Tsc1 is a Critical Regulator of Macrophage Survival and Function

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Chunmin Fang

2015-07-01

Full Text Available Background/Aims: Tuberous sclerosis complex 1 (Tsc1 has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. Methods: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1flox/flox; Tsc1 KO were obtained by crossing Tsc1flox/flox mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre. The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR. The phagocytosis was determined using a Vybrant™ phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. Results: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1 partially reversed the aberrance of Tsc1-deficient macrophages. Conclusion: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity.

six novel mutations in the TSC1 and TSC2 genes

Indian Academy of Sciences (India)

M. GLUSHKOVA

2018-04-30

Apr 30, 2018 ... RESEARCH ARTICLE ... nant disorder caused by inactivating TSC1 or TSC2 gene variants (Van ... premature protein truncation, while missense mutations are rare ..... TSC2 variants in our cohort are missense, frame-shift.

High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

Science.gov (United States)

Medvetz, Doug; Sun, Yang; Li, Chenggang; Khabibullin, Damir; Balan, Murugabaskar; Parkhitko, Andrey; Priolo, Carmen; Asara, John M; Pal, Soumitro; Yu, Jane; Henske, Elizabeth P

2015-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress-dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors. This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress-dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. ©2014 American Association for Cancer Research.

Tumor suppressors TSC1 and TSC2 differentially modulate actin cytoskeleton and motility of mouse embryonic fibroblasts.

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Elena A Goncharova

Full Text Available TSC1 and TSC2 mutations cause neoplasms in rare disease pulmonary LAM and neuronal pathfinding in hamartoma syndrome TSC. The specific roles of TSC1 and TSC2 in actin remodeling and the modulation of cell motility, however, are not well understood. Previously, we demonstrated that TSC1 and TSC2 regulate the activity of small GTPases RhoA and Rac1, stress fiber formation and cell adhesion in a reciprocal manner. Here, we show that Tsc1(-/- MEFs have decreased migration compared to littermate-derived Tsc1(+/+ MEFs. Migration of Tsc1(-/- MEFs with re-expressed TSC1 was comparable to Tsc1(+/+ MEF migration. In contrast, Tsc2(-/- MEFs showed an increased migration compared to Tsc2(+/+ MEFs that were abrogated by TSC2 re-expression. Depletion of TSC1 and TSC2 using specific siRNAs in wild type MEFs and NIH 3T3 fibroblasts also showed that TSC1 loss attenuates cell migration while TSC2 loss promotes cell migration. Morphological and immunochemical analysis demonstrated that Tsc1(-/- MEFs have a thin protracted shape with a few stress fibers; in contrast, Tsc2(-/- MEFs showed a rounded morphology and abundant stress fibers. Expression of TSC1 in either Tsc1(-/- or Tsc2(-/- MEFs promoted stress fiber formation, while TSC2 re-expression induced stress fiber disassembly and the formation of cortical actin. To assess the mechanism(s by which TSC2 loss promotes actin re-arrangement and cell migration, we explored the role of known downstream effectors of TSC2, mTORC1 and mTORC2. Increased migration of Tsc2(-/- MEFs is inhibited by siRNA mTOR and siRNA Rictor, but not siRNA Raptor. siRNA mTOR or siRNA Rictor promoted stress fiber disassembly in TSC2-null cells, while siRNA Raptor had little effect. Overexpression of kinase-dead mTOR induced actin stress fiber disassembly and suppressed TSC2-deficient cell migration. Our data demonstrate that TSC1 and TSC2 differentially regulate actin stress fiber formation and cell migration, and that only TSC2 loss promotes

Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish

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Seok-Hyung Kim

2013-07-01

Tuberous sclerosis complex (TSC is a multi-organ disorder caused by mutations of the TSC1 or TSC2 genes. A key function of these genes is to inhibit mTORC1 (mechanistic target of rapamycin complex 1 kinase signaling. Cells deficient for TSC1 or TSC2 have increased mTORC1 signaling and give rise to benign tumors, although, as a rule, true malignancies are rarely seen. In contrast, other disorders with increased mTOR signaling typically have overt malignancies. A better understanding of genetic mechanisms that govern the transformation of benign cells to malignant ones is crucial to understand cancer pathogenesis. We generated a zebrafish model of TSC and cancer progression by placing a heterozygous mutation of the tsc2 gene in a p53 mutant background. Unlike tsc2 heterozygous mutant zebrafish, which never exhibited cancers, compound tsc2;p53 mutants had malignant tumors in multiple organs. Tumorigenesis was enhanced compared with p53 mutant zebrafish. p53 mutants also had increased mTORC1 signaling that was further enhanced in tsc2;p53 compound mutants. We found increased expression of Hif1-α, Hif2-α and Vegf-c in tsc2;p53 compound mutant zebrafish compared with p53 mutant zebrafish. Expression of these proteins probably underlies the increased angiogenesis seen in compound mutant zebrafish compared with p53 mutants and might further drive cancer progression. Treatment of p53 and compound mutant zebrafish with the mTORC1 inhibitor rapamycin caused rapid shrinkage of tumor size and decreased caliber of tumor-associated blood vessels. This is the first report using an animal model to show interactions between tsc2, mTORC1 and p53 during tumorigenesis. These results might explain why individuals with TSC rarely have malignant tumors, but also suggest that cancer arising in individuals without TSC might be influenced by the status of TSC1 and/or TSC2 mutations and be potentially treatable with mTORC1 inhibitors.

The Role of TSC Proteins in Regulating Cell Adhesion and Motility

National Research Council Canada - National Science Library

Krymskaya, Vera P

2006-01-01

The goal of this project was to define the molecular signaling mechanisms by which TSCI and TSC2 proteins regulate cell adhesion and motility as it relates to the genetic disorder tuberous sclerosis complex (TSC...

Clinical management of tuberous sclerosis complex over the lifetime of a patient

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Frost M

2015-08-01

Full Text Available Michael Frost,1 John Hulbert2 1Minnesota Epilepsy Group, PA, St Paul, MN, USA; 2Urologic Physicians, PA, Edina, MN, USA Abstract: Tuberous sclerosis complex (TSC is a genetic disorder characterized by nonmalignant tumors (hamartomas that can occur in various organ systems, including the brain, kidneys, lungs, skin, eyes, and heart. Clinical manifestations of TSC can occur at any age, thereby making the diagnosis difficult. No typical disease presentation is known, and the clinical presentation usually differs between pediatric and adult patients. Furthermore, variable penetrance of the genetic mutation causes a range of disease severity from very mild to severe, and affected individuals can go undetected for years because many of the clinical manifestations of TSC lack specificity. Once a diagnosis is made, TSC management strategies should be tailored to address the symptoms and risks most relevant to the age of the patient. Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. In Phase II and III studies, everolimus has demonstrated efficacy and safety in the treatment of both brain (subependymal giant cell astrocytoma and renal (angiomyolipoma manifestations associated with TSC. It is important to bear in mind that TSC is a lifelong condition, and for those diagnosed as children, a continuum of care will be needed as they transition from pediatric to adult health services. Clearly identifying the likely differences among diagnosis, monitoring, and management of pediatric and adult patients with TSC is an important step in enabling efficiencies to be maximized without compromising the care provided to patients. Keywords: mammalian target of rapamycin inhibitors, mTOR treatment, treatment strategies

Biomarkers of Renal Tumor Burden and Progression in TSC

Science.gov (United States)

2013-09-01

implications. Standard of care should include routine genotyping and regular creatinine measurement in all TSC patients to help guide clinical...pressure, serum chemistries, urinalysis and urine chemistries). (B) Measure soluble growth factors, angiogenesis factors and renal injury molecules in...ELISA was unacceptably limited compared to the standard curve. This limitation restricts its ability to discriminate between samples from TSC patients

Modeling TSC and LAM Using Patient Derived Induced Pluripotent Stem Cells

Science.gov (United States)

2016-10-01

drug screens . We have now made TSC2 deficient human cells using patient induced pluripotent stem cells (iPSCs...Therapeutics.” Canadian Association of Research in Regenerative Medicine (CARRM), Ottawa, ON, CANADA March 7, 2015 • “ Stem cell approaches to model human... Stem cell approaches to model human development and disease.” Australian Regenerative Medicine Institute, Melbourne, Victoria, AUSTRALIA November

Comparison of Color Fundus Photography, Infrared Fundus Photography, and Optical Coherence Tomography in Detecting Retinal Hamartoma in Patients with Tuberous Sclerosis Complex.

Science.gov (United States)

Bai, Da-Yong; Wang, Xu; Zhao, Jun-Yang; Li, Li; Gao, Jun; Wang, Ning-Li

2016-05-20

A sensitive method is required to detect retinal hamartomas in patients with tuberous sclerosis complex (TSC). The aim of the present study was to compare the color fundus photography, infrared imaging (IFG), and optical coherence tomography (OCT) in the detection rate of retinal hamartoma in patients with TSC. This study included 11 patients (22 eyes) with TSC, who underwent color fundus photography, IFG, and spectral-domain OCT to detect retinal hamartomas. TSC1 and TSC2RESULTS: The mean age of the 11 patients was 8.0 ± 2.1 years. The mean spherical equivalent was -0.55 ± 1.42 D by autorefraction with cycloplegia. In 11 patients (22 eyes), OCT, infrared fundus photography, and color fundus photography revealed 26, 18, and 9 hamartomas, respectively. The predominant hamartoma was type I (55.6%). All the hamartomas that detected by color fundus photography or IFG can be detected by OCT. Among the methods of color fundus photography, IFG, and OCT, the OCT has higher detection rate for retinal hamartoma in TSC patients; therefore, OCT might be promising for the clinical diagnosis of TSC.

Long-term Follow-up Assessing Renal Angiomyolipoma Treatment Patterns, Morbidity, and Mortality : An Observational Study in Tuberous Sclerosis Complex Patients in the Netherlands

NARCIS (Netherlands)

Eijkemans, Marinus J C; van der Wal, Willem; Reijnders, Leida J; Roes, Kit C B; van Waalwijk van Doorn-Khosrovani, Sahar Barjesteh; Pelletier, Corey; Magestro, Matthew; Zonnenberg, Bernard

2015-01-01

BACKGROUND: Long-term data from patients with tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (angiomyolipoma) are limited. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Adult patients with TSC treated at the University Medical Center Utrecht (the

Repression of TSC1/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation.

Science.gov (United States)

Wang, Yuanyuan; Chen, Chen; Deng, Ziyu; Bian, Erbao; Huang, Cheng; Lei, Ting; Lv, Xiongwen; Liu, Liping; Li, Jun

2017-03-01

Pulmonary fibrosis (PF) is a severe inflammatory disease with limited effective treatments. It is known that the transdifferentiation of human embryo lung fibroblast (HELF) cells from pulmonary fibroblasts into myofibroblasts, contributes to the progression of pulmonary fibrogenesis. The tuberous sclerosis proteins TSC1 and TSC2 are two key signaling factors which can suppress cell growth and proliferation. However, the roles of TSC1 and TSC2 in lung fibroblast are unclear. Here, we developed a PF model with bleomycin (BLM) in mice and conducted several simulation experiments in HELF cells. Our study shows that the expression of TSC1 and TSC2 in fibrotic mice lung was reduced and stimulation of HELF cells with TGF-β1 resulted in a down-regulation of TSC1 and TSC2. In addition, overexpression of TSC1 or TSC2 decreased cell proliferation and differentiation. Furthermore, we found that reduced expression of TSC1 and TSC2 caused by TGF-β1 is associated with the promoter methylation status of TSC1 and TSC2. MeCP2, controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. We found that expression of TSC1 and TSC2 can be repressed by MeCP2, which regulates HELF cell differentiation and proliferation as myofibroblasts and lead to PF ultimately. Copyright © 2016. Published by Elsevier B.V.

Eye Involvement in TSC

Science.gov (United States)

... 50% of the individuals with TSC have normal intelligence, and inasmuch as these individuals may become parents, ... of vision may be difficult or impossible. Since growth and change of TSC lesions in the eye ...

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

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Angelika Mühlebner

Full Text Available Tuberous Sclerosis Complex (TSC is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1 activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

Science.gov (United States)

Mühlebner, Angelika; van Scheppingen, Jackelien; Hulshof, Hanna M; Scholl, Theresa; Iyer, Anand M; Anink, Jasper J; van den Ouweland, Ans M W; Nellist, Mark D; Jansen, Floor E; Spliet, Wim G M; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Comprehensive analysis of gene mutation and phenotype of tuberous sclerosis complex in China

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Guo-qiang HUANG

2015-04-01

Full Text Available Objective To summarize the clinical features of tuberous sclerosis complex (TSC, the distribution and description of TSC gene, and to probe into the correlation of genotype with phenotype.  Methods According to the 1998 International Tuberous Sclerosis Complex Diagnostic Criteria, a total of 163 TSC patients with pathogenic mutation in TSC gene (3 cases were detected in our hospital, and the other 160 cases were collected from other institutions in China were enrolled, and their gene detection results and clinical data were analyzed.  Results Among 163 cases, TSC1 mutation (31 cases accounted for 19.02% [32.26% (10/31 in exon 15, 16.13% (5/31 in exon 21, 12.90% (4/31 in exon 18], and TSC2 mutation (132 cases accounted for 80.98% [9.85% (13/132 in exon 37, 7.58% (10/132 in exon 40, 6.82%(9/132 in exon 33]. The proportion of base replacement in TSC1 was 41.94% (13/31, and 52.27% (69/132 in TSC2. Male patients exhibited significantly more subependymal nodules or calcifications than thefemale patients (χ2 = 8.016, P = 0.005. Sporadic patients exhibited significantly more cortical tubers than familial patients (χ2 = 6.273, P = 0.012. Patients with TSC2 mutations had significantly higher frequencies of hypomelanotic macules than patients with TSC1 mutations (χ2 = 6.756, P = 0.009. Patients with missense mutations were more likely to have facial angiofibromas compared with patients with other mutations (χ2 = 4.438, P = 0.035.  Conclusions Exon 15, 21 and 18 of TSC1 and exon 37, 40 and 33 of TSC2 accounted for higher percentage of mutations. Correlating genotypes with phenotypes should facilitate the individualized treatment and prognostic assessment of tuberous sclerosis complex. DOI: 10.3969/j.issn.1672-6731.2015.04.013

Identification of NPM and DDX5 as Therapeutic Targets in TSC

Science.gov (United States)

2017-12-01

Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited...9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort...complexes in TSC cells. 15. SUBJECT TERMS NPM, DDX5, TSC, chemical library , split-luciferase 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication.

Science.gov (United States)

Ho, Daniel W H; Chan, Lo K; Chiu, Yung T; Xu, Iris M J; Poon, Ronnie T P; Cheung, Tan T; Tang, Chung N; Tang, Victor W L; Lo, Irene L O; Lam, Polly W Y; Yau, Derek T W; Li, Miao X; Wong, Chun M; Ng, Irene O L

2017-08-01

We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC -mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2 -mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metastatic Group 3 Medulloblastoma in a Patient With Tuberous Sclerosis Complex: Case Description and Molecular Characterization of the Tumor.

Science.gov (United States)

Moavero, Romina; Folgiero, Valentina; Carai, Andrea; Miele, Evelina; Ferretti, Elisabetta; Po, Agnese; Diomedi Camassei, Francesca; Lepri, Francesca Romana; Vigevano, Federico; Curatolo, Paolo; Valeriani, Massimiliano; Colafati, Giovanna S; Locatelli, Franco; Tornesello, Assunta; Mastronuzzi, Angela

2016-04-01

Medulloblastoma is the most common pediatric brain tumor. We describe a child with tuberous sclerosis complex that developed a Group 3, myc overexpressed, metastatic medulloblastoma (MB). Considering the high risk of treatment-induced malignancies, a tailored therapy, omitting radiation, was given. Based on the evidence of mammalian target of rapamycin mTORC, mTOR Complex; RAS, Rat sarcoma; RAF, rapidly accelerated fibrosarcoma (mTOR) pathway activation in the tumor, targeted therapy was applied resulting in complete remission of disease. Although the PI3K/AKT/mTOR signaling pathway plays a role in MB, we did not find TSC1/TSC2 (TSC, tuberous sclerosis complex) mutation in our patient. We speculate that a different pathway resulting in mTOR activation is the basis of both TSC and MB in this child; H&E, haematoxilin and eosin; Gd, gadolinium. © 2015 Wiley Periodicals, Inc.

Epilepsy in Adults with TSC

Science.gov (United States)

... Privacy Policy Sitemap Learn Engage Donate About TSC Epilepsy in Adults with TSC Individuals with tuberous sclerosis ... being well controlled for long periods of time. Epilepsy and Seizures Epilepsy is any brain disorder that ...

Types of Seizures Affecting Individuals with TSC

Science.gov (United States)

... Policy Sitemap Learn Engage Donate About TSC Epilepsy/Seizure Disorders Seizures remain one of the most common neurological ... TSC Brain and Neurological Function Brain Abnormalities Epilepsy/Seizure Disorders Infantile Spasms Epilepsy in Adults with TSC Epilepsy ...

Time-dependent EQPET analysis of TSC

International Nuclear Information System (INIS)

Takahashi, Akito

2006-01-01

Time-dependent fusion rates for 2D and 4D reactions are calculated for squeezing of tetrahedral symmetric condensate (TSC) from about 100 pm size to its minimum size (about 10 fm), within about 75 fs squeezing motion. Life time of the minimum TSC state is yet to be studied. Time-averaged fusion rates are given by assuming the life time of minimum TSC state is negligible. Time-averaged 2D fusion rate was given as 2.9x10 -25 f/s/pair, and time-averaged 4D fusion rate was 5.5x10 -8 f/s/cl. These values are compared with 1.0x10 -20 f/s/pair for 2D and 1.0x10 -9 f/s/cl for 4D, respectively, of previously estimated values by electronic quasi-particle expansion theory/TSC models. Effective fusion time by the TSC squeezing motion was estimated as 0.014 fs: namely fusions may happen in very short time interval. (author)

A novel TSC2 mutation in a Chinese family with tuberous sclerosis ...

Indian Academy of Sciences (India)

1Department of Medical Genetics, College of Basic Medical Science and 2Undergraduate Student Brigade, ... Recent studies in the TSC patients indicated that mutations ... Because of the low back pain he ... tein of 946 amino acids instead of a normal tuberin protein ... In the TSC cohort, more than 90% had skin lesions,.

Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

NARCIS (Netherlands)

Curatolo, P.; Aronica, E.; Jansen, A.; Jansen, F.; Kotulska, K.; Lagae, L.; Moavero, R.; Jozwiak, S.

2016-01-01

BACKGROUND: In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a

Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

NARCIS (Netherlands)

Curatolo, Paolo; Aronica, Eleonora; Jansen, Anna; Jansen, Floor; Kotulska, Katarzyna; Lagae, Lieven; Moavero, Romina; Jozwiak, Sergiusz

2016-01-01

In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a causal role

Novel Mutation in the TSC2 Gene Associated with Prenatally Diagnosed Cardiac Rhabdomyomas and Cerebral Tuberous Sclerosis

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2006-01-01

Full Text Available Cardiac rhabdomyomas are prenatal echocardiographic markers for tuberous sclerosis complex (TSC. TSC is caused by mutations in the genes TSC1 and TSC2. We report a 28-year-old, gravida 5, para 2, woman with an uncomplicated pregnancy until prenatal ultrasound at 34 weeks' gestation revealed fetal cardiac tumors. Ultrafast magnetic resonance imaging (MRI at 36 weeks' gestation showed cardiac rhab-domyomas and small subependymal tubers. At 39 weeks' gestation, a 2262 g female infant was delivered uneventfully. Postnatal echocardiography confirmed cardiac rhabdomyomas and MRI verified small cerebral subependymal tubers. Mutational analysis of TSC1 and TSC2 genes using denaturing high-performance liquid chromatography and direct sequencing of the genes was performed and revealed that the parents had wildtype DNA, while the proband was heterozygous for a novel de novo nonsense mutation, c.4830 G > A, in exon 36 of the TSC2 gene, resulting in a change of codon 1610 TGG (tryptophan to TGA (stop codon. The mutation predicted a W1610X premature termination of the tuberin protein. These findings support an association between a TSC2 de novo nonsense mutation and prenatally detected cardiac rhabdomyomas and cerebral tuberous sclerosis. Familial molecular analysis of TSC1 and TSC2 in cases with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis lesions is helpful in prenatal diagnosis and genetic counseling.

Mechanism of Akt1 inhibition of breast cancer cell invasionreveals a protumorigenic role for TSC2

Energy Technology Data Exchange (ETDEWEB)

Liu, Hong; Radisky, Derek C.; Nelson, Celeste M.; Zhang, Hui; Fata, Jimmie; Roth, Richard A.; Bissell, Mina J.

2006-02-07

Akt1 is frequently upregulated in human tumors, and has been shown to accelerate cell proliferation and to suppress programmed cell death; consequently, inhibiting the activity of Akt1 has been seen as an attractive target for therapeutic intervention. Paradoxically, hyperactivation of the Akt1 oncogene can also prevent the invasive behavior that underlies progression to metastasis. Here we show that overexpression of activated myr-Akt1 in human breast cancer cells phosphorylates and thereby targets the tumor suppressor tuberous sclerosis complex 2 (TSC2) for degradation, leading to reduced Rho-GTPase activity, decreased actin stress fibers and focal adhesions, and reduced motility and invasion. Overexpression of TSC2 rescues the migration phenotype of myr-Akt1-expressing tumor cells, and high levels of TSC2 in breast cancer patients correlate with increased metastasis and reduced survival. These data indicate that the functional properties of genes designated as oncogenes or tumor suppressor genes depends on the context of the cell type and the tissues studied, and suggest the need for caution in designing therapies targeting the function of individual genes in epithelial tissues.

pTSC: Data file editing for the Tokamak Simulation Code

International Nuclear Information System (INIS)

Meiss, J.D.

1987-09-01

The code pTSC is an editor for the data files needed to run the Princeton Tokamak Simulation Code (TSC). pTSC utilizes the Macintosh interface to create a graphical environment for entering the data. As most of the data to run TSC consists of conductor positions, the graphical interface is especially appropriate

Results of ionospheric parameters measurements during injections of exhaust streams of TSC "Progress" OMS

Science.gov (United States)

Khakhinov, Vitaly; Alsatkin, Sergey; Medvedev, Andrey; Kushnarev, Dmitriy; Lebedev, Valentin; Potekhin, Alexander; Ratovsky, Konstantin; Shpynev, Boris

Since 2006 we have carried out active space experiments using the transport spacecraft (TSC) "Progress" and the ground-base Radio-Optic Complex of ISTP SB RAS including Irkutsk Incoherent Scatter Radar (IISR). Engine burns of TSC orbital maneuvering subsystem (OMS) were used as a source of ionospheric disturbances and changing radar signature characteristics of TSC. The flight altitudes were about 340 km. The amount of engine exhaust products was varied from 2 to 11 kg. The flow directions relative to IISR and amount of injected exhaust products were changed from flight to flight. The flows directed to IISR were almost parallel to the geomagnetic field line. For these cases the most pronounced effects were observed, the electron density depletion reached 20-40

Cell Type-Specific Contributions to the TSC Neuropathology

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

TSC mobile mining and extraction technology

Energy Technology Data Exchange (ETDEWEB)

Lavender, W.J. [TSC Company Ltd., Calgary, AB (Canada)

2001-11-01

This Power-Point presentation described an innovative mining and extraction technology developed by Calgary-based TSC Company Ltd. that has provided a major breakthrough in bitumen production from mineable oil sands. The presentation described the process and key mechanical components as demonstrated on oil sands leases. It also described the step change in cost structure and profitability. Oil sands mining provide a hugh resource base with no exploration costs and no decline in production. Despite these advantages, oil sands mining faces the challenge of high capital and operating costs and materials handling. Other challenges include the variability of the ore and environmental impacts. This paper described the fundamentals of the new technology called the Tar Sand Combine (TSC), a continuous mining machine, crusher, cyclone, tailings filter and stacker all in one mobile module. Several viewgraphs were included with the presentation to depict the recovery process as successfully demonstrated at a pilot project. Patent is pending on the process and components. The advantages of the TSC are reduced materials handling, and no tailings ponds are generated since tailings remain where they are mined. The final product is clean bitumen. The specifications of a commercial TSC are: 2000 ton/stream hour mining produce 25,000 bpsd bitumen at 12 per cent ore grade; mined ore bitumen recovery is greater than 95 per cent and the availability factor is 85 per cent. It was concluded that the TSC can maximize oil sands reserves, while providing significant cost savings and environmental benefits. 2 tabs., 24 figs.

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Chakraborty, Sanjukta; Mohiyuddin, SM Azeem; Gopinath, KS; Kumar, Arun

2008-01-01

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC. Expression of genes at the RNA and protein levels was examined by semi-quantitative RT-PCR and western blot analyses, respectively. Loss of heterozygosity was studied using matched blood and tumor DNA samples and microsatellite markers from the TSC1, TSC2 and PTEN candidate regions. The effect of promoter methylation on TSC gene expression was studied by treating cells with methyltransferase inhibitor 5-azacytidine. Methylation status of the TSC2 promoter in tissue samples was examined by combined bisulfite restriction analysis (COBRA). The semi-quantitative RT-PCR analysis showed downregulation of TSC1, TSC2, EIF4EBP1 and PTEN, and upregulation of PIK3C2A, AKT1, PDPK1, RHEB, FRAP1, RPS6KB1, EIF4E and RPS6 in tumors. A similar observation was made for AKT1 and RPS6KB1 expression in tumors at the protein level. Investigation of the mechanism of downregulation of TSC genes identified LOH in 36.96% and 39.13% of the tumors at the TSC1 and TSC2 loci, respectively. No mutation was found in TSC genes. A low LOH rate of 13% was observed at the PTEN locus. Treatment of an OSCC cell line with the methyltransferase inhibitor 5-azacytidine showed a significant increase in the expression of TSC genes, suggesting methylation of their promoters. However, the 5-azacytidine treatment of non-OSCC HeLa cells showed a significant increase in the expression of the TSC2 gene only. In order

Eye Involvement in TSC

Science.gov (United States)

... eye involvement. Nonretinal and Retinal Eye Findings Facial angiofibromas may involve the eyelids of individuals with TSC, ... the hamartomas have many blood vessels (as are angiofibromas of the skin). Less than half of the ...

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

International Nuclear Information System (INIS)

Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

2015-01-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

Energy Technology Data Exchange (ETDEWEB)

Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

2015-03-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Adriaensen, M.E.A.P.M., E-mail: miraude@gmail.com [Department of Radiology, Atrium Medical Center Parkstad, Heerlen (Netherlands); Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Schaefer-Prokop, C.M. [Department of Radiology, Meander Medical Center, Amersfoort (Netherlands); Duyndam, D.A.C. [Department of Radiology, OLVG, Amsterdam (Netherlands); Zonnenberg, B.A. [Department of Internal Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Prokop, M. [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

2011-07-15

Aim: To determine the gender-specific prevalence of pulmonary cysts typical for lymphangioleiomyomatosis (LAM) in adult patients with known tuberous sclerosis complex (TSC). Materials and methods: A retrospective, cross-sectional study in a cohort of 206 adult TSC patients was performed. Institutional review board approval was obtained, and patient informed consent was waived. Patients had routinely undergone abdominal CT scanning between 1996 and 2006. All 186 patients (mean age 38 years; range 19-72 years; 91 (49%) male patients) in whom at least the lung bases were depicted on computed tomography (CT) were included. Images were reviewed for the presence of pulmonary thin-walled cysts. Descriptive statistics, two sample t-test to compare means, and {chi}{sup 2}-test to compare proportions were applied. Results: CT demonstrated pulmonary thin-walled cysts in the lung bases in 52 (28%) of 186 patients. Size varied from 2 mm in diameter to more than 2 cm. Pulmonary cysts were detected in 40 (42%) of 95 female patients and in 12 (13%) of 91 male patients (p < 0.001). In general, cysts were larger and more numerous in women than in men. Only minimal cystic changes were found in four women and two men, moderate cystic changes were seen in three women and seven men, but considerable cystic changes were seen almost exclusively in women (33 women versus three men). Conclusion: CT demonstrated thin-walled pulmonary cysts in the lung bases in 28% of 186 included patients with tuberous sclerosis complex. Female patients were more affected than male patients.

Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex

International Nuclear Information System (INIS)

Adriaensen, M.E.A.P.M.; Schaefer-Prokop, C.M.; Duyndam, D.A.C.; Zonnenberg, B.A.; Prokop, M.

2011-01-01

Aim: To determine the gender-specific prevalence of pulmonary cysts typical for lymphangioleiomyomatosis (LAM) in adult patients with known tuberous sclerosis complex (TSC). Materials and methods: A retrospective, cross-sectional study in a cohort of 206 adult TSC patients was performed. Institutional review board approval was obtained, and patient informed consent was waived. Patients had routinely undergone abdominal CT scanning between 1996 and 2006. All 186 patients (mean age 38 years; range 19-72 years; 91 (49%) male patients) in whom at least the lung bases were depicted on computed tomography (CT) were included. Images were reviewed for the presence of pulmonary thin-walled cysts. Descriptive statistics, two sample t-test to compare means, and χ 2 -test to compare proportions were applied. Results: CT demonstrated pulmonary thin-walled cysts in the lung bases in 52 (28%) of 186 patients. Size varied from 2 mm in diameter to more than 2 cm. Pulmonary cysts were detected in 40 (42%) of 95 female patients and in 12 (13%) of 91 male patients (p < 0.001). In general, cysts were larger and more numerous in women than in men. Only minimal cystic changes were found in four women and two men, moderate cystic changes were seen in three women and seven men, but considerable cystic changes were seen almost exclusively in women (33 women versus three men). Conclusion: CT demonstrated thin-walled pulmonary cysts in the lung bases in 28% of 186 included patients with tuberous sclerosis complex. Female patients were more affected than male patients.

Mucocutaneous changes in tuberous sclerosis complex: A clinical profile of 27 Indian patients

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Ghosh Sudip

2009-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is an autosomal dominant neurocutaneous disease resulting in a wide array of clinical manifestations, primarily affecting the skin and central nervous system. Mucocutaneous features play a very important role in the recognition of this syndrome. Aims: To review the prevalence and patterns of cutaneous manifestations in tuberous sclerosis, in a group of patients from eastern India. Methods: Observational clinical study on twenty-seven consecutive patients of tuberous sclerosis collected during a period of four years. Results: Most were between 10-20 years of age; the male to female ratio was 2:1. Family history was found in two-thirds. The classical triad of tuberous sclerosis was present in only nine (33.3% patients. Adenoma sebaceum was the most common cutaneous feature (100%, followed by hypomelanotic macules (92.6%, connective tissue nevi (66.6%, and Koenen′s tumors (33.3%. Oral mucosal fibromas were seen in six (22.22% patients. Fibromatous plaque over forehead and scalp was seen in three patients. Limitation of the study was small size of study sample. Conclusion: Prominent mucocutaneous changes are extremely common manifestation of TSC, which may provide crucial diagnostic clues for primary care physicians.

Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex.

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Yanan Guo

Full Text Available Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis.

Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells

International Nuclear Information System (INIS)

Koike, Manabu; Ninomiya, Yasuharu; Koike, Aki

2008-01-01

The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation. (author)

Bilateral Giant Renal Angiomyolipoma in a Patient with Tuberous Sclerosis Complex: A Case Report

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Andika Afriansyah

2018-04-01

Full Text Available Tuberous sclerosis complex (TSC has several renal manifestations including angiomyolipomas (AML and renal epithelial neoplasms. A bilateral giant renal AML is extremely rare. We report a case of giant bilateral AML and discuss the diagnosis and treatment of it. The 22-year-old man was admitted due to bilateral flank pain, gross hematuria, and abdominal fullness. He had history of epilepsy, mental retardation, and delayed development during childhood. He had angiofibroma on his face since 10 years ago. Abdominal CT and MRI revealed large lobulated heterogeneous mass with fatty content. Based on those findings, we diagnosed the patient with bilateral giant renal AML. We gave conservative management for the patient and planned to total nephrectomy on the left kidney if the continued bleeding occurred. AML associated with TSC occur more frequently as multiple lesions and grows to larger size than idiopathic AML. Bilateral giant AML, which is very rare, could be treated with conservative management if no significant hemorrhage occurred.

Dermatologic and dental aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements.

Science.gov (United States)

Teng, Joyce M C; Cowen, Edward W; Wataya-Kaneda, Mari; Gosnell, Elizabeth S; Witman, Patricia M; Hebert, Adelaide A; Mlynarczyk, Greg; Soltani, Keyoumars; Darling, Thomas N

2014-10-01

The 2012 International Tuberous Sclerosis Complex Clinical Consensus Conference was convened to update the last consensus statement in 1998. Skin and dental lesions are common in tuberous sclerosis complex (TSC) and are a frequent concern for patients. Recognition of these lesions is imperative for early diagnosis, given the treatment advances that may improve patient outcomes. To detail recommendations for the diagnosis, surveillance, and management of skin and dental lesions in TSC. The TSC Dermatology and Dentistry Subcommittee, 1 of 12 subcommittees, reviewed the relevant literature from 1997 to 2012. A consensus on skin and dental issues was achieved within the Dermatology and Dentistry Subcommittee before recommendations were presented, discussed, and agreed on in a group meeting of all subcommittees from June 14 to 15, 2012. Skin and dental findings comprise 4 of 11 major features and 3 of 6 minor features in the diagnostic criteria. A definite diagnosis of TSC is defined as the presence of at least 2 major features or 1 major and 2 or more minor features; in addition, a pathological mutation in TSC1 or TSC2 is diagnostic. Skin and oral examinations should be performed annually and every 3 to 6 months, respectively. Intervention may be indicated for TSC skin or oral lesions that are bleeding, symptomatic, disfiguring, or negatively affecting function. Options presented include surgical excision, laser(s), or use of a mammalian target of rapamycin inhibitor.

Imaging of tuberous sclerosis complex: a pictorial review

Energy Technology Data Exchange (ETDEWEB)

Ranke, Felipe Mussi von; Faria, Igor Murad; Zanetti, Glaucia; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, (Brazil); Hochhegger, Bruno [Santa Casa de Porto Alegre, Porto Alegre, RS (Brazil); Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP) , SP (Brazil)

2017-01-15

Tuberous sclerosis complex (TSC) is a genetically determined hamartomatous neurocutaneous disease with high phenotypic variability. TSC is characterized by widespread hamartomas and benign, or rarely malignant, neoplasms distributed in several organs throughout the body, especially in the brain, skin, retina, kidney, heart, and lung. Common manifestations include cortical tubers, subependymal nodules, white matter abnormalities, retinal abnormalities, cardiac rhabdomyoma, lymphangioleiomyomatosis, renal angiomyolipoma, and skin lesions. The wide range of organs affected by the disease implies that TSC1 and TSC2 genes play important roles in the regulation of cell proliferation and differentiation. Although recent advances in treatment have improved morbidity, the prognosis remains quite poor and nearly 40% of patients die by the age of 35 years. Imaging is important in the evaluation of TSC because of its role not only in presumptive diagnosis, but also in defining the full extent of involvement. This information allows a better understanding of the behavioural phenotype, as related to lesion location. Imaging also contributes to treatment planning. This pictorial review describes common and uncommon imaging manifestations of TSC. (author)

Epilepsy in Adults with TSC

Science.gov (United States)

... individual with TSC deserves the best quality of life possible, so they should work with the caregivers to reach a balance between seizure control and side effects of the medication. Treatment Options There are many ...

The pathogenesis and imaging of the tuberous sclerosis complex

International Nuclear Information System (INIS)

Baskin, Henry J.

2008-01-01

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by the formation of hamartomatous lesions in multiple organ systems. It is the second most common neurocutaneous syndrome after neurofibromatosis type 1 and has been recognized since the late 1800s. Although the disease has complete penetrance, there is also high phenotypic variability: some patients have obvious signs at birth, while others remain undiagnosed for many years. In addition to skin lesions, TSC patients develop numerous brain lesions, angiomyolipoma (AMLs), lymphangiomyomatosis (LAM) in the lungs, cardiac rhabdomyomas, skeletal lesions, and vascular anomalies, all of which are well seen with medical imaging. Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC's interaction with the mTOR pathway has changed how we manage the disease. Meanwhile, medical imaging is playing an increasingly important role in the diagnosis, management, and treatment of TSC. We provide an update on the genetics and pathophysiology of TSC, review its clinical manifestations, and explore the breadth of imaging features in each organ system, from prenatal detection of cardiac rhabdomyomas to monitoring rapamycin therapy to treatment of AMLs by interventional radiology. (orig.)

The pathogenesis and imaging of the tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Baskin, Henry J. [Cincinnati Children' s Medical Center, Department of Radiology, Cincinnati, OH (United States)

2008-09-15

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by the formation of hamartomatous lesions in multiple organ systems. It is the second most common neurocutaneous syndrome after neurofibromatosis type 1 and has been recognized since the late 1800s. Although the disease has complete penetrance, there is also high phenotypic variability: some patients have obvious signs at birth, while others remain undiagnosed for many years. In addition to skin lesions, TSC patients develop numerous brain lesions, angiomyolipoma (AMLs), lymphangiomyomatosis (LAM) in the lungs, cardiac rhabdomyomas, skeletal lesions, and vascular anomalies, all of which are well seen with medical imaging. Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC's interaction with the mTOR pathway has changed how we manage the disease. Meanwhile, medical imaging is playing an increasingly important role in the diagnosis, management, and treatment of TSC. We provide an update on the genetics and pathophysiology of TSC, review its clinical manifestations, and explore the breadth of imaging features in each organ system, from prenatal detection of cardiac rhabdomyomas to monitoring rapamycin therapy to treatment of AMLs by interventional radiology. (orig.)

Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex

Science.gov (United States)

Tyburczy, Magdalena E.; Wang, Ji-an; Li, Shaowei; Thangapazham, Rajesh; Chekaluk, Yvonne; Moss, Joel; Kwiatkowski, David J.; Darling, Thomas N.

2014-01-01

Tuberous sclerosis complex (TSC) is characterized by the formation of tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes, TSC1 and TSC2. As for other tumor suppressor gene syndromes, the mechanism of somatic second-hit events in TSC tumors is unknown. We grew fibroblast-like cells from 29 TSC skin tumors from 22 TSC subjects and identified germline and second-hit mutations in TSC1/TSC2 using next-generation sequencing. Eighteen of 22 (82%) subjects had a mutation identified, and 8 of the 18 (44%) subjects were mosaic with mutant allele frequencies of 0 to 19% in normal tissue DNA. Multiple tumors were available from four patients, and in each case, second-hit mutations in TSC2 were distinct indicating they arose independently. Most remarkably, 7 (50%) of the 14 somatic point mutations were CC>TT ultraviolet ‘signature’ mutations, never seen as a TSC germline mutation. These occurred exclusively in facial angiofibroma tumors from sun-exposed sites. These results implicate UV-induced DNA damage as a cause of second-hit mutations and development of TSC facial angiofibromas and suggest that measures to limit UV exposure in TSC children and adults should reduce the frequency and severity of these lesions. PMID:24271014

A 28-Year-Old Male Patient with Nail Tumors, Skin Lesions, and Epilepsy.

Science.gov (United States)

Balak, Deepak M W; Zonnenberg, Bernard A; Spitzer-Naaijkens, Juliette M J; Hulshof, Mieke M

2017-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

A 28-Year-Old Male Patient with Nail Tumors, Skin Lesions, and Epilepsy

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Deepak M.W. Balak

2017-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. Methods: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Results: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Conclusions: Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

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Dan Ehninger

2014-01-01

Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

Energy Technology Data Exchange (ETDEWEB)

Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

2013-07-19

Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

Electrochemical behaviour of alkaline copper complexes

Indian Academy of Sciences (India)

Abstract. A search for non-cyanide plating baths for copper resulted in the development of alkaline copper complex baths containing trisodium citrate [TSC] and triethanolamine [TEA]. Voltammetric studies were carried out on platinum to understand the electrochemical behaviour of these complexes. In TSC solutions, the.

Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

Science.gov (United States)

Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

2011-04-01

Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

TOSCA - first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex.

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Kingswood, John C; Bruzzi, Paolo; Curatolo, Paolo; de Vries, Petrus J; Fladrowski, Carla; Hertzberg, Christoph; Jansen, Anna C; Jozwiak, Sergiusz; Nabbout, Rima; Sauter, Matthias; Touraine, Renaud; O'Callaghan, Finbar; Zonnenberg, Bernard; Crippa, Stefania; Comis, Silvia; d'Augères, Guillaume Beaure; Belousova, Elena; Carter, Tom; Cottin, Vincent; Dahlin, Maria; Ferreira, José Carlos; Macaya, Alfons; Benedik, Mirjana Perkovic; Sander, Valentin; Youroukos, Sotirios; Castellana, Ramon; Ulker, Bulent; Feucht, Martha

2014-11-26

Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies. TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a 'core' section and subsections or 'petals'. The 'core' section is designed to record general information on patients' background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24 months. A follow-up observation period of up to 5 years is planned. A pre-planned administrative analysis of 'core' data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to

Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches.

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Bongiorno, Michelle A; Nathan, Neera; Oyerinde, Oyetewa; Wang, Ji-An; Lee, Chyi-Chia Richard; Brown, G Thomas; Moss, Joel; Darling, Thomas N

2017-07-01

Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC. To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex. A retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to connective tissue nevi in patients with TSC. Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis

Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors

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Dabora Sandra L

2010-02-01

Full Text Available Abstract Background Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2+/- mice, we compared kidney cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/- mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas associated with TSC, the severity of kidney cystadenomas increases with age in A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but angiogenesis inhibitors (sunitinib and bevacizumab and asparaginase are effective as single agents. However, these drugs are not as effective as rapamycin in that they increased median survival only by 24-27%, while rapamycin increased median survival by 173%. Conclusions Our results indicate that the A/J Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC

Tuberous Sclerosis Complex in 29 Children: Clinical and Genetic Analysis and Facial Angiofibroma Responses to Topical Sirolimus.

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Wang, Senfen; Liu, Yuanxiang; Wei, Jinghai; Zhang, Jian; Wang, Zhaoyang; Xu, Zigang

2017-09-01

Tuberous sclerosis complex (TSC) is a genetic disorder and facial angiofibromas are disfiguring facial lesions. The aim of this study was to analyze the clinical and genetic features of TSC and to assess the treatment of facial angiofibromas using topical sirolimus in Chinese children. Information was collected on 29 patients with TSC. Genetic analyses were performed in 12 children and their parents. Children were treated with 0.1% sirolimus ointment for 36 weeks. Clinical efficacy and plasma sirolimus concentrations were evaluated at baseline and 12, 24, and 36 weeks. Twenty-seven (93%) of the 29 patients had hypomelanotic macules and 15 (52%) had shagreen patch; 11 of the 12 (92%) who underwent genetic analysis had gene mutations in the TSC1 or TSC2 gene. Twenty-four children completed 36 weeks of treatment with topical sirolimus; facial angiofibromas were clinically undetectable in four (17%). The mean decrease in the Facial Angiofibroma Severity Index (FASI) score at 36 weeks was 47.6 ± 30.4%. There was no significant difference in the FASI score between weeks 24 and 36 (F = 1.00, p = 0.33). There was no detectable systemic absorption of sirolimus. Hypomelanotic macules are often the first sign of TSC. Genetic testing has a high detection rate in patients with a clinical diagnosis of TSC. Topical sirolimus appears to be both effective and well-tolerated as a treatment of facial angiofibromas in children with TSC. The response typically plateaus after 12 to 24 weeks of treatment. © 2017 Wiley Periodicals, Inc.

Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex

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Arulrajah, Sahayini; Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M.; Jordan, Lori; Khaykin, Elizabeth; Izbudak, Izlem

2009-01-01

Patients with tuberous sclerosis complex (TSC) frequently present with neurocognitive deficits which may be related to impaired white matter maturation. The purposes of our study were (a) to evaluate the white matter maturation in children and young adults with TSC by comparing the apparent diffusion coefficient (ADC) values of normal-appearing white matter (NAWM) with age-matched healthy controls and (b) to determine the association of NAWM-ADC values with the severity of neurological symptoms in TSC patients. Twenty-three TSC patients who underwent magnetic resonance imaging/diffusion-weighted imaging between January 2000 and January 2009 were studied. ADC values of NAWM were measured in the frontal, parietal, occipital lobes, and in the pons. ADC data were compared with age-matched normative data derived from healthy controls. Patients were neurologically scored by a pediatric neurologist. Two-sample t tests and linear regression were conducted using STATA software. ADC values of NAWM were higher in TSC patients compared with healthy controls; the increase, however, only reached statistical significance in the frontal white matter and pons in the age group between 96 and 144 months and in the right parietal and occipital white matter in the age group above 144 months. There was no significant change in neurological severity score per unit increase in ADC measurement. ADC values of NAWM appear increased in TSC patients. The abnormal ADC values suggest that myelination may be delayed/impaired in TSC patients, which could explain global neurocognitive deficits. Larger prospective studies, including diffusion tensor imaging, are necessary to validate our results. (orig.)

Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex

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Arulrajah, Sahayini; Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M. [Johns Hopkins Hospital, Division of Pediatric Radiology, Department of Radiology and Radiological Science, Baltimore, MD (United States); Jordan, Lori [Johns Hopkins School of Public Health, Division of Pediatric Neurology, Baltimore, MD (United States); Khaykin, Elizabeth [Johns Hopkins School of Public Health, Department of Mental Health, Baltimore, MD (United States); Izbudak, Izlem [Johns Hopkins Hospital, Division of Neuroradiology, Department of Radiology and Radiological Science, Baltimore, MD (United States)

2009-11-15

Patients with tuberous sclerosis complex (TSC) frequently present with neurocognitive deficits which may be related to impaired white matter maturation. The purposes of our study were (a) to evaluate the white matter maturation in children and young adults with TSC by comparing the apparent diffusion coefficient (ADC) values of normal-appearing white matter (NAWM) with age-matched healthy controls and (b) to determine the association of NAWM-ADC values with the severity of neurological symptoms in TSC patients. Twenty-three TSC patients who underwent magnetic resonance imaging/diffusion-weighted imaging between January 2000 and January 2009 were studied. ADC values of NAWM were measured in the frontal, parietal, occipital lobes, and in the pons. ADC data were compared with age-matched normative data derived from healthy controls. Patients were neurologically scored by a pediatric neurologist. Two-sample t tests and linear regression were conducted using STATA software. ADC values of NAWM were higher in TSC patients compared with healthy controls; the increase, however, only reached statistical significance in the frontal white matter and pons in the age group between 96 and 144 months and in the right parietal and occipital white matter in the age group above 144 months. There was no significant change in neurological severity score per unit increase in ADC measurement. ADC values of NAWM appear increased in TSC patients. The abnormal ADC values suggest that myelination may be delayed/impaired in TSC patients, which could explain global neurocognitive deficits. Larger prospective studies, including diffusion tensor imaging, are necessary to validate our results. (orig.)

Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin

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Seok-Hyung Kim

2011-03-01

Tuberous sclerosis complex (TSC is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin or TSC2 (encodes tuberin genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242 in the tsc2 gene. This tsc2vu242 allele encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc2vu242 is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2vu242/vu242 homozygous zebrafish, and is moderately increased in tsc2vu242/+ heterozygotes. Forebrain neurons are poorly organized in tsc2vu242/vu242 homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in chimeric animals, tsc2vu242/vu242 mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.

Development of hypomelanotic macules is associated with constitutive activated mTORC1 in tuberous sclerosis complex

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Møller, Lisbeth Birk; Schönewolf-Greulich, Bitten; Rosengren, Thomas

2017-01-01

TSC1 and TSC2 are genes mutated in the syndrome TSC (tuberous sclerosis complex). We describe a 3-generation family with 17 affected members, all presenting classic TSC features except renal manifestations. The disease segregates with a silent substitution in TSC2, c.4149C>T, p.(Ser1838Ser), whic...

Rhinophyma in tuberous sclerosis complex: case report with brief review of literature

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Friedrich, Reinhard E.

2014-11-01

Full Text Available Tuberous sclerosis or tuberous sclerosis complex (TSC is an autosomal dominant inherited disease characterized by the triad epilepsy, hamartomas (angiofibroma and reduced intellectual capacity. Phenotype can vary considerably. Almost all patients with TSC have at least one characteristic dermatologic feature. Facial angiofibroma can cause severe disfigurement. It may involve the cheeks, perioral region and nose, resulting in thick layers of nodular and pustular skin. Aesthetic surgery of the face comprises an individually adapted ablation of the affected skin regions in order to improve physical appearance. Reports on the subject of surgery for nasal angiofibroma confirm the homogenous transformation of the connective tissues by this hamartoma. Hitherto there is only one report in the literature describing the typical epithelial alterations of the nasal skin compatible with a rhinophyma and adjacent angiofibroma. Here we report the successful electrosurgical treatment of a patient with TSC and extensive sebaceous glands giving rise to a rhinophyma in close association with angiofibroma.

Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study.

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David N Franz

Full Text Available Everolimus, a mammalian target of rapamycin (mTOR inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs and other manifestations of tuberous sclerosis complex (TSC. However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828.EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years who received ≥1 dose of everolimus (median duration, 47.1 months, 57.7% (95% confidence interval [CI], 47.9-67.0 achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2% achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence suspected to be treatment-related were stomatitis (43.2% and mouth ulceration (32.4%.Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a

Significance of tuber size for complications of tuberous sclerosis complex.

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Pascual-Castroviejo, I; Hernández-Moneo, J L; Pascual-Pascual, S I; Viaño, J; Gutiérrez-Molina, M; Velazquez-Fragua, R; Quiñones Tapia, D; Morales Bastos, C

2013-01-01

Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Tuberous sclerosis complex in a child: diagnosis and management

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Prastiya Indra Gunawan

2010-06-01

Full Text Available Tuberous sclerosis complex (TSC is a multisystem, autosomal dominant disorder affecting children and adults, resulted from mutations in one of two genes, TSC1 (encoding hamartin or TSC2 (encoding tuberin genes located on chromosomes 9 and 16 respectively.1,2 Synonyms of TSC are Bourneville Pringle syndrome, epiloia, or tuberosclerosis. This disorder is characterized by seizures, mental disability, and small noncancerous tumors on the skin and other body tissues, such as brain, eye, lung, and kidney. The classic triad are seizures, mental retardation, and cutaneous angiofibromas.3

Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

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Jeong, Anna; Wong, Michael

2016-09-01

Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley

TSC response of irradiated CVD diamond films

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Borchi, E; Bucciolini, M; Guasti, A; Mazzocchi, S; Pirollo, S; Sciortino, S

1999-01-01

CVD diamond films have been irradiated with electrons, sup 6 sup 0 Co photons and protons in order to study the dose response to exposure to different particles and energies and to investigate linearity with dose. The Thermally Stimulated Current (TSC) has been studied as a function of the dose delivered to polymethilmetacrilate (PMMA) in the range from 1 to 12 Gy with 20 MeV electrons from a linear accelerator. The TSC spectrum has revealed the presence of two components with peak temperatures of about 470 and 520 K, corresponding to levels lying in the diamond band gap with activation energies of the order of 0.7 - 1 eV. After the subtraction of the exponential background the charge emitted during the heating scan has been evaluated and has been found to depend linearly on the dose. The thermally emitted charge of the CVD diamond films has also been studied using different particles. The samples have been irradiated with the same PMMA dose of about 2 Gy with 6 and 20 MeV electrons from a Linac, sup 6 sup 0 ...

High gamma-aminobutyric acid level in cortical tubers in epileptic infants with tuberous sclerosis complex measured with the MEGA-editing J-difference method and a three-Tesla clinical MRI Instrument.

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Taki, Masako Minato; Harada, Masafumi; Mori, Kenji; Kubo, Hitoshi; Nose, Ayumi; Matsuda, Tsuyoshi; Nishitani, Hiromu

2009-10-01

The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development.

Analysis of twenty pediatric cases of tuberous sclerosis complex: Are we doing enough?

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Jyoti Nath

2015-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is a neuro-cutaneous disease characterized by hamartoma formation in various organs particularly the skin, brain, eye, kidney, heart and lungs. Patients usually have multisystem involvement and thus present to different medical specialties with varied complaints while the true nature of the disease and the hidden manifestations may remain unattended. A im: To assess the frequency and characteristics of various cutaneous and systemic manifestations in TSC and the total impact on different system in a cohort of pediatric patients. Methods: The study included 20 patients fulfilling the diagnostic criteria for TSC from dermatology, pediatrics, and neurology department. Detailed history, examination, and investigations such as chest X-ray, electrocardiography (ECG, ultrasonography (USG abdomen, echocardiography, fundoscopy, computed tomography (CT scan of brain and abdomen were done. Results: Dermatological manifestations included ash leaf macules, angiofibromas, shagreen patch, and fibrous plaque. Systemic findings observed were subependymal calcified nodules, subependymal giant cell astrocytoma, cortical tubers, renal cysts, angiomyolipomas, lung cyst, retinal hamartomas, mental deficits and epilepsy. Limitations: Wechsler′s Intelligence Scale for Children would have been more appropriate for assessing the intelligence. Dental check-up was not done in our group of patients. Conclusion: Our study highlights the wide variety of cutaneous and systemic manifestations of TSC. The study emphasizes the need for comprehensive multidisciplinary treatment and periodic follow-up which are necessary for appropriate management of this multisystem disorder. Counseling regarding education and rehabilitation of the patients and genetic counseling of parents are important.

Tuberous sclerosis complex: Recent advances in manifestations and therapy.

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Wataya-Kaneda, Mari; Uemura, Motohide; Fujita, Kazutoshi; Hirata, Haruhiko; Osuga, Keigo; Kagitani-Shimono, Kuriko; Nonomura, Norio

2017-09-01

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex. © 2017 The Japanese Urological Association.

TSC plasma halo simulation of a DIII-D vertical displacement episode

International Nuclear Information System (INIS)

Sayer, R.O.; Peng, Y.K.M.; Jardin, S.C.

1993-01-01

A benchmark of the Tokamak Simulation Code (TSC) plasma halo model has been achieved by calibration against a DIII-D vertical displacement episode (VDE) consisting of vertical drift, thermal quench and current quench. With a suitable halo surrounding the main plasma, the TSC predictions are in good agreement with experimental results for the plasma current decay, plasma trajectory, toroidal and poloidal vessel currents, and for the magnetic probe and flux loop values for the entire VDE. Simulations with no plasma halo yield much faster vertical motion and significantly worse agreement with the magnetics and flux loop data than do halo simulations. (author). 12 refs, 13 figs

Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R.

Science.gov (United States)

Filippakis, Harilaos; Alesi, Nicola; Ogorek, Barbara; Nijmeh, Julie; Khabibullin, Damir; Gutierrez, Catherine; Valvezan, Alexander J; Cunningham, James; Priolo, Carmen; Henske, Elizabeth P

2017-06-13

Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL-R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and pointing toward the translational potential of these pathways for the therapy of TSC.

Heat-Mirror Spectral Profile Optimization for TSC Hybrid Solar Conversion

Science.gov (United States)

Soule, D. E.; Wood, S. E.

1986-09-01

The efficiencies for total solar cogeneration (TSC) can be optimized by tailoring the transparent heat-mirror (HM) beam splitter spectral profile shape. The entire output is cogenerated by photovoltaic/photothermal conversions into three energy forms: electricity (PV) 18V d.c./module, high-temperature heat (HT) 400°C, and low-temperature heat (LT) 70°C. The emphasis is to maximize the high-quality energy sum PV + HT, while maintaining PV at a high level. A generalized 5-parameter double Fermi model for the HM spectral profile is investigated allowing for a wide parametric range and profile asymmetry. The projected optimized TSC conversion efficiencies are: PV = 14.3%, HT = 43.5%, and LT = 42.2% with a high-quality energy sum of PV + HT = 57.8%. The approach to this optimum HM spectral profile by experimental HM films such as ITO are discussed.

An Australian tuberous sclerosis cohort: are surveillance guidelines being met?

NARCIS (Netherlands)

Chopra, M.; Lawson, J.A.; Wilson, M.; Kennedy, S.E.; Taylor, P.; Buckley, M.F.; Wargon, O.; Parasivam, G.; Camphausen, C.; Yates, D.; Mowat, D.

2011-01-01

AIM: This study aims to describe the phenotypic and genotypic characteristics of 45 Australian patients with tuberous sclerosis complex (TSC), to assess risk factors for intellectual disability, to compare patients with TSC1 and TSC2 mutations and to assess adherence to surveillance recommendations.

Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.

Science.gov (United States)

Weston, Matthew C; Chen, Hongmei; Swann, John W

2014-01-01

The Pten and Tsc1 genes both encode proteins that repress mechanistic target of rapamycin (mTOR) signaling. Disruption of either gene in the brain results in epilepsy and autism-like symptoms in humans and mouse models, therefore it is important to understand the molecular and physiological events that lead from gene disruption to disease phenotypes. Given the similar roles these two molecules play in the regulation of cellular growth and the overlap in the phenotypes that result from their loss, we predicted that the deletion of either the Pten or Tsc1 gene from autaptic hippocampal neurons would have similar effects on neuronal morphology and synaptic transmission. Accordingly, we found that loss of either Pten or Tsc1 caused comparable increases in soma size, dendrite length and action potential properties. However, the effects of Pten and Tsc1 loss on synaptic transmission were different. Loss of Pten lead to an increase in both excitatory and inhibitory neurotransmission, while loss of Tsc1 did not affect excitatory neurotransmission and reduced inhibitory transmission by decreasing mIPSC amplitude. Although the loss of Pten or Tsc1 both increased downstream mTORC1 signaling, phosphorylation of Akt was increased in Pten-ko and decreased in Tsc1-ko neurons, potentially accounting for the different effects on synaptic transmission. Despite the different effects at the synaptic level, our data suggest that loss of Pten or Tsc1 may both lead to an increase in the ratio of excitation to inhibition at the network level, an effect that has been proposed to underlie both epilepsy and autism.

Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

International Nuclear Information System (INIS)

Yildirim, Hatice; Guler, Emine; Yavuz, Murat; Ozturk, Nurdan; Kose Yaman, Pelin; Subasi, Elif; Sahin, Elif; Timur, Suna

2014-01-01

A conformationally rigid half-sandwich organoruthenium (II) complex [(η 6 -p-cymene)RuClTSC N–S ]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh 3 ) 2 TSC N–S ] (2) have been synthesized from the reaction of [{(η 6 -p-cymene)RuCl} 2 (μ-Cl) 2 ] and [Ru(H)(Cl)(CO)(PPh 3 ) 3 ] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity

Renal angiomyolipoma bleeding in a patient with TSC2/PKD1 contiguous gene syndrome after 17 years of renal replacement therapy.

Science.gov (United States)

Furlano, Mónica; Barreiro, Yaima; Martí, Teresa; Facundo, Carme; Ruiz-García, César; DaSilva, Iara; Ayasreh, Nadia; Cabrera-López, Cristina; Ballarín, José; Ars, Elisabet; Torra, Roser

We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis (TS) and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML), which are common benign tumours in patients with TS. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding. Selective embolisation was performed. Our patient could have benefited from the administration of mTOR inhibitors at transplant. This therapy is immunosuppressive and reduces the size of benign tumours in TS as well as the risk of rupture and bleeding. This patient did not receive mTOR inhibitors at the time of the transplant because the relationship between mTOR inhibitors and TS was unknown at that time. This case confirms the persistent risk of renal AML bleeding for both transplanted patients and patients on dialysis. As a result, we would recommend routine check-ups of native kidneys and nephrectomy assessment. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex : A clinical epidemiological study

NARCIS (Netherlands)

S.E. Mous (Sabine); I.E. Overwater (Iris); R. Vidal Gato (Rita); J. Duvekot (Jorieke); L.W. ten Hoopen (Leontine); M. Leguin (Maarten); M.C.Y. de Wit (Marie Claire); G.C. Dieleman (Gwen)

2017-01-01

textabstractTuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial

Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

Energy Technology Data Exchange (ETDEWEB)

Yildirim, Hatice [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Guler, Emine [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Yavuz, Murat, E-mail: myavuz@dicle.edu.tr [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Dicle University, Faculty of Science, Department of Chemistry, 21280 Diyarbakir (Turkey); Ozturk, Nurdan; Kose Yaman, Pelin [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Subasi, Elif; Sahin, Elif [Dokuz Eylul University, Faculty of Science, Department of Chemistry, 35160 Buca, Izmir (Turkey); Timur, Suna [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Ege University, Institute on Drug Abuse, Toxicology and Pharmaceutical Science (BATI), 35100 Bornova, Izmir (Turkey)

2014-11-01

A conformationally rigid half-sandwich organoruthenium (II) complex [(η{sup 6}-p-cymene)RuClTSC{sup N–S}]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh{sub 3}){sub 2}TSC{sup N–S}] (2) have been synthesized from the reaction of [{(η"6-p-cymene)RuCl}{sub 2}(μ-Cl){sub 2}] and [Ru(H)(Cl)(CO)(PPh{sub 3}){sub 3}] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity.

Development of a Novel NMR-based Rheb GTPase Assay and Molecular Characterization of TSC2 GAP Activity

Science.gov (United States)

2010-05-01

GTPase) that belongs to the Ras superfamily and has homologs in yeast, fungi , slime mold, fruit fly, zebra fish, and mammals (1–3). Ge- netic and...characterization of TSC2 disease mutations affecting its GAP activity (months 9-12) While the final aspects of this task are yet to be completed, we have...domain mutants of TSC2 that we examined affected its enzymatic activ- ity. This method can now be applied to study the function and regulation of other

Rare lung manifestation of multifocal micronodular pneumocyte hyperplasia in a teenage girl with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Ha, Seung Mi; Yoon, Hye Kyung; Lee, Seung Koo [Kangwon National University Hospital, Chuncheon (Korea, Republic of)

2016-08-15

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a relatively rare pulmonary disorder that can be associated with tuberous sclerosis complex (TSC). It has been rarely reported in children or adolescents. MMPH is a hamartomatous process of the lung with multiple small nodules, composed of type II pneumocytes. Plain radiography and chest CT in MMPH may demonstrate numerous small nodules measuring 1-10 mm in diameters, distributed randomly throughout both lungs. If MMPH is an initial presentation of TSC, and unless we are familiar with this lung manifestation of TSC, radiologic findings can mimic miliary tuberculosis or metastatic disease. We report a teenage girl with TSC and histologically confirmed MMPH which mimicked miliary tuberculosis at the initial presentation.

Rare lung manifestation of multifocal micronodular pneumocyte hyperplasia in a teenage girl with tuberous sclerosis complex

International Nuclear Information System (INIS)

Ha, Seung Mi; Yoon, Hye Kyung; Lee, Seung Koo

2016-01-01

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a relatively rare pulmonary disorder that can be associated with tuberous sclerosis complex (TSC). It has been rarely reported in children or adolescents. MMPH is a hamartomatous process of the lung with multiple small nodules, composed of type II pneumocytes. Plain radiography and chest CT in MMPH may demonstrate numerous small nodules measuring 1-10 mm in diameters, distributed randomly throughout both lungs. If MMPH is an initial presentation of TSC, and unless we are familiar with this lung manifestation of TSC, radiologic findings can mimic miliary tuberculosis or metastatic disease. We report a teenage girl with TSC and histologically confirmed MMPH which mimicked miliary tuberculosis at the initial presentation

Development of a TSC-Setup for the Characterization of Electron and Hole Traps in Irradiated Silicon Sensors

CERN Document Server

Stricker, Miriam

2015-01-01

For the characterization of radiation damage in silicon detectors a low-noise TSC-Setup was built to analyze charge trapping in the temperature range between 15 K and 250 K. The setup offers the possibility to perform Thermally Stimulated Current (TSC) and IV measurements and also to anneal samples at temperatures up to 180 ◦C. A first annealing study on a proton irradiated silicon pad sensor was performed. This study focuses mainly on the variation of the trap concentration and the results are compared to literature.

Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous Sclerosis Complex; Case reports and review of literature

Directory of Open Access Journals (Sweden)

Amna Al-Futaisi

2016-11-01

Full Text Available Tuberous sclerosis complex (TSC is a multisystem neurocutaneous disorder inherited in an autosomal dominant manner and characterised by benign tumours in the brain and other vital organs such as the heart, eyes, kidneys, skin and lungs. Links between autism spectrum disorder (ASD and TSC have been postulated for many decades, with TSC considered to be one of the main syndromic causes of ASD; however, precise confirmation of a relationship between these two disorders required validated diagnostic tools. Fortunately, accurate evaluation of this relationship is now possible with standardised criteria for ASD diagnosis. We report three children who presented to the Sultan Qaboos University Hospital, Muscat, Oman, between 2014 and 2015 with ASD and TSC. These cases demonstrate the spectrum of neuropsychiatric involvement in TSC and highlight the importance of screening children with TSC for ASD features in order to encourage the early enrolment of these children in educational and rehabilitation programmes.

Recurrent meningitis associated with frontal sinus tuber encephalocele in a patient with tuberous sclerosis.

Science.gov (United States)

Elbabaa, Samer K; Riggs, Angela D; Saad, Ali G

2011-07-01

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that commonly affects the CNS. The most commonly associated brain tumors include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). The authors report an unusual case of recurrent meningitis due to a tuber-containing encephalocele via the posterior wall of the frontal sinus. An 11-year-old girl presented with a history of TSC and previous SEGA resection via interhemispheric approach. She presented twice within 4 months with classic bacterial meningitis. Cerebrospinal fluid cultures revealed Streptococcus pneumoniae. Computed tomography and MR imaging of the brain showed a right frontal sinus encephalocele via a posterior frontal sinus wall defect. Both episodes of meningitis were treated successfully with standard regimens of intravenous antibiotics. The neurosurgical service was consulted to discuss surgical options. Via a bicoronal incision, a right basal frontal craniotomy was performed. A large frontal encephalocele was encountered in the frontal sinus. The encephalocele was herniating through a bony defect of the posterior sinus wall. The encephalocele was ligated and resected followed by removing frontal sinus mucosa and complete cranialization of frontal sinus. Repair of the sinus floor was conducted with fat and pericranial grafts followed by CSF diversion via lumbar drain. Histopathology of the resected encephalocele showed a TSC tuber covered with respiratory (frontal sinus) mucosa. Tuber cells were diffusely positive for GFAP. The patient underwent follow-up for 2 years without evidence of recurrent meningitis or CSF rhinorrhea. This report demonstrates that frontal tubers of TSC can protrude into the frontal sinus as acquired encephaloceles and present with recurrent meningitis. To the authors' knowledge, recurrent meningitis is not known to coincide with TSC. Careful clinical and radiographic follow-up for frontal tubers in patients with TSC is

The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines

International Nuclear Information System (INIS)

Eeghen, Agnies M. van; Teran, Laura Ortiz; Johnson, Jason; Caruso, Paul; Pulsifer, Margaret B.; Thiele, Elizabeth A.

2013-01-01

The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging. Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients. A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007). A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features. (orig.)

The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines

Energy Technology Data Exchange (ETDEWEB)

Eeghen, Agnies M. van [Massachusetts General Hospital, Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Boston, MA (United States); Erasmus Medical Centre, ENCORE, Expertise Centre for Neurodevelopmental Disorders, Department of Neuroscience, Rotterdam (Netherlands); Teran, Laura Ortiz; Johnson, Jason; Caruso, Paul [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Pulsifer, Margaret B. [Massachusetts General Hospital, Department of Psychiatry, Psychological Assessment Center, Boston, MA (United States); Thiele, Elizabeth A. [Massachusetts General Hospital, Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Boston, MA (United States)

2013-08-15

The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging. Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients. A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007). A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features. (orig.)

Comment on "A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation": building a model of the mTOR signaling network with a potentially faulty tool.

Science.gov (United States)

Manning, Brendan D

2012-07-10

In their study published in Science Signaling (Research Article, 27 March 2012, DOI: 10.1126/scisignal.2002469), Dalle Pezze et al. tackle the dynamic and complex wiring of the signaling network involving the protein kinase mTOR, which exists within two distinct protein complexes (mTORC1 and mTORC2) that differ in their regulation and function. The authors use a combination of immunoblotting for specific phosphorylation events and computational modeling. The primary experimental tool employed is to monitor the autophosphorylation of mTOR on Ser(2481) in cell lysates as a surrogate for mTOR activity, which the authors conclude is a specific readout for mTORC2. However, Ser(2481) phosphorylation occurs on both mTORC1 and mTORC2 and will dynamically change as the network through which these two complexes are connected is manipulated. Therefore, models of mTOR network regulation built using this tool are inherently imperfect and open to alternative explanations. Specific issues with the main conclusion made in this study, involving the TSC1-TSC2 (tuberous sclerosis complex 1 and 2) complex and its potential regulation of mTORC2, are discussed here. A broader goal of this Letter is to clarify to other investigators the caveats of using mTOR Ser(2481) phosphorylation in cell lysates as a specific readout for either of the two mTOR complexes.

Clinical features of tuberous sclerosis complex in children with epilepsy

Directory of Open Access Journals (Sweden)

Dong LI

2014-12-01

Full Text Available Objective To explore the clinical features of tuberous sclerosis complex (TSC in children with epilepsy.  Methods The clinical data of 36 TSC children complicated with epilepsy were analyzed retrospectively.  Results All children had epilepsy as first symptom: 23 cases of seizures happened on age less than one year old (63.89%, 8 cases on age 1-3 years old (22.22%, and 5 cases on age more than 3 years old (13.89% . Main attack types were as follows: 12 cases with focal seizures (33.33% , 5 cases with generalized seizures (13.89% , 7 cases with spasms (19.44% and 12 cases (33.33% with mixed seizures. Mental retardation was found in 19 cases (67.86%. Among 30 cases who received brain MRI examination, all had subependymal nodules, 26 cases (86.67% were complicated with cortical and subcortical nodules, 2 cases (6.67% with subependymal giant cell astrocytoma (SEGA, one case (3.33% with pachygyria. EEG examination showed interictal epileptiform discharges in 34 cases (94.44% , including multifocal discharges in 12 patients (35.29% , generalized discharges in 8 patients (23.53% , focal discharges and hypsarrhythmia in 7 patients (20.59% respectively. Seizures were monitored in 8 patients, and the types included spasms in 4 cases, focal seizures in 3 cases, and myoclonic seizures in one case. Seventeen cases (47.22% took one single antiepileptic drug, 12 cases (33.33% took two drugs, and 7 cases (19.44% took three drugs, while one of them underwent surgical treatment. After 0.50-10 year follow-up, seizures free happened in 7 cases (19.44%, improved in 16 cases (44.44%, and invalid in 13 cases (36.11%.  Conclusions Epilepsy is the most common nervous system performance in children TSC, and most seizures begin to happen in infants. The main types of onset are partial seizures and spasms. Most of the patients get improved with antiepileptic drugs. doi: 10.3969/j.issn.1672-6731.2014.12.011

Pulmonary choriostoma in a case of tuberous sclerosis complex

Directory of Open Access Journals (Sweden)

S Spalgais

2015-01-01

Full Text Available A 52 years old lady was diagnosed to have Tuberous Sclerosis Complex (TSC on the basis of 2 major and one minor criterion. She had family history of similar complaints in her sister and two sons. There was involvement of kidney in the form of angiomyolipoma, skin in the form of facial angiofibroma and teeth with a dental pit. She had an unusual lung involvement in the form of multiple small choristomas. Choristoma was diagnosed on transbronchial lung biopsy and was present in the form of disorganised striated muscles. The reported pulmonary manifestations of TCS i.e. lymphangioleiomyomatosis (LAM and multifocal micronodular pneumocyte hyperplasia (MMPH are types of hamartomas. Hamartomas and choristomas are both types of disorganized tissue. ′Choristoma′of lung in TSC however is not reported. Clinopathological correlation of pulmonary hamartoma and choristoma, and treatment in TSC has been discussed.

The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

Science.gov (United States)

Bissler, John J; Franz, David N; Frost, Michael D; Belousova, Elena; Bebin, E Martina; Sparagana, Steven; Berkowitz, Noah; Ridolfi, Antonia; Kingswood, J Christopher

2018-01-01

Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m 2 /day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged 20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed. Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

Tuberous sclerosis complex in the Western Cape, South Africa: The ...

African Journals Online (AJOL)

107, No. 4. IN PRACTICE. Tuberous sclerosis complex (TSC) is a genetically inherited condition that manifests with benign non-invasive hamartomas in multiple .... Corticosteroids are the recommended treatment for infants with epileptic ...

Simulations of ITER disruption and VDE scenarios with TSC and comparison with DINA results

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2008-01-01

Vertical Displacement Events (VDEs) and plasma current disruptions pose one of the major concerns for the lifetime of in-vessel components in ITER, as well as for machine robustness, as large electromagnetic and thermal loads will induced at such events. Hence, accurate modelling of such events is crucial for estimating disruption induced forces. In the past, ITER disruption modelling has been carried out for ITER using the DINA code. However, since predictive simulations of such events depend on a large number of model assumptions, there exists chances of large error bars on the model predictions. As such it is imperative to validate the code results with other models. Towards this objective, we have carried out the VDE and Disruption simulations using the TSC code and the results are compared with the earlier DINA predictions. A detailed electromagnetic model of the ITER vessel, blankets and the first wall components has been created in TSC. In both VDE and disruption cases, the initial plasma is taken as ITER reference scenario 2 end of burn (EOB) specifications with I p = 15 MA, B t = 5 .3 T, e > 8.8 keV, e > = 1.1 x 10 20 m -3 . The plasma current disruption is initiated by dropping the plasma β in 1 msec, so that after the β crash e > = 6 eV, following which the plasma position control is switched off, resulting in a plasma current quench in about 65 msec. On the other hand, in the VDE case, the plasma control is switched off which results in either upward or downward VDE depending on the initial position of the plasma current centroid. In this case the plasma current remains close to 15 MA for a much longer time, about 700 msec in the simulations till the edge safety factor (q) becomes less than 1.5, following which the β is crashed resulting in plasma current quench. Significant differences exist in the DINA and TSC models, for example, even though the plasma current quench rate predicted by the models matches well in till the halo currents start flowing

Clinical features and genetic analysis of tuberous sclerosis pedigrees

Directory of Open Access Journals (Sweden)

LI Ya-qin

2012-06-01

Full Text Available Objective In order to understand tuberous sclerosis complex better, the clinical manifestation, imaging characteristics, and genetic characteristics of tuberous sclerosis complex from 3 pedigrees were investigated. Methods The clinical data of patients from 3 tuberous sclerosis families were collected. The gene mutation type of TSC2 of proband in pedigree one was determined by PCR and direct gene sequencing. Results All of the 3 probands went to our clinic for the reason of epilepsy. Brain imaging examination noted intracranial nodular calcification. EEG showed comprehensive spines and slow waves, sharp waves. The pedigree 1 has family history, two male patients and 3 female patients, all had facial angiofibromas and epilepsy. Gene mutation analysis of TSC2 demonstrated the c.1444-2A > C mutation in index patient. All the 3 index patients had mental retardation, autism and hypopigmented macule. Conclusion For infants and young children with epilepsy as the first symptom, accompanied by mental retardation, autism, facial angiofibromas or hypopigmented macule and other skin abnormalities, brain imaging examination noted intracranial nodular calcification are highly suggestive of tuberous sclerosis complex. TSC1 and TSC2 gene analysis contribute to the diagnosis of this disease, genentic counseling and prenatal diagnosis.

Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

Directory of Open Access Journals (Sweden)

Wyatt B Potter

Full Text Available Tuberous sclerosis complex (TSC is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/- CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/- hippocampal slices. We also report that adult TSC2(+/- mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.

Evaluation of the of antibacterial efficacy of polyvinylpyrrolidone (PVP) and tri-sodium citrate (TSC) silver nanoparticles

Science.gov (United States)

Dey, Arindam; Dasgupta, Abhirup; Kumar, Vijay; Tyagi, Aakriti; Verma, Anita Kamra

2015-09-01

We present silver nanoparticles as the new age broad spectrum antibiotic. Siver nanoparticles exhibit unique physical and chemical properties that make them suitable for understanding their biological potential as antimicrobials. In this study, we explored the antibacterial activity of silver nanoparticles (TSC-AgNPs) and silver nanoparticles doped with polyvinylpyrrolidone (PVP-AgNPs) against Gram-negative and Gram-positive bacteria, Escherichia coli (DH5α) and Staphylococcus aureus, (ATCC 13709). Nucleation and growth kinetics during the synthesis process of AgNPs were precisely controlled using citrate (TSC) and further doped with polyvinylpyrrolidone (PVP). This resulted in the formation of two different sized nanoparticles 34 and 54 nm with PDI of 0.426 and 0.643. The physical characterization was done by nanoparticle tracking analysis and scanning electron microscopy, the results of which are in unison with the digital light scattering data. We found the bactericidal effect for both TSC-AgNPs and PVP-AgNPs to be dose-dependent as determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against E. coli and S. aureus. Interestingly, we also observed that AgNPs showed enhanced antimicrobial activity with a MIC of 26.75 and 13.48 µg/ml for E. coli and S. aureus, respectively, while MBC for AgNPs are 53.23 and 26.75 µg/ml for E. coli and S. aureus, respectively. Moreover, AgNPs showed increased DNA degradation as observed confirming its higher efficacy as antibacterial agent than the PVP doped AgNPs.

siRNA-mediated Erc gene silencing suppresses tumor growth in Tsc2 mutant renal carcinoma model.

Science.gov (United States)

Imamura, Osamu; Okada, Hiroaki; Takashima, Yuuki; Zhang, Danqing; Kobayashi, Toshiyuki; Hino, Okio

2008-09-18

Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery of siRNAs for stable treatment except short hairpin RNAs (shRNAs). On the other hand, there are many reports of systemic delivery of siRNAs for transient treatment using liposome carriers and others. With regard to shRNAs, a report showed fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Therefore, we decided to use original siRNA microspheres instead of shRNA for stable treatment of disease. In this study, we designed rat-specific siRNA sequences for Erc/mesothelin, which is a tumor-specific gene expressed in the Eker (Tsc2 mutant) rat model of hereditary renal cancer and confirmed the efficacy of gene silencing in vitro. Then, by using siRNA microspheres, we found that the suppression of Erc/mesothelin caused growth inhibition of Tsc2 mutant renal carcinoma cells in tumor implantation experiments in mice.

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

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Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

2013-01-01

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

A time-resolved current method and TSC under vacuum conditions of SEM: Trapping and detrapping processes in thermal aged XLPE insulation cables

Science.gov (United States)

Boukezzi, L.; Rondot, S.; Jbara, O.; Boubakeur, A.

2017-03-01

Thermal aging of cross-linked polyethylene (XLPE) can cause serious concerns in the safety operation in high voltage system. To get a more detailed picture on the effect of thermal aging on the trapping and detrapping process of XLPE in the melting temperature range, Thermal Stimulated Current (TSC) have been implemented in a Scanning Electron Microscope (SEM) with a specific arrangement. The XLPE specimens are molded and aged at two temperatures (120 °C and 140 °C) situated close to the melting temperature of the material. The use of SEM allows us to measure both leakage and displacement currents induced in samples under electron irradiation. The first represents the conduction process of XLPE and the second gives information on the trapping of charges in the bulk of the material. TSC associated to the SEM leads to show spectra of XLPE discharge under thermal stimulation using both currents measured after electron irradiation. It was found that leakage current in the charging process may be related to the physical defects resulting in crystallinity variation under thermal aging. However the trapped charge can be affected by the carbonyl groups resulting from the thermo-oxidation degradation and the disorder in the material. It is evidenced from the TSC spectra of unaged XLPE that there is no detrapping charge under heat stimulation. Whereas the presence of peaks in the TSC spectra of thermally aged samples indicates that there is some amount of trapped charge released by heating. The detrapping behavior of aged XLPE is supported by the supposition of the existence of two trap levels: shallow traps and deep traps. Overall, physico-chemical reactions under thermal aging at high temperatures leads to the enhancement of shallow traps density and changes in range of traps depth. These changes induce degradation of electrical properties of XLPE.

Clinical report: a rare co-occurrence of tuberous sclerosis complex and Rett syndrome in a girl with mental retardation, epilepsy and autism

OpenAIRE

Belousova, Elena; Sukhorukov, Vladimir; Dorofeeva, Marina; Shagam, Lev; Vlodavetz, Dmitrii V.

2017-01-01

Introduction. There are some genetic disorders with combination of mental retardation, epilepsy and autism in which the abnormal mammalian Target of Rapamycin (m-TOR) signaling is implicated. The most important of them is tuberous sclerosis complex (TSC), but the disturbances of the m-TOR pathway can also be detected in Rett syndrome (RS), Fragile X syndrome and Down syndrome. We describe the rare case of co-occurrence of TSC and RS. Case study. The female child was born at term by normal de...

Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis

International Nuclear Information System (INIS)

Jahodova, A.; Krsek, P.; Kyncl, M.; Jezdik, P.; Kudr, M.; Komarek, V.; Jayakar, P.; Miller, I.; Resnick, T.

2014-01-01

Objective: Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data. Methods: Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC. Results: MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p < 0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients. Conclusion: Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by “FCD-like” changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC

Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis

Energy Technology Data Exchange (ETDEWEB)

Jahodova, A., E-mail: a.jagoda@email.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Krsek, P., E-mail: pavel.krsek@post.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Kyncl, M., E-mail: martinkyn@seznam.cz [Department of Radiology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Jezdik, P., E-mail: jezdip1@feld.cvut.cz [Department of Measurement, Faculty of Electric, Czech Technical University Prague, Technicka 2, CZ 166 27 Prague 6 (Czech Republic); Kudr, M., E-mail: mat.kudr@gmail.com [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Komarek, V., E-mail: vladimir.komarek@fnmotol.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Jayakar, P., E-mail: Prasanna.Jayakar@mch.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Miller, I., E-mail: ian.miller@mchdocs.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Resnick, T., E-mail: trevor.resnick@mch.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Department of Neurology, University of Miami Miller School of Medicine, Miami, FL (United States); and others

2014-04-15

Objective: Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data. Methods: Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC. Results: MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p < 0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients. Conclusion: Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by “FCD-like” changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC.

Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

Science.gov (United States)

... Privacy Policy Sitemap Learn Engage Donate About TSC Attention Deficit Hyperactivity Disorder and TSC What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a common neurobehavioral disorder. It is ...

Ballistic Simulation Method for Lithium Ion Batteries (BASIMLIB) Using Thick Shell Composites (TSC) in LS-DYNA

Science.gov (United States)

2016-08-04

BAllistic SImulation Method for Lithium Ion Batteries (BASIMLIB) using Thick Shell Composites (TSC) in LS-DYNA Venkatesh Babu, Dr. Matt Castanier, Dr...and behavior of the cells through experimental and modeling at their crash worthiness laboratory • Most of the simulation work on the batteries are...at a single cell level and gap exists to simulate the batteries at their full pack capacity - Firstly, requires an enormous amount of computational

Guidance of reactor operators and TSC personnel with the severe accident management guidance under shutdown and low power conditions

International Nuclear Information System (INIS)

Van Haesendonck, M.F.; Prior, R.P.

2000-01-01

The Westinghouse Owners Group Severe Accident Management Guidance (WOG SAMG) was developed between 1991 and 1994. The primary goals for severe accident management that form the basis of the WOG SAMG are to terminate any radioactive releases to the environment; to prevent failure of any containment fission product boundary and to return the plant to a controlled stable condition. The WOG SAMG is primarily a TSC tool for mitigation of low probability core damage events. The philosophy is that control room operators should remain focused on the prevention of core damage, whereas the TSC personnel should concentrate on the mitigation of the severe accident. The symptom based package is built up as a structured process for choosing appropriate actions based on actual plant conditions. No detailed knowledge of severe accident phenomena is required. The scope of the WOG SAMG is limited to severe accidents resulting from initiating events occurring during full power operation. However, a number of studies such as the EdF EPS 1300 Probabilistic Safety Assessment (PSA), the shutdown Probabilistic Risk Assessment (PRA) for Surry, the BERA shutdown PRA for Beznau, the EPRI/ Westinghouse ORAM methodology etc. have shown that the frequency of core damage (a severe accident) during shutdown and low power operation can be of the same order of magnitude as for full power operation. The at-power SAMG is viewed as the resolution of the severe accident issue. Similarly, it is expected that as shutdown PRAs mature, the final resolution of the severe accident issue will lie in SAMG for low power and shutdown operation. Therefore in resolution of this issue, Westinghouse has developed the Shutdown Severe Accident Management Guidance (SSAMG) which gives guidance for both control room and TSC personnel to mitigate a severe accident under shutdown or low power conditions. In the last few years, many LWR plants have been implementing SAMG. In the US, all plants have developed SAMG, and many

Thermal Scanning Conductometry (TSC) as a General Method for Studying and Controlling the Phase Behavior of Conductive Physical Gels.

Science.gov (United States)

Bielejewski, Michal

2018-01-23

The thermal scanning conductometry protocol is a new approach in studying ionic gels based on low molecular weight gelators. The method is designed to follow the dynamically changing state of the ionogels, and to deliver more information and details about the subtle change of conductive properties with an increase or decrease in the temperature. Moreover, the method allows the performance of long term (i.e. days, weeks) measurements at a constant temperature to investigate the stability and durability of the system and the aging effects. The main advantage of the TSC method over classical conductometry is the ability to perform measurements during the gelation process, which was impossible with the classical method due to temperature stabilization, which usually takes a long time before the individual measurement. It is a well-known fact that to obtain the physical gel phase, the cooling stage must be fast; moreover, depending on the cooling rate, different microstructures can be achieved. The TSC method can be performed with any cooling/heating rate that can be assured by the external temperature system. In our case, we can achieve linear temperature change rates between 0.1 and approximately 10 °C/min. The thermal scanning conductometry is designed to work in cycles, continuously changing between heating and cooling stages. Such an approach allows study of the reproducibility of the thermally reversible gel-sol phase transition. Moreover, it allows the performance of different experimental protocols on the same sample, which can be refreshed to initial state (if necessary) without removal from the measuring cell. Therefore, the measurements can be performed faster, in a more efficient way, and with much higher reproducibility and accuracy. Additionally, the TSC method can be also used as a tool to manufacture the ionogels with targeted properties, like microstructure, with an instant characterization of conductive properties.

Cumulative complexity: a functional, patient-centered model of patient complexity can improve research and practice.

Science.gov (United States)

Shippee, Nathan D; Shah, Nilay D; May, Carl R; Mair, Frances S; Montori, Victor M

2012-10-01

To design a functional, patient-centered model of patient complexity with practical applicability to analytic design and clinical practice. Existing literature on patient complexity has mainly identified its components descriptively and in isolation, lacking clarity as to their combined functions in disrupting care or to how complexity changes over time. The authors developed a cumulative complexity model, which integrates existing literature and emphasizes how clinical and social factors accumulate and interact to complicate patient care. A narrative literature review is used to explicate the model. The model emphasizes a core, patient-level mechanism whereby complicating factors impact care and outcomes: the balance between patient workload of demands and patient capacity to address demands. Workload encompasses the demands on the patient's time and energy, including demands of treatment, self-care, and life in general. Capacity concerns ability to handle work (e.g., functional morbidity, financial/social resources, literacy). Workload-capacity imbalances comprise the mechanism driving patient complexity. Treatment and illness burdens serve as feedback loops, linking negative outcomes to further imbalances, such that complexity may accumulate over time. With its components largely supported by existing literature, the model has implications for analytic design, clinical epidemiology, and clinical practice. Copyright © 2012 Elsevier Inc. All rights reserved.

Resting and Task-Modulated High-Frequency Brain Rhythms Measured by Scalp Encephalography in Infants with Tuberous Sclerosis Complex

Science.gov (United States)

Stamoulis, Catherine; Vogel-Farley, Vanessa; Degregorio, Geneva; Jeste, Shafali S.; Nelson, Charles A.

2015-01-01

The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide…

Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

Science.gov (United States)

Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

2016-01-01

Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Synthesis, structural characterization and cytotoxic activity of two new organoruthenium(II complexes

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SANJA GRGURIC-SIPKA

2008-06-01

Full Text Available Two new p-cymene ruthenium(II complexes containing as additional ligands N-methylpiperazine ([(η6-p-cymeneRuCl2(CH3NH(CH24NH]PF6, complex 1 or vitamin K3-thiosemicarbazone ([(η6-p-cymeneRuCl2(K3tsc], complex 2 were synthesized starting from [(η6-p-cymene2RuCl2]2 and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed “piano-stool” geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.

Computed tomographic features of lymphangioleiomyomatosis: Evaluation in 138 patients

Energy Technology Data Exchange (ETDEWEB)

Tobino, Kazunori, E-mail: tobino@juntendo.ac.jp [Department of Respiratory Medicine, Iizuka Hospital, 3-83 Yoshiomachi, Iizuka, Fukuoka 820-0018 (Japan); Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Johkoh, Takeshi [Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Kurumazuka 3-1, Itami, Hyogo 664-0872 (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine and Center for Diagnostic Imaging, Kurume University Hospital, 67 Asahi-machi, Kurume, Fukuoka 830-0011 (Japan); Sakai, Fumikazu [Department of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Arakawa, Hiroaki [Department of Radiology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293 (Japan); Kurihara, Masatoshi [The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Pneumothorax Center, Nissan Tamagawa Hospital, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Kumasaka, Toshio [The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Department of Pathology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-Ku, Tokyo 150-0012 (Japan); Koike, Kengo; Takahashi, Kazuhisa [Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); Seyama, Kuniaki [Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan)

2015-03-15

Highlights: •In our series, the frequency of pulmonary nodules was higher than in the previous reports. •Our sporadic LAM patients had a lower frequency of renal AML than in that of previous reports. •LAM patients may have a high incidence of renal and hepatic cysts. •LAM cells may originate in the pelvis then spread via the axial lymphatic system. -- Abstract: Purpose: The aim was to characterize the computed tomographic (CT) findings from Japanese patients with lymphangioleiomyomatosis (LAM). Materials and methods: CT scans of the chest, abdomen, and pelvis from 124 patients with sporadic LAM (S-LAM, mean age, 37.4 years) and 14 patients with tuberous sclerosis complex (TSC)-LAM (mean age, 35.6 years) were analyzed. Results: Pulmonary nodules (18.8%) and hepatic angiomyolipoma (AML, 24.3%) were more common in our patients than those in previous reports. Compared with TSC-LAM, S-LAM group had a higher frequency of pulmonary nodules (28.6% vs 32.3%, P < 0.01) and lower frequencies of air-space consolidation (21.4% vs 2.4%, P < 0.01), pneumothorax (28.6% vs 8.1%, P = 0.02), pulmonary hilar lymphadenopathy (14.3% vs 0.8%, P < 0.01), renal AML (85.7% vs 17.4%, P < 0.01), hepatic AML (71.4% vs 17.4%, P < 0.01), and retrocrural lymphadenopathy (14.3% vs 1.4%, P = 0.04). Axial lymphatic abnormalities (i.e., thoracic duct dilatation, lymphadenopathy, and lymphangioleiomyoma) were most common in the pelvis and tended to decrease in incidence with increased distance from the pelvis. Conclusion: The incidence of some CT findings in Japanese patients differed from those in previous reports. Axial lymphatic abnormalities noted here suggest that the origin of LAM cells may be the pelvis.

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

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Ilona Patursky-Polischuk

Full Text Available TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

ESCLEROSIS TUBEROSA Y AFECCIÓN RENAL: REPORTE DE UN CASO CLÍNICO

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Ciocchini M

2016-05-01

Full Text Available A 27 year-old woman was initially referred to the division of nephrology because of polyuria and the finding of renal cysts. She did not have nervous system manifestations. According to the "2012 International Tuberous Sclerosis Complex Consensus Conference" the diagnosis of Tuberous Sclerosis Complex (TSC was completed. TSC is an autosomal dominant inherited multisystem disease with nearly complete penetrance. Clinical manifestations can vary widely even in patients belonging to a same linage. The morbidity and mortality depends on renal or respiratory complications on adulthood. This report highlight the need of a high level of suspicions in patients with manifestations compatible with this disease and shows the importance of a multidisciplinary team working together to arrive to the appropriate diagnosis.

Diagnóstico Tardio de Esclerose Tuberosa

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Catarina Oliveira

2016-03-01

Full Text Available Tuberous sclerosis (also referred to as Tuberous Sclerosis Complex is an autosomal dominant neurocutaneous syndrome that can involve multiple organs such as the brain, heart, kidney, lung, liver, skin and eye. The diagnosis is clinical and most patients are identified during childhood, in the context of a severe epileptic or neuropsychiatric disorder. Here we report a case of TSC diagnosed in an adult woman with dermatological and vascular involvement that were only recognized as manifestations of TSC after the diagnosis of her infant daughter. This case highlights how important it is that physicians recognize the full spectrum of manifestations of TSC, including the most unusual, so not to miss the diagnosis

Cofortification of ferric pyrophosphate and citric acid/trisodium citrate into extruded rice grains doubles iron bioavailability through in situ generation of soluble ferric pyrophosphate citrate complexes.

Science.gov (United States)

Hackl, Laura; Cercamondi, Colin I; Zeder, Christophe; Wild, Daniela; Adelmann, Horst; Zimmermann, Michael B; Moretti, Diego

2016-05-01

Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability. We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains. We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios. Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice. Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

Science.gov (United States)

Salido-Vallejo, R; Ruano, J; Garnacho-Saucedo, G; Godoy-Gijón, E; Llorca, D; Gómez-Fernández, C; Moreno-Giménez, J C

2014-12-01

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients. © 2014 British Association of Dermatologists.

Tc-99m sulfur colloid spleen imaging following splenic artery and vein resection for pancreas organ donation

International Nuclear Information System (INIS)

Kuni, C.C.; Crass, J.R.; Du Cret, R.P.; Boudreau, R.J.; Loken, M.K.

1987-01-01

The authors retrospectively studied the records and Tc-99m sulfur colloid (TSC) splenic artery and vein resection for donation to HLA-compatible relatives. Of 37 patients with postoperative TSC studies, four had no postoperative splenic abnormalities. Nineteen of the abnormal TSC studies were followed with TSC studies 2 weeks to 14 months later; three showed no change, seven showed improvements,and ten became normal. One patient required splenectomy 2 days after pancreatectomy for splenic infarction; her TSC study showed no uptake. These data suggest that the spleen usually survives splenic artery and vein resection. Absent splenic TSC uptake raises the possibility of splenic infarction but usually improves

TSC measurements on proton-irradiated p-type Si-sensors

Energy Technology Data Exchange (ETDEWEB)

Donegani, Elena; Fretwurst, Eckhart; Garutti, Erika; Junkes, Alexandra [University of Hamburg (Germany)

2016-07-01

Thin n{sup +}p Si sensors are potential candidates for coping with neutron equivalent fluences up to 2.10{sup 16} n{sub eq}/cm{sup 2} and an ionizing dose in the order of a few MGy, which are expected e.g. for the HL-LHC upgrade. The aim of the present work is to provide experimental data on radiation-induced defects in order to: firstly, get a deeper understanding of the properties of hadron induced defects, and secondly develop a radiation damage model based on microscopic measurements. Therefore, the outcomes of Thermally Stimulated Current measurements on 200 μm thick Float-Zone (FZ) and Magnetic Czochralski (MCz) diodes will be shown, as a results of irradiation with 23 MeV protons and isothermal annealing. The samples were irradiated in the fluence range (0.3-1).10{sup 14} n{sub eq}/cm{sup 2}, so that the maximal temperature at which the TSC signal is still sharply distinguishable from the dark current is 200 K. In particular, special focus will be given to the defect introduction rate and to the issue of boron removal in p-type silicon. Annealing studies allow to distinguish which defects mainly contribute to the leakage current and which to the space charge, and thus correlate microscopic defects properties with macroscopic sensor properties.

The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains.

Science.gov (United States)

Han, Sangyeul; Kim, Sun; Bahl, Samira; Li, Lin; Burande, Clara F; Smith, Nicole; James, Marianne; Beauchamp, Roberta L; Bhide, Pradeep; DiAntonio, Aaron; Ramesh, Vijaya

2012-08-31

Pam and its homologs (the PHR protein family) are large E3 ubiquitin ligases that function to regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans. Phr1-deficient mouse models (Phr1(Δ8,9) and Phr1(Magellan), with deletions in the N-terminal putative guanine exchange factor region and the C-terminal ubiquitin ligase region, respectively) exhibit axon guidance/outgrowth defects and striking defects of major axon tracts in the CNS. Our earlier studies identified Pam to be associated with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Here, we examine the potential involvement of the TSC/mTOR complex 1(mTORC1) signaling pathway in Phr1-deficient mouse models. We observed attenuation of mTORC1 signaling in the brains of both Phr1(Δ8,9) and Phr1(Magellan) mouse models. Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains. To further address whether Pam regulates mTORC1 through two functionally independent domains, we undertook heterozygous mutant crossing between Phr1(Δ8,9) and Phr1(Magellan) mice to generate a compound heterozygous model to determine whether these two domains can complement each other. mTORC1 signaling was not attenuated in the brains of double mutants (Phr1(Δ8,9/Mag)), confirming that Pam displays dual regulation of the mTORC1 pathway through two functional domains. Our results also suggest that although dysregulation of mTORC1 signaling may be responsible for the corpus callosum defects, other neurodevelopmental defects observed with Phr1 deficiency are independent of mTORC1 signaling. The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency.

Clinical Complexity in Medicine: A Measurement Model of Task and Patient Complexity.

Science.gov (United States)

Islam, R; Weir, C; Del Fiol, G

2016-01-01

Complexity in medicine needs to be reduced to simple components in a way that is comprehensible to researchers and clinicians. Few studies in the current literature propose a measurement model that addresses both task and patient complexity in medicine. The objective of this paper is to develop an integrated approach to understand and measure clinical complexity by incorporating both task and patient complexity components focusing on the infectious disease domain. The measurement model was adapted and modified for the healthcare domain. Three clinical infectious disease teams were observed, audio-recorded and transcribed. Each team included an infectious diseases expert, one infectious diseases fellow, one physician assistant and one pharmacy resident fellow. The transcripts were parsed and the authors independently coded complexity attributes. This baseline measurement model of clinical complexity was modified in an initial set of coding processes and further validated in a consensus-based iterative process that included several meetings and email discussions by three clinical experts from diverse backgrounds from the Department of Biomedical Informatics at the University of Utah. Inter-rater reliability was calculated using Cohen's kappa. The proposed clinical complexity model consists of two separate components. The first is a clinical task complexity model with 13 clinical complexity-contributing factors and 7 dimensions. The second is the patient complexity model with 11 complexity-contributing factors and 5 dimensions. The measurement model for complexity encompassing both task and patient complexity will be a valuable resource for future researchers and industry to measure and understand complexity in healthcare.

Evaluation of the TSC Dolphin Computer Assisted Instructional System in the Chapter 1 Program of the District of Columbia Public Schools. Final Report 85-9.

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Harris, Carolyn DeMeyer; And Others

Dolphin is a computer-assisted instruction system used to teach and reinforce skills in reading, language arts, and mathematics. An evaluation of this system was conducted to provide information to TSC Division of Houghton Mifflin regarding its effectiveness and possible modifications to the system. The general design of the evaluation was to…

Two-stage clustering (TSC: a pipeline for selecting operational taxonomic units for the high-throughput sequencing of PCR amplicons.

Directory of Open Access Journals (Sweden)

Xiao-Tao Jiang

Full Text Available Clustering 16S/18S rRNA amplicon sequences into operational taxonomic units (OTUs is a critical step for the bioinformatic analysis of microbial diversity. Here, we report a pipeline for selecting OTUs with a relatively low computational demand and a high degree of accuracy. This pipeline is referred to as two-stage clustering (TSC because it divides tags into two groups according to their abundance and clusters them sequentially. The more abundant group is clustered using a hierarchical algorithm similar to that in ESPRIT, which has a high degree of accuracy but is computationally costly for large datasets. The rarer group, which includes the majority of tags, is then heuristically clustered to improve efficiency. To further improve the computational efficiency and accuracy, two preclustering steps are implemented. To maintain clustering accuracy, all tags are grouped into an OTU depending on their pairwise Needleman-Wunsch distance. This method not only improved the computational efficiency but also mitigated the spurious OTU estimation from 'noise' sequences. In addition, OTUs clustered using TSC showed comparable or improved performance in beta-diversity comparisons compared to existing OTU selection methods. This study suggests that the distribution of sequencing datasets is a useful property for improving the computational efficiency and increasing the clustering accuracy of the high-throughput sequencing of PCR amplicons. The software and user guide are freely available at http://hwzhoulab.smu.edu.cn/paperdata/.

Profile modification computations for LHCD experiments on PBX-M using the TSC/LSC model

International Nuclear Information System (INIS)

Kaita, R.; Ignat, D.W.; Jardin, S.C.; Okabayashi, M.; Sun, Y.C.

1996-01-01

The TSC-LSC computational model of the dynamics of lower hybrid current drive has been exercised extensively in comparison with data from a Princeton Beta Experiment-Modification (PBX-M) discharge where the measured q(0) attained values slightly above unity. Several significant, but plausible, assumptions had to be introduced to keep the computation from behaving pathologically over time, producing singular profiles of plasma current density and q. Addition of a heuristic current diffusion estimate, or more exactly, a smoothing of the rf-driven current with a diffusion-like equation, greatly improved the behavior of the computation, and brought theory and measurement into reasonable agreement. The model was then extended to longer pulse lengths and higher powers to investigate performance to be expected in future PBX-M current profile modification experiments. copyright 1996 American Institute of Physics

Exploring the role and function of trial steering committees: results of an expert panel meeting.

Science.gov (United States)

Harman, Nicola L; Conroy, Elizabeth J; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Lane, J Athene; Altman, Douglas G; Baigent, Colin; Bliss, Judith M; Campbell, Marion K; Elbourne, Diana; Evans, Stephen; Sandercock, Peter; Gamble, Carrol

2015-12-30

The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is

Effect of beta-agonists on LAM progression and treatment.

Science.gov (United States)

Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

2018-01-30

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

The complex patient: A concept clarification.

Science.gov (United States)

Manning, Eli; Gagnon, Marilou

2017-03-01

Over the last decade, the concept of the "complex patient" has not only been more widely used in multidisciplinary healthcare teams and across various healthcare disciplines, but it has also become more vacuous in meaning. The uptake of the concept of the "complex patient" spans across disciplines, such as medicine, nursing, and social work, with no consistent definition. We review the chronological evolution of this concept and its surrogate terms, namely "comorbidity," "multimorbidity," "polypathology," "dual diagnosis," and "multiple chronic conditions." Drawing on key principles of concept clarification, we highlight disciplinary usage in the literature published between 2005 and 2015 in health sciences, attending to overlaps and revealing nuances of the complex patient concept. Finally, we discuss the implications of this concept for practice, research, and theory. © 2017 John Wiley & Sons Australia, Ltd.

A rapid NGS strategy for comprehensive molecular diagnosis of Birt-Hogg-Dubé syndrome in patients with primary spontaneous pneumothorax.

Science.gov (United States)

Zhang, Xinxin; Ma, Dehua; Zou, Wei; Ding, Yibing; Zhu, Chengchu; Min, Haiyan; Zhang, Bin; Wang, Wei; Chen, Baofu; Ye, Minhua; Cai, Minghui; Pan, Yanqing; Cao, Lei; Wan, Yueming; Jin, Yu; Gao, Qian; Yi, Long

2016-05-27

Primary spontaneous pneumothorax (PSP) or pulmonary cysts is one of the manifestations of Birt-Hogg-Dube syndrome (BHDS) that is caused by heterozygous mutations in FLCN gene. Most of the mutations are SNVs and small indels, and there are also approximately 10 % large intragenic deletions and duplications of the mutations. These molecular findings are generally obtained by disparate methods including Sanger sequencing and Multiple Ligation-dependent Probe Amplification in the clinical laboratory. In addition, as a genetically heterogeneous disorder, PSP may be caused by mutations in multiple genes include FBN1, COL3A1, CBS, SERPINA1 and TSC1/TSC2 genes. For differential diagnosis, these genes should also be screened which makes the diagnostic procedure more time-consuming and labor-intensive. Forty PSP patients were divided into 2 groups. Nineteen patients with different pathogenic mutations of FLCN previously identified by conventional Sanger sequencing and MLPA were included in test group, 21 random PSP patients without any genetic screening were included in blinded sample group. 7 PSP genes including FLCN, FBN1, COL3A1, CBS, SERPINA1 and TSC1/TSC2 were designed and enriched by Haloplex system, sequenced on a Miseq platform and analyzed in the 40 patients to evaluate the performance of the targeted-NGS method. We demonstrated that the full spectrum of genes associated with pneumothorax including FLCN gene mutations can be identified simultaneously in multiplexed sequence data. Noteworthy, by our in-house copy number analysis of the sequence data, we could not only detect intragenic deletions, but also determine approximate deletion junctions simultaneously. NGS based Haloplex target enrichment technology is proved to be a rapid and cost-effective screening strategy for the comprehensive molecular diagnosis of BHDS in PSP patients, as it can replace Sanger sequencing and MLPA by simultaneously detecting exonic and intronic SNVs, small indels, large intragenic

Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: A rare case report

Directory of Open Access Journals (Sweden)

Dharmendra Jain

2013-01-01

Full Text Available A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.

lessons from tuberous sclerosis complex

African Journals Online (AJOL)

intellectual disability, autism, specific learning disorders) and mental health disorders (e.g. depression, psychosis and anxiety disorders). The first lesson, therefore, is ... of an adolescent with TSC, facial angiofibromas and a presumed fat-poor ...

Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

Science.gov (United States)

Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

2017-03-01

Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.

Science.gov (United States)

Ersoy, Baran A; Tarun, Akansha; D'Aquino, Katharine; Hancer, Nancy J; Ukomadu, Chinweike; White, Morris F; Michel, Thomas; Manning, Brendan D; Cohen, David E

2013-07-30

Phosphatidylcholine transfer protein (PC-TP) is a phospholipid-binding protein that is enriched in liver and that interacts with thioesterase superfamily member 2 (THEM2). Mice lacking either protein exhibit improved hepatic glucose homeostasis and are resistant to diet-induced diabetes. Insulin receptor substrate 2 (IRS2) and mammalian target of rapamycin complex 1 (mTORC1) are key effectors of insulin signaling, which is attenuated in diabetes. We found that PC-TP inhibited IRS2, as evidenced by insulin-independent IRS2 activation after knockdown, genetic ablation, or chemical inhibition of PC-TP. In addition, IRS2 was activated after knockdown of THEM2, providing support for a role for the interaction of PC-TP with THEM2 in suppressing insulin signaling. Additionally, we showed that PC-TP bound to tuberous sclerosis complex 2 (TSC2) and stabilized the components of the TSC1-TSC2 complex, which functions to inhibit mTORC1. Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP-THEM2 complex was associated with increased activation of both IRS2 and mTORC1. In livers of mice with genetic ablation of PC-TP or that had been treated with a PC-TP inhibitor, steady-state amounts of IRS2 were increased, whereas those of TSC2 were decreased. These findings reveal a phospholipid-dependent mechanism that suppresses insulin signaling downstream of its receptor.

The cochaperone BAG3 coordinates protein synthesis and autophagy under mechanical strain through spatial regulation of mTORC1.

Science.gov (United States)

Kathage, Barbara; Gehlert, Sebastian; Ulbricht, Anna; Lüdecke, Laura; Tapia, Victor E; Orfanos, Zacharias; Wenzel, Daniela; Bloch, Wilhelm; Volkmer, Rudolf; Fleischmann, Bernd K; Fürst, Dieter O; Höhfeld, Jörg

2017-01-01

The cochaperone BAG3 is a central protein homeostasis factor in mechanically strained mammalian cells. It mediates the degradation of unfolded and damaged forms of the actin-crosslinker filamin through chaperone-assisted selective autophagy (CASA). In addition, BAG3 stimulates filamin transcription in order to compensate autophagic disposal and to maintain the actin cytoskeleton under strain. Here we demonstrate that BAG3 coordinates protein synthesis and autophagy through spatial regulation of the mammalian target of rapamycin complex 1 (mTORC1). The cochaperone utilizes its WW domain to contact a proline-rich motif in the tuberous sclerosis protein TSC1 that functions as an mTORC1 inhibitor in association with TSC2. Interaction with BAG3 results in a recruitment of TSC complexes to actin stress fibers, where the complexes act on a subpopulation of mTOR-positive vesicles associated with the cytoskeleton. Local inhibition of mTORC1 is essential to initiate autophagy at sites of filamin unfolding and damage. At the same time, BAG3-mediated sequestration of TSC1/TSC2 relieves mTORC1 inhibition in the remaining cytoplasm, which stimulates protein translation. In human muscle, an exercise-induced association of TSC1 with the cytoskeleton coincides with mTORC1 activation in the cytoplasm. The spatial regulation of mTORC1 exerted by BAG3 apparently provides the basis for a simultaneous induction of autophagy and protein synthesis to maintain the proteome under mechanical strain. Copyright © 2016 Elsevier B.V. All rights reserved.

Breast-axillary complex in HIV/AIDS patients.

Science.gov (United States)

Eni, U E; Naaya, H U; Yawe, K D T; Lawan, M A; Bakari, A A

2010-01-01

HIV/AIDS have not only increased the health care burden especially in developing countries, it equally complicates the presentation of many diseases. Some well known disease entities now occur in fulminant complexities not previously described or known as such. The objective of this article is to report an unusual presentation of HIV/AIDS patients to the surgeon with Axillary and ipsilateral breast swelling. This is a report of three cases seen and managed by the authors. Three adult female patients presented with progressively increasing axillary and ipsilateral breast swellings. They also had associated fevers and weight loss. Their main concern had been development of breast cancer. One of the patients was a known retroviral positive on Highly Active Anti-Retroviral Therapy (HAART). Examination revealed axillary abscess and ipsilateral breast oedema in two cases. The patient on HAART had a hard breast-axillary mass complex. Biopsy (FNAB) revealed inflammatory cells and no malignancy in all three cases. HIV screening was positive in all cases. One of the patients had excision of breast-axillary mass complex, and the histology showed features of chronic inflammation, with no malignant cells. The other two had incision and drainage of their axillary abscess. This shows the ubiquitous presentation of HIV/AIDS in our environment and surgeons should be aware of the breast axillary complex in HIV/AIDS. Medical practitioners should be careful to obtain accurate diagnosis before embarking on treatment especially mutilating surgical procedures.

Comparing Effects of TCR and TSC on MHO Distance Protection Setting in 400 kV Algerian Transmission Line

Directory of Open Access Journals (Sweden)

Mohamed ZELLAGUI

2012-11-01

Full Text Available This paper presents a study on the performances of distance relays setting in 400 kV in Eastern Algerian transmission networks at Sonelgaz Group (Algerian company of Electrical and Gas compensated by shunt Flexible AC Transmission System (FACTS. The facts are used for controlling transmission voltage, power flow, reactive power, and damping of power system oscillations in high power transfer levels. The effects of SVC devices i.e. Thyristor Controlled Reactor (TCR and the Thyristor Switched Capacitors (TSC insertion, on the total impedance of a transmission line protected by MHO distance relay are investigated. The modified setting zones protections for three forward zones (Z1, Z2 and Z3 have been calculated in order to improve the performances of distance relay protection and prevent circuit breaker nuisance tripping.

Evaluation of thermal sprayed metallic coatings for use on the structures at Launch Complex 39

Science.gov (United States)

Welch, Peter J.

1990-01-01

The current status of the evaluation program is presented. The objective was to evaluate the applicability of Thermal Sprayed Coatings (TSC) to protect the structures in the high temperature acid environment produced by exhaust of the Solid Rocket Boosters during the launches of the Shuttle Transportation System. Only the relatively low cost aluminum TSC which provides some cathodic protection for steel appears to be a practical candidate for further investigation.

Dental implants in medically complex patients-a retrospective study.

Science.gov (United States)

Manor, Yifat; Simon, Roy; Haim, Doron; Garfunkel, Adi; Moses, Ofer

2017-03-01

Dental implant insertion for oral rehabilitation is a worldwide procedure for healthy and medically compromised patients. The impact of systemic disease risks on the outcome of implant therapy is unclear, since there are few if any published randomized controlled trials (RCTs). The objective of this study is to investigate the rate of complications and failures following dental implantation in medically compromised patients in order to elucidate risk factors and prevent them. A retrospective cohort study was conducted from patient files treated with dental implantation between the years 2008-2014. The study group consisted of medically complex patients while the control group consisted of healthy patients. Preoperative, intraoperative, and post operative clinical details were retrieved from patients' files. The survival rate and the success rate of the dental implants were evaluated clinically and radiographically. A total of 204 patients (1003 dental implants) were included in the research, in the study group, 93 patients with 528 dental implants and in the control group, 111 patients with 475 dental implants. No significant differences were found between the groups regarding implant failures or complications. The failure rate of dental implants among the patients was 11.8 % in the study group and 16.2 % in the control group (P = 0.04). It was found that patients with a higher number of implants (mean 6.8) had failures compared with patients with a lower number of implants (mean 4.2) regardless of their health status (P dental implantation in medically complex patients and in healthy patients. Medically complex patients can undergo dental implantation. There are similar rates of complications and failures of dental implants in medically complex patients and in healthy patients.

Volumetric localization of epileptic activities in tuberous sclerosis using synthetic aperture magnetometry

Energy Technology Data Exchange (ETDEWEB)

Xiao, Zheng [Hospital for Sick Children, Research Institute, Toronto (Canada); Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Xiang, Jing [Hospital for Sick Children, Research Institute, Toronto (Canada); Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Holowka, Stephanie; Chuang, Sylvester [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Hunjan, Amrita; Sharma, Rohit; Otsubo, Hiroshi [Hospital for Sick Children, Division of Neurology, Toronto (Canada)

2006-01-01

Magnetoencephalography (MEG) is a novel noninvasive technique for localizing epileptic zones. Tuberous sclerosis complex (TSC) is often associated with medically refractory epilepsy with multiple epileptic zones. Surgical treatment of TSC requires accurate localization of epileptogenic tubers. The objective of this study was to introduce a new MEG technique, synthetic aperture magnetometry (SAM), to volumetrically localize irritable zones and clarify the correlations between SAM, dipole modeling and anatomical tubers. Eight pediatric patients with TSC confirmed by clinical and neuroimaging findings were retrospectively studied. MEG data were recorded using a whole-cortex CTF OMEGA system. Sleep deprivation was employed to provoke epileptiform activity. Irritable zones were localized using both dipole modeling and SAM. MRI detected 42 tubers in the eight patients. Dipole modeling localized 28 irritable zones, and 19 out of the 28 zones were near tubers (19/42, 45%). SAM found 51 irritable zones, and 31 out of the 51 zones were near tubers (31/42, 74%). Among the 51 irritable zones determined by SAM, thirty-five zones were in 1-35 Hz, nine zones were in 35-60 Hz, and seven zones were in 60-120 Hz. The new method, SAM, yielded very plausible equivalent sources for patients who showed anatomical tubers on MRI. Compared to conventional dipole modeling, SAM appeared to offer increased detection of irritable zones and beneficial volumetric and frequency descriptions. (orig.)

[Tuberous sclerosis: clinical characteristics and their relationship to genotype/phenotype].

Science.gov (United States)

Monteiro, T; Garrido, C; Pina, S; Chorão, R; Carrilho, I; Figueiroa, S; Santos, M; Temudo, T

2014-11-01

Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. Our goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Retrospective analysis of patients with TS, including review of medical records and available MRI imaging. We studied 35 cases with a median age at diagnosis of ten months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioral disorders. A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and5 of them had refractory epilepsy. In our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature.

Science.gov (United States)

Starbuck, Kristen D; Drake, Richard D; Budd, G Thomas; Rose, Peter G

2016-11-01

Uterine perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. Many have malignant behavior, and no successful treatment strategy has been established. Identification of mutations in the tuberous sclerosis 1 (TSC1) and TSC2 genes producing constitutive activation of the mammalian target of rapamycin (mTOR) pathway presents an opportunity for targeted therapy. Patients with advanced malignant uterine PEComa treated with mTOR inhibitors were identified and records were retrospectively reviewed for treatment response based on radiographic assessment. Three patients with advanced uterine PEComas underwent debulking surgery followed by mTOR inhibitor therapy; two had a complete response to therapy and disease in one patient progressed. Given the absence of effective therapies for malignant uterine PEComas, targeting the mTOR pathway is a logical strategy to pursue given the known pathobiology involving the Tuberous Sclerosis complex. Treatment of malignant uterine PEComas with mTOR inhibitors was effective in two out of three patients after surgical resection, with durable response. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

lessons from tuberous sclerosis complex

African Journals Online (AJOL)

lot by studying and treating rare disorders, sometimes with profound clinical consequences. A careful look will identify ... and high rates of Alzheimer's disease, which led to the discovery of the molecular basis of familial ... diagnosis, monitoring and treatment of TSC,[14,15] we set out to draft a clinical update summarising an ...

Lungs in TSC

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... must be done in the hospital under general anesthesia. In general, lung biopsy is not required to ... be helpful for some LAM patients who have asthma like symptoms of wheezing and intermittent shortness of ...

Different Sex-Based Responses of Gut Microbiota During the Development of Hepatocellular Carcinoma in Liver-Specific Tsc1-Knockout Mice.

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Huang, Rong; Li, Ting; Ni, Jiajia; Bai, Xiaochun; Gao, Yi; Li, Yang; Zhang, Peng; Gong, Yan

2018-01-01

Gut microbial dysbiosis is correlated with the development of hepatocellular carcinoma (HCC). Therefore, analyzing the changing patterns in gut microbiota during HCC development, especially before HCC occurrence, is essential for the diagnosis and prevention of HCC based on gut microbial composition. However, these changing patterns in HCC are poorly understood, especially considering the sex differences in HCC incidence and mortality. Here, with an aim to determine the relationship between gut microbiota and HCC development in both sexes, and to screen potential microbial biomarkers for HCC diagnosis, we studied the changing patterns in the gut microbiota from mice of both sexes with liver-specific knockout of Tsc1 ( LTsc1KO ) that spontaneously developed HCC by 9-10 months of age and compared them to the patterns observed in their wide-type Tsc1 fl/fl cohorts using high-throughput sequencing. Using the LTsc1KO model, we were able to successfully exclude the continuing influence of diet on the gut microbiota. Based on gut microbial composition, the female LTsc1KO mice exhibited gut microbial disorder earlier than male LTsc1KO mice during the development of HCC. Our findings also indicated that the decrease in the relative abundance of anaerobic bacteria and the increase in the relative abundance of facultative anaerobic bacteria can be used as risk indexes of female HCC, but would be invalid for male HCC. Most of the changes in the gut bacteria were different between female and male LTsc1KO mice. In particular, the increased abundances of Allobaculum , Erysipelotrichaceae, Neisseriaceae, Sutterella , Burkholderiales, and Prevotella species have potential for use as risk indicators of female HCC, and the increased abundances of Paraprevotella, Paraprevotellaceae, and Prevotella can probably be applied as risk indicators of male HCC. These relationships between the gut microbiota and HCC discovered in the present study may serve as a platform for the identification

Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

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Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

2012-01-01

Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

Preliminary MRI study in patients with congenital complex strabismus

International Nuclear Information System (INIS)

Man Fengyuan; Wang Zhenchang; Zhao Bo; Zhu Lei; Xian Junfang; Wang Shijun; Jiao Yonghong; Wu Xiao; Zhao Kanxing

2009-01-01

Objective: Although the ocular motility examination has been traditionally used in the diagnosis of complex strabismus resulting from cranial nerve (CN) and extraocular muscles (EOM) abnormalities, magnetic resonance imaging (MRI) now permits the direct imaging of lesions in CNs and EOMs. Methods: Twenty-six patients with complex strabismus underwent MRI examination on 1.5 T MR unit (Twinspeed, GE). Nerves to EOMs were imaged with T 1 weighted in orbits in all patients using phase array surface coils. Results: Patients with Duane syndrome (15 cases, 19 eyes) all exhibited absence or hypoplasia of abducens nerve (CN6), always with mild hypoplasia and apparent misdirection of oculomotor nerve (CN3) to the lateral rectus muscle in the orbit, and there were no hypoplasia of EOMs. Patients with congenital fibrosis of EOMs (9 cases, 16 eyes) exhibited severe hypoplasia of CN3 and CN6, and EOMs appeared hypoptasia to a different degree, particularly severe for the superior rectus and levated palpted muscles. Multiple nerves displayed aplasia in patients with Mobius syndrome (1 ease, 2 eyes) and there was abnormal branch from CN3 to lateral rectus. The tendons of bilateral superior oblique muscles were thin in the patients with Brown syndrome (1 case, 2 eyes). Conclusion: MRI can directly demonstrate absence or hypoplasia of CNs and corresponding EOM abnormalities in congenital complex strabismus, which suggests that the mechanism of congenital complex strabismus is perhaps abnormal innervation or displasia of the ocular motor nerves. (authors)

Are malnourished patients complex patients? Health status and care complexity of malnourished patients detected by the Short Nutritional Assessment Questionnaire (SNAQ)

NARCIS (Netherlands)

Kruizenga, H. M.; de Jonge, P.; Seidell, J. C.; Neelemaat, F.; van Bodegraven, A. A.; Wierdsma, N. J.; van Bokhorst-de van der Schueren, M. A. E.

Background: This article describes the characteristics of patients identified as malnourished using the Short Nutritional Assessment Questionnaire (SNAQ) in terms of health status (quality of life, functional capacity, and body composition) and care complexity. We expected that by using the quick

Submental Intubation in Patients with Complex Maxillofacial Injuries

Science.gov (United States)

Cheong, Yuseon; Kang, Seong Sik; Kim, Minsoo; Son, Hee Jeong; Park, Jaewoo; Kim, Jeong-Mo

2016-01-01

Airway management in patients with complex maxillofacial injuries is a challenge to anesthesiologists. Submental intubation is a useful technique that is less invasive than tracheostomy in securing the airways where orotracheal and nasotracheal intubation cannot be performed. This procedure avoids the use of tracheostomy and bypasses its associated morbidities. A flexible and kink-resistant reinforced endotracheal tube with detachable universal connector is commonly used for submental intubation. Herein, we report cases involving submental intubation using a reinforced endotracheal tube with a non-detachable universal connector in patients with complex maxillofacial injuries. PMID:27924286

Inhibition of bovine viral diarrhea virus RNA synthesis by thiosemicarbazone derived from 5,6-dimethoxy-1-indanone.

Science.gov (United States)

Castro, Eliana F; Fabian, Lucas E; Caputto, María E; Gagey, Dolores; Finkielsztein, Liliana M; Moltrasio, Graciela Y; Moglioni, Albertina G; Campos, Rodolfo H; Cavallaro, Lucía V

2011-06-01

In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV).

Multimodality Renal Failure in a Patient with OEIS Complex

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Jonathan D. Santoro

2015-10-01

Full Text Available Omphalocele-exstrophy of the bladder-imperforate anus-spinal defect (OEIS complex is a rare constellation of clinical abnormalities with wide phenotypic presentation. We describe a case of a preterm neonate with OEIS complex with acute renal failure, and the challenges in diagnosis and management of this patient as renal failure can be a multifactorial process when encountered with this rare complex.

Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.

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Hegazy, Ahmed M; Yamada, Daisuke; Kobayashi, Masahiko; Kohno, Susumu; Ueno, Masaya; Ali, Mohamed A E; Ohta, Kumiko; Tadokoro, Yuko; Ino, Yasushi; Todo, Tomoki; Soga, Tomoyoshi; Takahashi, Chiaki; Hirao, Atsushi

2016-10-07

Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients. © 2016 by The American

mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis

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Veronica Costa

2016-04-01

Full Text Available Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD, including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2+/− and TSC2−/− neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis.

Complex orthopaedic management of patients with skeletal dysplasias

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A. G. Baindurashvili

2014-01-01

Full Text Available Skeletal dysplasias are challenging for diagnostics and treatment. We present a series of fifteen patients with different forms of skeletal dysplasias with age ranged from 6 to 17 years with variable clinical presentations managed as a part of the project of scientific cooperation between Turner Paediatric Orthopaedic Institute and Orthopaedic Hospital Vienna-Speising. The spectrum of diagnoses included multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia congenita, diastrophic dysplasia, metaphyseal dysplasia, spondylometaphyseal dysplasia, Stickler syndrome, Kniest dysplasia, and anauxetic dysplasia. Complex treatment, which included axial correction and juxta-articular realignment, was performed as a single-stage, or consecutive surgery. Surgical techniques included corrective osteotomies with internal fixation, guided growth technique and external fixation devices. Best results (full axial correction, normal alignment of the joint were achieved in 8 patients, including 2 patients with metaphyseal dysplasia, 2 patients with multiple epyphyseal dysplasia, 2 patients with spondyloepyphyseal dysplasia, patient with Stickler syndrome and patient with spondylometaphyseal dysplasia. Good results (partial correction at the present time were seen in 4 patients (2 patients with Kniest dysplasia, 1 - with multiple epyphyseal dysplasia and 1 - with anauxetic dysplasia. Satisfactory results (non-progressive condition in previous progression were obtained in 2 patients with diastrophic dysplasia, and poor results (progression of the deformity - in 1 patient with diastrophic dysplasia. Positive results in most of the cases of our series make promising future for usage of complex approach for orthopedic management of children with skeletal dysplasias; advanced international cooperation is productive and helpful for diagnostics and management of rare diseases.

The complexity of patient safety reporting systems in UK dentistry.

Science.gov (United States)

Renton, T; Master, S

2016-10-21

Since the 'Francis Report', UK regulation focusing on patient safety has significantly changed. Healthcare workers are increasingly involved in NHS England patient safety initiatives aimed at improving reporting and learning from patient safety incidents (PSIs). Unfortunately, dentistry remains 'isolated' from these main events and continues to have a poor record for reporting and learning from PSIs and other events, thus limiting improvement of patient safety in dentistry. The reasons for this situation are complex.This paper provides a review of the complexities of the existing systems and procedures in relation to patient safety in dentistry. It highlights the conflicting advice which is available and which further complicates an overly burdensome process. Recommendations are made to address these problems with systems and procedures supporting patient safety development in dentistry.

[Patient-related complexity in nursing care - Collective case studies in the acute care hospital].

Science.gov (United States)

Gurtner, Caroline; Spirig, Rebecca; Staudacher, Diana; Huber, Evelyn

2018-06-04

Patient-related complexity in nursing care - Collective case studies in the acute care hospital Abstract. Patient-related complexity of nursing is defined by the three characteristics "instability", "uncertainty", and "variability". Complexity increased in the past years, due to reduced hospital length of stay and a growing number of patients with chronic and multiple diseases. We investigated the phenomenon of patient-related complexity from the point of view of nurses and clinical nurse specialists in an acute care hospital. In the context of a collective case study design, nurses and clinical nurse specialists assessed the complexity of nursing situations with a questionnaire. Subsequently, we interviewed nurses and clinical nurse specialists about their evaluation of patient-related complexity. In a within-case-analysis we summarized data inductively to create case narratives. By means of a cross-case-analysis we compared the cases with regard to deductively derived characteristics. The four cases exemplarily showed that the degree of complexity depends on the controllability and predictability of clinical problems. Additionally, complexity increases or decreases, according to patients' individual resources. Complex patient situations demand professional expertise, experience, communicative competencies and the ability for reflection. Beginner nurses would benefit from support and advice by experienced nurses to develop these skills.

Coexistence of multiphase superconductivity and ferromagnetism in lithiated iron selenide hydroxide [(L i1 -xF ex) OH ]FeSe

Science.gov (United States)

Urban, Christian; Valmianski, Ilya; Pachmayr, Ursula; Basaran, Ali C.; Johrendt, Dirk; Schuller, Ivan K.

2018-01-01

We present experimental evidence for (a) multiphase superconductivity and (b) coexistence of magnetism and superconductivity in a single structural phase of lithiated iron selenide hydroxide [(L i1 -xF ex )OH]FeSe. Magnetic field modulated microwave spectroscopy data confirms superconductivity with at least two distinct transition temperatures attributed to well-defined superconducting phases at TSC 1=40 ±2 K and TSC 2=35 ±2 K. Magnetometry data for the upper critical fields reveal a change in the magnetic order (TM=12 K) below TSC 1 and TSC 2 that is consistent with ferromagnetism. This occurs because the superconducting coherence length is much smaller than the structural coherence length, allowing for several different electronic and magnetic states on a single crystallite. The results give insight into the physics of complex multinary materials, where several phenomena governed by different characteristic length scales coexist.

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

Science.gov (United States)

Randell, Elizabeth; McNamara, Rachel; Davies, D Mark; Owen-Jones, Eleri; Kirby, Nigel; Angel, Lianna; Drew, Cheney; Cannings-John, Rebecca; Smalley, Michelle; Saxena, Anurag; McDermott, Emer; Stockwell, Laura; de Vries, Petrus J; Hood, Kerry; Sampson, Julian R

2016-08-11

Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether

Inhibition of Bovine Viral Diarrhea Virus RNA Synthesis by Thiosemicarbazone Derived from 5,6-Dimethoxy-1-Indanone▿

Science.gov (United States)

Castro, Eliana F.; Fabian, Lucas E.; Caputto, María E.; Gagey, Dolores; Finkielsztein, Liliana M.; Moltrasio, Graciela Y.; Moglioni, Albertina G.; Campos, Rodolfo H.; Cavallaro, Lucía V.

2011-01-01

In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV). PMID:21430053

Primary care physician insights into a typology of the complex patient in primary care.

Science.gov (United States)

Loeb, Danielle F; Binswanger, Ingrid A; Candrian, Carey; Bayliss, Elizabeth A

2015-09-01

Primary care physicians play unique roles caring for complex patients, often acting as the hub for their care and coordinating care among specialists. To inform the clinical application of new models of care for complex patients, we sought to understand how these physicians conceptualize patient complexity and to develop a corresponding typology. We conducted qualitative in-depth interviews with internal medicine primary care physicians from 5 clinics associated with a university hospital and a community health hospital. We used systematic nonprobabilistic sampling to achieve an even distribution of sex, years in practice, and type of practice. The interviews were analyzed using a team-based participatory general inductive approach. The 15 physicians in this study endorsed a multidimensional concept of patient complexity. The physicians perceived patients to be complex if they had an exacerbating factor-a medical illness, mental illness, socioeconomic challenge, or behavior or trait (or some combination thereof)-that complicated care for chronic medical illnesses. This perspective of primary care physicians caring for complex patients can help refine models of complexity to design interventions or models of care that improve outcomes for these patients. © 2015 Annals of Family Medicine, Inc.

Composition of the cellular infiltrate in patients with simple and complex appendicitis.

Science.gov (United States)

Gorter, Ramon R; Wassenaar, Emma C E; de Boer, Onno J; Bakx, Roel; Roelofs, Joris J T H; Bunders, Madeleine J; van Heurn, L W Ernst; Heij, Hugo A

2017-06-15

It is now well established that there are two types of appendicitis: simple (nonperforating) and complex (perforating). This study evaluates differences in the composition of the immune cellular infiltrate in children with simple and complex appendicitis. A total of 47 consecutive children undergoing appendectomy for acute appendicitis between January 2011 and December 2012 were included. Intraoperative criteria were used to identify patients with either simple or complex appendicitis and were confirmed histopathologically. Immune histochemical techniques were used to identify immune cell markers in the appendiceal specimens. Digital imaging analysis was performed using Image J. In the specimens of patients with complex appendicitis, significantly more myeloperoxidase positive cells (neutrophils) (8.7% versus 1.2%, P appendicitis. In contrast, fewer CD8+ T cells (0.4% versus 1.3%, P = 0.016), CD20 + cells (2.9% versus 9.0%, P = 0.027), and CD21 + cells (0.2% versus 0.6%, P = 0.028) were present in tissue from patients with complex compared to simple appendicitis. The increase in proinflammatory innate cells and decrease of adaptive cells in patients with complex appendicitis suggest potential aggravating processes in complex appendicitis. Further research into the underlying mechanisms may identify novel biomarkers to be able to differentiate simple and complex appendicitis. Copyright © 2017 Elsevier Inc. All rights reserved.

Complexity of care and strategies of self-management in patients with colorectal cancer

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Ose D

2017-04-01

Full Text Available Dominik Ose,1,2 Eva C Winkler,3 Sarah Berger,1 Ines Baudendistel,1 Martina Kamradt,1 Felicitas Eckrich,1 Joachim Szecsenyi1 1Department of General Practice and Health Services Research, University Hospital Heidelberg, Heidelberg, Germany; 2Department of Population Health, Health System Innovation and Research, University of Utah, Salt Lake City, UT, USA; 3Program for Ethics and Patient-oriented Care in Oncology, National Centre for Tumour Diseases, University Hospital Heidelberg, Heidelberg, Germany Purpose: Given the inherent complexity of cancer care, in which personal, social, and clinical aspects accumulate and interact over time, self-management support need to become more comprehensive. This study has the following two aims: 1 to analyze and describe the complexity of individual patient situations and 2 to analyze and describe already established self-management strategies of patients to handle this complexity.Methods: A qualitative study was conducted. Ten focus groups were performed collecting perspectives of the following three user groups: patients with colorectal cancer (n=12 and representatives from support groups (n=2, physicians (n=17, and other health care professionals (HCPs; n=16. Data were analyzed using qualitative content analysis.Results: The results showed that cancer patients are struggling with the complexity of their individual situations characterized by the 1 “complexity of disease”, 2 “complexity of care”, and 3 “complexity of treatment-related data”. To deal with these multifaceted situations, patients have established several individual strategies. These strategies are “proactive demanding” (eg, to get support and guidance or a meaningful dialog with the doctor, “proactive behavior” (eg, preparation of visits, and “proactive data management” (eg, in terms of merging treatment-related data and to disseminate these to their health care providers.Conclusion: Patients with colorectal cancer

Classification of Patient Care Complexity: Cloud Technology.

Science.gov (United States)

de Oliveira Riboldi, Caren; Macedo, Andrea Barcellos Teixeira; Mergen, Thiane; Dias, Vera Lúcia Mendes; da Costa, Diovane Ghignatti; Malvezzi, Maria Luiza Falsarella; Magalhães, Ana Maria Muller; Silveira, Denise Tolfo

2016-01-01

Presentation of the computerized structure to implement, in a university hospital in the South of Brazil, the Patients Classification System of Perroca, which categorizes patients according to the care complexity. This solution also aims to corroborate a recent study at the hospital, which evidenced that the increasing workload presents a direct relation with the institutional quality indicators. The tools used were the Google applications with high productivity interconnecting the topic knowledge on behalf of the nursing professionals and information technology professionals.

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

Primary care providers' experiences caring for complex patients in primary care: a qualitative study.

Science.gov (United States)

Loeb, Danielle F; Bayliss, Elizabeth A; Candrian, Carey; deGruy, Frank V; Binswanger, Ingrid A

2016-03-22

Complex patients are increasingly common in primary care and often have poor clinical outcomes. Healthcare system barriers to effective care for complex patients have been previously described, but less is known about the potential impact and meaning of caring for complex patients on a daily basis for primary care providers (PCPs). Our objective was to describe PCPs' experiences providing care for complex patients, including their experiences of health system barriers and facilitators and their strategies to enhance provision of effective care. Using a general inductive approach, our qualitative research study was guided by an interpretive epistemology, or way of knowing. Our method for understanding included semi-structured in-depth interviews with internal medicine PCPs from two university-based and three community health clinics. We developed an interview guide, which included questions on PCPs' experiences, perceived system barriers and facilitators, and strategies to improve their ability to effectively treat complex patients. To focus interviews on real cases, providers were asked to bring de-identified clinical notes from patients they considered complex to the interview. Interview transcripts were coded and analyzed to develop categories from the raw data, which were then conceptualized into broad themes after team-based discussion. PCPs (N = 15) described complex patients with multidimensional needs, such as socio-economic, medical, and mental health. A vision of optimal care emerged from the data, which included coordinating care, preventing hospitalizations, and developing patient trust. PCPs relied on professional values and individual care strategies to overcome local and system barriers. Team based approaches were endorsed to improve the management of complex patients. Given the barriers to effective care described by PCPs, individual PCP efforts alone are unlikely to meet the needs of complex patients. To fulfill PCP's expressed concepts of

Strategy to fight against malnutrition in chronic patients with complex health needs

OpenAIRE

Burgos, Rosa; Joaquin, Clara; Blay, Carles; Ledesma, Albert; Figueiras, Guadalupe; Pérez-Portabella, Cleofe; Granados, Antonio; Gómez, Mª Dolores; González, Asunción; Sarquella, Esther; Amil, Paloma; Vaqué, Cristina

2016-01-01

Disease-related malnutrition (DRM) is a prevalent condition amongst older people as well as patients in all healthcare settings around the world. Chronic patients with complex health needs (CPCHN defined as those with complex chronic conditions that involve multiple health requirements, complex social support needs, or both) are especially vulnerable to malnutrition. Malnutrition is associated with increased morbidity, a higher hospital admission and readmission rate, increased needs for soci...

Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology.

Science.gov (United States)

Ikenaga, Chiseko; Kubota, Akatsuki; Kadoya, Masato; Taira, Kenichiro; Uchio, Naohiro; Hida, Ayumi; Maeda, Meiko Hashimoto; Nagashima, Yu; Ishiura, Hiroyuki; Kaida, Kenichi; Goto, Jun; Tsuji, Shoji; Shimizu, Jun

2017-09-05

To determine the clinical features of myositis patients with the histopathologic finding of CD8-positive T cells invading non-necrotic muscle fibers expressing major histocompatibility complex class 1 (CD8-MHC-1 complex), which is shared by polymyositis (PM) and inclusion body myositis (IBM), in relation to the p62 immunostaining pattern of muscle fibers. All 93 myositis patients with CD8-MHC-1 complex who were referred to our hospital from 1993 to 2015 were classified on the basis of the European Neuromuscular Center (ENMC) diagnostic criteria for IBM (Rose, 2013) or PM (Hoogendijk, 2004) and analyzed. The 93 patients included were 17 patients with PM, 70 patients with IBM, and 6 patients who neither met the criteria for PM nor IBM in terms of muscle weakness distribution (unclassifiable group). For these PM, IBM, and unclassifiable patients, their mean ages at diagnosis were 63, 70, and 64 years; autoimmune disease was present in 7 (41%), 13 (19%), and 4 (67%); hepatitis C virus infection was detected in 0%, 13 (20%), and 2 (33%); and p62 was immunopositive in 0%, 66 (94%), and 2 (33%), respectively. Of the treated patients, 11 of 16 PM patients and 4 of 6 p62-immunonegative patients in the unclassifiable group showed responses to immunotherapy, whereas all 44 patients with IBM and 2 p62-immunopositive patients in the unclassifiable group were unresponsive to immunotherapy. CD8-MHC-1 complex is present in patients with PM, IBM, or unclassifiable group. The data may serve as an argument for a trial of immunosuppressive treatment in p62-immunonegative patients with unclassifiable myositis. © 2017 American Academy of Neurology.

Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex.

Science.gov (United States)

Overwater, I E; Verhaar, B J H; Lingsma, H F; Bindels-de Heus, G C B; van den Ouweland, A M W; Nellist, M; Ten Hoopen, L W; Elgersma, Y; Moll, H A; de Wit, M C Y

2017-01-01

Cognitive development in patients with tuberous sclerosis complex is highly variable. Predictors in the infant years would be valuable to counsel parents and to support development. The aim of this study was to confirm factors that have been reported to be independently correlated with cognitive development. 102 patients included in this study were treated at the ENCORE-TSC expertise center of the Erasmus Medical Center-Sophia Children's Hospital. Data from the first 24 months of life were used, including details on epilepsy, motor development and mutation status. Outcome was defined as cognitive development (intellectual equivalent, IE) as measured using tests appropriate to the patients age and cognitive abilities (median age at testing 8.2 years, IQR 4.7-12.0). Univariable and multivariable regression analyses were used. In a univariable analysis, predictors of lower IE were: the presence of infantile spasms (β = -18.3, p = 0.000), a larger number of antiepileptic drugs used (β = -6.3, p = 0.000), vigabatrin not used as first drug (β = -14.6, p = 0.020), corticosteroid treatment (β = -33.2, p = 0.005), and a later age at which the child could walk independently (β = -2.1, p = 0.000). An older age at seizure onset predicted higher IE (β = 1.7, p = 0.000). In a multivariable analysis, only age at seizure onset was significantly correlated to IE (β = 1.2, p = 0.005), contributing to 28% of the variation in IE. In our cohort, age at seizure onset was the only variable that independently predicted IE. Factors predicting cognitive development could aid parents and physicians in finding the appropriate support and schooling for these patients.

Anatomical success in patients after retinectomy for complex retinal detachment

International Nuclear Information System (INIS)

Mukhtar, A.; Ishaq, M.; Islam, Q.U.

2015-01-01

To evaluate the efficacy of primary and redo retinectomy in eyes with complex retinal detachment. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Ophthalmology Rawalpindi from Jan 2012 to June 2013. Patients and Methods: Fifty eight eyes (patients) underwent relaxing retinectomies for complex retinal detachment with proliferative vitreoretinopathy or intrinsic retinal shortening. Operative technique included pars plana vitrectomy, proliferative vitreoretinopathy management, use of intraoperative perfluorocarbon liquid, retinectomy, endolaser and intraocular temponade. The main outcome was anatomic success, defined as complete retinal reattachment at four months follow up. Eighteen eyes out of the same primary group underwent second retinectomy because of anatomical failure. Results: Mean age of study population was 53.78 ± 15.11 years, 56.9% of patients were male(s). Anatomic success rate after 1st retinectomy was achieved in 68.96% (40 eyes out of 58). In eighteen eyes that underwent 2nd retinectomy, anatomic success rate was 72.22% (13 eyes out of 18). Overall success rate was 91.3% (53 eyes out of 58) in our study. Conclusions: Relaxing retinectomies for retinal shortening can improve the anatomical success rate in patients with complex RD. (author)

The Complexity of the Patient Perspective of Living with Atrial Fibrillation

DEFF Research Database (Denmark)

Høgh, Vibeke; Riahi, Sam; Delmar, Charlotte

2017-01-01

data on information related to the context of the patient’s daily life, family life and work life. The example provided in the article illustrates how the qualitative and quantitative information work as a synergy. Together, information gained from participant observations, on the challenge......The patients’ perspective is by nature complex. Investigating the patients’ perspective, which is important for the quality of care for patients living with atrial fibrillation, therefore calls for complex research processes. This article aims to illuminate the complexity of the patients......’ perspective of living with atrial fibrillation by combining qualitative and quantitative data sources and methods. Related to a one-year patient journey of living with paroxysmal atrial fibrillation it is here illustrated how scores from questionnaires can be explored by supporting the scores with qualitative...

Capturing the experiences of patients across multiple complex interventions: a meta-qualitative approach.

Science.gov (United States)

Webster, Fiona; Christian, Jennifer; Mansfield, Elizabeth; Bhattacharyya, Onil; Hawker, Gillian; Levinson, Wendy; Naglie, Gary; Pham, Thuy-Nga; Rose, Louise; Schull, Michael; Sinha, Samir; Stergiopoulos, Vicky; Upshur, Ross; Wilson, Lynn

2015-09-08

The perspectives, needs and preferences of individuals with complex health and social needs can be overlooked in the design of healthcare interventions. This study was designed to provide new insights on patient perspectives drawing from the qualitative evaluation of 5 complex healthcare interventions. Patients and their caregivers were recruited from 5 interventions based in primary, hospital and community care in Ontario, Canada. We included 62 interviews from 44 patients and 18 non-clinical caregivers. Our team analysed the transcripts from 5 distinct projects. This approach to qualitative meta-evaluation identifies common issues described by a diverse group of patients, therefore providing potential insights into systems issues. This study is a secondary analysis of qualitative data; therefore, no outcome measures were identified. We identified 5 broad themes that capture the patients' experience and highlight issues that might not be adequately addressed in complex interventions. In our study, we found that: (1) the emergency department is the unavoidable point of care; (2) patients and caregivers are part of complex and variable family systems; (3) non-medical issues mediate patients' experiences of health and healthcare delivery; (4) the unanticipated consequences of complex healthcare interventions are often the most valuable; and (5) patient experiences are shaped by the healthcare discourses on medically complex patients. Our findings suggest that key assumptions about patients that inform intervention design need to be made explicit in order to build capacity to better understand and support patients with multiple chronic diseases. Across many health systems internationally, multiple models are being implemented simultaneously that may have shared features and target similar patients, and a qualitative meta-evaluation approach, thus offers an opportunity for cumulative learning at a system level in addition to informing intervention design and

Selection and Characterization of Palmitic Acid Responsive Patients with an OXPHOS Complex I Defect

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Tom E. J. Theunissen

2017-10-01

Full Text Available Mitochondrial disorders are genetically and clinically heterogeneous, mainly affecting high energy-demanding organs due to impaired oxidative phosphorylation (OXPHOS. Currently, effective treatments for OXPHOS defects, with complex I deficiency being the most prevalent, are not available. Yet, clinical practice has shown that some complex I deficient patients benefit from a high-fat or ketogenic diet, but it is unclear how these therapeutic diets influence mitochondrial function and more importantly, which complex I patients could benefit from such treatment. Dietary studies in a complex I deficient patient with exercise intolerance showed increased muscle endurance on a high-fat diet compared to a high-carbohydrate diet. We performed whole-exome sequencing to characterize the genetic defect. A pathogenic homozygous p.G212V missense mutation was identified in the TMEM126B gene, encoding an early assembly factor of complex I. A complementation study in fibroblasts confirmed that the p.G212V mutation caused the complex I deficiency. The mechanism turned out to be an incomplete assembly of the peripheral arm of complex I, leading to a decrease in the amount of mature complex I. The patient clinically improved on a high-fat diet, which was supported by the 25% increase in maximal OXPHOS capacity in TMEM126B defective fibroblast by the saturated fatty acid palmitic acid, whereas oleic acid did not have any effect in those fibroblasts. Fibroblasts of other patients with a characterized complex I gene defect were tested in the same way. Patient fibroblasts with complex I defects in NDUFS7 and NDUFAF5 responded to palmitic acid, whereas ACAD9, NDUFA12, and NDUFV2 defects were non-responding. Although the data are too limited to draw a definite conclusion on the mechanism, there is a tendency that protein defects involved in early assembly complexes, improve with palmitic acid, whereas proteins defects involved in late assembly, do not. Our data show at

Understanding the Etiology of Tuberous Sclerosis Complex

Science.gov (United States)

2011-07-01

neurological symptoms (e.g. seizures), which are the most significant causes of disability and morbidity. Presently, there are no known cures for TSC and...diseases such as symptomatic epilepsy syndrome, fragile X syndrome, schizophrenia , and autism spectrum disorders (Orlova et al., 2010; Chu et al., 2009...hydramnios, megalencephaly, symptomatic epilepsy syndrome,  fragile X syndrome,  schizophrenia , and autism spectrum disorders  technical advance The

Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

International Nuclear Information System (INIS)

Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

2011-01-01

Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

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Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

2014-01-01

The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

A framework for complexity in palliative care: A qualitative study with patients, family carers and professionals.

Science.gov (United States)

Pask, Sophie; Pinto, Cathryn; Bristowe, Katherine; van Vliet, Liesbeth; Nicholson, Caroline; Evans, Catherine J; George, Rob; Bailey, Katharine; Davies, Joanna M; Guo, Ping; Daveson, Barbara A; Higginson, Irene J; Murtagh, Fliss Em

2018-02-01

Palliative care patients are often described as complex but evidence on complexity is limited. We need to understand complexity, including at individual patient-level, to define specialist palliative care, characterise palliative care populations and meaningfully compare interventions/outcomes. To explore palliative care stakeholders' views on what makes a patient more or less complex and insights on capturing complexity at patient-level. In-depth qualitative interviews, analysed using Framework analysis. Semi-structured interviews across six UK centres with patients, family, professionals, managers and senior leads, purposively sampled by experience, background, location and setting (hospital, hospice and community). 65 participants provided an understanding of complexity, which extended far beyond the commonly used physical, psychological, social and spiritual domains. Complexity included how patients interact with family/professionals, how services' respond to needs and societal perspectives on care. 'Pre-existing', 'cumulative' and 'invisible' complexity are further important dimensions to delivering effective palliative and end-of-life care. The dynamic nature of illness and needs over time was also profoundly influential. Adapting Bronfenbrenner's Ecological Systems Theory, we categorised findings into the microsystem (person, needs and characteristics), chronosystem (dynamic influences of time), mesosystem (interactions with family/health professionals), exosystem (palliative care services/systems) and macrosystem (societal influences). Stakeholders found it acceptable to capture complexity at the patient-level, with perceived benefits for improving palliative care resource allocation. Our conceptual framework encompasses additional elements beyond physical, psychological, social and spiritual domains and advances systematic understanding of complexity within the context of palliative care. This framework helps capture patient-level complexity and target

The altered complexity of cardiovascular regulation in depressed patients

International Nuclear Information System (INIS)

Schulz, Steffen; Voss, Andreas; Koschke, Mandy; Bär, Karl-Jürgen

2010-01-01

Major depressive disorders (MDD) are associated with an increased risk for cardiovascular morbidity and mortality. Even if it is known that MDD are accompanied by an autonomic dysbalance with increased sympathetic and/or reduced parasympathetic activity, to date only limited information is available about the degree and complexity of cardiovascular regulation. The aim of this study was to investigate the influence of MDD on the autonomous nervous system and cardiovascular complexity by means of linear and nonlinear indices from heart rate and blood pressure variability (HRV, BPV). From 57 non-medicated patients and 57 matched healthy controls with respect to age and gender HRV and BPV in time and frequency domain, symbolic dynamics, compression entropy, multiscale entropy, detrended fluctuation analysis, Poincaré plot analysis and baroreflex sensitivity were analysed from 30 min short-term recordings. Complexity indices from nonlinear dynamics demonstrated considerable changes in autonomous regulation due to MDD. For the first time we could show that non-medicated depressed patients who were matched with respect to age and gender reveal a significantly changed short-term as well as long-term complexity of cardiovascular regulation. These results suggest substantial changes in autonomic control probably due to a change of interactions between different physiological control loops in MDD

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

Relating illness complexity to reimbursement in CKD patients

Directory of Open Access Journals (Sweden)

Bessette RW

2011-09-01

Full Text Available Russell W Bessette1, Randy L Carter2,3 1Department of Health Sciences, Institute for Healthcare Informatics, 2Department of Biostatistics, 3Population Health Observatory, University at Buffalo, State University of New York, Buffalo, NY, USA Background: Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation. Objectives: Chronic kidney disease (CKD typifies these problems and is often associated with comorbidities that impact cost, health, and work productivity. Thus, the objective of this study was to evaluate an illness complexity score (ICS based on a linear regression of select blood values that might assist in predicting average monthly reimbursements in CKD patients. A second objective was to compare the results of this ICS prediction to results obtained by prediction of average monthly reimbursement using CKD stage. A third objective was to analyze the relationship between the change in ICS, estimated glomerular filtration rate (eGFR, and CKD stage over time to average monthly reimbursement. Methods: We calculated parsimonious values for select variables associated with CKD patients and compared the ICS to ordinal staging of renal disease. Data from 177 de-identified patients over 13 months was collected, which included 15 blood chemistry observations along with complete claims data for all medical expenses. To test for the relationship between average blood chemistry values, stages of CKD, age, and average monthly reimbursement, we modeled an association through a linear regression function of age, eGFR, and the Z-scores calculated from average

Complex dental anomalies in a belatedly diagnosed cleidocranial dysplasia patient

International Nuclear Information System (INIS)

Lu, Hui; Zeng, Bing Hui; Yu, Dong Sheng; Jing, Xiang Yi; Hu, Bin; Zhao, Wei; Wang, Yi Ming

2015-01-01

Cleidocranial dysplasia (CCD) is a rare congenital disorder, typically characterized by persistently open skull sutures, aplastic or hypoplastic clavicles, and supernumerary teeth. Mutations in the gene encoding the runt-related transcription factor 2 (RUNX2) protein are responsible for approximately two thirds of CCD patients. We report a 20-year-old CCD patient presenting not only with typical skeletal changes, but also complex dental anomalies. A previously undiagnosed odontoma, 14 supernumerary teeth, a cystic lesion, and previously unreported fused primary teeth were discovered on cone-beam computed tomography (CBCT) scans. Mutation analysis identified the causal c.578G>A (p.R193Q) mutation in the RUNX2 gene. At 20 years of age, the patient had already missed the optimal period for dental intervention. This report describes the complex dental anomalies in a belatedly diagnosed CCD patient, and emphasizes the significance of CBCT assessment for the detection of dental anomalies and the importance of early treatment to achieve good outcomes

Complex dental anomalies in a belatedly diagnosed cleidocranial dysplasia patient

Energy Technology Data Exchange (ETDEWEB)

Lu, Hui; Zeng, Bing Hui; Yu, Dong Sheng; Jing, Xiang Yi; Hu, Bin; Zhao, Wei; Wang, Yi Ming [Sun Yat-Sen University, Guangzhou (China)

2015-09-15

Cleidocranial dysplasia (CCD) is a rare congenital disorder, typically characterized by persistently open skull sutures, aplastic or hypoplastic clavicles, and supernumerary teeth. Mutations in the gene encoding the runt-related transcription factor 2 (RUNX2) protein are responsible for approximately two thirds of CCD patients. We report a 20-year-old CCD patient presenting not only with typical skeletal changes, but also complex dental anomalies. A previously undiagnosed odontoma, 14 supernumerary teeth, a cystic lesion, and previously unreported fused primary teeth were discovered on cone-beam computed tomography (CBCT) scans. Mutation analysis identified the causal c.578G>A (p.R193Q) mutation in the RUNX2 gene. At 20 years of age, the patient had already missed the optimal period for dental intervention. This report describes the complex dental anomalies in a belatedly diagnosed CCD patient, and emphasizes the significance of CBCT assessment for the detection of dental anomalies and the importance of early treatment to achieve good outcomes.

PHAKOMATOSIS : INTRESTING CASES OF TUBEROUS SCLEROSIS WITH RETINAL ASTROCYTOMA

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Srinivasa Rao

2015-05-01

Full Text Available NTRODUCTION: Tuberous sclerosis complex (TSC or Morbus Bourneville - Pringle disease is an autosomal dominant phakomatosis, first described by Desiree - Magloire Bourneville in 1880. Tuberous sclerosis is a genetic disorder characterized by the growth of numerous benign tumours in many parts of the body caused by mutations on either of two genes, TSC1 and TSC2. This rare genetic disorder is usually associated with a triad of seizures, mental retardation and cutaneous lesions. Approximately one half of all patients affected by TS develop at least one retinal astrocytoma in one eye. PRESENTATION OF CASES: In the department of ophthalmology, G.S.L M edical C ollege, Rajahmundry, we came across 3 cases of tuberous sclerosis involving multi organ systems. Out of 3 cases, 2 cases were reported to be familial and 1case is sporadic, with a history of epilepsy with angiofibromatosis lesions over the face, multiple ash - leaf lesions over the abdomen, renal angiomyolipomas, multiple subependymal nodules in brain and retinal astrocytic hamartomas in the retina. CONCLUSION: It is important to be cognizant of the likely presence of systemic and ocular pathology in a child with mental retardation and skin lesions. Identification of retinal phakomatosis during ocular evaluation in any suspected case of Tuberous sclerosis can aid in the establishment of the diagnosis of the disease

Targeted treatment trials for tuberous sclerosis and autism: no longer a dream.

Science.gov (United States)

Sahin, Mustafa

2012-10-01

Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual disability. Cell culture and mouse model experiments have identified the mTOR pathway as a therapeutic target in this disease. This review summarizes the advantages of using TSC as model of ASD and the recent advances in the translational and clinical treatment trials in TSC. Copyright © 2012 Elsevier Ltd. All rights reserved.

THE INFLUENCE OF THIOSEMICARBAZONE 2,3-DIHYDROXYBENZALDEHYDE ON CATALYTIC CURRENTS IN THE SYSTEM MOLYBDENUM (VI – POTASSIUM CHLORATE IN ACID SULFATE SOLUTIONS

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Ludmila Chiriac

2011-06-01

Full Text Available The polarographic catalytic current in acid solutions of Mo(VI, thiosemicarbazone 2,3-dihydroxybenzaldehyde (TSC 2,3-DHBA and chlorate ions has been investigated. The scheme of reactions, taking place in the solutions and on the electrode, has been proposed. The increase of the catalytic current is explained by the formation of an active intermediate complex [Mo(V×TSC 2,3-DHBA (ClO-3]. The rate constant of this complex formation K = 2.56 × 106 mol-1×dm3×s-1, the activation energy Ea = 15.9 kcal×mol-1 and the reaction activation entropy ∆Sa¹ = -23.5 e.u. have been calculated.

Relating illness complexity to reimbursement in CKD patients.

Science.gov (United States)

Bessette, Russell W; Carter, Randy L

2011-01-01

Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation. Chronic kidney disease (CKD) typifies these problems and is often associated with comorbidities that impact cost, health, and work productivity. Thus, the objective of this study was to evaluate an illness complexity score (ICS) based on a linear regression of select blood values that might assist in predicting average monthly reimbursements in CKD patients. A second objective was to compare the results of this ICS prediction to results obtained by prediction of average monthly reimbursement using CKD stage. A third objective was to analyze the relationship between the change in ICS, estimated glomerular filtration rate (eGFR), and CKD stage over time to average monthly reimbursement. We calculated parsimonious values for select variables associated with CKD patients and compared the ICS to ordinal staging of renal disease. Data from 177 de-identified patients over 13 months was collected, which included 15 blood chemistry observations along with complete claims data for all medical expenses. To test for the relationship between average blood chemistry values, stages of CKD, age, and average monthly reimbursement, we modeled an association through a linear regression function of age, eGFR, and the Z-scores calculated from average monthly values of phosphorus, parathyroid hormone, glucose, hemoglobin, bicarbonate, albumin, creatinine, blood urea nitrogen, potassium, calcium, sodium, alkaline phosphatase, alanine aminotransferase, and white blood cells. The results of our study demonstrated that the association

Effectiveness of Psychosocial Interventions in Complex Palliative Care Patients: A Quasi-Experimental, Prospective Multicenter Study.

Science.gov (United States)

Mateo-Ortega, Dolors; Gómez-Batiste, Xavier; Maté, Jorge; Beas, Elba; Ela, Sara; Lasmarias, Cristina; Limonero, Joaquín T

2018-03-13

To determine whether specific psychosocial interventions can ease discomfort in palliative care (PC) patients, particularly in those with high levels of pain or emotional distress. Changes in the psychological parameters of 8333 patients were assessed in a quasi-experimental, prospective, multicenter, single group pretest/post-test study. Psychosocial care was delivered by 29 psychosocial care teams (PSTs; 137 professionals). Pre- and post-intervention changes in these variables were assessed: mood, anxiety, and emotional distress. Patients were classified as complex, when presented with high levels of anxiety, mood, suffering (or perception of time as slow), and distress (or unease, or discomfort), or noncomplex. These groups were compared to assess changes in suffering-related parameters from baseline. Psychosocial interventions reduced patients' suffering. These interventions were more effective in complex patients. After successive psychosocial interventions, the level of suffering in complex patients decreased until close to parity with noncomplex patients, suggesting that patients with major complexity could benefit most from specific psychosocial treatment. These findings support the importance of assessing and treating patients' psychosocial needs.

Migrating Motor Complex in Colectomized Ileo Stoma Patients

DEFF Research Database (Denmark)

Hansen, Mark B; Wallin, Lene; Husebye, Einar

2011-01-01

In colectomized patients with ileo stoma, the reflex modulation of small intestinal functions is disturbed, resulting in high enteric stoma outputs and malabsorption. Serotonin has a pivotal role in initiating motor and secretory reflexes involving activation of neuronal 5-HT(3) and smooth muscle...... muscarinic receptors. We aimed to evaluate the effect of 5-hydroxytryptamine (5-HT), ondansetron and atropine on fasting and stimulated antro-duodeno-jejunal migrating motor complex (MMC) in colectomized patients with ileo stoma compared with healthy subjects. Manometric recordings were obtained in a blinded......-induced MMC phase III without affecting fasting or postprandial properties in colectomized patients with ileo stoma. Similar effects were observed for 5-HT and atropine in healthy subjects....

Patient-centred communication intervention study to evaluate nurse-patient interactions in complex continuing care

Science.gov (United States)

2012-01-01

Background Communication impairment is a frequent consequence of stroke. Patients who cannot articulate their needs respond with frustration and agitation, resulting in poor optimization of post-stroke functions. A key component of patient-centred care is the ability of staff to communicate in a way that allows them to understand the patient’s needs. We developed a patient-centred communication intervention targeting registered and unregulated nursing staff caring for complex continuing care patients with communication impairments post stroke. Research objectives include 1) examining the effects of the intervention on patients’ quality of life, depression, satisfaction with care, and agitation; and (2) examining the extent to which the intervention improves staff’s attitudes and knowledge in caring for patients with communication impairments. The intervention builds on a previous pilot study. Methods/design A quasi-experimental repeated measures non-equivalent control group design in a complex continuing care facility is being used. Patients with a communication impairment post-stroke admitted to the facility are eligible to participate. All staff nurses are eligible. Baseline data are collected from staff and patients. Follow-up will occur at 1 and 3 months post-intervention. Subject recruitment and data collection from 60 patients and 30 staff will take approximately 36 months. The Patient-Centred Communication Intervention consists of three components: (1) development of an individualized patient communication care plan; (2) a one-day workshop focused on communication and behavioural management strategies for nursing staff; and (3) a staff support system. The intervention takes comprehensive patient assessments into account to inform the development of communication and behavioural strategies specifically tailored to each patient. Discussion The Patient-Centred Communication Intervention will provide staff with strategies to facilitate interactions with

Patient-centred communication intervention study to evaluate nurse-patient interactions in complex continuing care

Directory of Open Access Journals (Sweden)

McGilton Katherine S

2012-10-01

Full Text Available Abstract Background Communication impairment is a frequent consequence of stroke. Patients who cannot articulate their needs respond with frustration and agitation, resulting in poor optimization of post-stroke functions. A key component of patient-centred care is the ability of staff to communicate in a way that allows them to understand the patient’s needs. We developed a patient-centred communication intervention targeting registered and unregulated nursing staff caring for complex continuing care patients with communication impairments post stroke. Research objectives include 1 examining the effects of the intervention on patients’ quality of life, depression, satisfaction with care, and agitation; and (2 examining the extent to which the intervention improves staff’s attitudes and knowledge in caring for patients with communication impairments. The intervention builds on a previous pilot study. Methods/design A quasi-experimental repeated measures non-equivalent control group design in a complex continuing care facility is being used. Patients with a communication impairment post-stroke admitted to the facility are eligible to participate. All staff nurses are eligible. Baseline data are collected from staff and patients. Follow-up will occur at 1 and 3 months post-intervention. Subject recruitment and data collection from 60 patients and 30 staff will take approximately 36 months. The Patient-Centred Communication Intervention consists of three components: (1 development of an individualized patient communication care plan; (2 a one-day workshop focused on communication and behavioural management strategies for nursing staff; and (3 a staff support system. The intervention takes comprehensive patient assessments into account to inform the development of communication and behavioural strategies specifically tailored to each patient. Discussion The Patient-Centred Communication Intervention will provide staff with strategies to

Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma – Single Centre Experience

Science.gov (United States)

Bejiqi, Ramush; Retkoceri, Ragip; Bejiqi, Hana

2017-01-01

BACKGROUND Cardiac rhabdomyoma (CRs) are the most common primary tumour of the heart in infants and children. Usually are multiple and, basing on the location can cause a haemodynamic disturbance, dysrhythmias or heart failure during the fetal and early postnatal period. CRs have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC). It has an association with tuberous sclerosis (TS), and in those, the tumour may regress and disappear completely, or remain consistent in size. AIM: We aimed to evaluate the prenatal diagnosis, clinical presentation and outcome of CRs and their association with TSC in a single centre. The median follow-up period was three years (range: 6 months - 5 years). MATERIAL AND METHODS: We reviewed medical records of all fetuses diagnosed prenatally with cardiac rhabdomyoma covering the period January 2010 to December 2016 which had undergone detailed ultrasound evaluation at a single centre with limited technical resources. RESULTS: Twelve fetuses were included in the study; mostly had multiple tumours and a total of 53 tumours were identified in all patients - the maximum was one fetus with16 tumours. All patients were diagnosed prenatally by fetal echocardiography. In two patient’s haemodynamic disturbances during the fetal period was noted and pregnancies have been terminated. After long consultation termination of pregnancy was chosen by the parents in totally 8 cases. In four continuing pregnancies during the first year of live tumours regressed. TSC was diagnosed in all patients during the follow-up. CONCLUSIONS: Cardiac rhabdomyoma are benign from the cardiovascular standpoint in most affected fetuses. An early prenatal diagnosis may help for an adequate planning of perinatal monitoring and treatment with the involvement of a multidisciplinary team. Large tumour size, the number of tumours and localisation may cause hydrops, and they are significantly associated with poor

Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

Science.gov (United States)

Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

2013-07-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

Faslodex Inhibits Estradiol-Induced Extracellular Matrix Dynamics and Lung Metastasis in a Model of Lymphangioleiomyomatosis

Science.gov (United States)

Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D.; Parkhitko, Andrey; Morrison, Tasha A.; Silverman, Edwin K.; Henske, Elizabeth P.

2013-01-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)–2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)–2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM. PMID:23526212

Complexities in euthanasia or physician-assisted suicide as perceived by Dutch physicians and patients' relatives.

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Snijdewind, Marianne C; van Tol, Donald G; Onwuteaka-Philipsen, Bregje D; Willems, Dick L

2014-12-01

The practice of euthanasia and physician-assisted suicide (EAS) is always complex, but some cases are more complex than others. The nature of these unusually complex cases is not known. To identify and categorize the characteristics of EAS requests that are more complex than others. We held in-depth interviews with 28 Dutch physicians about their perception of complex cases of EAS requests. We also interviewed 26 relatives of patients who had died by EAS. We used open coding and inductive analysis to identify various different aspects of the complexities described by the participants. Complexities can be categorized into relational difficulties-such as miscommunication, invisible suffering, and the absence of a process of growth toward EAS-and complexities that arise from unexpected situations, such as the capricious progress of a disease or the obligation to move the patient. The interviews showed that relatives of the patient influence the process toward EAS. First, the process toward EAS may be disrupted, causing a complex situation. Second, the course of the process toward EAS is influenced not only by the patient and his/her attending physician but also by the relatives who are involved. Communicating and clarifying expectations throughout the process may help to prevent the occurrence of unusually complex situations. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Identification and reproducibility of diagnostic DNA markers for tuber starch and yield optimization in a novel association mapping population of potato (Solanum tuberosum L.).

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Schönhals, E M; Ortega, F; Barandalla, L; Aragones, A; Ruiz de Galarreta, J I; Liao, J-C; Sanetomo, R; Walkemeier, B; Tacke, E; Ritter, E; Gebhardt, C

2016-04-01

SNPs in candidate genes Pain - 1, InvCD141 (invertases), SSIV (starch synthase), StCDF1 (transcription factor), LapN (leucine aminopeptidase), and cytoplasm type are associated with potato tuber yield, starch content and/or starch yield. Tuber yield (TY), starch content (TSC), and starch yield (TSY) are complex characters of high importance for the potato crop in general and for industrial starch production in particular. DNA markers associated with superior alleles of genes that control the natural variation of TY, TSC, and TSY could increase precision and speed of breeding new cultivars optimized for potato starch production. Diagnostic DNA markers are identified by association mapping in populations of tetraploid potato varieties and advanced breeding clones. A novel association mapping population of 282 genotypes including varieties, breeding clones and Andean landraces was assembled and field evaluated in Northern Spain for TY, TSC, TSY, tuber number (TN) and tuber weight (TW). The landraces had lower mean values of TY, TW, TN, and TSY. The population was genotyped for 183 microsatellite alleles, 221 single nucleotide polymorphisms (SNPs) in fourteen candidate genes and eight known diagnostic markers for TSC and TSY. Association test statistics including kinship and population structure reproduced five known marker-trait associations of candidate genes and discovered new ones, particularly for tuber yield and starch yield. The inclusion of landraces increased the number of detected marker-trait associations. Integration of the present association mapping results with previous QTL linkage mapping studies for TY, TSC, TSY, TW, TN, and tuberization revealed some hot spots of QTL for these traits in the potato genome. The genomic positions of markers linked or associated with QTL for complex tuber traits suggest high multiplicity and genome wide distribution of the underlying genes.

Serovars of Mycobacterium avium Complex isolated from patients in Denmark

DEFF Research Database (Denmark)

Askgaard, D. S.; Giese, Steen Bjørck; Thybo, S.

1994-01-01

Danish isolates of Mycobacterium avium complex were serotyped by the use of seroagglutination. The most prevalent serovars among patients with AIDS (n = 89) were 4 and 6, while among non-AIDS patients the most prevalent serovars were 1, 6, and 4, with no major differences between those in patients...... with pulmonary disease (n = 65) and those in patients with lymph node infection (n = 58). The results suggest a Scandinavian distribution of serovars with a predominance of serovar 6 and fail to demonstrate any selective protection against different serovars by Mycobacterium bovis ECG vaccination....

COMPLEX TREATMENT OF PATIENTS WITH POSTURAL PHOBIC DIZZINESS

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M. V. Romanоva

2013-01-01

Full Text Available A total of 25 patients with postural phobic dizziness were examined. Somatic state and neurological status were assessed, neurovisualization and stabilometric investigation were carried out as well as a neuropsychological testing using estimation scales. The efficiency of complex rehabilitation was revealed including vestibular gymnastics, stabilometric training, psychotherapy, and pharmacotherapy in correction of psychoemotional disturbances. 

Multi-Morbidity in Hospitalised Older Patients: Who Are the Complex Elderly?

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Ruiz, Milagros; Bottle, Alex; Long, Susannah; Aylin, Paul

2015-01-01

No formal definition for the "complex elderly" exists; moreover, these older patients with high levels of multi-morbidity are not readily identified as such at point of hospitalisation, thus missing a valuable opportunity to manage the older patient appropriately within the hospital setting. To empirically identify the complex elderly patient based on degree of multi-morbidity. Retrospective observational study using administrative data. English hospitals during the financial year 2012-13. All admitted patients aged 65 years and over. By using exploratory analysis (correspondence analysis) we identify multi-morbidity groups based on 20 target conditions whose hospital prevalence was ≥ 1%. We examined a total of 2788900 hospital admissions. Multi-morbidity was highly prevalent, 62.8% had 2 or more of the targeted conditions while 4.7% had six or more. Multi-morbidity increased with age from 56% (65-69yr age-groups) up to 67% (80-84yr age-group). The average multi-morbidity was 3.2±1.2 (SD). Correspondence analysis revealed 3 distinct groups of older patients. Group 1 (multi-morbidity ≤2), associated with cancer and/or metastasis; Group 2 (multi-morbidity of 3, 4 or 5), associated with chronic pulmonary disease, lung disease, rheumatism and osteoporosis; finally Group 3 with the highest level of multi-morbidity (≥6) and associated with heart failure, cerebrovascular accident, diabetes, hypertension and myocardial infarction. By using widely available hospital administrative data, we propose patients in Groups 2 and 3 to be identified as the complex elderly. Identification of multi-morbidity patterns can help to predict the needs of the older patient and improve resource provision.

Multi-Morbidity in Hospitalised Older Patients: Who Are the Complex Elderly?

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Milagros Ruiz

Full Text Available No formal definition for the "complex elderly" exists; moreover, these older patients with high levels of multi-morbidity are not readily identified as such at point of hospitalisation, thus missing a valuable opportunity to manage the older patient appropriately within the hospital setting.To empirically identify the complex elderly patient based on degree of multi-morbidity.Retrospective observational study using administrative data.English hospitals during the financial year 2012-13.All admitted patients aged 65 years and over.By using exploratory analysis (correspondence analysis we identify multi-morbidity groups based on 20 target conditions whose hospital prevalence was ≥ 1%.We examined a total of 2788900 hospital admissions. Multi-morbidity was highly prevalent, 62.8% had 2 or more of the targeted conditions while 4.7% had six or more. Multi-morbidity increased with age from 56% (65-69yr age-groups up to 67% (80-84yr age-group. The average multi-morbidity was 3.2±1.2 (SD. Correspondence analysis revealed 3 distinct groups of older patients. Group 1 (multi-morbidity ≤2, associated with cancer and/or metastasis; Group 2 (multi-morbidity of 3, 4 or 5, associated with chronic pulmonary disease, lung disease, rheumatism and osteoporosis; finally Group 3 with the highest level of multi-morbidity (≥6 and associated with heart failure, cerebrovascular accident, diabetes, hypertension and myocardial infarction.By using widely available hospital administrative data, we propose patients in Groups 2 and 3 to be identified as the complex elderly. Identification of multi-morbidity patterns can help to predict the needs of the older patient and improve resource provision.

Addressing the Evidence Gap in Stroke Rehabilitation for Complex Patients: A Preliminary Research Agenda.

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Nelson, Michelle L; McKellar, Kaileah A; Munce, Sarah; Kelloway, Linda; Hans, Parminder Kaur; Fortin, Martin; Lyons, Renee; Bayley, Mark

2018-06-01

Evidence suggests that a stroke occurs in isolation (no comorbid conditions) in less than 6% of patients. Multimorbidity, compounded by psychosocial issues, makes treatment and recovery for stroke increasingly complex. Recent research and health policy documents called for a better understanding of the needs of this patient population, and for the development and testing of models of care that meet their needs. A research agenda specific to complexity is required. The primary objective of the think tank was to identify and prioritize research questions that meet the information needs of stakeholders, and to develop a research agenda specific to stroke rehabilitation and patient complexity. A modified Delphi and World Café approach underpinned the think tank meeting, approaches well recognized to foster interaction, dialogue, and collaboration between stakeholders. Forty-three researchers, clinicians, and policymakers attended a 2-day meeting. Initial question-generating activities resulted in 120 potential research questions. Sixteen high-priority research questions were identified, focusing on predetermined complexity characteristics-multimorbidity, social determinants, patient characteristics, social supports, and system factors. The final questions are presented as a prioritized research framework. An emergent result of this activity is the development of a complexity and stroke rehabilitation research network. The research agenda reflects topics of importance to stakeholders working with stroke patients with increasingly complex care needs. This robust process resulted in a preliminary research agenda that could provide policymakers with the evidence needed to make improvements toward better-organized services, better coordination between settings, improved patient outcomes, and lower system costs. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

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Bruno C Jham

2011-04-01

Full Text Available Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear.Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression.Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

[Complex treatment of patients with cholangiogenic hepatic abscess].

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Nychytaĭlo, M Iu; Skums, A V; Medvets'kyĭ, Ie B; Ohorodnyk, P V; Mashkovs'kyĭ, H Iu; Shkarban, V P; Shkarban, P O; Farzolakh, Mekhraban Jafarlu

2005-07-01

Results of treatment of 47 patients with cholangiogenic hepatic abscess were analyzed. Clinical, laboratory and special methods of investigation were applied for diagnosis. The authors consider ultrasound investigation (USI), computer tomography and the abscess puncture under the USI control with subsequent cytological and bacterial control the decisive methods in diagnosis of hepatic abscess. In complex of treatment of patients miniinvasive technologies were applied--the abscess puncture, its cavity drainage under USI control transcutaneus transhepatic cholangiostomy, endoscopic papillosphincterotomy with lithotripsy and nasobiliary drainage, according to indications. Efficacy of the abscess cavity sanation, using miramistinum and decasan, was proved. In general therapy the directed transport of medicines was applied.

Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells.

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Peng, Hui; Kasada, Atsuo; Ueno, Masaya; Hoshii, Takayuki; Tadokoro, Yuko; Nomura, Naho; Ito, Chiaki; Takase, Yusuke; Vu, Ha Thi; Kobayashi, Masahiko; Xiao, Bo; Worley, Paul F; Hirao, Atsushi

2018-01-01

The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's energy status and environmental levels of nutrients and growth factors. In response, mTORC1 mediates signaling that controls protein translation and cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it remains unclear which upstream stimuli regulate mTORC1 activity in the context of hematopoietic stem cells (HSC) maintenance in vivo. In this study, we investigated the function of Rheb, a critical regulator of mTORC1 activity controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady-state and in HSC-derived hematopoiesis post-transplantation. In contrast to the severe hematopoietic dysfunction caused by Raptor deletion, which completely inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable hematopoietic failure. Lack of Rheb caused abnormalities in myeloid cells but did not have impact on hematopoietic regeneration in mice subjected to injury by irradiation. As previously reported, Rheb deficiency resulted in defective HSC-derived hematopoiesis post-transplantation. However, while Raptor is essential for HSC competitiveness in vivo, Rheb is dispensable for HSC maintenance under physiological conditions, indicating that the PI3K-AKT-TSC pathway does not contribute to mTORC1 activity for sustaining HSC self-renewal activity at steady-state. Thus, the various regulatory elements that impinge upstream of mTORC1 activation pathways are differentially required for HSC homeostasis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Patient dose in PTCA as a function of the complexity of the procedure

International Nuclear Information System (INIS)

Peterzol, A.; Kotre, J.

2002-01-01

This work focused attention on the relationship between patient irradiation parameters and the complexity of the procedure in percutaneous transluminal coronary angioplasty (PTCA). It continued the study performed by, whose aim was to evaluate the relationships of clinical (CFs), anatomic (AFs), and technical factors (TFs) versus fluoroscopy time (FT), the number of cine frames (NCF) acquired during cine angiography, and the dose/area product (DAP). There are several papers, being some of them, proving the connection of success, complications rates and clinical events at follow-up to the factors above mentioned. On the contrary, few studies have investigated how the complexity of PTCA affects patient radiation exposure. Like, all three works showed an increase in screening time and patient dose related to an increase in procedure complexity, which was mainly expressed by the number of lesions treated and the devices used (number of catheters, number of stents). In particular, examined the relation of lesion factors and procedural factors versus FT, NCF and DAP, producing an overall grade of 1-3 related to the procedure complexity

mTOR Inhibition and Tuberous Sclerosis Prevention

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J Gordon Millichap

2013-09-01

Full Text Available Investigators at Children's Memorial Health Institute, Warsaw, Poland, report monozygotic twin sisters with tuberous sclerosis complex (TSC, one treated with the mTOR inhibitor everolimus since age 4 years.

[Application of nootropic agents in complex treatment of patients with concussion of the brain].

Science.gov (United States)

Tkachev, A V

2007-01-01

65 patients with a mild craniocereberal trauma have been observed. Medical examination included among general clinical methods the following methods: KT (MRT) of the brain, oculist examination including the observation of eye fundus. For objectification of a patient' complaints the authors used orientation and Galvestona's amnesia tests, feeling scale (psychological test), the table to determine the level of memory. Tests have been carried out on the first, tenth and thirty day of the treatment. Patients of the first group received in a complex treatment -pramistar, patients of the second group - piracetam. Patients of both groups noted considerable improvement during a complex treatment (disappearance of headache, dizziness and nausea) and at the same time patients receiving pramistar had better restoration of orientation and feeling. Pramistar was also more effective in patients with amnesia.

Evaluation of a bovine antibody test for diagnosing Mycobacterium avium complex in patients with cystic fibrosis

DEFF Research Database (Denmark)

Qvist, Tavs; Pressler, Tacjana; Katzenstein, Terese L.

2017-01-01

Introduction: The aim of this study was to test a commercial bovine enzyme-linked immunosorbent assay for investigating antibody activity against Mycobacterium avium complex. Methods: All patients at the Copenhagen Cystic Fibrosis (CF) Center who had culture for nontuberculous mycobacteria...... before and after culture conversion was performed in case patients. Results: Out of 286 included subjects, six had clinical M. avium complex pulmonary disease at the time of sera sampling. These patients presented with higher antibody test values (P-value ... at ruling out pulmonary disease. Screening sera from patients with CF could guide clinicians to focus attention on patients at higher risk of M. avium complex pulmonary disease. Pediatr Pulmonol. 2017;52:34–40....

Older Patients' Perspectives on Managing Complexity in CKD Self-Management.

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Bowling, C Barrett; Vandenberg, Ann E; Phillips, Lawrence S; McClellan, William M; Johnson, Theodore M; Echt, Katharina V

2017-04-03

Patients with CKD are asked to perform self-management tasks including dietary changes, adhering to medications, avoiding nephrotoxic drugs, and self-monitoring hypertension and diabetes. Given the effect of aging on functional capacity, self-management may be especially challenging for older patients. However, little is known about the specific challenges older adults face maintaining CKD self-management regimens. We conducted an exploratory qualitative study designed to understand the relationship among factors facilitating or impeding CKD self-management in older adults. Six focus groups ( n =30) were held in August and September of 2014 with veterans≥70 years old with moderate-to-severe CKD receiving nephrology care at the Atlanta Veterans Affairs Medical Center. Grounded theory with a constant comparative method was used to collect, code, and analyze data. Participants had a mean age (range) of 75.1 (70.1-90.7) years, 60% were black, and 96.7% were men. The central organizing concept that emerged from these data were managing complexity. Participants typically did not have just one chronic condition, CKD, but a number of commonly co-occurring conditions. Recommendations for CKD self-management therefore occurred within a complex regimen of recommendations for managing other diseases. Participants identified overtly discordant treatment recommendations across chronic conditions ( e.g., arthritis and CKD). Prioritization emerged as one effective strategy for managing complexity ( e.g. , focusing on BP control). Some patients arrived at the conclusion that they could group concordant recommendations to simplify their regimens ( e.g. , protein restriction for both gout and CKD). Among older veterans with moderate-to-severe CKD, multimorbidity presents a major challenge for CKD self-management. Because virtually all older adults with CKD have multimorbidity, an integrated treatment approach that supports self-management across commonly occurring conditions may be

SYMPTOM COMPLEX OF CHRONICAL ATLANTOAXIAL SUBLUXATION IN PAEDIATRIC PATIENTS

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A. G. Baindurashvili

2012-01-01

Full Text Available The objective of this study is to determine the complex of symptoms, including both orthopedic and neurological changes that occur against the backdrop of long-existing disturbances of the atlanto-axial joint. The authors conducted in-depth analysis of the orthopedic and neurological examination of 58 children aged between 10 and 17 years with first diagnosed disturbances of relationship between C1 and C2 vertebrae. Complexes of symptoms are identified from the combination of clinical data obtained with in-depth orthopedic and neurological examinations that are pathognomonic for lateral and posterior atlanto-axial chronic subluxation. Rotational subluxation of C1-C2 vertebral-motor segment was associated with concomitant neurological disorders and additionally with the no gross structural deformity of the spine and the disturbed foot support function in all cases. Using of the study findings will allow to make an adequate diagnosis and to determine the correct choice of additional diagnostic and therapeutic methods for this category of patients on the stage of conventional examination of the patient in clinical practice.

Cross-sectional Imaging Review of Tuberous Sclerosis.

Science.gov (United States)

Krishnan, Anant; Kaza, Ravi K; Vummidi, Dharshan R

2016-05-01

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder characterized by development of hamartomas in the brain, abdomen, and thorax. It results from a mutation in one of 2 tumor suppressor genes that activates the mammalian target of rapamycin pathway. This article discusses the origins of the disorder, the recently updated criteria for the diagnosis of TSC, and the cross-sectional imaging findings and recommendations for surveillance. Familiarity with the diverse radiological features facilitates diagnosis and helps in treatment planning and monitoring response to treatment of this multisystem disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

Science.gov (United States)

Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment

DEFF Research Database (Denmark)

Nouws, Jessica; Wibrand, Flemming; van den Brand, Mariël

2014-01-01

fibroblasts partially rescued the complex I deficiency. Riboflavin supplementation did not ameliorate the complex I deficiency in patient fibroblasts. More than a dozen ACAD9 patients with complex I deficiency have been identified in the last 3 years, indicating that ACAD9 is important for complex I assembly...

The challenge of aging and pharmacoterapeutic complexity in the HIV + patient

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Ramón Morillo-Verdugo

2018-05-01

Full Text Available Objective: To describe the current knowledge and management of aging and pharmacotherapeutic complexity in HIV + patients. Method: A review of literature was carried out, including articles, originals or reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms «Polypharmacy»/»Polypharmacy», «Aging»/»Aging», «Frailty»/»Fragility», «Pharmacotherapeutic Complexity»/»Medication Regimen Complexity» and «HIV»/”HIV» were combined. The review was carried out independently by two authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An aging of the population and an increase in associated comorbidities have been identified, especially over 50 years-old. Immunological changes similar to those that are generated in a non-infected elderly population have been described. These conditions influencing the prescription of antiretroviral treatment, according to studies identified. In parallel, polypharmacy is increasingly present, being defined exclusively by the concomitant use of five drugs. Pharmacotherapeutic complexity, through the Medication Regimen Complexity Index, has begun to analyse and relate to health outcomes. There has been a need to know and apply concepts already known in non-HIV-aged population, such as de-prescription, potentially inappropriate medication, cholinergic risk, although few results are available. Conclusions: There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new concepts that help pharmacotherapeutic optimization in this population

Complex autism spectrum disorder in a patient with a 17q12 microduplication.

Science.gov (United States)

Brandt, Tracy; Desai, Khyati; Grodberg, David; Mehta, Lakshmi; Cohen, Ninette; Tryfon, Ana; Kolevzon, Alexander; Soorya, Latha; Buxbaum, Joseph D; Edelmann, Lisa

2012-05-01

Autism spectrum disorders (ASDs) are phenotypically complex developmental neuropsychiatric disorders affecting approximately 0.6% of the population. About 30-70% of affected children are also considered to have intellectual disability (ID). The underlying genetic causes of ASDs are diverse with a defined etiology in 16-20%. Array comparative genomic hybridization (aCGH) has proven useful in identifying sub-microscopic chromosome aberrations in a subset of patients, some of which have been shown to be recurrent. One such aberration is the 1.4 Mb microdeletion at chromosome 17q12, which has been reported to be associated with renal disease, growth restriction, diabetes, cognitive impairment, seizures, and in some cases an ASD. Patients with the reciprocal chromosome 17q12 microduplication typically have also been identified with ID and in some cases seizures and behavioral abnormalities. Here we report a patient with a de novo, 1.4 Mb microduplication diagnosed with significant ID involving complex deficits and autism. To our knowledge, this is the first report of a patient with the 17q12 microduplication and a complex ASD phenotype. Copyright © 2012 Wiley Periodicals, Inc.

Patient access to complex chronic disease records on the Internet

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Bartlett Cherry

2012-08-01

Full Text Available Abstract Background Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine available to patients over the Internet in a project involving more than half of renal units in the UK. Methods Content and presentation of the Renal PatientView (RPV system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrolments and usage were extracted from the webserver. Results By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enrol each patient. Conclusions Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular

Patient access to complex chronic disease records on the Internet.

Science.gov (United States)

Bartlett, Cherry; Simpson, Keith; Turner, A Neil

2012-08-06

Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine) available to patients over the Internet in a project involving more than half of renal units in the UK. Content and presentation of the Renal PatientView (RPV) system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrollment and usage were extracted from the webserver. By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs) but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enroll each patient. Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular, providing an increased sense of empowerment and understanding, with no

Does HIPE data capture the complexity of stroke patients in an acute hospital setting?

LENUS (Irish Health Repository)

Clarke, B

2010-01-01

The Hospital Inpatient Enquiry (HIPE) system is currently used as a principle source of national data on discharges from acute hospitals. The Casemix Programme is used to calculate funding for patient care (HIPE activity and Specialty Costs Returns). Th coding is usually undertaken by clerical personnel. We were concerned that the medical complexity of our stroke patients was not captured by the process. The aims of this study were to compare activity coded by HIPE coding staff and medical staff in consecutive stroke patients discharged from the hospital. One hundred consecutive discharged patients with stroke as primary diagnosis were coded by clerical staff [usual practice] and by medical staff. We compared the coding and any differences. We calculated the financial comparison of subsequent differences in Diagnostic Related Groups (DRGs) and Relative Values (RVs). Clinician coded DRGs resulted in a higher assigned RV in 45 cases. The total RV value for HIPE using clerical coding was 595,268.94 euros and using medical coding was 725,252.16 euros. We conclude that medical input is useful in detailing the complications arising in stroke patients. We suggest that physicians should assist in the HIPE coding process in order to capture clinical complexity, so that funding can be appropriately assigned to manage these complex patients.

Clinical-and-functional basing of the tactics of complex pharmacophysiothera-py of patients with primary glaucoma simplex

Directory of Open Access Journals (Sweden)

T.G. Kamenskikh

2010-03-01

Full Text Available The research goal was to estimate the effectiveness of complex pharmacophysiotherapy of patients with initial glaucoma simplex on the basis of analysis of morphology, visual cortex electrobiological activity and regional blood flow level. 80 patients (149 eyes aged 60-75 were examined. All of them had an initial glaucoma simplex of II or III stage and normalized intraocular pressure. Depending on the stage of glaucoma there were two groups of patients and each group contained two sub-groups. patients of sub-group A were treated by percutaneous electrostimulation with feedback based on visual evoked biopotentials; and patients of sub-group В were treated by traditional electrostimulation. All patients got complex eye examination before and after the therapeutic course, and in 3 months after it. Method of selection of optimal electrostimulation parameters was worked out for the appropriate retina ganglionary cell effect. Individually selected electrostimulation in combination with nootropics contributes to eye hemodynamics improvement. Addition of magnetotherapy to the complex therapy of patients with eye hemodynamics leads to improvement of functional results. the increase of functional results of complex therapy with magnetotherapy that affects cervical sympathetic ganglia has been determined in patients with eye hemodynamics

Patients' perceptions, treatment need, and complexity of orthodontic re-treatment

NARCIS (Netherlands)

Ren, Yijin; Boxum, Christo; Sandham, John

The aim of the present study was to investigate the subjective perception and objective treatment need and complexity of patients seeking orthodontic re-treatment. One hundred subjects (66 females, 34 males, age 26.7+/-8.2 years) seeking re-treatment were asked to complete a questionnaire which was

Complex correction of erectile and copulative violations at patients with obesity and reproductive function violation

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Kotenko K.V.

2013-12-01

Full Text Available The study aimed the development and assessment of features of corrective action of a medical complex on a lipid imbalance at patients with obesity. Material and methods. For an assessment of features of corrective action of a medical complex on a lipid imbalance at patients with obesity in research I was 50 male patients with obesity and frustration of the reproductive sphere aged from 24 to 68 years are included, middle age was 38,5±6,1 years and 7 healthy persons, men of comparable age without any pathological states, results of which all researches were accepted to values of norm. To all patients included in research, except all-clinical inspection calculation of an index of body weight and the relation of a circle of a waist to a circle of hips, measurement of arterial pressure were applied questioning concerning food and food behavior, anthropometry (growth the body weight, a circle of a waist and hips. Besides all patients conducted laboratory methods the researches including definition of atherogenic fractions of lipids (the general cholesterol, triglycerides, LPNP and LPVP. Researches were conducted before treatment and after a course of treatment. Results. The effective complex program for restoration of reproductive function at patients with obesity is developed. Conclusion. Application of the developed complex program more than its separate components caused the expressed reduction of body weight, mainly due to reduction of fatty tissue and manifestations of visceral obesity in patients with obesity and violation of reproductive function, including due to elimination of a metabolic imbalance.

Presence of Fragmented QRS Complexes in Patients with Obstructive Sleep Apnea Syndrome

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Muhammet Rasit Sayin

2015-01-01

Conclusions: In our study fragmented QRS frequency and QRS duration were found to increase in OSAS patients. Both parameters are related with increased cardiovascular mortality. Considering the prognostic importance of ECG parameters, it may be reasonable to recommend more detailed evaluation of OSAS patients with fragmented or prolonged QRS complexes with respect to presence of cardiovascular diseases.

The challenge of aging and pharmacoterapeutic complexity in the HIV + patient.

Science.gov (United States)

Morillo-Verdugo, Ramón; Blanco Ramos, José Ramón; Abdel-Kader Martín, Laila; Álvarez de Sotomayor, María

2018-05-01

To describe the current knowledge and management of aging and  pharmacotherapeutic complexity in HIV + patients. A review of literature was carried out, including articles, originals or  reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms  «Polypharmacy»/»Polypharmacy», «Aging»/»Aging», «Frailty»/»Fragility»,  «Pharmacotherapeutic Complexity»/»Medication Regimen Complexity» and  «HIV»/"HIV» were combined. The review was carried out independently by two  authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An  aging of the population and an increase in associated comorbidities have been  identified, especially over 50 years-old. Immunological changes similar to those  that are generated in a non-infected elderly population have been described.  These conditions influencing the prescription of antiretroviral treatment,  according to studies identified. In parallel, polypharmacy is increasingly present,  being defined exclusively by the concomitant use of five drugs.  Pharmacotherapeutic complexity, through the Medication Regimen Complexity  Index, has begun to analyse and relate to health outcomes. There has been a  need to know and apply concepts already known in non-HIV-aged population,  such as de-prescription, potentially inappropriate medication, cholinergic risk, although few results are available. There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is  beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new  concepts that help pharmacotherapeutic optimization in this population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All

Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration

DEFF Research Database (Denmark)

Angebault, Claire; Gueguen, Naig; Desquiret-Dumas, Valerie

2011-01-01

to impairment in some cases and stimulation in others. Conclusion: These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment....... of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements. Results: Complex I activity was 42% greater in treated fibroblasts compared to controls (p = 0.002). Despite this complex I activity improvement, the effects on mitochondrial respiration were contradictory, leading...

Giant renal artery pseudoaneurysm caused by rupture of renal angiomyolipoma following pregnancy: Endovascular treatment and review of the literature

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Ilkay S Idilman

2014-01-01

Full Text Available Renal angiomyolipoma is a hamartomatous, benign tumor composed of blood vessels, fatty tissue and smooth muscle cells, and is often detected incidentally. It can also be associated with the tuberous-sclerosis complex (TSC. Pregnancy and use of oral contraceptives are known to be associated with an increased risk of tumoral rupture and bleeding. Herein, we report a unique case of renal angiomyolipoma associated with TSC who presented with hypovolemic shock as a result of spontaneous rupture of a giant renal pseudoaneurysm, immediately after pregnancy. Emergency endovascular treatment was successful with sparing of most of the affected kidney as demonstrated by follow-up computed tomography imaging.

Study of multiparameter respiratory pattern complexity in surgical critically ill patients during weaning trials

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Maglaveras Nikos K

2011-01-01

Full Text Available Abstract Background Separation from mechanical ventilation is a difficult task, whereas conventional predictive indices have not been proven accurate enough, so far. A few studies have explored changes of breathing pattern variability for weaning outcome prediction, with conflicting results. In this study, we tried to assess respiratory complexity during weaning trials, using different non-linear methods derived from theory of complex systems, in a cohort of surgical critically ill patients. Results Thirty two patients were enrolled in the study. There were 22 who passed and 10 who failed a weaning trial. Tidal volume and mean inspiratory flow were analyzed for 10 minutes during two phases: 1. pressure support (PS ventilation (15-20 cm H2O and 2. weaning trials with PS: 5 cm H2O. Sample entropy (SampEn, detrended fluctuation analysis (DFA exponent, fractal dimension (FD and largest lyapunov exponents (LLE of the two respiratory parameters were computed in all patients and during the two phases of PS. Weaning failure patients exhibited significantly decreased respiratory pattern complexity, reflected in reduced sample entropy and lyapunov exponents and increased DFA exponents of respiratory flow time series, compared to weaning success subjects (p 0.1, SampEn and LLE predicted better weaning outcome compared with RSBI, P0.1 and RSBI* P0.1 (conventional model, R2 = 0.874 vs 0.643, p Conclusions We suggest that complexity analysis of respiratory signals can assess inherent breathing pattern dynamics and has increased prognostic impact upon weaning outcome in surgical patients.

Complex Osteotomies of Tibial Plateau Malunions Using Computer-Assisted Planning and Patient-Specific Surgical Guides.

Science.gov (United States)

Fürnstahl, Philipp; Vlachopoulos, Lazaros; Schweizer, Andreas; Fucentese, Sandro F; Koch, Peter P

2015-08-01

The accurate reduction of tibial plateau malunions can be challenging without guidance. In this work, we report on a novel technique that combines 3-dimensional computer-assisted planning with patient-specific surgical guides for improving reliability and accuracy of complex intraarticular corrective osteotomies. Preoperative planning based on 3-dimensional bone models was performed to simulate fragment mobilization and reduction in 3 cases. Surgical implementation of the preoperative plan using patient-specific cutting and reduction guides was evaluated; benefits and limitations of the approach were identified and discussed. The preliminary results are encouraging and show that complex, intraarticular corrective osteotomies can be accurately performed with this technique. For selective patients with complex malunions around the tibia plateau, this method might be an attractive option, with the potential to facilitate achieving the most accurate correction possible.

Research trend in thermally stimulated current method for development of materials and devices in Japan

Science.gov (United States)

Iwamoto, Mitsumasa; Taguchi, Dai

2018-03-01

Thermally stimulated current (TSC) measurement is widely used in a variety of research fields, i.e., physics, electronics, electrical engineering, chemistry, ceramics, and biology. TSC is short-circuit current that flows owing to the displacement of charges in samples during heating. TSC measurement is very simple, but TSC curves give very important information on charge behaviors. In the 1970s, TSC measurement contributed greatly to the development of electrical insulation engineering, semiconductor device technology, and so forth. Accordingly, the TSC experimental technique and its analytical method advanced. Over the past decades, many new molecules and advanced functional materials have been discovered and developed. Along with this, TSC measurement has attracted much attention in industries and academic laboratories as a way of characterizing newly discovered materials and devices. In this review, we report the latest research trend in the TSC method for the development of materials and devices in Japan.

Failure of Arm Movement Control in Stroke Patients, Characterized by Loss of Complexity.

Science.gov (United States)

Goh, Segun; Han, Kyungreem; Ryu, Jehkwang; Kim, Seonjin; Choi, MooYoung

2015-01-01

We study the mechanism of human arm-posture control by means of nonlinear dynamics and quantitative time series analysis methods. Utilizing linear and nonlinear measures in combination, we find that pathological tremors emerge in patient dynamics and serve as a main feature discriminating between normal and patient groups. The deterministic structure accompanied with loss of complexity inherent in the tremor dynamics is also revealed. To probe the underlying mechanism of the arm-posture dynamics, we further analyze the coupling patterns between joints and components, and discuss their roles in breaking of the organization structure. As a result, we elucidate the mechanisms in the arm-posture dynamics of normal subjects responding to the gravitational force and for the reduction of the dynamic degrees of freedom in the patient dynamics. This study provides an integrated framework for the origin of the loss of complexity in the dynamics of patients as well as the coupling structure in the arm-posture dynamics.

Alteration of complex negative emotions induced by music in euthymic patients with bipolar disorder.

Science.gov (United States)

Choppin, Sabine; Trost, Wiebke; Dondaine, Thibaut; Millet, Bruno; Drapier, Dominique; Vérin, Marc; Robert, Gabriel; Grandjean, Didier

2016-02-01

Research has shown bipolar disorder to be characterized by dysregulation of emotion processing, including biases in facial expression recognition that is most prevalent during depressive and manic states. Very few studies have examined induced emotions when patients are in a euthymic phase, and there has been no research on complex emotions. We therefore set out to test emotional hyperreactivity in response to musical excerpts inducing complex emotions in bipolar disorder during euthymia. We recruited 21 patients with bipolar disorder (BD) in a euthymic phase and 21 matched healthy controls. Participants first rated their emotional reactivity on two validated self-report scales (ERS and MAThyS). They then rated their music-induced emotions on nine continuous scales. The targeted emotions were wonder, power, melancholy and tension. We used a specific generalized linear mixed model to analyze the behavioral data. We found that participants in the euthymic bipolar group experienced more intense complex negative emotions than controls when the musical excerpts induced wonder. Moreover, patients exhibited greater emotional reactivity in daily life (ERS). Finally, a greater experience of tension while listening to positive music seemed to be mediated by greater emotional reactivity and a deficit in executive functions. The heterogeneity of the BD group in terms of clinical characteristics may have influenced the results. Euthymic patients with bipolar disorder exhibit more complex negative emotions than controls in response to positive music. Copyright © 2015 Elsevier B.V. All rights reserved.

Helical tomotherapy in patients with breast cancer and complex treatment volumes.

Science.gov (United States)

Cendales, Ricardo; Schiappacasse, Luis; Schnitman, Franco; García, Graciela; Marsiglia, Hugo

2011-04-01

To describe early clinical results of tomotherapy treatment in patients with breast cancer and complex treatment volumes. Ten patients were treated with tomotherapy between January 2009 and March 2010. Treatment planning objectives were to cover at least 95% of the planning target volume with the 95% isodose; to have a minimum dose of 90% and a maximum dose of 105%. All treatments included daily CT/megavoltage image guidance. Acute toxicity was recorded weekly. Six patients were treated because constraints were not accomplished for heart, lung or contralateral breast in a previous three-dimensional conformal plan; two for preexisting cardiac or pulmonary disease, and two more for bilateral breast irradiation. Treatment volumes included the whole breast in the majority of patients, as well as the supraclavicular and the internal mammary chain nodes when indicated. Most patients were older than 50 years, and had an early breast cancer, with positive oestrogen receptors, negative HER2 expression and a poorly differentiated, infiltrating ductal carcinoma. The majority of patients had received neoadjuvant chemotherapy associated to breast-conserving surgery and adjuvant hormonotherapy. Median homogeneity index was 1.09; median coverage index was 0.81. Median V20Gy and V10Gy for ipsilateral lung was 20% and 37.1% respectively. Median V25 and V35 for heart was 15% and 4% respectively. Median dose for contralateral breast was 7 Gy. Skin acute toxicity was grade 1 in 41.7% and grade 2 in 58.3%. Tomotherapy is a technique capable of delivering a well tolerated treatment with high homogeneity and coverage indexes and high capabilities for sparing the organs at risk in patients with anatomically complex breast cancer, bilateral breast cancer, indication for internal mammary chain node irradiation, cardiac toxicity derived from chemotherapy, or preexisting cardiac or pulmonary disease. Further studies are required to evaluate local control and late toxicity.

Role of out-patient chemo- and radiotherapy in complex treatment of pediatric nephroblastoma

International Nuclear Information System (INIS)

Kamarli, Z.P.

1987-01-01

The paper discusses application of out-patient procedures for complex chemo- and radiotreatment of pediatric nephroblastoma. The data on 101 out-patients with nephroblastoma were analysed. Out-patient prophylactic chemotherapy was not accompanied by higher rates of toxic or side-effects. Among the basic indications for certain procedures for treatment of nephroblastoma on the out-patient basis are: fair general condition, absence of severe complications in the hospital case history, parents' readiness the nurse, age over 18 months and stage 2 disease

Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

DEFF Research Database (Denmark)

Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E

1984-01-01

Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

Complex pharmaceutical care intervention in pulmonary care Part B. Patient opinion and process survey

NARCIS (Netherlands)

Stuurman-Bieze, A.GG; Kokenberg, M.E.A.P.; Tobi, H; de Boer, W.O.; van Doormaal, Jasperien E.; de Jong-van den Berg, Lolkje Theodora Wilhelmina; Tromp, Th.F.J.

2005-01-01

Objective: The IPMP study (Interventions on the principle of Pulmonary Medication Profiles) investigates and describes the results of complex pharmaceutical care interventions provided to selected pulmonary patients to improve their drug use. This paper describes the patients' opinions about the

SWOT Analysis of Total Sanitation Campaign in Yavatmal District of Maharashtra.

Science.gov (United States)

Pardeshi, Geeta; Shirke, Avinash; Jagtap, Minal

2008-10-01

To study the strengths, weaknesses, opportunities, and threats of the Total Sanitation Campaign (TSC) in the Yavatmal district of Maharashtra. Data was collected in December 2006 through interviews with stakeholders, house-to-house surveys, focus group discussions, and transect walks. Information in each category was finalized in a meeting after brainstorming and discussion with the TSC cell members. The strengths of the campaign were innovations in Information Education and Communication, motivation through incentives, competitive spirit, active participation and partnerships, involvement of women, and universal coverage. The main weaknesses of the program were the absence of Rural Sanitary Marts/Production Centers, poor maintenance of Women Sanitary Complexes, lack of facilities for monitoring/ follow-up and a temporary focus of the campaign approach. There is an opportunity to tap additional resources, learn from other experiences, and institute back-up agencies to support and guide the community in the post-TSC phase. A change in administration and local leadership and loss of priority and interest needed to sustain the momentum while scaling up the interventions are possible threats for the program.

Physical mapping of QTL for tuber yield, starch content and starch yield in tetraploid potato (Solanum tuberosum L.) by means of genome wide genotyping by sequencing and the 8.3 K SolCAP SNP array.

Science.gov (United States)

Schönhals, Elske Maria; Ding, Jia; Ritter, Enrique; Paulo, Maria João; Cara, Nicolás; Tacke, Ekhard; Hofferbert, Hans-Reinhard; Lübeck, Jens; Strahwald, Josef; Gebhardt, Christiane

2017-08-22

Tuber yield and starch content of the cultivated potato are complex traits of decisive importance for breeding improved varieties. Natural variation of tuber yield and starch content depends on the environment and on multiple, mostly unknown genetic factors. Dissection and molecular identification of the genes and their natural allelic variants controlling these complex traits will lead to the development of diagnostic DNA-based markers, by which precision and efficiency of selection can be increased (precision breeding). Three case-control populations were assembled from tetraploid potato cultivars based on maximizing the differences between high and low tuber yield (TY), starch content (TSC) and starch yield (TSY, arithmetic product of TY and TSC). The case-control populations were genotyped by restriction-site associated DNA sequencing (RADseq) and the 8.3 k SolCAP SNP genotyping array. The allele frequencies of single nucleotide polymorphisms (SNPs) were compared between cases and controls. RADseq identified, depending on data filtering criteria, between 6664 and 450 genes with one or more differential SNPs for one, two or all three traits. Differential SNPs in 275 genes were detected using the SolCAP array. A genome wide association study using the SolCAP array on an independent, unselected population identified SNPs associated with tuber starch content in 117 genes. Physical mapping of the genes containing differential or associated SNPs, and comparisons between the two genome wide genotyping methods and two different populations identified genome segments on all twelve potato chromosomes harboring one or more quantitative trait loci (QTL) for TY, TSC and TSY. Several hundred genes control tuber yield and starch content in potato. They are unequally distributed on all potato chromosomes, forming clusters between 0.5-4 Mbp width. The largest fraction of these genes had unknown function, followed by genes with putative signalling and regulatory functions. The

Functional MR imaging in the patients with complex partial seizures

International Nuclear Information System (INIS)

Chung, Jin Il; Chang, Kee Hyun; Song, In Chan; Goo, Jin Mo; Chung, Chun Kee; Lee, Sang Kun; Kim, Hong Dae; Han, Moon Hee; Kim, Sam Soo

1999-01-01

To evaluate the clinical usefulness of functional MR imaging (fMRI) for localization of the cerebral motor and sensory cortices and language center in patients with complex partial seizure. A total of 47 fMRIs were obtained in 14 patients (M:F = 9:5; age 15-50 years; 13 right handed and 1 ambidextrous) with complex partial seizure (6 temporal lobe epilepsy, 6 frontal lobe epilepsy, 1 occipitotemporal lobe epilepsy, 1 hemispheric epilepsy). Conventional MR imaging revealed no abnormality in four patients, localized cerebral atrophy in one, hippocampal sclerosis in four, and benign neoplasm in the remaining five. fMRI was performed on a 1.5 T MR scanner (GE Signa Horizon) using gradient-echo singleshot EPI. Nineteen fMRIs were obtained in eight patients who performed the language task, 16 fMRIs in ten who performed the motor task and 12 fMRIs in ten who performed the somatosensory task. The activation task consisted of three language tasks (silent picture naming , word generation from a character, categorical word generation), motor tasks (opposition of thumb and index finger for hand/dorsifexion or extension for foot), and sensory tasks (passive tactile stimulation of hand or foot using a toothbrush). The data were analyzed using z-score (p<0.05), clustering, and cross-correlation analysis based upon homemade software, IDL 5.1. The success rate for obtaining meaningful fMRI was evaluated and activated regions were assessed on the basis of each fMRI obtained during, language, motor, and somatosensory tasks. fMRI findings were compared with those of the Wada test (n = 7) for language lateralization and with invasive cortical mapping (n = 3) for the localization of eloquent cerebral cortex, especially around the central sulcus. The overall success rate of fMRI was 79 % (37/47); success rates of fMRI with language, sensory, and motor task were 89% (17/19), 83 % (10/12), and 63 % (10/16), respectively. Areas activated during language tasks (n=17) included the

Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

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Iain Hargreaves

2018-02-01

Full Text Available Objectives: Evidence of mitochondrial respiratory chain (MRC dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS. However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05 in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3. Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3 was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s of action of β-interferon.

mTOR up-regulation of PFKFB3 is essential for acute myeloid leukemia cell survival

International Nuclear Information System (INIS)

Feng, Yonghuai; Wu, Liusong

2017-01-01

Although mTOR (mammalian target of rapamycin) activation is frequently observed in acute myeloid leukemia (AML) patients, the precise function and the downstream targets of mTOR are poorly understood. Here we revealed that PFKFB3, but not PFKFB1, PFKFB2 nor PFKFB4 was a novel downstream substrate of mTOR signaling pathway as PFKFB3 level was augmented after knocking down TSC2 in THP1 and OCI-AML3 cells. Importantly, PFKFB3 silencing suppressed glycolysis and cell proliferation of TSC2 silencing OCI-AML3 cells and activated apoptosis pathway. These results suggested that mTOR up-regulation of PFKFB3 was essential for AML cells survival. Mechanistically, Rapamycin treatment or Raptor knockdown reduced the expression of PFKFB3 in TSC2 knockdown cells, while Rictor silencing did not have such effect. Furthermore, we also revealed that mTORC1 up-regulated PFKFB3 was dependent on hypoxia-inducible factor 1α (HIF1α), a positive regulator of glycolysis. Moreover, PFKFB3 inhibitor PFK15 and rapamycin synergistically blunted the AML cell proliferation. Taken together, PFKFB3 was a promising drug target in AML patients harboring mTOR hyper-activation.

Demographic Features in Patients with Complex Regional Pain Syndrome

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Berat Meryem Alkan

2011-12-01

Full Text Available Summary Özet Orijinal Araştırma / Original Investigation 77 Aim: Complex regional pain syndrome (CRPS is characterized by pain, vasomotor and sudomotor changes and trophic disturbances. It may develop as a result of trauma, especially extremity fractures and surgery. Although the pathogenesis of CRPS is not exactly clear explained, it has been suggested that central and periferal mechanisms play role and neurogenic inflamatuar and microvasculer functional impairmensts are accompanying to the process. Not all but some of the patients with past trauma or with other possible etiological factors develop CRPS. This suggests the presence of an individual predisposition. In this article, we searched post fractüred CRPS-I patients demographic characteristics, current systemic diseases and symptoms that accompany a CRPS in our records. Materials and Methods: In this retrospective study conducted in Ankara Atatürk Education and Research Hospital, medical records of 356 patients admitted to physical medicine and rehabilitation outpatient clinics with fractures between January 2011 and June 2011 were evaluated and 34 patients diagnosed as CRPS-1 were included in the study. Results: 34 of 356 patients (9.56% with fractures were diagnosed as CRPS-1 in our outpatient clinics. Mean age of the patients was 46.05 years and 10 patients were females (29.4% and 24 patients (70.6% were males. Fractures were in upper extremities in 18 patients (52.9% and in lower extremities in 16 (47.1% patients. Neuropsychiatric disorders and other systemic diseases that may have a role in etiology of CRPS were found in lower rates in medical records of our patients. Conclusion: CRPS does not develop in every patients after travma who has etiologic risk factors, so it reminds that there exists a tendency to CRPS. We have observed that CRPS-1 risk was increased in male patients and in upper extremity fractures. We did not observe any other impertant factor which increases

Conduction and TSC properties of LB films adsorbing cyanine dyes; Cyanine shikiso kyuchaku LB maku ni okeru denki dendo oyobi netsushigeki denryu tokusei

Energy Technology Data Exchange (ETDEWEB)

Shinbo, K.; Kato, K.; Kaneko, F.; Kobayashi, S. [Niigata University, Niigata (Japan)

1995-05-20

The electric properties were investigated for phosphatidic acid (PA) LB films adsorbing cyanide dyes (NK-3) with sandwich electrodes. PA LB adsorbing the dyes and the monolayers of Cd salt without the dyes are deposited using subphases, containing various concentrations of the dyes and containing CdCl2 instead of the dyes, respectively. Conduction currents are measured at room temperature for the PA LB film devices. Increases in the conduction currents are observed in the LB films containing the dyes. Furthermore, the conduction currents remarkably increase using the Au upper electrode. The current(I) vs. voltage (V) properties nearly follow the Poole conduction, log(I)-V. Therefore, the conduction currents are very complicated and are thought to be due to composite mechanisms in the film and at the interface. TSC measurements are used to examine the dipolar polarizations in the PA LB films, in the temperature region between 150 K and 300 K. Remarkable increase of TSCs are observed above 260 K for the devices containing the dyes. The TSCs are caused by the dipolar polarizations, and increase with the quantity of the dyes contained in the LB devices and/or aggregations of the dyes. The results are useful for applications of ultrathin film devices in the future. 16 refs., 11 figs., 3 tabs.

Separating complex compound patient motion tracking data using independent component analysis

Science.gov (United States)

Lindsay, C.; Johnson, K.; King, M. A.

2014-03-01

In SPECT imaging, motion from respiration and body motion can reduce image quality by introducing motion-related artifacts. A minimally-invasive way to track patient motion is to attach external markers to the patient's body and record their location throughout the imaging study. If a patient exhibits multiple movements simultaneously, such as respiration and body-movement, each marker location data will contain a mixture of these motions. Decomposing this complex compound motion into separate simplified motions can have the benefit of applying a more robust motion correction to the specific type of motion. Most motion tracking and correction techniques target a single type of motion and either ignore compound motion or treat it as noise. Few methods account for compound motion exist, but they fail to disambiguate super-position in the compound motion (i.e. inspiration in addition to body movement in the positive anterior/posterior direction). We propose a new method for decomposing the complex compound patient motion using an unsupervised learning technique called Independent Component Analysis (ICA). Our method can automatically detect and separate different motions while preserving nuanced features of the motion without the drawbacks of previous methods. Our main contributions are the development of a method for addressing multiple compound motions, the novel use of ICA in detecting and separating mixed independent motions, and generating motion transform with 12 DOFs to account for twisting and shearing. We show that our method works with clinical datasets and can be employed to improve motion correction in single photon emission computed tomography (SPECT) images.

White Matter Loss in a Mouse Model of Periventricular Leukomalacia Is Rescued by Trophic Factors

Directory of Open Access Journals (Sweden)

Pierre Gressens

2013-11-01

Full Text Available Periventricular leukomalacia (PVL is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME leads to abnormal oligodendrocytes (OLs, myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1 promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA. Comparing lesions produced by NMDA alone and those produced by NMDA + TSC1 we found that: NMDA affected survival and reduced migration of OL progenitors (OLPs. In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult. Olig2-mRNA expression showed 52% OLP survival in mice receiving a NMDA injection and increased to 78% when TSC1 + NMDA were injected simultaneously and ventricular size was reduced by TSC1. Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection. Thus, white matter loss after excitotoxicity can be partially rescued as TSC1 conferred neuroprotection to preexisting OLP and regeneration via OLP proliferation. Furthermore, we showed that early TSC1 administration maximizes neuroprotection.

Mixed-method research protocol: defining and operationalizing patient-related complexity of nursing care in acute care hospitals.

Science.gov (United States)

Huber, Evelyn; Kleinknecht-Dolf, Michael; Müller, Marianne; Kugler, Christiane; Spirig, Rebecca

2017-06-01

To define the concept of patient-related complexity of nursing care in acute care hospitals and to operationalize it in a questionnaire. The concept of patient-related complexity of nursing care in acute care hospitals has not been conclusively defined in the literature. The operationalization in a corresponding questionnaire is necessary, given the increased significance of the topic, due to shortened lengths of stay and increased patient morbidity. Hybrid model of concept development and embedded mixed-methods design. The theoretical phase of the hybrid model involved a literature review and the development of a working definition. In the fieldwork phase of 2015 and 2016, an embedded mixed-methods design was applied with complexity assessments of all patients at five Swiss hospitals using our newly operationalized questionnaire 'Complexity of Nursing Care' over 1 month. These data will be analysed with structural equation modelling. Twelve qualitative case studies will be embedded. They will be analysed using a structured process of constructing case studies and content analysis. In the final analytic phase, the quantitative and qualitative data will be merged and added to the results of the theoretical phase for a common interpretation. Cantonal Ethics Committee Zurich judged the research programme as unproblematic in December 2014 and May 2015. Following the phases of the hybrid model and using an embedded mixed-methods design can reach an in-depth understanding of patient-related complexity of nursing care in acute care hospitals, a final version of the questionnaire and an acknowledged definition of the concept. © 2016 John Wiley & Sons Ltd.

Perspectives on counseling patients about menopausal hormone therapy: strategies in a complex data environment.

Science.gov (United States)

Parish, Sharon J; Nappi, Rossella E; Kingsberg, Sheryl

2018-03-05

This narrative review strives to give healthcare providers (HCPs) who care for menopausal women better tools and skills to initiate discussions with women about menopause and hormone therapy (HT), communicate complex concepts and data, and promote shared decision-making. We review relevant studies on HT, barriers to treatment of menopausal symptoms, and effective communication strategies. We also provide recommendations for communicating with patients about HT based on the medical literature and our own professional experience. Both patient and HCP-related barriers can prevent women from accessing treatment for bothersome symptoms of menopause. Many women and HCPs have a poor understanding of the complex, nuanced data regarding HT. The benefits and risks vary with patient age and time since menopause, duration of use, inclusion of a progestin, and patient medical history. Women may also have fears about potential side effects of HT and feel unable to make informed choices. Strategies for effective patient communication and shared decision-making include use of open-ended questions to elicit patient's concerns and preferences, reflecting back to the patient what the HCP heard, presenting evidence about benefits and risks in language the patient can understand, keeping risks in perspective (eg, provide absolute, and also relative risks) without minimizing them, and making conscious efforts to minimize potential bias. Necessary components for achieving high-quality, shared decisions about HT involve a combination of medical evidence, communication skills, and recognition of patient goals and concerns. Use of such strategies can enhance women's satisfaction with care.

Circulating IgA immune complexes in patients with psoriasis

International Nuclear Information System (INIS)

Hall, R.P.; Peck, G.L.; Lawley, T.J.

1983-01-01

The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p . 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis

Thermally stimulated currents in α-HgI2 polycrystalline films

International Nuclear Information System (INIS)

Shiu, Y.-T.; Huang, T.-J.; Shih, C.-T.; Su, C.-F.; Lan, S.-M.; Chiu, K.-C.

2007-01-01

A study of thermally stimulated currents (TSC) is applied to α-HgI 2 polycrystalline films grown by physical vapour deposition with various thermal boundary conditions. Five TSC peaks are clearly observed and numerically fitted. The activation energy and the density of the trapping centre that corresponds to each TSC peak are then calculated. Finally, the effects of the deposition conditions on the TSC results are discussed

Sensitization of Cancer Cells through Reduction of Total Akt and Downregulation of Salinomycin-Induced pAkt, pGSk3β, pTSC2, and p4EBP1 by Cotreatment with MK-2206

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Ae-Ran Choi

2014-01-01

Full Text Available MK-2206 is an inhibitor of Akt activation. It has been investigated as an anticancer drug in clinical trials assessing the potential of pAkt targeting therapy. The purpose of this study was to identify conditions that increase the sensitivity of cancer cells to MK-2206. We found that the treatment of cancer cells with a high concentration of salinomycin (Sal reduced total Akt protein levels but increased activated Akt levels. When cancer cells were cotreated with MK-2206 and Sal, both pAkt and total Akt levels were reduced. Using microscopic observation, an assessment of cleaved PARP, FACS analysis of pre-G1 region, and Hoechst staining, we found that Sal increased apoptosis of MK-2206-treated cancer cells. These results suggest that cotreatment with MK-2206 and Sal sensitizes cancer cells via reduction of both pAkt and total Akt. Furthermore, cotreatment of cancer cells with Sal and MK-2206 reduced pp70S6K, pmTOR, and pPDK1 levels. In addition, Sal-induced activation of GSK3β, TSC2, and 4EBP1 was abolished by MK-2206 cotreatment. These results suggest that cotreatment using MK-2206 and Sal could be used as a therapeutic method to sensitize cancer cells through targeting of the PI3K/Akt/mTOR pathway. Our findings may contribute to the development of MK-2206-based sensitization therapies for cancer patients.

Complex Scapular Winging following Total Shoulder Arthroplasty in a Patient with Ehlers-Danlos Syndrome

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John G. Skedros

2015-01-01

Full Text Available This is a unique case of a female patient with features of classical and hypermobile types of Ehlers-Danlos syndrome (EDS who developed complex scapular winging from spinal accessory and long thoracic neuropathies. These neurological problems became manifest after an uncomplicated total shoulder arthroplasty (TSA. The patient had a complex postoperative course with extensive work-up in addition to revision shoulder surgery and manipulations to treat shoulder stiffness. It was eventually suspected that the periscapular nerve impairments occurred during physical therapy sessions after her TSA. This interpretation was further supported by genetic evidence that, in addition to EDS, the patient had an unrecognized genetic propensity for nerve palsies from stretch or pressure (“hereditary neuropathy with liability to pressure palsies” (HNPP. By two years after the TSA the neuropathies had only partially improved, leaving the patient with persistent scapular winging and shoulder weakness. With this case we alert surgeons and physical therapists that patients with EDS can have not only a complicated course after TSA, but rare concurrent conditions that can further increase the propensity of neurological injuries that result in compromised shoulder function.

Personality and Psychopathology of Patients with Grandmal and Complex Partial Seizures

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Najafi

2010-06-01

Full Text Available Introduction: Epileptic patients have special mental profile and experience emotional and psychopathological problems. Some studies have reported that epilepsy and psychopathology occur together. The aim of this study was to evaluate the mental profile of Complex partial seizure (CPS and Grandmal seizure (GMS patients and compare them with the control group. Methods: This descriptive-analytical study was carried out in 2008 at the neurological clinics of Isfahan and included 40 Patients with CPS and GMS epilepsy selected conveniently and control group included relatives of the patients. Psychological and personality profile was measured with MMPI inventory. The obtained data was analyzed with SPSS software, mainly through the analysis of Chi Square and ANOVA. Results: The findings of this research showed that although the scores of clinical scales in MMPI are higher than control group, this psychopathology isn’t abnormal. Epileptic patients in hypochondria, depression and hysteria had more elevated levels in comparison with the control group, but this difference was significant only in CPS patients. Conclusion: The results showed that epileptic patients tend to have more psychological disorders than normal people. These findings emphasize the necessity for psychological treatment along with drug therapy.

Complex and unstable simple elbow dislocations: a review and quantitative analysis of individual patient data

NARCIS (Netherlands)

de Haan, Jeroen; Schep, Niels; Tuinebreijer, Wim; den Hartog, Dennis

2010-01-01

The primary objective of this review of the literature with quantitative analysis of individual patient data was to identify the results of available treatments for complex elbow dislocations and unstable simple elbow dislocations. The secondary objective was to compare the results of patients with

Outcomes and Short-Term Follow-Up in Complex Ross Operations in Pediatric Patients Undergoing Damus-Kaye-Stansel Takedown.

Science.gov (United States)

Baird, Christopher W; Zurakowski, David; Bueno, Alejandra; Borisuk, Michele J; Raju, Vijayakumar; Mokashi, Suyog A; Emani, Sitaram; Marx, Gerald R; Del Nido, Pedro J

2016-01-01

Review echocardiography and outcomes before and after Ross procedures, including patients undergoing biventricular conversion with Damus-Kaye-Stansel (DKS) takedown. A retrospective review was performed on 62 patients undergoing simple (control group) and complex Ross procedures, including 12 patients who underwent biventricular conversion with Ross operation and DKS takedown (complex). Echocardiography was reviewed preoperatively and at discharge and late follow-up. Kaplan-Meier estimates of patient survival and freedom from reintervention were obtained. In all, 62 patients had a median age of 4.5 years (interquartile range [IQR]: 1-12.5), weight of 16.4kg (IQR: 8-41), and follow-up of 3.8 years (IQR: 1.3-6). The complex DKS takedown group had 2 deaths, no neoaortic valve or root reinterventions, and 3 right ventricular outflow tract (VOT) reinterventions. There were no differences from the control group in left VOT or right VOT reinterventions. Neither group showed differences between pre- and late follow-up aortic root and ascending aorta dimensions, and no correlations were found among preoperative pulmonary valve (PV) size, late aortic regurgitation (AR), aortic root, or ascending aortic Z-scores. Aortic valve size increased from discharge to late follow-up for both groups (P ≤ .05); 90% of patients at late follow-up had mild or less AR with similar distributions in severity between complex and control groups. Severity of late AR showed no correlation with preoperative PV size and is independent of it. The Ross procedure has good short-term results in simple and complex patients and should be considered in those undergoing Ross operation with biventricular conversion and DKS takedown. Moreover, native PV size should not be a contraindication for Ross procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

Motivation toward Physical Exercise and Subjective Wellbeing: The Mediating Role of Trait Self-Control

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Walid Briki

2016-10-01

Full Text Available Motivation toward physical exercise (MPE and trait self-control (TSC were identified as key predictors of subjective wellbeing (SWB. However, there has not been any research designed to examine the mediating role of TSC in the relationship between MPE and SWB. The present study utilizes self-determination theory, control-process theory of self-regulation, and theory of multiple pathways of TSC in order to examine whether TSC mediates the relationships of autonomous MPE (A-MPE, controlled MPE (C-MPE, and impersonal MPE (NO-MPE with SWB using structural equation modeling (XLSTAT PLS. Three hundred seventeen adult American individuals (Mage = 32.97, SDage = 11.30, who reported to be regular exercisers, voluntarily answered questionnaires assessing MPE, TSC, and SWB. Correlational analyses revealed positive relationships between A-MPE, TSC, and SWB, and negative relationships of C-MPE and NO-MPE with TSC and SWB. Mediation analyses revealed that TSC mediated the relationships of A-MPE (partial mediation and C-MPE (full mediation with SWB, but did not mediate the relationship between NO-MPE and SWB. The estimates of the quality of the hypothesized model were acceptable (outer model GoF = .935; absolute GoF = .330; relative GoF = .942; inner model GoF = 1.008; R2 = 36.947%. Finally, this study supports the view that MPE can influence SWB through TSC, and incites to pursue the examination of the relationships between self-determined motivation, self-regulation mechanisms, and health-related outcomes.

Primary myelodysplastic syndrome with complex chromosomal rearrangements in a patient with Klinefelter's syndrome.

OpenAIRE

Abidi, S M; Griffiths, M; Oscier, D G; Mufti, G J; Hamblin, T J

1986-01-01

A patient with Klinefelter's syndrome and diabetes mellitus was diagnosed as having myelodysplasia. Cytogenetic analysis of the peripheral blood and the bone marrow cells confirmed the presence of a constitutional 47,XXY chromosome complement. In addition, complex karyotypic abnormalities were present.

Patients with triangular fibrocartilage complex injuries and distal radioulnar joint instability have reduced rotational torque in the forearm.

Science.gov (United States)

Andersson, J K; Axelsson, P; Strömberg, J; Karlsson, J; Fridén, J

2016-09-01

A total of 20 patients scheduled for wrist arthroscopy, all with clinical signs of rupture to the triangular fibrocartilage complex and distal radioulnar joint instability, were tested pre-operatively by an independent observer for strength of forearm rotation. During surgery, the intra-articular pathology was documented by photography and also subsequently individually analysed by another independent hand surgeon. Arthroscopy revealed a type 1-B injury to the triangular fibrocartilage complex in 18 of 20 patients. Inter-rater reliability between the operating surgeon and the independent reviewer showed absolute agreement in all but one patient (95%) in terms of the injury to the triangular fibrocartilage complex and its classification. The average pre-operative torque strength was 71% of the strength of the non-injured contralateral side in pronation and supination. Distal radioulnar joint instability with an arthroscopically verified injury to the triangular fibrocartilage complex is associated with a significant loss of both pronation and supination torque. Case series, Level IV. © The Author(s) 2015.

Tuberous Sclerosis

Science.gov (United States)

... National Institute of Neurological Disorders and Stroke (NINDS). Esclerosis tuberosa Order NINDS Publications Patient Organizations Child Neurology ... National Institute of Neurological Disorders and Stroke (NINDS). Esclerosis tuberosa Order NINDS Publications Definition Tuberous sclerosis (TSC) ...

Mechanisms of Angiogenesis and Lymphangiogenesis in TSC Skin Tumors

Science.gov (United States)

2011-09-16

professional and personal life. I enjoyed tasting all the different cuisines as part of our birthday celebrations and also his Christmas decorations. I...associated with tuberous sclerosis complex, Am J Kidney Dis 2006, 48:e27-29 78. Hofbauer GF, Marcollo-Pini A, Corsenca A, Kistler AD, French LE, Wuthrich

Effects of Mediterranean diet supplemented with silybin-vitamin E-phospholipid complex in overweight patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Abenavoli, Ludovico; Greco, Marta; Nazionale, Immacolata; Peta, Valentina; Milic, Natasa; Accattato, Francesca; Foti, Daniela; Gulletta, Elio; Luzza, Francesco

2015-04-01

Non-alcoholic fatty liver disease is the most common liver disease worldwide. The aim of this study is to compare the metabolic effects of the Mediterranean diet versus the diet associated with silybin, phosphatidylcholine and vitamin E complex in overweight patients with non-alcoholic fatty liver disease. Thirty Caucasian overweight patients were randomized into three groups of 10 (Groups A, B and C). A personalized Mediterranean diet was started in Group A and B patients. In association with the diet, Group B patients were given Realsil complex, daily, for 6 months. Group C patients refused any treatment. We showed that the Mediterranean diet alone, or in association with the Realsil complex, led to the significant variation in BMI, waist circumference, total cholesterol and triglycerides. We also observed a statistically significant decrease in homeostasis model assessment technique in Group B patients.

SWOT analysis of total sanitation campaign in Yavatmal district of Maharashtra

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Pardeshi Geeta

2008-01-01

Full Text Available Aims: To study the strengths, weaknesses, opportunities, and threats of the Total Sanitation Campaign (TSC in the Yavatmal district of Maharashtra. Methodology: Data was collected in December 2006 through interviews with stakeholders, house-to-house surveys, focus group discussions, and transect walks. Information in each category was finalized in a meeting after brainstorming and discussion with the TSC cell members. Results: The strengths of the campaign were innovations in Information Education and Communication, motivation through incentives, competitive spirit, active participation and partnerships, involvement of women, and universal coverage. The main weaknesses of the program were the absence of Rural Sanitary Marts/Production Centers, poor maintenance of Women Sanitary Complexes, lack of facilities for monitoring/ follow-up and a temporary focus of the campaign approach. There is an opportunity to tap additional resources, learn from other experiences, and institute back-up agencies to support and guide the community in the post-TSC phase. A change in administration and local leadership and loss of priority and interest needed to sustain the momentum while scaling up the interventions are possible threats for the program.

Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

Science.gov (United States)

Kumagai, N; Kaneko, F; Tsunematsu, S; Tsuchimoto, K; Tada, S; Saito, H; Hibi, T

2007-07-01

Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

Radiofrequency ablation of stellate ganglion in a patient with complex regional pain syndrome

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Chinmoy Roy

2014-01-01

Full Text Available Complex regional pain syndrome (CRPS is characterized by a combination of sensory, motor, vasomotor, pseudomotor dysfunctions and trophic signs. We describe the use of radiofrequency (RF ablation of Stellate ganglion (SG under fluoroscopy, for long-term suppression of sympathetic nervous system, in a patient having CRPS-not otherwise specified. Although the effects of thermal RF neurolysis may be partial or temporary, they may promote better conditions toward rehabilitation. The beneficial effect obtained by the RF neurolysis of SG in this particular patient strongly advocates the use of this mode of therapy in patients with CRPS.

Metformin-treated patients with type 2 diabetes have normal mitochondrial complex I respiration

DEFF Research Database (Denmark)

Larsen, Steen; Rabøl, R; Hansen, C N

2012-01-01

The glucose-lowering drug metformin has been shown to inhibit complex I of the mitochondrial electron transport chain in skeletal muscle. To investigate this effect in vivo we studied skeletal muscle mitochondrial respiratory capacity and content from patients with type 2 diabetes treated...

Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome

DEFF Research Database (Denmark)

Llewellyn, A; McCabe, CS; Hibberd, Y

2018-01-01

Background: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. Objectives: To define recovery from the patient...

Investigation of obsessive-compulsive disorder and assessment of obsessionality as a personality trait in patients with complex partial seizure

Directory of Open Access Journals (Sweden)

Banihashemian K

2010-05-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Behavioral changes in patients with epilepsy could cause comorbid psychiatric disorders such as anxiety disorders. This study is concerned with investigation of obsessive-compulsive disorders and assessment of obsessionality as a personality trait in patients with complex partial seizure. "n"nMethods: Seventy six patients with complex partial seizure, 74 patients with generalized epilepsy that referred to Shiraz psychiatric professional center during three month (from July to September 2009, and 76 matched healthy controls were randomly selected and evaluated using the Yale-Brown obsessive compulsive scale (Y-BOCS, short form of Minnesota multiphasic personality inventory (MMPI and clinical interview. "n"nResults: Complex partial seizure and obsessive-compulsive disorder (%13.15 are significantly more prevalent than generalized seizure (%2.70 and than control groups (%1.31 (p<0.001, and mean of psychasthenia scale (Pt scale scores in patients with complex partial seizure is more than mean of Pt scores in generalized epilepsy and control groups (p<0.001. There is significant relationship between total score of Yale-Brown scale and Pt scale in MMPI (r=0.79, p<0.01."n"nConclusions: Patients with complex

Tokamak simulation code manual

International Nuclear Information System (INIS)

Chung, Moon Kyoo; Oh, Byung Hoon; Hong, Bong Keun; Lee, Kwang Won

1995-01-01

The method to use TSC (Tokamak Simulation Code) developed by Princeton plasma physics laboratory is illustrated. In KT-2 tokamak, time dependent simulation of axisymmetric toroidal plasma and vertical stability have to be taken into account in design phase using TSC. In this report physical modelling of TSC are described and examples of application in JAERI and SERI are illustrated, which will be useful when TSC is installed KAERI computer system. (Author) 15 refs., 6 figs., 3 tabs

Child Abuse and Dissociation in Patients with Complex Regional Pain Syndrome

Directory of Open Access Journals (Sweden)

Michael Williams

1999-01-01

Full Text Available >OBJECTIVE: In the absence of a proven medical explanation for the chronic pain syndrome Complex Regional Pain Syndrome type I (CRPS I, this study explored a hypothetical link between childhood physical and sexual abuse, and the subsequent development of CRPS I. The hypothesis predicts the existence of a subpopulation of CRPS I patients with a high frequency of dissociative experiences corresponding to a history of childhood trauma.

Philosophy at the bedside - phenomenology, complexity and virtue in the care of patients.

Science.gov (United States)

Mitchell, Derek

2014-12-01

This personal reflection, based partly on my own experience as a patient, is written from the triple perspective of patient, former Health Service manager and philosopher. By beginning with the accounts of the first-hand lived experiences of patients (my own and those of Havi Carel), which I argue are central to an understanding of illness, and by then moving through the complexity of the health care environment, I aim to show that only the promulgation of a virtue-based theory of ethics and action can lead to real improvements in the quality of care delivered to patients. The case is set out to bring together the philosophical insights of phenomenology, complexity theory and Virtue Ethics. The argument shows that only Virtue Ethics provides an adequate means to respond to the unique situation and feelings of the individual person who is ill. This conclusion inevitably implies criticism of the ways that the performance of the institutions and the people who provide health care have been measured and regulated in the UK National Health Service. Overall the conclusions of this paper suggest that an approach based on virtuous agency and more closely directed towards the lived experience of people who are ill is needed to ensure both safety and improved quality in health care services. © 2014 John Wiley & Sons, Ltd.

3He/4He production ratios by tetrahedral symmetric condensation

International Nuclear Information System (INIS)

Takahashi, Akito

2006-01-01

The present paper treats application of the Electronic Quasi-Particle Expansion Theory (EQPET) model for Tetrahedral Symmetric Condensate (TSC) of H/D mixed systems for Pd host metal. Production ratios of 3 He/ 4 He for multi-body fusion reactions in H/D mixed TSC systems are calculated as a function of H/D mixing ratio. The model is further extended to treat direct nuclear interactions between host-metal nucleus and TSC of pure four protons (or four deuterons), since TSC can become very small (far less than 1 pm radius) charge-neutral pseudo-particle. Results for the case of Ni + 4p/TSC are discussed with Ni + p capture reactions and Ni + 4p fission reactions. (authors)

CLINICAL AND MORPHOLOGICAL CHARACTERIZATION OF FETOPLACENTAL COMPLEX IN PREGNANT PATIENTS WITH DIFFUSE TOXIC GOITER

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V. A. Petrukhin

2015-01-01

Full Text Available Background: The course of pregnancy and delivery in patients with diffuse toxic goiter (DTG is often complicated by preeclampsia, fetoplacental insufficiency, placental abruption and associated with higher maternal and perinatal mortality. Aim: To study particulars of fetoplacental complex functioning in DTG. Materials and methods: We assessed pregnant patients with DTG (n = 92 and their newborns (n = 94. By the time of delivery, 86 of patients were clinically and biochemically euthyroid. Functions of fetoplacental complex (by levels of placental lactogen, α-fetoprotein, estriol, progesterone and cortisol were assessed by radioimmune and immunoenzyme assays. Fetometrical parameters of fetuses were studied by ultrasound method. Complex assessment of placentas was done by light and electronic microscopy. Results: Eighty seven (94,6% patients with DTG had combined complications of pregnancy. The most frequent were: the threat of termination of pregnancy, in 68 (73.9% of cases, low placenta placement, in 23 (25%, anemia, in 56 (60.9%, pre-eclampsia, in 56 (60.9%. In 59 of patients (64.1%, fetoplacental insufficiency was diagnosed, with predominance of strain or exhaustion reactions. Critical status of fetoplacental complex was found in pregnant patients with uncontrolled DTG and duration of control of less than 20 weeks, as well as in pregnant patients with DTG relapses. The values of main hormones (placental lactogen, α-fetoprotein and progesterone were below 10th percentile.According to the results of the ultrasound assessments, fetuses from mothers with DTG during gestation demonstrated decrease of the majority or percentile parameters, such as biparietal cranial size, fetal femoral length, abdomen diameter, that was especially prominent in the groups with relapsing DTG.Eighty eight of 94 newborns (93.6% were born full-term. In total, every third baby (29.3% had some degree of intrauterine developmental delay at birth. Among the cases with

Experimental study on the drying of natural latex medical gloves

Science.gov (United States)

Chankrachang, Mano; Yongyingsakthavorn, Pisit; Tohsan, Atitaya; Nontakaew, Udomkiat

2018-01-01

The purpose of this research was to study latex film drying at 70 °C using a laboratory drying oven. Two different total solid content (TSC) latex compounds, which 45% TSC and 35% TSC were used. The undried latex films were prepared according to the common procedures used in latex gloves manufacturers, that is, by dry coagulant dipping process. The experimental results such as initial moisture content, the amount of moisture and drying time of latex films in each latex compound formula were determined. After that, the results were projected to calculate on the production capacity expand by 1 million piece/day of natural latex medical gloves. Finally, the rate of moisture entering the latex drying oven and the energy consumption of the drying oven were estimated. The results indicated that when the 35% TSC of latex compound was used. The initial moisture content of latex film was higher than 45% TSC of latex compound about 7%. The drying time of 35% TSC was longer than 45% TSC for 2.5 min and consume more energy about 10%. As a result, the 45% TSC latex compound was the better way to saving energy and managing humidity in the production line. Therefore, it was found to very useful to an approximate design length and size of actual of latex drying oven and the rate of moisture entering the oven as well.

Managing the Lower Eyelid Complex in the Thick-Skinned Patient.

Science.gov (United States)

Floyd, Elizabeth Mia; Perkins, Stephen W

2018-02-01

Thick skin presents a unique set of challenges within the realm of facial plastic surgery, and addressing the lower lid complex is no exception. There are several procedures for addressing the lower lids, the first and foremost being lower lid blepharoplasty. However, the remaining procedures combined with surgical techniques have exclusive implications in thick skin. Understanding the anatomy and various techniques that can be applied to thick skin can help achieve aesthetically more pleasing results in comparison to those of thin skin. As will be discussed in this article, patients with skin color of Fitzpatrick's grade III or higher have several characteristics associated with their skin, including thicker dermis as well as different patterns of aging, which have implications for addressing the lower lid complex. The senior author has extensive experience performing lower lid procedures and seeks to impart how best to understand and adapt for these differences to allow for the best aesthetic result. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Estimation of doses to patients from ''complex'' conventional X-ray examinations

International Nuclear Information System (INIS)

Calzado, A.; Vano, E.; Moran, P.; Ruiz, S.; Gonzalez, L.; Castellote, C.

1991-01-01

A numerical method has been developed to estimate organ doses and effective dose-equivalent for patients undergoing three 'complex' examinations (barium meal, barium enema and intravenous urography). The separation of radiological procedures into a set of standard numerical views is based on the use of Monte Carlo conversion factors and measurements within a Remab phantom. Radiation doses measured in a phantom for such examinations were compared with predictions of the ''numerical'' method. Dosimetric measurements with thermoluminescent dosemeters attached to the patient's skin along with measurements of the dose-area product during the examination have enabled the derivation of organ doses and to estimate effective dose-equivalent. Mean frequency weighted values of dose-area product, energy imparted to the patient, doses to a set of organs and effective dose-equivalent in the area of Madrid are reported. Comparisons of results with those from similar surveys in other countries were made. (author)

Leadless pacemaker implantation in a patient with complex congenital heart disease and limited vascular access

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Paolo Ferrero

2016-11-01

Full Text Available Management of rhythm related issues might be particularly challenging in patients with congenital heart disease due to complex anatomy and restricted vascular access. The leadless technology appears a suitable and attractive alternative for this population. We describe a patient with single ventricle physiology who successfully underwent implantation of a leadless pacemaker.

From mTOR to Cognition: Molecular and Cellular Mechanisms of Cognitive Impairments in Tuberous Sclerosis

Science.gov (United States)

Ehninger, D.; de Vries, P. J.; Silva, A. J.

2009-01-01

Background: Tuberous sclerosis (TSC) is a multi-system disorder caused by heterozygous mutations in the "TSC1" or "TSC2" gene and is often associated with neuropsychiatric symptoms, including intellectual disability, specific neuropsychological deficits, autism, other behavioural disorders and epilepsy. Method: Here, we review evidence from animal…

Correlated analysis of 2 MeV proton-induced radiation damage in CdZnTe crystals using photoluminescence and thermally stimulated current techniques

Energy Technology Data Exchange (ETDEWEB)

Gu, Yaxu [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Jie, Wanqi, E-mail: jwq@nwpu.edu.cn [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Rong, Caicai [Institute of Modern Physics, Applied Ion Beam Physics Laboratory, Fudan University, Shanghai 200433 (China); Wang, Yuhan; Xu, Lingyan; Xu, Yadong [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Lv, Haoyan; Shen, Hao [Institute of Modern Physics, Applied Ion Beam Physics Laboratory, Fudan University, Shanghai 200433 (China); Du, Guanghua [Materials Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Fu, Xu [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); and others

2016-11-01

Highlights: • 2 MeV proton-induced radiation damage in CdZnTe crystals is investigated by PL and TSC techniques. • The influence of radiation damage on the luminescent and electrical properties of CdZnTe crystals is studied. • Intensity of PL spectrum is found to decrease significantly in irradiated regions, suggesting the increase of non-radiative recombination centers. • A correlated analysis of PL and TSC spectra suggests that the density of dislocations and A-centers increase after proton irradiation. - Abstract: Radiation damage induced by 2 MeV protons in CdZnTe crystals has been studied by means of photoluminescence (PL) and thermally stimulated current (TSC) techniques. A notable quenching of PL intensity is observed in the regions irradiated with a fluence of 6 × 10{sup 13} p/cm{sup 2}, suggesting the increase of non-radiative recombination centers. Moreover, the intensity of emission peak D{sub complex} centered at 1.48 eV dominates in the PL spectrum obtained from irradiated regions, ascribed to the increase of interstitial dislocation loops and A centers. The intensity of TSC spectra in irradiated regions decreases compared to the virgin regions, resulting from the charge collection inefficiency caused by proton-induced recombination centers. By comparing the intensity of identified traps obtained from numerical fitting using simultaneous multiple peak analysis (SIMPA) method, it suggests that proton irradiation under such dose can introduce high density of dislocation and A-centers in CdZnTe crystals, consistent with PL results.

Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients

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Adler Charles

2009-07-01

Full Text Available Abstract Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23.

Patterns of patient safety culture: a complexity and arts-informed project of knowledge translation.

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Mitchell, Gail J; Tregunno, Deborah; Gray, Julia; Ginsberg, Liane

2011-01-01

The purpose of this paper is to describe patterns of patient safety culture that emerged from an innovative collaboration among health services researchers and fine arts colleagues. The group engaged in an arts-informed knowledge translation project to produce a dramatic expression of patient safety culture research for inclusion in a symposium. Scholars have called for a deeper understanding of the complex interrelationships among structure, process and outcomes relating to patient safety. Four patterns of patient safety culture--blinding familiarity, unyielding determination, illusion of control and dismissive urgency--are described with respect to how they informed creation of an arts-informed project for knowledge translation.

Cancer treatment decision-making processes for older patients with complex needs: a qualitative study.

Science.gov (United States)

Bridges, Jackie; Hughes, Jane; Farrington, Naomi; Richardson, Alison

2015-12-14

Although older people can experience complex health and social care needs alongside a primary cancer diagnosis, little is understood about how cancer treatment decisions are made for this population. This study aimed to investigate how cancer treatment decisions are formulated for older people with complex health and social care needs and the factors that shape these processes. Qualitative study involving semistructured interviews and non-participant observations. Framework approach used for data analysis. Breast and colorectal cancer services in five English NHS hospital trusts. Interviews: purposive sample of 22 clinicians directly involved in a face-to-face clinical role with patients regarding cancer treatment and care, maximising variation across clinical roles, tumour types and trusts. purposive sample of five cancer multidisciplinary meetings, maximising variation across location, team size and tumour type. The initial stages of cancer treatment decision-making are team-based, medically dominated and focused on the cancer. For patients with complex health and social care needs that extend beyond cancer pathology, later and less visible stages in the decision-making process are more haphazard and may result in less effective and workable treatment plans, as individual clinicians struggle to devise and deliver these plans without breaching time-based targets. Service targets that focus resources solely on the presenting disease can disadvantage older patients with complex health and social care needs that extend beyond this primary diagnosis. Care should be taken to ensure time-based targets do not disincentivise thorough and timely assessment that can lead to the formulation of treatment plans tailored to individual needs and circumstances. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Fractal dimension and vessel complexity in patients with cerebral arteriovenous malformations.

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Gernot Reishofer

Full Text Available The fractal dimension (FD can be used as a measure for morphological complexity in biological systems. The aim of this study was to test the usefulness of this quantitative parameter in the context of cerebral vascular complexity. Fractal analysis was applied on ten patients with cerebral arteriovenous malformations (AVM and ten healthy controls. Maximum intensity projections from Time-of-Flight MRI scans were analyzed using different measurements of FD, the Box-counting dimension, the Minkowski dimension and generalized dimensions evaluated by means of multifractal analysis. The physiological significance of this parameter was investigated by comparing values of FD first, with the maximum slope of contrast media transit obtained from dynamic contrast-enhanced MRI data and second, with the nidus size obtained from X-ray angiography data. We found that for all methods, the Box-counting dimension, the Minkowski dimension and the generalized dimensions FD was significantly higher in the hemisphere with AVM compared to the hemisphere without AVM indicating that FD is a sensitive parameter to capture vascular complexity. Furthermore we found a high correlation between FD and the maximum slope of contrast media transit and between FD and the size of the central nidus pointing out the physiological relevance of FD. The proposed method may therefore serve as an additional objective parameter, which can be assessed automatically and might assist in the complex workup of AVMs.

Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients

NARCIS (Netherlands)

Santen, Gijs W. E.; Aten, Emmelien; Vulto-van Silfhout, Anneke T.; Pottinger, Caroline; van Bon, Bregje W. M.; van Minderhout, Ivonne J. H. M.; Snowdowne, Ronelle; van der Lans, Christian A. C.; Boogaard, Merel; Linssen, Margot M. L.; Vijfhuizen, Linda; van der Wielen, Michiel J. R.; Vollebregt, M. J. Ellen; Breuning, Martijn H.; Kriek, Marjolein; van Haeringen, Arie; den Dunnen, Johan T.; Hoischen, Alexander; Clayton-Smith, Jill; de Vries, Bert B. A.; Hennekam, Raoul C. M.; van Belzen, Martine J.; Almureikhi, Mariam; Baban, Anwar; Barbosa, Mafalda; Ben-Omran, Tawfeg; Berry, Katherine; Bigoni, Stefania; Boute, Odile; Brueton, Louise; van der Burgt, Ineke; Canham, Natalie; Chandler, Kate E.; Chrzanowska, Krystyna; Collins, Amanda L.; de Toni, Teresa; Dean, John; den Hollander, Nicolette S.; Flore, Leigh Anne; Fryer, Alan; Gardham, Alice; Graham, John M.; Harrison, Victoria; Horn, Denise; Jongmans, Marjolijn C.; Josifova, Dragana; Kant, Sarina G.; Kapoor, Seema; Kingston, Helen; Maas, Saskia M.

2013-01-01

De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2,

Complement, circulating immine complexes and cenral hemodynamics in patients with pulmonary tuberculosis

International Nuclear Information System (INIS)

Ershov, A.I.; Fedoseeva, V.N.; Mol'kov, Yu.N.; Evstaf'ev, Yu.A.; Bochkarev, E.G.; Shcheglova, V.T.

1987-01-01

By means of radiocardiography and radiometry central hemodynamic parameters were measured, using 131 I-labelled human serum albumin, pulmonary-artery systolic pressure (PASP) was assessed indirectly, and serum complement and circulating immune complexes (CIC) were measured before 48 hours after subcutaneous administration of 20 TU tuberculin in 65 patients with active pulmonary tuberculosis, 25 clinically-cured tuberculosis patients and 16 patients with chronic nonspecific pulmonary diseases (CNPD). A potent direct correlation was demonstrated between the CIC level and PASP elevation. It is suggested that close correlation between CIC and PASP elevation may be evidence of their pathogenetic involvement in chronic pulmonary heart, as well as the fact that prolonged and effective chemotherapy weakens adverse cardiovascular effects of immunologic factors, which can however persist in some individuals even after they are apparently cured from tuberculosis

Unpacking the Complexity of Patient Handoffs Through the Lens of Cognitive Load Theory.

Science.gov (United States)

Young, John Q; Ten Cate, Olle; O'Sullivan, Patricia S; Irby, David M

2016-01-01

The transfer of a patient from one clinician to another is a high-risk event. Errors are common and lead to patient harm. More effective methods for learning how to give and receive sign-out is an important public health priority. Performing a handoff is a complex task. Trainees must simultaneously apply and integrate clinical, communication, and systems skills into one time-limited and highly constrained activity. The task demands can easily exceed the information-processing capacity of the trainee, resulting in impaired learning and performance. Appreciating the limits of working memory can help identify the challenges that instructional techniques and research must then address. Cognitive load theory (CLT) identifies three types of load that impact working memory: intrinsic (task-essential), extraneous (not essential to task), and germane (learning related). The authors generated a list of factors that affect a trainee's learning and performance of a handoff based on CLT. The list was revised based on feedback from experts in medical education and in handoffs. By consensus, the authors associated each factor with the type of cognitive load it primarily effects. The authors used this analysis to build a conceptual model of handoffs through the lens of CLT. The resulting conceptual model unpacks the complexity of handoffs and identifies testable hypotheses for educational research and instructional design. The model identifies features of a handoff that drive extraneous, intrinsic, and germane load for both the sender and the receiver. The model highlights the importance of reducing extraneous load, matching intrinsic load to the developmental stage of the learner and optimizing germane load. Specific CLT-informed instructional techniques for handoffs are explored. Intrinsic and germane load are especially important to address and include factors such as knowledge of the learner, number of patients, time constraints, clinical uncertainties, overall patient

Treatment compliance and effectiveness in complex PTSD patients with co-morbid personality disorder undergoing stabilizing cognitive behavioral group treatment: a preliminary study

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Ethy Dorrepaal

2013-11-01

Full Text Available Background: In the empirical and clinical literature, complex posttraumatic stress disorder (PTSD and personality disorders (PDs are suggested to be predictive of drop-out or reduced treatment effectiveness in trauma-focused PTSD treatment. Objective: In this study, we aimed to investigate if personality characteristics would predict treatment compliance and effectiveness in stabilizing complex PTSD treatment. Method: In a randomized controlled trial on a 20-week stabilizing group cognitive behavioral treatment (CBT for child-abuse-related complex PTSD, we included 71 patients of whom 38 were randomized to a psycho-educational and cognitive behavioral stabilizing group treatment. We compared the patients with few PD symptoms (adaptive (N=14 with the non-adaptive patients (N=24 as revealed by a cluster analysis. Results: We found that non-adaptive patients compared to the adaptive patients showed very low drop-out rates. Both non-adaptive patients, classified with highly different personality profiles “withdrawn” and “aggressive,” were equally compliant. With regard to symptom reduction, we found no significant differences between subtypes. Post-hoc, patients with a PD showed lower drop-out rates and higher effect sizes in terms of complex PTSD severity, especially on domains that affect regulation and interpersonal problems. Conclusion: Contrary to our expectations, these preliminary findings indicate that this treatment is well tolerated by patients with a variety of personality pathology. Larger sample sizes are needed to study effectiveness for subgroups of complex PTSD patients.

Cost-efficiency of specialist hyperacute in-patient rehabilitation services for medically unstable patients with complex rehabilitation needs: a prospective cohort analysis.

Science.gov (United States)

Turner-Stokes, Lynne; Bavikatte, Ganesh; Williams, Heather; Bill, Alan; Sephton, Keith

2016-09-08

To evaluate functional outcomes, care needs and cost-efficiency of hyperacute (HA) rehabilitation for a cohort of in-patients with complex neurological disability and unstable medical/surgical conditions. A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2012-2015. Two HA specialist rehabilitation services in England, providing different service models for HA rehabilitation. All patients admitted to each of the units with an admission rehabilitation complexity M score of ≥3 (N=190; mean age 46 (SD16) years; males:females 63:37%). Diagnoses were acquired brain injury (n=166; 87%), spinal cord injury (n=9; 5%), peripheral neurological conditions (n=9; 5%) and other (n=6; 3%). Specialist in-patient multidisciplinary rehabilitation combined with management and stabilisation of intercurrent medical and surgical problems. Rehabilitation complexity and medical acuity: Rehabilitation Complexity Scale-version 13. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK FIM+FAM). (1) reduction in dependency and (2) cost-efficiency, measured as the time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of on-going care in the community. The mean length of stay was 103 (SD66) days. Some differences were observed between the two units, which were in keeping with the different service models. However, both units showed a significant reduction in dependency and acuity between admission and discharge on all measures (Wilcoxon: pspecialist HA rehabilitation can be highly cost-efficient, producing substantial savings in on-going care costs, and relieving pressure in the acute care services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Physio-balneotherapy factors in the complex treatment of patients with gouty arthritis at the sanatorium stage of rehabilitation

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Tеtіana Ananіeva

2017-12-01

Full Text Available Purpose: to analyze and summarize the main approaches to the appointment of the main physiotherapeutic and balneological factors in the complex treatment of patients with gouty arthritis in the conditions of sanatorium treatment. Material & Methods: analysis of modern scientific and scientific-methodological literature on the problem of physical rehabilitation of patients with gout. Results: the main approaches to the appointment of modern methods of physiotherapy in combination with hydropathic and mud factors in the complex treatment of patients with gouty arthritis at the sanatorium stage of rehabilitation. Conclusions: the results of the study can be used as a basis for compiling a comprehensive physical rehabilitation program for patients with gouty arthritis in a sanatorium stage of rehabilitation.

Analysis of the quantitative dermatoglyphics of the digito-palmar complex in patients with multiple sclerosis.

Science.gov (United States)

Supe, S; Milicić, J; Pavićević, R

1997-06-01

Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.

On rational complex of investigation methods in prophylactic examination of patients with chronic kidney diseases

International Nuclear Information System (INIS)

Yazykov, A.S.; Telichko, F.F.

1989-01-01

A retrospective evaluation of the total quantity of X-ray procedures and the radiation degree in 310 patients with chronic kidney diseases is given. It is ascertained that only account of integral absorbed dose in the organ tissues, comprising the doses of X-ray examinations of other organs during the patient lifetime, can serve as the main condition for developing well-grounded recommendations concerning rational complex of examination methods during prophylactic examination of patients with chronic kidney disease. 9 refs.; 4 figs

Clinical Phenomenology of Childhood Abuse-Related Complex PTSD in a Population of Female Patients: Patterns of Personality Disturbance

NARCIS (Netherlands)

Dorrepaal, E.; Thomaes, K.; Smit, J.H.; Hoogendoorn, A.; Veltman, D.J.; van Balkom, A.J.L.M.; Draijer, P.J.

2012-01-01

Objective: Complex posttraumatic stress disorder (PTSD) involves a variety of personality disturbances presumed to result from repeated interpersonal trauma such as child abuse. As Complex PTSD patients are a heterogeneous population, we searched for clinically relevant personality-based subtypes.

Triboelectric-Based Transparent Secret Code.

Science.gov (United States)

Yuan, Zuqing; Du, Xinyu; Li, Nianwu; Yin, Yingying; Cao, Ran; Zhang, Xiuling; Zhao, Shuyu; Niu, Huidan; Jiang, Tao; Xu, Weihua; Wang, Zhong Lin; Li, Congju

2018-04-01

Private and security information for personal identification requires an encrypted tool to extend communication channels between human and machine through a convenient and secure method. Here, a triboelectric-based transparent secret code (TSC) that enables self-powered sensing and information identification simultaneously in a rapid process method is reported. The transparent and hydrophobic TSC can be conformed to any cambered surface due to its high flexibility, which extends the application scenarios greatly. Independent of the power source, the TSC can induce obvious electric signals only by surface contact. This TSC is velocity-dependent and capable of achieving a peak voltage of ≈4 V at a resistance load of 10 MΩ and a sliding speed of 0.1 m s -1 , according to a 2 mm × 20 mm rectangular stripe. The fabricated TSC can maintain its performance after reciprocating rolling for about 5000 times. The applications of TSC as a self-powered code device are demonstrated, and the ordered signals can be recognized through the height of the electric peaks, which can be further transferred into specific information by the processing program. The designed TSC has great potential in personal identification, commodity circulation, valuables management, and security defense applications.

Personality assessment of patients with complex regional pain syndrome type I.

Science.gov (United States)

Monti, D A; Herring, C L; Schwartzman, R J; Marchese, M

1998-12-01

There is controversy regarding the importance of psychological/psychiatric factors in the development of the Complex Regional Pain Syndrome (CRPS). Our objective was to determine whether CRPS type I patients were psychiatrically different from other chronic pain patients, with particular attention to personality pathology. A standardized clinical assessment of all major psychiatric categories, including personality disorders, was performed on 25 CRPS type I patients and a control group of 25 patients with chronic low back pain from disc-related radiculopathy. Both sections of the Structured Clinical Interview for the Diagnostic and Statistical Manual (3rd ed., rev.) and the visual analog scale. Both groups were similar in terms of pain intensity and duration. Statistical analysis showed both groups to have a significant amount of major psychiatric comorbidity, in particular major depressive disorder, and a high incidence of personality disorders. Therefore, intense chronic pain was associated with significant psychiatric comorbidity in both groups and in similar proportions. The high incidence of personality pathology in both groups may represent an exaggeration of maladaptive personality traits and coping styles as a result of a chronic, intense, state of pain.

Complex antithrombotic therapy: determinants of patient preference and impact on medication adherence

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Abraham NS

2015-11-01

Full Text Available Neena S Abraham,1,2 Aanand D Naik,3,4 Richard L Street Jr,3–5 Diana L Castillo,3 Anita Deswal,6 Peter A Richardson,3,4 Christine M Hartman,3 George Shelton Jr,3,4 Liana Fraenkel7,8 1Division of Gastroenterology, Mayo Clinic, Scottsdale, AZ, USA; 2Divison of Healthcare Policy and Research, Department of Health Services Research, Rochester, MN, USA; 3Center for Innovations in Quality, Effectiveness, and Safety at the Michael E DeBakey VA Medical Center, Houston, TX, USA; 4Department of Medicine, Baylor College of Medicine, Houston, TX, USA; 5Department of Communication, Texas A&M University, College Station, TX, USA; 6Cardiology, Michael E DeBakey VAMC, Houston, TX, USA; 7Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA; 8Department of Medicine, Yale University, New Haven, CT, USA Purpose: For years, older patients have been prescribed multiple blood-thinning medications (complex antithrombotic therapy [CAT] to decrease their risk of cardiovascular events. These therapies, however, increase risk of adverse bleeding events. We assessed patient-reported trade-offs between cardioprotective benefit, gastrointestinal bleeding risk, and burden of self-management using adaptive conjoint analysis (ACA. As ACA could be a clinically useful tool to obtain patient preferences and guide future patient-centered care, we examined the clinical application of ACA to obtain patient preferences and the impact of ACA on medication adherence.Patients and methods: An electronic ACA survey led 201 respondents through medication risk–benefit trade-offs, revealing patients’ preferences for the CAT risk/benefit profile they valued most. The post-ACA prescription regimen was categorized as concordant or discordant with elicited preferences. Adherence was measured using VA pharmacy refill data to measure persistence of use prior to and 1 year following preference-elicitation. Additionally, we analyzed qualitative interviews of 56 respondents

Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Wener, M.H.; Mannik, M.; Schwartz, M.M.; Lewis, E.J.

1987-01-01

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc)

Prevalence and Prognostic Significance of Runs of Premature Atrial Complexes in Ischemic Stroke Patients

DEFF Research Database (Denmark)

Høeg Vinther, Kristina; Tveskov, Claus; Möller, Sören

2016-01-01

BACKGROUND AND PURPOSE: Runs of premature atrial complexes (PACs) are common in stroke patients and perceived to be clinically insignificant, but their prognostic significance is unclear. This study investigated the association between runs of PACs in ischemic stroke patients and the risk...... of recurrent ischemic strokes/transient ischemic attacks (TIAs) or death. METHODS: The study included consecutive patients admitted with an ischemic stroke from August 2008 to April 2011. Patients with known and newly detected atrial fibrillation were excluded. Runs of PACs were defined as 3 or more PACs...... lasting less than 30 seconds during 48 hours of continuous inpatient cardiac telemetry. The patients were followed for 4 years or until death, whichever came first. They were stratified according to stroke severity. The combined primary endpoint was a recurrent ischemic stroke/TIA or death. RESULTS...

The Effect of a Complex (3-week Therapy on the Hip and Knee Joints in Obese Patients

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Tóvári Anett

2015-05-01

Full Text Available Currently, overweight and obesity are the most widespread problems in life-style having a significant impact on everyday life, and thus, conduct of life. Further contributory problems may develop in patients with weight problems: deformities of the joints and skeleton (coxarthrosis and gonarthrosis, circulatory problems and arrhythmia. Overweight definitely has an effect on motion: some people are not involved in certain activities as it is impossible for them because of their weight problem. Thus, even more health problems are generated because of the overweight. The first question arising in discussing the actuality of this issue is what effect the applied therapy (massage, therapeutic exercises, electrotherapy and balneotherapy has on the knee and hip joints of patients with weight problems hospitalised in our Institute for a 3-week complex therapy. Based on my prior hypothesis, positive changes are detected in a minimum percentage in the condition of overweight or obese patients. My hypothesis was that the range of flexion and extension of the hip and knee joints would improve compared to other movements. Based on the results of the studied population (n=30, my hypothesis seems to be proven. After the 3-week complex therapy of obese patients, positive changes were found in the prearranged assessments and tests, thereby improving the general health, life-style, life quality and mental status of the patients. After the end of the complex therapy, patients were provided life-style counselling and exercise schemes to be performed in their home to maintain the achieved health status.

Changes of serum contents of LPO, SOD after treatment with vita. E-C complex in patients with liver spot

International Nuclear Information System (INIS)

Li Qing; Feng Zheng

2005-01-01

Objective: To investigate the changes of serum contents of LPO, SOD and therapeutic efficacy after treatment with Vita. E-C complex in patients with liver spot. Methods: Serum LPO and SOD contents were measured both before and after treatment with Vita E-C complex (Vita. E l00mg, Vita. C 200mg x 3/d for 3 months) in 30 patients with liver spot as well as in 10 controls. Results: Before treatment, the serum LPO contents in the patients were significantly higher than those in controls. After treatment, the LPO contents dropped markedly, being significantly lower than the values before treatment. However, the SOD contents were about the same as those in controls and changes little after treatment. Conclusion: Vita. E-C complex was of definite therapeutic value for the treatment of liver spot. (authors)

Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways

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W. Nie

2013-01-01

Full Text Available Xyloglucans (XGs of Tamarindus indica L. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed with cold water (TSw and copper complex precipitation (TSc. Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT and fibroblasts (NHDF in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show that T. indica xyloglucans promote skin regeneration by a direct influence on cell proliferation and migration.

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

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Souheil El-Chemaly

2012-09-01

Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

Mycobacterium avium complex pulmonary disease: characteristics and treatment in an Irish patient cohort.

LENUS (Irish Health Repository)

Judge, EP

2016-04-01

The prevalence of Mycobacterium avium complex (MAC) pulmonary disease is increasing globally. However, reliable national and international data relating to its epidemiology and management is lacking. During the period 2003-2014, MAC was isolated from the pulmonary samples of 75 patients at the Irish Mycobacteria Reference Laboratory (IMRL). Most patients (42, 56%) had underlying pulmonary disease, and 37 (49%) had clinical\\/radiographic characteristics consistent with MAC pulmonary disease. However, only 18 patients (24%) fulfilled internationally accepted criteria for diagnosis\\/treatment of this disease. Treatment was started in 13 (72%) of these cases, which is similar to internationally published treatment rates. The diagnosis of significant MAC pulmonary disease can be difficult, and treatment is not always warranted even when diagnostic criteria are met.

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

Science.gov (United States)

Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

2018-03-01

Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

Tailored information for cancer patients on the Internet: effects of visual cues and language complexity on information recall and satisfaction.

NARCIS (Netherlands)

Weert, J.C.M. van; Noort, G. van; Bol, N.; Dijk, L. van; Tates, K.; Jansen, J.

2011-01-01

Objective: This study was designed to investigate the effects of visual cues and language complexity on satisfaction and information recall using a personalised website for lung cancer patients. In addition, age effects were investigated. Methods: An experiment using a 2 (complex vs. non-complex

Tailored information for cancer patients on the Internet: effects of visual cues and language complexity on information recall and satisfaction

NARCIS (Netherlands)

van Weert, J.C.M.; van Noort, G.; Bol, N.; van Dijk, L.; Tates, K.; Jansen, J.

2011-01-01

Objective This study was designed to investigate the effects of visual cues and language complexity on satisfaction and information recall using a personalised website for lung cancer patients. In addition, age effects were investigated. Methods An experiment using a 2 (complex vs. non-complex

From DTCA-PD to patient information to health information: the complex politics and semantics of EU health policy.

Science.gov (United States)

Brooks, Eleanor; Geyer, Robert

2012-12-01

Between 2001 and 2011 the pharmaceutical industry, supported by DG Enterprise, was engaged in an ongoing campaign to repeal/amend the European Union (EU) ban on direct-to-consumer advertising of prescription drugs (DTCA-PD). As it became increasingly clear that the ban would not be repealed, DTCA-PD supporters tried to shift the debate away from advertising and towards the provision of 'patient information' and the rights of patients to access such information. Meanwhile, a variety of national and European health organizations, supported by DG SANCO, sought to maintain the ban and oppose the industry-supported 'patient information' campaign. Instead, they promoted a concept of 'health information' that included all aspects of citizens' health, not just pharmaceuticals. This article aims to analyse the transition from DTCA-PD to patient information to health information and examine its implications for EU health policy as a complex policy space. The article examines the emergence and development of EU health policy and the evolution of the DTCA-PD debate through the lens of complexity theory. It analyses the nature of the semantic, political and policy transition and asks why it occurred, what it tells us about EU health policy and future EU health legislation and how it may be understood from a complexity perspective. The article concludes that the complexity framework is ideally suited for the field of public health and, in particular, the DTCA-PD debate. Having successfully shifted the policy-focus of the debate to patients' rights and health information, opponents of the legislation are likely to face their next battle in the realm of cyberspace, where regulatory issues change the nature of advertising. © 2012 Blackwell Publishing Ltd.

Tokamak Simulation Code modeling of NSTX

International Nuclear Information System (INIS)

Jardin, S.C.; Kaye, S.; Menard, J.; Kessel, C.; Glasser, A.H.

2000-01-01

The Tokamak Simulation Code [TSC] is widely used for the design of new axisymmetric toroidal experiments. In particular, TSC was used extensively in the design of the National Spherical Torus eXperiment [NSTX]. The authors have now benchmarked TSC with initial NSTX results and find excellent agreement for plasma and vessel currents and magnetic flux loops when the experimental coil currents are used in the simulations. TSC has also been coupled with a ballooning stability code and with DCON to provide stability predictions for NSTX operation. TSC has also been used to model initial CHI experiments where a large poloidal voltage is applied to the NSTX vacuum vessel, causing a force-free current to appear in the plasma. This is a phenomenon that is similar to the plasma halo current that sometimes develops during a plasma disruption

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

Science.gov (United States)

Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

2013-11-01

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

Yes, but are they happy? Effects of trait self-control on affective well-being and life satisfaction.

Science.gov (United States)

Hofmann, Wilhelm; Luhmann, Maike; Fisher, Rachel R; Vohs, Kathleen D; Baumeister, Roy F

2014-08-01

Does trait self-control (TSC) predict affective well-being and life satisfaction--positively, negatively, or not? We conducted three studies (Study 1: N = 414, 64% female, Mage = 35.0 years; Study 2: N = 208, 66% female, Mage = 25.24 years; Study 3: N = 234, 61% female, Mage = 34.53 years). The key predictor was TSC, with affective well-being and life satisfaction ratings as key outcomes. Potential explanatory constructs including goal conflict, goal balancing, and emotional distress also were investigated. TSC is positively related to affective well-being and life satisfaction, and managing goal conflict is a key as to why. All studies, moreover, showed that the effect of TSC on life satisfaction is at least partially mediated by affect. Study 1's correlational study established the effect. Study 2's experience sampling approach demonstrated that compared to those low in TSC, those high in TSC experience higher levels of momentary affect even as they experience desire, an effect partially mediated through experiencing lower conflict and emotional distress. Study 3 found evidence for the proposed mechanism--that TSC may boost well-being by helping people avoid frequent conflict and balance vice-virtue conflicts by favoring virtues. Self-control positively contributes to happiness through avoiding and dealing with motivational conflict. © 2013 Wiley Periodicals, Inc.

Failure to detect circulating DNA-anti-DNA complexes by four radioimmunological methods in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Izui, S.; Lambert, P.H.; Miescher, P.A.

1977-01-01

The presence of DNA-anti-DNA complexes in sera from patients with systemic lupus erythematosus (SLE) was investigated by two new radioimmunoassays (RIA) developed for this purpose and by measuring the CLq and DNA binding activity of serum before and after treatment with DNAse. Two direct RIA developed in this study were based on the reactivity of [ 3 H]actinomycin D ([ 3 H]ACT-D) or solid-phase methylated bovine serum albumin (mBSA) with DNA-anti-DNA complexes. DNA-anti-DNA complexes prepared in vitro could be efficiently detected at various antigen-antibody ratios by these two RIA. Increased levels of circulating immune complexes as indicated by the CLq binding test were found in 52% of SLE sera. However, the frequency of specific DNA-anti-DNA complexes detected in SLE sera was very low. Only 6% of sera exhibited an increased value deviating by more than three s.d. from the normal mean when tested with the [ 3 H]ACT-D binding RIA or the solid-phase mBSA RIA. On the other hand, there was no significant difference in the serum CLq or DNA binding activity after treatment with DNAse. These results suggest that DNA-anti-DNA complexes do not occur frequently in circulating blood and represent only a very small portion of the immune complexes detected in serum from patients with SLE. (author)

Evaluation of brain metabolite in patients with complex regional pain syndrome by MR spectroscopy

International Nuclear Information System (INIS)

Iwashita, Narihito; Fukui, Mikio; Nitta, Kazuhito; Anzawa, Noriyuki; Tomie, Hisashi; Nakanishi, Miho; Matsumoto, Tomikichi; Nosaka, Shuichi

2010-01-01

Recently brain imaging studies have shown that patients with chronic pain have an altered cortical processing of nociceptive inputs. We evaluated brain metabolites in patients with complex regional pain syndrome (CRPS) using MR spectroscopy. Absolute concentrations of N-acetylaspartate (NAA) and choline (Cho) were measured in anterior cingulate (ACC) and prefrontal cortices (PFC) of patients and volunteers as matched control. Psychological aspects of patients were also evaluated with Hospital Anxiety and Depression (HAD) scale, in addition to the intensity of pain by visual analog scale. In the ACC, CRPS patients had a significant decrease of NAA and a significant increase of Cho compared to the control. Furthermore, patients with anxiety scored by HAD scale had reduced NAA concentration in ACC compared to the patients without anxiety. In the PFC, there was a reduction of NAA in the patients compared with that in control. No correlation was observed between intensity of pain and these metabolites. These results suggest that metabolite changes in ACC and PFC could reflect the pathogenesis of CRPS. (author)

Impaired recognition of social emotion in patients with complex regional pain syndrome.

Science.gov (United States)

Shin, Na Young; Kang, Do-Hyung; Jang, Joon Hwan; Park, Soo Young; Hwang, Jae Yeon; Kim, Sung Nyun; Byun, Min Soo; Park, Hye Youn; Kim, Yong Chul

2013-11-01

Multiple brain areas involved in nociceptive, autonomic, and social-emotional processing are disproportionally changed in patients with complex regional pain syndrome (CRPS). Little empirical evidence is available involving social cognitive functioning in patients with chronic pain conditions. We investigated the ability of patients with CRPS to recognize the mental/emotional states of other people. Forty-three patients with CRPS and 30 healthy controls performed the Reading Mind in the Eyes Test, which consists of photos in which human eyes express various emotional and mental states. Neuropsychological tests, including the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time test, were administered to evaluate other cognitive functions. Patients with CRPS were significantly less accurate at recognizing emotional states in other persons, but not on other cognitive tests, compared with control subjects. We found a significant association between the deficit in social-emotion recognition and the affective dimension of pain, whereas this deficit was not related to the sensory dimension of pain. Our findings suggest a disrupted ability to recognize others' mental/emotional states in patients with CRPS. This article demonstrated a deficit in inferring mental/emotional states of others in patients with CRPS that was related to pain affect. Our study suggests that additional interventions directed toward reducing distressful affective pain may be helpful to restore social cognitive processing in patients with CRPS. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

Science.gov (United States)

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Developing a complex intervention for the outpatient management of incidentally diagnosed pulmonary embolism in cancer patients.

Science.gov (United States)

Palmer, June; Bozas, George; Stephens, Andrew; Johnson, Miriam; Avery, Ged; O'Toole, Lorcan; Maraveyas, Anthony

2013-06-27

Most patients with pulmonary embolism (PE) spend 5-7 days in hospital even though only 4.5% will develop serious complications during this time. In particular, the group of patients with incidentally diagnosed PE (i-PE) includes many patients with low risk features potentially ideal for outpatient management; however the evidence for their optimal management is lacking hence relative practices may vary considerably. We describe the development process, components, links and function of a nurse-led service for the management of patients with i-PE, developed in accordance to the UK Medical Research Council complex intervention guidance. Phase 0 (Theoretical underpinning): The Pulmonary Embolism Severity Index (PESI) was selected for patient risk assessment and the American Society of Clinical Oncology (ASCO) guideline for the management of PE in cancer patients (2007) was selected as quality measure. Historical registry and audit data from our centre regarding i-PE incidence and management for the period between 2006 and 2009 illustrating the then current practices were reviewed. Phase 1 (Modelling): Modelling of the pathway included the following: a) Identification of training needs, planning and implementation of training schemes and development of transferable competencies and training materials. b) Mapping patient pathways and flow and c) Production of key documentation and Standard Operating Procedures for the delivery of the service. Phase 2 (Implementation and testing of the intervention): During the initial 12 months of implementation, remedial action was taken to address identified deficiencies regarding patient referral to the pathway, compliance with treatment protocol, patient follow up, selection challenges from the use of PESI in cancer patients and challenges regarding the "first-pass" identification of i-PE. We have developed and piloted a complex intervention to manage cancer patients with incidental PE in an outpatient setting. Adherence to evidence

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

Science.gov (United States)

Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

2017-04-01

The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Use of Prothrombin Complex Concentrate in Patients during Heart Transplantation after Implantation of a Left Ventricular Mechanical Support System

Directory of Open Access Journals (Sweden)

V. V. Lomivorotov

2012-01-01

Full Text Available Heart transplantation in patients after implantation of mechanical cardiac support devices entails an extremely high risk for perioperative bleeding. Recombinant activated coagulation factor VII is presently used to reduce the volume of bleeding in this patient group. There are parallel data on its administration-induced thromboembolic events in the literature. This paper describes a case of using a prothrombin complex concentrate in a patient during explantation of a left ventricular bypass system and subsequent orthotopic heart transplantation in the presence of significant hypocoagulation. At the end of a surgery, 1200 IU of the agent was used at a remaining bleeding rate of more than 1000 ml/hour. Within the first 24 hours after surgery, the rate of discharge drainage was less than 100 ml/hour. A control plain chest X-ray study revealed massive left-sided hydrothorax on day 2 postsurgery. The left pleural cavity was revised under thoracoscopic guidance and 1000 ml of blood clots were evacuated. Although the administration of prothrombin complex concentrate did not guard against re-intervention, its use seems a promising strategy in life-threatening bleedings in patients after explantation of mechanical cardiac support devices. Further multicenter investigations are required to determine the efficacy and safety of prothrom-bin complex concentration in cardiac surgery. Key words: Recombinant activated coagulation factor VII, prothrombin complex concentration, mechanical cardiac support device, orthotopic heart transplantation.

Development of a Pharmacokinetic Model to Describe the Complex Pharmacokinetics of Pazopanib in Cancer Patients

NARCIS (Netherlands)

Yu, Huixin; van Erp, Nielka; Bins, Sander; Mathijssen, Ron H J; Schellens, Jan H M; Beijnen, Jos H.; Steeghs, Neeltje; Huitema, Alwin D R

Background and Objective: Pazopanib is a multi-targeted anticancer tyrosine kinase inhibitor. This study was conducted to develop a population pharmacokinetic (popPK) model describing the complex pharmacokinetics of pazopanib in cancer patients. Methods: Pharmacokinetic data were available from 96

Development of a Pharmacokinetic Model to Describe the Complex Pharmacokinetics of Pazopanib in Cancer Patients

NARCIS (Netherlands)

Yu, H.; Erp, N. van; Bins, S.; Mathijssen, R.H.; Schellens, J.H.; Beijnen, J.H.; Steeghs, N.; Huitema, A.D.

2017-01-01

BACKGROUND AND OBJECTIVE: Pazopanib is a multi-targeted anticancer tyrosine kinase inhibitor. This study was conducted to develop a population pharmacokinetic (popPK) model describing the complex pharmacokinetics of pazopanib in cancer patients. METHODS: Pharmacokinetic data were available from 96

THE INFLUENCE OF COMPLEX THERAPY ON THE INFLAMMATORY MARKERS OF PATIENTS WITH SECONDARY OSTEOARTHRITIS

Directory of Open Access Journals (Sweden)

I. A. Starodubtseva

2015-01-01

Full Text Available The aim of the study is to evaluate the efficacy of complex therapy of secondary osteoarthritis in patients with rheumatoid arthritis with the use of inhibitor of interleukin-1, including the dynamics of inflammatory markers.Materials and methods: 248 patients with secondary osteoarthritis in rheumatoid arthritis were involved in the trial. The participants were divided into 4 groups: patients of group I took inhibitor of interleukin-1 (diacerein in combination with laser therapy and methotrexate; inhibitor of interleukin-1 in complex with methotrexate took patients from group II; group 3 — laser therapy + methotrexate and patients of group IV took only methotrexate. The efficacy of therapy we estimated in 6 months.Results: The constructed model surfaces indicated the decreased levels of IL-1, COMP and DAS 28 in group 1 till 6,68±0,37 pg/ml (p<0,001, 16,92±0,8 ng/ml х 10² (p<0,001 и 2,06±1,19 (p<0,05 accordingly in comparison with groups III and IV. Also the model surfaces revealed the interdependency of all these indicators. The control group (IV reacted to the treatment by decreasing the indicators as well. However, the dynamics of the changes was significantly less. In patients of groups I and II the levels of ESR and CRP decreased to 13,95±0,52* (*p<0,001 and 10,97±0,43* (*p<0,001; 16,53±0,63* (*p<0,001 and 12,81±0,77* (*p<0,001 accordingly.Conclusions: In comparison analysis we noted statistical significant advantages (p<0,01 of the use of diacerein with methotrexate regarding the dynamic of IL-1 and COMP, ESR, CRP in patient’s serum, which is accompanied by the reduction of basic disease activity on DAS 28.

Physical rehabilitation in complex therapy of the ureter stones patients in the Truskavets health resort area

Directory of Open Access Journals (Sweden)

Shologon R.P.

2010-05-01

Full Text Available Efficiency of rehabilitation measures is considered in complex therapy with the use of differentiated methods of medical physical education for patients with stones of ureter. Under a supervision there was 143 patients. 93 patients were made basic group, 50 patients - control. From them 51 (56 % are men and 42 (54% are women. Age of patients made from 20 to 60 years. A sanatorium-resort rehabilitation is recommended with the use of the differentiated methods of medical gymnastics. Application of method improved the indexes of the functional state of buds and overhead urinary ways. Frequency of advancement and output of concrements is also megascopic.

Thermal spray coating for corrosion under insulation (CUI) prevention

Science.gov (United States)

Fuad, Mohd Fazril Irfan Ahmad; Razak, Khalil Abdul; Alias, Nur Hashimah; Othman, Nur Hidayati; Lah, Nik Khairul Irfan Nik Ab

2017-12-01

Corrosion under insulation (CUI) is one of the predominant issues affecting process of Oil and Gas and Petrochemical industries. CUI refers to external corrosion, but it is difficult to be detected as the insulation cover masks the corrosion problem. One of the options to prevent CUI is by utilizing the protective coating systems. Thermal spray coating (TSC) is an advanced coating system and it shows promising performance in harsh environment, which could be used to prevent CUI. However, the application of TSC is not attractive due to the high initial cost. This work evaluates the potential of TSC based on corrosion performance using linear polarization resistance (LPR) method and salt spray test (SST). Prior to the evaluation, the mechanical performance of TSC was first investigated using adhesion test and bend test. Microstructure characterization of the coating was investigated using Scanning Electron Microscope (SEM). The LPR test results showed that low corrosion rate of 0.05 mm/years was obtained for TSC in compared to the bare steel especially at high temperature of 80 °C, where usually normal coating would fail. For the salt spray test, there was no sign of corrosion products especially at the center (fully coated region) was observed. From SEM images, no corrosion defects were observed after 336 hours of continuous exposure to salt fog test. This indicates that TSC protected the steel satisfactorily by acting as a barrier from a corrosive environment. In conclusion, TSC can be a possible solution to minimize the CUI in a long term. Further research should be done on corrosion performance and life cycle cost by comparing TSC with other conventional coating technology.

Neuroautonomic evaluation of patients with unexplained syncope: incidence of complex neurally mediated diagnoses in the elderly

Directory of Open Access Journals (Sweden)

Rafanelli M

2014-02-01

Full Text Available Martina Rafanelli, Alessandro Morrione, Annalisa Landi, Emilia Ruffolo, Valentina M Chisciotti, Maria A Brunetti, Niccolò Marchionni, Andrea Ungar Syncope Unit, Cardiology and Geriatric Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Background: The incidence of syncope increases in individuals over the age of 70 years, but data about this condition in the elderly are limited. Little is known about tilt testing (TT, carotid sinus massage (CSM, or supine and upright blood pressure measurement related to age or about patients with complex diagnoses, for example, those with a double diagnosis, ie, positivity in two of these three tests. Methods: A total of 873 consecutive patients of mean age 66.5±18 years underwent TT, CSM, and blood pressure measurement in the supine and upright positions according to the European Society of Cardiology guidelines on syncope.1 Neuroautonomic evaluation was performed if the first-line evaluation (clinical history, physical examination, electrocardiogram was suggestive of neurally mediated syncope, or if the first-line evaluation was suggestive of cardiac syncope but this diagnosis was excluded after specific diagnostic tests according to European Society of Cardiology guidelines on syncope, or if certain or suspected diagnostic criteria were not present after the first-line evaluation. Results: A diagnosis was reached in 64.3% of cases. TT was diagnostic in 50.4% of cases, CSM was diagnostic in 11.8% of cases, and orthostatic hypotension was present in 19.9% of cases. Predictors of a positive tilt test were prodromal symptoms and typical situational syncope. Increased age and a pathologic electrocardiogram were predictors of carotid sinus syndrome. Varicose veins and alpha-receptor blockers, nitrates, and benzodiazepines were associated with orthostatic hypotension. Twenty-three percent of the patients had a complex diagnosis. The most frequent association was

Evaluation of the potential application of 2-acetylpyridine N4- phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis; Avaliacao da potencial aplicacao de derivados de 2-acetilpiridina N-4 fenil tiossemicarbazonas em terapia e diagnostico oncologico

Energy Technology Data Exchange (ETDEWEB)

Soares, Marcella Araugio

2013-08-01

Despite the wide range of antineoplastic agents available, resistance of some types of cancer and toxicity to normal cells have been identified as the main causes of treatment failure and death. The lack of early and precise diagnosis is also responsible for reducing survival of cancer patients. In this context, the development of substances with low toxicity and therapeutic potential and/or diagnosis purpose, is the major tool in an attempt to increase the survival of patients and assure the safety and efficacy of treatment. Thiosemicarbazones (TSC) are a class of synthetic compounds that have several biological activities, including antitumor. Although several studies have shown the great potential of TSC as therapeutic and / or diagnostic agents, different chemical modifications performed on this class of molecules indicate new possibilities for applications and still require further studies. The objective of this study was to evaluate the potential applicability of 2-acetylpyridine N-4-phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis. The results showed that all 13 TSC tested were cytotoxic to breast and glioblastoma tumor cell lines, presenting higher in vitro antitumor activity than etoposide, an antineoplastic and inhibitor of topoisomerase II frequently used for cancer therapy. The TSC that have halogen or nitro on ortho position showed higher antitumor activity in vitro than their isomers with halogen or nitro on meta or para position of the phenyl group. H2Ac4oFPh and H2Ac4oClPh compounds showed the highest antitumor activity among all tested compounds, with IC{sub 50} in nanomolar order. These TSC induced cell death by apoptosis and oxidative stress was responsible, at least in part, for this type of cell death. The 5 mg.kg{sup -1} H2Ac4oFPh dose, administered s.c., for 4 consecutive days, did not induce important toxicity; however, the same treatment protocol was not effective for tumor growth reduction in an animal model of brain

Evaluation of the potential application of 2-acetylpyridine N4- phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis

International Nuclear Information System (INIS)

Soares, Marcella Araugio

2013-01-01

Despite the wide range of antineoplastic agents available, resistance of some types of cancer and toxicity to normal cells have been identified as the main causes of treatment failure and death. The lack of early and precise diagnosis is also responsible for reducing survival of cancer patients. In this context, the development of substances with low toxicity and therapeutic potential and/or diagnosis purpose, is the major tool in an attempt to increase the survival of patients and assure the safety and efficacy of treatment. Thiosemicarbazones (TSC) are a class of synthetic compounds that have several biological activities, including antitumor. Although several studies have shown the great potential of TSC as therapeutic and / or diagnostic agents, different chemical modifications performed on this class of molecules indicate new possibilities for applications and still require further studies. The objective of this study was to evaluate the potential applicability of 2-acetylpyridine N-4-phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis. The results showed that all 13 TSC tested were cytotoxic to breast and glioblastoma tumor cell lines, presenting higher in vitro antitumor activity than etoposide, an antineoplastic and inhibitor of topoisomerase II frequently used for cancer therapy. The TSC that have halogen or nitro on ortho position showed higher antitumor activity in vitro than their isomers with halogen or nitro on meta or para position of the phenyl group. H2Ac4oFPh and H2Ac4oClPh compounds showed the highest antitumor activity among all tested compounds, with IC 50 in nanomolar order. These TSC induced cell death by apoptosis and oxidative stress was responsible, at least in part, for this type of cell death. The 5 mg.kg -1 H2Ac4oFPh dose, administered s.c., for 4 consecutive days, did not induce important toxicity; however, the same treatment protocol was not effective for tumor growth reduction in an animal model of brain tumor

Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy

Science.gov (United States)

2013-01-01

Background Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Method Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Results Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the

Creation of complexity assessment tool for patients receiving home care

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Maria Leopoldina de Castro Villas Bôas

2016-06-01

Full Text Available Abstract OBJECTIVE To create and validate a complexity assessment tool for patients receiving home care from a public health service. METHOD A diagnostic accuracy study, with estimates for the tool's validity and reliability. Measurements of sensitivity and specificity were considered when producing validity estimates. The resulting tool was used for testing. Assessment by a specialized team of home care professionals was used as the gold standard. In the tool's reliability study, the authors used the Kappa statistic. The tool's sensitivity and specificity were analyzed using various cut-off points. RESULTS On the best cut-off point-21-with the gold standard, a sensitivity of 75.5% was obtained, with the limits of confidence interval (95% at 68.3% and 82.8% and specificity of 53.2%, with the limits of confidence interval (95% at 43.8% and 62.7%. CONCLUSION The tool presented evidence of validity and reliability, possibly helping in service organization at patient admission, care type change, or support during the creation of care plans.

Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency

NARCIS (Netherlands)

Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

Background: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate

Nurse-led case management for ambulatory complex patients in general health care: A systematic review

NARCIS (Netherlands)

Latour-Delfgaauw, C.H.M.; van der Windt, D.A.W.M.; de Jonge, P.; Riphagen, II; Vos, R.; Huyse, F.J.; Stalman, W.A.B.

2007-01-01

Objective: The aim of this study was to summarize the available literature on the effectiveness of ambulatory nurse-led case management for complex patients in general health care. Method: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and Cinahl. We included randomized

Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

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Rongen Michel A

2009-07-01

Full Text Available Abstract Background Complex chromosomal rearrangements (CCR are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes. Results Multicolour fluorescence in situ hybridization (M-FISH showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients. Conclusion Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.

Thermally stimulated current method applied to highly irradiated silicon diodes

CERN Document Server

Pintilie, I; Pintilie, I; Moll, Michael; Fretwurst, E; Lindström, G

2002-01-01

We propose an improved method for the analysis of Thermally Stimulated Currents (TSC) measured on highly irradiated silicon diodes. The proposed TSC formula for the evaluation of a set of TSC spectra obtained with different reverse biases leads not only to the concentration of electron and hole traps visible in the spectra but also gives an estimation for the concentration of defects which not give rise to a peak in the 30-220 K TSC temperature range (very shallow or very deep levels). The method is applied to a diode irradiated with a neutron fluence of phi sub n =1.82x10 sup 1 sup 3 n/cm sup 2.

Sibutramine-associated psychotic symptoms and zolpidem-induced complex behaviours: implications for patient safety.

Science.gov (United States)

Wiglusz, Mariusz S; Cubała, Wiesław Jerzy; Nowak, Paweł; Jakuszkowiak-Wojten, Katarzyna; Landowski, Jerzy; Krysta, Krzysztof

2013-09-01

Sibutramine is a weight loss agent recently withdrawn from the European market due to cardiovascular risk concerns. It was used for long-term obesity treatment. Zolpidem is a short acting hypnotic agent commonly used in the treatment of insomnia. A number of case reports describing psychotic reaction to sibutramine were reported in the literature. We present a case of a 61-year-old Caucasian woman who developed two psychotic episodes related to sibutramine treatment. The second psychotic episode was complicated with complex behaviours after zolpidem use due to insomnia. Sibutramine and zolpidem discontinuation resulted in rapid resolution of psychotic symptoms. This case suggests a possibility of incidence of psychotic symptoms and complex behaviour disturbances in patients prescribed sibutramine or other monoaminergic reuptake inhibitors.

[VGKC-complex antibodies].

Science.gov (United States)

Watanabe, Osamu

2013-04-01

Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

Role of CTGF in White Matter Development in Tuberous Sclerosis

Science.gov (United States)

2016-04-01

which lacks Tsc1 expression only in neurons . Here we show that, neurons lacking Tsc1 secrete excessive amounts of connective tissue growth factor...that, neurons lacking Tsc1 secrete excessive amounts of connective tissue growth factor (CTGF), which in turn blocks the maturation of...Columbia University Medical Center New York, NY 2015 Neuronal Connectivity in Tuberous Sclerosis / Keynote Stanley Manne Children’s Research Institute

Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression

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Bizik G

2014-04-01

Full Text Available Gustav Bizik,1 Petr Bob,1 Jiri Raboch,1 Josef Pavlat,1 Jana Uhrova,2 Hana Benakova,2 Tomas Zima2 1Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry and UHSL, 2Department of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Abstract: Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II, traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40, and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively, and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years. The results show that TNF-α is significantly related to DES (Spearman R=−0.42, P<0.01, SDQ-20 (Spearman R=−0.38, P<0.01, and TSC-40 (Spearman R=−0.41, P<0.01, but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients. Keywords: depression, dissociation, TNF-alpha, traumatic stress

The relation between intensity and complexity of coronary artery lesion and oxidative stress in patients with acute coronary syndrome.

Science.gov (United States)

Turan, Turhan; Menteşe, Ümit; Ağaç, Mustafa Tarık; Akyüz, Ali Rıza; Kul, Selim; Aykan, Ahmet Çağrı; Bektaş, Hüseyin; Korkmaz, Levent; Öztaş Menteşe, Seda; Dursun, İhsan; Çelik, Şükrü

2015-10-01

Oxidative stress plays a major role in the development of atherosclerosis. However, the relationship between oxidative stress and complexity and intensity of coronary artery disease is less clear. The aim of this study is to assess the relationship between oxidative stress markers and the complexity and intensity of coronary artery disease in patients with acute coronary syndrome (ACS). Sixty-seven consecutive patients with an early phase of ACS (=22). Likewise patients were divided into two CAD severity groups according to the median Gensini score of 64: less intensive CAD with Gensini score (=64. Blood samples were taken in 1 hour within administration in order to measure total oxidative status (TOS) and total antioxidant capacity (TAC) levels determined by Erel method. Oxidative stress index (OSI) was calculated by TOS /TAC. There was no significant difference between the two SYNTAX groups for oxidative stress markers. Median TOS and OSI values were significantly high in the intensive CAD group (p=0.005, p=0.04, respectively). The Gensini score was positively correlated with TOS and OSI (p=0.003, p=0.02, respectively). Oxidative stress markers may be considered supportive laboratory parameters related to CAD intensity but not complexity in ACS patients.

Failure to detect circulating DNA-anti-DNA complexes by four radioimmunological methods in patients with systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Izui, S; Lambert, P H; Miescher, P A [Hopital Cantonal Geneve (Switzerland)

1977-12-01

The presence of The DNA-anti-DNA complexes in sera from patients with systemic lupus erythematosus (SLE) was investigated by two new radioimmunoassays (RIA) developed for this purpose and by measuring the CLq and DNA binding activity of serum before and after treatment with DNAse. Two direct RIA developed in this study were based on the reactivity of (/sup 3/H)actinomycin D ((/sup 3/H)ACT-D) or solid-phase methylated bovine serum albumin (mBSA) with DNA-anti-DNA complexes. DNA-anti-DNA complexes prepared in vitro could be efficiently detected at various antigen-antibody ratios by these two RIA. Increased levels of circulating immune complexes as indicated by the CLq binding test were found in 52% of the SLE sera. However, the frequency of specific DNA-anti-DNA complexes detected in the SLE sera was very low. Only 6% of the sera exhibited an increased value deviating by more than three s.d. from the normal mean when tested with the (/sup 3/H)ACT-D binding RIA or the solid-phase mBSA RIA. On the other hand, there was no significant difference in the serum CLq or DNA binding activity after treatment with DNAse. These results suggest that DNA-anti-DNA complexes do not occur frequently in circulating blood and represent only a very small portion of the immune complexes detected in serum from patients with SLE.

Complex immunological monitoring of breast cancer patients treated postoperatively by electron beam irradiation

International Nuclear Information System (INIS)

Horvath, M.; Horvath, A.; Fekete, B.; Toth, J.

1986-01-01

To monitor the electron beam therapy some immunological parameters of breast cancer patients previously undergone surgery were tested before, during and after irradiation. Immune complex levels measured by complement consumption technique were not altered by irradiation. Killer cell activity tested in so-called antibody dependent cellular cytotoxicity (ADCC) capacity assay showed a marked decrease in some cases. Based on the phagocytic capacity of the granulocytes the patients could be divided into two groups: one with declining activity and another with rising activity: The majority of the patients (22/45) were humoral leukocyte adherence inhibition (H-LAI) negative before and during irradiation. Those showed positive H-LAI indices before electron therapy had unchanged (7/45) or decreasing (9/45) tendencies during the observation period. Further study is needed to establish the clinical relevance of these in vitro assays used by us. (orig.) [de

Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections

NARCIS (Netherlands)

P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

2003-01-01

textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections.

NARCIS (Netherlands)

Koraka, P.; Burghoorn-Maas, C.P.; Falconar, A.; Setiati, T.E.; Djamiatun, K.; Groen, J.; Osterhaus, A.D.

2003-01-01

Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot

Significance of fragmented QRS complexes for identifying culprit lesions in patients with non-ST-elevation myocardial infarction: a single-center, retrospective analysis of 183 cases

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Guo Rong

2012-06-01

Full Text Available Abstract Background Fragmented QRS (fQRS complexes are novel electrocardiographic signals, which reflect myocardial conduction delays in patients with coronary artery disease (CAD. The importance of fQRS complexes in identifying culprit vessels was evaluated in this retrospective study. Methods A 12-lead surface electrocardiogram was obtained in 183 patients who had non-ST-elevation myocardial infarction (NSTEMI and subsequently underwent coronary angiography (CAG. On the basis of the frequency of fQRS complexes, indices such as sensitivity, specificity, positive and negative predictive values, and likelihood ratio were evaluated to determine the ability of fQRS complexes to identify the culprit vessels. Results Among the patients studied, elderly patients (age ≥ 65 years and those with diabetes had a significantly higher frequency of fQRS complexes (p = 0.005, p = 0.003, respectively. The fQRS complexes recorded in the 4 precordial leads had the highest specificity (81.8% for indentifying the culprit vessel (left anterior descending artery. However, the specificity of fQRS complexes to identify lesions in the left circumflex and right coronary arteries was lower for the inferior and lateral leads than for the limb leads (65.5% versus 71.7%; however, the limb leads had higher sensitivity (92.3% versus 89.4%. And the total sensitivity and specificity of fQRS (77.1% and 71.5% were higher than those values for ischemic T-waves. Conclusions The frequency of fQRS complexes was higher in elderly and diabetic patients with NSTEMI. The frequency of fQRS complexes recorded in each of the ECG leads can be used to identify culprit vessels in patients with NSTEMI.

Harvey Cushing Treated the First Known Patient With Carney Complex.

Science.gov (United States)

Tsay, Cynthia J; Stratakis, Constantine A; Faucz, Fabio Rueda; London, Edra; Stathopoulou, Chaido; Allgauer, Michael; Quezado, Martha; Dagradi, Terry; Spencer, Dennis D; Lodish, Maya

2017-10-01

Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features of Cushing syndrome and acromegaly due to functional adrenal and pituitary gland tumors. CNC has been linked to mutations in the regulatory subunit of protein kinase A type I-alpha ( PRKAR1A ) gene. Tissue samples were taken from the hypothalamus or thalamus or tumors of patients with pituitary adenomas seen and operated on by neurosurgeon Harvey Cushing between 1913 and 1932. Following DNA extraction, sequencing for genes of interest was attempted, including PRKAR1A , AIP , USP8 , GNAS1 , and GPR101 , to explore the possibility that these mutations associated with acromegaly, CNC, and Cushing syndrome have been conserved over time. We report a patient described by Dr. Cushing in 1914 with a clinical presentation and postmortem findings suggestive of CNC. Genetic sequencing of the hypothalamus and pituitary adenoma revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene, a codon previously described as mutated in CNC, but with a novel amino acid change. This patient is, to our knowledge, the first molecularly confirmed individual with CNC. This case demonstrates the power of modern genetics in studying archived tissues and the importance of recording detailed clinical notes in the diagnosis of disease.

Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency

NARCIS (Netherlands)

Roef, MJ; Kalhan, SC; Reijngoud, DJ; De Meer, K; Berger, Ruud

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at

Building a measurement framework of burden of treatment in complex patients with chronic conditions: a qualitative study.

Science.gov (United States)

Eton, David T; Ramalho de Oliveira, Djenane; Egginton, Jason S; Ridgeway, Jennifer L; Odell, Laura; May, Carl R; Montori, Victor M

2012-01-01

Burden of treatment refers to the workload of health care as well as its impact on patient functioning and well-being. We set out to build a conceptual framework of issues descriptive of burden of treatment from the perspective of the complex patient, as a first step in the development of a new patient-reported measure. We conducted semistructured interviews with patients seeking medication therapy management services at a large, academic medical center. All patients had a complex regimen of self-care (including polypharmacy), and were coping with one or more chronic health conditions. We used framework analysis to identify and code themes and subthemes. A conceptual framework of burden of treatment was outlined from emergent themes and subthemes. Thirty-two patients (20 female, 12 male, age 26-85 years) were interviewed. Three broad themes of burden of treatment emerged including: the work patients must do to care for their health; problem-focused strategies and tools to facilitate the work of self-care; and factors that exacerbate the burden felt. The latter theme encompasses six subthemes including challenges with taking medication, emotional problems with others, role and activity limitations, financial challenges, confusion about medical information, and health care delivery obstacles. We identified several key domains and issues of burden of treatment amenable to future measurement and organized them into a conceptual framework. Further development work on this conceptual framework will inform the derivation of a patient-reported measure of burden of treatment.

The use of intravenous digital subtraction angiography in evaluating patients with complex congenital heart disease

International Nuclear Information System (INIS)

Moodie, D.S.

1986-01-01

The author previously described his experience in 450 patients with congenital heart disease using intravenous digital subtraction angiography (DSA) to define cardiac anatomy. He has been impressed by the utility of DSA in the evaluation of patients with congenital heart disease. It is now an integral part of his clinical practice to perform intravenous DSA studies both pre- and postoperatively on an inpatient as well as outpatient basis. This chapter details his DSA experience with complex forms of congenital heart disease

Pain increases during sympathetic arousal in patients with complex regional pain syndrome.

Science.gov (United States)

Drummond, P D; Finch, P M; Skipworth, S; Blockey, P

2001-10-09

To investigate the effect of sympathetic arousal on pain and vasomotor responses in healthy control subjects and patients with complex regional pain syndrome (CRPS), and to determine whether pain increases in patients with particular symptoms. In experiments 1 and 2, capsaicin was applied to the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular responses were monitored and subjects rated thermal hyperalgesia before and after being startled (experiment 1), and before, during, and after mental arithmetic, breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular and electrodermal responses were recorded after patients were startled and during forehead cooling. In experiment 1, thermal hyperalgesia decreased in healthy control subjects after they were startled, and digital blood vessels constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during and after other forms of sympathetic arousal. However, in experiment 3, ratings of clinical pain increased during forehead cooling or after being startled in over 70% of patients with CRPS. Pain increased most consistently during forehead cooling in patients with cold allodynia or punctate allodynia. Digital blood vessels constricted more intensely on the symptomatic than the nonsymptomatic side in patients with CRPS during sympathetic arousal. Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

Assessment of long-term effects of aneurysms trapping and extracranial-intracranial bypass surgery in patients with complex cerebral aneurysms

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MAO Zhi-qi

2012-02-01

Full Text Available Objective To study the long-term effects of extracranial-intracranial (EC-IC bypass and aneurysms trapping in patients with complex cerebral aneurysms. Methods Seventeen patients with complex aneurysms, who underwent EC-IC bypass and aneurysms trapping from 2008 to 2009, were followed up. Clinical records were reviewed, modified Rankin Scale (mRS was recorded at admission, discharging, and follow-up point, and activities of daily living (ADL scale (Barthel Index at admission and follow-up point. Results Seventeen patients (11 males and 6 females were followed up. At admission mRS scores were 1.06 ± 0.87, Barthel index 91.10 ± 10.30. Superficial temporal artery-middle cerebral artery (STA-MCA was performed in 8 cases, extracarotid artery-great saphenous vein-middle cerebral artery (ECA-GSV-MCA in 5 cases, extracarotid artery-radial artery-middle cerebral artery (ECA-RA-MCA in 3 cases, occipital artery-posterior inferior cerebellar artery (OA-PICA in 1 case. Patients were followed up for 19-39 months (mean 28.67 months. At follow-up point, 2 patients (11.76% died, operation-related mortality was 5.88% (1/17, operation-related morbidity 5.88% (1/17, mRS scores 1.07 ± 1.16, Barthel index 96.40 ± 10.30. Conclusion Patients with complex aneurysms who were impossible to be treated with surgical clipping or endovascular intervention could be cured with extracranial-intracranial bypass and aneurysms trapping, and good follow-up results were acquired.

Complexity analysis of EEG in patients with schizophrenia using fractal dimension

International Nuclear Information System (INIS)

Raghavendra, B S; Dutt, D Narayana; Halahalli, Harsha N; John, John P

2009-01-01

We computed Higuchi's fractal dimension (FD) of resting, eyes closed EEG recorded from 30 scalp locations in 18 male neuroleptic-naïve, recent-onset schizophrenia (NRS) subjects and 15 male healthy control (HC) subjects, who were group-matched for age. Schizophrenia patients showed a diffuse reduction of FD except in the bilateral temporal and occipital regions, with the reduction being most prominent bifrontally. The positive symptom (PS) schizophrenia subjects showed FD values similar to or even higher than HC in the bilateral temporo-occipital regions, along with a co-existent bifrontal FD reduction as noted in the overall sample of NRS. In contrast, this increase in FD values in the bilateral temporo-occipital region was absent in the negative symptom (NS) subgroup. The regional differences in complexity suggested by these findings may reflect the aberrant brain dynamics underlying the pathophysiology of schizophrenia and its symptom dimensions. Higuchi's method of measuring FD directly in the time domain provides an alternative for the more computationally intensive nonlinear methods of estimating EEG complexity

Complex pelvic ring injuries associated with floating knee in a poly-trauma patient

OpenAIRE

Zhou, Yuebin; Guo, Honggang; Cai, Zhiwei; Zhang, Yuan

2017-01-01

Abstract Rationale: Complex pelvic ring fracture associated with floating knee is comparatively rare which usually results from high-energy trauma including vehicle-related accidence, falls from height, and earthquake-related injury. To our knowledge, few literatures have documented such injuries in the individual patient. Management of both injuries present challenges for surgical management and postoperative care. The purpose of this study is to prove the feasibility and benefits of damage ...

Pilot Study: The Effectiveness of Complex Decongestive Therapy for Lymphedema in Palliative Care Patients with Advanced Cancer.

LENUS (Irish Health Repository)

Cobbe, Sinead

2017-12-05

Complex decongestive therapy (CDT) is a regimen of physical treatment for lymphedema. Its effectiveness is unknown in advanced cancer patients. This study evaluates effectiveness of CDT in this population.

Care for a Patient With Cancer As a Project: Management of Complex Task Interdependence in Cancer Care Delivery.

Science.gov (United States)

Trosman, Julia R; Carlos, Ruth C; Simon, Melissa A; Madden, Debra L; Gradishar, William J; Benson, Al B; Rapkin, Bruce D; Weiss, Elisa S; Gareen, Ilana F; Wagner, Lynne I; Khan, Seema A; Bunce, Mikele M; Small, Art; Weldon, Christine B

2016-11-01

Cancer care is highly complex and suffers from fragmentation and lack of coordination across provider specialties and clinical domains. As a result, patients often find that they must coordinate care on their own. Coordinated delivery teams may address these challenges and improve quality of cancer care. Task interdependence is a core principle of rigorous teamwork and is essential to addressing the complexity of cancer care, which is highly interdependent across specialties and modalities. We examined challenges faced by a patient with early-stage breast cancer that resulted from difficulties in understanding and managing task interdependence across clinical domains involved in this patient's care. We used team science supported by the project management discipline to discuss how various task interdependence aspects can be recognized, deliberately designed, and systematically managed to prevent care breakdowns. This case highlights how effective task interdependence management facilitated by project management methods could markedly improve the course of a patient's care. This work informs efforts of cancer centers and practices to redesign cancer care delivery through innovative, practical, and patient-centered approaches to management of task interdependence in cancer care. Future patient-reported outcomes research will help to determine optimal ways to engage patients, including those who are medically underserved, in managing task interdependence in their own care.

EFFICACY OF SOFT TISSUE APPLICATION, MANUALLY-THERAPEUTICAL TECHNIQUES FOR KNEE ARTHROKINEMATICS RECOVERY COMPLEX IN PATIENTS AFTER ARTHROSCOPIC MENISCECTOMY

Directory of Open Access Journals (Sweden)

Kostov Rostislav V

2015-07-01

Full Text Available Introduction: In this article we present the final effect of the application of complex soft tissue manually-treatment system for recovery of joint kinematics in patients with moderate and minimal protective period of rehabilitation after arthroscopic meniscectomy. Material and Methods: The study was conducted in 2005-2012 into three medical centers in Bulgaria: Blagoevgrad, Sofia and Pleven. The study included a total of 110 patients divided into three groups (Control and Experimental I and Experimental Group II who studied the effect of topical application of the manual therapeutic techniques compared to traditional rehabilitation methods applied. For testing the efficacy of a treatment approach in the three groups of patients, the results have processed by the method of variational analysis. Results: After analysis of results we find significantly more fully and without residual short violations recovery for all controlled parameters in patients who have implemented comprehensive manually-therapeutic treatment compared with control group patients. Conclusion: Application of adequate physiological and pedagogically grounded complex rehabilitation is required in patients after arthroscopic meniscectomy model with motor deficits in tractable routine rehabilitation. Observations allow us to offer a methodology for implementation in general practice rehabilitation in patients after meniscal ruptures treated by arthroscopic meniscectomy and motor deficits, intractable routine rehabilitation.

Interactive anatomical and surgical live stream lectures improve students' academic performance in applied clinical anatomy.

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Shiozawa, Thomas; Butz, Benjamin; Herlan, Stephan; Kramer, Andreas; Hirt, Bernhard

2017-01-01

Tuebingen's Sectio Chirurgica (TSC) is an innovative, interactive, multimedia, and transdisciplinary teaching method designed to complement dissection courses. The Tuebingen's Sectio Chirurgica (TSC) allows clinical anatomy to be taught via interactive live stream surgeries moderated by an anatomist. This method aims to provide an application-oriented approach to teaching anatomy that offers students a deeper learning experience. A cohort study was devised to determine whether students who participated in the TSC were better able to solve clinical application questions than students who did not participate. A total of 365 students participated in the dissection course during the winter term of the 2012/2013 academic year. The final examination contained 40 standard multiple-choice (S-MC) and 20 clinically-applied multiple-choice (CA-MC) items. The CA-MC items referred to clinical cases but could be answered solely using anatomical knowledge. Students who regularly participated in the TSC answered the CA-MC questions significantly better than the control group (75% and 65%, respectively; P  0.05). The CA-MC questions had a slightly higher level of difficulty than the S-MC questions (0.725 and 0.801, respectively; P = 0.083). The discriminatory power of the items was comparable (S-MC median Pearson correlations: 0.321; CA-MC: 0.283). The TSC successfully teaches the clinical application of anatomical knowledge. Students who attended the TSC in addition to the dissection course were able to answer CA-MC questions significantly better than students who did not attend the TSC. Thus, attending the TSC in addition to the dissection course supported students' clinical learning goals. Anat Sci Educ 10: 46-52. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Simple versus complex degenerative mitral valve disease.

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Javadikasgari, Hoda; Mihaljevic, Tomislav; Suri, Rakesh M; Svensson, Lars G; Navia, Jose L; Wang, Robert Z; Tappuni, Bassman; Lowry, Ashley M; McCurry, Kenneth R; Blackstone, Eugene H; Desai, Milind Y; Mick, Stephanie L; Gillinov, A Marc

2018-07-01

At a center where surgeons favor mitral valve (MV) repair for all subsets of leaflet prolapse, we compared results of patients undergoing repair for simple versus complex degenerative MV disease. From January 1985 to January 2016, 6153 patients underwent primary isolated MV repair for degenerative disease, 3101 patients underwent primary isolated MV repair for simple disease (posterior prolapse), and 3052 patients underwent primary isolated MV repair for complex disease (anterior or bileaflet prolapse), based on preoperative echocardiographic images. Logistic regression analysis was used to generate propensity scores for risk-adjusted comparisons (n = 2065 matched pairs). Durability was assessed by longitudinal recurrence of mitral regurgitation and reoperation. Compared with patients with simple disease, those undergoing repair of complex pathology were more likely to be younger and female (both P values < .0001) but with similar symptoms (P = .3). The most common repair technique was ring/band annuloplasty (3055/99% simple vs 3000/98% complex; P = .5), followed by leaflet resection (2802/90% simple vs 2249/74% complex; P < .0001). Among propensity-matched patients, recurrence of severe mitral regurgitation 10 years after repair was 6.2% for simple pathology versus 11% for complex pathology (P = .007), reoperation at 18 years was 6.3% for simple pathology versus 11% for complex pathology, and 20-year survival was 62% for simple pathology versus 61% for complex pathology (P = .6). Early surgical intervention has become more common in patients with degenerative MV disease, regardless of valve prolapse complexity or symptom status. Valve repair was associated with similarly low operative risk and time-related survival but less durability in complex disease. Lifelong annual echocardiographic surveillance after MV repair is recommended, particularly in patients with complex disease. Copyright © 2018 The American Association for Thoracic Surgery

Modified Hemocorrection in the Complex Treatment of Patients with Pyoinflammatory Lung Diseases

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V. V. Gavrikov

2007-01-01

Full Text Available Objective: To evaluate the efficiency of extracorporeal hemocorrection used in the complex therapy in patients with a pyoinflammatory process in the lung.Materials and methods: 62 patients, including 22 patients with lung abscess who underwent routine plasmapheresis and 40 patients with varying pyoinflammatory lung diseases who received modified hemocorrection — plasma exchange combined with laser extracorporeally washed-off cytomass irradiation, were examined and treated. The severity of their general condition was assessed by the SAPS scale and the severity of intoxication was evaluated by the content of low and medium-molecular weight substances (LMMWSs. The hemostatic system was studied by standardized studies.Results. Routine plasmapheresis was established to produce no impact on platelet functional activity within the first 24 hours and, three days later, promoted the progression of disseminated intravascular coagulation. A combination of plasma exchange and laser extracorporeally washed-off cytomass irradiation in patients with pyoinflam-matory lung diseases was attended by a lower blood coagulative activity and plasmin stabilization with attenuated throm-binemia. The plasma and erythrocytic levels of LMMWSs decreased and their urinary concentrations increased, which is indicative of the body’s detoxification block disorders irrespective of the severity of the disease.Conclusion. It is expedient to apply the plasma-exchanging technique in combination with laser extracorporeally washed-off cytomass irradiation to patients with the uncomplicated and complicated course of pulmonary pyoinflammatory processes without the signs of multiple organ dysfunction on admission to a specialized hospital. 

Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia.

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Biancotto, Angélique; Dagur, Pradeep K; Fuchs, John C; Wiestner, Adrian; Bagwell, C Bruce; McCoy, J Philip

2012-02-01

Increased numbers of T regulatory (T(reg)) cells are found in B-chronic lymphocytic leukemia, but the nature and function of these T(regs) remains unclear. Detailed characterization of the T(regs) in chronic lymphocytic leukemia has not been performed and the degree of heterogeneity of among these cells has not been studied to date. Using 15-color flow cytometry we show that T(reg) cells, defined using CD4, CD25, and forkhead box P3 (FOXP3), can be divided into multiple complex subsets based on markers used for naïve, memory, and effector delineation as well as markers of T(reg) activation. Furthermore FOXP3(+) cells can be identified among CD4(+)CD25(-) as well as CD8(+)CD4(-) populations in increased proportions in patients with chronic lymphocytic leukemia compared with healthy donors. Significantly different frequencies of naïve and effector T(regs) populations are found in healthy donor controls compared with donors with chronic lymphocytic leukemia. A population of CCR7(+)CD39(+) T(regs) was significantly associated with chronic lymphocytic leukemia. This population demonstrated slightly reduced suppressive activity compared with total T(regs) or T(regs) of healthy donors. These data suggest that FOXP3-expressing cells, particularly in patients with chronic lymphocytic leukemia are much more complex for T(reg) sub-populations and transitions than previously reported. These findings demonstrate the complexity of regulation of T-cell responses in chronic lymphocytic leukemia and illustrate the use of high-dimensional analysis of cellular phenotypes in facilitating understanding of the intricacies of cellular immune responses and their dysregulation in cancer.

Adult patient decision-making regarding implantation of complex cardiac devices: a scoping review.

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Malecki-Ketchell, Alison; Marshall, Paul; Maclean, Joan

2017-10-01

Complex cardiac rhythm management device (CRMD) therapy provides an important treatment option for people at risk of sudden cardiac death. Despite the survival benefit, device implantation is associated with significant physical and psychosocial concerns presenting considerable challenges for the decision-making process surrounding CRMD implantation for patients and physicians. The purpose of this scoping review was to explore what is known about how adult (>16 years) patients make decisions regarding implantation of CRMD therapy. Published, peer reviewed, English language studies from 2000 to 2016 were identified in a search across eight healthcare databases. Eligible studies were concerned with patient decision-making for first time device implantation. Quality assessment was completed using the mixed methods appraisal tool for all studies meeting the inclusion criteria. The findings of eight qualitative and seven quantitative studies, including patients who accepted or declined primary or secondary sudden cardiac death prevention devices, were clustered into two themes: knowledge acquisition and the process of decision-making, exposing similarities and distinctions with the treatment decision-making literature. The review revealed some insight in to the way patients approach decision-making but also exposed a lack of clarity and research activity specific to CRMD patients. Further research is recommended to support the development and application of targeted decision support mechanisms.

Transcatheter arterial embolization as therapy of renal angiomyolipomas: The evolution in 15 years of experience

International Nuclear Information System (INIS)

Chatziioannou, A.; Gargas, D.; Malagari, K.; Kornezos, I.; Ioannidis, I.; Primetis, E.; Moschouris, H.; Gouliamos, A.; Mourikis, D.

2012-01-01

Objective: This study aims at presenting the evolution of the embolization technique in treating renal angiomyolipomas (AMLs) either diagnosed in patients with acute bleeding or discovered accidentally. Methods: Ten patients with renal AMLs have been through thirteen selective transcatheter arterial embolizations for 15 years. Two patients had tuberous sclerosis complex (TSC) with bilateral tumors and were embolized twice. Four embolic materials were employed: PVA particles, Gianturco coils, microspheres and microcoils. Catheterization was achieved by means of 5F Cobra 2 catheters and coaxial microcatheter systems. Results: On an emergency basis, embolization was a first-line treatment. In one case, surgery was necessary; in two patients, a second embolization was performed. When treatment was preventive, a single embolization proved to be sufficient, as well. There was no significant deterioration of the serum creatinine levels in the post-embolization period. Conclusion: Selective arterial embolization is a rather safe and effective technique to treat AMLs both urgently and preventively. Different embolic materials can be employed. Microspheres and microcatheters stand for new promising materials

Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I.

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Walton, K D; Dubois, M; Llinás, R R

2010-07-01

Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Fuzzy Traffic Control with Vehicle-to-Everything Communication.

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Salman, Muntaser A; Ozdemir, Suat; Celebi, Fatih V

2018-01-27

Traffic signal control (TSC) with vehicle-to everything (V2X) communication can be a very efficient solution to traffic congestion problem. Ratio of vehicles equipped with V2X communication capability in the traffic to the total number of vehicles (called penetration rate PR) is still low, thus V2X based TSC systems need to be supported by some other mechanisms. PR is the major factor that affects the quality of TSC process along with the evaluation interval. Quality of the TSC in each direction is a function of overall TSC quality of an intersection. Hence, quality evaluation of each direction should follow the evaluation of the overall intersection. Computational intelligence, more specifically swarm algorithm, has been recently used in this field in a European Framework Program FP7 supported project called COLOMBO. In this paper, using COLOMBO framework, further investigations have been done and two new methodologies using simple and fuzzy logic have been proposed. To evaluate the performance of our proposed methods, a comparison with COLOMBOs approach has been realized. The results reveal that TSC problem can be solved as a logical problem rather than an optimization problem. Performance of the proposed approaches is good enough to be suggested for future work under realistic scenarios even under low PR.

Eating disorder emergencies: understanding the medical complexities of the hospitalized eating disordered patient.

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Cartwright, Martina M

2004-12-01

Eating disorders are maladaptive eating behaviors that typically develop in adolescence and early adulthood. Psychiatric maladies and comorbid conditions, especially insulin-dependent diabetes mellitus, frequently co-exist with eating disorders. Serious medical complications affecting all organs and tissues can develop and result in numerous emergent hospitalizations. This article reviews the pathophysiologies of anorexia nervosa, bulimia nervosa, and orthorexia nervosa and discusses the complexities associated with the treatment of medical complications seen in these patients.

Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients.

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Matthias Merker

Full Text Available Multidrug-resistant (MDR Mycobacterium tuberculosis complex (MTBC strains represent a major threat for tuberculosis (TB control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A and nine (Patient B polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and

Cognitive Challenges

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... Privacy Policy Sitemap Learn Engage Donate About TSC Cognitive Challenges Approximately 45% to 60% of individuals with TSC develop cognitive challenges (intellectual disabilities), although the degree of intellectual ...

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

Science.gov (United States)

2006-11-01

Neurobiol 25:795-805. Kenerson H, Dundon TA, Yeung RS. 2005. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res 57:67-75...hippocampal slice: a system for studying the pharmacology of seizures and for screening anticonvulsant drugs. Epilepsia 18:543-548. Onda H, Crino PB, Zhang...sclerosis in a 19-week fetus: immunohistochemical and molecular study of hamartin and tuberin. Pediatr Dev Pathol 5:448-464. Weiner HL, Ferraris N, LaJoie J

Complex rehabilitation and the clinical condition of working rheumatoid arthritis patients: does cryotherapy always overtop traditional rehabilitation?

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Księżopolska-Orłowska, Krystyna; Pacholec, Anna; Jędryka-Góral, Anna; Bugajska, Joanna; Sadura-Sieklucka, Teresa; Kowalik, Katarzyna; Pawłowska-Cyprysiak, Karolina; Łastowiecka-Moras, Elżbieta

2016-01-01

traditional approach showed decreased disease activity following the initial 3-week period; however, this improvement did not sustain to the end of follow-up, 3 months later. Complex rehabilitation in RA has a positive effect on patients' clinical condition. The rehabilitation programme that includes cryotherapy overtops traditional rehabilitation, particularly as regards improvement in locomotor function, disease activity and sustaining willingness to continue working and exerts long-lasting effect. Rehabilitation using cryotherapy is more effective in improving locomotor function, decreasing disease activity and sustaining willingness to continue working compared to traditional rehabilitation. Rehabilitation using cryotherapy significantly reduces the intensity of pain experienced by patients with RA, and this positive effect is maintained at 3 months post-rehabilitation. Complex rehabilitation, particularly treatment using cryotherapy, improves patients' subjective assessment of their overall well-being and perception of their disease. Complex rehabilitation in rheumatoid arthritis has a positive effect on patients' clinical condition.

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

OpenAIRE

Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

2015-01-01

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we ...

Trauma to the nail complex

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Jefferson Braga Silva

2014-04-01

Full Text Available OBJECTIVE: to analyze the results from surgical intervention to treat trauma of the nail complex.METHODS: we retrospectively reviewed a series of 94 consecutive patients with trauma of the nail complex who were treated between 2000 and 2009. In 42 patients, nail bed suturing was performed. In 27 patients, nail bed suturing was performed subsequent to osteosynthesis of the distal phalanx. In 15, immediate grafting was performed, and in 10, late-stage grafting of the nail bed. The growth, size and shape of the nail were evaluated in comparison with the contralateral finger. The results were obtained by summing scores and classifying them as good, fair or poor.RESULTS: the results were considered to be good particularly in the patients who underwent nail bed suturing or nail bed suturing with osteosynthesis of the distal phalanx. Patients who underwent immediate or late-stage nail grafting had poor results.CONCLUSION: trauma of the nail complex without loss of substance presented better results than did deferred treatment for reconstruction of the nail complex.

[Efficacy of complex therapy with metformin and ramipril combination for patients with metabolic syndrome].

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Kaĭdashev, I P; Savchenko, L H; Kaĭdasheva, E I; Kutsenko, N L; Kutsenko, L O; Solokhina, I L; Mamontova, T V

2010-01-01

We have studied efficiency of a complex therapy with metformin and ramipril combination (1000 mg and 5 mg per day) respectively in patients with metabolic syndrome (MS). The group of patients with MS which answered the basic criteria IDF (2005) was determined. Carbohydrate and Lipidic metabolism were studied. Patients were characterized with raised weight index (WI), arterial hypertension, increased concentration of triglycerides in blood serum, of glucose, of HbAlc level and S-peptide, and also high level of endotelin (1-38) and CD32+CD40+circulating particles of endothelium. Three months treatment lead to decrease in WI, arterial pressure, triglycerides concentration, HbAlc, glucose, except CD32+CD40+. Six months treatment lead to more expressed positive dynamics. Thus, metformin and ramipril combination in patients with MS leads to decrease in insulin resistancy, carbohydrate and lipid metabolism normalization, to restoration of endothelium functions that is possible to consider as prophylaxis of the development of type 2 diabetes melitus and its cardiovascular complications.

Reduced GABAA receptor density contralateral to a potentially epileptogenic MRI abnormality in a patient with complex partial seizures

International Nuclear Information System (INIS)

Kuwert, T.; Stodieck, S.R.G.; Puskas, C.; Diehl, B.; Puskas, Z.; Schuierer, G.; Vollet, B.; Schober, O.

1996-01-01

Imaging cerebral GABA A receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentialy epileptogenic structural lesions. (orig.)

Treatment with Makmiror-Complex for post-radiation infections volvo-vaginitis in cancer patients

International Nuclear Information System (INIS)

Borovtsova, T. M.; Krylov, S.V.; Udovichenko, V.I.

1996-01-01

The possibility of applying the Makmiror-Complex preparation for treating post-radiation and post-chemiotherapeutical infections volvo-vaginitis in cancer patients is considered. The multicenter clinical studies of the preparation were conducted by treatment of cervicovaginitis and volvo-vaginitis of mixed etiology, caused by the simplest fungus and various types of bacterial flora. The efficiency of the preparation is as follow: 88% of complete recovery; 9% of improvements and only in 3% of cases with no change

Atrial fibrillation management in older heart failure patients: a complex clinical problem

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Giovanni Pulignano

2016-09-01

Full Text Available BackgroundAtrial fibrillation (AF and heart failure (HF, two problems of growing prevalence as a consequence of the ageing population, are associated with high morbidity, mortality, and healthcare costs. AF and HF also share common risk factors and pathophysiologic processes such as hypertension, diabetes mellitus, ischemic heart disease, and valvular heart disease often occur together. Although elderly patients with both HF and AF are affected by worse symptoms and poorer prognosis, there is a paucity of data on appropriate management of these patients.MethodsPubMed was searched for studies on AF and older patients using the terms atrial fibrillation, elderly, heart failure, cognitive impairment, frailty, stroke, and anticoagulants.ResultsThe clinical picture of HF patients with AF is complex and heterogeneous with a higher prevalence of frailty, cognitive impairment, and disability. Because of the association of mental and physical impairment to non-administration of oral anticoagulants (OACs, screening for these simple variables in clinical practice may allow better strategies for intervention in this high-risk population. Since novel direct OACs (NOACs have a more favorable risk-benefit profile, they may be preferable to vitamin K antagonists (VKAs in many frail elderly patients, especially those at higher risk of falls. Moreover, NOACs are simple to administer and monitor and may be associated with better adherence and safety in patients with cognitive deficits and mobility impairments.ConclusionsLarge multicenter longitudinal studies are needed to examine the effects of VKAs and NOACs on long-term cognitive function and frailty; future studies should include geriatric conditions.

COMPLEX TREATMENT OF PATIENT WITH MULTIPLE FRACTURES OF THE VERTEBRAE IN THE THORACIC SPINE

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S. V. Vissarionov

2012-01-01

Full Text Available The authors presented an example of a complex treatment of pediatric patient with multiple fractures of the vertebrae in the thoracic spine. The child was operated on the burst fracture of a Th5 vertebra. Due to the presence of vertebral compression fractures Th8 a course of conservative treatment by the orthosis in hyperextension brace. Follow-up was 15 months.

Dimensionality and scaling properties of the Patient Categorisation Tool in patients with complex rehabilitation needs following acquired brain injury

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Richard J. Siegert

2018-03-01

Full Text Available Objective: To investigate the scaling properties of the Patient Categorisation Tool (PCAT as an instrument to measure complexity of rehabilitation needs. Design: Psychometric analysis in a multicentre cohort from the UK national clinical database. Patients: A total of 8,222 patents admitted for specialist inpatient rehabilitation following acquired brain injury. Methods: Dimensionality was explored using principal components analysis with Varimax rotation, followed by Rasch analysis on a random sample of n = 500. Results: Principal components analysis identified 3 components explaining 50% of variance. The partial credit Rasch model was applied for the 17-item PCAT scale using a “super-items” methodology based on the principal components analysis results. Two out of 5 initially created super-items displayed signs of local dependency, which significantly affected the estimates. They were combined into a single super-item resulting in satisfactory model fit and unidimensionality. Differential item functioning (DIF of 2 super-items was addressed by splitting between age groups (<65 and ≥ 65 years to produce the best model fit (χ2/df = 54.72, p = 0.235 and reliability (Person Separation Index (PSI = 0.79. Ordinal-to-interval conversion tables were produced. Conclusion: The PCAT has satisfied expectations of the unidimensional Rasch model in the current sample after minor modifications, and demonstrated acceptable reliability for individual assessment of rehabilitation complexity.

Complex tibial fractures are associated with lower social classes and predict early exit from employment and worse patient-reported QOL: a prospective observational study of 46 complex tibial fractures treated with a ring fixator.

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Elsoe, Rasmus; Larsen, Peter; Petruskevicius, Juozas; Kold, Søren

2018-04-01

The long-term outcomes following complex fractures of the tibia are reported to carry a risk of knee pain, malalignment, articular injury and post-traumatic osteoarthritis. The main objective of this study was to account for the patient-reported quality of life (QOL) 12 months after ring fixator removal in patients with a complex tibial fracture. Secondary objectives included a review of the socio-economic characteristics of the patient group and the rate of return to work in the study period. A prospective follow-up study was conducted of 60 patients with complex fractures of the tibia treated with ring external fixation. Patient-reported outcomes, radiological outcomes and socio-economic status including employment status of the patients were obtained 12 months after frame removal. Forty-six patients completed the assessment 12 months after frame removal (77%). The mean age of the patient at the time of fracture was 54.6 years (range 31-86). There were 19 males and 27 females. At 12 months after frame removal, the mean EQ5D-5L index was 0.66 (CI 0.60-0.72). The mean EQ5D-5L VAS was 69 (CI 61-76). When this was compared to the established reference population from Denmark, the study population showed a significantly worse EQ5D-5L index. The majority of patients (87%) were in the lower social classes suggesting a higher degree of social deprivation in the study population. Twenty-seven per cent of patients who were employed prior to injury had returned to employment at approximately 19 months following fracture. The onset of post-traumatic osteoarthritis was present in the knee joint in 29% of patients following a proximal intra-articular fracture, whereas osteoarthritis was present at the ankle joint in 35% of patients following a distal intra-articular fracture 12 months after frame removal. This study indicates that at 12 months after frame removal there are poorer patient-reported QOL as when compared to reference populations. Furthermore, this study

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

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Kathrin Thedieck

Full Text Available TOR (Target of Rapamycin is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1 and TOR complex 2 (TORC2. In the present study, we developed a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS based proteomic strategy to identify new mammalian TOR (mTOR binding proteins. We report the identification of Proline-rich Akt substrate (PRAS40 and the hypothetical protein Q6MZQ0/FLJ14213/CAE45978 as new mTOR binding proteins. PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate. PRAS40 inhibits mTORC1 autophosphorylation and mTORC1 kinase activity toward eIF-4E binding protein (4E-BP and PRAS40 itself. HeLa cells in which PRAS40 was knocked down were protected against induction of apoptosis by TNFalpha and cycloheximide. Rapamycin failed to mimic the pro-apoptotic effect of PRAS40, suggesting that PRAS40 mediates apoptosis independently of its inhibitory effect on mTORC1. Q6MZQ0 is structurally similar to proline rich protein 5 (PRR5 and was therefore named PRR5-Like (PRR5L. PRR5L binds specifically to mTORC2, via Rictor and/or SIN1. Unlike other mTORC2 members, PRR5L is not required for mTORC2 integrity or kinase activity, but dissociates from mTORC2 upon knock down of tuberous sclerosis complex 1 (TSC1 and TSC2. Hyperactivation of mTOR by TSC1/2 knock down enhanced apoptosis whereas PRR5L knock down reduced apoptosis. PRR5L knock down reduced apoptosis also in mTORC2 deficient cells. The above suggests that mTORC2-dissociated PRR5L may promote apoptosis when mTOR is hyperactive. Thus, PRAS40 and PRR5L are novel mTOR-associated proteins that control the balance between cell growth and cell death.

Sangrado de angiomiolipoma renal en paciente con síndrome de genes contiguos (TSC2/PKD1 tras 17 años de tratamiento renal sustitutivo

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Mónica Furlano

2017-01-01

Full Text Available Presentamos el caso de un varón de 32 años, con síndrome de genes contiguos TSC2/PKD1, que le ocasiona esclerosis tuberosa (ET y poliquistosis renal autosómica dominante simultáneamente. Evolucionó a enfermedad renal terminal y se realizó trasplante renal a los 12 años. Los riñones presentaban angiomiolipomas (AML, que son tumores benignos frecuentes en pacientes con ET. A los 17 años postrasplante, presentó un cuadro de dolor abdominal, anemización y hematoma retroperitoneal. Dicho hematoma se produjo por el sangrado de los AML. Como tratamiento se realizó embolización selectiva. Nuestro paciente podría haberse beneficiado en el momento del trasplante renal del tratamiento con inhibidores de mTOR. Este fármaco actúa como inmunosupresor y reductor tumoral en la ET, al disminuir el riesgo de rotura y hemorragia. En este paciente no se administró porque cuando se trasplantó no se conocía la relación de los inhibidores de mTOR con la ET. Este caso confirma que, a pesar de tratarse de pacientes trasplantados o en diálisis, el riesgo de sangrado por los AML persiste, por lo cual se propone realizar controles periódicos de los riñones propios y valorar la nefrectomía.

Screening and identification of host factors interacting with UL14 of herpes simplex virus 1.

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Wu, Fuqing; Xing, Junji; Wang, Shuai; Li, Meili; Zheng, Chunfu

2011-08-01

The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast two-hybrid system was employed to screen the cellular factors interacting with UL14, and five target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunofluorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological significance of UL14 during the HSV-1 replication cycle.

Effect of nutritional support on mitochondrial complex I activity in malnourished patients with anorexia nervosa.

Science.gov (United States)

De-Mateo-Silleras, Beatriz; Alonso-Torre, Sara R; Redondo-del-Río, Paz; Jeejeebhoy, Khursheed; Miján-de-la-Torre, Alberto

2013-11-01

Previous studies have shown a reduction in lymphocyte mitochondrial complex I activity (CIA) in malnourished patients, which is restored after refeeding. Our aim was to evaluate the usefulness of CIA as an indicator of nutritional status in anorexia nervosa patients. Twelve malnourished anorexia nervosa females (mean age, 24.5 years) were admitted to the Eating Disorders Unit. Basal and weekly anthropometrics, bioelectric impedance (BIA), body composition, and CIA were performed until discharge. Patients were matched to 25 healthy females and refeeding was adjusted according to the Unit's protocol. Statistics were used as appropriated and significance was reached at p anorexia nervosa have lower CIA than controls that is not recovered after refeeding. This could be because of a low FFM exacerbated by physical inactivity while in hospital.

Making mobility-related disability better: a complex response to a complex problem.

Science.gov (United States)

Rockwood, Kenneth

2012-10-15

Mobility disability in older adults can arise from single system problems, such as discrete musculoskeletal injury. In frail older adults, however, mobility disability is part of a complex web of problems. The approach to their rehabilitation must take that complexity into account, as is reported by Fairhall et al. First, their overall health state must be assessed, which is achieved by a comprehensive geriatric assessment. The assessment can show how a particular patient came to be disabled, so that an individualized care plan can be worked out. Whether this approach works in general can be evaluated by looking at group differences in mean mobility test scores. Knowing whether it has worked in the individual patient requires an individualized measure. This is because not every patient starts from the same point, and not every patient achieves success by aiming for the same goal. For one patient, walking unassisted for three metres would be a triumph; for another it would be a tragedy. Unless we understand the complexity of the needs of frail older adults, we will neither be able to treat them effectively nor evaluate our efforts sensibly.Please see related article http://www.biomedcentral.com/1741-7015/10/120.

[Comparative efficiency of nootropic drugs in complex treatment of patients with remote consequences of closed craniocereberal trauma].

Science.gov (United States)

Hliebova, O S; Tkachenko, O V

2008-01-01

Main data of the research were data obtained after a complex treatment of 120 persons with late consequences of closed craniocereberal trauma (CCRCT). The treatment included administration of one of nootropic agents (noophen, aminolon or entropil), magnesium sulfate, group B vitamins. All patients have passed a complex examination: specially developed questionnaire, anamnesis gathering, neurologic status, neuropsychological status with the use of multiple-aspect scales and questionnaires, examination of fundus of eye, rheoencephalography, echoencephalography, brain MRT. Results of a complex examination proved positive effect of the use of nootropic agents, in particular noophen, entropil and aminolon in complex treatment of late consequences of closed craniocereberal trauma. For optimisation of the use of nootropic agents in the treatment of late consequences of closed craniocereberal trauma it is recommended to consider features of influence of nootropic agents on certain clinical aspects of the disease.

Outcome of patients undergoing open heart surgery at the Uganda heart institute, Mulago hospital complex.

Science.gov (United States)

Aliku, Twalib O; Lubega, Sulaiman; Lwabi, Peter; Oketcho, Michael; Omagino, John O; Mwambu, Tom

2014-12-01

Heart disease is a disabling condition and necessary surgical intervention is often lacking in many developing countries. Training of the superspecialties abroad is largely limited to observation with little or no opportunity for hands on experience. An approach in which open heart surgeries are conducted locally by visiting teams enabling skills transfer to the local team and helps build to build capacity has been adopted at the Uganda Heart Institute (UHI). We reviewed the progress of open heart surgery at the UHI and evaluated the postoperative outcomes and challenges faced in conducting open heart surgery in a developing country. Medical records of patients undergoing open heart surgery at the UHI from October 2007 to June 2012 were reviewed. A total of 124 patients underwent open heart surgery during the study period. The commonest conditions were: venticular septal defects (VSDs) 34.7% (43/124), Atrial septal defects (ASDs) 34.7% (43/124) and tetralogy of fallot (TOF) in 10.5% (13/124). Non governmental organizations (NGOs) funded 96.8% (120/124) of the operations, and in only 4 patients (3.2%) families paid for the surgeries. There was increasing complexity in cases operated upon from predominantly ASDs and VSDs at the beginning to more complex cases like TOFs and TAPVR. The local team independently operated 19 patients (15.3%). Postoperative morbidity was low with arrhythmias, left ventricular dysfunction and re-operations being the commonest seen. Post operative sepsis occurred in only 2 cases (1.6%). The overall mortality rate was 3.2. Open heart surgery though expensive is feasible in a developing country. With increased direct funding from governments and local charities to support open heart surgeries, more cardiac patients access surgical treatment locally.

Care for a Patient With Cancer As a Project: Management of Complex Task Interdependence in Cancer Care Delivery

OpenAIRE

Trosman, Julia R.; Carlos, Ruth C.; Simon, Melissa A.; Madden, Debra L.; Gradishar, William J.; Benson, Al B.; Rapkin, Bruce D.; Weiss, Elisa S.; Gareen, Ilana F.; Wagner, Lynne I.; Khan, Seema A.; Bunce, Mikele M.; Small, Art; Weldon, Christine B.

2016-01-01

Cancer care is highly complex and suffers from fragmentation and lack of coordination across provider specialties and clinical domains. As a result, patients often find that they must coordinate care on their own. Coordinated delivery teams may address these challenges and improve quality of cancer care. Task interdependence is a core principle of rigorous teamwork and is essential to addressing the complexity of cancer care, which is highly interdependent across specialties and modalities. W...

Linfangioleiomiomatosis pulmonar: Caso clínico

OpenAIRE

Silva O,Rafael; Puelma C,Felipe; Retamal P,Víctor; Rojas SM,Pedro; Cruzat C,Claudio; Reyes G,Cecilia

2009-01-01

Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease, of unknown etiology, affecting almost exclusively women. Microscopically LAM consists of a diffuse proliferation of smooth muscle cells. LAM can occur without evidence of other diseases (sporadic LAM) or in conjunction with tuberous sclerosis complex (TSC). It presents with progressive breathlessness or with recurrent pneumothorax or chylothorax. We report a 33 year-old woman with a history of recurrent pneumothorax. Computed...

Triacylglycerol infusion does not improve hyperlactemia in resting patients with mitochondrial myopathy due to complex I deficiency

NARCIS (Netherlands)

Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

Background: A high-fat diet has been recommended for correction of biochemical abnormalities and muscle energy state in patients with complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or

Self-management support and training for patients with chronic and complex conditions improves health-related behaviour and health outcomes.

Science.gov (United States)

Harvey, Peter W; Petkov, John N; Misan, Gary; Fuller, Jeffrey; Battersby, Malcolm W; Cayetano, Teofilo N; Warren, Kate; Holmes, Paul

2008-05-01

The Sharing Health Care SA chronic disease self-management (CDSM) project in rural South Australia was designed to assist patients with chronic and complex conditions (diabetes, cardiovascular disease and arthritis) to learn how to participate more effectively in the management of their condition and to improve their self-management skills. Participants with chronic and complex conditions were recruited into the Sharing Health Care SA program and offered a range of education and support options (including a 6-week peer-led chronic disease self-management program) as part of the Enhanced Primary Care care planning process. Patient self-reported data were collected at baseline and subsequent 6-month intervals using the Partners in Health (PIH) scale to assess self-management skill and ability for 175 patients across four data collection points. Health providers also scored patient knowledge and self-management skills using the same scale over the same intervals. Patients also completed a modified Stanford 2000 Health Survey for the same time intervals to assess service utilisation and health-related lifestyle factors. Results show that both mean patient self-reported PIH scores and mean health provider PIH scores for patients improved significantly over time, indicating that patients demonstrated improved understanding of their condition and improved their ability to manage and deal with their symptoms. These results suggest that involvement in peer-led self-management education programs has a positive effect on patient self-management skill, confidence and health-related behaviour.

Does access to general dental treatment affect the number and complexity of patients presenting to the acute hospital service with severe dentofacial infections?

Science.gov (United States)

Bowe, Conor M; Gargan, Mary Louise; Kearns, Gerard J; Stassen, Leo F A

2015-01-01

This is a retrospective study to review the treatment and management of patients presenting with odontogenic infections in a large urban teaching hospital over a four-year period, comparing the number and complexity of odontogenic infections presenting to an acute general hospital in two periods, as follows: Group A (January 2008 to March 2010) versus Group B (April 2010 to December 2011). The background to the study is 'An alteration in patient access to primary dental care instituted by the Department of Health in April 2010'. a) to identify any alteration in the pattern and complexity of patients' presentation with odontogenic infections following recent changes in access to treatment via the Dental Treatment Services Scheme (DTSS) and the Dental Treatment Benefit Scheme (DTBS) in April 2010; and, b) to evaluate the management of severe odontogenic infections. Data was collated by a combination of a comprehensive chart review and electronic patient record analysis based on the primary discharge diagnosis as recorded in the Hospital In-Patient Enquiry (HIPE) system. Fifty patients were admitted to the National Maxillofacial Unit, St James's Hospital, under the oral and maxillofacial service over a four-year period, with an odontogenic infection as the primary diagnosis. There was an increased number of patients presenting with odontogenic infections during Group B of the study. These patients showed an increased complexity and severity of infection. Although there was an upward trend in the numbers and complexity of infections, this trending did not reach statistical significance. The primary cause of infection was dental caries in all patients. Dental caries is a preventable and treatable disease. Increased resources should be made available to support access to dental care, and thereby lessen the potential for the morbidity and mortality associated with serious odontogenic infections. The study at present continues as a prospective study.

Harnessing complex emergent metaphors for effective communication in palliative care: a multimodal perceptual analysis of hospice patients' reports of transcendence experiences.

Science.gov (United States)

Arnold, Bruce L; Lloyd, Linda S

2014-05-01

Terminally ill patients can have unexpected, enigmatic, and profound cognitive shifts that significantly alter their perception of themselves, thereby eliminating their fear of death and dying. However, there are no systematic studies into these remarkable yet ineffable transcendence experiences. They therefore remain easily overlooked or viewed as isolated anomalies and therefore excluded from quality-of-life patient considerations. We use a multimodal methodology for identifying the prevalence and thematic properties of complex emergent metaphors patients use to report these experiences. Although previous research has pioneered the importance of understanding conventional or primary metaphors at the end of life, our findings indicate the considerable potential of more complex metaphors for reducing barriers to effective communication in palliative care.

The relationship between the INTERMED patient complexity instrument and Level of Care Utilisation System (LOCUS).

Science.gov (United States)

Thurber, Steven; Wilson, Ann; Realmuto, George; Specker, Sheila

2018-03-01

To investigate the concurrent and criterion validity of two independently developed measurement instruments, INTERMED and LOCUS, designed to improve the treatment and clinical management of patients with complex symptom manifestations. Participants (N = 66) were selected from hospital records based on the complexity of presenting symptoms, with tripartite diagnoses across biological, psychiatric and addiction domains. Biopsychosocial information from hospital records were submitted to INTERMED and LOCUS grids. In addition, Global Assessment of Functioning (GAF) ratings were gathered for statistical analyses. The product moment correlation between INTERMED and LOCUS was 0.609 (p = .01). Inverse zero-order correlations for INTERMED and LOCUS total score and GAF were obtained. However, only the beta weight for LOCUS and GAF was significant. An exploratory principal components analysis further illuminated areas of convergence between the instruments. INTERMED and LOCUS demonstrated shared variance. INTERMED appeared more sensitive to complex medical conditions and severe physiological reactions, whereas LOCUS findings are more strongly related to psychiatric symptoms. Implications are discussed.

Cerebral glucose metabolism change in patients with complex regional pain syndrome. A PET study

International Nuclear Information System (INIS)

Shiraishi, Satoe; Kobayashi, Hidetoshi; Nihashi, Takashi

2006-01-01

The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). Brain activity was assessed using 18 F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation. (author)

Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

International Nuclear Information System (INIS)

Gozukirmizi, E.; Meyer, J.S.; Okabe, T.; Amano, T.; Mortel, K.; Karacan, I.

1982-01-01

Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significance was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements

[Adequacy of clinical interventions in patients with advanced and complex disease. Proposal of a decision making algorithm].

Science.gov (United States)

Ameneiros-Lago, E; Carballada-Rico, C; Garrido-Sanjuán, J A; García Martínez, A

2015-01-01

Decision making in the patient with chronic advanced disease is especially complex. Health professionals are obliged to prevent avoidable suffering and not to add any more damage to that of the disease itself. The adequacy of the clinical interventions consists of only offering those diagnostic and therapeutic procedures appropriate to the clinical situation of the patient and to perform only those allowed by the patient or representative. In this article, the use of an algorithm is proposed that should serve to help health professionals in this decision making process. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

Mirror box therapy added to cognitive behavioural therapy in three chronic complex regional pain syndrome type I patients : a pilot study

NARCIS (Netherlands)

Tichelaar, Y. I. G. Vladimir; Geertzen, Jan H. B.; Keizer, Doeke; van Wilgen, C. Paul

Complex regional pain syndrome type I is a disorder of the extremities with disability and pain as the most prominent features. This paper describes the results of cognitive behavioural therapy combined with mirror box therapy in three patients with chronic complex regional pain syndrome type I.

Práticas discursivas e o silenciamento do doente mental: sexualidade negada? Las prácticas discursivas y silencio del paciente mental: ¿Sexualidad negada? Discursive practices and silence of the mental patient: denied sexuality?

Directory of Open Access Journals (Sweden)

Francisco Arnoldo Nunes de Miranda

2008-03-01

was to identify the professionals nurses’s Social Representations about the sexuality of the mental patient. It is a research of exploratory-descriptive nature, with qualitative approach. The resource technicianmethodological used denominated Technique of Investigation in Daily Situations (TSC, applied to 17 nurses that worked in psychiatric services of Ribeirão Preto/SP. Through the discursive manifestations, was verified that the professional nurse denies the sexuality of the mental patient, as a silence form, establishing limits for the censorship on that subject. In this perspective happens the silentness about the sexuality of the mental patient, settling down a politics of the sense on the same. Such positioning reveals the strategy adopted on that knowledge and power, accomplishing the determinations of your professional statute that it is to go to the encounter to the institutional and social expectations.

Dynamics of Clinical and Biochemical Parameters in Patients with Liver Cirrhosis Under the Influence of Complex Therapy with Ursodeoxycholic Acid

Directory of Open Access Journals (Sweden)

M.I. Shved

2013-11-01

Full Text Available It was studied dynamics of clinical and biochemical parameters in patients with liver cirrhosis under the influence of complex treatment using ursosan. It is found that the inclusion of ursosan in complex treatment improves clinical and laboratory parameters, significantly reduces the manifestations of general inflammatory liver syndrome, which prevents the progression of the disease.