-stent minimal lumen diameter or in the rate of binary angiographic restenosis. Both PARAGON and PS stents are safe and associated with infrequent adverse events. The PARAGON stent can be delivered more frequently than the first-generation PS stent. Although there was no significant difference in in-stent minimal lumen diameter or the frequency of angiographic restenosis, clinical restenosis was

Midline thalamic reuniens lesions improve executive behaviors.

PubMed

Prasad, J A; Abela, A R; Chudasama, Y

2017-03-14

The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes. Following NRe lesions, the animals became more efficient in their performance, responding with shorter reaction times but also less impulsively than controls. This change, combined with a decrease in perseverative responses, led to focused attention in the CAM task and accelerated learning in the visual discrimination task. There were no observed changes in tasks involving either spatial memory or value-based decision making. These data complement ongoing efforts to understand the role of midline thalamic structures in human cognition, including the development of thalamic stimulation as a therapeutic strategy for acquired cognitive disabilities (Schiff, 2008; Mair et al., 2011), and point to the NRe as a potential target for clinical intervention. Published by Elsevier Ltd.

Small white matter lesion detection in cerebral small vessel disease

NASA Astrophysics Data System (ADS)

Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

2015-03-01

Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

PubMed Central

Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-01-01

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

A prospective observational cohort study in primary care practices to identify factors associated with treatment failure in Staphylococcus aureus skin and soft tissue infections.

PubMed

Lee, Grace C; Hall, Ronald G; Boyd, Natalie K; Dallas, Steven D; Du, Liem C; Treviño, Lucina B; Treviño, Sylvia B; Retzloff, Chad; Lawson, Kenneth A; Wilson, James; Olsen, Randall J; Wang, Yufeng; Frei, Christopher R

2016-11-22

The incidence of outpatient visits for skin and soft tissue infections (SSTIs) has substantially increased over the last decade. The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has made the management of S. aureus SSTIs complex and challenging. The objective of this study was to identify risk factors contributing to treatment failures associated with community-associated S. aureus skin and soft tissue infections SSTIs. This was a prospective, observational study among 14 primary care clinics within the South Texas Ambulatory Research Network. The primary outcome was treatment failure within 90 days of the initial visit. Univariate associations between the explanatory variables and treatment failure were examined. A generalized linear mixed-effect model was developed to identify independent risk factors associated with treatment failure. Overall, 21% (22/106) patients with S. aureus SSTIs experienced treatment failure. The occurrence of treatment failure was similar among patients with methicillin-resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19 vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with S. aureus SSTIs was a duration of infection of ≥7 days prior to initial visit [aOR, 6.02 (95% CI 1.74-19.61)] and a lesion diameter size ≥5 cm [5.25 (1.58-17.20)]. Predictors for treatment failure included a duration of infection for ≥7 days prior to the initial visit and a wound diameter of ≥5 cm. A heightened awareness of these risk factors could help direct targeted interventions in high-risk populations.

Postoperative chronic renal failure: a new syndrome?

PubMed Central

Merino, G E; Buselmeier, T J; Kjellstrand, C M

1975-01-01

Of 125 patients with postsurgical acute tubular necrosis, 87 died, 34 regained clinical normal renal function, and 4 survivors (9.5%) were left with severe permanent renal failure, two of whom required chronic dialysis and transplantation. Preoperatively these 4 patients had normal renal function. The 4 patients were above age 60, two had undergone methoxyflurane anesthesia, and nephrotoxic antibiotics were used in all. The incidence of permanent renal failure is much higher than ever reported and may reflect the survival of patients who previously died because of less ideal dialysis. We believe that the cause of this permanent lesion is multifactorial, including age (over 60 years), nephrotoxic antibiotics (particularly cephalothin and gentamicin sulfate), and nephrotoxic anesthetic (methoxyflurane) agents. This combination of factors should be avoided whenever possible. Images Fig. 2. PMID:1147707

Determination of lesion size by ultrasound during radiofrequency catheter ablation.

PubMed

Awad, S; Eick, O

2003-01-01

The catheter tip temperature that is used to control the radiofrequency generator output poorly correlates to lesion size. We, therefore, evaluated lesions created in vitro using a B-mode ultrasound imaging device as a potential means to assess lesion generation during RF applications non-invasively. Porcine ventricular tissue was immersed in saline solution at 37 degrees C. The catheter was fixed in a holder and positioned in a parallel orientation to the tissue with an array transducer (7.5 MHz) app. 3 cm above the tissue. Lesions were produced either in a temperature controlled mode with a 4-mm tip catheter with different target temperatures (50, 60, 70 and 80 degrees C, 80 W maximum output) or in a power controlled mode (25, 50 and 75 W, 20 ml/min irrigation flow) using an irrigated tip catheter. Different contact forces (0.5 N, 1.0 N) were tested, and RF was delivered for 60 s. A total of 138 lesions was produced. Out of these, 128 could be identified on the ultrasound image. The lesion depth and volume was on average 4.1 +/- 1.6 mm and 52 +/- 53 mm3 as determined by ultrasound and 3.9 +/- 1.7 mm and 52 +/- 55 mm3 as measured thereafter, respectively. A linear correlation between the lesion size determined by ultrasound and that measured thereafter was demonstrated with a correlation coefficient of r = 0.87 for lesion depth and r = 0.93 for lesion volume. We conclude that lesions can be assessed by B-mode ultrasound imaging.

The value of whole lesion ADC histogram profiling to differentiate between morphologically indistinguishable ring enhancing lesions-comparison of glioblastomas and brain abscesses.

PubMed

Horvath-Rizea, Diana; Surov, Alexey; Hoffmann, Karl-Titus; Garnov, Nikita; Vörkel, Cathrin; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Bäzner, Hansjörg; Gihr, Georg Alexander; Kalman, Marcell; Henkes, Elina; Henkes, Hans; Schob, Stefan

2018-04-06

Morphologically similar appearing ring enhancing lesions in the brain parenchyma can be caused by a number of distinct pathologies, however, they consistently represent life-threatening conditions. The two most frequently encountered diseases manifesting as such are glioblastoma multiforme (GBM) and brain abscess (BA), each requiring disparate therapeutical approaches. As a result of their morphological resemblance, essential treatment might be significantly delayed or even ommited, in case results of conventional imaging remain inconclusive. Therefore, our study aimed to investigate, whether ADC histogram profiling reliably can distinguish between both entities, thus enhancing the differential diagnostic process and preventing treatment failure in this highly critical context. 103 patients (51 BA, 52 GBM) with histopathologically confirmed diagnosis were enrolled. Pretreatment diffusion weighted imaging (DWI) was obtained in a 1.5T system using b values of 0, 500, and 1000 s/mm 2 . Whole lesion ADC volumes were analyzed using a histogram-based approach. Statistical analysis was performed using SPSS version 23. All investigated parameters were statistically different in comparison of both groups. Most importantly, ADCp10 was able to differentiate reliably between BA and GBM with excellent accuracy (0.948) using a cutpoint value of 70 × 10 -5 mm 2 × s -1 . ADC whole lesion histogram profiling provides a valuable tool to differentiate between morphologically indistinguishable mass lesions. Among the investigated parameters, the 10th percentile of the ADC volume distinguished best between GBM and BA.

Assessing Similarity Among Individual Tumor Size Lesion Dynamics: The CICIL Methodology

PubMed Central

Girard, Pascal; Ioannou, Konstantinos; Klinkhardt, Ute; Munafo, Alain

2018-01-01

Mathematical models of tumor dynamics generally omit information on individual target lesions (iTLs), and consider the most important variable to be the sum of tumor sizes (TS). However, differences in lesion dynamics might be predictive of tumor progression. To exploit this information, we have developed a novel and flexible approach for the non‐parametric analysis of iTLs, which integrates knowledge from signal processing and machine learning. We called this new methodology ClassIfication Clustering of Individual Lesions (CICIL). We used CICIL to assess similarities among the TS dynamics of 3,223 iTLs measured in 1,056 patients with metastatic colorectal cancer treated with cetuximab combined with irinotecan, in two phase II studies. We mainly observed similar dynamics among lesions within the same tumor site classification. In contrast, lesions in anatomic locations with different features showed different dynamics in about 35% of patients. The CICIL methodology has also been implemented in a user‐friendly and efficient Java‐based framework. PMID:29388396

Phantom experiments to improve parathyroid lesion detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Kenneth J.; Tronco, Gene G.; Tomas, Maria B.

2007-12-15

This investigation tested the hypothesis that visual analysis of iteratively reconstructed tomograms by ordered subset expectation maximization (OSEM) provides the highest accuracy for localizing parathyroid lesions using {sup 99m}Tc-sestamibi SPECT data. From an Institutional Review Board approved retrospective review of 531 patients evaluated for parathyroid localization, image characteristics were determined for 85 {sup 99m}Tc-sestamibi SPECT studies originally read as equivocal (EQ). Seventy-two plexiglas phantoms using cylindrical simulated lesions were acquired for a clinically realistic range of counts (mean simulated lesion counts of 75{+-}50 counts/pixel) and target-to-background (T:B) ratios (range=2.0 to 8.0) to determine an optimal filter for OSEM. Two experiencedmore » nuclear physicians graded simulated lesions, blinded to whether chambers contained radioactivity or plain water, and two observers used the same scale to read all phantom and clinical SPECT studies, blinded to pathology findings and clinical information. For phantom data and all clinical data, T:B analyses were not statistically different for OSEM versus FB, but visual readings were significantly more accurate than T:B (88{+-}6% versus 68{+-}6%, p=0.001) for OSEM processing, and OSEM was significantly more accurate than FB for visual readings (88{+-}6% versus 58{+-}6%, p<0.0001). These data suggest that visual analysis of iteratively reconstructed MIBI tomograms should be incorporated into imaging protocols performed to localize parathyroid lesions.« less

Outcomes of Patients Treated with the Everolimus- versus the Paclitaxel-Eluting Stents in a Consecutive Cohort of Patients at a Tertiary Medical Center.

PubMed

Shammas, Nicolas W; Shammas, Gail A; Nader, Elie; Jerin, Michael; Mrad, Luay; Ehrecke, Nicholas; Shammas, Waheeb J; Voelliger, Cara M; Hafez, Alexander; Kelly, Ryan; Reynolds, Emily

2013-09-01

In this study, we compare the outcomes of the paclitaxel-eluting stent (PES) versus the everolimus-eluting stent (EES) treated patients at a tertiary medical center and up to 2 years follow-up. Unselected consecutive patients were retrospectively recruited following stenting with PES (159 patients) or EES (189 patients). The primary endpoint of the study was target lesion failure (TLF), defined as the combined endpoint of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR). Secondary endpoints included target vessel revascularization (TVR), TLR, target vessel failure (TVF), acute stent thrombosis (ST), total death, cardiac death, and nonfatal MI. Patients treated with the PES stent had less congestive heart failure and restenotic lesions, but a higher prevalence of longer lesions, nonleft main bifurcations, required more stents per patient (4.3 ± 2.8 vs. 2.9 ± 2.1). TLF occurred in 32.3% PES versus 21.5% EES (p = 0.027). The secondary unadjusted endpoints for PES versus EES, respectively, were TVF 38.6 versus 30.7% (p = 0.140), TVR 35.7 versus 26.5% (p = 0.079), definite and probable ST 1.2 versus 0.0%, nonfatal MI 4.5 versus 4.2%, and mortality 9.6 versus 4.0%. Logistic regression analysis showed that the numbers of stents per patient (p = 0.001), age (p = 0.01), and renal failure (p = 0.045) were independent predictors of TLF. Using univariate analysis, EES had lower TLF than PES in a cohort of unselected patients undergoing percutaneous coronary intervention at 2 years follow-up. Multivariate analysis showed that the numbers of stents per patient, age, and renal failure, but not stent type, were predictors of TLF.

Neurophysiology and Neuroanatomy of Smooth Pursuit: Lesion Studies

ERIC Educational Resources Information Center

Sharpe, James A.

2008-01-01

Smooth pursuit impairment is recognized clinically by the presence of saccadic tracking of a small object and quantified by reduction in pursuit gain, the ratio of smooth eye movement velocity to the velocity of a foveal target. Correlation of the site of brain lesions, identified by imaging or neuropathological examination, with defective smooth…

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

PubMed

Kossard, S; Collins, A; McCrossin, I

1987-05-01

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

Evaluation of the 4-French Pulsar-18 Self-expanding Nitinol Stent in Long Femoropopliteal Lesions.

PubMed

Lichtenberg, Michael; Hailer, Birgit; Kaeunicke, Matthias; Stahlhoff, Wilhelm-Friedrich; Boese, Dirk; Breuckmann, Frank

2014-01-01

To evaluate the patency and the freedom of target lesion revascularization of the 4-French Pulsar-18 self-expandable (SE) nitinol stent for the treatment of long femoropopliteal occlusive disease in a two-center, prospective, all-comers registry with a follow-up period of 12 months. This registry enrolled 36 patients with symptomatic femoropopliteal long lesions for recanalization and implantation of the 4-French Pulsar-18 SE nitinol stent. Routine follow-up examination including duplex ultrasound was performed after 6 and 12 months. Primary patency was defined as no binary restenosis on duplex ultrasound (Peak systolic velocitiy ration (PSVR) <2.5) and no target lesion revascularization was performed within 12 months' follow-up. No drug-eluting devices were allowed in this registry. Average lesion length of the femoropopliteal segment was 182.3 ± 51.8 mm. Mean stent implantation length was 181.5 ± 35.4 mm. Total occlusion was present in 46 of the 48 (95.8%) treated lesions. Involvement of popliteal segment I-III was present in 3 (6.3%) lesions. The primary patency after 6 and 12 months was 87.5% and 85.4%, respectively. The clinically driven overall freedom from target lesion revascularization (fTLR) was 89.6% after 6 months and 87.5% after 12 months. ABI, pain-free walking distance and Rutherford category, all improved significantly (P < 0.001) after 6 and 12 months. The primary patency rate in patients with diabetes (P = 0.18) and renal insufficiency (P = 0.3) was not significantly lower as compared to the overall primary patency. In this two-center, all-comers registry, the use of the Pulsar-18 SE nitinol stent for endovascular intervention of femoropopliteal disease with a mean lesion length of 182.3 ± 51.8 mm showed promising primary patency and fTLR rates after 6 and 12 months. Diabetes and renal insufficiency had no negative impact on the patency rate.

Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions.

PubMed

Field, Scott S

2016-02-01

Type 1 herpes simplex virus (HSV-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. Genital acquisition of type 2 HSV is the usual mode for neonatal herpes, but HSV-1 transmission by genital or extragenital means may result in greater mortality rates. A very rare scenario is presented in which the mode of transmission was likely through breast lesions. The lesions were seen by nurses as well as the lactation consultant and obstetrician in the hospital after delivery of the affected baby but not recognized as possibly being caused by herpes. The baby died 9 days after birth with hepatic failure and disseminated intravascular coagulation. Peripartum health care workers need to be aware of potential nongenital (including from the breast[s]) neonatal herpes acquisition, which can be lethal. © The Author(s) 2015.

Five myofibrillar lesion types in eccentrically challenged, unloaded rat adductor longus muscle--a test model

NASA Technical Reports Server (NTRS)

Thompson, J. L.; Balog, E. M.; Fitts, R. H.; Riley, D. A.

1999-01-01

calcium homeostasis loss (focal contraction lesions) and "thick-filament-centering" failure of titin (wide A-band lesions) in the early stages of lesion development.

Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

PubMed

Hirayama, Ryuichi; Kinoshita, Manabu; Arita, Hideyuki; Kagawa, Naoki; Kishima, Haruhiko; Hashimoto, Naoya; Fujimoto, Yasunori; Yoshimine, Toshiki

2018-06-01

OBJECTIVE In the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques. METHODS Magnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D. RESULTS The 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities. CONCLUSIONS Using an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

A non-invasive navigation system for retargeting gastroscopic lesions.

PubMed

Liu, Jiquan; Wang, Bin; Hu, Weiling; Zong, Yun; Si, Jianmin; Duan, Huilong

2014-01-01

Biopsy is a traditional endoscopic surveillance of premalignant gastric lesions, and endoscopic tattooing is used for marking the biopsy's location. However, the tattooing has several disadvantages. For example, the procedure is an invasive operation and may not be durable due to the diffusion. Moreover, it is procedurally cumbersome with an associated risk of technical failure. In this study, a computer aided endoscopic navigation system (CAEN system) was developed for a non-invasive biopsy procedure. The CAEN system consists of a new, designed six degree of freedom (6-DOF) tracking endoscope device and a computer simulated work station. During the procedure, the endoscopist uses the tip of the tracking endoscope to touch the lesion. Then, the lesion's location is recorded in the work station, which then guides the endoscopist in retargeting the lesions in the follow-ups. The clinical experimental results demonstrate that the accuracy at the angularis is 5.2 ± 2.8 mm, at the antral lesser curvature is 7.2 ± 2.0 mm, at the antral greater curvature is 6.3 ± 3.1 mm, at the antral posterior wall is 8.2 ± 1.6 mm, and at the antral anterior wall is 7.9 ± 1.3 mm. The mean accuracy is 7.5 mm, and the P-value is 0.023, which is likely suitable for clinical practice. Furthermore, the proposed CAEN system requires less procedural time than the tattooing.

New Medications for Heart Failure

PubMed Central

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

Combining neuroendocrine inhibitors in heart failure: reflections on safety and efficacy.

PubMed

Jneid, Hani; Moukarbel, George V; Dawson, Bart; Hajjar, Roger J; Francis, Gary S

2007-12-01

Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors.

Multispectral near-infrared reflectance and transillumination imaging of occlusal carious lesions: variations in lesion contrast with lesion depth

NASA Astrophysics Data System (ADS)

Simon, Jacob C.; Curtis, Donald A.; Darling, Cynthia L.; Fried, Daniel

2018-02-01

In vivo and in vitro studies have demonstrated that near-infrared (NIR) light at λ=1300-1700-nm can be used to acquire high contrast images of enamel demineralization without interference of stains. The objective of this study was to determine if a relationship exists between the NIR image contrast of occlusal lesions and the depth of the lesion. Extracted teeth with varying amounts of natural occlusal decay were measured using a multispectral-multimodal NIR imaging system which captures λ=1300-nm occlusal transillumination, and λ=1500-1700-nm cross-polarized reflectance images. Image analysis software was used to calculate the lesion contrast detected in both images from matched positions of each imaging modality. Samples were serially sectioned across the lesion with a precision saw, and polarized light microscopy was used to measure the respective lesion depth relative to the dentinoenamel junction. Lesion contrast measured from NIR crosspolarized reflectance images positively correlated (p<0.05) with increasing lesion depth and a statistically significant difference between inner enamel and dentin lesions was observed. The lateral width of pit and fissures lesions measured in both NIR cross-polarized reflectance and NIR transillumination positively correlated with lesion depth.

Oral Mucosal Lesions in Indians From Northeast Brazil

PubMed Central

Cury, Patricia Ramos; Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; e Ribeiro, Livia Silva Figueiredo; de Aquino Xavier, Flavia Caló; Figueiredo, Andreia Leal; Ramalho, Luciana Maria Pedreira

2014-01-01

Abstract The aim of this cross-sectional study was to evaluate the prevalence of oral mucosal lesions, and their risk indicators in adult Kiriri Indians from Northeast Brazil. Clinical oral examination was performed on a representative sample of 223 Indians (age ≥19 years). A systematic evaluation of lips, labial mucosa and sulcus, commissures, buccal mucosa and sulcus, gingiva and alveolar ridge, tongue, floor of the mouth, and soft and hard palate was performed. Bivariate analysis was conducted to assess associations between mucosal conditions and age, gender, income, educational level, diabetic status, and smoking status. Mucosal lesions were found in 50 participants (22.4%). The most prevalent lesions were fistulae (6.2%) and traumatic ulcers (4.48%). Oral mucosal was associated with higher age (≥35 years; odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.05–3.76, P = 0.03) and lower education level (<9 years; OR = 2.13, 95% CI: 0.96–4.71, P = 0.06). Mucosal conditions are prevalent in Kiriri Indians and the presence of mucosal lesions is associated with advanced age and lower education. A public health program aimed at preventing and treating mucosal lesions and targeted toward the high-risk group is vital to improve the oral health status of this population. PMID:25501053

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

PubMed

Peca, Donatella; Petrini, Stefania; Tzialla, Chryssoula; Boldrini, Renata; Morini, Francesco; Stronati, Mauro; Carnielli, Virgilio P; Cogo, Paola E; Danhaive, Olivier

2011-08-25

Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

PubMed Central

2011-01-01

Background Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two

Visually guided locomotion and computation of time-to-collision in the mongolian gerbil (Meriones unguiculatus): the effects of frontal and visual cortical lesions.

PubMed

Shankar, S; Ellard, C

2000-02-01

Past research has indicated that many species use the time-to-collision variable but little is known about its neural underpinnings in rodents. In a set of three experiments we set out to replicate and extend the findings of Sun et al. (Sun H-J, Carey DP, Goodale MA. Exp Brain Res 1992;91:171-175) in a visually guided task in Mongolian gerbils, and then investigated the effects of lesions to different cortical areas. We trained Mongolian gerbils to run in the dark toward a target on a computer screen. In some trials the target changed in size as the animal ran toward it in such a way as to produce 'virtual targets' if the animals were using time-to-collision or contact information. In experiment 1 we confirmed that gerbils use time-to-contact information to modulate their speed of running toward a target. In experiment 2 we established that visual cortex lesions attenuate the ability of lesioned animals to use information from the visual target to guide their run, while frontal cortex lesioned animals are not as severely affected. In experiment 3 we found that small radio-frequency lesions, of either area VI or of the lateral extrastriate regions of the visual cortex also affected the use of information from the target to modulate locomotion.

Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review.

PubMed

Oussedik, Sam; Tsitskaris, Konstantinos; Parker, David

2015-04-01

We performed a systematic review of the treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation to determine the differences in patient outcomes after these procedures. We searched PubMed/Medline, Embase, and The Cochrane Library databases in the period from January 10 through January 20, 2013, and included 34 articles in our qualitative analysis. All studies showed improvement in outcome scores in comparison with baseline values, regardless of the treatment modality. The heterogeneity of the results presented in the studies precluded a meta-analysis. Microfracture appears to be effective in smaller lesions and is usually associated with a greater proportion of fibrocartilage production, which may have an effect on durability and eventual failure. Autologous chondrocyte implantation is an effective treatment that may result in a greater proportion of hyaline-like tissue at the repair site, which may in turn have a beneficial effect on durability and failure; it appears to be effective in larger lesions. Autologous chondrocyte implantation with periosteum has been shown to be associated with symptomatic cartilage hypertrophy more frequently than autologous chondrocyte implantation with collagen membrane. Matrix-associated autologous chondrocyte implantation is technically less challenging than the other techniques available, and in lesions greater than 4 cm(2), it has been shown to be more effective than microfracture. Level IV, systematic review of Level I-IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Initial load-to-failure and failure analysis in single- and double-row repair techniques for rotator cuff repair.

PubMed

Baums, M H; Buchhorn, G H; Gilbert, F; Spahn, G; Schultz, W; Klinger, H-M

2010-09-01

This experimental study aimed to compare the load-to-failure rate and stiffness of single- versus double-row suture techniques for repairing rotator cuff lesions using two different suture materials. Additionally, the mode of failure of each repair was evaluated. In 32 sheep shoulders, a standardized tear of the infraspinatus tendon was created. Then, n = 8 specimen were randomized to four repair methods: (1) Double-row Anchor Ethibond coupled with polyester sutures, USP No. 2; (2) Double-Row Anchor HiFi with polyblend polyethylene sutures, USP No. 2; (3) Single-Row Anchor Ethibond coupled with braided polyester sutures, USP No. 2; and (4) Single-Row Anchor HiFi with braided polyblend polyethylene sutures, USP No. 2. Arthroscopic Mason-Allen stitches were placed (single-row) and combined with medial horizontal mattress stitches (double-row). All specimens were loaded to failure at a constant displacement rate on a material testing machine. Group 4 showed lowest load-to-failure result with 155.7 +/- 31.1 N compared to group 1 (293.4 +/- 16.1 N) and group 2 (397.7 +/- 7.4 N) (P < 0.001). Stiffness was highest in group 2 (162 +/- 7.3 N/mm) and lowest in group 4 (84.4 +/- 19.9 mm) (P < 0.001). In group 4, the main cause of failure was due to the suture cutting through the tendon (n = 6), a failure case observed in only n = 1 specimen in group 2 (P < 0.001). A double-row technique combined with arthroscopic Mason-Allen/horizontal mattress stitches provides high initial failure strength and may minimize the risk of the polyethylene sutures cutting through the tendon in rotator cuff repair when a single load force is used.

Lack of magnetic resonance imaging lesion activity as a treatment target in multiple sclerosis: An evaluation using electronically collected outcomes.

PubMed

Conway, Devon S; Thompson, Nicolas R; Cohen, Jeffrey A

2016-09-01

The appropriate treatment target in multiple sclerosis (MS) is unclear. Lack of magnetic resonance imaging (MRI) lesion activity, a component of the no evidence of disease activity concept, has been proposed as a treatment target in MS. We used our MS database to investigate whether aggressively pursuing MRI stability by changing disease modifying therapy (DMT) when MRI activity is observed leads to better clinical and imaging outcomes. The Knowledge Program (KP) is a database linked to our electronic medical record allowing capture of patient and clinician reported outcomes. Through KP query and chart review, we identified all relapsing-remitting MS patients visiting between 1 January 2008 and 31 December 2014 with active MRIs despite DMT. Propensity modeling based on demographic and disease characteristics was used to match DMT switchers to non-switchers. KP and MRI outcomes were compared 18 months after the active MRI using mixed-effects linear regression models. We identified 417 patients who met criteria for our analysis. After propensity matching, 78 switchers and 91 non-switchers were analyzed. There was no difference in clinical or radiologic outcomes between these groups at 18 months. We did not find a short-term benefit of changing DMT to pursue MRI stability. Copyright © 2016 Elsevier B.V. All rights reserved.

Lesion size estimator of cardiac radiofrequency ablation at different common locations with different tip temperatures.

PubMed

Lai, Yu-Chi; Choy, Young Bin; Haemmerich, Dieter; Vorperian, Vicken R; Webster, John G

2004-10-01

Finite element method (FEM) analysis has become a common method to analyze the lesion formation during temperature-controlled radiofrequency (RF) cardiac ablation. We present a process of FEM modeling a system including blood, myocardium, and an ablation catheter with a thermistor embedded at the tip. The simulation used a simple proportional-integral (PI) controller to control the entire process operated in temperature-controlled mode. Several factors affect the lesion size such as target temperature, blood flow rate, and application time. We simulated the time response of RF ablation at different locations by using different target temperatures. The applied sites were divided into two groups each with a different convective heat transfer coefficient. The first group was high-flow such as the atrioventricular (AV) node and the atrial aspect of the AV annulus, and the other was low-flow such as beneath the valve or inside the coronary sinus. Results showed the change of lesion depth and lesion width with time, under different conditions. We collected data for all conditions and used it to create a database. We implemented a user-interface, the lesion size estimator, where the user enters set temperature and location. Based on the database, the software estimated lesion dimensions during different applied durations. This software could be used as a first-step predictor to help the electrophysiologist choose treatment parameters.

Functional lesional neurosurgery for tremor-a protocol for a systematic review and meta-analysis.

PubMed

Schreglmann, Sebastian R; Krauss, Joachim K; Chang, Jin Woo; Bhatia, Kailash P; Kägi, Georg

2017-05-09

The recent introduction of incision-less lesional neurosurgery using Gamma Knife and MRI-guided focused ultrasound has revived interest in lesional treatment options for tremor disorders. Preliminary literature researches reveal that the consistency of treatment effects after lesional neurosurgery for tremor has not formally been assessed yet. Similarly, the efficacy of different targets for lesional treatment and incidence of persistent side effects of lesional neurosurgical interventions has not been comprehensively assessed. This work therefore aims to describe a suitable process how to review the existing literature on efficacy and persistent side effects of lesional neurosurgical treatment for tremor due to Parkinson's disease, essential tremor, multiple sclerosis and midbrain/rubral tremor. We will search electronic databases (Medline, Cochrane) and reference lists of included articles for studies reporting lesional interventions for tremor in cohorts homogeneous for tremor aetiology and intervention (technique and target). We will include cohorts with a minimum number of five subjects and follow-up of 2 months. One investigator will perform the initial literature search and two investigators then independently decide which references to include for final efficacy and safety analysis. After settling of disagreement, data will be extracted from articles using a standardised template. We will perform a random-effect meta-analysis calculating standardised mean differences (Hedge's g) for comparison in Forest plots and subgroup analysis after assessment of heterogeneity using I 2 statistics. This study will summarise the available evidence on the efficacy of lesional interventions for the most frequent tremor disorders, as well as for the incidence rate of persisting side effects after unilateral lesional treatment. This data will be useful to guide future work on incision-less lesional interventions for tremor. This study has been registered with the PROSPERO

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

PubMed

Selim, Ahmed M; Sarswat, Nitasha; Kelesidis, Iosif; Iqbal, Muhammad; Chandra, Ramesh; Zolty, Ronald

2017-05-01

The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Orbital atherectomy for treating de novo, severely calcified coronary lesions: 3-year results of the pivotal ORBIT II trial.

PubMed

Lee, Michael; Généreux, Philippe; Shlofmitz, Richard; Phillipson, Daniel; Anose, Bynthia M; Martinsen, Brad J; Himmelstein, Stevan I; Chambers, Jeff W

2017-06-01

The presence of heavy coronary artery calcification increases the complexity of percutaneous coronary intervention (PCI) and increases the incidence of major adverse cardiac events (MACE): death, myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis. The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial reported low rates of procedural, 30-day, 1-year, and 2-year ischemic complications after treatment of de novo, severely calcified lesions with the Diamondback 360° Coronary Orbital Atherectomy System (OAS) (Cardiovascular Systems, Inc.). ORBIT II was a single-arm trial that enrolled 443 patients at 49U.S. sites; in this study, de novo, severely calcified coronary lesions were treated with OAS prior to stenting. The primary safety endpoint was 30-day MACE: the composite of cardiac death, MI, and TVR (inclusive of target lesion revascularization (TLR)). The primary efficacy endpoint was procedural success: stent delivery with a residual stenosis of <50% without the occurrence of in-hospital MACE.The present analysis reports the final, 3-year follow-up results from ORBIT II. The majority of subjects (88.2%) underwent PCI with drug-eluting stents after orbital atherectomy. There were 360 (81.3%) subjects who completed the protocol-mandated 3-year visit.The overall cumulative rate of 3-year MACE was 23.5%, including cardiac death (6.7%), MI (11.2%), and TVR (10.2%). The 3-year target lesion revascularization rate was 7.8%. In the final 3-year analysis of the ORBIT II trial, orbital atherectomy of severely calcified coronary lesions followed by stenting resulted in a low rate of adverse ischemic events compared with historical controls.Orbital atherectomy represents a safe and effective revascularization strategy for patients with severely calcified coronary lesions. The ORBIT II trial enrolled 443 subjects to study orbital atherectomy followed by stenting for de novo severely

Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis

PubMed Central

Seehusen, Frauke; Al-Azreg, Seham A.; Raddatz, Barbara B.; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

2016-01-01

In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease. PMID:27441688

Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

PubMed

Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

2016-01-01

In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

Sources of Phoneme Errors in Repetition: Perseverative, Neologistic, and Lesion Patterns in Jargon Aphasia

PubMed Central

Pilkington, Emma; Keidel, James; Kendrick, Luke T.; Saddy, James D.; Sage, Karen; Robson, Holly

2017-01-01

This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI) of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed. PMID:28522967

Example based lesion segmentation

NASA Astrophysics Data System (ADS)

Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

2014-03-01

Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

Drug-Coated Balloon Treatment of Femoropopliteal Lesions for Patients With Intermittent Claudication and Ischemic Rest Pain: 2-Year Results From the IN.PACT Global Study.

PubMed

Micari, Antonio; Brodmann, Marianne; Keirse, Koen; Peeters, Patrick; Tepe, Gunnar; Frost, Martin; Wang, Hong; Zeller, Thomas

2018-05-28

The IN.PACT Global Study is the largest prospective, multicenter, independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and/or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in randomized controlled trials. Randomized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter-Society Consensus Document II A and B lesions, but there is a need for large-scale prospective studies to evaluate a broader range of lesions. The IN.PACT Global Study enrolled 1,535 subjects, and 1,406 (1,773 lesions) were included in the pre-defined clinical cohort analysis. Freedom from clinically driven target lesion revascularization was evaluated at 24 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven target vessel revascularization within 24 months. Mean lesion length was 12.1 cm, 35.5% were total occlusions, and 18.0% had in-stent restenosis. Freedom from clinically driven target lesion revascularization at 24 months was 83.3%, the composite safety endpoint was met in 81.7%, the 2-year all-cause mortality rate was 7.0%, and the major target limb amputation rate was 0.7%. Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinically driven target lesion revascularization by 24 months. This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly designed randomized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment. (IN.PACT Global Clinical Study; NCT01609296). Copyright © 2018 The Authors. Published by

Human ventromedial prefrontal lesions alter incentivisation by reward

PubMed Central

Manohar, Sanjay G.; Husain, Masud

2016-01-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. PMID:26874940

Transient neonatal renal failure and massive polyuria in MEGDEL syndrome.

PubMed

Harbulot, Carole; Paquay, Stéphanie; Dorboz, Imen; Pichard, Samia; Bourillon, Agnès; Benoist, Jean-François; Jardel, Claude; Ogier de Baulny, Hélène; Boespflug-Tanguy, Odile; Schiff, Manuel

2016-06-01

MEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome) syndrome is a mitochondrial disorder associated with recessive mutations in SERAC1. To report transient neonatal renal findings in MEGDEL syndrome. This 7 year-old girl was the first child of consanguineous Turkish parents. She exhibited an acute neonatal deterioration with severe lactic acidosis and liver failure. Initial evaluation revealed massive polyuria and renal failure with 3-methylglutaconic aciduria. Symptoms and biological findings progressively improved with symptomatic treatment but lactic acidosis and high lactate to pyruvate ratio along with 3-methylglutaconic aciduria persisted. At 8 months of age, a subacute neurological degradation occurred with severe hypotonia, dystonia with extrapyramidal movements and failure to thrive. Brain MRI revealed basal ganglia lesions suggestive of Leigh syndrome. At 3 years of age, sensorineural deafness was documented. MEGDEL syndrome was further confirmed by the identification of an already reported homozygous mutation in SERAC1. Transient neonatal polyuria and renal failure have not been reported to date in SERAC1 defective patients. Such neonatal kidney findings expand the clinical spectrum of MEGDEL syndrome.

Treating vascular lesions.

PubMed

Astner, Susanne; Anderson, R Rox

2005-01-01

The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

PubMed

Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S; Langkilde, Annika; Paulson, Olaf B; Lange, Theis; Thomsen, Carsten; Olsen, Peter Skov; Ravn, Hanne Berg; Nilsson, Jens C

2018-04-24

Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min -1 ·m -2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0-118 mm 3 ; range, 0-25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0-143 mm 3 ; range, 0-22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P =0

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

PubMed

Gold, Samuel A; Hale, Graham R; Bloom, Jonathan B; Smith, Clayton P; Rayn, Kareem N; Valera, Vladimir; Wood, Bradford J; Choyke, Peter L; Turkbey, Baris; Pinto, Peter A

2018-05-21

Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

PubMed

Sandoval-Sus, Jose D; Mogollon-Duffo, Francis; Patel, Ankita; Visweshwar, Nathan; Laber, Damian A; Kim, Richard; Jagal, Michael V

2017-01-01

We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options

Humoral immunity in heart failure.

PubMed

Sarkar, Amrita; Rafiq, Khadija

2018-05-17

Cardiovascular disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including: hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to heart failure (HF). There are several treatments available all over the world, but still CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential, and may suggest potential new treatment strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

PubMed

Lane, E L; Cheetham, S; Jenner, P

2008-01-01

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

Added value of second biopsy target in screen-detected widespread suspicious breast calcifications.

PubMed

Falkner, Nathalie M; Hince, Dana; Porter, Gareth; Dessauvagie, Ben; Jeganathan, Sanjay; Bulsara, Max; Lo, Glen

2018-06-01

There is controversy on the optimal work-up of screen-detected widespread breast calcifications: whether to biopsy a single target or multiple targets. This study evaluates agreement between multiple biopsy targets within the same screen-detected widespread (≥25 mm) breast calcification to determine if the second biopsy adds value. Retrospective observational study of women screened in a statewide general population risk breast cancer mammographic screening program from 2009 to 2016. Screening episodes recalled for widespread calcifications where further views indicated biopsy, and two or more separate target areas were sampled within the same lesion were included. Percentage agreement and Cohen's Kappa were calculated. A total of 293317 women were screened during 761124 separate episodes with recalls for widespread calcifications in 2355 episodes. In 171 women, a second target was biopsied within the same lesion. In 149 (86%) cases, the second target biopsy result agreed with the first biopsy (κ = 0.6768). Agreement increased with increasing mammography score (85%, 86% and 92% for score 3, 4 and 5 lesions). Same day multiple biopsied lesions were three times more likely to yield concordant results compared to post-hoc second target biopsy cases. While a single target biopsy is sufficient to discriminate a benign vs. malignant diagnosis in most cases, in 14% there is added value in performing a second target biopsy. Biopsies performed prospectively are more likely to yield concordant results compared to post-hoc second target biopsy cases, suggesting a single prospective biopsy may be sufficient when results are radiological-pathological concordant; discordance still requires repeat sampling. © 2018 The Royal Australian and New Zealand College of Radiologists.

Ballistic Experiments with Titanium and Aluminum Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gogolewski, R.; Morgan, B.R.

1999-11-23

During the course of the project we conducted two sets of fundamental experiments in penetration mechanics in the LLNL Terminal Ballistics Laboratory of the Physics Directorate. The first set of full-scale experiments was conducted with a 14.5mm air propelled launcher. The object of the experiments was to determine the ballistic limit speed of 6Al-4V-alloy titanium, low fineness ratio projectiles centrally impacting 2024-T3 alloy aluminum flat plates and the failure modes of the projectiles and the targets. The second set of one-third scale experiments was conducted with a 14.5mm powder launcher. The object of these experiments was to determine the ballisticmore » limit speed of 6Al-4V alloy titanium high fineness ratio projectiles centrally impacting 6Al-4V alloy titanium flat plates and the failure modes of the projectiles and the target. We employed radiography to observe a projectile just before and after interaction with a target plate. Early on, we employed a non-damaging ''soft-catch'' technique to capture projectiles after they perforated targets. Once we realized that a projectile was not damaged during interaction with a target, we used a 4-inch thick 6061-T6-alloy aluminum witness block with a 6.0-inch x 6.0-inch cross-section to measure projectile residual penetration. We have recorded and tabulated below projectile impact speed, projectile residual (post-impact) speed, projectile failure mode, target failure mode, and pertinent comments for the experiments. The ballistic techniques employed for the experiments are similar to those employed in an earlier study.« less

Natriuretic peptide-guided management in heart failure.

PubMed

Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

2016-08-01

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Two patients with TAFRO syndrome exhibiting strikingly similar anterior mediastinal lesions with predominantly fat attenuation on chest computed tomography.

PubMed

Ozawa, Yoko; Yamamoto, Hiroshi; Yasuo, Masanori; Takahashi, Hidekazu; Tateishi, Kazunari; Ushiki, Atsuhito; Kawakami, Satoshi; Fujinaga, Yasunari; Asaka, Shiho; Sano, Kenji; Takayama, Hiroshi; Imamura, Hiroshi; Hanaoka, Masayuki

2017-03-01

We herein report on two middle-aged men with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis or renal failure, and organomegaly) syndrome, a unique clinicopathological variant of multicentric Castleman׳s disease recently proposed in Japan. Strikingly similar anterior mediastinal fat swellings with soft tissue density were observed in the patients on chest computed tomography. In TAFRO syndrome, bilateral pleural effusion and slight lymph node swelling are common in the thoracic region; however, anterior mediastinal lesions have not been previously observed. Although the mechanisms of anterior mediastinal lesions have not been defined, these lesions seem to have a close relationship with TAFRO syndrome. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Eradication of melanomas by targeted elimination of a minor subset of tumor cells

PubMed Central

Schmidt, Patrick; Kopecky, Caroline; Hombach, Andreas; Zigrino, Paola; Mauch, Cornelia; Abken, Hinrich

2011-01-01

Proceeding on the assumption that all cancer cells have equal malignant capacities, current regimens in cancer therapy attempt to eradicate all malignant cells of a tumor lesion. Using in vivo targeting of tumor cell subsets, we demonstrate that selective elimination of a definite, minor tumor cell subpopulation is particularly effective in eradicating established melanoma lesions irrespective of the bulk of cancer cells. Tumor cell subsets were specifically eliminated in a tumor lesion by adoptive transfer of engineered cytotoxic T cells redirected in an antigen-restricted manner via a chimeric antigen receptor. Targeted elimination of less than 2% of the tumor cells that coexpress high molecular weight melanoma-associated antigen (HMW-MAA) (melanoma-associated chondroitin sulfate proteoglycan, MCSP) and CD20 lastingly eradicated melanoma lesions, whereas targeting of any random 10% tumor cell subset was not effective. Our data challenge the biological therapy and current drug development paradigms in the treatment of cancer. PMID:21282657

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

PubMed Central

Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

2014-01-01

Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion

Failure Patterns in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

PubMed Central

Welsh, James; Settle, Stephen H.; Amini, Arya; Xiao, Lianchun; Suzuki, Akihiro; Hayashi, Yuki; Hofstetter, Wayne; Komaki, Ritsuko; Liao, Zhongxing; Ajani, Jaffer A.

2012-01-01

Purpose Local failure after definitive chemoradiation therapy for unresectable esophageal cancer remains problematic. Little is known about the failure pattern based on modern day radiation treatment volumes. We hypothesized that most local failures would be within the gross tumor volume (GTV), where the bulk of the tumor burden resides. Methods and Materials We reviewed treatment volumes for 239 patients who underwent definitive chemoradiation therapy and compared this information with failure patterns on follow-up positron emission (PET). Failures were categorized as within the GTV, the larger clinical target volume (CTV, which encompasses microscopic disease), or the still larger planning target volume (PTV, which encompasses setup variability) or outside the radiation field. Results At a median follow-up time of 52.6 months (95% CI: 46.1 – 56.7 months), 119 patients (50%) had experienced local failure, 114 (48%) had distant failure, and 74 (31%) had no evidence of failure. Of all local failures, 107 (90%) were in the GTV, 27 (23%) in the CTV; and 14 (12%) in the PTV. In multivariate analysis, GTV failure was associated with tumor status (T3/T4 vs. T1/T2: OR=6.35, p value =0.002), change in standardized uptake value on PET before and after treatment (decrease >52%: OR=0.368, p value = 0.003) and tumor length (>8 cm: 4.08, p value = 0.009). Conclusions Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the GTV. Future therapeutic strategies should focus on enhancing local control. PMID:22565611

Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue.

PubMed

Laughner, Jacob I; Sulkin, Matthew S; Wu, Ziqi; Deng, Cheri X; Efimov, Igor R

2012-04-01

High intensity focused ultrasound (HIFU) has been introduced for treatment of cardiac arrhythmias because it offers the ability to create rapid tissue modification in confined volumes without directly contacting the myocardium. In spite of the benefits of HIFU, a number of limitations have been reported, which hindered its clinical adoption. In this study, we used a multimodal approach to evaluate thermal and nonthermal effects of HIFU in cardiac ablation. We designed a computer controlled system capable of simultaneous fluorescence mapping and HIFU ablation. Using this system, linear lesions were created in isolated rabbit atria (n=6), and point lesions were created in the ventricles of whole-heart (n=6) preparations by applying HIFU at clinical doses (4-16 W). Additionally, we evaluate the gap size in ablation lines necessary for conduction in atrial preparations (n=4). The voltage sensitive dye di-4-ANEPPS was used to assess functional damage produced by HIFU. Optical coherence tomography and general histology were used to evaluate lesion extent. Conduction block was achieved in 1 (17%) of 6 atrial preparations with a single ablation line. Following 10 minutes of rest, 0 (0%) of 6 atrial preparations demonstrated sustained conduction block from a single ablation line. Tissue displacement of 1 to 3 mm was observed during HIFU application due to acoustic radiation force along the lesion line. Additionally, excessive acoustic pressure and high temperature from HIFU generated cavitation, causing macroscopic tissue damage. A minimum gap size of 1.5 mm was found to conduct electric activity. This study identified 3 potential mechanisms responsible for the failure of HIFU ablation in cardiac tissues. Both acoustic radiation force and acoustic cavitation, in conjunction with inconsistent thermal deposition, can increase the risk of lesion discontinuity and result in gap sizes that promote ablation failure.

IL-17/Th17 Pathway Is Activated in Acne Lesions

PubMed Central

Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

2014-01-01

The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

Failure mode and effects analysis to reduce risk of anticoagulation levels above the target range during concurrent antimicrobial therapy.

PubMed

Daniels, Lisa M; Barreto, Jason N; Kuth, John C; Anderson, Jeremy R; Zhang, Beilei; Majka, Andrew J; Morgenthaler, Timothy I; Tosh, Pritish K

2015-07-15

A failure mode and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to above-target International Normalized Ratios (INRs) in warfarin-treated patients receiving concurrent antimicrobial therapy. The INRs of patients on long-term warfarin therapy who received a course of trimethoprim-sulfamethoxazole, metronidazole, fluconazole, miconazole, or voriconazole (highly potentiating antimicrobials, or HPAs) between September 1 and December 31, 2011, were compared with patients on long-term warfarin therapy who did not receive any antimicrobial during the same period. A multidisciplinary team of physicians, pharmacists, and a systems analyst was then formed to complete a step-by-step outline of the processes involved in warfarin management and concomitant HPA therapy, followed by an FMEA. Patients taking trimethoprim-sulfamethoxazole, metronidazole, or fluconazole demonstrated a significantly increased risk of having an INR of >4.5. The FMEA identified 134 failure modes. The most common failure modes were as follows: (1) electronic medical records did not identify all patients receiving warfarin, (2) HPA prescribers were unaware of recommended warfarin therapy when HPAs were prescribed, (3) HPA prescribers were unaware that a patient was taking warfarin and that the drug interaction is significant, and (4) warfarin managers were unaware that an HPA had been prescribed for a patient. An FMEA determined that the risk of adverse events caused by concomitantly administering warfarin and HPAs can be decreased by preemptively identifying patients receiving warfarin, having a care process in place, alerting providers about the patient's risk status, and notifying providers at the anticoagulation clinic. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Added Value of Contrast-Enhanced Ultrasound on Biopsies of Focal Hepatic Lesions Invisible on Fusion Imaging Guidance.

PubMed

Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

2017-01-01

To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5-1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making.

Human ventromedial prefrontal lesions alter incentivisation by reward.

PubMed

Manohar, Sanjay G; Husain, Masud

2016-03-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury

PubMed Central

Vaněček, Václav; Zablotskii, Vitalii; Forostyak, Serhiy; Růřička, Jiří; Herynek, Vít; Babič, Michal; Jendelová, Pavla; Kubinová, Šárka; Dejneka, Alexandr; Syková, Eva

2012-01-01

The transplantation of mesenchymal stem cells (MSC) is currently under study as a therapeutic approach for spinal cord injury, and the number of transplanted cells that reach the lesioned tissue is one of the critical parameters. In this study, intrathecally transplanted cells labeled with superparamagnetic iron oxide nanoparticles were guided by a magnetic field and successfully targeted near the lesion site in the rat spinal cord. Magnetic resonance imaging and histological analysis revealed significant differences in cell numbers and cell distribution near the lesion site under the magnet in comparison to control groups. The cell distribution correlated well with the calculated distribution of magnetic forces exerted on the transplanted cells in the subarachnoid space and lesion site. The kinetics of the cells’ accumulation near the lesion site is described within the framework of a mathematical model that reveals those parameters critical for cell targeting and suggests ways to enhance the efficiency of magnetic cell delivery. In particular, we show that the targeting efficiency can be increased by using magnets that produce spatially modulated stray fields. Such magnetic systems with tunable geometric parameters may provide the additional level of control needed to enhance the efficiency of stem cell delivery in spinal cord injury. PMID:22888231

Sealing occlusal caries lesions in adults referred for restorative treatment: 2-3 years of follow-up.

PubMed

Bakhshandeh, Azam; Qvist, Vibeke; Ekstrand, Kim R

2012-04-01

The aim of this study was to assess the possibility to arrest occlusal caries lesions in adults by sealant as well as to assess the presence of radiographic progression, arrest, and regression of the sealed lesions. Seventy-two occlusal caries lesions in 52 adult patients referred to restorative treatment by senior lecturers at School of Dentistry, Copenhagen, Denmark were included. In case the patient had more than one occlusal caries lesion, randomization between sealing and restoration was made; otherwise, the lesion was sealed. In total, 60 resin sealants and 12 composite restorations were made. Follow-up period was 25-38 months (mean = 33 months). Data were analyzed using non-parametric statistics including kappa statistics. After 2-3 years, the dropout rate was 15%; two patients did not show up for control and nine previously sealed lesions were restored by the patients' general practitioners. All 12 restorations and 39 of the remaining 49 sealants were well functioning, seven (14%) sealants were repaired/replaced due to failure, and three (6%) sealed lesions were restored due to caries progression (p > 0.05). The radiographic assessment showed caries progression beneath five (10%) sealants, caries regression beneath one (2%) sealant, and unchanged depth beneath 43 (88%) sealants and all restorations (p > 0.05). The majority of the referred lesions were successfully arrested by sealants, indicating the possibility for extending the criteria for sealing occlusal caries lesions in adults. However, a longer observation period is needed for final conclusion. Extending the criteria of therapeutic sealing of occlusal caries lesions in adults will lead to increased dental health.

[Associated factors to non-operative management failure of hepatic and splenic lesions secondary to blunt abdominal trauma in children].

PubMed

Echavarria Medina, Adriana; Morales Uribe, Carlos Hernando; Echavarria R, Luis Guillermo; Vélez Marín, Viviana María; Martínez Montoya, Jorge Alberto; Aguillón, David Fernando

2017-01-01

The non operative management (NOM) is the standard management of splenic and liver blunt trauma in pediatric patients.Hemodynamic instability and massive transfusions have been identified as management failures. Few studies evaluate whether there exist factors allowing anticipation of these events. The objective was to identify factors associated with the failure of NOM in splenic and liver injuries for blunt abdominal trauma. Retrospective analysis between 2007-2015 of patients admitted to the pediatric surgery at University Hospital Saint Vincent Foundation with liver trauma and/or closed Spleen. 70 patients were admitted with blunt abdominal trauma, 3 were excluded for immediate surgery (2 hemodynamic instability, 1 peritoneal irritation). Of 67 patients who received NOM, 58 were successful and 9 showed failure (8 hemodynamic instability, 1 hollow viscera injury). We found 3 factors associated with failure NOM: blood pressure (BP) < 90 mmHg at admission (p = 0.0126; RR = 5.19), drop in hemoglobin (Hb) > 2 g/dl in the first 24 hours (p = 0.0009; RR = 15.3), and transfusion of 3 or more units of red blood cells (RBC) (0.00001; RR = 17.1). Mechanism and severity of trauma and Pediatric Trauma Index were not associated with failure NOM. Children with blunted hepatic or splenic trauma respond to NOM. Factors such as BP < 90 mmHg at admission, an Hb fall > 2 g/dl in the first 24 hours and transfusion of 3 or more units of RBC were associated with the failure in NOM.

Targeting galectin-1-induced angiogenesis mitigates the severity of endometriosis.

PubMed

Bastón, Juan I; Barañao, Rosa I; Ricci, Analía G; Bilotas, Mariela A; Olivares, Carla N; Singla, José J; Gonzalez, Alejandro M; Stupirski, Juan C; Croci, Diego O; Rabinovich, Gabriel A; Meresman, Gabriela F

2014-11-01

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvic pain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of the disease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutic targets, we investigated the involvement of galectin-1 (Gal-1), an endogenous glycan-binding protein endowed with both immunosuppressive and pro-angiogenic activities, in the pathophysiology of endometriotic lesions. Here we show that Gal-1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Using an experimental endometriosis model induced in wild-type and Gal-1-deficient (Lgals1(-/-) ) mice, we showed that this lectin orchestrates the formation of vascular networks in endometriotic lesions in vivo, facilitating their ectopic growth independently of vascular endothelial growth factor (VEGF) and the keratinocyte-derived CXC-motif (CXC-KC) chemokine. Targeting Gal-1 using a specific neutralizing mAb reduced the size and vascularized area of endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal-1 during endometriosis and validate this lectin as a possible target for the treatment of disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Communicating the location of potential skin neoplasms for excision between the referring and the operating doctor--an audit of skin lesion referrals in Whanganui, New Zealand.

PubMed

Welsh, Fraser; Bullen, Naomi; Aiono, Semisi

2013-08-30

The importance of correctly defining the location of potential skin cancer when surgical treatment may be required is self-evident. Clear communication is essential if the professional diagnosing potential skin cancer is not the same professional providing treatment. We aimed to assess the nature of the localising information provided in referrals to the local anaesthetic skin lesion theatre in our institution. Information localising target lesions for new patients seen in our local anaesthetic skin excision theatre was recorded during a 2-month period April to May 2012 inclusive 100 patients were seen in our skin excision theatre during the study period; 16 patients were not able to identify the target skin lesion at the time they entered the operating theatre. The target lesion could not be determined from the referral text in 30/100 cases. Diagrams were provided in 19/100 cases. Photographs were provided in 3/100 cases. Pictorial and photographic means of communicating the location of suspicious lesions are under-utilised in our service. Relying on the patient or the referral text to correctly identify the lesion leaves considerable room for error. We suggest that photographic information for skin lesion referrals is adopted as a minimum standard.

Initial load-to-failure and failure analysis in single- and double-row repair techniques for rotator cuff repair

PubMed Central

Buchhorn, G. H.; Gilbert, F.; Spahn, G.; Schultz, W.; Klinger, H.-M.

2010-01-01

Aim This experimental study aimed to compare the load-to-failure rate and stiffness of single- versus double-row suture techniques for repairing rotator cuff lesions using two different suture materials. Additionally, the mode of failure of each repair was evaluated. Method In 32 sheep shoulders, a standardized tear of the infraspinatus tendon was created. Then, n = 8 specimen were randomized to four repair methods: (1) Double-row Anchor Ethibond® coupled with polyester sutures, USP No. 2; (2) Double-Row Anchor HiFi® with polyblend polyethylene sutures, USP No. 2; (3) Single-Row Anchor Ethibond® coupled with braided polyester sutures, USP No. 2; and (4) Single-Row Anchor HiFi® with braided polyblend polyethylene sutures, USP No. 2. Arthroscopic Mason–Allen stitches were placed (single-row) and combined with medial horizontal mattress stitches (double-row). All specimens were loaded to failure at a constant displacement rate on a material testing machine. Results Group 4 showed lowest load-to-failure result with 155.7 ± 31.1 N compared to group 1 (293.4 ± 16.1 N) and group 2 (397.7 ± 7.4 N) (P < 0.001). Stiffness was highest in group 2 (162 ± 7.3 N/mm) and lowest in group 4 (84.4 ± 19.9 mm) (P < 0.001). In group 4, the main cause of failure was due to the suture cutting through the tendon (n = 6), a failure case observed in only n = 1 specimen in group 2 (P < 0.001). Conclusions A double-row technique combined with arthroscopic Mason-Allen/horizontal mattress stitches provides high initial failure strength and may minimize the risk of the polyethylene sutures cutting through the tendon in rotator cuff repair when a single load force is used. PMID:20049605

CT-Guided Biopsy of Small Liver Lesions: Visibility, Artifacts, and Corresponding Diagnostic Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stattaus, Joerg, E-mail: joerg.stattaus@uni-due.de; Kuehl, Hilmar; Ladd, Susanne

2007-09-15

Purpose. Our study aimed to determine the visibility of small liver lesions during CT-guided biopsy and to assess the influence of lesion visibility on biopsy results. Material and Methods. Fifty patients underwent CT-guided core biopsy of small focal liver lesions (maximum diameter, 3 cm); 38 biopsies were performed using noncontrast CT, and the remaining 12 were contrast-enhanced. Visibility of all lesions was graded on a 4-point-scale (0 = not visible, 1 = poorly visible, 2 = sufficiently visible, 3 = excellently visible) before and during biopsy (with the needle placed adjacent to and within the target lesion). Results. Forty-three biopsiesmore » (86%) yielded diagnostic results, and seven biopsies were false-negative. In noncontrast biopsies, the rate of insufficiently visualized lesions (grades 0-1) increased significantly during the procedure, from 10.5% to 44.7%, due to needle artifacts. This resulted in more (17.6%) false-negative biopsy results compared to lesions with good visualization (4.8%), although this difference lacks statistical significance. Visualization impairment appeared more often with an intercostal or subcostal vs. an epigastric access and with a subcapsular vs. a central lesion location, respectively. With contrast-enhanced biopsy the visibility of hepatic lesions was only temporarily improved, with a risk of complete obscuration in the late phase. Conclusion. In conclusion, visibility of small liver lesions diminished significantly during CT-guided biopsy due to needle artifacts, with a fourfold increased rate of insufficiently visualized lesions and of false-negative histological results. Contrast enhancement did not reveal better results.« less

Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions.

PubMed

Brown, Maxwell W; Kim, Yoori; Williams, Gregory M; Huck, John D; Surtees, Jennifer A; Finkelstein, Ilya J

2016-02-03

DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2-Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2-Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2-Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2-Msh3 and Msh2-Msh6 navigate on a crowded genome and suggest how Msh2-Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin.

Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

PubMed

Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

2015-09-01

The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions.

PubMed

Sobic-Saranovic, Dragana P; Pavlovic, Smiljana V; Artiko, Vera M; Saranovic, Djordjije Z; Jaksic, Emilija D; Subotic, Dragan; Nagorni-Obradovic, Ljudmila; Kozarevic, Nebojsa; Petrovic, Nebojsa; Grozdic, Isidora T; Obradovic, Vladimir B

2012-01-01

The aim of our study was to assess diagnostic accuracy of Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary lesions that appeared ambiguous on computed tomography (CT). Forty-nine consecutive patients (37 men and 12 women; mean age, 60 ± 11 years) with 60 pulmonary lesions on chest radiography and CT were referred for nuclear imaging. They were prospectively allocated to undergo whole-body scintigraphy (WBS) and single photon emission computed tomography (SPECT) using either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging (23 patients, group 2). Histologic findings after tissue biopsy served as a gold standard for determining diagnostic accuracy of the 2 somatostatin analogs. Visual assessment was complemented by semiquantitative analysis based on target to background ratio. Among the 32 pulmonary lesions scanned with Tc-99m depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and 88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m-EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%, and accuracy 86%). Overall, target to background ratios were higher on SPECT than WBS but not significantly different between groups 1 and 2 (SPECT 2.72 ± 0.70 vs. 2.71 ± 0.50, WBS 1.61 ± 0.32 vs. 1.62 ± 0.28, respectively). This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC have similar diagnostic value for characterizing pulmonary lesions that appear ambiguous on CT.

Endobronchial ultrasonography using a guide sheath technique for diagnosis of peripheral pulmonary lesions

PubMed Central

Zhang, Lei; Wu, Hongxu; Wang, Guiqi

2017-01-01

Endobronchial ultrasonography using a guide sheath (EBUS-GS) is a novel method used for collecting peripheral pulmonary lesion (PPL) samples. EBUS-GS is performed by introducing a guide sheath-covered miniprobe into the target bronchus and then withdrawing the miniprobe after lesion detection, leaving the guide sheath in situ as a working channel for obtaining lesion samples. EBUS-GS can improve PPL diagnosis rates and be used for obtaining specimens for molecular analysis. In this review, we discuss the clinical applications of EBUS-GS, the factors that affect its diagnostic sensitivity, and potential complications. We also compare EBUS-GS with other available diagnostic techniques and discuss the strengths and limitations of this method. PMID:29063872

Enhanced UGT1A1 Gene and Protein Expression in Endometriotic Lesions.

PubMed

Piccinato, Carla A; Neme, Rosa M; Torres, Natália; da Silva Victor, Elivane; Brudniewski, Heloísa F; Rosa E Silva, Júlio C; Ferriani, Rui A

2018-01-01

The cellular function in endometriosis lesions depends on a highly estrogenic milieu. Lately, it is becoming evident that, besides the circulating levels of estrogens, the balance of synthesis versus inactivation (metabolism) of estrogens by intralesion steroid-metabolizing enzymes also determines the local net estrogen availability. In order to extend the knowledge of the role of estrogen-metabolizing enzymes in endometriosis, we investigated the gene and protein expression of a key uridine diphospho-glucuronosyltransferase (UGT) for estrogen glucuronidation, UGT1A1, in eutopic endometrial samples obtained from nonaffected and endometriosis-affected women and also from endometriotic lesions. Although UGT1A1 messenger RNA (mRNA) expression was detected at similar frequencies in endometriotic lesions and in eutopic endometrial samples, the levels of mRNA expression were greater in deep-infiltrating endometriotic lesions and in non-deep-infiltrating lesions when compared with either control endometrium or eutopic endometrium from women with endometriosis. Overall, we observed that protein expression of UGT1A1 was significantly more frequent in samples from endometriotic lesions in comparison with endometria. In addition, expression of UGT1A1 protein was greater in deep-infiltrating than in non-deep-infiltrating endometriotic lesions. We suggest that the finding of increased expression of UGT1A1 in lesions versus endometria might be related to impairment of regulatory mechanisms, in response to a highly estrogenic milieu, and that this enzyme may be a new target for therapy.

Neural networks supporting audiovisual integration for speech: A large-scale lesion study.

PubMed

Hickok, Gregory; Rogalsky, Corianne; Matchin, William; Basilakos, Alexandra; Cai, Julia; Pillay, Sara; Ferrill, Michelle; Mickelsen, Soren; Anderson, Steven W; Love, Tracy; Binder, Jeffrey; Fridriksson, Julius

2018-06-01

Auditory and visual speech information are often strongly integrated resulting in perceptual enhancements for audiovisual (AV) speech over audio alone and sometimes yielding compelling illusory fusion percepts when AV cues are mismatched, the McGurk-MacDonald effect. Previous research has identified three candidate regions thought to be critical for AV speech integration: the posterior superior temporal sulcus (STS), early auditory cortex, and the posterior inferior frontal gyrus. We assess the causal involvement of these regions (and others) in the first large-scale (N = 100) lesion-based study of AV speech integration. Two primary findings emerged. First, behavioral performance and lesion maps for AV enhancement and illusory fusion measures indicate that classic metrics of AV speech integration are not necessarily measuring the same process. Second, lesions involving superior temporal auditory, lateral occipital visual, and multisensory zones in the STS are the most disruptive to AV speech integration. Further, when AV speech integration fails, the nature of the failure-auditory vs visual capture-can be predicted from the location of the lesions. These findings show that AV speech processing is supported by unimodal auditory and visual cortices as well as multimodal regions such as the STS at their boundary. Motor related frontal regions do not appear to play a role in AV speech integration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monitoring evolution of HIFU-induced lesions with backscattered ultrasound

NASA Astrophysics Data System (ADS)

Anand, Ajay; Kaczkowski, Peter J.

2003-04-01

Backscattered radio frequency (rf) data from a modified commercial ultrasound scanner were collected in a series of in vitro experiments in which high intensity focused ultrasound (HIFU) was used to create lesions in freshly excised bovine liver tissue. Two signal processing approaches were used to visualize the temporal evolution of lesion formation. First, apparent tissue motion due to temperature rise was detected using cross-correlation techniques. Results indicate that differential processing of travel time can provide temperature change information throughout the therapy delivery phase and after HIFU has been turned off, over a relatively large spatial region. Second, changes in the frequency spectrum of rf echoes due to changes in the scattering properties of the heated region were observed well before the appearance of hyper-echogenic spots in the focal zone. Furthermore, the increase in attenuation in the lesion zone changes the measured backscatter spectrum from regions distal to it along the imaging beam. Both effects were visualized using spectral processing and display techniques that provide a color spatial map of these features for the clinician. Our results demonstrate potential for these ultrasound-based techniques in targeting and monitoring of HIFU therapy, and perhaps post-treatment visualization of HIFU-induced lesions.

Photonics: From target recognition to lesion detection

NASA Technical Reports Server (NTRS)

Henry, E. Michael

1994-01-01

Since 1989, Martin Marietta has invested in the development of an innovative concept for robust real-time pattern recognition for any two-dimensioanal sensor. This concept has been tested in simulation, and in laboratory and field hardware, for a number of DOD and commercial uses from automatic target recognition to manufacturing inspection. We have now joined Rose Health Care Systems in developing its use for medical diagnostics. The concept is based on determining regions of interest by using optical Fourier bandpassing as a scene segmentation technique, enhancing those regions using wavelet filters, passing the enhanced regions to a neural network for analysis and initial pattern identification, and following this initial identification with confirmation by optical correlation. The optical scene segmentation and pattern confirmation are performed by the same optical module. The neural network is a recursive error minimization network with a small number of connections and nodes that rapidly converges to a global minimum.

Electromagnetic Navigation Bronchoscopy-directed Pleural Tattoo to Aid Surgical Resection of Peripheral Pulmonary Lesions.

PubMed

Tay, Jun H; Wallbridge, Peter D; Larobina, Marco; Russell, Prudence A; Irving, Louis B; Steinfort, Daniel P

2016-07-01

Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically with conversion to open thoracotomy or incomplete resection being potential limitations to this approach. Multiple methods have been described to aid video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules, including hookwire localization, percutaneous tattoo, or intraoperative ultrasound. We report on our experience using electromagnetic navigation bronchoscopic dye marking of small subpleural lesions to aid VATS wedge resection. A retrospective cohort study of consecutive patients undergoing VATS wedge resection of peripheral lesions. Preoperative bronchoscopy with electromagnetic navigation was utilized to guide a 25 G needle to within/adjacent to the target lesion with injection of 1 mL of methylene blue or indigo carmine under fluoroscopic vision. Six patients underwent bronchoscopic marking of peripheral pulmonary lesions, navigation deemed successful in all patients, with no procedural complications. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all 6 lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining. Electromagnetic navigation bronchoscopic dye marking of peripheral lesions is feasible, without complications commonly associated with percutaneous marking procedures. Further experience is required but early findings suggest that this method may have utility in aiding minimally invasive resection of small subpleural lesions.

Therapeutic potential of microRNAs in heart failure.

PubMed

Dorn, Gerald W

2010-05-01

There is an ongoing explosion of information about microRNAs (miRs) in cardiac disease. These small noncoding RNAs regulate protein expression by destabilization and translational inhibition of target mRNAs. Similar to mRNAs, miRs are regulated in cardiac hypertrophy and heart failure, but miR expression profiles appear to be more sensitive than mRNA signatures to changes in clinical status, suggesting that miR levels in myocardium or plasma could enhance clinical diagnostics. Single miRs can target dozens or hundreds of different mRNAs, complicating attempts to determine their individual physiologic effects. However, manipulating individual miRs by overexpression or gene ablation in experimental models has begun to unravel this conundrum: Single miRs tend to regulate numerous effectors within the same functional pathway, producing a coherent physiologic response via multiple parallel perturbations. miRs are attractive nodal therapeutic targets, and stable miR mimetics (agomiRs) and antagonists (antagomiRs) are being evaluated to prevent or reverse heart failure.

Impact of the Occlusion Duration on the Performance of J-CTO Score in Predicting Failure of Percutaneous Coronary Intervention for Chronic Total Occlusion.

PubMed

de Castro-Filho, Antonio; Lamas, Edgar Stroppa; Meneguz-Moreno, Rafael A; Staico, Rodolfo; Siqueira, Dimytri; Costa, Ricardo A; Braga, Sergio N; Costa, J Ribamar; Chamié, Daniel; Abizaid, Alexandre

2017-06-01

The present study examined the association between Multicenter CTO Registry in Japan (J-CTO) score in predicting failure of percutaneous coronary intervention (PCI) correlating with the estimated duration of chronic total occlusion (CTO). The J-CTO score does not incorporate estimated duration of the occlusion. This was an observational retrospective study that involved all consecutive procedures performed at a single tertiary-care cardiology center between January 2009 and December 2014. A total of 174 patients, median age 59.5 years (interquartile range [IQR], 53-65 years), undergoing CTO-PCI were included. The median estimated occlusion duration was 7.5 months (IQR, 4.0-12.0 months). The lesions were classified as easy (score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score ≥3) in 51.1%, 33.9%, 9.2%, and 5.7% of the patients, respectively. Failure rate significantly increased with higher J-CTO score (7.9%, 20.3%, 50.0%, and 70.0% in groups with J-CTO scores of 0, 1, 2, and ≥3, respectively; P<.001). There was no significant difference in success rate according to estimated duration of occlusion (P=.63). Indeed, J-CTO score predicted failure of CTO-PCI independently of the estimated occlusion duration (P=.24). Areas under receiver-operating characteristic curves were computed and it was observed that for each occlusion time period, the discriminatory capacity of the J-CTO score in predicting CTO-PCI failure was good, with a C-statistic >0.70. The estimated duration of occlusion had no influence on the J-CTO score performance in predicting failure of PCI in CTO lesions. The probability of failure was mainly determined by grade of lesion complexity.

Radial-probe EBUS for the diagnosis of peripheral pulmonary lesions

PubMed Central

Jacomelli, Marcia; Demarzo, Sergio Eduardo; Cardoso, Paulo Francisco Guerreiro; Palomino, Addy Lidvina Mejia; Figueiredo, Viviane Rossi

2016-01-01

ABSTRACT Objective: Conventional bronchoscopy has a low diagnostic yield for peripheral pulmonary lesions. Radial-probe EBUS employs a rotating ultrasound transducer at the end of a probe that is passed through the working channel of the bronchoscope. Radial-probe EBUS facilitates the localization of peripheral pulmonary nodules, thus increasing the diagnostic yield. The objective of this study was to present our initial experience using radial-probe EBUS in the diagnosis of peripheral pulmonary lesions at a tertiary hospital. Methods: We conducted a retrospective analysis of 54 patients who underwent radial-probe EBUS-guided bronchoscopy for the investigation of pulmonary nodules or masses between February of 2012 and September of 2013. Radial-probe EBUS was performed with a flexible 20-MHz probe, which was passed through the working channel of the bronchoscope and advanced through the bronchus to the target lesion. For localization of the lesion and for collection procedures (bronchial brushing, transbronchial needle aspiration, and transbronchial biopsy), we used fluoroscopy. Results: Radial-probe EBUS identified 39 nodules (mean diameter, 1.9 ∓ 0.7 cm) and 19 masses (mean diameter, 4.1 ∓ 0.9 cm). The overall sensitivity of the method was 66.7% (79.5% and 25.0%, respectively, for lesions that were visible and not visible by radial-probe EBUS). Among the lesions that were visible by radial-probe EBUS, the sensitivity was 91.7% for masses and 74.1% for nodules. The complications were pneumothorax (in 3.7%) and bronchial bleeding, which was controlled bronchoscopically (in 9.3%). Conclusions: Radial-probe EBUS shows a good safety profile, a low complication rate, and high sensitivity for the diagnosis of peripheral pulmonary lesions. PMID:27832231

Surgical Treatment, Oral Rehabilitation, and Orthognathic Surgery After Failure of Pharmacologic Treatment of Central Giant Cell Lesion: A Case Report.

PubMed

Maia Nogueira, Renato Luiz; Osterne, Rafael Lima Verde; Cavalcante, Roberta Barroso; Abreu, Ricardo Teixeira

2016-12-01

Although pharmacologic treatments for central giant cell lesions have gained much emphasis, these treatment modalities do not always have successful outcomes, and surgical treatment may be necessary. The purpose of the present study was to report a case of aggressive central giant cell lesion initially treated by nonsurgical methods without satisfactory results, necessitating segmental mandibular resection for definitive treatment and oral rehabilitation. A 20-year-old woman was diagnosed with an aggressive central giant cell lesion in the mandible. The patient was first treated with intralesional corticosteroid injections. Subsequently, the lesion increased in size. Therefore, a second pharmacologic treatment was proposed with salmon calcitonin nasal spray, but no signs of a treatment response were noted. Because of the lack of response, surgical excision was performed, and a mandibular reconstruction plate was installed. At 12 months after surgical resection, the patient underwent mandibular reconstruction with bone grafts. After 6 months, 7 dental implants were installed, and fixed prostheses were made. After installation of the prostheses, the patient experienced persistent mandibular laterognathism, and a mandibular orthognathic surgery was performed to correct the laterognathia. The follow-up examination 4 years after orthognathic surgery showed no signs of recurrence and good facial symmetry. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Calcified lesion modeling for excimer laser ablation

NASA Astrophysics Data System (ADS)

Scott, Holly A.; Archuleta, Andrew; Splinter, Robert

2009-06-01

Objective: Develop a representative calcium target model to evaluate penetration of calcified plaque lesions during atherectomy procedures using 308 nm Excimer laser ablation. Materials and Methods: An in-vitro model representing human calcified plaque was analyzed using Plaster-of-Paris and cement based composite materials as well as a fibrinogen model. The materials were tested for mechanical consistency. The most likely candidate(s) resulting from initial mechanical and chemical screening was submitted for ablation testing. The penetration rate of specific multi-fiber catheter designs and a single fiber probe was obtained and compared to that in human cadaver calcified plaque. The effects of lasing parameters and catheter tip design on penetration speed in a representative calcified model were verified against the results in human cadaver specimens. Results: In Plaster of Paris, the best penetration was obtained using the single fiber tip configuration operating at 100 Fluence, 120 Hz. Calcified human lesions are twice as hard, twice as elastic as and much more complex than Plaster of Paris. Penetration of human calcified specimens was highly inconsistent and varied significantly from specimen to specimen and within individual specimens. Conclusions: Although Plaster of Paris demonstrated predictable increases in penetration with higher energy density and repetition rate, it can not be considered a totally representative laser ablation model for calcified lesions. This is in part due to the more heterogeneous nature and higher density composition of cadaver intravascular human calcified occlusions. Further testing will require a more representative model of human calcified lesions.

Pathogenesis of apical periodontitis and the causes of endodontic failures.

PubMed

Nair, P N R

2004-11-01

Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. The treatment of apical periodontitis, as a disease of root canal infection, consists of eradicating microbes or substantially reducing the microbial load from the root canal and preventing re-infection by orthograde root filling. The treatment has a remarkably high degree of success. Nevertheless, endodontic treatment can fail. Most failures occur when treatment procedures, mostly of a technical nature, have not reached a satisfactory standard for the control and elimination of infection. Even when the highest standards and the most careful procedures are followed, failures still occur. This is because there are root canal regions that cannot be cleaned and obturated with existing equipments, materials, and techniques, and thus, infection can persist. In very rare cases, there are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The data on the biological causes of endodontic failures are recent and scattered in various journals. This communication is meant to provide a comprehensive overview of the etio-pathogenesis of apical periodontitis and the causes of failed endodontic treatments that can be visualized in radiographs as asymptomatic post-treatment periapical radiolucencies.

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale.

PubMed

Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

Dynamic Failure and Fragmentation of a Hot-Pressed Boron Carbide

NASA Astrophysics Data System (ADS)

Sano, Tomoko; Vargas-Gonzalez, Lionel; LaSalvia, Jerry; Hogan, James David

2017-12-01

This study investigates the failure and fragmentation of a hot-pressed boron carbide during high rate impact experiments. Four impact experiments are performed using a composite-backed target configuration at similar velocities, where two of the impact experiments resulted in complete target penetration and two resulted in partial penetration. This paper seeks to evaluate and understand the dynamic behavior of the ceramic that led to either the complete or partial penetration cases, focusing on: (1) surface and internal failure features of fragments using optical, scanning electron, and transmission electron microscopy, and (2) fragment size analysis using state-of-the-art particle-sizing technology that informs about the consequences of failure. Detailed characterization of the mechanical properties and the microstructure is also performed. Results indicate that transgranular fracture was the primary mode of failure in this boron carbide material, and no stress-induced amorphization features were observed. Analysis of the fragment sizes for the partial and completely penetrated experiments revealed a possible correlation between larger fragment sizes and impact performance. The results will add insight into designing improved advanced ceramics for impact protection applications.

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.

PubMed

van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E

2012-07-01

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.

Added Value of Contrast-Enhanced Ultrasound on Biopsies of Focal Hepatic Lesions Invisible on Fusion Imaging Guidance

PubMed Central

Kang, Tae Wook; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

2017-01-01

Objective To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. Materials and Methods The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Results Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5–1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). Conclusion The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making. PMID:28096725

Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

PubMed

Ogawa, Yukihisa; Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Saunders, Alan T; Dake, Michael D

2017-11-01

Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF. This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency. Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively. This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF. Level 3, Post-Market Surveillance Study.

Multiple sclerosis lesion segmentation using an automatic multimodal graph cuts.

PubMed

García-Lorenzo, Daniel; Lecoeur, Jeremy; Arnold, Douglas L; Collins, D Louis; Barillot, Christian

2009-01-01

Graph Cuts have been shown as a powerful interactive segmentation technique in several medical domains. We propose to automate the Graph Cuts in order to automatically segment Multiple Sclerosis (MS) lesions in MRI. We replace the manual interaction with a robust EM-based approach in order to discriminate between MS lesions and the Normal Appearing Brain Tissues (NABT). Evaluation is performed in synthetic and real images showing good agreement between the automatic segmentation and the target segmentation. We compare our algorithm with the state of the art techniques and with several manual segmentations. An advantage of our algorithm over previously published ones is the possibility to semi-automatically improve the segmentation due to the Graph Cuts interactive feature.

Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration.

PubMed

Stichel, Christine C.; Lausberg, Friederike; Hermanns, Susanne; Müller, Hans Werner

1999-01-01

After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons.Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods.A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration.These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.

Optical Coherence Tomography Substudy of A Prospective Multicenter Randomized Post-Market Trial to Assess the Safety and Effectiveness of the Firehawk™ Rapamycin Target Eluting Cobalt Chromium Coronary Stent System for the Treatment of Atherosclerotic Lesions: TARGET All Comers.

PubMed

Baumbach, Andreas; Lansky, Alexandra J; Onuma, Yoshi; Asano, Taku; Johnson, Thomas; Anderson, Richard; Kiemeneij, Ferdinand; Zheng, Ming; Van Royen, Niels; Slagboom, Ton; Vlachojannis, Georg; Xu, Bo; Serruys, Patrick; Wijns, William

2018-06-12

Durable polymer drug-eluting stents (DP DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this Optical Coherence Tomography (OCT) sub-study was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (FIREHAWK®) (BP DES) versus the DP DES (XIENCE) at 90 days in an all comers patient population. The TARGET All Comers study is a prospective multicenter randomised post-market trial of 1656 patients randomised 1:1 to FIREHAWK or XIENCE at 21 centers in 10 European countries. The TARGET OCT sub-study enrolled 36 consecutive patients with 52 lesions at 6 centers proficient in OCT. Follow-up OCT was performed at 3 months or prior to revascularisation when occurring before the 3-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions, Firehawk, n=24; Xience, n=28), was not significantly different between groups (Firehawk 75.5μm vs Xience V 82.3 μm) meeting the primary endpoint of non-inferiority (Pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9% ± 0.3 vs 100% ± 0.1, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups. Based on OCT, the FIREHAWK BP DES has a similar healing response 3 months after implantation compared to the DP DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

DNA repair targeted therapy: the past or future of cancer treatment?

PubMed Central

Gavande, Navnath S.; VanderVere-Carozza, Pamela S.; Hinshaw, Hilary D.; Jalal, Shadia I.; Sears, Catherine R.; Pawelczak, Katherine S.; Turchi, John J.

2016-01-01

The repair of DNA damage is a complex process that relies on particular pathways to remedy specific types of damage to DNA. The range of insults to DNA includes small, modest changes in structure including mismatched bases and simple methylation events to oxidized bases, intra- and interstrand DNA crosslinks, DNA double strand breaks and protein-DNA adducts. Pathways required for the repair of these lesions include mismatch repair, base excision repair, nucleotide excision repair, and the homology directed repair/Fanconi anemia pathway. Each of these pathways contributes to genetic stability, and mutations in genes encoding proteins involved in these pathways have been demonstrated to promote genetic instability and cancer. In fact, it has been suggested all cancers display defects in DNA repair. It has also been demonstrated that the ability of cancer cells to repair therapeutically induced DNA damage impacts therapeutic efficacy. This has led to targeting DNA repair pathways and proteins to develop anti-cancer agents that will increase sensitivity to traditional chemotherapeutics. While initial studies languished and were plagued by a lack of specificity and a defined mechanism of action, more recent approaches to exploit synthetic lethal interaction and develop high affinity chemical inhibitors have proven considerably more effective. In this review we will highlight recent advances and discuss previous failures in targeting DNA repair to pave the way for future DNA repair targeted agents and their use in cancer therapy. PMID:26896565

Autism spectrum disorder, but not amygdala lesions, impairs social attention in visual search.

PubMed

Wang, Shuo; Xu, Juan; Jiang, Ming; Zhao, Qi; Hurlemann, Rene; Adolphs, Ralph

2014-10-01

People with autism spectrum disorders (ASD) have pervasive impairments in social interactions, a diagnostic component that may have its roots in atypical social motivation and attention. One of the brain structures implicated in the social abnormalities seen in ASD is the amygdala. To further characterize the impairment of people with ASD in social attention, and to explore the possible role of the amygdala, we employed a series of visual search tasks with both social (faces and people with different postures, emotions, ages, and genders) and non-social stimuli (e.g., electronics, food, and utensils). We first conducted trial-wise analyses of fixation properties and elucidated visual search mechanisms. We found that an attentional mechanism of initial orientation could explain the detection advantage of non-social targets. We then zoomed into fixation-wise analyses. We defined target-relevant effects as the difference in the percentage of fixations that fell on target-congruent vs. target-incongruent items in the array. In Experiment 1, we tested 8 high-functioning adults with ASD, 3 adults with focal bilateral amygdala lesions, and 19 controls. Controls rapidly oriented to target-congruent items and showed a strong and sustained preference for fixating them. Strikingly, people with ASD oriented significantly less and more slowly to target-congruent items, an attentional deficit especially with social targets. By contrast, patients with amygdala lesions performed indistinguishably from controls. In Experiment 2, we recruited a different sample of 13 people with ASD and 8 healthy controls, and tested them on the same search arrays but with all array items equalized for low-level saliency. The results replicated those of Experiment 1. In Experiment 3, we recruited 13 people with ASD, 8 healthy controls, 3 amygdala lesion patients and another group of 11 controls and tested them on a simpler array. Here our group effect for ASD strongly diminished and all four subject

Autism spectrum disorder, but not amygdala lesions, impairs social attention in visual search

PubMed Central

Wang, Shuo; Xu, Juan; Jiang, Ming; Zhao, Qi; Hurlemann, Rene; Adolphs, Ralph

2015-01-01

People with autism spectrum disorders (ASD) have pervasive impairments in social interactions, a diagnostic component that may have its roots in atypical social motivation and attention. One of the brain structures implicated in the social abnormalities seen in ASD is the amygdala. To further characterize the impairment of people with ASD in social attention, and to explore the possible role of the amygdala, we employed a series of visual search tasks with both social (faces and people with different postures, emotions, ages, and genders) and non-social stimuli (e.g., electronics, food, and utensils). We first conducted trial-wise analyses of fixation properties and elucidated visual search mechanisms. We found that an attentional mechanism of initial orientation could explain the detection advantage of non-social targets. We then zoomed into fixation-wise analyses. We defined target-relevant effects as the difference in the percentage of fixations that fell on target-congruent vs. target-incongruent items in the array. In Experiment 1, we tested 8 high-functioning adults with ASD, 3 adults with focal bilateral amygdala lesions, and 19 controls. Controls rapidly oriented to target-congruent items and showed a strong and sustained preference for fixating them. Strikingly, people with ASD oriented significantly less and more slowly to target-congruent items, an attentional deficit especially with social targets. By contrast, patients with amygdala lesions performed indistinguishably from controls. In Experiment 2, we recruited a different sample of 13 people with ASD and 8 healthy controls, and tested them on the same search arrays but with all array items equalized for low-level saliency. The results replicated those of Experiment 1. In Experiment 3, we recruited 13 people with ASD, 8 healthy controls, 3 amygdala lesion patients and another group of 11 controls and tested them on a simpler array. Here our group effect for ASD strongly diminished and all four subject

Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

PubMed

Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

2009-01-01

Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale

PubMed Central

Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583

[Severe pruriginous acne in dialysed renal failure. Diagnostic difficulties and efficacy of isotretinoin].

PubMed

Grange, F; Mitschler, A; Genestier, S; Guillaume, J C

2001-11-01

The occurrence of acne in dialysed renal failure patients has rarely been reported and the clinical characteristics and therapeutic issues rarely studied in these patients. Two men and two women, 33 to 56 years-old, with chronic renal failure and no past history of acne, developed severe acne under dialysis. The acne was excoriated in all cases and associated with prurigo-like lesions and intense pruritus, which made diagnosis difficult. Acne was profuse on the face and the trunk, but also on the neck (1 case) and the upper limbs (2 cases). No patient was taking acne-inducing substances. Various to therapies attempting to control pruritus were ineffective. However, anti-acne treatments (cyclines associated with local tretinoin in 1 case and oral isotreninoin in 3 cases) led to complete regression of the acne, pruritus and the prurigo-like lesions without relapse after a follow-up time of 4 months to 2 years. Pruritus is frequent during renal failure. However, the occurrence of unexplained acne has only rarely been reported. Our patients' clinical picture was original, characterized by the late development, under dialysis, of severe and pruriginous acne, the pathogenesis of which is unknown. Because of the clinical and therapeutic implications (impaired quality of life, pigmentation or scarring and remarkable efficacy of oral isotretinoin) this clinical picture merits more attention, and the modalities for the prescription of isotretinoin in this context should be defined.

Targeting Ovarian Cancer with Porphysome Nanotechnology

DTIC Science & Technology

2016-10-01

ORGANIZATION: University Health Network Toronto, ON, Canada M5G 2C4 REPORT DATE : October 2016 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army...THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) October 2016 2. REPORT TYPE Annual 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Targeting...non-targeted Porphysomes for the detection of orthotopic ovarian lesions. Methods : Two ovarian tumour xenograft models are established with human SK

Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats.

PubMed

Vitaic, S; Stupnisek, M; Drmic, D; Bauk, L; Kokot, A; Klicek, R; Vcev, A; Luetic, K; Seiwerth, S; Sikiric, P

2017-04-01

The sphincters failure is a part of NSAIDs-toxicity that can be accordingly counteracted. We used a safe stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, external and internal fistulas in rats, and particularly counteracts all NSAIDs-lesions. We assessed lower esophageal sphincter and pyloric sphincter pressure (cmH 2 O) in rats treated with various NSAIDs regimens, at corresponding time points, known to produce stomach, small intestine lesions, hepatotoxicity and encephalopathy. Assessment was after diclofenac (12.5 mg/kg, 40 mg/kg intraperitoneal challenge), ibuprofen (400 mg/day/kg intraperitoneally for 4 weeks), paracetamol (5.0 g/kg intraperitoneal challenge), aspirin (400 mg/kg intraperitoneally or intragastrically), celecoxib (0.5 mg/kg, 1.0 mg/kg intraperitoneally). BPC 157 (10 μg/kg, 10 ng/kg) was given immediately after NSAIDs (intraperitoneally or intragastrically) or given in drinking water. Regularly, in all control NSAIDs fall of pressure occurred in both sphincters rapidly and then persisted. By contrast, in all NSAIDs-rats that received BPC 157, initial fall of pressure was minimized and pressure values restored to normal values. All tested NSAIDs decrease pressure in both sphincters, whilst BPC 157 counteracts their effects and restored both sphincters function.

Basolateral amygdala lesions abolish mutual reward preferences in rats.

PubMed

Hernandez-Lallement, Julen; van Wingerden, Marijn; Schäble, Sandra; Kalenscher, Tobias

2016-01-01

In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding ("Both Reward") or not rewarding a partner rat ("Own Reward"), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

A case report of disappearing pigmented skin lesions associated with pembrolizumab treatment for metastatic melanoma.

PubMed

Wolner, Z J; Marghoob, A A; Pulitzer, M P; Postow, M A; Marchetti, M A

2018-01-01

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side-effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo and lichenoid skin and mucosal reactions. Here we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes and scalp and body hair. Compared with baseline high-resolution three-dimensional total-body photography, we observed fading or disappearance of solar lentigines, seborrhoeic keratoses and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow-up, altered lesions showed either blue-grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue-grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrhoeic keratosis with melanophages. Further studies are required to elucidate the effects of PD-1 inhibition on benign skin lesions. © 2017 British Association of Dermatologists.

Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions

PubMed Central

Brown, Maxwell W.; Kim, Yoori; Williams, Gregory M.; Huck, John D.; Surtees, Jennifer A.; Finkelstein, Ilya J.

2016-01-01

DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2–Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2–Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2–Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2–Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2–Msh3 and Msh2–Msh6 navigate on a crowded genome and suggest how Msh2–Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin. PMID:26837705

Parietal substrates for dimensional effects in visual search: evidence from lesion-symptom mapping

PubMed Central

Humphreys, Glyn W.; Chechlacz, Magdalena

2013-01-01

In visual search, the detection of pop-out targets is facilitated when the target-defining dimension remains the same compared with when it changes across trials. We tested the brain regions necessary for these dimensional carry-over effects using a voxel-based morphometry study with brain-lesioned patients. Participants had to search for targets defined by either their colour (red or blue) or orientation (right- or left-tilted), and the target dimension either stayed the same or changed on consecutive trials. Twenty-five patients were categorized according to whether they showed an effect of dimensional change on search or not. The two groups did not differ with regard to their performance on several working memory tasks, and the dimensional carry-over effects were not correlated with working memory performance. With spatial, sustained attention and working memory deficits as well as lesion volume controlled, damage within the right inferior parietal lobule (the angular and supramarginal gyri) extending into the intraparietal sulcus was associated with an absence of dimensional carry-over (P < 0.001, cluster-level corrected for multiple comparisons). The data suggest that these regions of parietal cortex are necessary to implement attention shifting in the context of visual dimensional change. PMID:23404335

Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks☆

PubMed Central

Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.; Vrenken, H.

2014-01-01

Background In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks. Methods 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests. Results Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST. Discussion These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS. PMID:24567908

Clinical and pathological analysis of IgA nephropathy with chronic renal failure.

PubMed

Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi

2016-10-01

To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p < 0.05, respectively). The most common pathological type was proliferative sclerosis glomerulonephritis (PSGN) and M1S1E0T0 according to WHO definition and Oxford Classification, respectively, and most of the 65 cases had glomerulosclerosis. Simple IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

Two-Year Clinical Outcomes of Newer-Generation Drug-Eluting Stent Implantation Following Rotational Atherectomy for Heavily Calcified Lesions.

PubMed

Jinnouchi, Hiroyuki; Kuramitsu, Shoichi; Shinozaki, Tomohiro; Kobayashi, Yohei; Hiromasa, Takashi; Morinaga, Takashi; Mazaki, Toru; Sakakura, Kenichi; Soga, Yoshimitsu; Hyodo, Makoto; Shirai, Shinichi; Ando, Kenji

2015-01-01

Clinical outcomes of implantation of the newer-generation drug-eluting stent (DES) following rotational atherectomy for heavily calcified lesions remain unclear in the real-world setting. We enrolled 252 consecutive patients (273 lesions) treated with newer-generation DES following rotational atherectomy. The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, clinically-driven target lesion revascularization, and definite stent thrombosis. Complete clinical follow-up information at 2-year was obtained for all patients. The mean age was 73.2±9.0 years and 155 patients (61.5%) were male. Cumulative 2-year incidence of MACE (cardiac death, myocardial infarction, clinically-driven target lesion revascularization and definite stent thrombosis) was 20.3% (7.0%, 2.1%, 18.1% and 2.1%, respectively). Predictors of MACE were presenting with acute coronary syndrome (hazard ratio [HR]: 3.80, 95% confidence interval [CI]: 1.29-11.2, P=0.02), hemodialysis (HR: 1.93, 95% CI: 1.04-3.56, P=0.04) and previous coronary artery bypass graft (HR: 2.26, 95% CI: 1.02-5.00, P=0.045). PCI for calcified lesions requiring rotational atherectomy is still challenging even in the era of newer-generation DES.

Genous™ endothelial progenitor cell capturing stent vs. the Taxus Liberté stent in patients with de novo coronary lesions with a high-risk of coronary restenosis: a randomized, single-centre, pilot study

PubMed Central

Beijk, Marcel A.M.; Klomp, Margo; Verouden, Niels J.W.; van Geloven, Nan; Koch, Karel T.; Henriques, José P.S.; Baan, Jan; Vis, Marije M.; Scheunhage, Esther; Piek, Jan J.; Tijssen, Jan G.P.; de Winter, Robbert J.

2010-01-01

Aims The purpose of this study was to evaluate the GenousTM endothelial progenitor cell capturing stent vs. the Taxus Liberté paclitaxel-eluting stent in patients with de novo coronary lesions with a high-risk of coronary restenosis. Methods and results We randomly assigned 193 patients with lesions carrying a high risk of restenosis to have the Genous stent or the Taxus stent implanted. Lesions were considered high risk of restenosis if one of the following applied: chronic total occlusion, lesion length >23 mm, vessel diameter <2.8 mm, or any lesion in a diabetic patient. At 1-year, the rate of the primary end point, target vessel failure (TVF), was 17.3% in the Genous stent group when compared with 10.5% in the Taxus stent group [risk difference (RD) 6.8%, 95% CI −3.1 to 16.7%], a difference predominantly due to a higher incidence of repeat revascularization in patients treated with the Genous stent. In contrast, no stent thrombosis was observed in the Genous stent group compared to 4 stent thromboses in the Taxus stent group (RD −4.2%; 95% CI −10.3 to 0.3%). Repeat angiography between 6 and 12 months in a subgroup of patients showed a significantly higher late loss in the Genous stent compared with the Taxus stent (1.14 ± 0.64 and 0.55 ± 0.61 mm). Conclusion In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant higher rate of TVF compared with the Taxus stent mainly due to more repeat revascularizations in the Genous stent group. There were four stent thromboses with Taxus stent, none with the Genous stent. PMID:19933225

Orbital atherectomy for severely calcified lesions: More dissections in women but similar 30-day outcomes to men.

PubMed

Chandrasekhar, Jaya; Mehran, Roxana

2016-03-01

Calcified lesions are associated with lower rates of successful percutaneous coronary intervention (PCI), greater stent thrombosis, and increased target vessel revascularization. Women undergoing PCI are more often older than men and likely to present with severe lesion calcification. The ORBIT II study, for the first time compares the effect of the orbital atherectomy system (OAS) in men and women undergoing PCI for severely calcified lesions. Although the adjusted risk of severe dissections was higher in women, the incidence of in-hospital and 30-day outcomes was similar to men. Randomized comparisons of the OAS with rotational atherectomy and with stenting without atherectomy are needed to further elucidate sex-based differences in calcified lesion PCI. © 2016 Wiley Periodicals, Inc.

A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer

PubMed Central

Yano, Tomonori; Kasai, Hiroi; Horimatsu, Takahiro; Yoshimura, Kenichi; Teramukai, Satoshi; Morita, Satoshi; Tada, Harue; Yamamoto, Yoshinobu; Kataoka, Hiromi; Kakushima, Naomi; Ishihara, Ryu; Isomoto, Hajime; Muto, Manabu

2017-01-01

Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible patients were enrolled and all were treated with PDT. Twenty three patients with 25 lesions were assessed L-CR after PDT; the L-CR rate per patients was 88.5% (95% CI: 69.8%-97.6%). No skin phototoxicity was observed, and no grade 3 or worse non-hematological toxicities related to PDT were observed. PDT using talaporfin sodium and a diode laser is a safe and curative salvage treatment for local failure after CRT or RT for patients with esophageal cancer. PMID:28212527

Iron deficiency and anemia in heart failure.

PubMed

Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

2017-03-01

Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

Dubinett - Targeted Sequencing 2012 — EDRN Public Portal

Cancer.gov

we propose to use targeted massively parallel DNA sequencing to identify somatic alterations within mutational hotspots in matched sets of primary lung tumors, premalignant lesions, and adjacent,histologically normal lung tissue.

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

PubMed

Tzoulis, Charalampos; Neckelmann, Gesche; Mørk, Sverre J; Engelsen, Bernt E; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A

2010-05-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both

Metabolic enzymes dysregulation in heart failure: the prospective therapy.

PubMed

Parihar, Priyanka; Parihar, Mordhwaj Singh

2017-01-01

The heart failure accounts for the highest mortality rate all over the world. The development of preventive therapeutic approaches is still in their infancy. Owing to the extremely high energy demand of the heart, the bioenergetics pathways need to respond efficiently based on substrate availability. The metabolic regulation of such heart bioenergetics is mediated by various rate limiting enzymes involved in energy metabolism. Although all the pertinent mechanisms are not clearly understood, the progressive decline in the activity of metabolic enzymes leading to diminished ATP production is known to cause progression of the heart failure. Therefore, metabolic therapy that can maintain the appropriate activities of metabolic enzymes can be a promising approach for the prevention and treatment of the heart failure. The flavonoids that constitute various human dietary ingredients also effectively offer a variety of health benefits. The flavonoids target a variety of metabolic enzymes and facilitate effective management of the equilibrium between production and utilization of energy in the heart. This review discusses the broad impact of metabolic enzymes in the heart functions and explains how the dysregulated enzyme activity causes the heart failure. In addition, the prospects of targeting dysregulated metabolic enzymes by developing flavonoid-based metabolic approaches are discussed.

Double versus single stenting for coronary bifurcation lesions: a meta-analysis.

PubMed

Katritsis, Demosthenes G; Siontis, George C M; Ioannidis, John P A

2009-10-01

Several trials have addressed whether bifurcation lesions require stenting of both the main vessel and side branch, but uncertainty remains on the benefits of such double versus single stenting of the main vessel only. We have conducted a meta-analysis of randomized trials including patients with coronary bifurcation lesions who were randomly selected to undergo percutaneous coronary intervention by either double or single stenting. Six studies (n=1642 patients) were eligible. There was increased risk of myocardial infarction with double stenting (risk ratio, 1.78; P=0.001 by fixed effects; risk ratio, 1.49 with Bayesian meta-analysis). The summary point estimate suggested also an increased risk of stent thrombosis with double stenting, but the difference was not nominally significant given the sparse data (risk ratio, 1.85; P=0.19). No obvious difference was seen for death (risk ratio, 0.81; P=0.66) and target lesion revascularization (risk ratio, 1.09; P=0.67). Stenting of both the main vessel and side branch in bifurcation lesions may increase myocardial infarction and stent thrombosis risk compared with stenting of the main vessel only.

Adjunctive Strategies in the Management of Resistant, ‘Undilatable’ Coronary Lesions After Successfully Crossing a CTO with a Guidewire

PubMed Central

Fairley, Sara L.; Spratt, James C.; Rana, Omar; Talwar, Suneel; Hanratty, Colm; Walsh, Simon

2014-01-01

Successful revascularisation of chronic total occlusions (CTOs) remains one of the greatest challenges in the era of contemporary percutaneous coronary intervention (PCI). Such lesions are encountered with increasing frequency in current clinical practice. A predictable increase in the future burden of CTO management can be anticipated given the ageing population, increased rates of renal failure, graft failure and diabetes mellitus. Given recent advances and developments in CTO PCI management, successful recanalisation can be anticipated in the majority of procedures undertaken at high-volume centres when performed by expert operators. Despite advances in device technology, the management of resistant, calcific lesions remains one of the greatest challenges in successful CTO intervention. Established techniques to modify calcific lesions include the use of high-pressure non-compliant balloon dilation, cutting-balloons, anchor balloons and high speed rotational atherectomy (HSRA). Novel approaches have proven to be safe and technically feasible where standard approaches have failed. A step-wise progression of strategies is demonstrated, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. These methods will be described in the setting of clinical examples and include use of very high-pressure non-compliant balloon dilation, intentional balloon rupture with vessel dissection or balloon assisted micro-dissection (BAM), excimer coronary laser atherectomy (ECLA) and use of HSRA in various ‘offlabel’ settings. PMID:24694106

Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer.

PubMed

Costa, Daniel N; Lotan, Yair; Rofsky, Neil M; Roehrborn, Claus; Liu, Alexander; Hornberger, Brad; Xi, Yin; Francis, Franto; Pedrosa, Ivan

2016-01-01

We assess the performance of prospectively assigned magnetic resonance imaging based Likert scale scores for the detection of clinically significant prostate cancer, and analyze the pre-biopsy imaging variables associated with increased cancer detection using targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy. In this retrospective review of prospectively generated data including men with abnormal multiparametric prostate magnetic resonance imaging (at least 1 Likert score 3 or greater lesion) who underwent subsequent targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy, we determined the association between different imaging variables (Likert score, lesion size, lesion location, prostate volume, radiologist experience) and targeted biopsy positivity rate. We also compared the detection of clinically significant cancer according to Likert scale scores. Tumors with high volume (50% or more of any core) Gleason score 3+4 or any tumor with greater Gleason score were considered clinically significant. Each lesion served as the elementary unit for analysis. We used logistic regression for univariate and multivariate (stepwise selection) analysis to assess for an association between targeted biopsy positivity rate and each tested variable. The relationship between Likert scale and Gleason score was evaluated using the Spearman correlation coefficient. A total of 161 men with 244 lesions met the study eligibility criteria. Targeted biopsies diagnosed cancer in 41% (66 of 161) of the men and 41% (99 of 244) of the lesions. The Likert score was the strongest predictor of targeted biopsy positivity (OR 3.7, p <0.0001). Other imaging findings associated with a higher targeted biopsy positivity rate included smaller prostate volume (OR 0.7, p <0.01), larger lesion size (OR 2.2, p <0.001) and anterior location (OR 2.0, p=0.01). On multiple logistic regression analysis Likert score, lesion size and prostate volume were significant

Contrast-Enhanced Computed Tomography Evaluation of Hepatic Metastases in Breast Cancer Patients Before and After Cytotoxic Chemotherapy or Targeted Therapy.

PubMed

He, Hongying; Cai, Chunyan; Charnsangavej, Chusilp; Theriault, Richard L; Green, Marjorie; Quraishi, Mohammad A; Yang, Wei T

2015-11-01

To evaluate change in size vs computed tomography (CT) density of hepatic metastases in breast cancer patients before and after cytotoxic chemotherapy or targeted therapy. A database search in a single institution identified 48 breast cancer patients who had hepatic metastases treated with either cytotoxic chemotherapy alone or targeted therapy alone, and who had contrast-enhanced CT (CECT) scans of the abdomen at baseline and within 4 months of initiation of therapy in the past 10 years. Two radiologists retrospectively evaluated CT scans and identified up to 2 index lesions in each patient. The size (centimeters) of each lesion was measured according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and CT density (Hounsfield units) was measured by drawing a region of interest around the margin of the entire lesion. The percent change in sum of lesion size and mean CT density on pre- and post-treatment scans was computed for each patient; results were compared within each treatment group. Thirty-nine patients with 68 lesions received cytotoxic chemotherapy only; 9 patients with 15 lesions received targeted therapy only. The mean percent changes in sum of lesion size and mean CT density were statistically significant within the cytotoxic chemotherapy group before and after treatment, but not significant in the targeted therapy group. The patients in the targeted therapy group tend to have better 2-year survival. The patients who survived at 2 years tend to have more decrease in tumour size in the cytotoxic chemotherapy group. Cytotoxic chemotherapy produced significant mean percent decrease in tumour size and mean CT density of hepatic metastases from breast cancer before and after treatment, whereas targeted therapy did not. Nonetheless, there is a trend that the patients in the targeted therapy group had better 2-year survival rate. This suggests that RECIST is potentially inadequate in evaluating tumour response in breast cancer liver

Uterine Vascular Lesions

PubMed Central

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

A retrospective analysis of dermatological lesions in kidney transplant patients

PubMed Central

Castello, Michela; Gregorini, Marilena; Rampino, Teresa; Bosio, Francesca; Bedino, Giulia; Piotti, Giovanni; Soccio, Grazia; Esposito, Pasquale; Klersy, Catherine; Abelli, Massimo; Borroni, Giovanni; Canton, Antonio Dal

2013-01-01

Background & objectives: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. Methods: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5±11.8 yr) with transplant age 52.3±34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. Results: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis

Chronicity of Anterior Cruciate Ligament Deficiency, Part 2: Radiographic Predictors of Early Graft Failure

PubMed Central

Tanaka, Yoshinari; Kita, Keisuke; Takao, Rikio; Amano, Hiroshi; Uchida, Ryohei; Shiozaki, Yoshiki; Yonetani, Yasukazu; Kinugasa, Kazutaka; Mae, Tatsuo; Horibe, Shuji

2018-01-01

Background: Accumulating evidence suggests that long-term anterior cruciate ligament (ACL) deficiency can give rise to an abnormal tibiofemoral relationship and subsequent intra-articular lesions. However, the effects of chronic ACL deficiency (ACLD) on early graft failure after anatomic reconstruction remain unclear. Hypothesis: We hypothesized that patients with long-term ACLD lasting more than 5 years would have a greater rate of early graft failure due to insufficient intraoperative reduction of the tibia and that the preoperative and immediately postoperative abnormal tibiofemoral relationship in the sagittal plane, such as anterior tibial subluxation (ATS), would correlate with the graft status on postoperative magnetic resonance imaging (MRI). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 358 patients who had undergone anatomic ACL reconstruction with hamstring grafts were divided into 5 groups based on chronicity of ACLD: (1) 0 to 6 months, (2) 6 months to 1 year, (3) 1 to 2 years, (4) 2 to 5 years, and (5) longer than 5 years. Preoperatively and immediately postoperatively, lateral radiographs in full extension were taken in all patients to evaluate the tibiofemoral relationship, specifically with regard to ATS, space for the ACL (sACL), and extension angle. All patients underwent MRI at 6 months to reveal graft status. Groups with a high rate of graft failure were further analyzed to compare demographic and radiographic factors between the intact and failure subgroups, followed by multivariate logistic regression analysis to identify predisposing factors. Results: Graft failure without trauma was observed in 4 (1.8%), 0 (0%), 1 (3.7%), 3 (9.7%), and 8 patients (17.7%) in groups 1, 2, 3, 4, and 5, respectively. Of the 76 patients in groups 4 and 5, significant differences were noted between the failure and intact subgroups in preoperative ATS (4.9 vs 2.4 mm, respectively; P < .01), side-to-side differences in sACL (sACL-SSD) (4.7 vs

MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential.

PubMed

Shah, Palak; Bristow, Michael R; Port, J David

2017-12-01

Heart failure is increasing in prevalence with a lack of recently developed therapies that produce major beneficial effects on its associated mortality. MicroRNAs are small non-coding RNA molecules that regulate gene expression, are differentially regulated in heart failure, and are found in the circulation serving as a biomarker of heart failure. Data suggests that microRNAs may be used to detect allograft rejection in cardiac transplantation and may predict the degree of myocardial recovery in patients with a left ventricular assist device or treated with beta-blocker therapy. Given their role in regulating cellular function, microRNAs are an intriguing target for oligonucleotide therapeutics, designed to mimic or antagonize (antagomir) their biological effects. We review the current state of microRNAs as biomarkers of heart failure and associated conditions, the mechanisms by which microRNAs control cellular function, and how specific microRNAs may be targeted with novel therapeutics designed to treat heart failure.

Microarray Analysis of Microbiota of Gingival Lesions in Noma Patients

PubMed Central

Huyghe, Antoine; François, Patrice; Mombelli, Andrea; Tangomo, Manuela; Girard, Myriam; Baratti-Mayer, Denise; Bolivar, Ignacio; Pittet, Didier; Schrenzel, Jacques

2013-01-01

Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma. PMID:24086784

Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome.

PubMed

Cavet, Madeleine; Balu, Marie; Garel, Catherine; Mitanchez, Delphine; Renolleau, Sylvain; Alexandre, Marie; Pariente, Danièle; Ducou le Pointe, Hubert

2008-10-01

Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia.

Variation in Anthropometric Status and Growth Failure in Low- and Middle-Income Countries.

PubMed

Mejía-Guevara, Iván; Corsi, Daniel J; Perkins, Jessica M; Kim, Rockli; Subramanian, S V

2018-02-22

Addressing anthropometric failure in low- and middle-income countries can have 2 targets of inference: addressing differences between individuals within populations (W pop ) or differences between populations (B pop ). We present a multilevel framework to apply both targets of inference simultaneously and quantify the extent to which variation in anthropometric status and growth failure is reflective of undernourished children or undernourished populations. Cross-sectional data originated from the Demographic and Health Surveys program, covering children under age 5 from 57 countries surveyed between 2001 and 2015. A majority of variation in child anthropometric status and growth failure was attributable to W pop -associated differences, accounting for 89%, 83%, and 85% of the variability in z scores for height for age, weight for age, and weight for height. B pop -associated differences (communities, regions, and countries combined) were associated with 11%, 17%, and 15% of the variation in height-for-age z score, weight-for-age z score, and weight-for-height z score. Prevalence of anthropometric failure was closely correlated with mean levels of height and weight. Approximately 1% of W pop variability, compared with 30% to 50% of the B pop variability, was explained by mean values of maternal correlates of anthropometric status and failure. Although there is greater explanatory power B pop , this varied because of modifiability of what constitutes population. Our results suggest that universal strategies to prevent future anthropometric failure in populations combined with targeted strategies to address both the impending and existing burden among children are needed. Copyright © 2018 by the American Academy of Pediatrics.

Analysis of factors affecting failure of glass cermet tunnel restorations in a multi-center study.

PubMed

Pilebro, C E; van Dijken, J W

2001-06-01

The aim of this study was to analyze factors influencing the failures of tunnel restorations performed with a glass cermet cement (Ketac Silver). Caries activity, lesion size, tunnel cavity opening size, partial or total tunnel, composite lamination or operating time showed no significant correlation to failure rate. Twelve dentists in eight clinics clinically experienced and familiar with the tunnel technique placed 374 restorations. The occlusal sections of fifty percent of the restorations were laminated with hybrid resin composite. The results of the yearly clinical and radiographic evaluations over the course of 3 years were correlated to factors that could influence the failure rate using logistic regression analysis. At the 3-year recall a cumulative number of 305 restorations were available. The cumulative replacement rate was 20%. The main reasons for replacement were marginal ridge fracture (14%) and dentin caries (3%). Another 7% of the restorations which had not been replaced were classified as failures because of untreated dentin caries. The only significant variable observed was the individual failure rate of the participating dentists varying between 9 and 50% (p=0.013).

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

PubMed

Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

2017-09-01

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

PubMed

Basu, Sandip; Ranade, Rohit

2016-06-01

This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

PubMed

Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

2015-07-01

Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

COULD INTERFERON-GAMMA BE A THERAPEUTIC TARGET FOR TREATING HEART FAILURE?

PubMed Central

Levick, Scott P.; Goldspink, Paul H.

2013-01-01

The cytokine interferon-gamma (IFN-γ), is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. Whilst a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will: 1) discuss the source of IFN-γ in the diseased heart; 2) summarize the data from animal studies; 3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; 4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and 5) present the clinical evidence supporting a role for IFN-γ in heart failure. PMID:23589353

Pathologic lesions in children with acquired immunodeficiency syndrome an autopsy study of 11 cases from Mumbai, India.

PubMed

Lanjewar, Dhanesheshwar N; Bhatia, Varsha Omprakash; Lanjewar, Sonali Dhaneshwar

2016-01-01

Human immunodeficiency virus (HIV) infection in India has now been prevalent over three decades, and an increasing number of children are being affected with HIV. The spectrum of pathologic lesions in children with acquired immunodeficiency syndrome (AIDS) in India has not been well described. A review of systematically conducted autopsies of 11 (10 boys and 1 girl) children with AIDS is presented. The mode of HIV transmission in 6 children was vertical; in one it was blood transfusion and in 4 children route was presumably vertical as these were children of orphanage. The clinical manifestations were failure to thrive; 9 children, persistent gastroenteritis; 8, recurrent fever; 5, bacterial infections; 5, hepatosplenomegaly; 5, candidiasis; 1, scabies; 1, skin rash; 2, tuberculous (TB) meningitis; 1 and paraplegia; in 1 child. The spectrum of pathologic lesions observed were precocious involution in thymus in 3 and dysinvolution in 2 cases. Infectious diseases comprised of TB; 4 cases, cytomegalovirus infection (CMV) 4; bacterial pneumonia and meningitis; 7, and esophageal candidiasis in 2 cases. Dual or multiple infections were observed in 9 (82%) cases; these comprised of two lesions in 2, three lesions in 2, four lesions in 4, and five lesions in 1 case. TB, bacterial pneumonia, meningitis, and CMV infection are the most frequent causes of death in children with AIDS. Vascular lesions showing features of arteriopathy were observed in 5 cases and brain in one case showed non-Hodgkin's lymphoma. This study provides a better insight into the spectrum of pathologic lesions in children with AIDS in India. TB and CMV infection has been found to be the most prevalent infection in our children.

Orthograde retreatment failure with extruded MTA apical plug in a large periradicular lesion followed by surgical intervention: case report.

PubMed

Brito-Junior, Manoel; Faria-e-Silva, Andre Luis; Quintino, Alex Carvalho; Moreira-Junior, Gil; Geber, Mauro; Camilo, Carla Cristina; Soares, Janir Alves

2012-01-01

Absence of periapical healing after orthograde retreatment using an apical plug with mineral trioxide aggregate (MTA) can require surgical intervention. A patient with a root-filled maxillary central incisor with chronic apical periodontitis and sinus tract was referred for endodontic retreatment. Excessive apical enlargement was verified, indicating an MTA apical plug placement; however, an unintentional extrusion of MTA occurred during this step. The root canal was filled with gutta-percha and sealer, and periodic recalls were scheduled. The sinus tract was observed after six months and the lesion remained unaltered, although the extruded MTA had resorbed; therefore, an apicoectomy and retrograde root-end filling with MTA were performed. Absence of sinus tract, normal clinical aspect, and complete repair of the lesion were observed at the two-year follow-up.

Global left atrial failure in heart failure.

PubMed

Triposkiadis, Filippos; Pieske, Burkert; Butler, Javed; Parissis, John; Giamouzis, Gregory; Skoularigis, John; Brutsaert, Dirk; Boudoulas, Harisios

2016-11-01

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Robustness and fragility in coupled oscillator networks under targeted attacks.

PubMed

Yuan, Tianyu; Aihara, Kazuyuki; Tanaka, Gouhei

2017-01-01

The dynamical tolerance of coupled oscillator networks against local failures is studied. As the fraction of failed oscillator nodes gradually increases, the mean oscillation amplitude in the entire network decreases and then suddenly vanishes at a critical fraction as a phase transition. This critical fraction, widely used as a measure of the network robustness, was analytically derived for random failures but not for targeted attacks so far. Here we derive the general formula for the critical fraction, which can be applied to both random failures and targeted attacks. We consider the effects of targeting oscillator nodes based on their degrees. First we deal with coupled identical oscillators with homogeneous edge weights. Then our theory is applied to networks with heterogeneous edge weights and to those with nonidentical oscillators. The analytical results are validated by numerical experiments. Our results reveal the key factors governing the robustness and fragility of oscillator networks.

Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

PubMed Central

Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

Intravascular Ultrasound and Angiographic Predictors of In-Stent Restenosis of Chronic Total Occlusion Lesions.

PubMed

Kang, Jeehoon; Cho, Young-Seok; Kim, Seong-Wook; Park, Jin Joo; Yoon, Yeonyee E; Oh, Il-Young; Yoon, Chang-Hwan; Suh, Jung-Won; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju

2015-01-01

Despite the benefits of successful percutaneous coronary interventions (PCIs) for chronic total occlusion (CTO) lesions, PCIs of CTO lesions still carry a high rate of adverse events, including in-stent restenosis (ISR). Because previous reports have not specifically investigated the intravascular ultrasound (IVUS) predictors of ISR in CTO lesions, we focused on these predictors. We included 126 patients who underwent successful PCIs, using drug-eluting stents, and post-PCI IVUS of CTO lesions. Patient and lesion characteristics were analyzed to elucidate the ISR predictors. In each lesion, an average of 1.7 ± 0.7 (mean length, 46.4 ± 20.3 mm) stents were used. At 9 months follow-up, 14 (11%) patients demonstrated ISR, and 8 (6.3%) underwent target lesion revascularization. Multivariate logistic regression analysis showed that the independent predictors of ISR were the post-PCI minimal luminal diameter (MLD) and the stent expansion ratio (SER; minimal stent cross-sectional area (CSA) over the nominal CSA of the implanted stent), measured using quantitative coronary angiography (QCA) and IVUS, respectively. A receiver operating characteristic analysis indicated that the best post-PCI MLD and SER cut-off values for predicting ISR were 2.4 mm (area under the curve [AUC], 0.762; 95% confidence interval (CI), 0.639-0.885) and 70% (AUC, 0.714; 95% CI, 0.577-0.852), respectively. Lesions with post-PCI MLD and SER values less than these threshold values were at a higher risk of ISR, with an odds ratio of 23.3 (95% CI, 2.74-198.08), compared with lesions having larger MLD and SER values. Thus, the potential predictors of ISR, after PCI of CTO lesions, are the post-PCI MLD and SER values. The ISR rate was highest in lesions with a post-PCI MLD ≤2.4 mm and an SER ≤70%.

Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

PubMed Central

Kuo, Cheng-Hsiang; Leon, Lorraine; Chung, Eun Ji; Huang, Ru-Ting; Sontag, Timothy J.; Reardon, Catherine A.; Getz, Godfrey S.; Tirrell, Matthew; Fang, Yun

2015-01-01

Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation. Furthermore, to enhance specificity and transfection efficiency, polyelectrolyte complex micelles can be modified to include targeting capabilities. Here, we describe the design of targeted polyelectrolyte complex micelles containing inhibitors against dys-regulated microRNAs (miRNAs) that promote atherosclerosis, a leading cause of human mortality and morbidity. Inhibition of dys-regulated miRNAs in diseased cells associated with atherosclerosis has resulted in therapeutic efficacy in animal models and has been proposed to treat human diseases. However, the non-specific targeting of microRNA inhibitors via systemic delivery has remained an issue that may cause unwanted side effects. For this reason, we incorporated two different peptide sequences to our miRNA inhibitor containing polyelectrolyte complex micelles. One of the peptides (Arginine-Glutamic Acid-Lysine-Alanine or REKA) was used in another micellar system that demonstrated lesion-specific targeting in a mouse model of atherosclerosis. The other peptide (Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine or VHPKQHR) was identified via phage display and targets vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1). In this study we have tested the in vitro efficacy and efficiency of lesion- and cell-specific delivery of microRNA inhibitors to the cells associated with atherosclerotic lesions via peptide-targeted polyelectrolyte complex micelles. Our results show that REKA-containing micelles (fibrin-targeting) and VHPKQHR-containing micelles (VCAM-1 targeting) can be used to carry and deliver microRNA inhibitors into macrophages and human endothelial cells, respectively

Type 2 Diabetes and Heart Failure: Challenges and Solutions

PubMed Central

Thomas, Merlin C.

2016-01-01

Increasing numbers of older patients with type 2 diabetes, and their improved survival from cardiovascular events is seeing a massive increase in patients with both diabetes and heart failure. Already, at least a third of all patients with heart failure have diabetes. This close association is partly because all the major risk factors for heart failure also cluster in patients with type 2 diabetes, including obesity, hypertension, advanced age, sleep apnoea, dyslipidaemia, anaemia, chronic kidney disease, and coronary heart disease. However, diabetes may also cause cardiac dysfunction in the absence of overt macrovascular disease, as well as complicate the response to therapy. Current management is focused on targeting modifiable risk factors for heart failure including hyperglycaemia, dyslipidaemia, hypertension, obesity and anemia. But although these are important risk markers, none of these interventions substantially prevents heart failure or improves its outcomes. Much more needs to be done to focus on this issue, including the inclusion of hospital admission for heart failure as a pre-specified component of the primary composite cardiovascular outcomes and new trials in heart failure management specifically in the context of diabetes. PMID:27280301

Nonrandom Intrafraction Target Motions and General Strategy for Correction of Spine Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Hossain, Sabbir

2009-11-15

Purpose: To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed. Methods and Materials: Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case,more » time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions. Results: Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1 deg. of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level). Conclusions: A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions.« less

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

PubMed Central

Labarrere, Carlos A.; DiCarlo, Hector L.; Bammerlin, Elaine; Hardin, James W.; Kim, Yeon Mee; Chaemsaithong, Piya; Haas, David M.; Kassab, Ghassan S.; Romero, Roberto

2018-01-01

Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators

Organ failure avoidance and mitigation strategies in surgery.

PubMed

McConnell, Kevin W; Coopersmith, Craig M

2012-04-01

Postoperative organ failure is a challenging disease process that is better prevented than treated. Providers should use close observation and clinical judgment, and checklists of best practices to minimize the risk of organ failure in their patients. The treatment of multiorgan dysfunction syndrome (MODS) generally remains supportive, outside of rapid initiation of source control (when appropriate) and targeted antibiotic therapy. More specific treatments may be developed as the complex pathophysiology of MODS is better understood and more homogenous patient populations are selected for study. Copyright © 2012 Elsevier Inc. All rights reserved.

The Genomic Architecture of Sporadic Heart Failure

PubMed Central

Dorn, Gerald W

2011-01-01

Common or sporadic systolic heart failure (heart failure) is the clinical syndrome of insufficient forward cardiac output resulting from myocardial disease. Most heart failure is the consequence of ischemic or idiopathic cardiomyopathy. There is a clear familial predisposition to heart failure, with a genetic component estimated to confer between 20 and 30% of overall risk. The multifactorial etiology of this syndrome has complicated identification of its genetic underpinnings. Until recently, almost all genetic studies of heart failure were designed and deployed according to the common disease-common variant hypothesis, in which individual risk alleles impart a small positive or negative effect and overall genetic risk is the cumulative impact of all functional genetic variations. Early studies employed a candidate gene approach, focused mainly on factors within adrenergic and renin-angiotensin pathways that affect heart failure progression and are targeted by standard pharmacotherapeutics. Many of these reported allelic associations with heart failure have not been replicated. However, the preponderance of data support risk-modifier effects for the Arg389Gly polymorphism of β1-adrenergic receptors and the intron 16 in/del polymorphism of angiotensin converting enzyme. Recent unbiased studies using genome-wide single nucleotide polymorphism (SNP) microarrays have shown fewer positive results than when these platforms were applied to hypertension, myocardial infarction, or diabetes, possibly reflecting the complex etiology of heart failure. A new cardiovascular gene-centric sub-genome SNP array identified a common heat failure risk allele at 1p36 in multiple independent cohorts, but the biological mechanism for this association is still uncertain. It is likely that common gene polymorphisms account for only a fraction of individual genetic heart failure risk, and future studies using deep resequencing are likely to identify rare gene variants with larger

Imaging review of lipomatous musculoskeletal lesions

PubMed Central

Burt, Ashley M.; Huang, Brady K.

2017-01-01

Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT), and magnetic resonance imaging (MRI) is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented. PMID:28474576

Hock lesions and free-stall design.

PubMed

Weary, D M; Taszkun, I

2000-04-01

We compared the prevalence and severity of skin lesions on the hocks of lactating dairy cows in southern British Columbia, comparing 20 farms using three common bedding surfaces: sawdust, sand, and geotextile mattresses. Skin lesions were scored at five positions on the hock. For each position we noted if the lesion showed inflammatory attributes, and then assigned a severity score. Of the 1752 lactating cows scored, 1267 cows (73%) had at least one hock lesion. Of those cows with lesions, 87% had lesions on both legs, 76% had lesions on more than one location on the hock, and 78% had a lesion of at least moderate severity (i.e., evidence of skin breakage or an area of hair loss >10 cm2). Lesions were most prevalent on farms that used geotextile mattresses (91% of cows) and least common on farms that used sand (24% of cows). Moreover, lesions on cows from farms using mattresses were more numerous and more severe than those on cows from sand-bedded farms. The prevalence and severity of lesions on farms using sawdust was intermediate. Lesions also varied in relation to location on the hock. For farms using geotextile mattresses, lesions were more common and more severe on the lateral surfaces of both the tuber calcis and the tarsal joint. On farms using sawdust, lesions were common on the dorsal surface of the tuber calcis and the lateral surfaces of both the tuber calcis and the tarsal joint. Lesions were rare on all five positions for cows from sand-bedded farms. Among the 10 farms sampled using sawdust, we found a significant negative relationship between the length of the stall and severity of lesions. For cows with lesions, the number and severity of lesions increased with age.

Repair-Resistant DNA Lesions

PubMed Central

2017-01-01

The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

[A case of systemic lupus erythematosus discovered from left heart failure due to lupus induced mitral regurgitation].

PubMed

Ueno, K; Fujimoto, S; Fujimoto, T; Nakano, H; Nakajima, T; Yamano, S; Shiiki, H; Hashimoto, T; Imoto, K; Miyagawa, S; Dohi, K

1999-10-01

A 50-year-old female was admitted to a local hospital because of dyspnea, and diagnosed as having left heart failure secondary to mitral regurgitation. After the improvement of congestive heart failure, polyarthralgia, fever, and positive anti-nuclear antibody were pointed out. She was referred to our hospital for the further evaluation. Serological test showed anti-double stranded DNA antibodies, anti-SS-A antibodies, anti-beta 2-GPI antibodies and biological false positive for syphilis. The diagnosis of SLE has been made from the clinical signs and the serology. Therefore mitral valvular lesion of this patient was considered to be one of the symptoms of SLE. We reported a rare case in which left heart failure was a initial clinical manifestation of SLE.

Failure strength of a new meniscus arrow repair technique: biomechanical comparison with horizontal suture.

PubMed

Albrecht-Olsen, P; Lind, T; Kristensen, G; Falkenberg, B

1997-04-01

A new method for arthroscopic all-inside repair of vertical meniscus lesions by use of a biodegradable fixation device ("meniscus arrow") has been developed, including a set of cannulas for easy insertion via standard arthroscopic portals. The technique is described. A study to test the fixation properties was performed in the laboratory. Twenty-four fresh frozen bovine medial menisci were defreezed and divided into three groups. In all menisci an artificial vertical lesion was created with a scalpel 3mm from the peripheral rim. Repair in group I was done with a single horizontal Maxon-O suture using an Acufex double-barrel cannula (Acufex Meniscal Stitcher; Acufex Microsurgical, Norwood, MA). A knot was tied on the capsular side. Repair in group II was made with one 13 mm Biofix Meniscus arrow (Bioscience Ltd, Tampere, Finland). In group III repair was performed like in group II but the menisci were incubated in isotonic saline at 21 degrees C for 24 hours before testing. Menisci in group I and II were tested within 3 hours after defreezing. Prior to testing total separation of central and peripheral part of meniscus was performed. Thus only the repair site was tested. Pull-out tests to failure were made in a computer-based Nene M5 testing machine with a cross-head speed of 5 mm/min. Median failure load in group I: 49 N (range 43 to 77 N), in group II: 53 N (range 42 to 65 N) and in group III: 54 N (range 35 to 74 N). No statistically significant differences in failure load was found between the groups. Thus initial failure strength for arrow-repaired bovine menisci is comparable to that of a horizontal suture.

High dose rate brachytherapy with customized applicators for malignant facial skin lesions.

PubMed

Jumeau, R; Renard-Oldrini, S; Courrech, F; Buchheit, I; Oldrini, G; Vogin, G; Peiffert, D

2016-07-01

Brachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system. Patients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg(®) Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10mm to 20mm). The dose schedules were 25Gy in five fractions for postoperative lesions, 30Gy in six fractions for exclusive treatments and a single session of 8Gy could be considered for palliative treatments. In 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1cm(2) with a mean thickness of 6.1mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg(®) Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity. High dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Evaluation of a Dedicated Balloon Catheter for Infrapopliteal Difficult Calcified Lesions in Diabetic Patients With Critical Limb Ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lupattelli, Tommaso, E-mail: tommasolupattelli@hotmail.com

2011-02-15

The purpose of this study was to assess the technical performance and immediate procedural outcome of a new balloon catheter in the treatment of calcified lesions in infrapopliteal arterial disease. Sixty-one patients (81 vessels) with infrapopliteal arterial disease were evaluated. Seventy-four of the 81 treated vessels had total occlusions. The ReeKross 18 peripheral transluminal angioplasty catheter (ClearStream, Wexford, Ireland) is an 0.018-inch guidewire system with 4F sheath compatibility and a rigid shaft intended for enhanced pushability. Only technical procedural outcomes were recorded. In 37 of 61 patients (50 infrapopliteal severely stenosed or occluded vessels), an attempt with a standard balloonmore » was made before the ReeKross 18 was used. In 24 patients, the ReeKross 18 was used as the primary catheter in 23 cases involving crural arteries and in 8 cases involving the foot. The ReeKross 18 crossed the lesion in 55 of 59 (93.2%) patients and 72 of 77 (94.5%) vessels, respectively. Postdilatation results for the 51 patients (64 target lesions) in whom ReeKross 18 balloon dilation was achieved showed <30% residual stenosis in all but 4 patients (5 lesions). Of the patients treated with the ReeKross 18 as the primary catheter, the technical success rate (no adjunctive treatment/stent) was obtained in 20 of 24 (83.3%) patients (27 of 31 [87.1%] target lesions). In the treatment of difficult calcified lesions, the choice of a high-pushability angioplasty catheter, such as the ReeKross 18, warrants consideration.« less

A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial.

PubMed

Stone, Gregg W; Teirstein, Paul S; Meredith, Ian T; Farah, Bruno; Dubois, Christophe L; Feldman, Robert L; Dens, Joseph; Hagiwara, Nobuhisa; Allocco, Dominic J; Dawkins, Keith D

2011-04-19

We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI). Randomized trials have demonstrated an excellent safety and efficacy profile for the CoCr-EES. The PtCr-EES uses the identical antiproliferative agent and polymer but with a novel platinum chromium scaffold designed for enhanced deliverability, vessel conformability, side-branch access, radiopacity, radial strength, and fracture resistance. A total of 1,530 patients undergoing PCI of 1 or 2 de novo native lesions were randomized at 132 worldwide sites to CoCr-EES (n = 762) or PtCr-EES (n = 768). The primary endpoint was the 12-month rate of target lesion failure (TLF), the composite of target vessel-related cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) in the per-protocol population (patients who received ≥1 assigned study stent), powered for noninferiority. The 12-month rate of TLF in the per-protocol population occurred in 2.9% versus 3.4% of patients assigned to CoCr-EES versus PtCr-EES, respectively (difference: 0.5%, 95% confidence interval: -1.3% to 2.3%, p(noninferiority) = 0.001, p(superiority) = 0.60). By intention-to-treat, there were no significant differences between CoCr-EES and PtCr-EES in the 12-month rates of TLF (3.2% vs. 3.5%, p = 0.72), cardiac death or MI (2.5% vs. 2.0%, p = 0.56), TLR (1.9% vs. 1.9%, p = 0.96), or Academic Research Consortium definite or probable stent thrombosis (0.4% vs. 0.4%, p = 1.00). In this large-scale, prospective, single-blind randomized trial, a novel PtCr-EES was noninferior to the predicate CoCr-EES for TLF, with nonsignificant differences in measures of safety and efficacy through 12-month follow-up after PCI. Copyright © 2011 American College of Cardiology Foundation. Published by

Examination of contrast mechanisms in optoacoustic imaging of thermal lesions

NASA Astrophysics Data System (ADS)

Richter, Christian; Spirou, Gloria; Oraevsky, Alexander A.; Whelan, William M.; Kolios, Michael C.

2006-02-01

Optoacoustic Imaging is based on the thermal expansion of tissue caused by a temperature rise due to absorption of short laser pulses. At constant laser fluence, optoacoustic image contrast is proportional to differences in optical absorption and the thermoacoustic efficiency, expressed by the Grueuneisen parameter, Γ. Γ is proportional to the thermal expansion coefficient, the sound velocity squared and the inverse heat capacity at constant pressure. In thermal therapies, these parameters may be modified in the treated area. In this work experiments were performed to examine the influence of these parameters on image contrast. A Laser Optoacoustic Imaging System (LOIS, Fairway Medical Technologies, Houston, Texas) was used to image tissue phantoms comprised of cylindrical Polyvinyl Chloride Plastisol (PVCP) optical absorbing targets imbedded in either gelatin or PVCP as the background medium. Varying concentrations of Black Plastic Color (BPC) and titanium dioxide (TiO II) were added to targets and background to yield desired tissue relevant optical absorption and effective scattering coefficients, respectively. In thermal therapy experiments, ex-vivo bovine liver was heated with laser fibres (805nm laser at 5 W for 600s) to create regions of tissue coagulation. Lesions formed in the liver tissue were visible using the LOIS system with reasonable correspondence to the actual region of tissue coagulation. In the phantom experiments, contrast could be seen with low optical absorbing targets (μ a of 0.50cm -1 down to 0.13cm-1) embedded in a gelatin background (see manuscript for formula). Therefore, the data suggest that small objects (< 5mm) with low absorption coefficients (in the range < 1cm -1) can be imaged using LOIS. PVCP-targets in gelatin were visible, even with the same optical properties as the gelatin, but different Γ. The enhanced contrast may also be caused by differences in the mechanical properties between the target and the surrounding medium

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

[Managing focal incidental renal lesions].

PubMed

Nicolau, C; Paño, B; Sebastià, C

2016-01-01

Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: implications for radiation target volume design.

PubMed

Olszyna-Serementa, Marta; Socha, Joanna; Wierzchowski, Marek; Kępka, Lucyna

2013-05-01

Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser

Base Excision Repair and Lesion-Dependent Subpathways for Repair of Oxidative DNA Damage

PubMed Central

Svilar, David; Goellner, Eva M.; Almeida, Karen H.

2011-01-01

Abstract Nuclear and mitochondrial genomes are under continuous assault by a combination of environmentally and endogenously derived reactive oxygen species, inducing the formation and accumulation of mutagenic, toxic, and/or genome-destabilizing DNA lesions. Failure to resolve these lesions through one or more DNA-repair processes is associated with genome instability, mitochondrial dysfunction, neurodegeneration, inflammation, aging, and cancer, emphasizing the importance of characterizing the pathways and proteins involved in the repair of oxidative DNA damage. This review focuses on the repair of oxidative damage–induced lesions in nuclear and mitochondrial DNA mediated by the base excision repair (BER) pathway in mammalian cells. We discuss the multiple BER subpathways that are initiated by one of 11 different DNA glycosylases of three subtypes: (a) bifunctional with an associated β-lyase activity; (b) monofunctional; and (c) bifunctional with an associated β,δ-lyase activity. These three subtypes of DNA glycosylases all initiate BER but yield different chemical intermediates and hence different BER complexes to complete repair. Additionally, we briefly summarize alternate repair events mediated by BER proteins and the role of BER in the repair of mitochondrial DNA damage induced by ROS. Finally, we discuss the relation of BER and oxidative DNA damage in the onset of human disease. Antioxid. Redox Signal. 14, 2491–2507. PMID:20649466

Nonsurgical management of periapical lesions: a prospective study.

PubMed

Shah, N

1988-09-01

A total of 93 cases comprising 132 teeth with signs and symptoms or radiographic evidence of periapical pathoses were treated endodontically and were followed up for a period of 2 years. Nonsurgical management was successful in 84.4% of the cases. Histopathologic examination of tissue specimens from cases in which treatment failed revealed that only 35.7% of the cases involved apical cysts, while the remaining 64.3% involved chronic inflammatory tissue. Interestingly, 50% of the failures were observed at or 1 year after completion of treatment, which stresses the need for long-term follow-up of treated endodontic cases. In this study, a successful outcome did not seem to be dependent on either the nature or the size of the lesion, even though it is true that treatment of larger lesions failed more frequently. There seems to be some individual immunologic response variation, which may influence the final outcome of the treatment. Gyromatic instruments were used in 44 of the 93 cases treated and were evaluated and compared with hand instruments in clinical situations. Gyromatic instruments were found to be more convenient and safer to use, since their use improved visibility and eliminated the risk of the instruments' falling into the throat and being aspirated. They exhibited good flexibility and could easily negotiate curved canals without breaking. Used judiciously, these would be efficient tools in the endodontist's armamentarium.

Response disengagement on a spatial self-ordered sequencing task: effects of regionally selective excitotoxic lesions and serotonin depletion within the prefrontal cortex.

PubMed

Walker, Susannah C; Robbins, Trevor W; Roberts, Angela C

2009-05-06

Prefrontal cortex (PFC) is critical for self-ordered response sequencing. Patients with frontal lobe damage are impaired on response sequencing tasks, and increased blood flow has been reported in ventrolateral and dorsolateral PFC in subjects performing such tasks. Previously, we have shown that large excitotoxic lesions of the lateral PFC (LPFC) and orbitofrontal cortex FC (OFC), but not global prefrontal dopamine depletion, markedly impaired marmoset performance on a spatial self-ordered sequencing task (SSOST). To determine whether LPFC or OFC was responsible for the previously observed impairments and whether the underlying neural mechanism was modulated by serotonin, the present study compared the effects of selective LPFC and OFC excitotoxic lesions and 5,7-DHT-induced PFC serotonin depletions in marmosets on SSOST performance. Severe and long-lasting impairments in SSOST performance, including robust perseverative responding, followed LPFC but not OFC lesions. The deficit was ameliorated by task manipulations that precluded perseveration. Depletions of serotonin within LPFC and OFC had no effect, despite impairing performance on a visual discrimination reversal task, thus providing further evidence for differential monaminergic regulation of prefrontal function. In the light of the proposed attentional control functions of ventrolateral PFC and the failure of LPFC-lesioned animals to disengage from the immediately preceding response, it is proposed that this deficit may be due to a failure to attend to and register that a response has been made and thus should not be repeated. However, 5-HT does not appear to be implicated in this response inhibitory capacity.

The role of macrophages and eosinophils in reactive lesions of the oral cavity.

PubMed

Aghbali, Amir Ala; Akbarzadeh, Ayshin; Kouhsoltani, Maryam

2018-01-01

Many studies have reported that macrophages and eosinophils are involved in the pathogenesis of several diseases. To the best of our knowledge, this is the first study comparing macrophages and eosinophils in oral reactive lesions. In this study, we aimed to determine the contribution of macrophages and eosinophils to the pathogenesis of oral reactive lesions and the relationships between these biomarkers and the diverse histopathologic features. Seventy-five paraffin-embedded tissue samples were assessed in this study. Five categories (15 cases for each group), including peripheral ossifying fibroma, pyogenic granuloma, fibroma, inflammatory fibrous hyperplasia, and peripheral giant-cell granuloma, were considered. Anti-CD68 immunohistochemical and hematoxylin-eosin staining was carried out. We found that macrophages, but not eosinophils, were a significant internal component of oral reactive lesions. Macrophages were observed in high densities in all studied groups and diffusely distributed or clustered throughout these lesions. The number of macrophages was increased in peripheral giant-cell granuloma compared with other groups. Our findings suggest that macrophages are involved in the pathogenesis and the variation of microscopic features of oral reactive lesions. However, further clinical studies should be conducted to identify the biological process behind macrophages and the molecular interactions of these cells, with the ultimate aim of suggesting a new potential therapeutic target for these lesions. We found that eosinophils were not involved in the fibrotic process and the variation of microscopic features in oral reactive lesions. Our results showed that peripheral giant-cell granulomas highly demonstrated histiocytic characteristics.

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popescu, Bogdan F.; Frischer, Josa M.; Webb, Samuel M.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distributionmore » of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Furthermore, upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage.« less

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions

DOE PAGES

Popescu, Bogdan F.; Frischer, Josa M.; Webb, Samuel M.; ...

2017-03-22

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distributionmore » of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Furthermore, upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage.« less

Effect of Root Filling on Stress Distribution in Premolars with Endodontic-Periodontal Lesion: A Finite Elemental Analysis Study.

PubMed

Belli, Sema; Eraslan, Oğuz; Eskitascioglu, Gürcan

2016-01-01

Endodontic-periodontal (EP) lesions require both endodontic and periodontal therapies. Impermeable sealing of the root canal system after cleaning and shaping is essential for a successful endodontic treatment. However, complete healing of the hard and soft tissue lesions takes time, and diseased bone, periodontal ligament, and tooth fibrous joints are reported to have an increased failure risk for a given load. Considering that EP lesions may affect the biomechanics of teeth, this finite elemental analysis study aimed to test the effect of root fillings on stress distribution in premolars with EP lesions. Three finite elemental analysis models representing 3 different types of EP lesions (primary endodontic disease [PED], PED with secondary periodontic involvement, and true combined) were created. The root canals were assumed as nonfilled or filled with gutta-percha, gutta-percha/apical mineral trioxide aggregate (MTA) plug, and MTA-based sealer. Materials used were assumed to be homogenous and isotropic. A 300-N load was applied from the buccal cusp of the crown with a 135° angle. The Cosmoworks structural-analysis program (SolidWorks Corp, Waltham, MA) was used for analysis. Results were presented considering von Mises criteria. Stresses at the root apex increased with an increase in lesion dimensions. Root filling did not affect stress distribution in the PED model. An MTA plug or MTA-based sealer created more stress areas within the root compared with the others in the models representing PED with periodontic involvement and true combined lesions. Stresses at the apical end of the root increase with increases in lesion dimensions. MTA-based sealers or an MTA plug creates more stresses when there is periodontic involvement or a true combined lesion. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Lesion mapping of social problem solving.

PubMed

Barbey, Aron K; Colom, Roberto; Paul, Erick J; Chau, Aileen; Solomon, Jeffrey; Grafman, Jordan H

2014-10-01

Accumulating neuroscience evidence indicates that human intelligence is supported by a distributed network of frontal and parietal regions that enable complex, goal-directed behaviour. However, the contributions of this network to social aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 144) that investigates the neural bases of social problem solving (measured by the Everyday Problem Solving Inventory) and examine the degree to which individual differences in performance are predicted by a broad spectrum of psychological variables, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores for each variable were obtained, followed by voxel-based lesion-symptom mapping. Stepwise regression analyses revealed that working memory, processing speed, and emotional intelligence predict individual differences in everyday problem solving. A targeted analysis of specific everyday problem solving domains (involving friends, home management, consumerism, work, information management, and family) revealed psychological variables that selectively contribute to each. Lesion mapping results indicated that social problem solving, psychometric intelligence, and emotional intelligence are supported by a shared network of frontal, temporal, and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The results support an integrative framework for understanding social intelligence and make specific recommendations for the application of the Everyday Problem Solving Inventory to the study of social problem solving in health and disease. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved

Lesion network localization of criminal behavior

PubMed Central

Darby, R. Ryan; Horn, Andreas; Fox, Michael D.

2018-01-01

Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior. PMID:29255017

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

2017-07-01

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Inter-algorithm lesion volumetry comparison of real and 3D simulated lung lesions in CT

NASA Astrophysics Data System (ADS)

Robins, Marthony; Solomon, Justin; Hoye, Jocelyn; Smith, Taylor; Ebner, Lukas; Samei, Ehsan

2017-03-01

The purpose of this study was to establish volumetric exchangeability between real and computational lung lesions in CT. We compared the overall relative volume estimation performance of segmentation tools when used to measure real lesions in actual patient CT images and computational lesions virtually inserted into the same patient images (i.e., hybrid datasets). Pathologically confirmed malignancies from 30 thoracic patient cases from Reference Image Database to Evaluate Therapy Response (RIDER) were modeled and used as the basis for the comparison. Lesions included isolated nodules as well as those attached to the pleura or other lung structures. Patient images were acquired using a 16 detector row or 64 detector row CT scanner (Lightspeed 16 or VCT; GE Healthcare). Scans were acquired using standard chest protocols during a single breath-hold. Virtual 3D lesion models based on real lesions were developed in Duke Lesion Tool (Duke University), and inserted using a validated image-domain insertion program. Nodule volumes were estimated using multiple commercial segmentation tools (iNtuition, TeraRecon, Inc., Syngo.via, Siemens Healthcare, and IntelliSpace, Philips Healthcare). Consensus based volume comparison showed consistent trends in volume measurement between real and virtual lesions across all software. The average percent bias (+/- standard error) shows -9.2+/-3.2% for real lesions versus -6.7+/-1.2% for virtual lesions with tool A, 3.9+/-2.5% and 5.0+/-0.9% for tool B, and 5.3+/-2.3% and 1.8+/-0.8% for tool C, respectively. Virtual lesion volumes were statistically similar to those of real lesions (< 4% difference) with p >.05 in most cases. Results suggest that hybrid datasets had similar inter-algorithm variability compared to real datasets.

Imaging of cerebellopontine angle lesions: an update. Part 2: intra-axial lesions, skull base lesions that may invade the CPA region, and non-enhancing extra-axial lesions.

PubMed

Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

2007-11-01

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions responsible for cerebellopontine angle (CPA) syndrome. However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion- and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Non-enhancing extra-axial CPA masses are cystic (epidermoid cyst, arachnoid cyst, neurenteric cyst) or contain fat (dermoid cyst, lipoma). Tumours can also extend into the CPA by extension from the skull base (paraganglioma, chondromatous tumours, chordoma, cholesterol granuloma, endolymphatic sac tumour). Finally, brain stem or ventricular tumours can present with a significant exophytic component in the CPA that may be difficult to differentiate from an extra-axial lesion (lymphoma, hemangioblastoma, choroid plexus papilloma, ependymoma, glioma, medulloblastoma, dysembryoplastic neuroepithelial tumour).

The target sign in colorectal liver metastases: an atypical Gd-EOB-DTPA "uptake" on the hepatobiliary phase of MR imaging.

PubMed

Granata, Vincenza; Catalano, Orlando; Fusco, Roberta; Tatangelo, Fabiana; Rega, Daniela; Nasti, Guglielmo; Avallone, Antonio; Piccirillo, Mauro; Izzo, Francesco; Petrillo, Antonella

2015-10-01

To describe the MRI findings in colorectal cancer liver metastases using gadoxetic acid (Gd-EOB-DTPA), with special emphasis on the target feature seen on the hepatobiliary phase. The medical records of 45 colorectal cancer patients with an overall number of 150 liver metastases were reviewed. All patients underwent Gd-EOB-DTPA-enhanced MRI before any kind of treatment. We retrospectively evaluated, for each lesion, the signal intensity on the T1-weighted, T2-weighted, and diffusion-weighted images. Additionally, the enhancement pattern during the arterial-, portal-, equilibrium-, and hepatobiliary-phase was assessed. Fourteen lesions had a pathological correlation. Lesions size was 5-40 mm (mean 15 mm). All metastases were hypointense on T1-w imaging. Ninety-nine lesions (66%) had a central area of very high signal intensity on T2-w imaging. Fifty-one metastases (34%) were hyperintense on the T2-w images. In DWI, all lesions had a restricted diffusion. The mean ADC value was 1.31 × 10(-3) mm(2)/s (range 1.10-1.45 × 10(-3) mm(2)/s). During the arterial-phase imaging, 61 lesions (41%) showed a rim enhancement, while 89 lesions (59%) appeared as hypointense. All lesions had low signal intensity in the portal and equilibrium phase. Thirty-nine percent of the lesions also showed an enhancing rim on the portal-phase images. During the hepatobiliary phase, 80 lesions (53.3%) were hypointense, while 70 lesions (46.7%) had a target appearance. A number of metastases show an atypical contrast medium uptake during the hepatobiliary phase of gadoxetic acid-enhanced MRI, consisting in a target appearance.

Clinical Outcomes from Unselected "Real-World" Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent.

PubMed

Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

2015-01-01

Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in "real-world" patients.

Toll-like receptor 2 expression in refractory periapical lesions.

PubMed

Desai, S V; Love, R M; Rich, A M; Seymour, G J

2011-10-01

To investigate the expression of TLR2 in refractory periapical lesions. Refractory periapical lesion biopsies were histopathologically and clinically categorized into asymptomatic periapical granuloma (n=10), symptomatic periapical granuloma (n=10) or periapical cyst (n=10) and prepared for immunohistochemical staining using antibodies to TLR2, CD3 and CD19 or staining with methyl green pyronin. Sections were viewed under light microscopy and the presence or absence of the target cells was correlated with the histopathological and clinical data. Additionally, TLR2 expression was quantified by counting TLR(+) cells. Various mononuclear inflammatory cells in the bacteria-induced periapical lesions were reactive to TLR2 antibody, with many showing morphological similarities to lymphocytes and plasma cells. Lymphocytes were the most numerous cells in the inflammatory infiltrate. In refractory periapical granuloma, CD3(+) T cells were more numerous, whereas in periapical cysts, CD19(+) B cells were more numerous. There was a statistically significant (P<0.05) higher expression of TLR2 in symptomatic periapical granuloma than asymptomatic periapical granuloma or periapical cyst. The presence of TLR-expressing cells in periapical granulomas and cysts provides further evidence that periapical cysts are likely to be sustained by the immune system via reaction to bacterial antigens. © 2011 International Endodontic Journal.

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

PubMed

Arbula, Sandra; Pacella, Valentina; De Pellegrin, Serena; Rossetto, Marta; Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Vallesi, Antonino

2017-06-01

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. Copyright © 2017 The Authors

Using GIS for spatial analysis of rectal lesions in the human body

PubMed Central

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-01-01

Background Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Results Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. Conclusion This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process. PMID:17362510

Using GIS for spatial analysis of rectal lesions in the human body.

PubMed

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-03-15

Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process.

A prospective clinical study to evaluate the safety and performance of wireless localization of nonpalpable breast lesions using radiofrequency identification technology.

PubMed

Dauphine, Christine; Reicher, Joshua J; Reicher, Murray A; Gondusky, Christina; Khalkhali, Iraj; Kim, Michelle

2015-06-01

The purpose of this study was to evaluate the safety and performance of localizing nonpalpable breast lesions using radiofrequency identification technology. Twenty consecutive women requiring preoperative localization of a breast lesion were recruited. Subjects underwent placement of both a hook wire and a radiofrequency identification tag immediately before surgery. The radiofrequency identification tag was the primary method used by the operating surgeon to localize each lesion during excision, with the hook wire serving as backup in case of tag migration or failed localization. Successful localization with removal of the intended lesion was the primary outcome measured. Tag migration and postoperative infection were also noted to assess safety. Twenty patients underwent placement of a radiofrequency identification tag, 12 under ultrasound guidance and eight with stereotactic guidance. In all cases, the radiofrequency identification tag was successfully localized by the reader at the level of the skin before incision, and the intended lesion was removed along with the radiofrequency identification tag. There were no localization failures and no postoperative infections. Tag migration did not occur before incision, but in three cases, occurred as the lesion was being retracted with fingers to make the final cut along the deep surface of the specimen. In this initial clinical study, radiofrequency tags were safe and able to successfully localize nonpalpable breast lesions. Radiofrequency identification technology may represent an alternative method to hook wire localization.

Gene Therapy in Heart Failure.

PubMed

Fargnoli, Anthony S; Katz, Michael G; Bridges, Charles R; Hajjar, Roger J

2017-01-01

Heart failure is a significant burden to the global healthcare system and represents an underserved market for new pharmacologic strategies, especially therapies which can address root cause myocyte dysfunction. Modern drugs, surgeries, and state-of-the-art interventions are costly and do not improve survival outcome measures. Gene therapy is an attractive strategy, whereby selected gene targets and their associated regulatory mechanisms can be permanently managed therapeutically in a single treatment. This in theory could be sustainable for the patient's life. Despite the promise, however, gene therapy has numerous challenges that must be addressed together as a treatment plan comprising these key elements: myocyte physiologic target validation, gene target manipulation strategy, vector selection for the correct level of manipulation, and carefully utilizing an efficient delivery route that can be implemented in the clinic to efficiently transfer the therapy within safety limits. This chapter summarizes the key developments in cardiac gene therapy from the perspective of understanding each of these components of the treatment plan. The latest pharmacologic gene targets, gene therapy vectors, delivery routes, and strategies are reviewed.

Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model

PubMed Central

Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

2016-01-01

The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model.

PubMed

Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

2016-01-01

The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions

PubMed Central

Saini, Rajan; Lee, Nathan V.; Liu, Kelly Y. P.; Poh, Catherine F.

2016-01-01

Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

Oral lesions in HIV+/AIDS adolescents perinatally infected undergoing HAART.

PubMed

Gaitán-Cepeda, Luis-Alberto; Domínguez-Sánchez, Anitza; Pavía-Ruz, Noris; Muñoz-Hernández, Rocío; Verdugo-Díaz, Roberto; Valles-Medina, Ana-María; Meráz-Acosta, Héctor

2010-07-01

To assess the prevalence of the oral lesions related to HIV-infection (HIV-OL) in HIV+/AIDS adolescents (=13 years old), and the differences with HIV+/AIDS children (=3 - <13 years old) perinatally infected. 25 HIV+/AIDS adolescents and 62 HIV+/AIDS children, undergoing Highly Active Antiretroviral Therapy, were orally examined. HIV-OL was diagnosed in accordance with EC-Clearinghouse-World Health Organization. The patients were classifies with respect to their immune status in relation with the CD4+ cell counts as moderately immunodeficient; mildly immunodeficient and severely immunodeficient in accordance to the revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years (CDC-USA). The virological status was established in relation to the copies of RNA-HIV-1/mL as follows: with undetectable viral load (UDVL); with low viral load and with high viral load. A chi-square test was performed (p<0.05 IC95%). The prevalence of HIV-OL in HIV+/AIDS adolescents was 20% while in HIV/AIDS children was 30.6% (p>0.05). Oral candidiasis was the most prevalent oral lesion in both groups. Association (p<0.05) of a high prevalence of HIV-OL and oral candidiasis with a high viral load was observed in both study groups. Adolescents perinatally HIV-infected have a high prevalence of HIV-OL. Oral Candidiasis still is the most frequent oral opportunistic infection. Oral lesions could have association to viral failure in HIV+/AIDS adolescents undergoing HAART.

Parenteral Nutrition and Intestinal Failure.

PubMed

Bielawska, Barbara; Allard, Johane P

2017-05-06

Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.

Skull base lesions: extracranial origins.

PubMed

Mosier, Kristine M

2013-10-01

A number of extracranial anatomical sites, including the nasopharynx, paranasal sinuses, and masticator space, may give rise to lesions involving the skull base. Implicit in the nature of an invasive lesion, the majority of these lesions are malignant. Accordingly, for optimal patient outcomes and treatment planning, it is imperative to include a search pattern for extracranial sites and to assess accurately the character and extent of these diverse lesions. Of particular importance to radiologists are lesions arising from each extracranial site, the search patterns, and relevant information important to convey to the referring clinician. Copyright © 2013 Elsevier Inc. All rights reserved.

Real-time estimation of lesion depth and control of radiofrequency ablation within ex vivo animal tissues using a neural network.

PubMed

Wang, Yearnchee Curtis; Chan, Terence Chee-Hung; Sahakian, Alan Varteres

2018-01-04

Radiofrequency ablation (RFA), a method of inducing thermal ablation (cell death), is often used to destroy tumours or potentially cancerous tissue. Current techniques for RFA estimation (electrical impedance tomography, Nakagami ultrasound, etc.) require long compute times (≥ 2 s) and measurement devices other than the RFA device. This study aims to determine if a neural network (NN) can estimate ablation lesion depth for control of bipolar RFA using complex electrical impedance - since tissue electrical conductivity varies as a function of tissue temperature - in real time using only the RFA therapy device's electrodes. Three-dimensional, cubic models comprised of beef liver, pork loin or pork belly represented target tissue. Temperature and complex electrical impedance from 72 data generation ablations in pork loin and belly were used for training the NN (403 s on Xeon processor). NN inputs were inquiry depth, starting complex impedance and current complex impedance. Training-validation-test splits were 70%-0%-30% and 80%-10%-10% (overfit test). Once the NN-estimated lesion depth for a margin reached the target lesion depth, RFA was stopped for that margin of tissue. The NN trained to 93% accuracy and an NN-integrated control ablated tissue to within 1.0 mm of the target lesion depth on average. Full 15-mm depth maps were calculated in 0.2 s on a single-core ARMv7 processor. The results show that a NN could make lesion depth estimations in real-time using less in situ devices than current techniques. With the NN-based technique, physicians could deliver quicker and more precise ablation therapy.

A deep learning framework for supporting the classification of breast lesions in ultrasound images.

PubMed

Han, Seokmin; Kang, Ho-Kyung; Jeong, Ja-Yeon; Park, Moon-Ho; Kim, Wonsik; Bang, Won-Chul; Seong, Yeong-Kyeong

2017-09-15

In this research, we exploited the deep learning framework to differentiate the distinctive types of lesions and nodules in breast acquired with ultrasound imaging. A biopsy-proven benchmarking dataset was built from 5151 patients cases containing a total of 7408 ultrasound breast images, representative of semi-automatically segmented lesions associated with masses. The dataset comprised 4254 benign and 3154 malignant lesions. The developed method includes histogram equalization, image cropping and margin augmentation. The GoogLeNet convolutionary neural network was trained to the database to differentiate benign and malignant tumors. The networks were trained on the data with augmentation and the data without augmentation. Both of them showed an area under the curve of over 0.9. The networks showed an accuracy of about 0.9 (90%), a sensitivity of 0.86 and a specificity of 0.96. Although target regions of interest (ROIs) were selected by radiologists, meaning that radiologists still have to point out the location of the ROI, the classification of malignant lesions showed promising results. If this method is used by radiologists in clinical situations it can classify malignant lesions in a short time and support the diagnosis of radiologists in discriminating malignant lesions. Therefore, the proposed method can work in tandem with human radiologists to improve performance, which is a fundamental purpose of computer-aided diagnosis.

A deep learning framework for supporting the classification of breast lesions in ultrasound images

NASA Astrophysics Data System (ADS)

Han, Seokmin; Kang, Ho-Kyung; Jeong, Ja-Yeon; Park, Moon-Ho; Kim, Wonsik; Bang, Won-Chul; Seong, Yeong-Kyeong

2017-10-01

In this research, we exploited the deep learning framework to differentiate the distinctive types of lesions and nodules in breast acquired with ultrasound imaging. A biopsy-proven benchmarking dataset was built from 5151 patients cases containing a total of 7408 ultrasound breast images, representative of semi-automatically segmented lesions associated with masses. The dataset comprised 4254 benign and 3154 malignant lesions. The developed method includes histogram equalization, image cropping and margin augmentation. The GoogLeNet convolutionary neural network was trained to the database to differentiate benign and malignant tumors. The networks were trained on the data with augmentation and the data without augmentation. Both of them showed an area under the curve of over 0.9. The networks showed an accuracy of about 0.9 (90%), a sensitivity of 0.86 and a specificity of 0.96. Although target regions of interest (ROIs) were selected by radiologists, meaning that radiologists still have to point out the location of the ROI, the classification of malignant lesions showed promising results. If this method is used by radiologists in clinical situations it can classify malignant lesions in a short time and support the diagnosis of radiologists in discriminating malignant lesions. Therefore, the proposed method can work in tandem with human radiologists to improve performance, which is a fundamental purpose of computer-aided diagnosis.

Proposed Optimal Fluoroscopic Targets for Cooled Radiofrequency Neurotomy of the Sacral Lateral Branches to Improve Clinical Outcomes: An Anatomical Study.

PubMed

Stout, Alison; Dreyfuss, Paul; Swain, Nathan; Roberts, Shannon; Loh, Eldon; Agur, Anne

2017-11-23

Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies confirm significant variation in LB positions. To determine if common fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3 LBs. If not, would different targets improve lesion accuracy? The LBs of 20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard targets were assessed, as judged by a clockface on the right, for S1 and S2 at 2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of LBs that would not be ablated for each level was determined. Imaging through the superior end plate of S1 was compared against segment specific (SS) imaging. Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2 vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current targets. SS imaging did not improve results. Alternate target locations could improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95% of SIJs. Using a conservative 8-mm lesion measurement, contemporary cooled RF needle targets are inadequate to lesion all target LBs. Modifications to current targets are recommended to increase the effectiveness of the procedure. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Study on the Failure and Energy Absorption Mechanism of Multilayer Explosively Welded Plates Impacted by Spherical Fragments

NASA Astrophysics Data System (ADS)

Zhou, N.; Wang, J. X.; Tang, S. Z.; Tao, Q. C.; Wang, M. X.

2018-01-01

A stereomicroscope, microscopic metallograph, scanning electron microscope, and the ANSYS/LS-DYNA 3D finite-element code were employed to investigate the failure and energy absorption mechanism of two-layer steel/aluminum and three-layer steel/aluminum/steel and aluminum/steel/aluminum explosively welded composite plates impacted by spherical fragments. The effects of layer number, target order, and the combination state of interfaces on the failure and energy absorption mechanism are analyzed based on experimental and numerical results. Results showed that the effect of the combination state of interfaces on the failure mode was pronounced the most compared with other factors. The failure mechanism of the front and middle plates were shearing and plugging, and that of rear plate was ductile deformation when the tied interface failed by tension (or by shearing and plugging when the interface combination remained connected). A narrow adiabatic shear band was formed in the locally yielding plate damaged by shearing and plugging during the penetration process. The amount of energy needed to completely perforate the three-layer composite target was greater than that for a two-layer composite target with the same areal density and total thickness. The protective performance of the steel/aluminum/steel target was better than that of the aluminum/steel/aluminum target with the same areal density.

Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions.

PubMed

Grgurevic, Ivica; Bokun, Tomislav; Salkic, Nermin N; Brkljacic, Boris; Vukelić-Markovic, Mirjana; Stoos-Veic, Tajana; Aralica, Gorana; Rakic, Mislav; Filipec-Kanizaj, Tajana; Berzigotti, Annalisa

2018-06-01

To analyse elastographic characteristics of focal liver lesions (FLL)s and diagnostic performance of real-time two-dimensional shear-wave elastography (RT-2D-SWE) in order to differentiate benign and malignant FLLs. Consecutive patients diagnosed with FLL by abdominal ultrasound (US) underwent RT-2D-SWE of FLL and non-infiltrated liver by intercostal approach over the right liver lobe. The nature of FLL was determined by diagnostic work-up, including at least one contrast-enhanced imaging modality (MDCT/MRI), check-up of target organs when metastatic disease was suspected and FLL biopsy in inconclusive cases. We analysed 196 patients (median age 60 [range 50-68], 50.5% males) with 259 FLLs (57 hepatocellular carcinomas, 17 cholangiocarcinomas, 94 metastases, 71 haemangiomas, 20 focal nodular hyperplasia) of which 70 (27%) were in cirrhotic liver. Malignant lesions were stiffer (P < .001) with higher variability in intralesional stiffness (P = .001). The best performing cut-off of lesion stiffness was 22.3 kPa (sensitivity 83%; specificity 86%; positive predictive value [PPV] 91.5%; negative predictive value [NPV] 73%) for malignancy. Lesion stiffness <14 kPa had NPV of 96%, while values >32.5 kPa had PPV of 96% for malignancy. Lesion stiffness, lesion/liver stiffness ratio and lesion stiffness variability significantly predicted malignancy in stepwise logistic regression (P < .05), and were used to construct a new Liver Elastography Malignancy Prediction (LEMP) score with accuracy of 96.1% in validation cohort (online calculator available at http://bit.do/lemps). The comprehensive approach demonstrated in this study enables correct differentiation of benign and malignant FLL in 96% of patients by using RT-2D-SWE. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Effect of Sex and Anthropometry on Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention for Complex Coronary Lesions.

PubMed

Lee, Seung Yul; Shin, Dong Ho; Kim, Jung Sun; Kim, Byeong Keuk; Ko, Young Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong Ki

2017-03-01

To evaluate the effects of sex and anthropometry on clinical outcomes in patients who underwent percutaneous coronary intervention (PCI). From three randomized trials (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation, Impact of intraVascular UltraSound guidance on outcomes of Xience Prime stents in Long lesions, Chronic Total Occlusion InterVention with drUg-eluting Stents), we compared 333 pairs of men and women matched by propensity scores, all of whom underwent intravascular ultrasound (IVUS)-guided PCI for complex lesions. For 12 months, the incidence of adverse cardiac events, defined as the composite of cardiac death, target lesion-related myocardial infarction, and target lesion revascularization, was not different between women and men (2.4% vs. 2.4%, p=0.939). Using multivariable Cox's regression analysis, post-intervention minimum lumen area [MLA; hazard ratio (HR)=0.620, 95% confidence interval (CI)=0.423-0.909, p=0.014] by IVUS was a predictor of adverse cardiac events. Height on anthropometry and lesions with chronic total occlusion were significantly related to post-intervention MLA. However, female sex was not independently associated with post-intervention MLA. In an age and sex-adjusted model, patients in the low tertile of height exhibited a greater risk for adverse cardiac events than those in the high tertile of height (HR=6.391, 95% CI=1.160-35.206, p=0.033). Sex does not affect clinical outcomes after PCI for complex lesions. PCI outcomes, however, may be adversely affected by height.

The method for detecting small lesions in medical image based on sliding window

NASA Astrophysics Data System (ADS)

Han, Guilai; Jiao, Yuan

2016-10-01

At present, the research on computer-aided diagnosis includes the sample image segmentation, extracting visual features, generating the classification model by learning, and according to the model generated to classify and judge the inspected images. However, this method has a large scale of calculation and speed is slow. And because medical images are usually low contrast, when the traditional image segmentation method is applied to the medical image, there is a complete failure. As soon as possible to find the region of interest, improve detection speed, this topic attempts to introduce the current popular visual attention model into small lesions detection. However, Itti model is mainly for natural images. But the effect is not ideal when it is used to medical images which usually are gray images. Especially in the early stages of some cancers, the focus of a disease in the whole image is not the most significant region and sometimes is very difficult to be found. But these lesions are prominent in the local areas. This paper proposes a visual attention mechanism based on sliding window, and use sliding window to calculate the significance of a local area. Combined with the characteristics of the lesion, select the features of gray, entropy, corner and edge to generate a saliency map. Then the significant region is segmented and distinguished. This method reduces the difficulty of image segmentation, and improves the detection accuracy of small lesions, and it has great significance to early discovery, early diagnosis and treatment of cancers.

Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions.

PubMed

Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

2007-10-01

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions in the cerebellopontine angle (CPA). However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Part 1 describes the different enhancing extra-axial CPA masses primarily arising from the cerebellopontine cistern and its contents, including vestibular and non-vestibular schwannomas, meningioma, metastasis, aneurysm, tuberculosis and other miscellaneous meningeal lesions.

Epicardial Radiofrequency Ablation Failure During Ablation Procedures for Ventricular Arrhythmias: Reasons and Implications for Outcomes.

PubMed

Baldinger, Samuel H; Kumar, Saurabh; Barbhaiya, Chirag R; Mahida, Saagar; Epstein, Laurence M; Michaud, Gregory F; John, Roy; Tedrow, Usha B; Stevenson, William G

2015-12-01

Radiofrequency ablation (RFA) from the epicardial space for ventricular arrhythmias is limited or impossible in some cases. Reasons for epicardial ablation failure and the effect on outcome have not been systematically analyzed. We assessed reasons for epicardial RFA failure relative to the anatomic target area and the type of heart disease and assessed the effect of failed epicardial RFA on outcome after ablation procedures for ventricular arrhythmias in a large single-center cohort. Epicardial access was attempted during 309 ablation procedures in 277 patients and was achieved in 291 procedures (94%). Unlimited ablation in an identified target region could be performed in 181 cases (59%), limited ablation was possible in 22 cases (7%), and epicardial ablation was deemed not feasible in 88 cases (28%). Reasons for failed or limited ablation were unsuccessful epicardial access (6%), failure to identify an epicardial target (15%), proximity to a coronary artery (13%), proximity to the phrenic nerve (6%), and complications (<1%). Epicardial RFA was impeded in the majority of cases targeting the left ventricular summit region. Acute complications occurred in 9%. The risk for acute ablation failure was 8.3× higher (4.5-15.0; P<0.001) after no or limited epicardial RFA compared with unlimited RFA, and patients with unlimited epicardial RFA had better recurrence-free survival rates (P<0.001). Epicardial RFA for ventricular arrhythmias is often limited even when pericardial access is successful. Variability of success is dependent on the target area, and the presence of factors limiting ablation is associated with worse outcomes. © 2015 American Heart Association, Inc.

Accuracy in clinically evaluating pigmented lesions.

PubMed Central

Curley, R. K.; Cook, M. G.; Fallowfield, M. E.; Marsden, R. A.

1989-01-01

OBJECTIVE--To determine the ability of three doctors experienced in managing melanocytic lesions to diagnose correctly melanoma, dysplastic naevi, and various benign pigmented lesions. DESIGN--Independent clinical evaluation and histopathological assessment. SETTING--Pigmented lesion clinic, which patients attend without an appointment for early diagnosis of melanoma. PATIENTS--86 Patients with lesions that were judged to be benign by at least one of the three doctors. INTERVENTIONS--The lesions were excised under local anaesthesia and sent for histopathological examination in coded bottles without clinical details. MAIN OUTCOME MEASURE--Comparison of clinical with histopathological diagnosis for each lesion. RESULTS--A total of 120 lesions were evaluated by at least two of the three doctors. The histopathological diagnoses were made by the same pathologist. The overall sensitivity (diagnostic accuracy) for the three doctors for all types of lesion was 50%. Of the 39 dysplastic naevi, only 19 were identified correctly by all observers, and a further 24 banal lesions were wrongly diagnosed as dysplastic by at least one doctor. Particular difficulty was experienced with small (less than 5 mm), flat lesions, which can be banal or potentially malignant. CONCLUSIONS--Critical diagnosis and management decisions concerning pigmented lesions should always be based on a combination of clinical and histopathological assessments and the history of the patient. PMID:2503192

Restoring Behavior via Inverse Neurocontroller in a Lesioned Cortical Spiking Model Driving a Virtual Arm

PubMed Central

Dura-Bernal, Salvador; Li, Kan; Neymotin, Samuel A.; Francis, Joseph T.; Principe, Jose C.; Lytton, William W.

2016-01-01

Neural stimulation can be used as a tool to elicit natural sensations or behaviors by modulating neural activity. This can be potentially used to mitigate the damage of brain lesions or neural disorders. However, in order to obtain the optimal stimulation sequences, it is necessary to develop neural control methods, for example by constructing an inverse model of the target system. For real brains, this can be very challenging, and often unfeasible, as it requires repeatedly stimulating the neural system to obtain enough probing data, and depends on an unwarranted assumption of stationarity. By contrast, detailed brain simulations may provide an alternative testbed for understanding the interactions between ongoing neural activity and external stimulation. Unlike real brains, the artificial system can be probed extensively and precisely, and detailed output information is readily available. Here we employed a spiking network model of sensorimotor cortex trained to drive a realistic virtual musculoskeletal arm to reach a target. The network was then perturbed, in order to simulate a lesion, by either silencing neurons or removing synaptic connections. All lesions led to significant behvaioral impairments during the reaching task. The remaining cells were then systematically probed with a set of single and multiple-cell stimulations, and results were used to build an inverse model of the neural system. The inverse model was constructed using a kernel adaptive filtering method, and was used to predict the neural stimulation pattern required to recover the pre-lesion neural activity. Applying the derived neurostimulation to the lesioned network improved the reaching behavior performance. This work proposes a novel neurocontrol method, and provides theoretical groundwork on the use biomimetic brain models to develop and evaluate neurocontrollers that restore the function of damaged brain regions and the corresponding motor behaviors. PMID:26903796

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Clinical Adoption of Prognostic Biomarkers The Case for Heart Failure

PubMed Central

Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Butler, Javed

2013-01-01

The recent explosion of scientific knowledge and technological progress has led to the discovery of a large array of circulating molecules commonly referred to as biomarkers. Biomarkers in heart failure research have been used to provide pathophysiological insights, aid in establishing the diagnosis, refine prognosis, guide management, and target treatment. However, beyond diagnostic applications of natriuretic peptides, there are currently few widely recognized applications for biomarkers in heart failure. This represents a remarkable discordance considering the number of molecules that have been shown to correlate with outcomes, refine risk prediction, or track disease severity in heart failure in the past decade. In this article, we use a broad framework proposed for cardiovascular risk markers to summarize the current state of biomarker development for heart failure patients. We utilize this framework to identify the challenges of biomarker adoption for risk prediction, disease management, and treatment selection for heart failure and suggest considerations for future research. PMID:22824105

Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

PubMed

Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

2018-06-01

Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from

Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges

PubMed Central

Saxena, Amit; Russo, Ilaria; Frangogiannis, Nikolaos G

2015-01-01

In the infarcted myocardium, necrotic cardiomyocytes release danger signals, activating an intense inflammatory response. Inflammatory pathways play a crucial role in regulation of a wide range of cellular processes involved in injury, repair and remodeling of the infarcted heart. Pro-inflammatory cytokines, such as tumor necrosis factor-a and interleukin (IL)-1, are markedly upregulated in the infarcted myocardium and promote adhesive interactions between endothelial cells and leukocytes, by stimulating chemokine and adhesion molecule expression. Distinct chemokine/chemokine receptor pairs are implicated in recruitment of various leukocyte subpopulations in the infarcted myocardium. Over the last 30 years, extensive experimental work has explored the role of inflammatory signals and the contributions of leukocyte subpopulations, in myocardial infarction. Robust evidence derived from experimental models of myocardial infarction has identified inflammatory targets that may attenuate cardiomyocyte injury, or protect from adverse remodeling. Unfortunately, attempts to translate the promising experimental findings to clinical therapy have failed. This review manuscript discusses the biology of the inflammatory response following myocardial infarction, attempts to identify the causes for the translational failures of the past, and proposes promising new therapeutic directions. Because of their potential involvement in injurious, reparative and regenerative responses, inflammatory cells may hold the key for design of new therapies in myocardial infarction. PMID:26241027

Congenital lesions of epithelial origin.

PubMed

Hills, Susannah E; Maddalozzo, John

2015-02-01

Defects of embryologic development give rise to a variety of congenital lesions arising from the epithelium and are among the most common congenital lesions of the head and neck in the pediatric population. This article presents several congenital lesions of epithelial origin, including congenital midline cervical cleft, pilomatrixoma, dermoid, foregut duplication cysts, and preauricular sinuses and pits. In addition, the management of these lesions is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Dissecting and Targeting Latent Metastasis

DTIC Science & Technology

2013-09-01

particular. Developing and using experimental models of LMBC to elucidate these survival mechanisms will provide a basis for therapeutically targeting...stochastic, low frequency generation of lethal macrometastatic lesion. Progress Item 1.1. Using this approach, we have successfully isolated latent...cells lines are being used to illuminate the molecular basis for the latent metastasis state. Progress Item 1.2. In parallel with the isolation of

Concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.

PubMed

Li, John; Weissberg, Zoe; Bevilacqua, Thomas A; Yu, Gordon; Weber, Kristy; Sebro, Ronnie

2018-04-01

To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation. Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size. Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10 -3 ; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (- 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05). FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions.

Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

PubMed

Zailaie, Mohammad Z

2017-01-01

It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

Endoscopic debridement and fibrin glue injection of a chronic Morel-Lavallée lesion of the knee in a professional soccer player: A case report and literature review.

PubMed

Koc, Baris B; Somorjai, Nicolaas; P M Kiesouw, Egid; Vanderdood, Kurt; Meesters-Caberg, Marleen; Draijer, Frits W; Jansen, Edwin J P

2017-01-01

A Morel-Lavallée lesion is a post-traumatic closed degloving injury of soft tissue. The lesion is due to a shearing trauma with separation of subcutaneous tissue from underlying fascia. When conservative treatment fails, surgical treatment is imperative. Commonly, open drainage and debridement is performed. This case report describes a Morel-Lavallée lesion of the knee in a professional soccer player who was successfully treated with endoscopic debridement and fibrin glue injection after failure of conservative management. This method achieves the goal of an open surgical debridement without exposing patients to an increased morbidity. Copyright © 2016. Published by Elsevier B.V.

Defining the optimal method for reporting prostate cancer grade and tumor extent on magnetic resonance/ultrasound fusion-targeted biopsies.

PubMed

Gordetsky, Jennifer B; Schultz, Luciana; Porter, Kristin K; Nix, Jeffrey W; Thomas, John V; Del Carmen Rodriguez Pena, Maria; Rais-Bahrami, Soroush

2018-06-01

Magnetic resonance (MR)/ultrasound fusion-targeted biopsy (TB) routinely samples multiple cores from each MR lesion of interest. Pathologists can evaluate the extent of cancer involvement and grade using an individual core (IC) or aggregate (AG) method, which could potentially lead to differences in reporting. We reviewed patients who underwent TB followed by radical prostatectomy (RP). TB cores were evaluated for grade and tumor extent by 2 methods. In the IC method, the grade for each TB lesion was based on the core with the highest Gleason score. Tumor extent for each TB was based on the core with the highest percent of tumor involvement. In the AG method, the tumor from all cores within each TB lesion was aggregated to determine the final composite grade and percentage of tumor involvement. Each method was compared with MR lesional volume, MR lesional density (lesion volume/prostate volume), and RP. Fifty-five patients underwent TB followed by RP. Extent of tumor by the AG method showed a better correlation with target lesion volume (r= 0.27,P= .022) and lesional density (r = 0.32, P = .008) than did the IC method (r= 0.19 [P = .103] andr= 0.22 [P = .062]), respectively. Extent of tumor on TB was associated with extraprostatic extension on RP by the AG method (P= .04), but not by the IC method. This association was significantly higher in patients with a grade group (GG) of 3 or higher (P= .03). A change in cancer grade occurred in 3 patients when comparing methods (2 downgraded GG3 to GG2, 1 downgraded GG4 to GG3 by the AG method). For multiple cores obtained via TB, the AG method better correlates with target lesion volume, lesional density, and extraprostatic extension. Copyright © 2018 Elsevier Inc. All rights reserved.

Covalently Linked Tandem Lesions in DNA

PubMed Central

Patrzyc, Helen B.; Dawidzik, Jean B.; Budzinski, Edwin E.; Freund, Harold G.; Wilton, John H.; Box, Harold C.

2013-01-01

Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution. PMID:23106212

Effects of lesions of the amygdala central nucleus on autoshaped lever pressing

PubMed Central

Chang, Stephen E.; Wheeler, Daniel S.; Holland, Peter C.

2012-01-01

Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues. PMID:22386516

The Mayo Clinic experience with Morel-Lavallée lesions: establishment of a practice management guideline.

PubMed

Nickerson, Terry P; Zielinski, Martin D; Jenkins, Donald H; Schiller, Henry J

2014-02-01

Although uncommon, Morel-Lavallée lesions (also called closed degloving injuries) are associated with considerable morbidity in trauma patients. There is lack of consensus regarding proper management of these lesions. Management options include nonoperative therapies, along with percutaneous and operative techniques. We sought to define the factors associated with failure of percutaneous aspiration to better identify patients requiring immediate operative management. We retrospectively searched our prospectively collected database for patient records containing the terms Morel-Lavallée, closed degloving injury, or posttraumatic seroma from February 2, 2004, through December 23, 2011. Treatment methods included compression wraps or observation (nonoperative management), percutaneous aspiration, or operative management with incision/drainage or formal debridement of skin and soft tissues that resulted in wound vacuum-assisted closure placement and/or split-thickness skin graft (operative management). The treatment groups were compared using univariate analysis and χ testing. We identified 79 patients with 87 Morel-Lavallée lesions in the setting of trauma. Most were caused by motor vehicle collisions (25%). No difference was observed between the treatment groups in sex, body mass index, anticoagulation treatment, diabetes mellitus, smoking history, or alcohol use. The percutaneous aspiration group had higher rates of recurrence (56% vs. 19% and 15% in nonoperative and operative groups, respectively). The percentage of patients who had aspiration of more than 50 mL of fluid was higher for lesions that recurred than for lesions that resolved (83% vs. 33%, p = 0.02). Aspiration of more than 50 mL of fluid from Morel-Lavallée lesions was much more common among lesions that recurred (83%) than among those that resolved (33%). We therefore recommend that aspiration of more than 50 mL of fluid from a Morel-Lavallée lesion prompts operative intervention. We have now

Presence of Candida Albicans in Root Canal System of Teeth Requiring Endodontic Retreatment with and without Periapical Lesions

PubMed Central

Ashraf, Hengameh; Samiee, Mohammad; Eslami, Gita; Ghodse Hosseini, Mohammad Reza

2007-01-01

INTRODUCTION: An important consideration in endodontic treatment is the elimination of microorganisms, including fungi, from the complex three- dimensional root canal system. Candida Albicans (CA) has a major role in endodontic treatment failure as the most important fungus isolated from the root canal system. The present study was carried out to evaluate the presence of CA in the teeth requiring endodontic retreatment, with or without periapical lesions. MATERIALS AND METHODS: This study was carried out on 60 root canals from human molars requiring endodontic retreatment. The root canals were randomly divided into two equal groups of 30 canals with versus without periapical lesions. Samples were collected from the root canals and cultured on MacConkey and blood agar culture media. The samples suspected of having CA were streaked on Sabouraud’s Dextrose Agar (SDA) and evaluated under a light microscope. Data was analyzed and compared using Chi- square and Kappa tests. RESULTS: CA was found in 11 patients (36.7%) with periapical lesions. In the patients without periapical lesions only 4 samples demonstrated CA in the root canal systems (13.3%). The difference between the two groups as to the presence of CA was statistically significant (p<0.037). In addition, evaluation of salivary samples revealed 15 cases (50%) of CA presence in the patients with periapical lesions and 16 cases (53.3%) of CA in the patients without periapical lesions, demonstrating no statistically significant difference between the two groups. CONCLUSION: Considering the fact that the presence of CA in the root canal systems of teeth with periapical lesions was more noticeable and statistically significant compared to the teeth without periapical lesions, the elimination of this microorganism from the root canal system, using appropriate intracanal solutions and medications is of utmost importance. PMID:24348654

Optimising self-care support for people with heart failure and their caregivers: development of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention using intervention mapping.

PubMed

Greaves, Colin J; Wingham, Jennifer; Deighan, Carolyn; Doherty, Patrick; Elliott, Jennifer; Armitage, Wendy; Clark, Michelle; Austin, Jackie; Abraham, Charles; Frost, Julia; Singh, Sally; Jolly, Kate; Paul, Kevin; Taylor, Louise; Buckingham, Sarah; Davis, Russell; Dalal, Hasnain; Taylor, Rod S

2016-01-01

We aimed to establish the support needs of people with heart failure and their caregivers and develop an intervention to improve their health-related quality of life. We used intervention mapping to guide the development of our intervention. We identified "targets for change" by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We then used behaviour change theory, expert opinion and a taxonomy of behaviour change techniques, to identify barriers to and facilitators of change and to match intervention strategies to each target. A patient and public involvement group helped to identify patient and caregiver needs, refine the intervention objectives and strategies and deliver training to the intervention facilitators. A feasibility study (ISRCTN25032672) involving 23 patients, 12 caregivers and seven trained facilitators at four sites assessed the feasibility and acceptability of the intervention and quality of delivery and generated ideas to help refine the intervention. The Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention is a comprehensive self-care support programme comprising the "Heart Failure Manual", a choice of two exercise programmes for patients, a "Family and Friends Resource" for caregivers, a "Progress Tracker" tool and a facilitator training course. The main targets for change are engaging in exercise training, monitoring for symptom deterioration, managing stress and anxiety, managing medications and understanding heart failure. Secondary targets include managing low mood and smoking cessation. The intervention is facilitated by trained healthcare professionals with specialist cardiac experience over 12 weeks, via home and telephone contacts. The feasibility study found high levels of satisfaction and engagement with the intervention from facilitators, patients and caregivers. Intervention fidelity analysis and stakeholder feedback suggested

Emerging role of liver X receptors in cardiac pathophysiology and heart failure.

PubMed

Cannon, Megan V; van Gilst, Wiek H; de Boer, Rudolf A

2016-01-01

Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure.

Experimental and computed results investigating time-dependent failure in a borosilicate glass

NASA Astrophysics Data System (ADS)

Chocron, Sidney; Barnette, Darrel; Holmquist, Timothy; Anderson, Charles E.; Bigger, Rory; Moore, Thomas

2017-01-01

Symmetric plate-impact tests of borosilicate glass were performed from low (116 m/s) to higher (351 m/s) velocities. The tests were recorded with an ultra-high-speed camera to see the shock and failure propagation. The velocity of the back of the target was also recorded with a PDV (Photon Doppler Velocimeter). The images show failure nucleation sites that trail the shock wave. Interestingly, even though the failure wave is clearly seen, the PDV never detected the expected recompression wave. The reason might be that at these low impact velocities the recompression wave is too small to be seen and is lost in the noise. This work also presents a new way to interpret the signals from the PDV. By letting part of the signal travel through the target and reflect on the impact side, it is possible to see the PDV decrease in intensity with time, probably due to the damage growth behind the shock wave.

Glucocorticoid and calcitonin receptor expression in central giant cell lesions: implications for therapy.

PubMed

Nogueira, R L M; Faria, M H G; Osterne, R L V; Cavalcante, R B; Ribeiro, R A; Rabenhorst, S H B

2012-08-01

Central giant cell lesion is an uncommon benign jaw lesion, with uncertain aetiology, and variable clinical behaviour. Studies of molecular markers may help to understand the nature and behaviour of this lesion, and eventually may represent a target for pharmacological approaches to treatment. The aim of this study was to analyse the expression of glucocorticoid and calcitonin receptors in central giant cell lesions before and after treatment with intralesional steroid. Paraffin-embedded blocks from patients who underwent treatment with intralesional triamcinolone hexacetonide injections were stained immunohistochemically. Biological material from patients who underwent a surgical procedure after treatment were tested immunohistochemically. 18 cases (9 aggressive and 9 non-aggressive) were included. The difference in calcitonin receptor expression was not statistically significant between the aggressive and non-aggressive lesions and between the patients with a good response and those with a moderate/negative response to treatment. Glucocorticoid receptor expression in the multinucleated giant cells was higher in patients with a good response. It can be postulated that immunohistochemical staining for glucocorticoid receptors may provide a tool for selecting the therapeutic strategy. An H-score greater than 48 for glucocorticoid receptors in multinucleated giant cells predicted a good response in this study. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Comprehensive in-hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Parissis, John; Brunner-La Rocca, Hans-Peter; Čelutkienė, Jelena; Chioncel, Ovidiu; Collins, Sean P; De Backer, Daniel; Filippatos, Gerasimos S; Gayat, Etienne; Hill, Loreena; Lainscak, Mitja; Lassus, Johan; Masip, Josep; Mebazaa, Alexandre; Miró, Òscar; Mortara, Andrea; Mueller, Christian; Mullens, Wilfried; Nieminen, Markku S; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar M; Sionis, Alessandro; Vieillard-Baron, Antoine; Weinstein, Jean Marc; de Boer, Rudolf A; Crespo Leiro, Maria G; Piepoli, Massimo; Riley, Jillian P

2018-04-30

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

Ultrasound-guided cable-free 13-gauge vacuum-assisted biopsy of non-mass breast lesions

PubMed Central

Seo, Jiwoon; Jang, Mijung; Yun, Bo La; Lee, Soo Hyun; Kim, Eun-Kyu; Kang, Eunyoung; Park, So Yeon; Moon, Woo Kyung; Choi, Hye Young; Kim, Bohyoung

2017-01-01

Purpose To compare the outcomes of ultrasound-guided core biopsy for non-mass breast lesions by the novel 13-gauge cable-free vacuum-assisted biopsy (VAB) and by the conventional 14-gauge semi-automated core needle biopsy (CCNB). Materials and methods Our institutional review board approved this prospective study, and all patients provided written informed consent. Among 1840 ultrasound-guided percutaneous biopsies performed from August 2013 to December 2014, 145 non-mass breast lesions with suspicious microcalcifications on mammography or corresponding magnetic resonance imaging finding were subjected to 13-gauge VAB or 14-gauge CCNB. We evaluated the technical success rates, average specimen numbers, and tissue sampling time. We also compared the results of percutaneous biopsy and final surgical pathologic diagnosis to analyze the rates of diagnostic upgrade or downgrade. Results Ultrasound-guided VAB successfully targeted and sampled all lesions, whereas CCNB failed to demonstrate calcification in four (10.3%) breast lesions with microcalcification on specimen mammography. The mean sampling time were 238.6 and 170.6 seconds for VAB and CCNB, respectively. No major complications were observed with either method. Ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) lesions were more frequently upgraded after CCNB (8/23 and 3/5, respectively) than after VAB (2/26 and 0/4, respectively P = 0.028). Conclusion Non-mass breast lesions were successfully and accurately biopsied using cable-free VAB. The underestimation rate of ultrasound-detected non-mass lesion was significantly lower with VAB than with CCNB. Trial registration CRiS KCT0002267. PMID:28628656

Effect of Lesion Baseline Severity and Mineral Distribution on Remineralization and Progression of Human and Bovine Dentin Caries Lesions.

PubMed

Lippert, Frank; Churchley, David; Lynch, Richard J

2015-01-01

The aims of this laboratory study were to compare the effects of lesion baseline severity, mineral distribution and substrate on remineralization and progression of caries lesions created in root dentin. Lesions were formed in dentin specimens prepared from human and bovine dentin using three protocols, each utilizing three demineralization periods to create lesions of different mineral distributions (subsurface, moderate softening, extreme softening) and severity within each lesion type. Lesions were then either remineralized or demineralized further and analyzed using transverse microradiography. At lesion baseline, no differences were found between human and bovine dentin for integrated mineral loss (x0394;Z). Differences in mineral distribution between lesion types were apparent. Human dentin lesions were more prone to secondary demineralization (x0394;x0394;Z) than bovine dentin lesions, although there were no differences in x0394;L. Likewise, smaller lesions were more susceptible to secondary demineralization than larger ones. Subsurface lesions were more acid-resistant than moderately and extremely softened lesions. After remineralization, differences between human and bovine dentin lesions were not apparent for x0394;x0394;Z although bovine dentin lesions showed greater reduction in lesion depth L. For lesion types, responsiveness to remineralization (x0394;x0394;Z) was in the order extremely softened>moderately softened>subsurface. More demineralized lesions exhibited greater remineralization than shallower ones. In summary, some differences exist between human and bovine dentin and their relative responsiveness to de- and remineralization. These differences, however, were overshadowed by the effects of lesion baseline mineral distribution and severity. Thus, bovine dentin appears to be a suitable substitute for human dentin in mechanistic root caries studies. © 2015 S. Karger AG, Basel.

Application of radiosurgical techniques to produce a primate model of brain lesions

PubMed Central

Kunimatsu, Jun; Miyamoto, Naoki; Ishikawa, Masayori; Shirato, Hiroki; Tanaka, Masaki

2015-01-01

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans. PMID:25964746

Clinical application of ghrelin for chronic respiratory failure.

PubMed

Matsumoto, Nobuhiro; Tsubouchi, Hironobu; Imazu, Yoshifumi; Arimura, Yasuji; Yanagi, Shigehisa; Iiboshi, Hirotoshi; Nakazato, Masamitsu

2017-01-01

Chronic respiratory failure, which is often caused by chronic obstructive pulmonary disease, chronic lower respiratory tract infection, or interstitial pneumonia, often leads to cachexia with disease progression. Patients who have chronic respiratory failure with cachexia exhibit increased morbidity. Although cachectic status is an important clinical problem, there are no effective therapies for cachexia. Ghrelin has various effects, including increasing food intake, attenuating sympathetic nerve activity, inhibiting inflammation, increasing cardiac output, and controlling fat utilization. These effects of ghrelin are ideal targets for the treatment of severely wasting chronic respiratory disease. In a few clinical studies, including a small randomized controlled trial, ghrelin administration to cachectic patients with chronic respiratory failure improved exercise tolerance, dyspnea, and appetite. The patients in these studies gained muscle mass and weight. In another study of chronic lower respiratory tract infection with cachexia, ghrelin suppressed airway inflammation by decreasing neutrophil accumulation in the airway, resulting in improvements in oxygenation and exercise tolerance. Although further clinical investigations are needed to clarify its usefulness, ghrelin is expected to become a novel therapy for cachectic patients with chronic respiratory failure.

Is the morphology and activity of the occlusal carious lesion related to the lesion progression stage?

PubMed

Neves, Aline Almeida; Vargas, Daniel Otero Amaral; Santos, Thais Maria Pires; Lopes, Ricardo Tadeu; Sousa, Frederico Barbosa

2016-12-01

To investigate the relationship between degree of dentin demineralization with both lesion activity and morphology of the occlusal carious cavity. Occlusal sites (n=138) were identified by visual examination (Nyvad's scores 0-6) in 67 extracted teeth which were scanned in a high energy micro-CT. After 3D reconstruction, each stack was resliced in the mesio-distal direction and tooth mineral density (MD) was measured along a path from enamel to the deepest part of dentin in the slice showing the most severe carious involvement. Each site was classified in "open" or "closed" (if cavitated) depending on the morphology of the surrounding enamel walls as measured using micro-CT and as active or inactive in enamel or dentin by a clinical scoring system. Lesions showing dentin cavitation presented higher demineralization degree compared to non-cavitated, or enamel cavitated lesions. Inactive lesions presented lower demineralization degree compared to active lesions, although with a low effect size. According to the morphological aspect of the carious cavity, open enamel lesions showed lower dentin demineralization degree than closed lesion environments. Active lesions showed higher dentin demineralization degree than inactive ones, while lesions showing closed cavitation resulted in higher dentin demineralization degree only for enamel lesions. Including those parameters in treatment decisions may help to improve prognosis and increase effectiveness of the caries diagnostic systems in the clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Muscle wasting and sarcopenia in heart failure and beyond: update 2017.

PubMed

Springer, Jochen; Springer, Joshua-I; Anker, Stefan D

2017-11-01

Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF-1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta.

PubMed

Labarrere, Carlos A; DiCarlo, Hector L; Bammerlin, Elaine; Hardin, James W; Kim, Yeon M; Chaemsaithong, Piya; Haas, David M; Kassab, Ghassan S; Romero, Roberto

2017-03-01

Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. We sought to determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. A cross-sectional study of 123 placentas (19-42 weeks' gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1. Investigators examining microscopic sections

Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response.

PubMed

Pelle, Dominic W; Ringler, Jonathan W; Peacock, Jacqueline D; Kampfschulte, Kevin; Scholten, Donald J; Davis, Mary M; Mitchell, Deanna S; Steensma, Matthew R

2014-08-01

Aneurysmal bone cyst (ABC) is a benign tumor of bone presenting as a cystic, expansile lesion in both the axial and appendicular skeleton. Axial lesions demand special consideration, because treatment-related morbidity can be devastating. In similar lesions, such as giant cell tumor of bone (GCTB), the receptor-activator of nuclear kappaB ligand (RANKL)-receptor-activator of nuclear kappaB (RANK) signaling axis is essential to tumor progression. Although ABC and GCTB are distinct entities, they both contain abundant multinucleated giant cells and are osteolytic characteristically. We hypothesize that ABCs express both RANKL and RANK similarly in a cell-type specific manner, and that targeted RANKL therapy will mitigate ABC tumor progression. Cellular expression of RANKL and RANK was determined in freshly harvested ABC samples using laser confocal microscopy. A consistent cell-type-specific pattern was observed: fibroblastlike stromal cells expressed RANKL strongly whereas monocyte/macrophage precursor and multinucleated giant cells expressed RANK. Relative RANKL expression was determined by quantitative real-time polymerase chain reaction in ABC and GCTB tissue samples; no difference in relative expression was observed (P > 0.05). In addition, we review the case of a 5-year-old boy with a large, aggressive sacral ABC. After 3 months of targeted RANKL inhibition with denosumab, magnetic resonance imaging demonstrated tumor shrinkage, bone reconstitution, and healing of a pathologic fracture. Ambulation, and bowel and bladder function were restored at 6 months. Denosumab treatment was well tolerated. Post hoc analysis demonstrated strong RANKL expression in the pretreatment tumor sample. These findings demonstrate that RANKL-RANK signal activation is essential to ABC tumor progression. RANKL-targeted therapy may be an effective alternative to surgery in select ABC presentations. Copyright © 2014 Mosby, Inc. All rights reserved.

Image-based numerical modeling of HIFU-induced lesions

NASA Astrophysics Data System (ADS)

Almekkaway, Mohamed K.; Shehata, Islam A.; Haritonova, Alyona; Ballard, John; Casper, Andrew; Ebbini, Emad

2017-03-01

Atherosclerosis is a chronic vascular disease affecting large and medium sized arteries. Several treatment options are already available for treatment of this disease. Targeting atherosclerotic plaques by high intensity focused ultrasound (HIFU) using dual mode ultrasound arrays (DMUA) was recently introduced in literature. We present a finite difference time domain (FDTD) simulation modeling of the wave propagation in heterogeneous medium from the surface of a 3.5 MHz array prototype with 32-elements. After segmentation of the ultrasound image obtained for the treatment region in-vivo, we integrated this anatomical information into our simulation to account for different parameters that may be caused by these multi-region anatomical complexities. The simulation program showed that HIFU was able to induce damage in the prefocal region instead of the target area. The HIFU lesions, as predicted by our simulation, were well correlated with the actual damage detected in histology.

Acoustic radiation force impulse imaging for real-time observation of lesion development during radiofrequency ablation procedures

NASA Astrophysics Data System (ADS)

Fahey, Brian J.; Trahey, Gregg E.

2005-04-01

When performing radiofrequency ablation (RFA) procedures, physicians currently have little or no feedback concerning the success of the treatment until follow-up assessments are made days to weeks later. To be successful, RFA must induce a thermal lesion of sufficient volume to completely destroy a target tumor or completely isolate an aberrant cardiac pathway. Although ultrasound, computed tomography (CT), and CT-based fluoroscopy have found use in guiding RFA treatments, they are deficient in giving accurate assessments of lesion size or boundaries during procedures. As induced thermal lesion size can vary considerably from patient to patient, the current lack of real-time feedback during RFA procedures is troublesome. We have developed a technique for real-time monitoring of thermal lesion size during RFA procedures utilizing acoustic radiation force impulse (ARFI) imaging. In both ex vivo and in vivo tissues, ARFI imaging provided better thermal lesion contrast and better overall appreciation for lesion size and boundaries relative to conventional sonography. The thermal safety of ARFI imaging for use at clinically realistic depths was also verified through the use of finite element method models. As ARFI imaging is implemented entirely on a diagnostic ultrasound scanner, it is a convenient, inexpensive, and promising modality for monitoring RFA procedures in vivo.

Autologous Chondrocyte Implantation for Bipolar Chondral Lesions in the Tibiofemoral Compartment.

PubMed

Ogura, Takahiro; Bryant, Tim; Mosier, Brian A; Minas, Tom

2018-05-01

Treating bipolar chondral lesions in the tibiofemoral (TF) compartment with cartilage repair procedures is challenging, and a suitable treatment remains unclear. To evaluate clinical outcomes after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the TF compartment. Case series; Level of evidence, 4. We evaluated 57 patients who underwent ACI for the treatment of symptomatic bipolar chondral lesions in the TF compartment by a single surgeon between October 1995 and June 2014. One patient did not return for follow-up. Thus, 56 patients (58 knees) were included with a minimum of 2 years' follow-up. A mean of 3.1 lesions per knee were treated, representing a mean total surface area of 16.1 cm 2 (range, 3.2-44.5 cm 2 ) per knee. Bipolar lesions were present in the medial compartment (32 knees) and in the lateral compartment (26 knees). Patients were evaluated with the modified Cincinnati Knee Rating Scale, visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form-36. Patients also answered questions regarding self-rated knee function and satisfaction with the procedure. Standard radiographs were evaluated with the Kellgren-Lawrence grading system. The survival rate was 80% at 5 years and 76% at 10 years. A significantly better survival rate was found in patients with the use of a collagen membrane than periosteum (97% vs 61% at 5 years, respectively; P = .0014). Of 46 knees with retained grafts, all functional scores significantly improved postoperatively, with a very high satisfaction rate (91%) at a mean of 8.3 ± 5.1 years (range, 2-20 years) after ACI. At last follow-up, 24 of 46 successful knees were radiographically assessed (mean, 5.5 ± 4.0 years [range, 2.0-18.7 years]) and showed no significant osteoarthritis progression ( P = .3173). Outcomes for 12 patients were considered as failures at a mean of 4.1 years. Of these, 9 patients were converted to partial or total

Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions.

PubMed

Makris, D; Scherpereel, A; Leroy, S; Bouchindhomme, B; Faivre, J-B; Remy, J; Ramon, P; Marquette, C-H

2007-06-01

The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic. The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean+/-sem 23.5+/-1.5 mm and the depth from the visceral-costal pleura was 14.9+/-2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy. All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25-40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was

Imaging inflammatory acne: lesion detection and tracking

NASA Astrophysics Data System (ADS)

Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

2010-02-01

It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

Diagnostic criteria for proliferative hepatic lesions in brown bullhead Ameiurus nebulosus

USGS Publications Warehouse

Blazer, V.S.; Fournie, J.W.; Wolf, J.C.; Wolfe, M.J.

2006-01-01

Brown bullhead Ameiurus nebulosus is used as indicator species for contaminant effects at areas of concern (AOC) in the Great Lakes and other areas. One of the beneficial use impairments at numerous AOC is 'fish tumors and other deformities'. An impairment occurs when the prevalence of fish tumors and other deformities exceeds those at unimpacted or control sites or when survey data confirm the presence of neoplastic or preneoplastic liver lesions in bullhead or white sucker Catostomus commersonii. Numerous surveys have been conducted over the years assessing neoplasia in these fishes, both liver and skin tumors. However, a major problem in comparing the results has been a lack of consistent criteria for evaluating histological changes in bullhead livers. As individual AOC develop and implement remedial action plans, realistic and attainable delisting targets need to be specified. For this to occur and be consistent from site to site there must be standardization of the criteria being used to evaluate specific impairments. In this report, specific diagnostic criteria are provided for both non-neoplastic and neoplastic proliferative hepatocellular and biliary lesions. These criteria should assist fish pathologists in describing and categorizing proliferative liver lesions from brown bullhead. ?? Inter-Research 2006.

Genetic determinants of heart failure: facts and numbers.

PubMed

Czepluch, Frauke S; Wollnik, Bernd; Hasenfuß, Gerd

2018-06-01

The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing. Due to this development, genetic testing has become increasingly accessible and NGS-based sequencing is now applied in clinical routine diagnostics. One of the most common reasons of heart failure are cardiomyopathies such as the dilated or the hypertrophic cardiomyopathy. Nearly 100 disease-associated genes have been identified for cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic counselling, risk and prognosis determination, therapy guidance and hence for a more effective treatment. Besides, family cascade screening for a known familial, pathogenic mutation can lead to an early diagnosis in affected individuals. At that timepoint, a preventative intervention could be used to avoid or delay disease onset or delay disease progression. Understanding the cellular basis of genetic heart failure syndromes in more detail may provide new insights into the molecular biology of physiological and impaired cardiac (cell) function. As our understanding of the molecular and genetic pathophysiology of heart failure will increase, this might help to identify novel therapeutic targets and may lead to the development of new and specific treatment options in patients with heart failure. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European

Hysteroscopic Findings in Patients with A History of Two Implantation Failures Following In Vitro Fertilization

PubMed Central

Moini, Ashraf; Kiani, Kiandokht; Ghaffari, Firouzeh; Hosseini, Fatemeh

2012-01-01

Background This study was designed to evaluate the incidence of uterine pathologies in infertile women with a history of two implantation failures after in vitro fertilization (IVF) and estimate the effect of hysteroscopic correction on achieving a pregnancy in these patients. Materials and Methods The retrospective study population included 238 infertile women attended the outpatient infertility clinic between November 2007 and December 2008. Patients with at least two previous IVF failures were eligible for this study. All patients had normal findings on hysterosalpingography performed prior their first attempt for IVF. Standard transvaginal ultrasonography and diagnostic hysteroscopy were performed in patients before the subsequent IVF attempt. Results Out of 238 patients with previous IVF failure who underwent hysteroscopic evaluation, 158 patients (66.4%) showed normal uterine cavity. Abnormal cavity was found in 80 patients (33.6%). We found polyp as the most common abnormality (19.7%) in the patients with previous history of IVF failure. The pregnancy rate was similar between IVF failure patients who treated by hysteroscopy for a detected uterine abnormality (24.6%) and similar patients with normal uterine cavity (21.2%) in hysteroscopic examinations. Conclusion The intrauterine lesions diagnosed by hysteroscopy in patients with previous IVF failure ranges from 0.8%-19.7%. Correction of abnormalities such as myoma and polyp showed good outcome, similar to that achieved in patients with a normal hysteroscopy. PMID:25505508

Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

PubMed

Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

2010-03-01

White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI-RADS 3 lesions?

PubMed

Schoots, Ivo G

2018-02-01

This review focuses on indeterminate lesions on prostate magnetic resonance imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index lesion in the diagnostic work-up is significant, varying between one in three (32%) to one in five (22%) men, depending on patient cohort of first biopsies, previously negative biopsies, and active surveillance biopsies. A management strategy must be developed for this group of men with an indeterminate suspicion of having clinically significant prostate cancer (csPCa). Currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary between patients groups from one in five (21%) to one in six (16%), depending on previous biopsy status. Although this prevalence is lower in comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore be adequately managed. In general, the clinical approach of using a threshold of PI-RADS ≥4 instead of PI-RADS ≥3 to select MRI for targeted biopsies is not supported by data from our explorative literature search using current definitions of csPCa. A possible adaptation to the threshold of PI-RADS ≥4 in combination with other clinical markers could be considered within an active surveillance protocol, where the balance between the individual risk of missing csPCa and the constant process of repeating prostate biopsies is crucial. In the future, improvements in MR imaging and interpretation, combined with molecular biomarkers and multivariate risk models will all be employed in prostate cancer detection and monitoring. These combinations will aid decision-making in challenging circumstances, such as unclear and diagnostic equivocal results for csPCa at early detection.

A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue

PubMed Central

Peyster, Eliot G.; Frank, Renee; Margulies, Kenneth B.; Feldman, Michael D.

2018-01-01

Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome. PMID:29614076

A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue.

PubMed

Nirschl, Jeffrey J; Janowczyk, Andrew; Peyster, Eliot G; Frank, Renee; Margulies, Kenneth B; Feldman, Michael D; Madabhushi, Anant

2018-01-01

Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome.

SU-F-T-568: QA of a Multi-Target Multi-Dose VMAT SRS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roa, D; Kuo, J; Gonzales, A

2016-06-15

Purpose: To, experimentally, corroborated the prescribed doses utilizing dosimeters (e.g. films and TLDs) that can provide high spatial resolution, allow dose measurement of multiple targets at once, and provide accurate dosimetric results. Methods: A single-isocenter 6FFF SRS VMAT plan consisting of one 358° arc at 0° couch angle and four 179° arcs at 30°, 60°, 330° and 300° couch angles respectively, was generated in ECLIPSE v.11 using a Rando-Alderson anthropomorphic head phantom CT study. This plan was a reproduction of a clinical plan generated for a stage-IV melanoma patient diagnosed with 19 intracranial lesions. The phantom was loaded with axiallymore » mounted (between phantom slabs) Gafchromic EBT3 film and TLDs strategically positioned within various target volumes. Film and TLDS were calibrated according to established protocols. Target prescription doses were 16 Gy (3cc≤, 3 lesions), 18 Gy (∼1–3cc, 10 lesions) and 20 Gy (≤1cc, 6 lesions). Phantom setup was verified through CBCT imaging prior to irradiation. Gafchromic films were scanned in transmission mode and TLDs were read, respectively, ∼24 hrs after irradiation. Results: Dose calibrated Gafchromic film data were compared to the ECLIPSE calculated data using a 3% / 3mm gamma function analysis. Results for the gamma values were 96–99% in agreement with the calculated data and with 84–90% of the film pixels within the 3% dose difference. TLD data showed a dose difference of 0.4–8% while the film data for those same locations yielded a difference of 0.4–4%. It was observed that the highest dose discrepancies correlated with the location of the small volume targets. Conclusion: Overall this study corroborated that a VMAT SRS treatment, employing various treatment table rotations and arcs, to multiple intracranial lesions with multiple dose prescriptions can be delivered accurately with the existing radiotherapy technology.« less

Failure-probability driven dose painting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). Themore » total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of

Parenteral Nutrition and Intestinal Failure

PubMed Central

Bielawska, Barbara; Allard, Johane P.

2017-01-01

Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient’s home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes. PMID:28481229

Protein Cage Nanoparticles Bearing the LyP-1 Peptide for Enhanced Imaging of Macrophage-Rich Vascular Lesions

PubMed Central

Uchida, Masaki; Kosuge, Hisanori; Terashima, Masahiro; Willits, Deborah A.; Liepold, Lars O.; Young, Mark J.; McConnell, Michael V.; Douglas, Trevor

2011-01-01

Cage-like protein nano particles are promising platforms for cell and tissue specific targeted delivery of imaging and therapeutic agents. Here, we have successfully modified the 12 nm small heat shock protein from Methanococcus jannaschii (MjHsp) to detect atherosclerotic plaque lesions in a mouse model system. As macrophages are centrally involved in the initiation and progression of atherosclerosis, targeted imaging of macrophages is valuable to assess the biologic status of the blood vessel wall. LyP-1, a nine residue peptide, has been shown to target tumor-associated macrophages. Thus, LyP-1 was genetically incorporated onto the exterior surface of MjHsp, while a fluorescent molecule (Cy5.5) was conjugated on the interior cavity. This bioengineered protein cage, LyP-Hsp, exhibited enhanced affinity to macrophage in vitro. Furthermore, in vivo injection of LyP-Hsp allowed visualization of macrophage-rich murine carotid lesions by in situ and ex vivo fluorescence imaging. These results demonstrate the potential of LyP-1-conjugated protein cages as nano-scale platforms for delivery of imaging agents for the diagnosis of atherosclerosis. PMID:21391720

Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions

PubMed Central

Furusho, M; Roulois, A; Franklin, RJM; Bansal, R

2015-01-01

Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of pro-regenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease. PMID:25913734

Skin Cancer of the Head and Neck With Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluck, Iris; Ibrahim, Mohannad; Popovtzer, Aron

2009-05-01

Purpose: To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Methods and Materials: Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Results: Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure patternmore » was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Conclusions: Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.« less

Natural history of β-cell adaptation and failure in type 2 diabetes

PubMed Central

Alejandro, Emilyn U.; Gregg, Brigid; Blandino-Rosano, Manuel; Cras-Méneur, Corentin; Bernal-Mizrachi, Ernesto

2014-01-01

Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure. PMID:25542976

Retrospective analysis of nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions in a population of Taiwanese patients.

PubMed

Huang, Hsun-Yu; Chen, Yuk-Kwan; Ko, Edward Cheng-Chuan; Chuang, Fu-Hsiung; Chen, Ping-Ho; Chen, Ching-Yi; Wang, Wen-Chen

2017-07-01

We aimed to evaluate nonendodontic periapical lesions clinically misdiagnosed as endodontic periapical pathoses in a population of Taiwanese patients. Cases (2000-2014) of histopathological diagnoses of nonendodontic periapical lesions were retrieved from all cases with a clinical diagnosis of radicular cyst, apical granuloma, or apical periodontitis in the institution. These cases were regarded as misdiagnosed nonendodontic periapical lesions, of which the types and frequencies, in addition to the demographic data, were determined. Four thousand and four specimens were clinically diagnosed as endodontically associated pathoses, of which 118 cases (2.95%) received a histopathological diagnosis of a nonendodontic pathologic entity, the most frequent lesion being keratocystic odontogenic tumor (KCOT, n = 38, 32.20%), followed by fibro-osseous lesion (n = 18, 15.25%), and dentigerous cyst (n = 13, 11.02%). Nine malignant lesions in the periapical area [squamous cell carcinoma (n = 7, 5.93%), adenoid cystic carcinoma (n = 1, 0.85%), and Langerhans cell histiocytosis (n = 1, 0.85%)] were also noted. A wide variety of histopathological diagnoses, including benign odontogenic and non-odontogenic cystic and tumorous lesions and infectious diseases, as well as malignant lesions, was noted in these 118 cases of nonendodontic periapical lesions. Squamous cell carcinoma was the most predominant malignancy of nonendodontic periapical lesions misdiagnosed as apical periodontitis lesions from imaging examination overlooking the clinical findings. The current data form a useful basis for clinicopathological investigation and educational teaching regarding nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions.

Targeting Apoptosis for Optical Imaging of Infection

PubMed Central

Thakur, Mathew L.; Zhang, Kaijun; Paudyal, Bishnuhari; Devakumar, Devadhas; Covarrubias, Maria Y.; Cheng, Changpo; Gray, Brian D.; Wickstrom, Eric; Pak, Koon Y.

2018-01-01

Purpose Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging. Methods Bacterial infection and sterile inflammation were induced in separate groups (n=5) of mice. PS was targeted with a NIR fluorophore, PSVue®794 (2.7 pmol). Imaging was performed (ex=730 nm, em=830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity. Results Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6±0.2) were greater than those in inflammation (3.2±0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS. Conclusions Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection. PMID:21538153

Higher contact force during radiofrequency ablation leads to a much larger increase in edema as compared to chronic lesion size.

PubMed

Thomas, Samuel; Silvernagel, Josh; Angel, Nathan; Kholmovski, Eugene; Ghafoori, Elyar; Hu, Nan; Ashton, John; Dosdall, Derek J; MacLeod, Rob; Ranjan, Ravi

2018-05-18

Reversible edema is a part of any radiofrequency ablation but its relationship with contact force is unknown. The goal of this study was to characterize through histology and MRI, acute and chronic ablation lesions and reversible edema with contact force. In a canine model (n = 14), chronic ventricular lesions were created with a 3.5-mm tip ThermoCool SmartTouch (Biosense Webster) catheter at 25 W or 40 W for 30 seconds. Repeat ablation was performed after 3 months to create a second set of lesions (acute). Each ablation procedure was followed by in vivo T2-weighted MRI for edema and late-gadolinium enhancement (LGE) MRI for lesion characterization. For chronic lesions, the mean scar volumes at 25 W and 40 W were 77.8 ± 34.5 mm 3 (n = 24) and 139.1 ± 69.7 mm 3 (n = 12), respectively. The volume of chronic lesions increased (25 W: P < 0.001, 40 W: P < 0.001) with greater contact force. For acute lesions, the mean volumes of the lesion were 286.0 ± 129.8 mm 3 (n = 19) and 422.1 ± 113.1 mm 3 (n = 16) for 25 W and 40 W, respectively (P < 0.001 compared to chronic scar). On T2-weighted MRI, the acute edema volume was on average 5.6-8.7 times higher than the acute lesion volume and increased with contact force (25 W: P = 0.001, 40 W: P = 0.011). With increasing contact force, there is a marginal increase in lesion size but accompanied with a significantly larger edema. The reversible edema that is much larger than the chronic lesion volume may explain some of the chronic procedure failures. © 2018 Wiley Periodicals, Inc.

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

PubMed

Rosen, Allyson C; Soman, Salil; Bhat, Jyoti; Laird, Angela R; Stephens, Jeffrey; Eickhoff, Simon B; Fox, P Mickle; Long, Becky; Dinishak, David; Ortega, Mario; Lane, Barton; Wintermark, Max; Hitchner, Elizabeth; Zhou, Wei

2018-01-01

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

FGF-2 and Anosmin-1 are selectively expressed in different types of multiple sclerosis lesions.

PubMed