Six uneventful pregnancy outcomes in an extended vascular Ehlers-Danlos syndrome family.

PubMed

Baas, Annette F; Spiering, Wilko; Moll, Frans L; Page-Christiaens, Lieve; Beenakkers, Ingrid C M; Dooijes, Dennis; Vonken, Evert-Jan P A; van der Smagt, Jasper J; Knoers, Nine V; Koenen, Steven V; van Herwaarden, Joost A; Sieswerda, Gertjan Tj

2017-02-01

Vascular Ehlers-Danlos Syndrome (vEDS) is caused by heterozygous mutations in COL3A1 and is characterized by fragile vasculature and hollow organs, with a high risk of catastrophic events at a young age. During pregnancy and delivery, maternal mortality rates up until 25% have been reported. However, recent pedigree analysis reported a substantial lower pregnancy-related mortality rate of 4.9%. Here, we describe an extended vEDS family with multiple uneventful pregnancy outcomes. In the proband, a 37-year-old woman, DNA-analysis because of an asymptomatic iliac artery dissection revealed a pathogenic mutation in COL3A1 (c.980G>A; p. Gly327Asp). She had had three uneventful vaginal deliveries. At the time of diagnosis, her 33-year-old niece was 25 weeks pregnant. She had had one uneventful vaginal delivery. Targeted DNA-analysis revealed that she was carrier of the COL3A1 mutation. Ultrasound detected an aneurysm in the abdominal aorta with likely a dissection. An uneventful elective cesarean section was performed at a gestational age of 37 weeks. The 40-year-old sister of our proband had had one uneventful vaginal delivery and an active pregnancy wish. Cascade DNA-screening showed her to carry the COL3A1 mutation. Computed Tomography Angiography (CTA) of her aorta revealed a type B dissection with the most proximal entry tear just below the superior mesenteric artery. Pregnancy was therefore discouraged. This familial case illustrates the complexity and challenges of reproductive decision-making in a potentially lethal condition as vEDS, and highlights the importance of a multidisciplinary approach. Moreover, it suggests that previous pregnancy-related risks of vEDS may be overestimated. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Ehler-Danlos syndrome (type V) with urethra bifida and polydactyly: an unusual combination].

PubMed

Manna, R; Modugno, I; Pala, M A; Caputo, S; Caradonna, E; Greco, A V

1981-06-30

Ehlers-Danlos syndrome is currently regarded as a connective tissue dysplasia. Its genetic, biochemical, histological and clinical features are described, together with a personal case in a patient who presented the fundamental symptoms, plus polydactyly and bifid urethra. This association had not been hitherto reported in the literature. The case itself is classed as Ehlers-Danlos syndrome type V.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

PubMed

Sundelin, Heléne E K; Stephansson, Olof; Johansson, Kari; Ludvigsson, Jonas F

2017-01-01

An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected. In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes. Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome. Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Subjective health complaints and illness perception amongst adults with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-HypermobilityType - a cross-sectional study.

PubMed

Hope, Lena; Juul-Kristensen, Birgit; Løvaas, Helene; Løvvik, Camilla; Maeland, Silje

2017-10-17

To investigate the prevalence and severity of subjective health complaints and describe illness perception in a population of Joint Hypermobility Syndrome or Ehlers-Danlos Syndrome-Hypermobile Type. This study was a postal survey with a questionnaire battery on demographic data, subjective health complaints inventory, and illness perception. A total of 110 individuals diagnosed with Joint Hypermobility Syndrome or Ehlers-Danlos Syndrome-Hypermobile Type from two specialized hospitals in Norway were offered participation. Further, 140 gender- and age-matched healthy controls from statistics Norway representing the general population were sent the questionnaire for reference. Overall response rate was 30.4% (n = 76), with 44.5% (n = 49) in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type and 19.3% (n = 27) in controls. Subjective health complaints were significantly higher in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type - than in the controls (32.06 vs. 11.08; p < 0.001). Further the brief illness perception questionnaire indicated that the adults with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type had low understanding of their illness and symptoms (understanding, mean: 3.93, SD 2.88), and reported to have moderate personal and treatment control over their illness. Adults with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported higher frequency and severity of subjective health complaints than the matched controls from the general adult population in Norway. Furthermore, Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported low understanding of their illness and associated symptoms, and moderate belief that their illness can be kept under control through self-management or treatment. This may indicate one of the reasons why prognosis for these patients is poor. Implications for rehabilitation Awareness of the complexity of the subjective health complaints and inquiry into illness perception could contribute with valuable information about these patients' perceptions of their condition. Such information could in its turn be of value for clinicians as they work towards facilitating a more holistic treatment approach, for example patient education and cognitive behavioural therapy.

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

PubMed

Park, Min A; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-11-01

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Aortic dissection

MedlinePlus

... of the aorta Connective tissue disorders (such as Marfan syndrome and Ehlers-Danlos syndrome) and rare genetic disorders ... cause dissections If you have been diagnosed with Marfan or Ehlers-Danlos syndrome, making sure you regularly follow-up with your ...

Vascular type Ehlers-Danlos Syndrome with fatal spontaneous rupture of a right common iliac artery dissection: case report and review of literature

PubMed Central

Abayazeed, Aly; Hayman, Emily; Moghadamfalahi, Mana; Cain, Darren

2014-01-01

Vascular Ehlers-Danlos Syndrome (previously Ehlers-Danlos IV) is a rare autosomal dominant collagen vascular disorder caused by a 2q31 COL3A1 gene mutation encoding pro-alpha1 chain of type III collagen (in contrast to classic Ehlers-Danlos, caused by a COL5A1 mutation). The vascular type accounts for less than 4% of all Ehlers-Danlos cases and usually has a poor prognosis due to life threatening vascular ruptures and difficult, frequently unsuccessful surgical and vascular interventions. In 70% of cases, vascular rupture or dissection, gastrointestinal perforation, or organ rupture is a presenting sign. We present a case of genetically proven vascular Ehlers-Danlos with fatal recurrent retroperitoneal hemorrhages secondary to a ruptured right common iliac artery dissection in a 30-year-old male. This case highlights the need to suspect collagen vascular disorders when a young adult presents with unexplained retroperitoneal hemorrhage, even without family history of such diseases. PMID:24967021

Visceroptosis and the Ehlers-Danlos Syndrome.

PubMed

Kucera, Stephen; Sullivan, Stephen N

2017-11-08

The case of a patient with visceroptosis and Ehlers-Danlos syndrome hypermobility type (RDS-HT) is reported here. The literature on this unusual but probably under-recognized complication is reviewed.

Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history.

PubMed

Tinkle, Brad; Castori, Marco; Berglund, Britta; Cohen, Helen; Grahame, Rodney; Kazkaz, Hanadi; Levy, Howard

2017-03-01

The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hyperelastic skin

MedlinePlus

... is most often seen in people who have Ehlers-Danlos syndrome. People with this disorder have very elastic skin. ... any member of your family been diagnosed with Ehlers-Danlos syndrome? What other symptoms are present? Genetic counseling may ...

[Bilateral spontaneous carotid-cavernous fistula revealing Ehler-Danlos disease].

PubMed

Girardin, M; Puzenat, E; Humbert, P; Aubin, F

2013-04-01

A 34-year-old woman with an extensive surgical history developed two spontaneous carotido-cavernous fistula bilaterally. Skin examination revealed an acrogeric form of vascular Ehlers-Danlos syndrome and this diagnosis was confirmed by genetic analysis. Vascular Ehlers-Danlos syndrome is a rare autosomal dominant genetic disease that may be suspected on the grounds of clinical symptoms. Severe complications can occur in early life and are associated with a high mortality rate. The prognosis of vascular Ehlers-Danlos syndrome has been radically changed by the use of beta-blockers. The originality of our observation lies in the long time to onset of the initial complications in the absence of any problems during the numerous operations undergone by the patient, as well as the two childbirths. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Two cases of rehabilitation in Ehler-Danlos syndrome].

PubMed

Le Tallec, H; Lassalle, A; Khenioui, H; Durufle, A; Plassat, R; Gallien, P

2006-03-01

Ehlers-Danlos syndrome is rare and little known. It comprises a heterogeneous group of heritable connective tissue disorders characterized by articular hypermobility, skin extensibility and tissue fragility. Diagnosis may be difficult and often delayed. Here we describe 2 cases of women with Ehlers-Danlos syndrome. The first had scoliosis with back pain and joint hypermobility. The second presented with hypermobility and joint dislocation, which increased during pregnancy. In these 2 cases, rehabilitation management produced clinical improvement. Orthopaedic complications such joint pain, joint swelling, joint dislocation, back pain, with walking and hand function disability are the main problems in Ehlers-Danos syndrome. Surgery may be necessary to correct dislocated joints but is often not sufficient to resolve the handicap, and physical therapy has an important place in management. Ehlers-Danlos syndrome is an evolving disease that can lead to great impairment. Thus, physicians must be aware of this syndrome to offer the best management, with the appropriate use of orthotic devices, specific strengthening routines, education in proper body mechanics and assistive devices, to prevent joint dislocation and subluxations responsible for pain and handicap.

Carotid stiffness change over the cardiac cycle by ultrafast ultrasound imaging in healthy volunteers and vascular Ehlers-Danlos syndrome.

PubMed

Mirault, Tristan; Pernot, Mathieu; Frank, Michael; Couade, Mathieu; Niarra, Ralph; Azizi, Michel; Emmerich, Joseph; Jeunemaître, Xavier; Fink, Mathias; Tanter, Mickaël; Messas, Emmanuel

2015-09-01

Arterial stiffness is related to age and collagen properties of the arterial wall and can be indirectly evaluated by the pulse wave velocity (PWV). Ultrafast ultrasound imaging, a unique ultrahigh frame rate technique (>10, 000 images/s), recently emerged enabling direct measurement of carotid PWV and its variation over the cardiac cycle. Our goal was to characterize the carotid diastolic-systolic arterial stiffening using ultrafast ultrasound imaging in healthy individuals and in vascular Ehlers-Danlos syndrome (vEDS), in which collagen type III is defectuous. Ultrafast ultrasound imaging was performed on common carotids of 102 healthy individuals and 37 consecutive patients with vEDS. Results are mean ± standard deviation. Carotid ultrafast ultrasound imaging PWV in healthy individuals was 5.6 ± 1.2 in early systole and 7.3 ± 2.0  m/s in end systole, and correlated with age (r = 0.48; P < 0.0001 and r = 0.68; P < 0.0001, respectively). Difference between early and end-systole PWV increased with age independently of blood pressure (r = 0.54; P < 0.0001). In patients with vEDS, ultrafast ultrasound imaging PWV was 6.0 ± 1.5 in early systole and 6.7 ± 1.5  m/s in end systole. Carotid stiffness change over the cardiac cycle was lower than in healthy people (0.021 vs. 0.057  m/s per mmHg; P = 0.0035). Ultrafast ultrasound imaging can evaluate carotid PWV and its variation over the cardiac cycle. This allowed to demonstrate the age-induced increase of the arterial diastolic-systolic stiffening in healthy people and a lower stiffening in vEDS, both characterized by arterial complications. We believe that this easy-to-use technique could offer the opportunity to go beyond the diastolic PWV to better characterize arterial stiffness change with age or other collagen alterations.

Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome

PubMed Central

Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco

2018-01-01

Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of several structural proteins crucial to the integrity of soft connective tissues. PMID:29346445

Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

PubMed

Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco; Colombi, Marina

2018-01-01

Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of several structural proteins crucial to the integrity of soft connective tissues.

Exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type.

PubMed

Simmonds, Jane V; Herbland, Anthony; Hakim, Alan; Ninis, Nelly; Lever, William; Aziz, Qasim; Cairns, Mindy

2017-11-10

To explore exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type and to explore patient experiences of physiotherapy. A cross sectional questionnaire survey design was used to collect quantitative and qualitative data from adult members of the Hypermobility Syndromes Association and Ehlers-Danlos Syndrome Support UK. Descriptive and inferential statistics were used to analyse the data. Qualitative data was analysed thematically. 946 questionnaires were returned and analysed. Participants who received exercise advice from a physiotherapist were 1.75 more likely to report high volumes of weekly exercise (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.30-2.36, p < 0.001) than those with no advice. Participants who believed that exercise is important for long-term management were 2.76 times more likely to report a high volume of weekly exercise compared to the participants who did not hold this belief (OR = 2.76, 95% CI = 1.38-5.50, p = 0.004). Three themes emerged regarding experience of physiotherapy; physiotherapist as a partner, communication - knowledge, experience and safety. Pain, fatigue and fear are common barriers to exercise. Advice from a physiotherapist and beliefs about the benefits of exercise influenced the reported exercise behaviours of individuals with Ehlers-Danlos syndrome - hypermobility type in this survey. Implications for rehabilitation Exercise is a cornerstone of treatment for Ehlers-Danlos syndrome/Ehlers-Danlos syndrome - hypermobility type. Pain, fatigue and fear of injury are frequently reported barriers to exercise. Advice from physiotherapists may significantly influence exercise behaviour. Physiotherapists with condition specific knowledge and good verbal and non-verbal communication facilitate a positive therapeutic experience.

Ehlers-Danlos Syndrome in Orthopaedics

PubMed Central

Shirley, Eric D.; DeMaio, Marlene; Bodurtha, Joanne

2012-01-01

Ehlers-Danlos syndrome is a heterogeneous connective tissue condition characterized by varying degrees of skin hyperextensibility, joint hypermobility, and vascular fragility. Joint dislocations, musculoskeletal pain, atrophic scars, easy bleeding, vessel/viscera rupture, severe scoliosis, and obstetric complications may occur. These manifestations are secondary to abnormal collagen, with specific molecular defects in types I, III, and V collagen; they may also be related to tenascin-X, which has been identified in some patients. Ehlers-Danlos syndrome has been classified into 6 types, with variable degrees of joint instability, skin hyperextensibility, wound healing difficulty, and vascular fragility. Diagnosis begins with recognition of the signs and symptoms of global hypermobility and referring appropriate patients for genetic consultation. It is important to accurately identify patients with Ehlers-Danlos syndrome to initiate appropriate musculoskeletal treatment, optimize anesthetic and postoperative management, perform appropriate vascular screening, and help families address their concerns with other families and advocacy groups. PMID:23016112

[Ehlers Danlos type IV syndrome presenting with simultaneous dissection of both internal carotid and both vertebral arteries].

PubMed

Mondon, K; de Toffol, B; Georgesco, G; Cassarini, J-F; Machet, M-C; Cottier, J-P; Arbeille, B; Autret, A

2004-04-01

Dissection of cervical arteries is a frequent cause of stroke in young subjects. We report the case of a 34-year-old patient who experienced simultaneous dissection of both internal carotid arteries and both vertebral arteries leading to repeated motor deficit of the right half-body associated with persistent otalgia. Search for an etiology led to the diagnosis of Ehlers-Danlos syndrome type IV. Search for the cause of cervical artery dissection must consider connective tIssue disease, particularly vascular forms of Ehler-Danlos syndrome. Diagnostic, therapeutic as well as prognostic aspects are discussed.

Gait Strategy in Patients with Ehlers-Danlos Syndrome Hypermobility Type and Down Syndrome

ERIC Educational Resources Information Center

Rigoldi, Chiara; Galli, Manuela; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Tenore, Nunzio; Albertini, Giorgio

2012-01-01

People suffering from Ehlers-Danlos syndrome (EDS) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission. The same condition is present in people suffering from Down syndrome (DS) even if their clumsy movements are due to cerebral and cognitive impairments. The aim of this study was to…

Relationship between Fatigue and Gait Abnormality in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

ERIC Educational Resources Information Center

Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Albertini, Giorgio; Camerota, Filippo

2012-01-01

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The…

Stroke in Ehlers-Danlos Syndrome Kyphoscoliotic Type: Dissection or Vasculitis?

PubMed

Quade, Annegret; Wiesmann, Martin; Weis, Joachim; Kurth, Ingo; Jalaie, Houman; Rohrbach, Marianne; Häusler, Martin

2017-09-01

Patients with the kyphoscoliotic type of Ehlers-Danlos syndrome have an increased risk of vascular complications such as aortic dissection and perforation. Cerebral ischemia has only rarely been documented. This 13-year-old girl with the kyphoscoliotic type of Ehlers-Danlos syndrome experienced a large right middle cerebral artery distribution infarction. Full intravenous heparinization was started in response to presumed arterial dissection. Magnetic resonance imaging studies including magnetic resonance angiography and digital subtraction angiography, however, did not confirm dissection but suggested with cerebral vasculitis extending from the intradural right internal carotid artery to the M2 branches of the middle cerebral artery. Combined steroid and cyclophosphamide therapy was associated with clinical improvement. Two months later she died from hemorrhagic shock caused by a two-sided spontaneous rupture of the aortic artery. Cerebral vasculitis should be included in the differential diagnosis of vascular complications in kyphoscoliotic type of Ehlers-Danlos syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

Mean Platelet Volume as an Indicator of Platelet Rejuvenation Following Bone Marrow Transplantation.

DTIC Science & Technology

1986-07-01

al., 1972 Family R ACD volume D D Murphy et al., 1972 Connective Tissue Disorders Ehlers - Danlos Syndrome diameter N I Estes, 1968 Marlan Syndrome ...autosomal dominant), Maran syndrome (autosomal dominant), Mucopolysaccharidosis syndrome (sex-linked), Ehlers - Danlos syndrome (autosomal dominant...individuals with hyperdestructive syndromes (Paulus, 1975). If macrothrombocytosis in hyperdestruction is due only to the young age of the circulating

Tenascin-X, Collagen, Elastin and the Ehlers-Danlos Syndrome

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

Bristow, James; Carey, William; Schalkwijk, Joost

2005-08-31

Tenascin-X is an extracellular matrix protein initially identified because of its overlap with the human CYP21B gene. Because studies of gene and protein function of other tenascins had been poorly predictive of essential functions in vivo, we used a genetic approach that critically relied on an understanding of the genomic locus to uncover an association between inactivating tenascin-X mutations and novel recessive and dominant forms of Ehlers-Danlos syndrome. Tenascin-X provides the first example of a gene outside of the fibrillar collagens and their processing enzymes that causes Ehlers-Danlos syndrome. Tenascin-X null mice recapitulate the skin findings of the human disease,more » confirming a causative role for this gene in Ehlers-Danlos syndrome. Further evaluation of these mice showed that tenascin-X is an important regulator of collagen deposition in vivo, suggesting a novel mechanism of disease in this form of Ehlers-Danlos syndrome. Further studies suggest that tenascin-X may do this through both direct and indirect interactions with the collagen fibril. Recent studies show that TNX effects on matrix extend beyond the collagen to the elastogenic pathway and matrix remodeling enzymes. Tenascin-X serves as a compelling example of how human experiments of nature can guide us to an understanding of genes whose function may not be evident from their sequence or in vitro studies of their encoded proteins.« less

Tenascin-x deficiency mimics ehlers-danlos syndrome in mice through alteration of collagen deposition

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

Mao, J.R.; Taylor, G.; Dean, W.B.

2002-03-01

Tenascin-X is a large extracellular matrix protein of unknown function1-3. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome4,5, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens6. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme7-14, we suggested that tenascin-X might regulate collagen synthesis or deposition15. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologicallymore » normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.« less

Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive*

PubMed Central

Pinto, Raimundo José Almeida de Oliveira; dos Santos, Adaílton Araújo; Azevedo, Mablo de Castro; Meira, Saulo Sacramento

2015-01-01

Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change that results in the formation of structurally or functionally altered collagen. The clinical manifestations are varied, being the most obvious skin hypermotility and increased joint flexibility, although other systems - such as cardiovascular, respiratory and neurological - may also be affected. This paper presents the report of a patient who sought medical attention with complaints of atypical chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram, echocardiogram and 24 hours holter allowed the confirmation of the first hypothesis. A skin biopsy performed later associated clinical data and confirmed the second hypothesis. PMID:26312722

Ehlers-Danlos syndrome associated with fatal spontaneous vascular rupture in a dog.

PubMed

Uri, M; Verin, R; Ressel, L; Buckley, L; McEwan, N

2015-01-01

A 7-month-old male cross breed dog was presented with hyperextensible skin and atrophic scarring. A diagnosis of Ehlers-Danlos syndrome was made based on clinical signs, histopathology and electron microscopy. Two weeks after presentation, the dog died suddenly. Post-mortem examination revealed haemothorax and rupture of the left subclavian artery. Histological findings, including Goldner's modified Masson's trichrome staining and transmission electron microscopy of the subclavian artery, revealed abnormalities in the structure and arrangement of collagen fibrils, suggesting that the defective collagen formation extended to the vasculature. To the authors' knowledge, this is the first report of Ehlers-Danlos syndrome with vascular involvement in animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effects of Muscle Hypotonia and Weakness on Balance: A Study on Prader-Willi and Ehlers-Danlos Syndrome Patients

ERIC Educational Resources Information Center

Galli, Manuela; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Prader-Willi syndrome (PWS) and Ehlers-Danlos syndrome (EDS) are two different genetical disorders both characterized, among other features, by muscular hypotonia. Postural control seems to be impaired in both conditions. The aim of the present study was to quantitatively compare postural control in adult PWS and EDS using stabilometric platform…

Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers-Danlos syndrome: a case report.

PubMed

Lo, Tony Chung Tung; Yeung, Stephen Tung; Lee, Sujin; Skavinski, Kira; Liao, Solomon

2016-01-01

Ehlers-Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers-Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. A 27-year-old Caucasian female with a history of Ehlers-Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7-8 out of 10 to 0-3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of physiological balance between pain inhibition and facilitation. The present report shows that this treatment option can be used in patients with refractory central pain syndrome in the setting of spinal cord myelopathy secondary to Ehlers-Danlos syndrome. In addition, as seen in this case, this protocol can potentially decrease the chronic use of pain medication, such as opioids.

The Academic and Psychosocial Impacts of Ehlers-Danlos Syndrome on Postsecondary Students: An Integrative Review of the Literature

ERIC Educational Resources Information Center

Giroux, Catherine M.; Corkett, Julie K.; Carter, Lorraine M.

2016-01-01

Ehlers-Danlos Syndrome (EDS) is a complex, often invisible, connective tissue disorder that has arguably profound psychosocial and academic impact on postsecondary students. It is an underdiagnosed and misunderstood condition that is the focus of little research, particularly within the social sciences. Several factors influence the academic…

Intermolecular Slip Mechanism in Tropocollagen Nanofibrils

DTIC Science & Technology

2009-01-01

Imperfecta or Ehlers - Danlos Syndrome . REPORT DOCUMENTATION PAGE (SF298) (Continuation Sheet) Continuation for Block 13 ARO Report Number Intermolecular slip...our studies could advance our knowledge of mechan- isms underlying important collagen-related diseases like Osteogenesis Imperfecta or Ehlers - Danlos ... Syndrome . Keywords: Collagen; Shear; Nanomechanics; Steered mo- lecular dynamics; Adhesion strength; Materiomics 1. Introduction Collagen is the

Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

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

Hagspiel, Klaus D., E-mail: kdh2n@virginia.edu; Bonatti, Hugo; Sabri, Saher

2011-04-15

Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

Matrix metalloproteinase inhibitor therapy to prevent complications as well as therapy for Ehler-Danlos syndrome.

PubMed

Sastry, P S R K

2002-09-01

Matrixmetalloproteinase inhibitors have been developed as anti-cancer agents. Their usage in pancreatic cancer and other such malignancies is under trial at present. An interesting undesired-effect of one of these agents is contracture of the hand. Ehler-Danlos syndrome is an inherited group of diseases with varying types. At present there is no known treatment or prevention for the complications associated with this inherited condition. Sometimes it is the adverse events of a drug, which provides an insight into its efficacy for another indication. It is hereby being hypothesized that the matrixmetalloproteinase inhibitors especially marimastat may be an effective drug for treatment of Ehler-Danlos syndrome and/or prevention of its major complications.

Gait Pattern in Two Rare Genetic Conditions Characterized by Muscular Hypotonia: Ehlers-Danlos and Prader-Willi Syndrome

ERIC Educational Resources Information Center

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters…

Ehlers-Danlos syndrome in a Zimbabwean child.

PubMed

Olaosebikan, A; Wolf, B

1993-01-01

An isolated case of Ehler-Danlos syndrome, Type 1, in a two year old Zimbabwean boy is described. The patient presented with failure to thrive and inability to stand. Examination revealed hyperextensibility of the joints and skin, umbilical and inguinal hernias and a perimembranous ventricular septal defect. To the best of our knowledge this is the first pediatric case described in the African literature.

Postural Analysis in Time and Frequency Domains in Patients with Ehlers-Danlos Syndrome

ERIC Educational Resources Information Center

Galli, Manuela; Rigoldi, Chiara; Celletti, Claudia; Mainardi, Luca; Tenore, Nunzio; Albertini, Giorgio; Camerota, Filippo

2011-01-01

The goal of this work is to analyze postural control in Ehlers-Danlos syndrome (EDS) participants in time and frequency domain. This study considered a pathological group composed by 22 EDS participants performing a postural test consisting in maintaining standing position over a force platform for 30 s in two conditions: open eyes (OE) and closed…

Friable but treatable: coronary artery dissections in Ehlers-Danlos syndrome.

PubMed

Zago, Alexandre C; Matte, Bruno S

2013-01-01

Vascular Ehlers-Danlos syndrome is a rare connective tissue disorder associated with arterial dissection or rupture. Percutaneous coronary intervention (PCI) is often critical in patients with this syndrome because their coronary arteries are prone to dissection, enhancing the risk of stent borders dissection when conventional stent deployment pressures are used. Coronary artery bypass graft (CABG) treatment for these patients may also raise concerns because the left internal mammary artery is probably friable. Therefore, coronary artery revascularization in vascular Ehlers-Danlos syndrome either using PCI or CABG is challenging due to the arteries friability. A small number of cases have been published describing the friability of the vessels and associated complications; nevertheless, the optimum treatment remains unclear. We report the case of a 54-year-old woman treated successfully with PCI and CABG in two different acute coronary syndrome episodes, in which specific technical issues related to both procedures were decisive. Copyright © 2011 Wiley Periodicals, Inc.

Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III.

PubMed

Cheng, Jem L; Au, Jason S; Guzman, Juan C; Morillo, Carlos A; MacDonald, Maureen J

2017-04-01

The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.

Retrobulbar Hematoma from Warfarin Toxicity and the Limitations of Bedside Ocular Sonography

DTIC Science & Technology

2010-05-01

Nontraumatic RBH occurs rarely and has been associated with arteriovenous malformations,1 following thrombolysis,2 Type IV Ehlers - Danlos Syndrome ,3...infarction. N Engl J Med. 2007; 357:1448-9. 3. Shaikh S, Braun M, Eliason J. Spontaneous retrobulbar hemorrhage in type IV Ehlers - Danlos syndrome . Am J...compartment syndrome . DISCUSSION We believe this is the first case report of a nontraumatic RBH associated with warfarin toxicity. Our patient also had

Gait Strategy in Patients with Ehlers-Danlos Syndrome Hypermobility Type: A Kinematic and Kinetic Evaluation Using 3D Gait Analysis

ERIC Educational Resources Information Center

Galli, Manuela; Cimolin, Veronica; Rigoldi, Chiara; Castori, Marco; Celletti, Claudia; Albertini, Giorgio; Camerota, Filippo

2011-01-01

The aim of this study was to quantify the gait patterns of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome (JHS/EDS-HT) hypermobility type, using Gait Analysis. We quantified the gait strategy in 12 JHS/EDS-HT adults individuals (age: 43.08 + 6.78 years) compared to 20 healthy controls (age: 37.23 plus or minus 8.91 years), in…

Measuring Regularity of Human Postural Sway Using Approximate Entropy and Sample Entropy in Patients with Ehlers-Danlos Syndrome Hypermobility Type

ERIC Educational Resources Information Center

Rigoldi, Chiara; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Mainardi, Luca; Galli, Manuela

2013-01-01

Ligament laxity in Ehlers-Danlos syndrome hypermobility type (EDS-HT) patients can influence the intrinsic information about posture and movement and can have a negative effect on the appropriateness of postural reactions. Several measures have been proposed in literature to describe the planar migration of CoP over the base of support, and the…

Fatal Peritoneal Bleeding Following Embolization of a Carotid-Cavernous Fistula in Ehlers-Danlos Syndrome Type IV

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

Usinskiene, Jurgita; Mazighi, Mikael; Bisdorff, Annouk

2006-12-15

We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed.

Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome.

PubMed

Byers, Peter H; Belmont, John; Black, James; De Backer, Julie; Frank, Michael; Jeunemaitre, Xavier; Johnson, Diana; Pepin, Melanie; Robert, Leema; Sanders, Lynn; Wheeldon, Nigel

2017-03-01

Vascular Ehlers Danlos syndrome (vEDS) is an uncommon genetic disorders characterized by arterial aneurysm, dissection and rupture, bowel rupture, and rupture of the gravid uterus. The frequency is estimated as 1/50,000-1/200,000 and results from pathogenic variants in COL3A1, which encodes the chains of type III procollagen, a major protein in vessel walls and hollow organs. Initial diagnosis depends on the recognitions of clinical features, including family history. Management is complex and requires multiple specialists who can respond to and manage the major complications. A summary of recommendations for management include: Identify causative variants in COL3A1 prior to application of diagnosis, modulate life style to minimize injury, risk of vessel/organ rupture, identify and create care team, provide individual plans for emergency care ("vascular EDS passport") with diagnosis and management plan for use when traveling, centralize management at centers of excellence (experience) when feasible, maintain blood pressure in the normal range and treat hypertension aggressively, surveillance of vascular tree by doppler ultrasound, CTA (low radiation alternatives) or MRA if feasible on an annual basis. These recommendations represent a consensus of an international group of specialists with a broad aggregate experience in the care of individuals with vascular EDS that will need to be assessed on a regular basis as new information develops. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Open inferior capsular shift for multidirectional shoulder instability in adolescents with generalized ligamentous hyperlaxity or Ehlers-Danlos syndrome.

PubMed

Vavken, Patrick; Tepolt, Frances A; Kocher, Mininder S

2016-06-01

The objective of this study was to assess the outcome of open inferior capsular shift for multidirectional shoulder instability in patients with generalized ligamentous hyperlaxity or Ehlers-Danlos syndrome. Data were obtained for 18 open inferior capsular shift surgeries in 15 adolescent patients with generalized ligamentous hyperlaxity or Ehlers-Danlos syndrome with a mean follow-up of 7.5 years. End points were subjective clinical outcome (pain, stability, satisfaction, return to sport), objective clinical outcome (recurrence, complications), and functional outcome scores (American Shoulder and Elbow Surgeons, 11-item version of the Disabilities of Arm, Shoulder and Hand). Thirteen patients (87%) reported improved pain and stability and were satisfied with the procedure. Nine patients (64%) were able to return to sports. One patient (7%) was dissatisfied with continuous pain and recurrent instability and considered a surgical failure. Seven patients (47%) reported no further episodes of instability. The mean American Shoulder and Elbow Surgeons score at a mean of 7.5 years of follow-up was 88 ± 10 points, and the mean score for the 11-item version of the Disabilities of Arm, Shoulder and Hand was 14 ± 14 points. The management of multidirectional shoulder instability in adolescent patients with generalized ligamentous hyperlaxity or Ehlers-Danlos syndrome is challenging. Open inferior capsular shift results in improvement in subjective and objective shoulder function and stability in adolescent patients with ligamentous hyperlaxity or Ehlers-Danlos who have failed nonoperative treatment. We found no effect of the recalled number of prior dislocations, laterality, and type of hyperlaxity on subjective and objective clinical outcomes. Level IV; Case Series; Treatment Study. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Evaluation of a patient with classical Ehlers-Danlos syndrome due to a 9q34 duplication affecting COL5A1.

PubMed

Kuroda, Yukiko; Ohashi, Ikuko; Naruto, Takuya; Ida, Kazumi; Enomoto, Yumi; Saito, Toshiyuki; Nagai, Jun-Ichi; Kurosawa, Kenji

2018-03-09

Ehlers-Danlos syndrome classical type is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and joint hypermobility. The condition typically results from mutations in COL5A1 or COL5A2 leading to the functional haploinsufficiency. Here, we report of a 24-year-old male with mild intellectual disability, dysmorphic features, and a phenotype consistent with Ehlers-Danlos syndrome classical type. A copy number variant-calling algorithm from panel sequencing data identified the deletions exons 2-11 and duplications of exons 12-67 within COL5A1. Array comparative genomic hybridization confirmed a 94 kb deletion at 9q34.3 involving exons 2-11 of COL5A1, and a 3.4 Mb duplication at 9q34.3 involving exons 12-67 of COL5A1. © 2018 Japanese Teratology Society.

Features that exacerbate fatigue severity in joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type.

PubMed

Krahe, Anne Maree; Adams, Roger David; Nicholson, Leslie Lorenda

2018-08-01

To assess the prevalence, severity and impact of fatigue on individuals with joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome - hypermobility type (EDS-HT) and establish potential determinants of fatigue severity in this population. Questionnaires on symptoms and signs related to fatigue, quality of life, mental health, physical activity participation and sleep quality were completed by people with JHS/EDS-HT recruited through two social media sites. Multiple regression analysis was performed to identify predictors of fatigue in this population. Significant fatigue was reported by 79.5% of the 117 participants. Multiple regression analysis identified five predictors of fatigue severity, four being potentially modifiable, accounting for 52.3% of the variance in reported fatigue scores. Predictors of fatigue severity were: the self-perceived extent of joint hypermobility, orthostatic dizziness related to heat and exercise, levels of participation in personal relationships and community, current levels of physical activity and dissatisfaction with the diagnostic process and management options provided for their condition. Fatigue is a significant symptom associated with JHS/EDS-HT. Assessment of individuals with this condition should include measures of fatigue severity to enable targeted management of potentially modifiable factors associated with fatigue severity. Implications for rehabilitation Fatigue is a significant symptom reported by individuals affected by joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type. Potentially modifiable features that contribute to fatigue severity in this population have been identified. Targeted management of these features may decrease the severity and impact of fatigue in joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type.

Patients with Ehlers Danlos syndrome and CRPS: a possible association?

PubMed

Stoler, Joan M; Oaklander, Anne Louise

2006-07-01

Rare patients are left with chronic pain, vasodysregulation, and other symptoms that define complex regional pain syndrome (CRPS), after limb traumas. The predisposing factors are unknown. Genetic factors undoubtedly contribute, but have not yet been identified. We report four CRPS patients also diagnosed with the classical or hypermobility forms of Ehlers Danlos syndrome (EDS), inherited disorders of connective tissue. These patients had been diagnosed using standard diagnostic criteria for CRPS and for EDS. All had sustained joint injury; in three this had been surgically treated. The association of these two diagnoses leads us to hypothesize that EDS might contribute to the development of CRPS in one or more of the following ways: via stretch injury to nerves traversing hypermobile joints, increased fragility of nerve connective tissue, or nerve trauma from more frequent surgery. We review the clinical presentation of the different Ehlers Danlos syndromes and provide clinical criteria that can be used to screen CRPS patients for EDS for clinical or research purposes.

Brugada Syndrome in a Patient with Vascular Ehlers-Danlos Syndrome: Sudden Death Risk Amplified.

PubMed

D'Souza, Jason; Malhotra, Divyanshu; Goud, Aditya; Dahagam, Chanukya; Everett, George

2017-04-19

The vast majority of sudden cardiac arrests occur in patients with structural heart disease and in approximately 10% of the cases, it can occur in those with structurally normal hearts. Brugada syndrome is an autosomal dominant sodium channelopathy that has been implicated in sudden deaths. Given their low prevalence, our knowledge about Brugada syndrome is still evolving. Apart from schizophrenia, there have been no reports of associated medical conditions. We recently encountered a patient with vascular Ehlers-Danlos syndrome who was also found to have Brugada syndrome. Both these conditions share some common clinical presentations including a propensity for sudden death.

Single-Ventricle Palliation in a 4-Year-Old With Ehlers-Danlos Syndrome.

PubMed

DeBoard, Zach M; Eckhauser, Aaron W; Griffiths, Eric

2018-01-01

We report the case of a 4-year-old boy with Ehlers-Danlos syndrome undergoing single-ventricle palliation for an unbalanced atrioventricular canal defect. No reports of single-ventricle palliation in the setting of connective tissue disorders exist in the current literature. Unique findings on the patient's preoperative imaging included a disproportionately large neoaortic root and a regurgitant atrioventricular valve, which may foretell the need for future intervention. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility type): it is a challenge.

PubMed

Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul Hh

2015-01-01

Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers-Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3).

Joint hypermobility and headache: understanding the glue that binds the two together--part 1.

PubMed

Neilson, Derek; Martin, Vincent T

2014-09-01

Heritable connective tissue disorders (HCTD) present with a wide array of findings, including headache. Because of their unusual substrate, headaches in HCTD can derive from both common and uncommon circumstances. Literature review. Ehlers-Danlos hypermobile type can be recognized by multiple joint findings and its tendency to progress to a multisystem chronic pain syndrome. Ehlers-Danlos classic type also manifests joint laxity and similar pain complaints, but is differentiated by its skin laxity and fragility. Ehlers-Danlos vascular type presents the most severe risk due to blood vessel and hollow organ rupture. Marfan syndrome demonstrates skeletal abnormalities, lens dislocations, and aortic root dilation that can result in dissection. In a headache patient, recognizing the presence of an HCTD improves the strategy for diagnosis and management. A brief review of findings related to joints, skin, and arteries may prompt further investigation into the HCTDs. © 2014 American Headache Society.

Systemic Multiple Aneurysms Caused by Vascular Ehlers-Danlos Syndrome.

PubMed

Gui, Xinyu; Li, Fangda; Wu, Lingeer; Zheng, Yuehong

2016-07-01

Systemic multiple aneurysms are rare and usually associated with collagen tissue disease, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome. In the present case, we describe a 39-year-old male patient with systemic multiple aneurysms and acute intraperitoneal hemorrhage who was clinically diagnosed with vascular EDS. Coil embolization of the distal segment of the common hepatic artery was performed, which resolved the patient's symptoms. With this case presentation, we aim to increase the awareness of vascular EDS among clinicians and emphasize the extreme fragility of the arteries in patients with vascular EDS. © The Author(s) 2016.

Subclavian artery aneurysm in a patient with vascular Ehlers-Danlos syndrome.

PubMed

Yasuda, Shota; Imoto, Kiyotaka; Uchida, Keiji; Uranaka, Yasuko; Kurosawa, Kenji; Masuda, Munetaka

2016-02-01

We describe our experience of surgical treatment in a 28-year-old woman with vascular Ehlers-Danlos syndrome. A right subclavian artery aneurysm was detected. The right vertebral artery arose from the aneurysm. Digital subtraction angiography showed interruption of the left vertebral artery. The aneurysm was excised and the right vertebral artery was anastomosed end-to-side to the right common carotid artery under deep hypothermia and circulatory arrest. The patient remained very well 4 years after surgery, with no late vascular complication. © The Author(s) 2014.

CE: Nursing Management of Patients with Ehlers-Danlos Syndrome.

PubMed

Anderson, Linda K

2015-07-01

Ehlers-Danlos syndrome (EDS), a hereditary connective tissue disorder, has historically been misunderstood and underdiagnosed by health care providers. Because of the high degree of phenotypic variability, patients are often correctly diagnosed only after years of seemingly unrelated but debilitating injuries and illnesses. Specific genetic mutations have been identified for some, but not all, EDS types; patients presenting with a high index of suspicion should be referred to a geneticist. As awareness and recognition of the syndrome improve, nurses are increasingly likely to care for patients with EDS. This article gives a brief overview of the syndrome and provides guidance on ways to manage symptoms, recognize and prevent serious complications, and improve patients' quality of life.

Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome in a Chinese man.

PubMed

Lu, Yanqin; Wang, Yanzhou; Rauch, Frank; Li, Hu; Zhang, Yao; Zhai, Naixiang; Zhang, Jian; Ren, Xiuzhi; Han, Jinxiang

2018-02-01

Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are rare genetic disorders that are typically inherited in an autosomal dominant manner. Few cases of OI/EDS overlap syndrome have been documented. Described here is a 30-year-old Chinese male with OI type III and EDS. Sequencing of genomic DNA revealed a heterozygous COL1A1 mutation (c.671G>A, p.Gly224Asp) that affected the N-anchor domain of the alpha 1 chain of collagen type I. Ultrastructural analysis of a skin biopsy specimen revealed thin collagen fibers with irregular alignment of collagen fibers. These findings have expanded the genotypic spectrum of the OI/EDS overlap syndrome.

Pregnancy and mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

PubMed

Radetskaya, L S; Makatsariya, A D; Bitsadze, V O; Khizroeva, J K

2018-07-01

The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.

Anterior Cruciate Ligament Reconstruction in Ehlers-Danlos Syndrome

PubMed Central

Williams, John; Hutt, Jonathan; Rickman, Mark

2015-01-01

This report details the reconstruction of the anterior cruciate ligament in an 18-year-old man with Ehlers-Danlos syndrome (EDS). The reduced mechanical properties of the tissue in EDS can pose a challenge to the orthopaedic surgeon. In this case, we describe the use of a hamstring autograft combined with a Ligament Advanced Reinforcement System (LARS). There was a good radiographical, clinical, and functional outcome after two years. This technique gave a successful outcome in the reconstruction of the ACL in a patient with EDS and therefore may help surgeons faced with the same clinical scenario. PMID:26221555

A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome.

PubMed

Watanabe, Miki; Nakagawa, Ryuji; Naruto, Takuya; Kohmoto, Tomohiro; Suga, Ken-Ichi; Goji, Aya; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg].

Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique.

PubMed

Huynh, Thien J; Morton, Ryan P; Levitt, Michael R; Ghodke, Basavaraj V; Wink, Onno; Hallam, Danial K

2017-08-18

We report successful transvenous treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture. 2017 BMJ Publishing Group Ltd.

Endovascular Treatment of a Carotid Dissecting Pseudoaneurysm in a Patient with Ehlers-Danlos Syndrome Type IV with Fatal Outcome

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

Lim, Siok Ping, E-mail: siokpinglim@yahoo.co.uk; Duddy, Martin J.

2008-01-15

We present a patient with Ehlers-Danlos syndrome type IV (EDS IV) with a carotid dissecting pseudoaneurysm causing severe carotid stenosis. This lesion was treated endovascularly. Unfortunately, the patient died of remote vascular catastrophes (intracranial hemorrhage and abdominal aortic rupture). This unique case illustrates the perils of endovascular treatment of EDS IV patients and the need for preoperative screening for concomitant lesions. It also shows that a dissecting pseudoaneurysm can feasibly be treated with a covered stent and that closure is effective using Angioseal in patients with EDS IV.

Ehlers-Danlos syndrome type IV

PubMed Central

Germain, Dominique P

2007-01-01

Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering from EDS type IV. Surgery may, however, be required urgently to treat potentially fatal complications. PMID:17640391

The neuromuscular differential diagnosis of joint hypermobility.

PubMed

Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

2015-03-01

Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. © 2015 Wiley Periodicals, Inc.

[The genetics of collagen diseases].

PubMed

Kaplan, J; Maroteaux, P; Frezal, J

1986-01-01

Heritable disorders of collagen include Ehler-Danlos syndromes (11 types are actually known), Larsen syndrome and osteogenesis imperfecta. Their clinical, genetic and biochemical features are reviewed. Marfan syndrome is closely related to heritable disorders of collagen.

Difficulty eating and significant weight loss in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Baeza-Velasco, Carolina; Van den Bossche, Thomas; Grossin, Daniel; Hamonet, Claude

2016-06-01

Joint Hypermobility Syndrome, also known as Ehlers-Danlos Syndrome Hypermobility Type (JHS/EDS-HT), is a heritable disorder of connective tissue, common but poorly known by the medical community. Although generalized joint hypermobility and fragility of tissues have been described as core features, recent research highlights the multisystemic nature of JHS/EDS-HT, which presents with a wide range of articular and extra-articular symptoms. Among these, gastrointestinal problems, temporomandibular disorders, and smell and taste abnormalities are common among those affected, having significant implications for eating. The present work reviews the literature linking JHS/EDS-HT and eating problems. Two illustrative case reports, in which JHS/EDS-HT manifestations contribute to developing and maintaining disturbed eating behaviors and significant weight loss, are presented.

75 FR 58404 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification. Applications... component of the addictive syndrome, with approximately two-thirds of patients relapsing within three months...

Endovascular repair of an iliac artery aneurysm in a patient with Ehlers-Danlos syndrome type IV.

PubMed

Tonnessen, Britt H; Sternbergh, W Charles; Mannava, Krishna; Money, Samuel R

2007-01-01

Ehlers-Danlos type IV (EDS-IV) is an inherited condition most notable for its associated vascular complications. Patients are prone to aneurysm formation, arterial dissection, and spontaneous vessel rupture. Intervention for the vascular pathology of EDS-IV carries high morbidity and mortality. We describe a case of a 57-year-old man with EDS-IV and an expanding iliac aneurysm who underwent successful endovascular repair with a stent-graft. Endovascular aneurysm repair is feasible and should be considered for patients with EDS-IV.

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

PubMed Central

Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun

2014-01-01

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803

Pregnancy with aortic dissection in Ehler-Danlos syndrome. Staged replacement of the total aorta (10-year follow-up).

PubMed

Babatasi, G; Massetti, M; Bhoyroo, S; Khayat, A

1997-10-01

Pregnancy complicated by aortic dissection in patients with hereditary disorder of connective tissue presents interesting considerations including management of caesarean section with the unexpected need for cardiac surgery in emergency. Generalizations can be made on management principles with long-term follow-up requiring an aggressive individualized approach by a multidisciplinary team. A 33-year-old parturient presenting an aortic dissection at 37 weeks gestation required prompt diagnosis of Ehlers-Danlos syndrome in combination with correct surgical therapy resulted in the survival of both the mother and infant. During the 10-year follow-up, multiple complex dissection required transverse aortic arch and thoracoabdominal aortic replacement.

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome.

PubMed

Kim, Jeong Gyun; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Jeong Eun

2014-02-01

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

Dermal Ultrastructure in Low Beighton Score Members of 17 Families with Hypermobile-Type Ehlers-Danlos Syndrome

PubMed Central

Hermanns-Lê, Trinh; Reginster, Marie-Annick; Piérard-Franchimont, Claudine; Delvenne, Philippe; Piérard, Gérald E.; Manicourt, Daniel

2012-01-01

The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH. PMID:23091361

Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: A review for the gastroenterologist.

PubMed

Beckers, A B; Keszthelyi, D; Fikree, A; Vork, L; Masclee, A; Farmer, A D; Aziz, Q

2017-08-01

Joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) is the most common hereditary non-inflammatory disorder of connective tissue, characterized by a wide range of symptoms, mainly joint hyperextensibility and musculoskeletal symptoms. A majority of patients also experiences gastrointestinal (GI) symptoms. Furthermore, JHS/EDS-HT has specifically been shown to be highly prevalent in patients with functional GI disorders, such as functional dyspepsia and irritable bowel syndrome. The aim of this review was to examine the nature of GI symptoms and their underlying pathophysiology in JHS/EDS-HT. In addition, we consider the clinical implications of the diagnosis and treatment of JHS/EDS-HT for practicing clinicians in gastroenterology. Observations summarized in this review may furthermore represent the first step toward the identification of a new pathophysiological basis for a substantial subgroup of patients with functional GI disorders. © 2017 John Wiley & Sons Ltd.

Mobile Cecum in a Young Woman with Ehlers-Danlos Syndrome Hypermobility type: A Case Report and Review of the Literature.

PubMed

Fukuda, Yoshihisa; Higuchi, Yusuke; Shinozaki, Kanae; Tanigawa, Yuji; Abe, Taro; Hanaoka, Nobuyoshi; Matsubayashi, Sunao; Yamaguchi, Tomomi; Kosho, Tomoki; Nakamichi, Koji

2017-10-15

Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is unexpectedly common and is associated with a high rate of gastrointestinal manifestations. We herein report the first documented case of mobile cecum associated with EDS-HT. A 21-year-old woman with repeated right lower abdominal pain was initially diagnosed with EDS-HT. Abdominal examinations performed in the supine position, such as CT and ultrasonography, showed no gross abnormalities. In contrast, oral barium gastrointestinal transit X-ray images obtained with changes in the patient's body position revealed position-dependent cecal volvulus with mobile cecum. She was finally discharged with a dramatic resolution of her symptoms after laparoscopic cecopexy for mobile cecum.

Mobile Cecum in a Young Woman with Ehlers-Danlos Syndrome Hypermobility type: A Case Report and Review of the Literature

PubMed Central

Fukuda, Yoshihisa; Higuchi, Yusuke; Shinozaki, Kanae; Tanigawa, Yuji; Abe, Taro; Hanaoka, Nobuyoshi; Matsubayashi, Sunao; Yamaguchi, Tomomi; Kosho, Tomoki; Nakamichi, Koji

2017-01-01

Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is unexpectedly common and is associated with a high rate of gastrointestinal manifestations. We herein report the first documented case of mobile cecum associated with EDS-HT. A 21-year-old woman with repeated right lower abdominal pain was initially diagnosed with EDS-HT. Abdominal examinations performed in the supine position, such as CT and ultrasonography, showed no gross abnormalities. In contrast, oral barium gastrointestinal transit X-ray images obtained with changes in the patient's body position revealed position-dependent cecal volvulus with mobile cecum. She was finally discharged with a dramatic resolution of her symptoms after laparoscopic cecopexy for mobile cecum. PMID:28924124

[Severe Mast Cell Activation Syndrome in a 15-year-old patient with an hypermobile Ehlers-Danlos syndrome].

PubMed

Daens, S; Grossin, D; Hermanns-Lê, T; Peeters, D; Manicourt, D

2018-02-01

We report the history of a 15-year old patient with a hypermobile Ehlers-Danlos syndrome (hEDS) (his mother, his two brothers and his sister have the same phenotype as him). He suffers mainly from a severe mast cell activation syndrome (MCAS) with an overreaction of the skin to any kind of contact (water of the shower, clothes, bed sheets) but he has also fatigue, headaches, and rash. This impressive rash is exacerbated after the shower and he has the urge to rest («shower's sign»). We describe the MCAS and its easy, fast and very effective medication management, without any significant side effects as well as its frequent association with the hEDS. We finally introduce the original term of «MASED» to this MCAS, associated, linked or entangled to hEDS.

Ehlers-Danlos syndrome

MedlinePlus

... down to children. This can be determined through testing and evaluations suggested by your provider or genetic counselor. Identifying any significant health risks may help prevent severe complications by vigilant screening ...

Thoracic aortic aneurysm

MedlinePlus

... the part of the body's largest artery (the aorta) that passes through the chest. ... Marfan or Ehlers-Danlos syndrome Inflammation of the aorta Injury from falls or motor vehicle accidents Syphilis

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ClinicalTrials.gov

2018-02-19

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

Suspicious scars: physical child abuse vs Ehlers-Danlos syndrome.

PubMed

Vadysinghe, Amal Nishantha; Wickramashinghe, Chatula Usari; Nanayakkara, Dineshi Nadira; Kaluarachchi, Chandishni Ishara

2018-01-01

Child abuse is a sensitive topic among many medical practitioners and the diagnosis of this entity requires awareness about conditions which can mimic physical child abuse. Here, the authors present a case of a 13-year-old school non-attendee who was referred due to multiple scars, over areas prone to accidental as well as non-accidental injury, who underwent medicolegal examination due to suspicion of physical child abuse. On further inquiry, it was discovered that she had easy bruising and poor wound healing. A diagnosis of Ehlers-Danlos syndrome was established and physical child abuse was excluded. This case emphasizes the importance of identifying conditions which may confound the diagnosis of physical child abuse. This is of utmost importance in avoiding adverse legal and psycho-social implications on the child, family and society.

Recommendations for anesthesia and perioperative management in patients with Ehlers-Danlos syndrome(s)

PubMed Central

2014-01-01

Ehlers-Danlos syndrome (EDS, ORPHA98249) comprises a group of clinically and genetically heterogeneous heritable connective tissue disorders, chiefly characterized by joint hypermobility and instability, skin texture anomalies, and vascular and soft tissue fragility. As many tissues can be involved, the underlying molecular defect can manifest itself in many organs and with varying degrees of severity, with widespread implications for anesthesia and perioperative management. This review focuses on issues relevant for anesthesia for elective and emergency surgery in EDS. We searched the literature for papers related to all EDS variants; at the moment most of the published data deals with the vascular subtype and, to a lesser extent, classic and hypermobility EDS. Knowledge is fragmented and consists mostly of case reports, small case series and expert opinion. Because EDS patients commonly require surgery, we have summarized some recommendations for general, obstetrical and regional anesthesia, as well as for hemostatic therapy. PMID:25053156

Congenital cervical kyphosis in an infant with Ehlers-Danlos syndrome.

PubMed

Kobets, Andrew J; Komlos, Daniel; Houten, John K

2018-07-01

Ehler-Danlos syndome (EDS) refers to a group of heritable connective tissue disorders; rare manifestations of which are cervical kyphosis and clinical myelopathy. Surgical treatment is described for the deformity in the thoracolumbar spine in adolescents but not for infantile cervical spine. Internal fixation for deformity correction in the infantile cervical spine is challenging due to the diminutive size of the bony anatomy and the lack of spinal instrumentation specifically designed for young children. We describe the first case of successful surgical treatment in an infant with a high cervical kyphotic deformity in EDS. A 15-month-old female with EDS presented with several months of regression in gross motor skills in all four extremities. Imaging demonstrated 45° of kyphosis from the C2-4 levels with spinal cord compression. Corrective surgery consisted of a C3 corpectomy and C2-4 anterior fusion with allograft block and anterior fixation with dual 2 × 2 hole craniofacial miniplates, supplemented by C2-4 posterior fusion using four craniofacial miniplates fixated to the lamina. Radiographs at 20 months post-surgery demonstrated solid fusion both anteriorly and posteriorly with maintenance of correction. Ehlers-Danlos syndrome may present in the pediatric population with congenital kyphosis from cervical deformity in addition to the more commonly seen thoracolumbar deformities.

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

PubMed

Eller-Vainicher, C; Bassotti, A; Imeraj, A; Cairoli, E; Ulivieri, F M; Cortini, F; Dubini, M; Marinelli, B; Spada, A; Chiodini, I

2016-08-01

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients. The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients. Fifty consecutive Caucasian patients, aged 30-50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects' calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed. Patients showed reduced BMD (Z-scores LS -0.45 ± 1.00, FN -0.56 ± 1.01, FT -0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency. EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

Complexities of management of a urostomy in Ehlers-Danlos syndrome: a reflective account.

PubMed

Oxenham, Julie

Mary (pseudonym) is a 30-year-old woman who underwent a urinary diversion and formation of an ileal conduit/urostomy (urinary stoma) due to the formation of multiple bladder diverticula, which caused micturition difficulties and recurrent urinary tract infections with associated pain and discomfort. The bladder diverticula were caused by Ehlers-Danlos syndrome (EDS), a hereditary disorder of the connective tissue or, particulary, defective collagen. Surgical intervention in patients with EDS is prone to complications due to poor wound healing, including issues of dehiscence, postoperative bleeding and poor uptake of anaesthesia and analgesia. After an initial presentation of the syndrome of EDS and Mary's history, this article offers a reflective account (informed by Gibbs' Reflective Cycle) and illustrates the complexities of caring for an individual with EDS who undergoes stoma formation. The author, a stoma care nurse, demonstrates how using purposeful reflection resulted in better understanding and awareness of caring for an individual with a rare syndrome and the nursing challenges this presented.

Genetics Home Reference: Ehlers-Danlos syndrome

MedlinePlus

... one affected parent . Other cases result from new (de novo) gene mutations and occur in people with ... 31550. Review. Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, ...

Resolution of Large Azygos Vein Aneurysm Following Stent-Graft Shunt Placement in a Patient with Ehlers-Danlos Syndrome Type IV

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

D'Souza, Estelle S.; Williams, David M.; Deeb, G.M.

2006-10-15

Ehlers-Danlos syndrome (EDS) type IV is a rare connective tissue disorder associated with thin-walled, friable arteries and veins predisposing patients to aneurysm formation, dissection, fistula formation, and vessel rupture. Azygos vein aneurysm is an extremely rare condition which has not been reported in association with EDS in the literature. We present a patient with EDS type IV and interrupted inferior vena cava (IVC) with azygos continuation who developed an azygos vein aneurysm. In order to decrease flow through the azygos vein and reduce the risk of aneurysm rupture, a stent-graft shunt was created from the right hepatic vein to themore » azygos vein via a transhepatic, retroperitoneal route. At 6 month follow-up the shunt was open and the azygos vein aneurysm had resolved.« less

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

PubMed

Rowe, P C; Barron, D F; Calkins, H; Maumenee, I H; Tong, P Y; Geraghty, M T

1999-10-01

To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Ehlers-Danlos Syndrome Network C.A.R.E.S.

MedlinePlus

... abnormal proteins that confer an inherited frailty of collagen (the normal protein "glue" of our tissues). In ... an inherited abnormality in a protein other than collagen that also normally plays a role in binding ...

Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

DTIC Science & Technology

2009-06-01

fibro- blasts, we were able to identify the genes involved in 6 out of 10 types of Ehlers – Danlos syndrome , a congenital disease characterized by skin...hand–- foot–genital syndrome , a disease char- acterized by syndactyly, hypospadias, and malformations of the urogenital system. These results indicate

Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

PubMed

Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

1995-09-01

Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

[The Ehlers-Danlos syndrome: hystory of a clinical hendiadys].

PubMed

Brazzaventre, Cristina; Celletti, Claudia; Gobattoni, Paolo; Santilli, Valter; Camerota, Filippo

2013-01-01

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility and tissue fragility, which results in easy bruising and abnormal scarring. The condition shows a phenotypic variance from milder to serious presentations. Complaints related to activity (hypermobility, dislocations, impaired balance), to pain (general pain, headache, jaw and tooth pain) and to skin (bruises, fragility, impaired wound healing) are frequent. It was first noted by Hippocrates in 400 BC in his writing 'Airs Water and Places' that the nomads Scythians had lax joints and multiple scars. Whereas the additional flexibility can give benefits in term of mobility and agility, adverse effects of tissue laxity and fragility can give rise to clinical consequences. We recognize that it is important that, in those hypermobility patients, who develop potentially debilitating symptoms of chronicfatigue or widespread pain, there should be prompt an appropriate intervention.

Hemothorax in vascular Ehlers-Danlos syndrome.

PubMed

Álvarez, Kevin; Jordi, López; Jose Angel, Hernández

2017-10-16

Vascular Ehlers-Danlos syndrome (EDS IV) is a rare genetic disorder characterized by an alteration in the COL3A1 gene which encodes type III collagen. It is the most common type of collagen in vessels of medium size and certain organs such as the intestines and the uterus. The alteration of this type of collagen produces aneurisms and ruptures of vessels and organs. A high level of clinical suspicion is required for diagnosis. It is a complex disease whose management requires a multidisciplinary team to treat the different complications that may occur. We report the case of a 50-year-old man diagnosed with EDS IV detected incidentally after hemothorax secondary to a coughing spell. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Clinical presentations of Ehlers Danlos syndrome type IV.

PubMed Central

Pope, F M; Narcisi, P; Nicholls, A C; Liberman, M; Oorthuys, J W

1988-01-01

Ehlers Danlos syndrome type IV is an often lethal disease caused by various mutations of type III collagen genes. It presents in infancy and childhood in several ways, and the symptoms and signs include low birth weight, prematurity, congenital dislocation of the hips, easy inappropriate bruising (sometimes suspected as child battering), and a diagnostic facial phenotype. These features predict a lethal adult disease often complicated by fatal arterial rupture in early or middle adult life. Most affected patients can be diagnosed from radiolabelled collagen protein profiles by polyacrylamide gel electrophoresis. Prenatal diagnosis by specific type III collagen restriction fragment length polymorphisms is possible in some families, and will become increasingly important. Prenatal diagnosis and prevention of the disease in selected families is already possible and will be widely available in the future. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 PMID:3178263

Chronic pain in a patient with Ehlers-Danlos syndrome (hypermobility type): The role of myofascial trigger point injections.

PubMed

Tewari, Saipriya; Madabushi, Rajashree; Agarwal, Anil; Gautam, Sujeet K; Khuba, Sandeep

2017-01-01

Chronic widespread musculoskeletal pain is a cardinal symptom in hypermobility type of Ehler Danlos Syndrome (EDS type III). The management of pain in EDS, however, has not been studied in depth. A 30 year old female, known case of EDS, presented to the pain clinic with complaints of severe upper back pain for 6 months. Physical examination of the back revealed two myofascial trigger points over the left rhomboids and the left erector spinae. Local anaesthetic trigger point injections were given at these points, followed by stretching exercises under analgesic cover for the first week. After 1 week the patient reported 60-80% pain relief. This case highlights that we must keep a high index of suspicion for the more treatable causes of pain like myofascial pain syndrome in patients suffering from EDS, and should address it promptly and appropriately in order to maximise patient comfort. Copyright © 2016 Elsevier Ltd. All rights reserved.

Further delineation of FKBP14-related Ehlers-Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review.

PubMed

Dordoni, Chiara; Ciaccio, Claudia; Venturini, Marina; Calzavara-Pinton, Piergiacomo; Ritelli, Marco; Colombi, Marina

2016-08-01

FKBP14-related Ehlers-Danlos syndrome (EDS) is an extremely rare recessive connective tissue disorder described for the first time in 2012 by Baumann and coworkers. The causal gene, FKBP14, encodes a member of the F506-binding family of peptidyl-prolyl cis-trans isomerases. The paucity of patients described so far makes this disorder poorly defined at clinical level. Here, we report an additional pediatric patient, who is compound heterozygous for a recurrent and a novel FKBP14 mutation, and compare his phenotype with those available in literature. This evaluation confirms that kyphoscoliosis (either progressive or non-progressive), myopathy, joint hypermobility, and congenital hearing loss (sensorineural, conductive, or mixed) are the typical features of the syndrome. Since the patient showed a severe cardiovascular event in childhood and atlantoaxial instability, this report expands the phenotype of the disorder and the allelic repertoire of FKBP14. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ehlers-Danlos syndrome in a young woman with anorexia nervosa and complex somatic symptoms.

PubMed

Lee, Michelle; Strand, Mattias

2018-03-01

The Ehler-Danlos syndromes (EDS) are a group of clinically heterogeneous connective tissue disorders characterized by joint hypermobility, hyperextensibility of the skin, and a general connective tissue fragility that can induce symptoms from multiple organ systems. We present a case of comorbid anorexia nervosa and EDS in a 23-year old woman with a multitude of somatic symptoms that were initially attributed to the eating disorder but that were likely caused by the underlying EDS. Various EDS symptoms, such as gastrointestinal complaints, smell and taste abnormalities, and altered somatosensory awareness may resemble or mask an underlying eating disorder, and vice versa. Because of the large clinical heterogeneity, correctly identifying symptoms of EDS presents a challenge for clinicians, who should be aware of this group of underdiagnosed and potentially serious syndromes. The Beighton Hypermobility Score is an easily applicable screening instrument in assessing potential EDS in patients with joint hypermobility. © 2017 Wiley Periodicals, Inc.

Hypermobility, the Ehlers-Danlos syndromes and chronic pain.

PubMed

Syx, Delfien; De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska

2017-01-01

Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes. The genetic basis of hEDS remains however unknown, in contrast to other well-described EDS subtypes. In view of the considerable clinical overlap with JHS, many consider it and hEDS to be a single clinical entity. Clinical experience and a limited number of clinical studies show that chronic pain also is common in EDS patients, especially in hEDS. The specific underlying causes and mechanisms of pain in JHS and EDS remain poorly understood. Factors likely contributing to the generation and chronicity of pain include nociceptive pain, directly based on structural changes in affected joints, muscle and connective tissue; neuropathic pain; impaired proprioception and muscle weakness; and central sensitisation. These mechanisms are not mutually exclusive, and likely more than one mechanism may be present. Furthermore, anxiety, depression, and other variables may influence the phenotype. Chronic pain in JHS and EDS patients often is inadequately controlled by traditional analgesics and physical therapy. In view of the high prevalence of these underrecognised conditions, future studies addressing the nature and mediators of chronic pain are needed in order to potentially identify novel targets for therapeutic intervention and optimise treatment.

Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

PubMed

Patzkowski, Michael S

2016-03-01

Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. Published by Elsevier Inc.

Oral phenotype and scoring of vascular Ehlers–Danlos syndrome: a case–control study

PubMed Central

Frank, Michael; Gogly, Bruno; Golmard, Lisa; Naveau, Adrien; Chérifi, Hafida; Emmerich, Joseph; Gaultier, Frédérick; Berdal, Ariane; Jeunemaitre, Xavier; Fournier, Benjamin P J

2012-01-01

Objective Vascular Ehlers–Danlos syndrome (vEDS) is a rare genetic condition related to mutations in the COL3A1 gene, responsible of vascular, digestive and uterine accidents. Difficulty of clinical diagnosis has led to the design of diagnostic criteria, summarised in the Villefranche classification. The goal was to assess oral features of vEDS. Gingival recession is the only oral sign recognised as a minor diagnostic criterion. The authors aimed to check this assumption since bibliographical search related to gingival recession in vEDS proved scarce. Design Prospective case–control study. Setting Dental surgery department in a French tertiary hospital. Participants 17 consecutive patients with genetically proven vEDS, aged 19–55 years, were compared with 46 age- and sex-matched controls. Observations Complete oral examination (clinical and radiological) with standardised assessment of periodontal structure, temporomandibular joint function and dental characteristics were performed. COL3A1 mutations were identified by direct sequencing of genomic or complementary DNA. Results Prevalence of gingival recession was low among patients with vEDS, as for periodontitis. Conversely, patients showed marked gingival fragility, temporomandibular disorders, dentin formation defects, molar root fusion and increased root length. After logistic regression, three variables remained significantly associated to vEDS. These variables were integrated in a diagnostic oral score with 87.5% and 97% sensitivity and specificity, respectively. Conclusions Gingival recession is an inappropriate diagnostic criterion for vEDS. Several new specific oral signs of the disease were identified, whose combination may be of greater value in diagnosing vEDS. PMID:22492385

Hyperelastosis in the Horse

USDA-ARS?s Scientific Manuscript database

Equine hyperelastosis cutis, also known as dermatosporaxis and Ehlers-Danlos Syndrome (HERDA), is an autosomal recessive inheritable disease and has been reported in Thoroughbreds, Morgans, Haflingers , Hanoverians, a Swiss Warmblood, a mule and several Arabian cross horses in the United Kingdom, U...

Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

DTIC Science & Technology

2008-06-01

identify the genes involved in 6 out of 10 types of Ehlers – Danlos syndrome , a congenital disease characterized by skin fragility and joint laxity...Similarly, we observed that HOXA13 is induced in toe and foreskin fibroblasts, and mutation of HOXA13 in humans leads to hand–- foot–genital syndrome , a

The effects of neuromuscular taping on gait walking strategy in a patient with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.

PubMed

Camerota, Filippo; Galli, Manuela; Cimolin, Veronica; Celletti, Claudia; Ancillao, Andrea; Blow, David; Albertini, Giorgio

2015-02-01

In this case study, biomechanical alterations induced by neuromuscular taping (NMT) were quantified, during walking, in a patient with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). A female JHS/EDS-HT patient underwent NMT applications over the low back spine and bilaterally to the knee. Quantitative gait analyses were collected before the NMT application and at the end of the treatment (2 weeks after the first application of NMT). At the end of treatment following the NMT application, left step length showed improvements in cadence and velocity, the left knee showed a reduction in its flexed position at initial contact, and the right ankle joint improved its position at initial contact and in the swing phase. Improvements were also found in kinetics, in terms of the ankle moment and power. Results show that NMT seems to be a promising low-cost intervention for improving gait strategy in patients with JHS/EDS-HT. Further investigations are needed to assess the effects of this treatment intervention on pathological symptoms.

National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions

ClinicalTrials.gov

2016-12-19

Marfan Syndrome; Turner Syndrome; Ehlers-Danlos Syndrome; Loeys-Dietz Syndrome; FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation; Bicuspid Aortic Valve Without Known Family History; Bicuspid Aortic Valve With Family History; Bicuspid Aortic Valve With Coarctation; Familial Thoracic Aortic Aneurysm and Dissections; Shprintzen-Goldberg Syndrome; Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo; Other Congenital Heart Disease

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

PubMed

Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

2017-01-01

Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

PubMed Central

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.

PubMed

Jukkola, A; Kauppila, S; Risteli, L; Vuopala, K; Risteli, J; Leisti, J; Pajunen, L

1998-06-01

We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The child died because of failure of the connective tissue structures joining the skull and the spine, leading to progressive spinal stenosis. The aortic valve was translucent and insufficient. The clinical symptoms and signs, together with histological findings, suggested a collagen defect. Studies on both skin fibroblast cultures and the patient's serum showed reduced synthesis of collagen types I and III at the protein and RNA levels. The sizes of the mRNAs and newly synthesised proteins were normal, excluding gross structural abnormalities. These findings are not in accordance with any other collagen defect characterised so far.

Juvenile muscular atrophy of the distal upper extremities associated with x-linked periventricular heterotopia with features of Ehlers-Danlos syndrome.

PubMed

Hommel, Alyson L; Jewett, Tamison; Mortenson, Megan; Caress, James B

2016-10-01

Juvenile muscular atrophy of the distal upper extremities (JMADUE) is a rare, sporadic disorder that affects adolescent males and is characterized by progressive but self-limited weakness of the distal upper extremities. The etiology is unknown, but cervical hyperflexion has been hypothesized. We report a case of an adolescent male who presented with typical JMADUE but also had joint hypermobility and multiple congenital anomalies, including periventricular heterotopias, suggesting a multisystem syndrome. Subsequent diagnostic testing confirmed a diagnosis of JMADUE, and sequencing of the filamin-A gene showed a novel, pathogenic mutation that confirmed an additional diagnosis of X-linked periventricular heterotopias with features of Ehlers-Danlos syndrome (XLPH-EDS). The concurrent diagnosis of these 2 rare conditions suggests a pathogenic connection. It is likely that the joint hypermobility from XLPH-EDS predisposed this patient to developing JMADUE. This supports the cervical hyperflexion theory of pathogenesis. This case also expands the phenotype associated with FLNA mutations. Muscle Nerve 54: 794-797, 2016. © 2016 Wiley Periodicals, Inc.

Endovascular repair of an iliac arteriovenous fistula secondary to perforation from a common iliac aneurysm in a patient with Ehler-Danlos syndrome.

PubMed

Sala Almonacil, Vicente Andrés; Zaragozá García, José Miguel; Gómez Palonés, Francisco Julián; Plaza Martínez, Ángel; Ortíz Monzón, Eduardo

2012-08-01

Type IV Ehler-Danlos syndrome (EDS) patients are prone to life-threatening vascular complications. Surgical management of those complications is challenging owing to vessel wall fragility, which may result in hemorrhagic events and high mortality rates. Here we report a case of left common iliac aneurysm perforation of the ipsilateral iliac vein repaired using endovascular technique in a patient with EDS. A 54-year-old patient presented with heart failure symptoms that evolved over 1 week in association with left leg edema and steal syndrome due to a perforation of the left iliac vein caused by a left common iliac aneurysm. A thrombosed right common iliac aneurysm and several other visceral and peripheral aneurysms were discovered on computed tomographic scan at admission. An aortouniiliac stent graft was used to seal the fistula. After 18 months of follow-up, the patient remained asymptomatic. We suggest that endovascular therapy is useful to manage vascular complications in patients with EDS. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Molecular pathogenesis of Spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins

PubMed Central

Bin, Bum-Ho; Hojyo, Shintaro; Hosaka, Toshiaki; Bhin, Jinhyuk; Kano, Hiroki; Miyai, Tomohiro; Ikeda, Mariko; Kimura-Someya, Tomomi; Shirouzu, Mikako; Cho, Eun-Gyung; Fukue, Kazuhisa; Kambe, Taiho; Ohashi, Wakana; Kim, Kyu-Han; Seo, Juyeon; Choi, Dong-Hwa; Nam, Yeon-Ju; Hwang, Daehee; Fukunaka, Ayako; Fujitani, Yoshio; Yokoyama, Shigeyuki; Superti-Furga, Andrea; Ikegawa, Shiro; Lee, Tae Ryong; Fukada, Toshiyuki

2014-01-01

The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mutant ZIP13 proteins found in human patients: ZIP13G64D, in which Gly at amino acid position 64 is replaced by Asp, and ZIP13ΔFLA, which contains a deletion of Phe-Leu-Ala. We demonstrated that both the ZIP13G64D and ZIP13ΔFLA protein levels are decreased by degradation via the valosin-containing protein (VCP)-linked ubiquitin proteasome pathway. The inhibition of degradation pathways rescued the protein expression levels, resulting in improved intracellular Zn homeostasis. Our findings uncover the pathogenic mechanisms elicited by mutant ZIP13 proteins. Further elucidation of these degradation processes may lead to novel therapeutic targets for SCD-EDS. PMID:25007800

Treatment of periodontal disease in a patient with Ehlers-Danlos syndrome. A case report and literature review.

PubMed

Perez, Luis A; Al-Shammari, Khalaf F; Giannobile, William V; Wang, Hom-Lay

2002-05-01

Ehlers-Danlos syndrome (EDS) designates a heterogeneous group of connective tissue disorders characterized by skin elasticity, tissue fragility, and chronic joint pain. Dental findings have been reported with some types of EDS. This case report describes the periodontal findings in a patient with a previously undiagnosed EDS type VIII. Diagnostic aids utilized included microbial testing, histological examination, gingival crevicular fluid (GCF) analysis for the levels of C-telopeptide pyridinoline cross-links (ICTP), and genetic counseling. Periodontal treatment consisted of mechanical debridement and adjunctive antibiotic therapy. Genetic counseling and clinical presentation confirmed the diagnosis of EDS type VIII. Periodontal treatment led to marked clinical improvements and GCF levels of the bone resorptive marker ICTP were significantly reduced. The patient and her siblings are currently pursuing appropriate medical care and genetic counseling. Periodontal involvement may lead to the diagnosis of an underlying systemic condition. Identification of suspected etiological factors of periodontal disease may prove critical for the general well-being of some patients.

Thermal capsulorraphy of bilateral glenohumeral joints in a pediatric patient with Ehlers-Danlos syndrome.

PubMed

Aldridge, Julian M; Perry, John J; Osbahr, Daryl C; Speer, Kevin P

2003-01-01

Ehlers-Danlos syndrome (EDS) is a heterogeneous collection of inherited connective tissue disorders characterized by hypermobility of the joints and hyperextensibility and fragility of the skin. For many patients, the hypermobile joints become problematic. To date, the mainstay of surgical treatment for EDS-related joint laxity has been open surgical capsulorraphy, which, although usually effective, confers significant morbidity to the patient. We present the case of a 9-year-old girl diagnosed with a variant of EDS and severely disabled from multidirectional instability of her shoulders and recurrent dislocations of her hips. After 1 year of nonoperative treatment (physical therapy, bracing, and activity restriction) failed, we performed a sequential arthroscopic thermal capsulorraphy of both shoulders. At a 2-year follow-up, the patient has no instability in the left shoulder and only occasional subluxations of the contralateral shoulder. We believe that thermal capsulorraphy is a viable addition to the shoulder surgeon's armamentarium in treating multidirectional instability in children with EDS.

Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

PubMed Central

Castori, Marco

2012-01-01

Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners' awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists. PMID:23227356

COL5A1: Genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II

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

Greenspan, D.S.; Northrup, H.; Au, K.S.

1995-02-10

COL5A1, the gene for the {alpha}1 chain of type V collagen, has been considered a candidate gene for certain diseases based on chromosomal location and/or disease phenotype. We have employed 3{prime}-untranslated region RFLPs to exclude COL5A1 as a candidate gene in families with tuberous sclerosis 1, Ehlers-Danlos syndrome type H, and nail-patella syndrome. In addition, we describe a polymorphic simple sequence repeat (SSR) within a COL5A1 intron. This SSR is used to exclude COL5A1 as a candidate gene in hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and to add COL5A1 to the existing map of {open_quotes}index{close_quotes} markers of chromosome 9 by evaluationmore » of the COL5A1 locus on the CEPH 40-family reference pedigree set. This genetic mapping places COL5A1 between markers D9S66 and D9S67. 14 refs., 1 fig., 2 tabs.« less

The effects of muscle hypotonia and weakness on balance: a study on Prader-Willi and Ehlers-Danlos syndrome patients.

PubMed

Galli, Manuela; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Prader-Willi syndrome (PWS) and Ehlers-Danlos syndrome (EDS) are two different genetical disorders both characterized, among other features, by muscular hypotonia. Postural control seems to be impaired in both conditions. The aim of the present study was to quantitatively compare postural control in adult PWS and EDS using stabilometric platform to unveil possible common determinants of impaired balance. We enrolled 11 PWS and 21 EDS adult patients and 20 age-matched controls. They were instructed to maintain an upright standing position for 30s with open eyes (OEs) focusing on a 6 cm black circle positioned at a distance of 1.5m. Both PWS and EDS patients were characterized by higher RANGEML, RANGEAP and trajectory length of CoP values as compared to CG. No statistically differences were found between PWS and EDS in terms of any of these parameters. The results demonstrated that both PWS and EDS are characterized by a severe postural instability. Muscle hypotonia and weakness may account for reduced balance capacity. Quantitative characterization of instability is important to identify, develop and enhance rehabilitation interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient

PubMed Central

Refaat, Marwan; Hotait, Mostafa; Winston, Brion

2014-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting. PMID:24653990

Clinical Heterogeneity in Patients with the Hypermobility Type of Ehlers-Danlos Syndrome

ERIC Educational Resources Information Center

De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska; De Backer, Tine; De Paepe, Anne; Calders, Patrick

2013-01-01

EDS-HT is a connective tissue disorder characterized by large inter-individual differences in the clinical presentation, complicating diagnosis and treatment. We aim to describe the clinical heterogeneity and to investigate whether differences in the symptom profile are also reflected as disparity in functional impairment and pain experience. In…

Neurological manifestations of Ehlers-Danlos syndrome(s): A review

PubMed Central

Castori, Marco; C. Voermans, Nicol

2014-01-01

The term “Ehlers-Danlos syndrome” (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, dermal dysplasia with abnormal skin texture and repair, and variable range of the hollow organ and vascular dysfunctions. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been posed on neurological manifestations of EDSs, such as musculoskeletal pain, fatigue, headache, muscle weakness and paresthesias. Here, a comprehensive overview of neurological findings of these conditions is presented primarily intended for the clinical neurologist. Features are organized under various subheadings, including pain, fatigue, headache, stroke and cerebrovascular disease, brain and spine structural anomalies, epilepsy, muscular findings, neuropathy and developmental features. The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling. Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral. A set of basic tools for patient’s recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders. PMID:25632331

Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia.

PubMed

Chen, Wuyan; Perritt, Ashley F; Morissette, Rachel; Dreiling, Jennifer L; Bohn, Markus-Frederik; Mallappa, Ashwini; Xu, Zhi; Quezado, Martha; Merke, Deborah P

2016-09-01

Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein. Two types of CAH tenascin-X (CAH-X) chimeras have been described with a total deletion of CYP21A2 and characteristic TNXB variants. CAH-X CH-1 has a TNXB exon 35 120-bp deletion resulting in haploinsufficiency, and CAH-X CH-2 has a TNXB exon 40 c.12174C>G (p.Cys4058Trp) variant resulting in a dominant-negative effect. We present here three patients with biallelic CAH-X and identify a novel dominant-negative chimera termed CAH-X CH-3. Compared with monoallelic CAH-X, biallelic CAH-X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin-X function and computational data linking the type of TNXB variant to disease severity. © 2016 WILEY PERIODICALS, INC.

Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

PubMed Central

Mitra, Arijit; Ramakrishnan, R.; Kader, Mohideen Abdul

2014-01-01

A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

Successful vaginal birth after caesarean section in patient with Ehler-Danlos syndrome type 2.

PubMed

Maraj, Hemant; Mohajer, Michelle; Bhattacharjee, Deepannita

2011-12-01

We present the case of a 31-year-old woman with Ehler-Danlos syndrome (EDS) type 2. She had a previous caesarean section and went on to have an uncomplicated vaginal birth in her last pregnancy. To our knowledge, this is the first case of a successful vaginal birth after caesarean section in a patient with EDS. EDS is a multisystem disorder involving a genetic defect in collagen and connective-tissue synthesis and structure. It is a heterogeneous group of 11 different inherited disorders. Obstetric complications in these patients include miscarriages, stillbirths, premature rupture of the membranes, preterm labour, uterine prolapse, uterine rupture and severe postpartum haemorrhage. There has been much controversy over the appropriate mode of delivery. Abdominal deliveries are complicated by delayed wound healing and increased perioperative blood loss. Vaginal deliveries may be complicated by tissue friability causing extensive perineal tears, pelvic floor and bladder lesions. Our case highlights that in specific, controlled situations it is possible to have a vaginal delivery even after previous caesarean section in patients with EDS.

Successful vaginal birth after caesarean section in patient with Ehler-Danlos syndrome type 2

PubMed Central

Maraj, Hemant; Mohajer, Michelle; Bhattacharjee, Deepannita

2011-01-01

We present the case of a 31-year-old woman with Ehler-Danlos syndrome (EDS) type 2. She had a previous caesarean section and went on to have an uncomplicated vaginal birth in her last pregnancy. To our knowledge, this is the first case of a successful vaginal birth after caesarean section in a patient with EDS. EDS is a multisystem disorder involving a genetic defect in collagen and connective-tissue synthesis and structure. It is a heterogeneous group of 11 different inherited disorders. Obstetric complications in these patients include miscarriages, stillbirths, premature rupture of the membranes, preterm labour, uterine prolapse, uterine rupture and severe postpartum haemorrhage. There has been much controversy over the appropriate mode of delivery. Abdominal deliveries are complicated by delayed wound healing and increased perioperative blood loss. Vaginal deliveries may be complicated by tissue friability causing extensive perineal tears, pelvic floor and bladder lesions. Our case highlights that in specific, controlled situations it is possible to have a vaginal delivery even after previous caesarean section in patients with EDS. PMID:27579117

Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

PubMed

Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul

2014-08-01

A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

Ehlers-Danlos syndrome and wound healing: injury in a collagen disorder.

PubMed

Trudgian, Julie; Trotman, Sara

Ehlers-Danlos syndrome (EDS) is a rare familial disorder affecting the production, quality and strength of collagen. It presents in many forms, and many individuals experience hypermobile joints and soft, elastic skin. When injury occurs, EDS can result in severe bruising, the development of wide open wounds and delayed healing (Babak et al, 2003). In the case discussed, Lilly, a 10-year-old girl, presented with a wide trauma injury to her lower leg. Healing was influenced by the poor collagen production associated with EDS, and the presence of a high bacterial burden that resulted in infection. Manuka honey was used to reduce the level of invading bacilli and stimulate production of collagen. Following this intervention, complete healing was achieved in two weeks. The action of manuka honey appears to be beneficial in the management of complex wounds, and further research is needed to determine its value in EDS. Involvement of Lilly and her family in clinical decision-making and in the production of this article resulted in a growth in understanding for all parties and the development of a relationship that optimized the nurse/patient experience.

Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome.

PubMed

Teraishi, Mika; Takaishi, Mikiro; Nakajima, Kimiko; Ikeda, Mitsunori; Higashi, Yujiro; Shimoda, Shinji; Asada, Yoshinobu; Hijikata, Atsushi; Ohara, Osamu; Hiraki, Yoko; Mizuno, Seiji; Fukada, Toshiyuki; Furukawa, Takahisa; Wakamatsu, Nobuaki; Sano, Shigetoshi

2017-04-19

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

Effect of Interleukin-1beta and Tumor Necrosis Factor-alpha on Gene Expression in Human Endothelial Cells

DTIC Science & Technology

2003-06-01

type Ill, alpha 1 ( Ehlers - Danlos syndrome type IV, autosomal dominant) T98612 multimerin AA423867 ribonuclease, RNase A family, 1 (pancreatic...tax-responsive enhancer element 967) AA600217 jagged1 (Alagille syndrome ) R70685 TNF receptor-associated factor 1 R71691 glycyl-tRNA synthetase...in patients succumbing to sepsis and systemic inflamma- tion. The effects of removing one syndrome -causing agent may be compensated by others with

Repair of an aneurysm of the ascending aorta and arch in an infant with Loeys-Dietz syndrome.

PubMed

Jaiswal, Pratiksha; Shetty, Varun; Patel, Ebrahim; Shetty, Deviprasad

2018-05-01

Aortic aneurysms in childhood are rare disease entities and are usually seen in patients with genetic connective tissue disorders such as Marfans, Ehler-Danlos, and Loeys-Dietz syndrome (LDS). Patients affected with LDS present early in life and have a rapid disease progression. We report a case of repair of an ascending and aortic arch aneurysm in an infant with Loeys-Dietz syndrome. © 2018 Wiley Periodicals, Inc.

Cognitive, emotional, and behavioral considerations for chronic pain management in the Ehlers-Danlos syndrome hypermobility-type: a narrative review.

PubMed

Baeza-Velasco, Carolina; Bulbena, Antonio; Polanco-Carrasco, Roberto; Jaussaud, Roland

2018-01-22

Ehlers-Danlos syndrome (EDS) hypermobility-type is the most common hereditary disorder of the connective tissue. The tissue fragility characteristic of this condition leads to multi-systemic symptoms in which pain, often severe, chronic, and disabling, is the most experienced. Clinical observations suggest that the complex patient with EDS hypermobility-type is refractory toward several biomedical and physical approaches. In this context and in accordance with the contemporary conceptualization of pain (biopsychosocial perspective), the identification of psychological aspects involved in the pain experience can be useful to improve interventions for this under-recognized pathology. Review of the literature on joint hypermobility and EDS hypermobility-type concerning psychological factors linked to pain chronicity and disability. A comprehensive search was performed using scientific online databases and references lists, encompassing publications reporting quantitative and qualitative research as well as unpublished literature. Despite scarce research, psychological factors associated with EDS hypermobility-type that potentially affect pain chronicity and disability were identified. These are cognitive problems and attention to body sensations, negative emotions, and unhealthy patterns of activity (hypo/hyperactivity). As in other chronic pain conditions, these aspects should be more explored in EDS hypermobility-type, and integrated into chronic pain prevention and management programs. Implications for Rehabilitation Clinicians should be aware that joint hypermobility may be associated with other health problems, and in its presence suspect a heritable disorder of connective tissue such as the Ehlers-Danlos syndrome (EDS) hypermobility-type, in which chronic pain is one of the most frequent and invalidating symptoms. It is necessary to explore the psychosocial functioning of patients as part of the overall chronic pain management in the EDS hypermobility-type, especially when they do not respond to biomedical approaches as psychological factors may be operating against rehabilitation. Further research on the psychological factors linked to pain chronicity and disability in the EDS hypermobility-type is needed.

[Vascular Ehlers-Danlos syndrome].

PubMed

Perdu, Jérôme; Boutouyrie, Pierre; Lahlou-Laforêt, Khadija; Khau Van Kien, Philippe; Denarié, Nicolas; Mousseaux, Elie; Sapoval, Marc; Julia, Pierre; Zinzindohoué, Frank; Touraine, Philippe; Dumez, Yves; Trystram, Denis; Vignal-Clermont, Catherine; Gimenez-Roqueplo, Anne-Paule; Jeunemaitre, Xavier; Fiessinger, Jean-Noël

2006-12-01

The vascular type of Ehlers-Danlos syndrome (EDS) is a rare genetic disease transmitted as an autosomal dominant trait. It is distinguished from other forms of EDS by its unstable acrogeric morphotype and by vascular, gastrointestinal, and obstetrical complications. Diagnosis is based on various clinical signs, noninvasive imaging, and on the identification of a mutation of the COL3A1 gene, which provides diagnostic certainty but has a sensitivity of only 61%. When two major diagnostic criteria are present, a genetic test should be proposed, performed and its result presented in a multidisciplinary group. The precautionary principle requires that preventive measures be implemented when the diagnosis is suspected. All artery puncture, surgery, and gastrointestinal and uterine endoscopy are contraindicated, permissible only in life-threatening emergencies. Straining against a closed glottis and all other situations or drugs likely to raise blood pressure must be avoided. Contraception must be discussed to avoid pregnancy during the diagnostic period. Arterial lesions suggestive of the disease include dissecting aneurysms of the internal carotid and iliac arteries and of the anterior visceral branches of the abdominal aorta, fusiform aneurysms of the splenic artery, and early onset nontraumatic direct carotid-cavernous fistulae. Early-onset varicose veins, spontaneous peritonitis or unusually important perineal lesions after giving birth should also attract the physician's attention. Psychological treatment and support of patients and their families is essential, to help them both to live with their disease and to deal with the information and screening issues. The prognosis of Ehlers-Danlos syndrome, vascular type, is grim but there is wide interindividual variability and life expectancy is best among patients receiving regular follow-up. Management by an experienced multidisciplinary team, implementation of drastic prevention measures and, depending on the results of the BBEST study, the possible prescription of beta-blockers should help to reduce the risk of complications and justify hope for a real improvement in prognosis in the near future.

My Dog's Cheeks: A PBL Project on Collagen for Cell Biology and Genetics Courses

ERIC Educational Resources Information Center

Casla, Alberto Vicario; Zubiaga, Isabel Smith

2010-01-01

Students often have an oversimplified view of biological facts, which may hinder subsequent understanding when conceptual complexity gives rise to cognitive conflicts. To avoid this situation here, we present a PBL approach for the analysis of Ehlers-Danlos syndrome (EDS), which integrates a variety of topics in cell biology, genetics, and…

Alterations in collagen structure in hypermobility and Ehlers-Danlos syndromes detected by Raman spectroscopy in vivo

NASA Astrophysics Data System (ADS)

Johansson, Carina K.; Gniadecka, Monika; Ullman, Susanne; Halberg, Poul; Kobayasi, Takasi; Wulf, Hans Christian

2000-11-01

Patients with hypermobility syndrome (HS) and Ehlers-Danlos syndrome (EDS) were investigated by means of in vivo near- infrared Fourier-transform Raman spectroscopy. HS is a benign and common condition (up to 5 percent of the population of the Western World). EDS is a rare, inherited connective tissue disease characterized by joint hypermobility, skin hyperextensibility, and other, occasionally serious, organ changes. EDS and HS may be related disorders. We investigated 13 patients with HS, 8 patients with EDS, and 24 healthy volunteers by means of in vivo Raman spectroscopy. The patients were classified according to Beighton and Holzberg et al. No difference in age between the three groups was found (HS 41 (33-49), EDS 36 (25-47), controls 37 (31-42); mean, 95% confidence intervals, respectively). Spectral differences were found in the intensity of the amide-III bands around 1245 and 1270 cm-1 in HS and EDS compared with healthy skin (Kruskal-Wallis, p equals 0,02 for intensity ratios (I1245/I1270) between the investigated groups). To elucidate the character of the alterations in the amide-III bands a curve fitting procedure was applied. In conclusion, Raman spectroscopy may aid in the diagnosis of HS and EDS. Moreover the technique may be useful for analyzing the molecular changes occurring in these syndromes.

[Ehler-Danlos syndrome type VIII].

PubMed

Ciarloni, L; Perrigouard, C; Lipsker, D; Cribier, B

2010-03-01

Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of diseases involving genetic collagen fibre impairment. We describe a case of a patient presenting the rare type VIII, in which dermatitis ocre was associated with parodontal disease, and which was diagnosed late. A 29-year-old man consulted for a pretibial ulcer present for seven years, resulting from a post-traumatic haematoma that had failed to heal. In view of the longiliner morphology, it had previously been diagnosed as Marfan syndrome. Subsequently, edentation was observed as well as "alveolar bone fragility". Examination revealed a marfanoid morphotype, a pretibial ulcer set within long-standing bilateral dermatitis ocre and papyraceous scars, but no joint hyperlaxity or cutaneous hyperelasticity. The diagnosis was consequently corrected to EDS type VIII. Type VIII is a rare form of EDS, and the molecular mechanism is poorly understood. The involvement of parodontal connective tissue suggests impairment of collagen I and III proteins. It is important to identify this type of the disease since it involves parodontal disease for which early treatment is required in order to try to prevent edentation. The present case demonstrates the importance of diagnosis, which may be based upon appearance of bilateral dermatitis ocre from the age of 15 years associated with skin fragility. This sign is not part of the classical picture of Marfan syndrome, with which EDS type VIII is often confounded. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

PubMed

Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

1992-08-01

Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules.

[Ehlers-Danlos syndromes: we are all concerned].

PubMed

de Wazières, B; Plauchu, H; Boucand, M H

1998-10-17

EHLERS-DANLOS SYNDROMES (EDS): A heterogeneous group of hereditary conditions having in common a molecular anomaly of the extracellular matrix comprise EDS. Clinical and genetic features are used for classification and in some cases the molecular anomaly can be demonstrated. Six main types are recognized and termed classic, hypermobile, vascular, cyphoscoliotic, arthrochalasic and dermatosparaxis. Skin and joint signs predominate, visceral disease is fortunately rare. The skin is hyperelastic and heals poorly. Joint involvement may lead to luxations and early-onset osteoarthritis causing chronic pain. The prognosis is severe in certain types such as vascular EDS where arterial ruptures may be life-threatening. Patients with cyphoscoliotic EDS may become bedridden due to the scoliosis and muscular hypotrophy. Minor forms as well as rapidly fatal major forms often go undiagnosed or are identified late after a complication which could have been avoided. A multidisciplinary approach is needed as certain interventions, technical procedures or explorations may have catastrophic consequences. The creation of an EDS association would be helpful in federating specialists and allow global management. The gravity of certain forms, the poorly understood epidemiology and the progressive nature of EDS point to the need for a national registry.

A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing.

PubMed

Colombi, Marina; Dordoni, Chiara; Cinquina, Valeria; Venturini, Marina; Ritelli, Marco

2018-01-01

The 2017 EDS revised nosology indicates that minimal criteria suggestive for classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic scarring together with either generalized joint hypermobility (gJHM) and/or at least three minor criteria that include cutaneous features and gJHM complications. Confirmatory molecular testing is obligatory to reach a final diagnosis. Although the large majority of the patients presents with these clinical features, some do not and might remain undiagnosed or misdiagnosed. Here we describe a family with 2 affected members, a 23-year-old proposita and her 51-year-old mother, who presented subtle cutaneous signs, including a variable degree of skin hyperextensibility without extensive widened atrophic scars that apparently better fitted with the overlapping hypermobile EDS. The proposita also presented gastrointestinal symptoms secondary to aberrant mast cells mediators release, making the clinical picture even more puzzling. Both patients were diagnosed by molecular testing that revealed a COL5A1 splice mutation. This report highlights the relevance of molecular analysis in patients presenting rather mild signs of EDS, especially in familial cases, and the importance of clinical expertise to make such a diagnosis. Copyright © 2017. Published by Elsevier Masson SAS.

Successful surgical treatment of intramural aortoatrial fistula, severe aortic regurgitation, mitral prolapse, and tricuspid insufficiency in a patient with Ehlers-Danlos syndrome type IV.

PubMed

Jiang, Shengli; Gao, Changqing; Ren, Chonglei; Zhang, Tao

2012-06-01

Patients with Ehlers-Danlos syndrome (EDS) type IV, an inherited connective tissue disorder, are predisposed to vascular and digestive ruptures, and arterial ruptures account for the majority of deaths. A 31-year-old man with EDS presented with an intramural aortoatrial fistula, severe aortic regurgitation, mitral valve prolapse, and severe tricuspid valve insufficiency combined with a severely dilated left ventricle. Determining the best surgical option for the patient was not easy, especially regarding the course of action for the aortic root with a tear in the sinus of Valsalva. The fistula tract was closed at the aorta with suture and with a patch in the right atrium, the mitral valve was repaired with edge-to-edge suture and then annuloplasty with a Cosgrove ring, the aortic valve was replaced with a mechanical prosthesis, and a modified De Vega technique was used for the tricuspid valvuloplasty. The postoperative course was uncomplicated, and the patient was discharged 2 weeks later. The considerations made to arrive at the chosen surgical course of action in this complex case are reviewed.

Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

PubMed

Busch, Albert; Hoffjan, Sabine; Bergmann, Frauke; Hartung, Birgit; Jung, Helena; Hanel, Daniela; Tzschach, Andeas; Kadar, Janos; von Kodolitsch, Yskert; Germer, Christoph-Thomas; Trobisch, Heiner; Strasser, Erwin; Wildenauer, René

2016-08-03

The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

Aspects on dental hard tissues in primary teeth from patients with Ehlers-Danlos syndrome.

PubMed

Klingberg, Gunilla; Hagberg, Catharina; Norén, Jörgen G; Nietzsche, Sandor

2009-07-01

Ehlers-Danlos syndrome (EDS) is a rare hereditary condition affecting connective tissues and dental hard tissues. Primary enamel and dentine from EDS patients were expected to differ from those of healthy subjects regarding morphology and chemical composition. Forty-seven exfoliated primary teeth from 25 patients with EDS were investigated. Morphology was studied using a polarized light microscope, scanning electron microscope, and X-ray microanalysis. Comparisons were made with 36 primary teeth from 36 healthy patients. Morphological analysis of enamel in EDS teeth showed a high frequency of postnatally hypomineralized enamel and postnatally located incremental lines, whereas dentine was normal in all patients. Chemical analysis could not reveal any differences between EDS and control patients except for lower content of C and a higher Ca/P ratio in the enamel in the EDS teeth, indicating porous enamel. Regarding dentine, EDS teeth had a lower content of C, and a higher content of Ca, P, and O. Ratios for Ca/C and Ca/O were also higher compared with controls. There are several aberrations of booth enamel and dentine in primary teeth from patients with EDS. These could explain the occurrence of both more dental caries and tooth fractures in patients with EDS.

Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

PubMed

Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

2015-03-01

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. © 2015 Wiley Periodicals, Inc.

Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised.

PubMed

Sinibaldi, Lorenzo; Ursini, Gianluca; Castori, Marco

2015-03-01

Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers-Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome - JHS/EDS-HT), and significantly contributes to the quality of life of affected individuals. Most published articles dealt with the link between gJHM (or JHS/EDS-HT) and anxiety-related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi-systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS-HT. Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with depression, attention deficit (and hyperactivity) disorder, autism spectrum disorders, and obsessive-compulsive personality disorder were also found. Few papers investigated the relationship with schizophrenia with contrasting results. The mind-body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system. The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS-HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS-HT in clinical practice. © 2015 Wiley Periodicals, Inc.

Quality of life, unmet needs, and iatrogenic injuries in rehabilitation of patients with Ehlers-Danlos Syndrome hypermobility type/Joint Hypermobility Syndrome.

PubMed

Bovet, Claire; Carlson, Matthew; Taylor, Matthew

2016-08-01

Ehlers-Danlos Syndrome, hypermobility type (EDS-HT) and the joint hypermobility syndrome (JHS) are connective tissue disorders that form an overlapping clinical syndrome and are associated with frequent medical visits and substantial morbidity. EDS-HT/JHS-associated pain correlates with poor quality of life. While physical therapy is the recommended treatment for EDS-HT/JHS, little is known about therapy-related patient experiences and iatrogenic injuries. We studied 38 adult EDS-HT/JHS patients, eliciting health-related quality of life (HRQoL) from 28 patients through the RAND SF-36 questionnaire. We also explored physical therapy experiences through focus groups with 13 patients. Our patients displayed poor HRQoL, with 71% reporting worse health over the past year. SF-36 scores were significantly lower than the scores of the average American population (P < 0.001 for 8 of 10 categories assessed), but were comparable to EDS-HT/JHS populations in Belgium, the Netherlands, Sweden, and Italy. Focus groups identified factors associated with: negative past physical therapy experiences, iatrogenic joint injuries, positive treatment experiences, and unmet rehabilitation needs. This group of EDS-HT/JHS patients has significant decrements in HRQoL and many unmet treatment needs, as well as a risk for iatrogenic injuries. We identify several approaches to help meet patients' needs and improve joint rehabilitation in patients with EDS-HT/JHS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Screening for Ataxia-Telangiectasia Mutations in a Population-Based Sample of Women with Early-Onset Breast Cancer

DTIC Science & Technology

1999-09-01

nuclear phosphoprotein. J Biol Chem 271: skipping of fibrillin-1 gene in Marfan syndrome . Nat Genet 33693-33697 16:328-329 Concannon P, Gatti RA (1997...1989) ATFresno: a phenotype linking ataxia-tel- ilnikova OM, Lenoir GM (1998) A BRCA1 nonsense mu- angiectasia with the Nijmegen breakage syndrome ...effectors. Am J Hum Genet 62:269-277 tions and Ehlers-Danlos syndrome type IV. Am J Hum Genet Hull J, Shackleton S, Harris A (1994) The stop mutation 61:1276

Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child.

PubMed

Gera, D N; Ghuge, P P; Gandhi, S; Vanikar, A V; Shrimali, J D; Kute, V B; Trivedi, H L

2013-11-01

Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors.

Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child

PubMed Central

Gera, D. N.; Ghuge, P. P.; Gandhi, S.; Vanikar, A. V.; Shrimali, J. D.; Kute, V. B.; Trivedi, H. L.

2013-01-01

Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors. PMID:24339527

Vascular Ehlers–Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci

PubMed Central

Park, Min A.; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-01-01

Abstract Rationale: Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. Patient concerns: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Diagnoses: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. Interventions: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Outcomes: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. Lessons: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients. PMID:29381997

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; De Wandele, Inge; O'Callaghan, Chris; Pocinki, Alan; Rowe, Peter

2017-03-01

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

PubMed Central

Cazzato, Daniele; Castori, Marco; Lombardi, Raffaella; Caravello, Francesca; Bella, Eleonora Dalla; Petrucci, Antonio; Grammatico, Paola; Dordoni, Chiara; Colombi, Marina

2016-01-01

Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. PMID:27306637

Ehlers-Danlos syndrome: a cause of epilepsy and periventricular heterotopia.

PubMed

Verrotti, Alberto; Monacelli, Debora; Castagnino, Miriam; Villa, Maria Pia; Parisi, Pasquale

2014-11-01

Ehlers-Danlos syndrome (EDS) comprises a variety of inherited connective tissue disorders that have been described in association with various neurological features. Until now the neurological symptoms have not been studied in detail; therefore, the aim of this review is to analyze the possible association between EDS, epilepsy and periventricular heterotopia (PH). We have carried out a critical review of all cases of epilepsy in EDS patients with and without PH. Epilepsy is a frequent neurological manifestation of EDS; generally, it is characterized by focal seizures with temporo-parieto-occipital auras and the most common EEG findings epileptiform discharges and slow intermittent rhythm with delta-theta waves. Epilepsy in EDS patients is usually responsive to common antiepileptic therapy; very few cases of drug resistant focal epilepsy requested surgical treatment, with favorable results in terms of outcome. Epilepsy is the most common presenting neurological manifestation associated with PH in EDS patients. Abnormal anatomic circuitries (including heterotopic nodules) could generate epilepsy in patients with PH. Among the principal neurological manifestations, epilepsy and PH have a considerable importance and can influence the long-term evolution of these patients. We hypothesize that PH may determine the epileptic manifestations in patients with EDS; much remains to be learnt about the relationships between nodules and the epileptic manifestations in EDS syndrome. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings.

PubMed

Cederlöf, Martin; Larsson, Henrik; Lichtenstein, Paul; Almqvist, Catarina; Serlachius, Eva; Ludvigsson, Jonas F

2016-07-04

To assess the risk of psychiatric disorders in Ehlers-Danlos syndrome (EDS) and hypermobility syndrome. Nationwide population-based matched cohort study. EDS, hypermobility syndrome and psychiatric disorders were identified through Swedish national registries. Individuals with EDS (n = 1,771) were matched with comparison individuals (n = 17,710). Further, siblings to individuals with EDS who did not have an EDS diagnosis themselves were compared with matched comparison siblings. Using conditional logistic regression, risk of autism spectrum disorder (ASD), bipolar disorder, attention deficit hyperactivity disorder (ADHD), depression, attempted suicide, suicide and schizophrenia were estimated. The same analyses were conducted in individuals with hypermobility syndrome (n = 10,019) and their siblings. EDS was associated with ASD: risk ratio (RR) 7.4, 95 % confidence interval (95 % CI) 5.2-10.7; bipolar disorder: RR 2.7, CI 1.5-4.7; ADHD: RR 5.6, CI 4.2-7.4; depression: RR 3.4, 95 % CI 2.9-4.1; and attempted suicide: RR 2.1, 95 % CI 1.7-2.7, but not with suicide or schizophrenia. EDS siblings were at increased risk of ADHD: RR 2.1, 95 % CI 1.4-3.3; depression: RR 1.5, 95 % CI 1.1-1.8; and suicide attempt: RR 1.8, 95 % CI 1.4-2.3. Similar results were observed for individuals with hypermobility syndrome and their siblings. Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders.

Ehlers-Danlos Syndrome Type VI in a 17-Year-Old Iranian Boy with Severe Muscular Weakness – A Diagnostic Challenge?

PubMed Central

Kariminejad, Ariana; Bozorgmehr, Bita; Khatami, Alireza; Kariminejad, Mohamad-Hasan; Giunta, Cecilia; Steinmann, Beat

2010-01-01

Background The Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessive connective tissue disease which is characterized by severe hypotonia at birth, progressive kyphoscoliosis, skin hyperelasticity and fragility, joint hypermobility and (sub-)luxations, microcornea, rupture of arteries and the eye globe, and osteopenia. The enzyme collagen lysyl hydroxylase (LH1) is deficient in these patients due to mutations in the PLOD1 gene. Case Presentation We report a 17-year-old boy, born to related parents, with severe kyphoscoliosis, scar formation, joint hypermobility and multiple dislocations, muscular weakness, rupture of an ocular globe, and a history of severe infantile hypotonia. EDS VI was suspected clinically and confirmed by an elevated ratio of urinary total lysyl pyridinoline to hydroxylysyl pyridinoline, abnormal electrophoretic mobility of the α-collagen chains, and mutation analysis. Conclusion Because of the high rate of consanguineous marriages in Iran and, as a consequence thereof, an increased rate of autosomal recessive disorders, we urge physicians to consider EDS VI in the differential diagnosis of severe infantile hypotonia and muscular weakness, a disorder which can easily be confirmed by the analysis of urinary pyridinolines that is highly specific, sensitive, robust, fast, non-invasive, and inexpensive. PMID:23056730

Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

PubMed Central

Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

1992-01-01

Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules. Images Figure 5 Figure 2 Figure 3 Figure 1 Figure 4 Figure 6 PMID:1642226

Dispersal of radioisotope labelled solution following deep dermal injection in Ehlers-Danlos syndrome.

PubMed

Oliver, D W; Balan, K K; Burrows, N P; Hall, P N

2000-06-01

Ehlers-Danlos syndrome (EDS) is the commonest inherited disorder of connective tissue, affecting around 10 000 patients in the UK. Patients with EDS have reported that local anaesthetic is often ineffective. Patients with less severe skin laxity often have the most problems. We have postulated that this resistance to local anaesthetics is not due to the lax connective tissues as is often assumed. This study used radioactively labelled solution ((99m)Tc-pertechnetate) administered as a deep dermal injection in the forearm. The rate of dispersal of isotope was measured over 60 min and found to be identical between six patients with EDS and three controls. The effects of local anaesthetics are complex and depend on the individual chemical properties of the agent and a number of tissue factors. This study would suggest that the lack of effectiveness of local anaesthetic solutions is not due to rapid dispersal of solution. It is unlikely therefore that its lack of effect can be compensated for by simply increasing the amount used. The diagnosis of EDS should be considered in any patient who complains unexpectedly of pain during their procedure, particularly when the surgeon knows that an adequate volume of local anaesthetic has been used. Copyright 2000 The British Association of Plastic Surgeons.

Ex vivo nonlinear microscopy imaging of Ehlers-Danlos syndrome-affected skin.

PubMed

Kiss, Norbert; Haluszka, Dóra; Lőrincz, Kende; Kuroli, Enikő; Hársing, Judit; Mayer, Balázs; Kárpáti, Sarolta; Fekete, György; Szipőcs, Róbert; Wikonkál, Norbert; Medvecz, Márta

2018-07-01

Ehlers-Danlos syndrome (EDS) is the name for a heterogenous group of rare genetic connective tissue disorders with an overall incidence of 1 in 5000. The histological characteristics of EDS have been previously described in detail in the late 1970s and early 1980s. Since that time, the classification of EDS has undergone significant changes, yet the description of the histological features of collagen morphology in different EDS subtypes has endured the test of time. Nonlinear microscopy techniques can be utilized for non-invasive in vivo label-free imaging of the skin. Among these techniques, two-photon absorption fluorescence (TPF) microscopy can visualize endogenous fluorophores, such as elastin, while the morphology of collagen fibers can be assessed by second-harmonic generation (SHG) microscopy. In our present work, we performed TPF and SHG microscopy imaging on ex vivo skin samples of one patient with classical EDS and two patients with vascular EDS and two healthy controls. We detected irregular, loosely dispersed collagen fibers in a non-parallel arrangement in the dermis of the EDS patients, while as expected, there was no noticeable impairment in the elastin content. Based on further studies on a larger number of patients, in vivo nonlinear microscopic imaging could be utilized for the assessment of the skin status of EDS patients in the future.

Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review

PubMed Central

D'hondt, Sanne; Van Damme, Tim; Malfait, Fransiska

2018-01-01

Purpose Within the spectrum of the Ehlers-Danlos syndromes (EDS), vascular complications are usually associated with the vascular subtype of EDS. Vascular complications are also observed in other EDS subtypes, but the reports are anecdotal and the information is dispersed. To better document the nature of vascular complications among “nonvascular” EDS subtypes, we performed a systematic review. Methods We queried three databases for English-language studies from inception until May 2017, documenting both phenotypes and genotypes of patients with nonvascular EDS subtypes. The outcome included the number and nature of vascular complications. Results A total of 112 papers were included and data were collected from 467 patients, of whom 77 presented with a vascular phenotype. Severe complications included mainly hematomas (53%), frequently reported in musculocontractural and classical-like EDS; intracranial hemorrhages (18%), with a high risk in dermatosparaxis EDS; and arterial dissections (16%), frequently reported in kyphoscoliotic and classical EDS. Other, more minor, vascular complications were reported in cardiac-valvular, arthrochalasia, spondylodysplastic, and periodontal EDS. Conclusion Potentially life-threatening vascular complications are a rare but important finding in several nonvascular EDS subtypes, highlighting a need for more systematic documentation. This review will help familiarize clinicians with the spectrum of vascular complications in EDS and guide follow-up and management. PMID:28981071

The differential diagnosis of children with joint hypermobility: a review of the literature

PubMed Central

Tofts, Louise J; Elliott, Elizabeth J; Munns, Craig; Pacey, Verity; Sillence, David O

2009-01-01

Background In this study we aimed to identify and review publications relating to the diagnosis of joint hypermobility and instability and develop an evidence based approach to the diagnosis of children presenting with joint hypermobility and related symptoms. Methods We searched Medline for papers with an emphasis on the diagnosis of joint hypermobility, including Heritable Disorders of Connective Tissue (HDCT). Results 3330 papers were identified: 1534 pertained to instability of a particular joint; 1666 related to the diagnosis of Ehlers Danlos syndromes and 330 related to joint hypermobility. There are inconsistencies in the literature on joint hypermobility and how it relates to and overlaps with milder forms of HDCT. There is no reliable method of differentiating between Joint Hypermobility Syndrome, familial articular hypermobility and Ehlers-Danlos syndrome (hypermobile type), suggesting these three disorders may be different manifestations of the same spectrum of disorders. We describe our approach to children presenting with joint hypermobility and the published evidence and expert opinion on which this is based. Conclusion There is value in identifying both the underlying genetic cause of joint hypermobility in an individual child and those hypermobile children who have symptoms such as pain and fatigue and might benefit from multidisciplinary rehabilitation management. Every effort should be made to diagnose the underlying disorder responsible for joint hypermobility which may only become apparent over time. We recommend that the term "Joint Hypermobility Syndrome" is used for children with symptomatic joint hypermobility resulting from any underlying HDCT and that these children are best described using both the term Joint Hypermobility Syndrome and their HDCT diagnosis. PMID:19123951

COL5A1: Fine genetic mapping, intron/exon organization, and exclusion as candidate gene in families with tuberous sclerosis complex 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II

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

Greenspan, D.S.; Papenberg, K.A.; Marchuk, D.A.

1994-09-01

Type V collagen is the only fibrillar collagen which has yet to be implicated in the pathogenesis of genetic diseases in humans or mice. To begin examining the possible role of type V collagen in genetic disease, we have previously mapped COL5A1, the gene for the {alpha}1 chain of type V collagen, to 9q23.2{r_arrow}q34.3 and described two restriction site polymorphisms which allowed us to exclude COL5A1 as candidate gene for nail-patella syndrome. We have now used these polymorphisms to exclude COL5A1 as candidate gene for tuberous sclerosis complex 1 and Ehlers-Danlos syndrome type II. In addition, we describe a CAmore » repeat, with observed heterozygosity of about 0.5, in a COL5A1 intron, which has allowed us to exclude COL5A1 as a candidate gene in hereditary hemorrhagic telangiectasia and to place COL5A1 on the CEPH family genetic map between markers D9S66 and D9S67. We have also determined the entire intron/exon organization of COL5A1, which will facilitate characterization of mutations in genetic diseases with which COL5A1 may be linked in future studies.« less

Arterial complications of vascular Ehlers-Danlos syndrome.

PubMed

Eagleton, Matthew J

2016-12-01

Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates. A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1. The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention. With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The role of narrative medicine in the management of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Knight, Isobel

2015-03-01

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a hereditary connective tissue disorder affecting every bodily system. It is largely underdiagnosed by many practitioners, with the result of a considerable delay in diagnosis and, consequently, in the onset of adequate management schedule and treatment. Patients may also experience to be misbelieved, erroneously considered affected by a psychiatric or psychosomatic disorders, and rejected by the medical profession, which can lead to feelings of anger and resentment. Patient journeys are often long and complicated, but if doctors allowed the patient time to tell the full story, and were more prepared to think holistically, there may be a far more positive outcome. Here, the patients' perspective is presented with a narrative medicine approach, illustrating the tri-dimensional experience of a JHS/EDS-HT patient, who is also a Bowen Practitioner and a medical writer/educator. Narrative medicine would be invaluable in working with JHS/EDS-HT so that the patient can tell the story, and offer the practitioner a whole picture of her/his suffering and, often, the key for understanding the cause(s). Once this has been achieved, it might be possible to build upon a more positive and therapeutic dialogue which would result in better treatment and more effective management. It is also important for doctors to communicate with JHS/EDS-HT experts who will ultimately improve the patient journey and treatment outcomes of such a complex connective tissue disorder. © 2015 Wiley Periodicals, Inc.

Nationwide population-based cohort study of celiac disease and risk of Ehlers-Danlos syndrome and joint hypermobility syndrome.

PubMed

Laszkowska, Monika; Roy, Abhik; Lebwohl, Benjamin; Green, Peter H R; Sundelin, Heléne E K; Ludvigsson, Jonas F

2016-09-01

Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). This study examines the risks of EDS/JHS in patients with CD. This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969-2008 (n=28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n=16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95%CI=1.07-2.07). The HR for EDS was 2.43 (95%CI=1.20-4.91) and for JHS 1.34 (95%CI=0.93-1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio=2.29; 95%CI=1.21-4.34). Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

PubMed

Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

2015-03-01

In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. © 2015 Wiley Periodicals, Inc.

Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Castori, Marco; Dordoni, Chiara; Morlino, Silvia; Sperduti, Isabella; Ritelli, Marco; Valiante, Michele; Chiarelli, Nicola; Zanca, Arianna; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina

2015-03-01

Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT. © 2015 Wiley Periodicals, Inc.

Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

2016-09-01

Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

Pain control methods in use and perceived effectiveness by patients with Ehlers-Danlos syndrome: a descriptive study.

PubMed

Arthur, Karen; Caldwell, Karen; Forehand, Samantha; Davis, Keith

2016-01-01

The purpose of this study was to assess the pain control methods in use by patients who have Ehlers-Danlos Syndrome (EDS), a group of connective tissue disorders, and their perceived effectiveness. This descriptive study involved 1179 adults diagnosed with EDS who completed an anonymous on-line survey. The survey consisted of demographics information, the Patient Reported Outcomes Measurement Information System (PROMIS) Pain-Behavior, PROMIS Pain-Interference, and Neuro QOL Satisfaction with Social Roles and Activities scales, as well as a modified version of the Pain Management Strategies Survey. Respondents reported having to seek out confirmation of their EDS diagnosis with multiple healthcare providers, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Patients with EDS experience higher levels of pain interference and lower satisfaction with social roles and activities compared to national norms. Among the treatment modalities in this study, those perceived as most helpful for acute pain control were opioids, surgical interventions, splints and braces, avoidance of potentially dangerous activities and heat therapy. Chronic pain treatments rated as most helpful were opioids, splints or braces and surgical interventions. For methods used for both acute and chronic pain, those perceived as most helpful were opioids, massage therapies, splints or braces, heat therapy and avoiding potentially dangerous activities. EDS is a complex, multi-systemic condition that can be difficult to diagnose and poses challenges for healthcare practitioners who engage with EDS patients in holistic care. Improved healthcare provider knowledge of EDS is needed, and additional research on the co-occurring diagnoses with EDS may assist in comprehensive pain management for EDS patients. Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders associated with defective production of collagen, which can dramatically reduce musculoskeletal functioning by symptoms of joint laxity and frequent dislocations eventually leading to disability. Respondents to an on-line survey reported having to seek out confirmation of their EDS diagnosis with multiple physicians, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Participants with EDS reported the most helpful methods for managing acute pain were opioids, surgical interventions, splints and braces, heat therapy, nerve blocks and physical therapy, while chronic pain was treated most effectively with opioids, heat therapy, splints or braces and surgical interventions.

[True myelinic neuroma. Its associations (neurocrestopathies)].

PubMed

Cortijo, A T; Pons, S; Ortíz Medina, A; Grinberg, A

1975-01-01

A case of true mielinic neuroma is described. An exhaustive review of the literature on this subject, basically of the Bolande article is carried out by the authors. The mielinic neuromata are a partial aspect of the complexe neuro-crestopathic syndromes associating the cutaneous lesions to: 1) Medullary tyroid carcinoma, 2) pheocromocytoma and 3) neurofibromatous lesions. The observation related by the authors shows: 1) Ehlers-Danlos disease (not described previously), 2) skeletal abnormalities, 3) medullary tyroid carcinoma and 4) pheochromocytoma symptoms.

Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients.

PubMed

Demirdas, S; Dulfer, E; Robert, L; Kempers, M; van Beek, D; Micha, D; van Engelen, B G; Hamel, B; Schalkwijk, J; Loeys, B; Maugeri, A; Voermans, N C

2017-03-01

The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non-sense mRNA mediated decay. In short, patients with the TNX-deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis of Ehlers-Danlos syndrome after a first shoulder dislocation.

PubMed

Nourissat, Geoffroy; Vigan, Marie; Hamonet, Claude; Doursounian, Levon; Deranlot, Julien

2018-01-01

Shoulder dislocation is often the first symptom of Ehlers-Danlos syndrome (EDS). Whether it occurs in early-onset EDS is unknown. In most cases, surgical failure leads to the diagnosis. We aimed to determine whether clinical symptoms can signal the presence of EDS at a first dislocation. In this retrospective study, we analyzed clinical and radiologic data for 27 patients with EDS and shoulder instability and a control population of 40 consecutive non-EDS patients undergoing surgery for an unstable shoulder. Data were collected on gender, age, single or bilateral disease, general hyperlaxity, shoulder hyperlaxity, number of dislocations or subluxations, nontraumatic onset, and pain specificity. Nerve and vascular injuries, joint disorders, and family history were recorded, and radiologic data were reported. Age <14 years, female sex, bilateral disorder, and general hyperlaxity were significantly more frequent in patients with EDS and a first dislocation than in those without EDS. Painless dislocation with pain after dislocation and concomitant nerve injury were more frequent in affected patients, as were hemostasis disorders and a family history of joint hyperlaxity. Bone lesions were not seen on radiographs. Only the hyperlaxity sign (external rotation >85°) did not differ between the groups. After a first dislocation in a young girl with global hyperlaxity but not necessarily shoulder hyperlaxity, painless atraumatic dislocation with pain after reduction can suggest EDS. Copyright © 2018. Published by Elsevier Inc.

Multimodal Chiropractic Care for Pain and Disability in a Patient Diagnosed With Ehlers-Danlos Syndrome-Hypermobility Type: A Case Report.

PubMed

Strunk, Richard G

2017-06-01

The purpose of this article is to describe the clinical response to multimodal chiropractic treatment of a patient diagnosed with Ehlers-Danlos syndrome, hypermobility type (EDS-HT), and chronic pain. A 22-year-old woman presented with severe chronic neck and low back pain, headaches, and bilateral hand pain and stiffness. In addition to these pain complaints, the patient had a family history of EDS, weekly or daily recurring joint dislocations, and upper and lower extremity joint hypermobility. As a result of her significant history and examination findings, which met the Brighton and Villefranche criteria, she was diagnosed with EDS-HT. Treatment primarily consisted of low force joint manipulative therapy and soft tissue therapy intermittently over 21 months concurrently with conventional and complementary medical care. Multiple outcome questionnaires were administered pragmatically at follow-up intervals of 3, 5½, 8½, 19, and 21 months, including but not limited to the Headache and Neck Disability Indices and the Oswestry Low Back Questionnaire. The patient had clinically meaningful improvements on the Neck Disability Index, the Headache Disability Index, and the Revised Oswestry after 3, 5½, 8½, and 21 months from baseline. This patient with EDS-HT had clinically meaningful decreases in disability, headache, and spine pain after a course of multimodal chiropractic care combined with conventional and complementary medical care.

Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.

PubMed

Weerakkody, Ruwan A; Vandrovcova, Jana; Kanonidou, Christina; Mueller, Michael; Gampawar, Piyush; Ibrahim, Yousef; Norsworthy, Penny; Biggs, Jennifer; Abdullah, Abdulshakur; Ross, David; Black, Holly A; Ferguson, David; Cheshire, Nicholas J; Kazkaz, Hanadi; Grahame, Rodney; Ghali, Neeti; Vandersteen, Anthony; Pope, F Michael; Aitman, Timothy J

2016-11-01

Ehlers-Danlos syndrome (EDS) comprises a group of overlapping hereditary disorders of connective tissue with significant morbidity and mortality, including major vascular complications. We sought to identify the diagnostic utility of a next-generation sequencing (NGS) panel in a mixed EDS cohort. We developed and applied PCR-based NGS assays for targeted, unbiased sequencing of 12 collagen and aortopathy genes to a cohort of 177 unrelated EDS patients. Variants were scored blind to previous genetic testing and then compared with results of previous Sanger sequencing. Twenty-eight pathogenic variants in COL5A1/2, COL3A1, FBN1, and COL1A1 and four likely pathogenic variants in COL1A1, TGFBR1/2, and SMAD3 were identified by the NGS assays. These included all previously detected single-nucleotide and other short pathogenic variants in these genes, and seven newly detected pathogenic or likely pathogenic variants leading to clinically significant diagnostic revisions. Twenty-two variants of uncertain significance were identified, seven of which were in aortopathy genes and required clinical follow-up. Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype-phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes. These data may be of value in guiding future clinical pathways for genetic diagnosis in EDS.Genet Med 18 11, 1119-1127.

Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients.

PubMed

Colombi, M; Dordoni, C; Venturini, M; Ciaccio, C; Morlino, S; Chiarelli, N; Zanca, A; Calzavara-Pinton, P; Zoppi, N; Castori, M; Ritelli, M

2017-12-01

Classical Ehlers-Danlos syndrome (cEDS) is characterized by marked cutaneous involvement, according to the Villefranche nosology and its 2017 revision. However, the diagnostic flow-chart that prompts molecular testing is still based on experts' opinion rather than systematic published data. Here we report on 62 molecularly characterized cEDS patients with focus on skin, mucosal, facial, and articular manifestations. The major and minor Villefranche criteria, additional 11 mucocutaneous signs and 15 facial dysmorphic traits were ascertained and feature rates compared by sex and age. In our cohort, we did not observe any mandatory clinical sign. Skin hyperextensibility plus atrophic scars was the most frequent combination, whereas generalized joint hypermobility according to the Beighton score decreased with age. Skin was more commonly hyperextensible on elbows, neck, and knees. The sites more frequently affected by abnormal atrophic scarring were knees, face (especially forehead), pretibial area, and elbows. Facial dysmorphism commonly affected midface/orbital areas with epicanthal folds and infraorbital creases more commonly observed in young patients. Our findings suggest that the combination of ≥1 eye dysmorphism and facial/forehead scars may support the diagnosis in children. Minor acquired traits, such as molluscoid pseudotumors, subcutaneous spheroids, and signs of premature skin aging are equally useful in adults. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Knowledge, assessment, and management of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type among Flemish physiotherapists.

PubMed

Rombaut, Lies; Deane, Janet; Simmonds, Jane; De Wandele, Inge; De Paepe, Anne; Malfait, Fransiska; Calders, Patrick

2015-03-01

Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS-HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists' knowledge of JHS/EDS-HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty-five Flemish physiotherapists participated in the study by filling out electronically a modified version of the "Hypermobility and Hypermobility Syndrome Questionnaire" (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS-HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS-HT. Knowledge of hypermobility and JHS/EDS-HT is weak, especially regarding the features associated with JHS/EDS-HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS-HT is under-recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed. © 2015 Wiley Periodicals, Inc.

Thoracic aortic aneurysm: How to counsel, when to refer.

PubMed

Cikach, Frank; Desai, Milind Y; Roselli, Eric E; Kalahasti, Vidyasagar

2018-06-01

Thoracic aortic aneurysm (TAA) is usually clinically silent and progresses slowly until a tipping point is reached, after which the aortic diameter can expand more rapidly and the condition can potentially end in aortic dissection or rupture. Causes include bicuspid aortic valve and genetic syndromes (Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes) and familial associations, but many cases are idiopathic. Clinicians should therefore be alert for clues on chest imaging, and consider screening in first-degree relatives of patients known to have aortic disease. Early referral to a cardiologist specializing in aortic disease is key. Copyright © 2018 Cleveland Clinic.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome.

PubMed

Meester, Josephina A N; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart L

2017-11-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1 , coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2 , SMAD2/3 , or TGFB2/3 , all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

PubMed Central

Meester, Josephina A. N.; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut

2017-01-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1, coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2, SMAD2/3, or TGFB2/3, all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation. PMID:29270370

Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?

PubMed

Miglis, Mitchell G; Schultz, Brittany; Muppidi, Srikanth

2017-12-01

It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls). While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; O'Callaghan, Chris; De Wandele, Inge; Stiles, Lauren; Pocinki, Alan; Rowe, Peter

2017-03-01

Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Spontaneous coronary artery dissection and its association with heritable connective tissue disorders.

PubMed

Henkin, Stanislav; Negrotto, Sara M; Tweet, Marysia S; Kirmani, Salman; Deyle, David R; Gulati, Rajiv; Olson, Timothy M; Hayes, Sharonne N

2016-06-01

Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. 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/

The genetics and genomics of thoracic aortic disease

PubMed Central

Pomianowski, Pawel

2013-01-01

Genetic studies over the past several decades have helped to better elucidate the genomics and inheritance of thoracic aortic diseases. Seminal work from various researchers have identified several genetic factors and mutations that predispose to aortic aneurysms, which will aid in better screening and early intervention, resulting in better clinical outcomes. Syndromic aneurysms have been associated with Marfan syndrome, Loeys-Dietz syndrome, aneurysm osteoarthritis syndrome, arterial tortuosity syndrome, Ehlers-Danlos Syndrome, and TGFβ mutation. Mutations in MYH11, TGFβR1, TGFβR2, MYLK, and ACTA2 genes have been linked to familial non-syndromic cases, although linkage analysis is limited by incomplete penetrance and/or locus heterogeneity. This overview presents a summary of key genetic and genomic factors that are associated with thoracic aortic diseases. PMID:23977594

Refining patterns of joint hypermobility, habitus, and orthopedic traits in joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type.

PubMed

Morlino, Silvia; Dordoni, Chiara; Sperduti, Isabella; Venturini, Marina; Celletti, Claudia; Camerota, Filippo; Colombi, Marina; Castori, Marco

2017-04-01

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two overlapping heritable disorders (JHS/EDS-HT) recognized by separated sets of diagnostic criteria and still lack a confirmatory test. This descriptive research was aimed at better characterizing the clinical phenotype of JHS/EDS-HT with focus on available diagnostic criteria, and in order to propose novel features and assessment strategies. One hundred and eighty-nine (163 females, 26 males; age: 2-73 years) patients from two Italian reference centers were investigated for Beighton score, range of motion in 21 additional joints, rate and sites of dislocations and sprains, recurrent soft-tissue injuries, tendon and muscle ruptures, body mass index, arm span/height ratio, wrist and thumb signs, and 12 additional orthopedic features. Rough rates were compared by age, sex, and handedness with a series of parametric and non-parametric tools. Multiple correspondence analysis was carried out for possible co-segregations of features. Beighton score and hypermobility at other joints were influenced by age at diagnosis. Rate and sites of joint instability complications did not vary according to age at diagnosis except for soft-tissue injuries. No major difference was registered by sex and dominant versus non-dominant body side. At multiple correspondence analysis, selected features tend to co-segregate in a dichotomous distribution. Dolichostenomelia and arachnodactyly segregated independently. This study pointed out a more protean musculoskeletal phenotype than previously considered according to available diagnostic criteria for JHS/EDS-HT. Our findings corroborated the need for a re-thinking of JHS/EDS-HT on clinical grounds in order to find better therapeutic and research strategies. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type.

PubMed

Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina

2016-01-01

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients.

The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome.

PubMed

Engelbert, Raoul H H; Juul-Kristensen, Birgit; Pacey, Verity; de Wandele, Inge; Smeenk, Sandy; Woinarosky, Nicoleta; Sabo, Stephanie; Scheper, Mark C; Russek, Leslie; Simmonds, Jane V

2017-03-01

New insights into the phenotype of Joint Hypermobility Syndrome (JHS) and Ehlers-Danlos Syndrome-hypermobile type (hEDS) have raised many issues in relation to classification, diagnosis, assessment, and treatment. Within the multidisciplinary team, physical therapy plays a central role in management of individuals with hypermobility related disorders. However, many physical therapists are not familiar with the diagnostic criteria, prevalence, common clinical presentation, and management. This guideline aims to provide practitioners with the state of the art regarding the assessment and management of children, adolescents, and adults with JHS/hEDS. Due to the complexity of the symptoms in the profile of JHS/hEDS, the International Classification of Functioning, Disability and Health (ICF) is adopted as a central framework whereby the umbrella term of disability is used to encompass functions, activities and participation, as well as environmental and personal factors. The current evidence-based literature regarding the management of JHS/hEDS is limited in size and quality and there is insufficient research exploring the clinical outcomes of a number of interventions. Multicenter randomized controlled trials are warranted to assess the clinical and cost-effectiveness of interventions for children and adults. Until further multicenter trials are conducted, clinical decision-making should be based on theoretical and the current limited research evidence. For all individuals diagnosed with JHS/hEDS, international consensus and combined efforts to identify risk profiles would create a better understanding of the pathological mechanisms and the potential for optimizing health care for affected individuals. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Syndromology: an updated conceptual overview. VI. Molecular and biochemical aspects of dysmorphology.

PubMed

Cohen, M M

1989-12-01

The role of chance using a stochastic single gene model has been shown to generate a continuous liability curve resembling that obtained from a multifactorial threshold model. Segregation of some malformations may be explained by a single defective gene that predisposes to, but does not necessarily result in, the malformation. Low penetrance and remarkably variable expressivity that characterize a number of presumed autosomal dominant malformation syndromes are possibly reflections of specific stochastic influences that are intrinsic to the embryonic process itself. Gene analysis is discussed and illustrated. Using polymorphic DNA probes to study cleft palate and ankyloglossia in males and ankyloglossia only in females in a large Icelandic family, the responsible gene was found to be located on the long arm of the X chromosome in the Xq21.1 region. In addition to gene analysis, some of the implications of transgenic analysis using mice are discussed. Among disorders of collagen metabolism, both the osteogenesis imperfectas and the Ehlers-Danlos syndromes are shown to represent genetically heterogeneous groups of connective tissue disorders. The days of thinking about osteogenesis imperfecta as one disorder and the Ehlers-Danlos syndrome as another are a thing of the past; persistence of such thinking is erroneous and misleading. Of the many disorders affecting bone mineral, the complexities of hypophosphatasia and pseudohypoparathyroidism are singled out for discussion. For lysosomal storage disorders, an overview of the mucopolysaccharidoses is provided. Finally, the recently delineated peroxisomal disorders--hyperpipecolic acidemia, rhizomelic chondrodysplasia, neonatal adrenoleukodystrophy, Zellweger syndrome, and infantile Refsum disease--are known to share a distinctive biochemical phenotype, although fibroblast complementation analysis suggests that some of these disorders are etiologically distinct.

Severe periodontitis in Marfan's syndrome: a case report.

PubMed

Straub, Antje M; Grahame, Rodney; Scully, Crispian; Tonetti, Maurizio S

2002-07-01

Connective tissue disorders, such as some forms of Ehlers-Danlos syndrome, have been associated with severe periodontitis. This report describes a case of Marfan's syndrome, an inherited disorder of connective tissue caused by mutations in the fibrillin-1 gene, in which the patient presented with severe periodontitis. At examination, an average full-mouth clinical attachment level loss of 5.6+/-2.1 mm, furcation involvement, and severe alveolar bone loss were observed in a 41-year-old Caucasian male. Tooth hypermobility was also present. This case appears to be the first documentation of severe periodontitis in a patient with Marfan's syndrome. It supports the hypothesis that a variety of connective tissue disorders may confer increased susceptibility to periodontal tissue breakdown.

Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome

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

Ottenheijm, Coen A.C.; Voermans, Nicol C.; Hudson, Bryan D.

Tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence leads to Ehlers-Danlos Syndrome (EDS). TNX-deficient EDS patients present with joint hypermobility and muscle weakness attributable to increased compliance of the extracellular matrix. We hypothesized that in response to the increased compliance of the extracellular matrix in TNX-deficient EDS patients, intracellular adaptations take place in the elastic properties of the giant muscle protein titin. We performed extensive single muscle fiber mechanical studies to determine active and passive properties in TNX-deficient EDS patients. Gel-electrophoresis, Western blotting, and microarray studies were used to evaluate titin expression and phosphorylation. X-ray diffraction was used tomore » measure myofilament lattice spacing. Passive tension of muscle fibers from TNX-deficient EDS patients was markedly increased. Myofilament extraction experiments indicated that the increased passive tension is attributable to changes in the properties of the sarcomeric protein titin. Transcript and protein data indicated no changes in titin isoform expression. Instead, differences in posttranslational modifications within titin's elastic region were found. In patients, active tension was not different at maximal activation level, but at submaximal activation level it was augmented attributable to increased calcium sensitivity. This increased calcium sensitivity might be attributable to stiffer titin molecules. In response to the increased compliance of the extracellular matrix in muscle of TNX-deficient EDS patients, a marked intracellular stiffening occurs of the giant protein titin. The stiffening of titin partly compensates for the muscle weakness in these patients by augmenting submaximal active tension generation.« less

Bowel perforation in type IV vascular Ehlers-Danlos syndrome. A systematic review.

PubMed

El Masri, H; Loong, T-H; Meurette, G; Podevin, J; Zinzindohoue, F; Lehur, P-A

2018-05-01

Spontaneous gastrointestinal (GI) perforation is a well-known complication occurring in patients suffering from Type IV vascular Ehlers-Danlos syndrome (EDS IV). The aim of the present study was to review the current literature on spontaneous GI perforation in EDS IV and illustrate the surgical management and outcome when possible. A systematic review of all the published data on EDS IV patients with spontaneous GI perforation between January 2000 and December 2015 was conducted using three major databases PUBMED, EMBASE, and Cochrane Central Register of Controlled Trails. References of the selected articles were screened to avoid missing main articles. Twenty-seven published case reports and four retrospective studies, including 31 and 527 cases, respectively, matched the search criteria. A case from our institution was added. Mean age was 26 years (range 6-64 years). The most frequent site of perforation was the colon, particularly the sigmoid, followed by small bowel, upper rectum, and finally stomach. The majority of cases were initially managed with Hartmann's procedure. In recurrent perforations, total colectomy was performed. The reperforation rate was considerably higher in the "partial colectomy with anastomosis" group than in the Hartmann group. Colonic perforation is the most common spontaneous GI perforation in EDS IV patients. An unexpected fragility of the tissues should raise the possibility of a connective tissue disorder and prompt further investigation with eventual management of these high-risk patients with a multidisciplinary team approach in dedicated centres. In the emergency setting, a Hartmann procedure should be performed.

A multimodal physical therapy approach utilizing the Maitland concept in the management of a patient with cervical and lumbar radiculitis and Ehlers-Danlos syndrome-hypermobility type: A case report.

PubMed

Pennetti, Adelina

2018-07-01

The purpose of this case report is to present a multimodal approach for patient management using the Maitland concept framework for cervical and lumbar radiculitis with an underlying diagnosis of Ehlers-Danlos Syndrome-Hypermobility Type (EDS-HT). This case presents care guided by evidence, patient values, and rationale for the selected course of physical therapy treatment provided by therapist experience. A 35-year-old female with a 2-year history of worsening lumbar and cervical pain was referred to physical therapy to address these musculoskeletal issues concurrent with diagnostic testing for EDS. A multimodal approach including manual therapy, therapeutic exercise, postural and body mechanics education, and a home exercise program was used. The patient specific functional scale (PSFS) was used to gauge patient's perceived improvements which were demonstrated by increased scores at reevaluation and at discharge. Following the Maitland concept framework, the physical therapist was able to make sound clinical decisions by tracking the logical flow of constant patient assessment. A 10-month course of treatment designed to maximize recovery of function was successful with a chronic history of pain and the EDS-HT diagnosis. The role of education and empowering the patient is shown to be of utmost importance. Optimizing therapeutic outcomes long-term for this patient population requires maintaining a home exercise program, adaptation and modifications of work and lifestyle activities.

[Temporomandibular disorders and Ehlers-Danlos syndrome, hypermobility type: A case-control study].

PubMed

Diep, D; Fau, V; Wdowik, S; Bienvenu, B; Bénateau, H; Veyssière, A

2016-09-01

The Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is a rare genetic disease. Diagnosis is based on a combination of clinical criteria described in the classification of Villefranche. Diagnosis is difficult to make because of the lack of specific clinical signs and the absence of genetic testing. The EDS-TH manifests itself manly by musculoskeletal pain and joint hypermobility. Temporomandibular disorders (TMD) are also reported. Our aim was to objectify the presence and to qualify the type of TMD associated with the EDS-HT in order to propose an additional diagnostic argument. A prospective, monocenter case-control study, comparing a cohort of patients suffering from EDS-HT to a paired control group of healthy volunteers has been conducted. Clinical examination was standardized, including a general questioning, an oral examination and a temporomandibular joint examination following the TMD/RDC (temporomandibular disorders/research diagnostic criteria). Fourteen EDS-HT patients and 58 control patients were examined. The prevalence of TMDs (n=13; 92.9% vs. n=4; 6.9%; P=10(-11)) was significantly higher in the EDS-HT group. TMDs occurring in the EDS-HT group were complex, combining several mechanisms in contrast to the control group, where only one mechanism was found in all the patients (n=13; 92.9% vs. n=0; 0.0%). TMDs are strongly associated with RDS-HT. TMDs could therefore be used in the diagnosis of this disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Postural analysis in time and frequency domains in patients with Ehlers-Danlos syndrome.

PubMed

Galli, Manuela; Rigoldi, Chiara; Celletti, Claudia; Mainardi, Luca; Tenore, Nunzio; Albertini, Giorgio; Camerota, Filippo

2011-01-01

The goal of this work is to analyze postural control in Ehlers-Danlos syndrome (EDS) participants in time and frequency domain. This study considered a pathological group composed by 22 EDS participants performing a postural test consisting in maintaining standing position over a force platform for 30s in two conditions: open eyes (OE) and closed eyes (CE). In order to compare pathological group we acquired in the same conditions a control group composed by 20 healthy participants. The obtained center of pressure (COP) signal was analyzed in time and frequency domain using an AR model. Results revealed differences between pathological and control group: EDS participants pointed out difficulties in controlling COP displacements trying to keep it inside the BOS in AP direction and for this reason increased the use of ML mechanism in order to avoid the risk of fall. Also in CE conditions they demonstrated more difficulties in maintaining posture revealing the proprioceptive system is impaired, due to ligament laxity that characterized EDS participants. Frequency domain analysis showed no differences between the two groups, affirming that the changes in time domain reflected really the impairment to the postural control mechanism and not a different strategy assumed by EDS participants. These data could help in decision-making process to establish a correct rehabilitation approach, based on the reinforcing of muscle tone to supply the ligament laxity in order to prevent risks of falls and its consequences. Copyright © 2010 Elsevier Ltd. All rights reserved.

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

PubMed Central

Cury, Marcelo; Zeidan, Fernanda; Lobato, Armando C.

2013-01-01

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research. PMID:23401778

MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.

PubMed

Chiu, Bing Q; Tsui, Edmund; Hussnain, Syed Amal; Barbazetto, Irene A; Smith, R Theodore

2018-02-13

To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up. Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained. Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks. We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

The influence of Ehlers-Danlos syndrome - hypermobility type, on motherhood: A phenomenological, hermeneutical study.

PubMed

De Baets, Stijn; Vanhalst, Marieke; Coussens, Marieke; Rombaut, Lies; Malfait, Fransiska; Van Hove, Geert; Calders, Patrick; Vanderstraeten, Guy; van de Velde, Dominique

2017-01-01

The consequences of the Ehlers-Danlos Syndrome hypermobility type (EDS-HT) affect many aspects of daily life. "Living with limitations" is a central theme in the life of patients affected by this heritable disorder of connective tissue. The aim of the present study was to explore the lived experiences of women with EDS-HT concerning diagnosis, influence on daily life and becoming and being a mother. A phenomenological-hermeneutical study, using in-depth interviews. Patients were selected by a purposive sampling strategy. This study shows that the EDS-HT syndrome affects daily life. Ten woman between 31 and 65 years were interviewed. They have between 2 and 5 children. The data analysis results in six themes. (1) Getting a diagnosis is a relief and supports the choice to become a mother; (2) EDS-HT causes emotional distress, imposes a physical burden and has a major impact on social behavior; (3) EDS-HT demands a restructuring of everyday activities; (4) Children's and mothers' expectations do not correspond; (5) Having a supportive social and physical environment is of major importance; (6) The presence of the child reduces the feeling of illness of the mother. The diagnosis of EDS-HT is a catalysing factor in the choice of whether or not to become a mother. EDS-HT has a huge impact on bodily functions, which in turn influences activities and participation. This study gives insight in the activities of daily life of persons with EDS-HT. Health care professionals can be of great importance to help patients in (re)organizing their lives according to the available energy and in supporting their choices. They can help defining goals and setting priorities in daily life. Copyright © 2016 Elsevier Ltd. All rights reserved.

CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome.

PubMed

Kosho, Tomoki

2016-02-01

Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers-Danlos syndrome (EDS) caused by recessive loss-of-function mutations in CHST14. The disorder has been independently termed "adducted thumb-clubfoot syndrome", "EDS, Kosho type", and "EDS, musculocontractural type". To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro-retrognathia; multiple congenital contractures including adduction-flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility-related manifestations, establishment of a comprehensive and detailed natural history and health-care guidelines as well as further elucidation of the pathophysiology in view of future etiology-based therapy are crucial. © 2015 Japan Pediatric Society.

[Postural tachycardia syndrome (PoTS): An up-to-date].

PubMed

Astudillo, L; Laure, A; Fabry, V; Pugnet, G; Maury, P; Labrunée, M; Sailler, L; Pavy-Le Traon, A

2018-06-13

Postural tachycardia syndrome (PoTS) is a multifactorial syndrome defined by an increase in heart rate ≥30bpm, within 10minutes of standing (or during a head up tilt test to at least 60°), in absence of orthostatic hypotension. It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve in supine position. Patients have an intense fatigue with a high incidence on quality of life. This syndrome can be explained by many pathophysiological mechanisms. It can be associated with Ehlers-Danlos disease and some autoimmune disorders. The treatment is based on nonpharmacological measures and treatment with propranolol, fludrocortisone or midodrine. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

The Phenotype of the Musculocontractural Type of Ehlers-Danlos Syndrome due to CHST14 Mutations

PubMed Central

Janecke, Andreas R.; Li, Ben; Boehm, Manfred; Krabichler, Birgit; Rohrbach, Marianne; Müller, Thomas; Fuchs, Irene; Golas, Gretchen; Katagiri, Yasuhiro; Ziegler, Shira G.; Gahl, William A.; Wilnai, Yael; Zoppi, Nicoletta; Geller, Herbert M.; Giunta, Cecilia; Slavotinek, Anne; Steinmann, Beat

2016-01-01

The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with biallelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients hadmildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS. PMID:26373698

Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome.

PubMed

Blackburn, Patrick R; Xu, Zhi; Tumelty, Kathleen E; Zhao, Rose W; Monis, William J; Harris, Kimberly G; Gass, Jennifer M; Cousin, Margot A; Boczek, Nicole J; Mitkov, Mario V; Cappel, Mark A; Francomano, Clair A; Parisi, Joseph E; Klee, Eric W; Faqeih, Eissa; Alkuraya, Fowzan S; Layne, Matthew D; McDonnell, Nazli B; Atwal, Paldeep S

2018-04-05

AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 -/- mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581 ∗ ]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs ∗ 3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study.

PubMed

Hugon-Rodin, Justine; Lebègue, Géraldine; Becourt, Stéphanie; Hamonet, Claude; Gompel, Anne

2016-09-13

Hypermobile Ehlers-Danlos syndrome (hEDS), is probably the most common disease among heritable connective tissue disorders. It affects women more than men and causes symptoms in multiple organs. It is associated with chronic pain, skin fragility and abnormal bleeding. These characteristics may hamper reproductive life. We conducted a study to evaluate the gynecologic and obstetric outcomes in women with hEDS. We also explored a possible hormonal modulation of the hEDS symptoms. The gynecologic and obstetric history of 386 consecutive women diagnosed with hEDS was collected by a standardized questionnaire and a medical consultation performed by a senior gynecologist in an expert centre for hEDS between May 2012 and December 2014. We observed a high frequency of gynecologic complaints, specifically: menorrhagia (76 %), dysmenorrhea (72 %) and dyspareunia (43 %). Endometriosis was not highly prevalent in this population. The obstetric outcomes were similar to those of the general French population for deliveries by cesarean section (14.6 %) and premature births (6.2 %) but the incidence of multiple spontaneous abortion (13 %) and spontaneous abortion (28 %) were significantly higher. A subset of women were sensitive to hormonal fluctuations with more severe symptoms occurring during puberty, prior to menstruation, during the postpartum period as well as on oral contraception. Increased awareness of the gynecological symptomatology in women with hEDS can help discriminate between endometriosis and thus prevent useless, and potentially dangerous, surgery. This study also suggests that hormonal modulation may be an appropriate treatment for a subset of women with hEDS.

Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.

PubMed

Johnston, Jessica M; Connizzo, Brianne K; Shetye, Snehal S; Robinson, Kelsey A; Huegel, Julianne; Rodriguez, Ashley B; Sun, Mei; Adams, Sheila M; Birk, David E; Soslowsky, Louis J

2017-12-01

Classic Ehlers-Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1 +/- mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1 +/- ) with wild-type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1 +/- tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild-type tendons, which recovered their pre-injury values by 6 weeks post injury. Additionally, the Col5a1 +/- tendons demonstrated altered fibril morphology and diameter distributions compared to the wild-type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2707-2715, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Low- and high-anxious hypermobile Ehlers-Danlos syndrome patients: comparison of psychosocial and health variables.

PubMed

Baeza-Velasco, Carolina; Bourdon, Caroline; Montalescot, Lucile; de Cazotte, Cécile; Pailhez, Guillem; Bulbena, Antonio; Hamonet, Claude

2018-05-01

Despite the frequent co-ocurrence of hypermobile Ehler-Danlos syndrome (hEDS) and pathological anxiety, little is known about the psychosocial and health implications of such comorbidity. Our aim was to explore the association between high levels of anxiety and psychosocial (catastrophizing, kinesiophobia, somatosensory amplification, social support and functioning), health (pain, fatigue, BMI, tobacco/alcohol use, depression, diagnosis delay, general health), and sociodemographic factors in people with hEDS. In this cross-sectional study, 80 hEDS patients were divided into two groups according to self-reported anxiety levels: low and high. Psychosocial, sociodemographic and health variables were compared between the groups. Forty-one participants reported a high level of anxiety (51.2%). No differences were found in the sociodemographic variables between high-anxious and low-anxious patients. The percentage of participants with severe fatigue and high depressive symptomatology was significantly higher in the high-anxious group (80.5 vs 56.4; 26.8 vs 12.8%, respectively). High-anxious hEDS patients also showed significantly higher levels of pain catastrophizing, somatosensory amplification as well as a poorer social functioning and general health. Multivariate analyses showed that somatosensory amplification, pain catastrophizing and poor social functioning are variables that increase the probability of belonging to the high-anxious group. Despite limitations, this first study comparing high-anxious versus low-anxious hEDS patients with respect to health aspects, highlight the importance of considering the psychosocial factors (many susceptible to modification), to improve the adjustment to this chronic condition and provide support to those affected through a biopsychosocial approach.

Fatigue is associated with muscle weakness in Ehlers-Danlos syndrome: an explorative study.

PubMed

Voermans, N C; Knoop, H; Bleijenberg, G; van Engelen, B G

2011-06-01

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The aim of this study was to investigate the relationship between fatigue severity and subjective and objective measures of muscle weakness. Furthermore, the predictive value of muscle weakness for fatigue severity was determined, together with that of pain and physical activity. An explorative, cross-sectional, observational study. Thirty EDS patients, recruited from the Dutch patient association, were investigated at the neuromuscular outpatient department of a tertiary referral centre in The Netherlands. Muscle strength measured with manual muscle strength testing and hand-held dynamometry. Self-reported muscle weakness, pain, physical activity levels and fatigue were assessed with standardised questionnaires. Fatigue severity in EDS was significantly correlated with measured and self-reported muscle weakness (r=-0.408 for manual muscle strength, r=0.461 for hand-held dynamometry and r=0.603 for self-reported muscle weakness). Both muscle weakness and pain severity were significant predictors of fatigue severity in a multiple regression analysis. The results suggest a positive and direct relationship between fatigue severity and muscle weakness in EDS. Future research should focus on the relationship between fatigue, muscle weakness and objectively measured physical activity, preferably in a larger cohort of EDS patients. Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Postural orthostatic tachycardia syndrome: Dental treatment considerations.

PubMed

Brooks, John K; Francis, Laurie A P

2006-04-01

Postural orthostatic tachycardia syndrome (POTS) is a chronic, relatively common autonomic disorder typically affecting younger females. It is distinguished by a dramatic increase in heart rate on the assumption of an upright posture from the supine position. The authors provide an overview of the demographics, clinical assessment, diagnostic features, differential diagnoses, pathogeneses and medical treatment of patients with POTS, with an emphasis on the clinical treatment of the dental patient affected by the syndrome. Patients frequently exhibit symptoms of lightheadedness, fatigue, palpitations and syncope. Patients with POTS may have Ehlers-Danlos syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the Brugada syndrome. Despite widespread dissemination of information regarding POTS in the medical literature, scant information on it has appeared in dental publications. Dentists need to be familiar with the clinical features of POTS and be prepared to treat patients at risk of developing syncope.

Use of the gait profile score for the evaluation of patients with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.

PubMed

Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Tenore, Nunzio; Albertini, Giorgio; Camerota, Filippo

2013-11-01

Gait analysis (GA) is widely used for clinical evaluations in various pathological states, both in children and in adults, such as in patients with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). Otherwise, GA produces a large volume of data and there is the clinical need to provide also a quantitative measure of the patient's overall gait. Starting from this aim some global indexes were proposed by literature as a summary measure of the patient's gait, such as the Gait Profile Score (GPS). While validity of the GPS was demonstrated for the evaluation of the functional limitation of children with Cerebral Palsy, no studies have been conducted in patients JHS/EDS-HT. The aim of our study was therefore to investigate the effectiveness of the GPS in the quantification of functional limitation of patients with JHS/EDS-HT. Twenty-one adult (age: 36.1 ± 12.7 years) individuals with JHS/EDS-HT were evaluated using GA and from GA data the GPS was computed. The results evidenced that the GPS value of patients was 8.9 ± 2.6, statistically different from 4.6 ± 0.9 displayed by the control group. In particular, all values of Gait Variable Scores (GVS) which compose the GPS were higher if compared to controls, with the exception of Pelvic Tilt and Foot Progression. The correlations between GPS/GVS and Lower Extremity Functional Scale (LEFS) showed significant relationship between GPS and the item 11 ("Walking 2 blocks") (ρ=-0.56; p<0.05) and 12 ("Walking a mile") of LEFS (ρ=-0.76; p<0.05). Our results showed that GPS and GVS seem to be appropriate outcome measures for the evaluation of the functional limitation during gait of patients with JHS/EDS-HT. Copyright © 2013 Elsevier Ltd. All rights reserved.

Generalized Hyperalgesia in Children and Adults Diagnosed With Hypermobility Syndrome and Ehlers-Danlos Syndrome Hypermobility Type: A Discriminative Analysis.

PubMed

Scheper, M C; Pacey, V; Rombaut, L; Adams, R D; Tofts, L; Calders, P; Nicholson, L L; Engelbert, R H H

2017-03-01

Lowered pressure-pain thresholds have been demonstrated in adults with Ehlers-Danlos syndrome hypermobility type (EDS-HT), but whether these findings are also present in children is unclear. Therefore, the objectives of the study were to determine whether generalized hyperalgesia is present in children with hypermobility syndrome (HMS)/EDS-HT, explore potential differences in pressure-pain thresholds between children and adults with HMS/EDS-HT, and determine the discriminative value of generalized hyperalgesia. Patients were classified in 1 of 3 groups: HMS/EDS-HT, hypermobile (Beighton score ≥4 of 9), and healthy controls. Descriptive data of age, sex, body mass index, Beighton score, skin laxity, and medication usage were collected. Generalized hyperalgesia was quantified by the average pressure-pain thresholds collected from 12 locations. Confounders collected were pain locations/intensity, fatigue, and psychological distress. Comparisons between children with HMS/EDS-HT and normative values, between children and adults with HMS/EDS-HT, and corrected confounders were analyzed with multivariate analysis of covariance. The discriminative value of generalized hyperalgesia employed to differentiate between HMS/EDS-HT, hypermobility, and controls was quantified with logistic regression. Significantly lower pressure-pain thresholds were found in children with HMS/EDS-HT compared to normative values (range -22.0% to -59.0%; P ≤ 0.05). When applying a threshold of 30.8 N/cm 2 for males and 29.0 N/cm 2 for females, the presence of generalized hyperalgesia discriminated between individuals with HMS/EDS-HT, hypermobility, and healthy controls (odds ratio 6.0). Children and adults with HMS/EDS-HT are characterized by hypermobility, chronic pain, and generalized hyperalgesia. The presence of generalized hyperalgesia may indicate involvement of the central nervous system in the development of chronic pain. © 2016, American College of Rheumatology.

Pathophysiology and management of spontaneous intracranial hypotension--a review.

PubMed

Syed, Nadir Ali; Mirza, Farhan Arshad; Pabaney, Aqueel Hussain; Rameez-ul-Hassan

2012-01-01

Spontaneous Intracranial Hypotension is a syndrome involving reduced intracranial pressure secondary to a dural tear which occurs mostly due to connective tissue disorders such as Marfans Syndrome, and Ehler Danlos Syndrome. Patients with dural ectasias leading to CSF leakage into the subdural or epidural space classically present with orthostatic headaches and cranial nerve deficits mostly seen in cranial nerves V-VIII. Diagnosis of SIH is confirmed with the aid of neuroimaging modalities of which Cranial MR imaging is most widely used. SIH can be treated conservatively or with epidural blood patches which are now widely being used to repair dural tears, and their effectiveness is being recognized. Recently epidural injection of fibrin glue has also been used which has been found to be effective in certain patients.

Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.

PubMed

Niederhoffer, Karen Y; Fahiminiya, Somayyeh; Eydoux, Patrice; Mawson, John; Nishimura, Gen; Jerome-Majewska, Loydie A; Patel, Millan S

2016-09-01

Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Skin turgor

MedlinePlus

... eds. Seidel's Guide to Physical Examination . 8th ed. Elsevier Mosby; 2015:chap 8. Ferri FF. Ehlers-Danlos ... FF, ed. Ferri's Clinical Advisor 2016 . Philadelphia, PA: Elsevier; 2016:451-451. Gorgas DL, McGrath JL. Vital ...

Vascular Ehlers-Danlos syndrome mutations in type III collagen differently stall the triple helical folding.

PubMed

Mizuno, Kazunori; Boudko, Sergei; Engel, Jürgen; Bächinger, Hans Peter

2013-06-28

Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at a low temperature. At 33 °C, the natural collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at Gly-910 and at the C terminus at Gly-1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue.

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

PubMed Central

Wu, Zhiping; Aron, Abraham W.; Macksoud, Elyse E.; Iozzo, Renato V.; Hai, Chi-Ming; Lechner, Beatrice E.

2012-01-01

Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction. PMID:22253749

The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study.

PubMed

Scheper, Mark C; Nicholson, Lesley L; Adams, Roger D; Tofts, Louise; Pacey, Verity

2017-12-01

The objective of the manuscript was to describe the natural history of complaints and disability in children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the constructs that underlie functional decline. One hundred and one JHS/EDS-HT children were observed over 3 years and assessed at three time points on the following: functional impairments, quality of life, connective tissue laxity, muscle function, postural control and musculoskeletal and multi-systemic complaints. Cluster analysis was performed to identify subgroups in severity. Clinical profiles were determined for these subgroups, and differences were assessed by multivariate analysis of covariance. Mixed linear regression models were used to determine the subsequent trajectories. Finally, an exploratory factor analysis was used to uncover the underlying constructs of functional impairment. Three clusters of children were identified in terms of functional impairment: mild, moderately and severely affected. Functional impairment at baseline was predictive of worsening trajectories in terms of reduced walking distance and decreased quality of life (P ⩽ 0.05) over 3 years. Multiple interactions between the secondary outcomes were observed, with four underlying constructs identified. All four constructs (multi-systemic effects, pain, fatigue and loss of postural control) contributed significantly to disability (P ⩽ 0.046). Children diagnosed with JHS/EDS-HT who have a high incidence of multi-systemic complaints (particularly, orthostatic intolerance, urinary incontinence and diarrhoea) and poor postural control in addition to high levels of pain and fatigue at baseline are most likely to have a deteriorating trajectory of functional impairment and, accordingly, warrant clinical prioritization. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Sleep Disorders and Their Management in Children With Ehlers-Danlos Syndrome Referred to Sleep Clinics.

PubMed

Domany, Keren Armoni; Hantragool, Sumalee; Smith, David F; Xu, Yuanfang; Hossain, Monir; Simakajornboon, Narong

2018-04-15

The nature of sleep disorders in children with Ehlers-Danlos syndrome (EDS) is unknown. We aimed to describe the type, the management, and the short-term outcome of sleep disorders in children with EDS referred to sleep clinics. This is a retrospective review of medical records and polysomnography tests of children with EDS younger than 18 years who were referred to the sleep clinic. Demographic information and medical history were collected, and polysomnography tests were reviewed. Questionnaires completed during previous clinic visits, including the Pediatrics Sleep Questionnaire (PSQ), Epworth Sleepiness Scale (ESS), and Pediatric Quality of Life Inventory (PedsQL), were also evaluated. Sixty-five patients with EDS-hypermobility type were included. The mean age was 13.15 ± 3.9 years. There were 68% of patients who were female, and 91% of patients were Caucasian. The mean follow-up period was 1.14 ± 1.55 years. Common sleep diagnoses included insomnia (n = 14, 22%), obstructive sleep apnea (OSA) (n = 17, 26%), periodic limb movement disorder (PLMD) (n = 11, 17%), and hypersomnia (n = 10, 15%). In addition, 65% required pharmacologic treatment and 29% were referred to behavioral sleep medicine. For OSA, two patients required continuous positive airway pressure. A significant improvement was observed in the PSQ, ESS, and PedsQL scores during follow-up visits after treatment (n = 34; P = .0004, 0.03, and 0.01, respectively). There is a high prevalence of sleep disorders, including OSA, insomnia, PLMD, and hypersomnia in children with EDS referred to sleep clinics. Specific management can improve quality of life and questionnaire scores of this patient population. Our study emphasizes the importance of screening for sleep disorders in children with EDS. © 2018 American Academy of Sleep Medicine.

Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency.

PubMed

Mizumoto, Shuji; Kosho, Tomoki; Hatamochi, Atsushi; Honda, Tomoko; Yamaguchi, Tomomi; Okamoto, Nobuhiko; Miyake, Noriko; Yamada, Shuhei; Sugahara, Kazuyuki

2017-08-01

Dermatan sulfate (DS) plays a number of roles in a wide range of biological activities such as cell signaling and tissue morphogenesis through interactions with various extracellular matrix proteins including collagen. Mutations in the carbohydrate sulfotransferase 14 gene (CHST14) encoding CHST14/dermatan 4-O-sulfotransferase-1 (D4ST1), which is responsible for the biosynthesis of DS, cause a recently delineated form of Ehlers-Danlos syndrome (EDS, musculocontractural type 1), an autosomal recessive connective tissue disorder characterized by congenital malformations (specific craniofacial features, and congenital multiple contractures) and progressive fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; and large subcutaneous hematomas). In an attempt to develop a diagnostic screening method for this type of EDS, the amount of DS in the urine of patients was analyzed. Urinary DS was quantified by an anion-exchange chromatography after treatment with DS-specific degrading enzyme. DS was not detected in the urine of patients with homo- or compound heterozygous mutations in CHST14. These results suggest that the quantification of DS in urine is applicable to an initial diagnosis of DS-defective EDS. This is the first study to perform a urinary disaccharide compositional analysis of chondroitin sulfate (CS)/DS chains in patients with EDS caused by a CHST14/D4ST1 deficiency, and demonstrated the absence of DS chains. This result suggests systemic DS depletion in this disorder, and also proposes the usefulness of a urinary disaccharide compositional analysis of CS/DS chains as a non-invasive screening method for this disorder. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers-Danlos syndrome cohort.

PubMed

Ritter, Alyssa; Atzinger, Carrie; Hays, Brandon; James, Jeanne; Shikany, Amy; Neilson, Derek; Martin, Lisa; Weaver, Kathryn Nicole

2017-06-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue disorder characterized by joint hypermobility. The natural history of aortic root dilation (AoD), a potential complication of EDS, has not been well characterized in this population. We describe the natural history of aortic root size in a large cohort of patients with hEDS. A cohort of 325 patients with HEDS was identified at Cincinnati Children's Hospital Medical Center (CCHMC), including 163 patients from a previous study. Medical records were reviewed and each participant's height, weight, and aortic dimensions from up to four echocardiograms were documented. Aortic root z-scores were calculated using two established formulas based on age (Boston or Devereux). Overall prevalence of AoD and prevalence by age were calculated and longitudinal regression was performed. The prevalence of AoD with a z-score ≥ 2.0 was 14.2% (46/325) and with a z-score of ≥3.0 was 5.5% (18/325). No significant increases in z-score were seen over time for patients with multiple echocardiograms. Participants under the age of 15 years had an average decline of 0.1 standard deviations (SDs)/year. No significant change was found after 15 of age. Between the ages of 15 and 21 years, Boston z-scores were 0.96 higher than Devereux z-scores. The nearly 1 z-score unit difference between formulas indicates caution prior to diagnosing AoD in patients with hEDS. In light of the low prevalence and lack of progression of AoD, routine echocardiograms may not be warranted for pediatric patients with hEDS. © 2017 Wiley Periodicals, Inc.

Establishment and baseline characteristics of a nationwide Danish cohort of patients with Ehlers-Danlos syndrome.

PubMed

Kulas Søborg, Marie-Louise; Leganger, Julie; Quitzau Mortensen, Laura; Rosenberg, Jacob; Burcharth, Jakob

2017-05-01

The aim of this study was to investigate national prevalence, general demographic characteristics and survival of Danish patients with Ehlers-Danlos syndrome (EDS). A population-based cohort study was conducted using a database consisting of the entire Danish population alive at any given time between 1 January 2000 and 31 December 2012, based upon longitudinal Danish national registers. All patients with EDS were identified, and the cohort was described by disease prevalence, basic demographic characteristics, mean age at death and mortality for the observational period of 13 years. The cohort held 1427 unique persons with EDS, giving a national prevalence of 0.02%. The EDS population had a mean ( s . d .) age of 34.9 (18.6) years and comprised 73.9% females and 26.1% males. Of the cohort, 95.9% originated from Denmark and 57% were unmarried. We found that 31.6% of the cohort received state-granted subsidies, of which 77% were in the form of early retirement pension. Regarding educational status, 28.1% of the EDS cohort had completed primary education (⩽10th grade) as their highest educational level, while 71.9% had completed a higher level. During the observation period, 42 patients died, with a mean ( s . d .) age at death of 53.6 (21.7) years. This study confirmed a small national prevalence of patients diagnosed with EDS and showed that the majority of patients diagnosed are female. The EDS cohort had a lower educational level, mean age and life expectancy compared with the background population and showed a predisposition for receiving state-granted subsidies. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA.

PubMed

Ritelli, Marco; Morlino, Silvia; Giacopuzzi, Edoardo; Carini, Giulia; Cinquina, Valeria; Chiarelli, Nicola; Majore, Silvia; Colombi, Marina; Castori, Marco

2017-01-01

Filamin A is an X-linked, ubiquitous actin-binding protein whose mutations are associated to multiple disorders with limited genotype-phenotype correlations. While gain-of-function mutations cause various bone dysplasias, loss-of-function variants are the most common cause of periventricular nodular heterotopias with variable soft connective tissue involvement, as well as X-linked cardiac valvular dystrophy (XCVD). The term "Ehlers-Danlos syndrome (EDS) with periventricular heterotopias" has been used in females with neurological, cardiovascular, integument and joint manifestations, but this nosology is still a matter of debate. We report the clinical and molecular update of an Italian family with an X-linked recessive soft connective tissue disorder and which was described, in 1975, as the first example of EDS type V of the Berlin nosology. The cutaneous phenotype of the index patient was close to classical EDS and all males died for a lethal cardiac valvular dystrophy. Whole exome sequencing identified the novel c.1829-1G>C splice variation in FLNA in two affected cousins. The nucleotide change was predicted to abolish the canonical splice acceptor site of exon 13 and to activate a cryptic acceptor site 15 bp downstream, leading to in frame deletion of five amino acid residues (p.Phe611_Gly615del). The predicted in frame deletion clusters with all the mutations previously identified in XCVD and falls within the N-terminus rod 1 domain of filamin A. Our findings expand the male-specific phenotype of FLNA mutations that now includes classical-like EDS with lethal cardiac valvular dystrophy, and offer further insights for the genotype-phenotype correlations within this spectrum. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

PubMed

Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

2016-09-01

Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between diverticular disease and Ehlers-Danlos syndrome: a 13-year nationwide population-based cohort study.

PubMed

Leganger, Julie; Søborg, Marie-Louise Kulas; Mortensen, Laura Quitzau; Gregersen, Rasmus; Rosenberg, Jacob; Burcharth, Jakob

2016-12-01

The aim of this study was to examine occurrence and consequences of diverticular disease in patients with Ehlers-Danlos syndrome (EDS) compared with a matched cohort. This nationwide population-based cohort study was conducted using data from medical registers in Denmark from year 2000 to 2012. The EDS cohort was identified using the specific diagnosis code for EDS and was randomly matched in a ratio of 1:20 by sex and date of birth (±1 year) with persons from the Danish general population. The occurrence of diverticular disease and the clinical characteristics of the initial diverticular event were compared between the EDS cohort and the comparison cohort. The first admission with diverticulitis was identified, and severity of diverticulitis, treatment, colonoscopies, length of stay, and 30-day mortality were investigated. We identified 1336 patients with EDS and matched a control cohort of 26,720 patients. The occurrence of diverticular disease in the EDS cohort (2.0 %) and the comparison cohort (0.68 %) differed significantly (p < 0.001). At the first diverticular event, the majority of patients were women (85 % for EDS and 87 % for the comparison cohort). Mean age, localization, and type of contact did not differ significantly. Admission with diverticulitis (1.0 % for EDS and 0.34 % for the comparison cohort) differed significantly (p < 0.001). We found no significant difference in severity of diverticulitis, treatment, length of stay, or 30-day mortality between the EDS and the comparison cohorts. Patients with EDS had an increased occurrence of overall diverticular events and admissions with diverticulitis compared with the general population.

An outcomes analysis of patients undergoing body contouring surgery after massive weight loss.

PubMed

Shermak, Michele A; Chang, David; Magnuson, Thomas H; Schweitzer, Michael A

2006-09-15

Although published reports about technical management of massive weight loss patients are beginning to appear, risk factors for complications following body contouring operations are not known. A retrospective analysis of massive weight loss patients who had body contouring operations between March of 1998 and October of 2004 was performed. Demographic and surgical factors were analyzed. Outcome measures included seroma, wound dehiscence, thromboembolic complications, blood transfusion after surgery, and extended lengths of stay (>2 days). A total of 139 patients were analyzed; 82.7 percent of them were female; mean age was 41 years. On multiple logistic regression, male gender was associated with significant risks for wound dehiscence (odds ratio, 6.4; p = 0.01). There were also trends toward increased risk for wound dehiscence with hypothyroidism (odds ratio, 4.3; p = 0.06) and Ehlers-Danlos syndrome (odds ratio, 18.7; p = 0.05). In terms of risk of blood transfusion, asthma and having three or more procedures were the two variables that emerged with significant association (odds ratio, 16.8 and 13.7, respectively; both p < 0.01). Increased length of stay to greater than 2 days was also significantly associated with having three or more procedures (odds ratio, 4.72; p < 0.01). Male gender, hypothyroidism, and Ehlers-Danlos syndrome may be risk factors for wound dehiscence following body contour operations for massive weight loss. Asthma may be a marker of poor general health status, and asthmatic patients are at increased risk for requiring blood transfusions. Having three or more procedures is associated with an increased risk of blood transfusion and increased length of stay.

Primary extracranial vertebral artery aneurysms.

PubMed

Morasch, Mark D; Phade, Sachin V; Naughton, Peter; Garcia-Toca, Manuel; Escobar, Guillermo; Berguer, Ramon

2013-05-01

Extracranial vertebral artery aneurysms are uncommon and are usually associated with trauma or dissection. Primary cervical vertebral aneurysms are even rarer and are not well described. The presentation and natural history are unknown and operative management can be difficult. Accessing aneurysms at the skull base can be difficult and, because the frail arteries are often afflicted with connective tissue abnormalities, direct repair can be particularly challenging. We describe the presentation and surgical management of patients with primary extracranial vertebral artery aneurysms. In this study we performed a retrospective, multi-institutional review of patients with primary aneurysms within the extracranial vertebral artery. Between January 2000 and January 2011, 7 patients, aged 12-56 years, were noted to have 9 primary extracranial vertebral artery aneurysms. All had underlying connective tissue or another hereditary disorder, including Ehler-Danlos syndrome (n=3), Marfan's disease (n=2), neurofibromatosis (n=1), and an unspecified connective tissue abnormality (n=1). Eight of 9 aneurysms were managed operatively, including an attempted bypass that ultimately required vertebral ligation; the contralateral aneurysm on this patient has not been treated. Open interventions included vertebral bypass with vein, external carotid autograft, and vertebral transposition to the internal carotid artery. Special techniques were used for handling the anastomoses in patients with Ehler-Danlos syndrome. Although endovascular exclusion was not performed in isolation, 2 hybrid procedures were performed. There were no instances of perioperative stroke or death. Primary extracranial vertebral artery aneurysms are rare and occur in patients with hereditary disorders. Operative intervention is warranted in symptomatic patients. Exclusion and reconstruction may be performed with open and hybrid techniques with low morbidity and mortality. Copyright © 2013 Elsevier Inc. All rights reserved.

Gait pattern in two rare genetic conditions characterized by muscular hypotonia: Ehlers-Danlos and Prader-Willi syndrome.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of 20 normal-weight controls (CG). The results showed that PWS patients walked with longer stance duration and reduced velocity than EDS, close to CG. Both EDS and PWS showed reduced anterior step length than CG. EDS kinematics evidenced a physiological position at proximal joints (pelvis and hip joint) while some deficits were displayed at knee (reduced flexion in swing phase) and ankle level (plantar flexed position in stance and reduced dorsal flexion in swing). PWS showed a forward tilted pelvis in the sagittal plane, excessive hip flexion during the whole gait cycle and an increased hip movement in the frontal plane. Their knees were flexed at initial contact with reduced range of motion while ankle joints showed a plantar flexed position during stance. No differences were found in terms of ankle kinetics and joint stiffness. Our data showed that EDS and PWS patients were characterized by a different gait strategy: PWS showed functional limitations at every level of the lower limb joints, whereas in EDS limitations, greater than PWS, were reported mainly at the distal joints. PWS patients should be encouraged to walk for its positive impact on muscle mass and strength and energy balance. For EDS patients the rehabilitation program should be focused on ankle strategy improvement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1.

PubMed

Monroe, Glen R; Harakalova, Magdalena; van der Crabben, Saskia N; Majoor-Krakauer, Danielle; Bertoli-Avella, Aida M; Moll, Frans L; Oranen, Björn I; Dooijes, Dennis; Vink, Aryan; Knoers, Nine V; Maugeri, Alessandra; Pals, Gerard; Nijman, Isaac J; van Haaften, Gijs; Baas, Annette F

2015-06-01

Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes and associated genes. Vascular EDS, caused by heterozygous mutations in the COL3A1 gene, is characterized by fragile vasculature with a high risk of catastrophic vascular events at a young age. Classic EDS, caused by heterozygous mutations in the COL5A1 or COL5A2 genes, is characterized by fragile, hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated classic EDS patients with a confirmed COL5A1 mutation has been reported. We describe familial occurrence of a phenotype resembling vascular EDS in a mother and her two sons, who all died at an early age from arterial ruptures. Diagnostic Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1, COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed using a next-generation sequencing approach targeting 554 genes linked to vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was detected, resulting in an essential glycine substitution at the C-terminal end of the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was also present in DNA isolated from autopsy material of the index's brother. No material was available from the mother, but the mutation was excluded in her parents, siblings and in the father of her sons, suggesting that the COL5A1 mutation occurred in the mother's genome de novo. In conclusion, we report familial occurrence of lethal arterial events caused by a COL5A1 mutation. © 2015 Wiley Periodicals, Inc.

[Multiple bladder diverticula caused by occipital horn syndrome].

PubMed

Legros, L; Revencu, N; Nassogne, M-C; Wese, F-X; Feyaerts, A

2015-11-01

We report on the case of a child who presented with recurrent, multiple, and voluminous bladder diverticula. Bladder diverticula are defined as a herniation of the mucosa through the bladder muscle or the detrusor. Causes are numerous and diverticula can be classified into primary congenital diverticula (para-ureteral - or Hutch diverticula - and posterolateral diverticula); secondary diverticula (resulting from chronic mechanical obstruction or from neurological disease; and diverticula secondary to connective tissue or muscle fragility. The latter is seen in disease entities such as prune belly syndrome, Ehlers-Danlos syndrome, cutis laxa syndrome, OHS (occipital horn syndrome), Menkes disease, and Williams-Beuren syndrome. In this patient, the cause of these diverticula was OHS, a genetic, recessive X-chromosome-linked syndrome, responsible for abnormal tissue caused by a disorder in copper metabolism. This case reminds us of the importance of pushing the diagnostic workup when presented with multiple and/or large bladder diverticula, and in particular to search for rare malformation syndromes after exclusion of an obstacle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Neurovascular manifestations of connective-tissue diseases: A review

PubMed Central

Kim, Sarasa T; Lanzino, Giuseppe; Kallmes, David F

2016-01-01

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases. PMID:27511817

Tratamento endovascular de aneurisma de tronco braquiocefálico em paciente com síndrome de Ehlers-Danlos tipo IV

PubMed Central

Belczak, Sergio Quilici; Klajner, Rafael Kogan; Ogawa, Lara Cote; Lucato, Laís Leite; Zeque, Bruna Stecca; de Macedo, Felipe Basso; da Silva, Ingredy Tavares; Atihe, Luís Felipe

2016-01-01

Resumo A síndrome de Ehlers-Danlos é uma doença genética que acarreta alteração na síntese de colágeno, causando extrema fragilidade do tecido conjuntivo. Tal fragilidade predispõe a uma série de doenças vasculares, como dissecções, aneurismas e pseudoaneurismas. Os autores relatam o histórico de um indivíduo de 19 anos com aneurisma de tronco braquiocefálico que foi submetido ao tratamento endovascular com implante de stents revestidos. O caso evoluiu com complicação do sítio de punção, que também foi tratada em caráter de emergência pela técnica endovascular com o implante de stent revestido.

Familial Aggregation of Chiari Malformation: Presentation, Pedigree, and Review of the Literature.

PubMed

Nagy, Laszlo; Mobley, James; Ray, Coby

2016-01-01

This article reports the largest familial aggregation of Chiari malformation in a single family to date as reported in the literature. This study is a retrospective case series of a family of whom five individuals have a confirmed case of Chiari malformation and three additional individuals have Chiari signs and symptoms. This contribution further supports the implication of genetics in the transmission of Chiari malformation. The family reported in this study also has a significant incidence of Ehlers-Danlos. Three sisters, including a set of twins, presented with confirmed cases of Chiari malformation and four of the five children of the twin sisters presented with confirmed or suspected Chiari malformation. Of note, the non-twin sister has three children who are unaffected. This report provides further evidence for a shared loci between the Chiari malformation and Ehlers-Danlos.

Musculocontractural Ehlers-Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin.

PubMed

Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders; Pera, Edgar M

2016-06-01

Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers-Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial-mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. © 2016. Published by The Company of Biologists Ltd.

The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers–Danlos syndrome

PubMed Central

Frank, Michael; Albuisson, Juliette; Ranque, Brigitte; Golmard, Lisa; Mazzella, Jean-Michael; Bal-Theoleyre, Laurence; Fauret, Anne-Laure; Mirault, Tristan; Denarié, Nicolas; Mousseaux, Elie; Boutouyrie, Pierre; Fiessinger, Jean-Noël; Emmerich, Joseph; Messas, Emmanuel; Jeunemaitre, Xavier

2015-01-01

Vascular Ehlers–Danlos syndrome (vEDS) is a rare and severe autosomal dominant disorder caused by variants at the COL3A1 gene. Clinical characteristics and course of disease of 215 molecularly proven patients (146 index cases and 69 relatives) were analysed. We found 126 distincts variants that were divided into five groups: (1) Glycine substitutions (n=71), (2) splice-site and in-frame insertions–deletions (n=36), (3) variants leading to haplo-insufficiency (n=7), (4) non-glycine missense variants within the triple helix (n=4 variants), and (5) non-glycine missense variants or in-frame insertions–deletions, in the N- or C-terminal part of the protein (n=8). Overall, our cohort confirmed the severity of the disease with a median age at first complication of 29 years (IQR 22–39), the most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1 were significantly more severe than groups 3–5, with extreme median ages at first major complication of 23–47 years. Patients of groups 3–5 had a less typical phenotype and remarkably absence of digestive events. The distribution of glycine-replacing amino acids was strongly biased towards more destabilizing residues of the collagen assembly. Thus the natural course of vEDS and the clinical phenotype of patients are influenced by the type of COL3A1 variant. This study also confirms that patients with variants located in the C- and N-termini or leading to haplo-insufficiency have milder course of the disease and less prevalent diagnostic criteria. These findings may help refine diagnostic strategy, genetic counselling and clinical care. PMID:25758994

Prosthetic Valve Endocarditis Caused by Bartonella henselae: A Case Report of Molecular Diagnostics Informing Nonsurgical Management

PubMed Central

Bartley, Patricia; Angelakis, Emmanouil; Raoult, Didier; Sampath, Rangarajan; Bonomo, Robert A.

2016-01-01

Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result. This, in turn, permitted early initiation of pathogen-directed therapy and subsequent successful medical management of B henselae prosthetic valve endocarditis and aortic graft infection. PMID:27844027

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

Okada, Takuya, E-mail: okabone@gmail.com; Frank, Michael, E-mail: michael.frank@egp.aphp.fr; Pellerin, Olivier, E-mail: olivier@pellerin.as

PurposeTo evaluate the safety and efficacy of transarterial embolization of life-threatening arterial rupture in patients with vascular Ehlers–Danlos syndrome (vEDS) in a single tertiary referral center.MethodsWe retrospectively analyzed transarterial embolization for vEDS performed at our institution from 2000 to 2012. The indication of embolization was spontaneous arterial rupture or pseudoaneurysm with acute bleeding. All interventions used a percutaneous approach through a 5F or less introducer sheath. Embolic agents were microcoils and glue in 3 procedures, glue alone in 2, and microcoils alone in 2.ResultsFive consecutive vEDS patients were treated by 7 embolization procedures (4 women, mean age 29.8 years). All proceduresmore » were successfully performed. Two patients required a second procedure for newly arterial lesions at a different site from the first procedure. Four of the five patients were still alive after a mean follow-up of 19.4 (range 1–74.7) months. One patient died of multiple organ failure 2 days after procedure. Minor procedural complications were observed in 3 procedures (43 %), all directly managed during the same session. Remote arterial lesions occurred after 3 procedures (43 %); one underwent a second embolization, and the other 2 were observed conservatively. Puncture site complication was observed in only one procedure (14 %).ConclusionEmbolization for vEDS is a safe and effective method to manage life-threatening arterial rupture.« less

Rare Autosomal Recessive Cardiac Valvular Form of Ehlers-Danlos Syndrome Results from Mutations in the COL1A2 Gene That Activate the Nonsense-Mediated RNA Decay Pathway

PubMed Central

Schwarze, Ulrike; Hata, Ryu-Ichiro; McKusick, Victor A.; Shinkai, Hiroshi; Hoyme, H. Eugene; Pyeritz, Reed E.; Byers, Peter H.

2004-01-01

Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate, or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility, and cardiac valvular defects); in two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon, and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of proα2(I) chains has the surprising effect of producing cardiac valvular disease without bone involvement. PMID:15077201

Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway.

PubMed

Schwarze, Ulrike; Hata, Ryu-Ichiro; McKusick, Victor A; Shinkai, Hiroshi; Hoyme, H Eugene; Pyeritz, Reed E; Byers, Peter H

2004-05-01

Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate, or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility, and cardiac valvular defects); in two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon, and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of pro alpha 2(I) chains has the surprising effect of producing cardiac valvular disease without bone involvement.

Dermal fibroblast-to-myofibroblast transition sustained by αvß3 integrin-ILK-Snail1/Slug signaling is a common feature for hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders.

PubMed

Zoppi, Nicoletta; Chiarelli, Nicola; Binetti, Silvia; Ritelli, Marco; Colombi, Marina

2018-04-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with unknown molecular basis mainly characterized by generalized joint hypermobility, joint instability complications, and minor skin changes. The phenotypic spectrum is broad and includes multiple associated symptoms shared with chronic inflammatory systemic diseases. The stricter criteria defined in the 2017 EDS nosology leave without an identity many individuals with symptomatic joint hypermobility and/or features of hEDS; for these patients, the term Hypermobility Spectrum Disorders (HSD) was introduced. We previously reported that in vitro cultured hEDS and HSD patients' skin fibroblasts show a disarray of several extracellular matrix (ECM) components and dysregulated expression of genes involved in connective tissue homeostasis and inflammatory/pain/immune responses. Herein, we report that hEDS and HSD skin fibroblasts exhibit in vitro a similar myofibroblast-like phenotype characterized by the organization of α-smooth muscle actin cytoskeleton, expression of OB-cadherin/cadherin-11, enhanced migratory capability associated with augmented levels of the ECM-degrading metalloproteinase-9, and altered expression of the inflammation mediators CCN1/CYR61 and CCN2/CTGF. We demonstrate that in hEDS and HSD cells this fibroblast-to-myofibroblast transition is triggered by a signal transduction pathway that involves αvβ3 integrin-ILK complexes, organized in focal adhesions, and the Snail1/Slug transcription factor, thus providing insights into the molecular mechanisms related to the pathophysiology of these protean disorders. The indistinguishable phenotype identified in hEDS and HSD cells resembles an inflammatory-like condition, which correlates well with the systemic phenotype of patients, and suggests that these multisystemic disorders might be part of a phenotypic continuum rather than representing distinct clinical entities. Copyright © 2018 Elsevier B.V. All rights reserved.

Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome.

PubMed

De Wandele, Inge; Rombaut, Lies; De Backer, Tine; Peersman, Wim; Da Silva, Hellen; De Mits, Sophie; De Paepe, Anne; Calders, Patrick; Malfait, Fransiska

2016-08-01

To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT). Eighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalized hypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale. Patients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63) vs controls: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16) vs controls: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity. OI is an important determinant of fatigue in EDS-HT. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry.

PubMed

Dolan, A L; Arden, N K; Grahame, R; Spector, T D

1998-10-01

Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature. This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameters compared with age and sex matched controls. 23 cases of EDS (mean (SD) age 38.5 (15.5)) were compared with 23 controls (mean age 37.8 (14.5)). A significant reduction in bone density measured by dual energy x ray absorptiometry was found at the neck of femur by 0.9 SD, p = 0.05, and lumbar spine by 0.74 SD, p = 0.02. At the calcaneum, broad band ultrasound attenuation and speed of sound were significantly reduced compared with controls by 0.95 SD (p = 0.004) and 0.49 SD (p = 0.004) for broad band ultrasound attenuation and speed of sound respectively. Broad band ultrasound attenuation and speed of sound remained significantly reduced after adjusting for bone mineral density (BMD). After adjusting for functional status (HAQ), age and sex, hypermobility was inversely correlated with broad band ultrasound attenuation and SOS, but not BMD at hip or spine. Previous fracture was 10 times more common in EDS (p < 0.001), with 86.9% of patients reporting a total of 47 low impact fractures, compared with 8.7% of controls. This study has identified a tendency of EDS patients to fracture, have low bone mass and abnormal bone structure. The aetiology is likely to be multifactorial, with an inherited structural element, accentuated by immobility or reduced exercise. This is one of the first clinical studies to suggest ultrasound can detect structural differences in bone, independent of dual energy x ray absorptiometry.

Sudden onset of artery dissection in a 32-year-old woman with vascular Ehlers-Danlos syndrome due to psychological stress of her mother's death: a case series.

PubMed

Shimoyama, Yuichiro; Umegaki, Osamu; Agui, Tomoyuki; Kadono, Noriko; Minami, Toshiaki

2017-01-01

Patients with vascular Ehlers-Danlos syndrome (EDS) are susceptible to significant vascular complications, such as aortic and visceral arterial ruptures, aneurysms, and dissection. We describe a case of repeated bleeding in a 57-year-old woman and a case of sudden onset of artery dissection in her daughter, both of whom were previously diagnosed with vascular EDS and managed at our institution. A 57-year-old woman was admitted to our emergency department due to sudden onset of left low back pain. Her past history included vascular EDS. An urgent abdominal computed tomography (CT) scan revealed a left-sided retroperitoneal hematoma and left external iliac artery dissection. Stent graft repair was performed. Five hours postoperatively, cardiac arrest occurred and resuscitation attempts failed. The 32-year-old daughter with genetically diagnosed vascular EDS was notified of the death of her mother during the customary end-of-life conference. Six hours after her mother's death, she was admitted to our emergency department due to sudden onset of left low back pain. On examination, she was not in hypovolemic shock, and weak pulses were palpable in the bilateral dorsalis pedis. An urgent abdominal CT scan revealed a right-sided retroperitoneal hematoma around the right external iliac artery and left external iliac artery dissection. She was admitted to the intensive care unit and underwent conservative therapy consisting of bed rest and antihypertensive therapy with nicardipine. She developed no further vascular complications requiring surgical intervention and was discharged on the 21st hospital day. Vascular rupture can be fatal in patients with vascular EDS. This report underscores the importance of strategic management of vascular complications to prevent rupture, and the importance of psychological care for the bereaved family given the hereditary nature of vascular EDS.

Current Evidence and Insights about Genetics in Thoracic Aorta Disease

PubMed Central

Muneretto, Claudio

2013-01-01

Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve. PMID:24453931

Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene.

PubMed

Walker, L C; Teebi, A S; Marini, J C; De Paepe, A; Malfait, F; Atsawasuwan, P; Yamauchi, M; Yeowell, H N

2004-12-01

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2.

Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

PubMed Central

Zoppi, Nicoletta; Chiarelli, Nicola; Ritelli, Marco; Colombi, Marina

2018-01-01

The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field. PMID:29587413

[Peripheral artery disease in patients younger than 50 years old: Which etiology?].

PubMed

Cotard, S; Nouni, A; Jaquinandi, V; Gladu, G; Kaladji, A; Mahé, G

2016-09-01

Peripheral arterial disease (PAD) encompasses disease of all arteries of the body except the coronary arteries. The main etiology whatever the patient's age is atherosclerosis. Different etiologies can induce PAD especially when patients are younger than 50 years old and have no cardiovascular risk factors (smoking, hypertension, diabetes…). PAD that appears before 50 years old can be named juvenile PAD (JPAD) although there is no consensus about the definition. The aim of this work is to present the different etiologies of JPAD according to their hereditary, acquired or mixed origins. The following hereditary causes are addressed: Marfan syndrome, Ehlers-Danlos syndrome, homocystinuria, pseudoxanthoma elasticum, osteogenesis imperfecta "mid-aortic" syndrome. Among the acquired etiologies, inflammatory JPADs without extravascular signs such as atherosclerosis and Buerger's disease, inflammatory JPADs with extravascular signs as Takayasu's disease, Behçet's disease and Cogan's syndrome, JPADs like aortitis, embolic JPADs, iatrogenic JPADs, and mechanical or traumatic JPADs are described. Finally, mixed origins as thrombotic disease and fibromuscular dysplasia are presented. This work will assist clinicians in the diagnosis of JPAD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Vasculitis mimics.

PubMed

Molloy, Eamonn S; Langford, Carol A

2008-01-01

There are many disorders that may closely resemble the clinical, radiologic and/or pathologic features of the primary vasculitides. In this review, we focus on recently described and under-recognized syndromes that may mimic vasculitis. Hereditary causes of large-artery aneurysms such as Marfan's syndrome have long been recognized; recent years have seen a greater understanding of the genetics of Marfan's and other such disorders, including Loeys-Dietz syndrome and Ehler-Danlos syndrome type IV. Under-recognized mimics of medium-vessel vasculitis include segmental arterial mediolysis and Grange syndrome. A large number of entities can mimic small-vessel vasculitis. Recent descriptions of antibodies to human neutrophil elastase have provided insight into the occurrence of antineutrophil cytoplasmic antibodies in cocaine-induced midline destructive lesions. The differential diagnosis of cerebral vasculitis can be particularly difficult. Reversible cerebral vasoconstriction syndromes represent an important class of entities that can readily mimic cerebral vasculitis but have a very different management approach and outcome. The diagnosis of vasculitis requires careful assessment of all available clinical, laboratory, radiologic and pathologic information, and consideration of many competing differential diagnoses. Awareness of noninflammatory mimics of vasculitis is essential to avoid unnecessary and potentially harmful treatment with immunosuppressive agents.

Direct carotid cavernous fistula after submucous resection of the nasal septum.

PubMed

Bizri, A R; al-Ajam, M; Zaytoun, G; al-Kutoubi, A

2000-01-01

A carotid cavernous fistula (CCF) is an abnormal arteriovenous anastomosis between the carotid artery and the cavernous sinus. Etiologies of this condition reported in the literature so far include facial trauma, rupture of an intracavernous aneurysm of the carotid artery, Ehler-Danlos syndrome and fibromuscular dysplasia of the cerebral arteries. Such fistulae were reported as complications of rhinoplasty, transsphenoidal surgery, embolization of cavernous sinus meningioma, and rhinocerebral mucormycosis. CCF may also occur spontaneously in children or as a congenital malformation. However, to our knowledge, submucous resection of the nasal septum has not been reported before to cause direct carotid-cavernous fistula. CT and angiographic findings are presented and a review of the literature for reported causes of CCF is made as well as a brief discussion of the possible pathophysiology.

Vascular Ehlers–Danlos Syndrome in siblings with biallelic COL3A1 sequence variants and marked clinical variability in the extended family

PubMed Central

Jørgensen, Agnete; Fagerheim, Toril; Rand-Hendriksen, Svend; Lunde, Per I; Vorren, Torgrim O; Pepin, Melanie G; Leistritz, Dru F; Byers, Peter H

2015-01-01

Vascular Ehlers–Danlos Syndrome (vEDS), also known as EDS type IV, is considered to be an autosomal dominant disorder caused by sequence variants in COL3A1, which encodes the chains of type III procollagen. We identified a family in which there was marked clinical variation with the earliest death due to extensive aortic dissection at age 15 years and other family members in their eighties with no complications. The proband was born with right-sided clubfoot but was otherwise healthy until he died unexpectedly at 15 years. His sister, in addition to signs consistent with vascular EDS, had bilateral frontal and parietal polymicrogyria. The proband and his sister each had two COL3A1 sequence variants, c.1786C>T, p.(Arg596*) in exon 26 and c.3851G>A, p.(Gly1284Glu) in exon 50 on different alleles. Cells from the compound heterozygote produced a reduced amount of type III procollagen, all the chains of which had abnormal electrophoretic mobility. Biallelic sequence variants have a significantly worse outcome than heterozygous variants for either null mutations or missense mutations, and frontoparietal polymicrogyria may be an added phenotype feature. This genetic constellation provides a very rare explanation for marked intrafamilial clinical variation due to sequence variants in COL3A1. PMID:25205403

Positional Magnetic Resonance Imaging for People With Ehlers-Danlos Syndrome or Suspected Craniovertebral or Cervical Spine Abnormalities: An Evidence-Based Analysis

PubMed Central

2015-01-01

Background Ehlers-Danlos syndrome (EDS) is an inherited disorder affecting the connective tissue. EDS can manifest with symptoms attributable to the spine or craniovertebral junction (CVJ). In addition to EDS, numerous congenital, developmental, or acquired disorders can increase ligamentous laxity in the CVJ and cervical spine. Resulting abnormalities can lead to morbidity and serious neurologic complications. Appropriate imaging and diagnosis is needed to determine patient management and need for complex surgery. Some spinal abnormalities cause symptoms or are more pronounced while patients sit, stand, or perform specific movements. Positional magnetic resonance imaging (pMRI) allows imaging of the spine or CVJ with patients in upright, weight-bearing positions and can be combined with dynamic maneuvers, such as flexion, extension, or rotation. Imaging in these positions could allow diagnosticians to better detect spinal or CVJ abnormalities than recumbent MRI or even a combination of other available imaging modalities might allow. Objectives To determine the diagnostic impact and clinical utility of pMRI for the assessment of (a) craniovertebral or spinal abnormalities among people with EDS and (b) major craniovertebral or cervical spine abnormalities among symptomatic people. Data Sources A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, and EBM Reviews, for studies published from January 1, 1998, to September 28, 2014. Review Methods Studies comparing pMRI to recumbent MRI or other available imaging modalities for diagnosis and management of spinal or CVJ abnormalities were reviewed. All studies of spinal or CVJ imaging in people with EDS were included as well as studies among people with suspected major CVJ or cervical spine abnormalities (cervical or craniovertebral spine instability, basilar invagination, cranial settling, cervical stenosis, spinal cord compression, Chiari malformation). Results No studies were identified that met the inclusion criteria. Conclusions We did not identify any evidence that assessed the diagnostic impact or clinical utility of pMRI for (a) craniovertebral or spinal abnormalities among people with EDS or (b) major craniovertebral or cervical spine abnormalities among symptomatic people relative to currently available diagnostic modalities. PMID:26366238

Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review.

PubMed

Colombi, Marina; Dordoni, Chiara; Venturini, Marina; Zanca, Arianna; Calzavara-Pinton, Piergiacomo; Ritelli, Marco

2017-02-01

Classical Ehlers-Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in COL5A1 and COL5A2 encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C>T mutation in COL1A1 that results in an uncommon substitution of a non-glycine residue in one Gly-Xaa-Yaa repeat of the pro-α1(I)-chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N-propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as "(classic) vascular-like" EDS patients. Herein, we describe a three-generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) COL1A1 mutation from those with COL5A1 and COL5A2 defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in COL1A1 should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Ehlers-Danlos Syndrome.

PubMed

Kim, Sarasa T; Cloft, Harry; Flemming, Kelly D; Kallmes, David F; Lanzino, Giuseppe; Brinjikji, Waleed

2017-08-01

Small studies have suggested that Ehlers-Danlos syndrome (EDS) is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of EDS is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). Using the 2000-2012 NIS, we performed a case-control study matching cases of EDS to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups was compared, and multivariate logistic regression was used to adjust for suspected comorbidities. Between 2000 and 2012, there were a total of 9067 discharges carrying a diagnosis of EDS. On univariate analysis, patients with EDS were more likely to be hospitalized for carotid dissection (.2% versus .01%, odds ratio [OR] = 18.0, confidence interval [CI] = 2.41-135.12, P < .0001), vertebral dissection (.1% versus 0%, P = .008), cervical artery aneurysm (.1% versus .01%, OR = 9.01, CI = 1.14-71.11, P < .0001), cerebral aneurysm (.4% versus .09%, OR = 4.89, CI = 2.28-10.47, P < .0001), and cerebrovascular malformation (.1% versus .02%, OR = 5, CI = 1.10-22.85, P = .021), compared to the controls. On multivariate analysis adjusted for age, race, and comorbidities, EDS patients had significantly higher odds of carotid dissection (OR = 15.02, CI = 3.08-270.87, P < .0001), vertebral dissection (OR = 2406539.5, P = .0037), cervical artery aneurysm (OR = 11.75, CI = 2.11-220.71, P = .0026), cerebral aneurysm (OR = 5.59, CI = 2.69-13.18, P < .0001), and cerebrovascular malformation (OR = 4.67, CI = 1.20-30.87, P = .0243). Carotid and vertebral dissections, cervical and cerebral aneurysms, as well as other cerebrovascular malformations are more common in hospitalized patients with EDS compared to controls. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chronic bilateral dislocation of temporomandibular joint.

PubMed

Shakya, S; Ongole, R; Sumanth, K N; Denny, C E

2010-01-01

Dislocation of the condyle of the mandible is a common condition that may occur in an acute or chronic form. It is characterised by inability to close the mouth with or without pain. Dislocation has to be differentiated from subluxation which is a self reducible condition. Dislocation can occur in any direction with anterior dislocation being the commonest one. Various predisposing factors have been associated with dislocation like muscle fatigue and spasm, the defect in the bony surface like shallow articular eminence, and laxity of the capsular ligament. People with defect in collagen synthesis like Ehler Danlos syndrome, Marfan syndrome are said to be genetically predisposed to this condition. Various treatment modalities have been used ranging from conservative techniques to surgical methods. Acute dislocations can be reduced manually or with conservative approach and recurrent and chronic cases can be reduced by surgical intervention. Though the dislocation in our case was 4 months a simple manual reduction proved to be successful. We believe that manual reduction can be attempted as first line of treatment prior to surgical intervention.

The real malady of Marcel Proust and what it reveals about diagnostic errors in medicine.

PubMed

Douglas, Yellowlees

2016-05-01

Marcel Proust, author of À La Recherche du Temps Perdu, was considered a hypochondriac not only by the numerous specialists he consulted during his lifetime but also by every literary critic who ventured an opinion on his health, among them several clinicians. However, Proust's voluminous correspondence, as detailed in its attention to his every symptom as his novel, provides valuable clues to Proust's real, organic, and rare illness. Proust, in fact, was not only genuinely ill but far sicker than he even he believed, most likely suffering from the vascular subtype of Ehlers-Danlos Syndrome. Ironically, Proust's own doctors and his clinician-critics replicated the same kinds of diagnostic errors clinicians still routinely make today, shedding light on the plight of patients with rare illnesses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factitious aortic dissection leading to thoracotomy in a 20-year-old man.

PubMed

Chambers, Elise; Yager, Joel; Apfeldorf, William; Camps-Romero, Eduardo

2007-01-01

A 20-year-old man presented to an emergency department with dramatic, sudden-onset, tearing chest pain. He also claimed to have been previously diagnosed with Ehler-Danlos syndrome and a previous Type I aortic dissection (intimal tear of ascending aorta), rapidly increasing his treating physician's suspicion of an emergent aortic dissection. The patient was quickly transferred to a large university hospital, where he underwent a median sternotomy and thoracotomy, with no aortic pathology found on operation and biopsy. After the patient's postoperative recovery, he was treated at a mental health facility, where he remained ambivalent about his psychiatric condition and did not respond well to treatment. This case report describes a unique case of factitious disorder that led to a serious operative intervention and subsequent psychiatric care and assesses factors that might have contributed to his hospital course.

Williams-Beuren's Syndrome: A Case Report.

PubMed

Zamani, Hassan; Babazadeh, Kazem; Fattahi, Saeid; Mokhtari-Esbuie, Farzad

2012-01-01

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome. Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem.

Syndromes with supernumerary teeth.

PubMed

Lubinsky, Mark; Kantaputra, Piranit Nik

2016-10-01

While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein-Taybi syndrome; Nance-Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg-Pakistani syndrome (craniosynostosis and dental anomalies), and insulin-resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann-Streiff syndrome, Fabry disease, Ehlers-Danlos syndrome, Apert and Crouzon syndromes, Zimmermann-Laband syndrome, and Ellis-van Creveld syndrome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Lin, I.C.; Ko, S.F.; Shieh, C.S.

Ehlers-Danlos syndrome (EDS) includes a group of connective tissue disorders with abnormal collagen metabolism and a diverse clinical spectrum. We report two siblings with EDS who both presented with congenital diaphragmatic hernia (CDH). The elder sister suffered from recurrent diaphragmatic hernia twice and EDS was overlooked initially. Echocardiography as well as contrast-enhanced magnetic resonance angiography (MRA) showed dilatation of the pulmonary artery, and marked elongation and tortuosity of the aorta and its branches. A diagnosis of EDS was eventually established when these findings were coupled with the clinical features of hyperelastic skin. Her younger brother also had similar features. Thismore » report emphasizes that EDS may present as CDH in a small child which could easily be overlooked. Without appropriate surgery, diaphragmatic hernia might occur. Echocardiographic screening is recommended in patients with CDH. Contrast-enhanced MRA can be helpful in delineation of abnormally tortuous aortic great vessels that are an important clue to the early diagnosis of EDS.« less

[Systemic lupus erythematosus and pregnancy].

PubMed

Basheva, S; Nikolov, A; Stoilov, R; Stoilov, N

2012-01-01

Connective-tissue disorders, also referred to as collagen-vascular disorders, are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. Lupus erythematosus (LE) is the main and most important disease in the group of systemic connective tissue diseases. It is heterogeneous, multiple organs autoimmune inflammatory disease with complex pathogenesis, which is the result of interaction between the susceptible genes and environmental factors that lead to abnormal immune response. In this review will consider: its incidence, pathogenesis, clinical forms and clinical features and diagnosis set based on generally accepted clinical criteria developed by the American College of Rheumatology (ACR), the course of pregnancy in patients suffering from LE, the most common complications of LE during pregnancy and antiphospholipid syndrome as part of LE.

Williams-Beuren's Syndrome: A Case Report

PubMed Central

Zamani, Hassan; Babazadeh, Kazem; Fattahi, Saeid; Mokhtari-Esbuie, Farzad

2012-01-01

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome. Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem. PMID:22927862

Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

PubMed

Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

2013-04-01

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

Joint hypermobility and headache: the glue that binds the two together--part 2.

PubMed

Martin, Vincent T; Neilson, Derek

2014-09-01

Past studies have reported that connective tissue disorders (CTDs) are more common in patients with specific types of headache disorders. The objectives of this study are (1) to review and critique the clinical studies reporting an association between joint hypermobility, CTDs and headache and (2) to postulate mechanisms though which CTDs might predispose to headache disorders. PubMed was searched for relevant articles with search terms that included joint hypermobility, Ehlers-Danlos syndrome, Marfan syndrome, and specific headache disorders. A narrative review was performed of these articles as well as those identified from the bibliography of these articles. Case reports and case control studies confirm an association between CTDs and migraine, coat-hanger headaches, carotid arterial dissections, intracranial hypotension, Arnold Chiari malformations-type 1, cervical spine disorders, and temporomandibular joint disorders. Observational cross-sectional studies suggest that the prevalence of CTDs is increased in patients with specific types of headache disorders. It is unknown if the CTDs directly cause these headaches disorders or are associated with them through other mechanisms. © 2014 American Headache Society.

Multiple fractures in infants who have Ehlers-Danlos/hypermobility syndrome and or vitamin D deficiency: A case series of 72 infants whose parents were accused of child abuse and neglect

PubMed Central

Hossein-Nezhad, A.; Tabatabaei, F.

2017-01-01

ABSTRACT Objective: To increase the level of awareness that Ehlers-Danlos/hypermobility syndrome (EDS) and vitamin D deficiency are associated with infantile fragility fractures and radiologic features that may be mistakenly reported to be caused by non-accidental trauma due to Child Abuse and Neglect (CAN). Patients and Methods: We constructed a case series, the largest to date, of infants with EDS who were vitamin D sufficient, insufficient and deficient and infants without EDS but with documented vitamin D deficiency and radiologic evidence of rickets who presented with multiple fractures originally diagnosed as being non-accidental and caused by child abuse. These infants were referred to the outpatient Bone Health Care Clinic at Boston University Medical Campus over a 6-year (2010–2015) period. We also present 6 index cases in which the court concluded that there was no convincing evidence of child abuse and the infants were returned to their parents. Institutional Review Board (IRB) approval was obtained. Results: We present 72 cases of infants with multiple fractures diagnosed to be caused by non-accidental trauma. All infants were younger than one year of age. Among them, 93%(67) had clinical evidence of EDS and/or a family history with a confirmed clinical diagnosis of at least one parent having EDS and the other 7%(5) without evidence of EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common fractures noted at diagnosis were ribs and extremity fractures (including classic metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH)D] were reported in 48 infants (18.0 ± 8.5 ng/ml) and in 30 mothers (21.3 ± 11.7 ng/ml). Sixty-three percent (27) of the EDS infants who had their serum 25(OH)D measured were vitamin D deficient 25(OH)D<20 ng/ml and 5 were vitamin D sufficient 25(OH)D>30 ng/ml. The mean serum level for infants with vitamin D deficiency/rickets was (10.2 ± 3.0 ng/ml) Conclusion: EDS, OI/EDS and vitamin D deficiency/infantile rickets are associated with fragility fractures in infants that can be misinterpreted as caused by non-accidental trauma due to child abuse. PMID:29511428

The association between muscle strength and activity limitations in patients with the hypermobility type of Ehlers-Danlos syndrome: the impact of proprioception.

PubMed

Scheper, Mark; Rombaut, Lies; de Vries, Janneke; De Wandele, Inge; van der Esch, Martin; Visser, Bart; Malfait, Franciska; Calders, Patrick; Engelbert, Raoul

2017-07-01

The patients diagnosed with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) are characterized by pain, proprioceptive inacuity, muscle weakness, potentially leading to activity limitations. In EDS-HT, a direct relationship between muscle strength, proprioception and activity limitations has never been studied. The objective of the study was to establish the association between muscle strength and activity limitations and the impact of proprioception on this association in EDS-HT patients. Twenty-four EDS-HT patients were compared with 24 controls. Activity limitations were quantified by Health Assessment Questionnaire (HAQ), Six-Minute Walk test (6MWT) and 30-s chair-rise test (30CRT). Muscle strength was quantified by handheld dynamometry. Proprioception was quantified by movement detection paradigm. In analyses, the association between muscle strength and activity limitations was controlled for proprioception and confounders. Muscle strength was associated with 30CRT (r = 0.67, p = <0.001), 6MWT (r = 0.58, p = <0.001) and HAQ (r = 0.63, p= <0.001). Proprioception was associated with 30CRT (r = 0.55, p < 0.001), 6MWT (r = 0.40, p = <0.05) and HAQ (r = 0.46, p < 0.05). Muscle strength was found to be associated with activity limitations, however, proprioceptive inacuity confounded this association. Muscle strength is associated with activity limitations in EDS-HT patients. Joint proprioception is of influence on this association and should be considered in the development of new treatment strategies for patients with EDS-HT. Implications for rehabilitation Reducing activity limitations by enhancing muscle strength is frequently applied in the treatment of EDS-HT patients. Although evidence regarding treatment efficacy is scarce, the current paper confirms the rationality that muscle strength is an important factor in the occurrence of activity limitations in EDS-HT patients. Although muscle strength is the most dominant factor that is associated with activity limitations, this association is confounded by proprioception. In contrast to common belief proprioception was not directly associated with activity limitations but confounded this association. Controlling muscle strength on the bases of proprioceptive input may be more important for reducing activity limitations than just enhancing sheer muscle strength.

Vertebral Column Resection for Kyphoscoliosis in a Patient with Ehlers-Danlos Syndrome: An Intraoperative Neurophysiological Monitoring Alert.

PubMed

Jahangiri, Faisal R; Al Eissa, Sami; Sayegh, Samir; Al Helal, Fahad; Al-Sharif, Shomoukh A; Annaim, Monerah M; Muhammad, Sheryar; Aziz, Tanweer

2016-08-31

A 16-year-old male patient with Ehler-Danlos syndrome (EDS) and a back deformity since birth presented with severe kyphoscoliosis. The patient was neurologically intact but had respiratory and cardiac insufficiencies. A two-stage vertebral column resection (VCR) at T9-T10 with multiple level fusion with multimodality intraoperative neurophysiological monitoring (IONM) was planned.  During the first stage, pedicle screws were placed at multiple spinal levels above and below the VCR level. Upper and lower somatosensory evoked potentials (SSEP), transcranial electrical motor evoked potentials (TCeMEP), and electromyography were monitored continuously and showed no significant changes. The second stage was performed one week later. Baseline SSEP and TCeMEP responses were present in all extremities. The surgeon was informed of a sudden 70% amplitude drop in TCeMEP in the lower limbs with stable SSEP after ligating one of the left nerves/vessels fully stretching the spinal cord. The surgeon removed the ligation, and an improvement in motor responses followed. Surgery proceeded with the highest levels of caution. Later, there was a sudden loss of TCeMEP and SSEP in the lower limbs bilaterally. The correction was released, mean arterial pressure was increased, and intravenous dexamethasone was administered. The surgical correction was aborted, and the decision was made to close the site. Lower SSEP and TCeMEP responses remained absent until closing, while upper SSEP and TCeMEP responses remained stable. A wake-up test was done after closing. The patient moved his upper limbs but was unable to move his lower limbs bilaterally. The patient was sent for a magnetic resonance imaging scan while intubated and then sent to the intensive care unit. At 24 hours and 36 hours post-operation, the patient had no sensory and motor function below the T8 level. Forty-eight hours post-operation, the patient started to feel sensory stimuli at the T10 level. At one week post-operation, the patient regained sphincter functions, and at four weeks postoperatively, the patient's hip flexors started to recover. VCR in patients with EDS has a very high risk of damaging the spinal cord due to the fragile vasculature of the spinal cord. Real-time IONM is useful in the early identification of spinal cord injury in cases of this nature.

Vertebral Column Resection for Kyphoscoliosis in a Patient with Ehlers-Danlos Syndrome: An Intraoperative Neurophysiological Monitoring Alert

PubMed Central

Al Eissa, Sami; Sayegh, Samir; Al Helal, Fahad; Al-Sharif, Shomoukh A; Annaim, Monerah M; Muhammad, Sheryar; Aziz, Tanweer

2016-01-01

A 16-year-old male patient with Ehler-Danlos syndrome (EDS) and a back deformity since birth presented with severe kyphoscoliosis. The patient was neurologically intact but had respiratory and cardiac insufficiencies. A two-stage vertebral column resection (VCR) at T9-T10 with multiple level fusion with multimodality intraoperative neurophysiological monitoring (IONM) was planned.  During the first stage, pedicle screws were placed at multiple spinal levels above and below the VCR level. Upper and lower somatosensory evoked potentials (SSEP), transcranial electrical motor evoked potentials (TCeMEP), and electromyography were monitored continuously and showed no significant changes. The second stage was performed one week later. Baseline SSEP and TCeMEP responses were present in all extremities. The surgeon was informed of a sudden 70% amplitude drop in TCeMEP in the lower limbs with stable SSEP after ligating one of the left nerves/vessels fully stretching the spinal cord. The surgeon removed the ligation, and an improvement in motor responses followed. Surgery proceeded with the highest levels of caution. Later, there was a sudden loss of TCeMEP and SSEP in the lower limbs bilaterally. The correction was released, mean arterial pressure was increased, and intravenous dexamethasone was administered. The surgical correction was aborted, and the decision was made to close the site. Lower SSEP and TCeMEP responses remained absent until closing, while upper SSEP and TCeMEP responses remained stable. A wake-up test was done after closing. The patient moved his upper limbs but was unable to move his lower limbs bilaterally. The patient was sent for a magnetic resonance imaging scan while intubated and then sent to the intensive care unit. At 24 hours and 36 hours post-operation, the patient had no sensory and motor function below the T8 level. Forty-eight hours post-operation, the patient started to feel sensory stimuli at the T10 level. At one week post-operation, the patient regained sphincter functions, and at four weeks postoperatively, the patient’s hip flexors started to recover. VCR in patients with EDS has a very high risk of damaging the spinal cord due to the fragile vasculature of the spinal cord. Real-time IONM is useful in the early identification of spinal cord injury in cases of this nature.  PMID:27766191

Pigment dispersion syndrome associated with spontaneous subluxation of crystalline lens.

PubMed

Veerwal, Vikas; Goyal, Jawahar Lal; Jain, Parul; Arora, Ritu

2017-01-01

Pigment dispersion syndrome (PDS) is an ocular condition characterized by a dispersion of iris pigment throughout the eye. This pigment is deposited in a characteristic manner on the corneal endothelium as Krukenberg's spindle, anterior surface of the iris, in the trabecular meshwork, on the lens and zonule and occasionally on the anterior hyaloid face. Even with deposition of pigment on zonular fibers, no zonular weakness, or zonular dehiscence has been reported in these cases. We report a unique case of PDS with bilateral spontaneous subluxation of crystalline lens. With characteristic findings of pigment distribution in both his eyes, the patient had concave iris configuration with heavily pigmented trabecular meshwork confirming the diagnosis of PDS. The patient had bilateral 180° temporal subluxation of crystalline lens in both his eyes. The usual cause of lens subluxation such as Marfan's Syndrome and Ehler's Danlos Syndrome was ruled out. The patient underwent right eye followed by left eye intracapsular cataract extraction with ab-interno technique with postoperative best-corrected visual acuity (BCVA) of 6/9 in both eyes. Spontaneous subluxation of crystalline lens in isolated PDS is not known to occur and has been reported by means of this case. We recommend a thorough assessment of zonular status in all cases of PDS.

[Diagnosis and treatment of aortic diseases : new guidelines of the European Society of Cardiology 2014].

PubMed

Eggebrecht, H

2014-12-01

In September 2014 the European Society of Cardiology issued guidelines for the diagnosis and treatment of aortic diseases in adults. Contrast-enhanced computed tomography (CT) represents the imaging modality of first choice as it is rapidly and almost ubiquitously available and can evaluate the entire aorta in a single-step examination. In patients with a high clinical suspicion of an acute aortic syndrome based on (family) history and symptoms, CT should be performed without further delay to confirm or refute the diagnosis. Diseases involving the ascending aorta remain a domain of open surgery, be it on an emergency basis in an acute type A dissection or electively in asymptomatic aneurysms with an aortic diameter >5.5 cm. The presence of risk factors (e. g. bicuspid aortic valve, Marfan syndrome and aortic dissection/rupture in the family history) may prompt earlier surgical repair at a lower threshold diameter. The treatment of descending aortic disease is primarily conservative including modification of cardiovascular risk factors. If indicated, endovascular aortic stent graft repair appears to be superior to open surgery for descending thoracic aortic disease or equivalent in the treatment of infrarenal abdominal aortic aneurysms. The management of aortic diseases related to genetic connective tissue diseases (e. g. Marfan syndrome, Loeys-Dietz syndrome and Ehlers-Danlos syndrome) is complex and requires special multidisciplinary expertise.

Pre- and Postoperative Imaging of the Aortic Root

PubMed Central

Chan, Frandics P.; Mitchell, R. Scott; Miller, D. Craig; Fleischmann, Dominik

2016-01-01

Three-dimensional datasets acquired using computed tomography and magnetic resonance imaging are ideally suited for characterization of the aortic root. These modalities offer different advantages and limitations, which must be weighed according to the clinical context. This article provides an overview of current aortic root imaging, highlighting normal anatomy, pathologic conditions, imaging techniques, measurement thresholds, relevant surgical procedures, postoperative complications and potential imaging pitfalls. Patients with a range of clinical conditions are predisposed to aortic root disease, including Marfan syndrome, bicuspid aortic valve, vascular Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Various surgical techniques may be used to repair the aortic root, including placement of a composite valve graft, such as the Bentall and Cabrol procedures; placement of an aortic root graft with preservation of the native valve, such as the Yacoub and David techniques; and implantation of a biologic graft, such as a homograft, autograft, or xenograft. Potential imaging pitfalls in the postoperative period include mimickers of pathologic processes such as felt pledgets, graft folds, and nonabsorbable hemostatic agents. Postoperative complications that may be encountered include pseudoaneurysms, infection, and dehiscence. Radiologists should be familiar with normal aortic root anatomy, surgical procedures, and postoperative complications, to accurately interpret pre- and postoperative imaging performed for evaluation of the aortic root. Online supplemental material is available for this article. ©RSNA, 2015 PMID:26761529

Lysine hydroxylation of collagen in a fibroblast cell culture system

NASA Technical Reports Server (NTRS)

Uzawa, Katsuhiro; Yeowell, Heather N.; Yamamoto, Kazushi; Mochida, Yoshiyuki; Tanzawa, Hideki; Yamauchi, Mitsuo

2003-01-01

The lysine (Lys) hydroxylation pattern of type I collagen produced by human fibroblasts in culture was analyzed and compared. Fibroblasts were cultured from normal human skin (NSF), keloid (KDF), fetal skin (FDF), and skin tissues of Ehlers-Danlos syndrome type VIA and VIB patients (EDS-VIA and -VIB). The type I collagen alpha chains with or without non-helical telopeptides were purified from the insoluble matrix and analyzed. In comparison with NSFs, KDF and FDF showed significantly higher Lys hydroxylation, particularly in the telopeptide domains of both alpha chains. Both EDS-VIA and -VIB showed markedly lower Lys hydroxylation in the helical domains of both alpha chains whereas that in the telopeptides was comparable with those of NSFs. A similar profile was observed in the tissue sample of the EDS-VIB patient. These results demonstrate that the Lys hydroxylation pattern is domain-specific within the collagen molecule and that this method is useful to characterize the cell phenotypes in normal/pathological connective tissues.

Measurement of the Mechanical Properties of Intact Collagen Fibrils

NASA Astrophysics Data System (ADS)

Mercedes, H.; Heim, A.; Matthews, W. G.; Koob, T.

2006-03-01

Motivated by the genetic disorder Ehlers-Danlos syndrome (EDS), in which proper collagen synthesis is interrupted, we are investigating the structural and mechanical properties of collagen fibrils. The fibrous glycoprotein collagen is the most abundant protein found in the human body and plays a key role in the extracellular matrix of the connective tissue, the properties of which are altered in EDS. We have selected as our model system the collagen fibrils of the sea cucumber dermis, a naturally mutable tissue. This system allows us to work with native fibrils which have their proteoglycan complement intact, something that is not possible with reconstituted mammalian collagen fibrils. Using atomic force microscopy, we measure, as a function of the concentration of divalent cations, the fibril diameter, its response to force loading, and the changes in its rigidity. Through these experiments, we will shed light on the mechanisms which control the properties of the sea cucumber dermis and hope to help explain the altered connective tissue extracellular matrix properties associated with EDS.

Genetics of ischaemic stroke; single gene disorders.

PubMed

Flossmann, Enrico

2006-08-01

Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler-Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.

Carotid-cavernous fistula after functional endoscopic sinus surgery.

PubMed

Karaman, Emin; Isildak, Huseyin; Haciyev, Yusuf; Kaytaz, Asim; Enver, Ozgun

2009-03-01

Carotid-cavernous fistulas (CCFs) are anomalous communications between the carotid arterial system and the venous cavernous sinus. They can arise because of spontaneous or trauma causes. Most caroticocavernous fistulas are of spontaneous origin and unknown etiology. Spontaneous CCF may also be associated with cavernous sinus pathology such as arteriosclerotic changes of the arterial wall, fibromuscular dysplasia, or Ehler-Danlos syndrome. Traumatic CCFs may occur after either blunt or penetrating head trauma. Their clinical presentation is related to their size and to the type of venous drainage, which can lead to a variety of symptoms, such as visual loss, proptosis, bruit, chemosis, cranial nerve impairment, intracranial hemorrhage (rare), and so on. Treatment by endovascular transarterial embolization with electrolytically detachable coils is a very effective method for CCF with good outcomes. Carotid-cavernous fistulas have been rarely reported after craniofacial surgery and are uncommon pathologies in otolaryngology practice. In this study, we report a 40-year-old woman with CCF secondary to blunt trauma of functional endoscopic sinus surgery.

Biological functions of iduronic acid in chondroitin/dermatan sulfate.

PubMed

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-05-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS.

Congenital keratoglobus with multiple cardiac anomalies: a case presentation and literature review.

PubMed

Ozer, Pinar A; Yalniz-Akkaya, Zuleyha

2015-07-01

Keratoglobus is a rare condition of bilateral corneal ectasia, which results in high myopia, irregular astigmatism, scarring, and rarely spontaneous globe rupture. Globoid protrusion of a clear, diffusely thin cornea is the pathology. The congenital form has been associated with blue sclera in which there is a systemic connective tissue disorder with abnormal collagen synthesis like Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Some concomitant abnormalities reported with kertoglobus include joint hypermobility, dental and skeletal abnormalities, osteal fragility, and deafness. Acquired forms have been reported to be associated with vernal keratoconjunctivitis and thyroid ophthalmopathy. We report the case of a 16-year-old boy with keratoglobus who presented with a history of photophobia and a low vision in both eyes since birth. He has been followed up by our pediatric cardiology department due to multiple cardiac anomalies. He had hypermobility of large joints, easy bruising, thin and hyperextensible skin with visible veins, which were also described in his elder brother. We aimed to discuss the etiology and the association of keratoglobus with some systemic abnormalities caused by collogen tissue disturbance, and make a brief review about the recent literature concerning the management of keratoglobus patients.

A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations.

PubMed

Ritelli, M; Morlino, S; Giacopuzzi, E; Bernardini, L; Torres, B; Santoro, G; Ravasio, V; Chiarelli, N; D'Angelantonio, D; Novelli, A; Grammatico, P; Colombi, M; Castori, M

2018-01-01

Deletions encompassing TAK1-binding protein 2 (TAB2) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole-exome sequencing (WES) disclosed the novel TAB2 c.1398dup (p.Thr467Tyrfs*6) variant that eliminates the C-terminal zinc finger domain essential for activation of TAK1 (TGFβ-activated kinase 1)-dependent signaling pathways. The sporadic case carryed a ~2 Mb de novo deletion including 28 genes also comprising TAB2. This study reveal an association between TAB2 mutations and a phenotype resembling Ehlers-Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with TAB2 perturbations and emphasize the role of TAK1 signaling network in human development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Attention-deficit/hyperactivity disorder, joint hypermobility-related disorders and pain: expanding body-mind connections to the developmental age.

PubMed

Baeza-Velasco, Carolina; Sinibaldi, Lorenzo; Castori, Marco

2018-02-14

Attention-deficit/hyperactivity disorder (ADHD) and generalized joint hypermobility (JH) are two separated conditions, assessed, and managed by different specialists without overlapping interests. Recently, some researchers highlighted an unexpected association between these two clinical entities. This happens in a scenario of increasing awareness on the protean detrimental effects that congenital anomalies of the connective tissue may have on human health and development. To review pertinent literature to identify possible connections between ADHD and GJH, special emphasis was put on musculoskeletal pain and syndromic presentations of GJH, particularly the hypermobile Ehlers-Danlos syndrome. A comprehensive search of scientific databases and references lists was conducted, encompassing publications based on qualitative and quantitative research. Impaired coordination and proprioception, fatigue, chronic pain, and dysautonomia are identified as potential bridges between ADHD and JH. Based on these findings, a map of the pathophysiological and psychopathological pathways connecting both conditions is proposed. Although ADHD and JH are traditionally separated human attributes, their association may testify for the dyadic nature of mind-body connections during critical periods of post-natal development. Such a mixed picture has potentially important consequences in terms of disability and deserves more clinical and research attention.

Periodontal disease associated to systemic genetic disorders.

PubMed

Nualart Grollmus, Zacy Carola; Morales Chávez, Mariana Carolina; Silvestre Donat, Francisco Javier

2007-05-01

A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefévre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefévre syndrome, where an established treatment protocol is available.

A patient with ascending aortic dilatation, similar to phenotypes of connective tissue disorders.

PubMed

Onrat, S T; Emmiler, M; Sivaci, Y; Söylemez, Z; Ozgöz, A; Imirzalioğlu, N

2009-04-14

We report on the clinical and molecular findings of a patient who presented alopecia, epicanthus, micrognathia, retrognathia, high arched palate, hypertelorism, Chiari type I malformation, mixed-type hearing loss but with normal heartbeat Q-T interval, malformed earlobes, down-slanted palpebral fissures, downturned corners of the mouth, syndactyly, atopic eczema, and seizures. The patient was a male adult, 23 years old, with short stature (153 cm) and low weight (50.5 kg), due to severe aortic insufficiency and dilatation of the ascending aorta. Conventional cytogenetic screening did not show any chromosomal gains or losses. Molecular genetic screening was conducted for gene mutations involved in various syndromes; the mutations found included [beta-fibrinogen -455 G>A wt/wt (wt/mut), PAI-1 4G/5G (4G/4G), HPA1 a/b (a/a), MTHFR C677T wt/wt (wt/mut), ACE I/D (I/I), and Apo E E3/E4]. Many clinical and molecular genetics findings overlapped with other conditions associated with arterial tortuosity and arterial aneurysms, including the Marfan, Ehler-Danlos, Shprintzen-Goldberg, and Loeys-Dietz syndromes. Although a diagnosis of Shprintzen-Goldberg syndrome was based on clinical findings and radiographic findings indicate other syndromes, aortic root dilatation seems to be a new symptom, similar to phenotypes of connective tissue disorders. The unique grouping of clinical manifestations in this patient and the molecular genetics findings lead us to suggest that this case could be an example of a previously unrecognized syndrome.

Management of pregnancy in women with genetic disorders, Part 1: Disorders of the connective tissue, muscle, vascular, and skeletal systems.

PubMed

Chetty, Shilpa Prema; Shaffer, Brian L; Norton, Mary E

2011-11-01

Due to early diagnosis and increasingly effective medical advances, the number of women with various genetic syndromes who are undergoing pregnancy is increasing, and this represents an important issue for providers of obstetric care. Each year more women with genetic disease reach childbearing age. Advances in assisted reproductive technology have enabled pregnancy in a cohort of woman who may experience impaired fertility due to their underlying diagnosis. Management of these women requires coordination of care by healthcare providers from multiple specialties to optimize outcomes. Potentially serious medical issues specific to each diagnosis often exist in the preconception, antepartum, intrapartum, and postpartum periods, all of which must be recognized to allow timely diagnosis and treatment. The fetus may also face issues related to risk for inheritance of the genetic disorder itself, as well as risks related to the chronic disease status of the mother. This article will explore the issues faced by women with various genetic disorders that may affect connective tissue, muscular, vascular, and skeletal systems. Obstetricians & Gynecologists and Family Physicians. After the completing the CME activity, physicians should be better able to classify the cardiovascular manifestations observed in Marfan syndrome and Ehlers-Danlos, evaluate prenatal diagnostic options and limitations for various genetic syndromes, assess the risks to the fetus in women with various genetic syndromes. Determine whether there is a preferred mode of delivery for pregnant patients with various genetic syndromes described in this paper.

A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some β3GalT6-pathy mutations.

PubMed

Ben-Mahmoud, A; Ben-Salem, S; Al-Sorkhy, M; John, A; Ali, B R; Al-Gazali, L

2018-06-01

Al-Gazali syndrome encompasses several clinical features including prenatal growth retardation, large joints contractures with camptodactyly, bilateral talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and early lethality. Recently, a baby with features very similar to Al-Gazali syndrome was found to have compound heterozygous variants in B3GALT6. This gene encodes Beta-1,3-galactosyltransferase 6 (β3GalT6), an essential component of the glycosaminoglycan synthesis pathway. Pathogenic variants in B3GALT6 have also been shown to cause Ehlers-Danlos syndrome spondylodysplastic type (spEDS-B3GALT6) and spondyloepimetaphyseal dysplasia with joint laxity type I (SEMD-JL1). In 2017, a new international classification of EDS included these 2 conditions together with the child reported to have features similar to Al-Gazali syndrome under spondylodysplastic EDS (spEDS). We report a disease-causing variant c.618C > G, p.(Cys206Trp) in 1 patient originally described as Al-Gazali syndrome and reported in 1999. We evaluated the involvement of the endoplasmic reticulum-associated protein degradation, in the pathogenesis of 13 B3GALT6 variants. Retention in endoplasmic reticulum was evident in 6 of them while the c.618C > G, p.(Cys206Trp) and the other 6 variants trafficked normally. Our findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome and suggest that Al-Gazali syndrome represents the severe end of the spectrum of the phenotypes caused by pathogenic variants in this gene. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Orthostatic intolerance: potential pathophysiology and therapy.

PubMed

Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se

2004-09-30

Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

PubMed

Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N Cooke; Willoughby, Colin E; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P; Polašek, Ozren; Siscovick, David; Mitchell, Paul; Tham, Yih Chung; Haines, Jonathan L; Kearns, Lisa S; Hayward, Caroline; Shi, Yuan; van Leeuwen, Elisabeth M; Taylor, Kent D; Bonnemaijer, Pieter; Rotter, Jerome I; Martin, Nicholas G; Zeller, Tanja; Mills, Richard A; Staffieri, Sandra E; Jonas, Jost B; Schmidtmann, Irene; Boutin, Thibaud; Kang, Jae H; Lucas, Sionne E M; Wong, Tien Yin; Beutel, Manfred E; Wilson, James F; Uitterlinden, André G; Vithana, Eranga N; Foster, Paul J; Hysi, Pirro G; Hewitt, Alex W; Khor, Chiea Chuen; Pasquale, Louis R; Montgomery, Grant W; Klaver, Caroline C W; Aung, Tin; Pfeiffer, Norbert; Mackey, David A; Hammond, Christopher J; Cheng, Ching-Yu; Craig, Jamie E; Rabinowitz, Yaron S; Wiggs, Janey L; Burdon, Kathryn P; van Duijn, Cornelia M; MacGregor, Stuart

2018-05-14

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10 -5 ) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A

PubMed Central

Reinstein, Eyal; Frentz, Sophia; Morgan, Tim; García-Miñaúr, Sixto; Leventer, Richard J; McGillivray, George; Pariani, Mitchel; van der Steen, Anthony; Pope, Michael; Holder-Espinasse, Muriel; Scott, Richard; Thompson, Elizabeth M; Robertson, Terry; Coppin, Brian; Siegel, Robert; Bret Zurita, Montserrat; Rodríguez, Jose I; Morales, Carmen; Rodrigues, Yuri; Arcas, Joaquín; Saggar, Anand; Horton, Margaret; Zackai, Elaine; Graham, John M; Rimoin, David L; Robertson, Stephen P

2013-01-01

Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice

PubMed Central

Egging, David F.; van Vlijmen-Willems, Ivonne; Choi, Jiwon; Peeters, Anita C. T. M.; van Rens, Desiree; Veit, Guido; Koch, Manuel; Davis, Elaine C.

2008-01-01

Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition. PMID:18335242

The echinoderm collagen fibril: a hero in the connective tissue research of the 1990s.

PubMed

Szulgit, Greg

2007-07-01

Collagen fibrils are some of the most-abundant and important extracellular structures in our bodies, yet we are unsure of their shape and size. This is largely due to an inherent difficulty in isolating them from their surrounding tissues. Echinoderms have collagenous tissues that are similar to ours in many ways, yet they can be manipulated to easily relinquish their collagen fibrils, providing an excellent opportunity to study native fibrillar structure. In the early 1990s, they were found to defy the commonly accepted fibrillar model of the time in that they were much shorter, they were shaped like double-ended spindles, and their centers exhibited a reversal in molecular polarity. Realization of these features helped to reform the questions that were being asked about vertebrate fibrils, shifting the focus toward shape and size. Since then, researchers working with both groups (echinoderms and vertebrates) have worked together to find the structure of native fibrils. This information will be fundamental in understanding what holds collagenous tissues together at the fibrillar level, and could have important implications for people with Ehlers-Danlos syndrome. (c) 2007 Wiley Periodicals, Inc.

Chronic pain in hypermobility syndrome and Ehlers–Danlos syndrome (hypermobility type): it is a challenge

PubMed Central

Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul HH

2015-01-01

Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers–Danlos syndrome. However, within the Ehlers–Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers–Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3). PMID:26316810

[Arterial involvements in hereditary dysplasia of the connective tissue].

PubMed

Beylot, C; Doutre, M S; Beylot-Barry, M; Busquet, M

1994-03-01

Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases detailed in this paper constitute the main areas of this subject, but arterial involvement may occur in other inheritable disorders of connective tissue (osteogenesis imperfecta, cutis laxa, Werner syndrome, Menkes syndrome, etc).

Tissue-specific mosaicism for a lethal osteogenesis imperfecta COL1A1 mutation causes mild OI/EDS overlap syndrome.

PubMed

Symoens, Sofie; Steyaert, Wouter; Demuynck, Lynn; De Paepe, Anne; Diderich, Karin E M; Malfait, Fransiska; Coucke, Paul J

2017-04-01

Type I collagen is the predominant protein of connective tissues such as skin and bone. Mutations in the type I collagen genes (COL1A1 and COL1A2) mainly cause osteogenesis imperfecta (OI). We describe a patient with clinical signs of Ehlers-Danlos syndrome (EDS), including fragile skin, easy bruising, recurrent luxations, and fractures resembling mild OI. Biochemical collagen analysis of the patients' dermal fibroblasts showed faint overmodification of the type I collagen bands, a finding specific for structural defects in type I collagen. Bidirectional Sanger sequencing detected an in-frame deletion in exon 44 of COL1A1 (c.3150_3158del), resulting in the deletion of three amino acids (p.Ala1053_Gly1055del) in the collagen triple helix. This COL1A1 mutation was hitherto identified in four probands with lethal OI, and never in EDS patients. As the peaks on the electropherogram corresponding to the mutant allele were decreased in intensity, we performed next generation sequencing of COL1A1 to study mosaicism in skin and blood. While approximately 9% of the reads originating from fibroblast gDNA harbored the COL1A1 deletion, the deletion was not detected in gDNA from blood. Most likely, the mild clinical symptoms observed in our patient can be explained by the mosaic state of the mutation. © 2017 Wiley Periodicals, Inc.

Celiprolol

PubMed Central

Cheng-Lai, Angela; Frishman, William H.

2017-01-01

Celiprolol is a β-blocker with a unique pharmacologic profile: it is a β1-andrenoceptor antagonist with partial β2 agonist activity. Given this combination of effects, celiprolol may be better described as a selective adrenoreceptor modulator. It has antihypertensive and antianginal properties and is indicated for those uses in various countries around the world. In the United States, however, the proposed indication for this drug will be for the treatment of vascular type Ehlers–Danlos syndrome, a rare connective tissue disorder characterized by fragile arterial structure and an increased risk of life-threatening vascular complications. By reducing heart rate and pulsatile pressure, celiprolol may reduce the mechanical stress on collagen fibers within the arterial wall and be of benefit in patients with vascular type Ehlers–Danlos syndrome. The largest investigation of celiprolol in vascular Ehlers–Danlos syndrome was prematurely terminated due to significant benefit with celiprolol in reducing arterial events in patients with this condition. Celiprolol, therefore, represents a β-blocker that is unique from others in its class in both its pharmacology and clinical applications. PMID:28742547

A novel truncating mutation in FLNA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia.

PubMed

Ieda, Daisuke; Hori, Ikumi; Nakamura, Yuji; Ohshita, Hironori; Negishi, Yutaka; Shinohara, Tsutomu; Hattori, Ayako; Kato, Takenori; Inukai, Sachiko; Kitamura, Katsumasa; Kawai, Tomoki; Ohara, Osamu; Kunishima, Shinji; Saitoh, Shinji

2018-06-01

Filamin A (FLNA) is located in Xq28, and encodes the actin binding protein, filamin A. A mutation in FLNA is the most common cause of periventricular nodular heterotopia (PVNH), but a clear phenotype-genotype correlation has not been established. Indeed, some patients with a FLNA mutation have recently been shown to additionally have Ehlers-Danlos-like collagenopathy or macrothrombocytopenia. In an attempt to establish a clearer correlation between clinical symptoms and genotype, we have investigated a phenotype that involves thrombocytopenia in a patient with a truncation of the FLNA gene. We present the case of a 4-year-old girl who, at birth, showed a ventral hernia. At 2 months of age, she was diagnosed with patent ductus arteriosus (PDA) and aortic valve regurgitation. At 11 months, she underwent ligation of the PDA. She was also diagnosed with diaphragmatic eventration by a preoperative test. At 19 months, motor developmental delay was noted, and brain MRI revealed bilateral PVNH with mega cisterna magna. Presently, there is no evidence of epilepsy, intellectual disability or motor developmental delay. She has chronic, mild thrombocytopenia, and a platelet count that transiently decreases after viral infection. Dilation of the ascending aorta is progressing gradually. Genetic testing revealed a de novo nonsense heterozygous mutation in FLNA (NM_001456.3: c.1621G > T; p.Glu541Ter). Immunofluorescence staining of a peripheral blood smear showed a lack of filamin A expression in 21.1% of her platelets. These filamin A-negative platelets were slightly larger than her normal platelets. Our data suggests immunofluorescence staining of peripheral blood smears is a convenient diagnostic approach to identify patients with a FLNA mutation, which will facilitate further investigation of the correlation between FLNA mutations and patient phenotype. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling Pathways

PubMed Central

Shimoda, Shinji; Mishima, Kenji; Higashiyama, Hiroyuki; Idaira, Yayoi; Asada, Yoshinobu; Kitamura, Hiroshi; Yamasaki, Satoru; Hojyo, Shintaro; Nakayama, Manabu; Ohara, Osamu; Koseki, Haruhiko; dos Santos, Heloisa G.; Bonafe, Luisa; Ha-Vinh, Russia; Zankl, Andreas; Unger, Sheila; Kraenzlin, Marius E.; Beckmann, Jacques S.; Saito, Ichiro; Rivolta, Carlo; Ikegawa, Shiro; Superti-Furga, Andrea; Hirano, Toshio

2008-01-01

Background Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. Methodology/Principal Findings Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-β signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. Conclusions/Significance Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction. PMID:18985159

Ehlers-Danlos syndrome, classical type.

PubMed

Bowen, Jessica M; Sobey, Glenda J; Burrows, Nigel P; Colombi, Marina; Lavallee, Mark E; Malfait, Fransiska; Francomano, Clair A

2017-03-01

Classical EDS is a heritable disorder of connective tissue. Patients are affected with joint hypermobility, skin hyperextensibilty, and skin fragility leading to atrophic scarring and significant bruising. These clinical features suggest consideration of the diagnosis which then needs to be confirmed, preferably by genetic testing. The most recent criteria for the diagnosis of EDS were devised in Villefranche in 1997. [Beighton et al. (1998); Am J Med Genet 77:31-37]. The aims set out in the Villefranche Criteria were: to enable diagnostic uniformity for clinical and research purposes, to understand the natural history of each subtype of EDS, to inform management and genetic counselling, and to identify potential areas of research. The authors recognized that the criteria would need updating, but viewed the Villefranche nosology as a good starting point. Since 1997, there have been major advances in the molecular understanding of classical EDS. Previous question marks over genetic heterogeneity have been largely surpassed by evidence that abnormalities in type V collagen are the cause. Advances in molecular testing have made it possible to identify the causative mutation in the majority of patients. This has aided the further clarification of this diagnosis. The aim of this literature review is to summarize the current knowledge and highlight areas for future research. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Association between hyperflexibility of the thumb and an unexplained bleeding tendency: is it a rule of thumb?

PubMed

Kaplinsky, C; Kenet, G; Seligsohn, U; Rechavi, G

1998-05-01

A bleeding tendency manifested by petechiae and ecchymoses is one of the most common causes for referral of patients to haematology clinics. Vessel wall pathology is not usually considered to be a cause for deranged haemostasis, although coexistence of increased capillary fragility and joint hypermobility have been reported. We determined the frequency of thumb hyperextensibility and scored the findings in a series of 44 patients referred because of ecchymoses and petechiae, as well as 261 control children and their mothers. All 44 patients had normal coagulation studies. Thumb flexibility score was +4 in 30 patients, +3 in eight patients, +2 in five patients and +1 in one of the index patients. In the control group, only one of 261 had a +4, and three had a +3 score, and two of 260 mothers had a +4 score. Ecchymoses were not observed in any of these subjects, nor in the +1 patients. Based on clinical presentation and normal coagulation studies, we suggest that our patients had an underlying subtype of Ehlers-Danlos syndrome. In view of the dramatically high occurrence of thumb hyperextensibility in patients with unexplained mild bleeding tendency, costly haemostatic and coagulation studies on such patients may not be necessary.

Non-operative management of diverticular perforation in a patient with suspected Ehlers–Danlos syndrome☆

PubMed Central

Casey, M.C.; Robertson, I.; Waters, P.S.; Hanaghan, J.; Khan, W.; Barry, K.

2014-01-01

INTRODUCTION No consensus exists regarding definitive management of colonic perforation in Ehlers–Danlos syndrome (EDS), with various authors advocating different operative techniques. Spontaneous colonic perforation is a recognised complication of vascular-type EDS (type IV), with many reported cases in the literature. No such cases have been reported concerning classical-type EDS (type I/II). PRESENTATION OF CASE A 55-year-old male with a family history of EDS presented with acute lower abdominal pain and signs of localised peritonitis. Following resuscitation, computerised tomography identified perforation of a sigmoid diverticulum with localised intraperitoneal air. Considering the potential complications associated with laparotomy in a patient with EDS, a trial of conservative management was undertaken including image-guided drainage of a mesenteric abscess. Intensive care monitoring, nutritional support and intravenous antibiotics also facilitated successful non-operative management. Following discharge, molecular studies confirmed COL5A1 mutation, and a diagnosis of classical Ehlers–Danlos syndrome was established. DISCUSSION This is the first reported case of successful conservative management of colonic diverticular perforation in a patient with classical Ehlers–Danlos syndrome. CONCLUSION EDS is highly significant in the surgical context, with the causative genetic factors serving to further complicate the course of surgical intervention. In the absence of consensus regarding best surgical management, due consideration should be given to non-operative management of benign colonic perforation. PMID:24534685

A novel missense mutation of COL5A2 in a patient with Ehlers–Danlos syndrome

PubMed Central

Watanabe, Miki; Nakagawa, Ryuji; Naruto, Takuya; Kohmoto, Tomohiro; Suga, Ken-ichi; Goji, Aya; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg]. PMID:27656288

Ehlers–Danlos Syndrome—Hypermobility Type: A Much Neglected Multisystemic Disorder

PubMed Central

Gazit, Yael; Jacob, Giris; Grahame, Rodney

2016-01-01

Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems. PMID:27824552

Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

PubMed Central

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F.; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

2013-01-01

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. PMID:23664117

Crystal and Molecular Structure of a Collagen-Like Peptide at 1.9 overset{circ}{A} Resolution

NASA Astrophysics Data System (ADS)

Bella, Jordi; Eaton, Mark; Brodsky, Barbara; Berman, Helen M.

1994-10-01

The structure of a protein triple helix has been determined at 1.9 angstrom resolution by x-ray crystallographic studies of a collagen-like peptide containing a single substitution of the consensus sequence. This peptide adopts a triple-helical structure that confirms the basic features determined from fiber diffraction studies on collagen: supercoiling of polyproline II helices and interchain hydrogen bonding that follows the model II of Rich and Crick. In addition, the structure provides new information concerning the nature of this protein fold. Each triple helix is surrounded by a cylinder of hydration, with an extensive hydrogen bonding network between water molecules and peptide acceptor groups. Hydroxyproline residues have a critical role in this water network. The interaxial spacing of triple helices in the crystal is similar to that in collagen fibrils, and the water networks linking adjacent triple helices in the crystal structure are likely to be present in connective tissues. The breaking of the repeating (X-Y-Gly)_n pattern by a Gly-->Ala substitution results in a subtle alteration of the conformation, with a local untwisting of the triple helix. At the substitution site, direct interchain hydrogen bonds are replaced with interstitial water bridges between the peptide groups. Similar conformational changes may occur in Gly-->X mutated collagens responsible for the diseases osteogenesis imperfecta, chondrodysplasias, and Ehlers-Danlos syndrome IV.

[Congenital bladder diverticula and vesicoureteral reflux].

PubMed

Garat, José María; Angerri, Oriol; Caffaratti, Jorge; Moscatiello, Pietro

2008-03-01

To analyze our series of primary congenital diverticula (PCD) and their association with vesicoureteral reflux. We have taken care of 23 children with PCD. Eleven of them had big diverticula (> 2 cm) and twelve small. In the first group, 4 children had vesicoureteral reflux and 5 in the second group. In group A, ureteral reimplantation was performed at the time of diverticulum excision. Nor diverticula neither refluxes were operated in group B. We analyze separately results in both groups. Group A: Patients were operated including diverticulum excision. There were not recurrences except in one case with Ehler-Danlos Syndrome. No reimplanted ureter showed postoperative reflux. Nevertheless, one case with multiple bladder diverticula without reflux presented reflux after the excision of several diverticula without reimplantation. Group B: Small diverticula did not undergo surgery Spontaneous outcome of reflux was similar to that of the general population without diverticula. Bladder diverticula are frequently associated with vesicoureteral reflux. The presence of reflux is not an absolute condition for surgical or endoscopic treatment. When diverticula are big in size (Group A) the indication for surgery comes from recurrent infection or voiding disorders, not from reflux. If they undergo surgery, ureteral reimplantation is performed in the case they had reflux or for technical reasons like bladder wall weakness. When diverticula are small (Group B) the presence of reflux does not condition treatment, being the rate of spontaneous resolution similar to the general population.

Pectus Excavatum and Heritable Disorders of the Connective Tissue

PubMed Central

Tocchioni, Francesca; Ghionzoli, Marco; Messineo, Antonio; Romagnoli, Paolo

2013-01-01

Pectus excavatum, the most frequent congenital chest wall deformity, may be rarely observed as a sole deformity or as a sign of an underlying connective tissue disorder. To date, only few studies have described correlations between this deformity and heritable connective tissue disorders such as Marfan, Ehlers-Danlos, Poland, MASS (Mitral valve prolapse, not progressive Aortic enlargement, Skeletal and Skin alterations) phenotype among others. When concurring with connective tissue disorder, cardiopulmonary and vascular involvement may be associated to the thoracic defect. Ruling out the concomitance of pectus excavatum and connective tissue disorders, therefore, may have a direct implication both on surgical outcome and long term prognosis. In this review we focused on biological bases of connective tissue disorders which may be relevant to the pathogenesis of pectus excavatum, portraying surgical and clinical implication of their concurrence. PMID:24198927

Potential adverse effects of prophylactic bilateral salpingo-oophorectomy on skin aging in premenopausal women undergoing hysterectomy for benign conditions.

PubMed

Töz, Emrah; Özcan, Aykut; Balsak, Deniz; Avc, Muhittin Eftal; Eraslan, Arzu Görgülü; Balc, Didem Didar

2016-02-01

This study aimed to assess the effects of hysterectomy and bilateral salpingo-oophorectomy (BSO)--compared with the effects of hysterectomy alone--on skin aging in premenopausal women undergoing hysterectomy for benign conditions. One hundred thirty-five premenopausal women who underwent hysterectomy with BSO were compared with a control group of women who underwent hysterectomy alone based on skin parameters (including wrinkling, laxity/sagging, and texture/dryness) and Skindex-29 questionnaire scores. The inclusion criteria were as follows: aged between 40 and 50 years, follicle-stimulating hormone level lower than 40 mIU/mL, undergoing hysterectomy with or without BSO for benign conditions, and not receiving estrogen or progesterone treatment. The exclusion criteria were as follows: adrenocortical hyperplasia or Cushing's syndrome; use of corticosteroids for autoimmune diseases; malignancy, connective tissue diseases (eg, Ehlers-Danlos syndrome), or dermatological diseases (eg, lichen sclerosus); or regular use of medications known to interfere with the condition of the skin. All skin parameters in the hysterectomy group and the hysterectomy with BSO group worsened on weeks 24 and 48. Laxity/sagging and texture/dryness scores on weeks 24 and 48 were significantly worse in the BSO group; laxity/sagging and texture/dryness scores continued to worsen between 24 and 48 weeks. Scores for the Skindex-29 questionnaire emotion and symptom subscales were significantly higher in the BSO group compared with the non-BSO group. Prophylactic BSO during hysterectomy is a significant independent risk factor for worsening skin laxity/sagging and texture/dryness in premenopausal women undergoing hysterectomy for benign conditions. Prophylactic BSO in the presence of dermatological conditions is also associated with reduced quality of life.

Disability in Adolescents and Adults Diagnosed With Hypermobility-Related Disorders: A Meta-Analysis.

PubMed

Scheper, Mark C; Juul-Kristensen, Birgit; Rombaut, Lies; Rameckers, Eugene A; Verbunt, Jeanine; Engelbert, Raoul H

2016-12-01

To (1) establish the association of the most common reported symptoms on disability; and (2) study the effectiveness of treatment on disability in patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT)/hypermobility syndrome (HMS). An electronic search (Medical Subject Headings and free-text terms) was conducted in bibliographic databases CENTRAL/MEDLINE. Comparative, cross-sectional, longitudinal cohort studies and (randomized) controlled trials including patients with HMS/EDS-HT aged ≥17 years were considered for inclusion. A class of symptoms was included when 5 publications were available. In regards to treatment (physical, cognitive interventions), only (randomized) controlled trials were considered. Surgical and medicinal interventions were excluded. Bias was assessed according to the methodological scoring tools of the Cochrane collaboration. Z-score transformations were applied to classify the extent of disability in comparison with healthy controls and to ensure comparability between studies. Initially, the electronic search yielded 714 publications, and 21 articles remained for analysis after selection. The following symptoms were included for meta-analysis: pain (n=12), fatigue (n=6), and psychological distress (n=7). Pain (r=.64, P=.021), fatigue (r=.91, P=.011), and psychological distress (r=.86, P=.018) had a significant impact on disability. Regarding treatment, a significant pain reduction was achieved by a variety of physical and cognitive approaches. Treatment effectiveness on disability was not established. Disability can affect patients with HMS/EDS-HT significantly and is highly correlated with both physical and psychological factors. Although evidence is available that physical and psychological treatment modalities can induce significant pain reduction, the evidence regarding disability reduction is lacking. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Congenital anomalies of cerebral artery and intracranial aneurysm].

PubMed

Nakajima, K; Ito, Z; Hen, R; Uemura, K; Matsuoka, S

1976-02-01

It is well known that congenital anomalies such as polycystic kidney, aortic coarctation, Marfan syndrome, Ehler-Danlos syndrome are apt to be complicated by intracranial aneurysms. In this report we attempt to reveal the relation and incidence between cerebrovascular anomalies and intracranial aneurysms. The etiology of aneurysms has been discussed, too. 12 cases of persistent trigeminl artery, 2 cases of persistent hypoglossal artery and 11 cases of fenestration were obtained from 3841 patients who were angiographically examined in our clinic for 5 years. The incidence is 0.31%, 0.05% and 0.29%, respectively. Persistent trigeminal arteries were complicated by 2 cases of intracranial aneurysms and one case of arterivenous malformations (AVM), persistent hypoglossal arteries were complicated by one case of aneurysm, and fenestrations were complicated by 2 cases of aneurysms and one case of AVM. One case of congenital agenesis of right internal carotid artery was obtained which was complicated by aneurysm of anterior communicating artery. Totally, 8 cases of aneurysms and AVM were obtained from 26 cases of cerebrovascular anomalies (incidence 30.8%). On the other hand, thalamic or caudate hemorrhage revealed the highest incidence of complication of intracranial aneurysms among intracerebral hematomas (10.7%). Compared with the incidence of aneurysms between cerebro vascular anomalies (30.8%) and thalamic or caudate hemorrhage (10.7%), the difference is statistically signigicant (P less than 0.05). The cause of intracranial aneurysm has not yet been clarified. But it is well accepted that the defect of tunica media vasorum is most responsible factor as to the occurrence of intracranial aneurysms. We concluded that the genetic error of cerebral vessels including defect of media caused intracranial aneurysms, and this result was supported from the evidence that cerebrovascular anomalies showed statistically high incidence of complication of intracranial aneurysms.

Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome.

PubMed

Ritelli, Marco; Dordoni, Chiara; Cinquina, Valeria; Venturini, Marina; Calzavara-Pinton, Piergiacomo; Colombi, Marina

2017-09-07

Spondylodysplastic EDS (spEDS) is a rare connective tissue disorder that groups the phenotypes caused by biallelic B4GALT7, B3GALT6, and SLC39A13 mutations. In the 2017 EDS nosology, minimal criteria (general and gene-specific) for a clinical suspicion of spEDS have been proposed, but molecular analysis is required to reach a definite diagnosis. The majority of spEDS patients presented with short stature, skin hyperextensibility, facial dysmorphisms, peculiar radiological findings, muscle hypotonia and joint laxity and/or its complications. To date only 7 patients with β4GALT7-deficiency (spEDS-B4GALT7) have been described and their clinical data suggested that, in addition to short stature and muscle hypotonia, radioulnar synostosis, hypermetropia, and delayed cognitive development might be a hallmark of this specific type of spEDS. Additional 22 patients affected with an overlapping phenotype, i.e., Larsen of Reunion Island syndrome, all carrying a homozygous B4GALT7 mutation, are also recognized. Herein, we report on a 30-year-old Moroccan woman who fitted the minimal criteria to suspect spEDS, but lacked radioulnar synostosis and intellectual disability and presented with neurosensorial hearing loss and limb edema of lymphatic origin. Sanger sequencing of B4GALT7 was performed since the evaluation of the spEDS gene-specific minor criteria suggested this specific subtype. Mutational screening revealed the homozygous c.829G>T, p.Glu277* pathogenetic variant leading to aberrant splicing. Our findings expand both the clinical and mutational spectrum of this ultrarare connective tissue disorder. The comparison of the patient's features with those of the other spEDS and Larsen of Reunion Island syndrome patients reported up to now offers future perspectives for spEDS nosology and clinical research in this field.

Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders.

PubMed

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

2013-06-06

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The effects of neuromuscular taping on gait walking strategy in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type

PubMed Central

Camerota, Filippo; Galli, Manuela; Celletti, Claudia; Ancillao, Andrea; Blow, David; Albertini, Giorgio

2015-01-01

Objective: In this case study, biomechanical alterations induced by neuromuscular taping (NMT) were quantified, during walking, in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT). Methods: A female JHS/EDS-HT patient underwent NMT applications over the low back spine and bilaterally to the knee. Quantitative gait analyses were collected before the NMT application and at the end of the treatment (2 weeks after the first application of NMT). Results: At the end of treatment following the NMT application, left step length showed improvements in cadence and velocity, the left knee showed a reduction in its flexed position at initial contact, and the right ankle joint improved its position at initial contact and in the swing phase. Improvements were also found in kinetics, in terms of the ankle moment and power. Conclusions: Results show that NMT seems to be a promising low-cost intervention for improving gait strategy in patients with JHS/EDS-HT. Further investigations are needed to assess the effects of this treatment intervention on pathological symptoms. PMID:25649985

[S2-Guideline: Pediatric Flat Foot].

PubMed

Hell, Anna K; Döderlein, Leo; Eberhardt, Oliver; Hösl, Matthias; von Kalle, Thekla; Mecher, Frauke; Simon, Angela; Stinus, Hartmut; Wilken, Bernd; Wirth, Thomas

2018-04-09

In pediatric flat foot a differentiation has to be made between the flexible and the rigid form. The diagnosis is based on the history, clinical examination as well as pedobarography, gait analysis and imaging techniques. It is important to rule out neuropediatric conditions such as muscular dystrophies, Ehlers-Danlos- or Marfan syndrome. In children six years of age and younger a flexible flat foot is nearly always physiological (97% of all 19 months old children). Up to the age of ten years the medial column of the foot is developing. Only a minority of children (4% in ten year olds) has a persistent or progressive deformity. Beyond to age of ten there is a danger of deformity decompensation as well as an increased rigidity. Only a minority of children develops some pain (< 2%). A clear risk factor for persistent pediatric flat foot is obesity (62% of six year old children with flat foot are obese). Pathogenetic factors include muscular, bony or soft tissue conditions. However, there specific rule is still unclear. Prevention consists in a thorough parent information about the normal development as well as encouragement of regular sportive activities. Soft and large enough shoes should be carried as a protection. Barfoot walking has to be encouraged on uneven grounds. If physiotherapy is needed different methods can be applied. Orthosis treatment should include a proprioceptive approach. Surgical interventions in children are rare. If surgical treatment is planned a detailed algorhythm should be used before utilizing one of the many different surgical methods. Georg Thieme Verlag KG Stuttgart · New York.

A Cohort Study Comparing Women with Autism Spectrum Disorder with and without Generalized Joint Hypermobility

PubMed Central

Sharp, Julia L.; Edelson, Stephen M.; Kelly, Desmond P.; Casanova, Manuel F.

2018-01-01

Reports suggest comorbidity between autism spectrum disorder (ASD) and the connective tissue disorder, Ehlers-Danlos syndrome (EDS). People with EDS and the broader spectrum of Generalized Joint Hypermobility (GJH) often present with immune- and endocrine-mediated conditions. Meanwhile, immune/endocrine dysregulation is a popular theme in autism research. We surveyed a group of ASD women with/without GJH to determine differences in immune/endocrine exophenotypes. ASD women 25 years or older were invited to participate in an online survey. Respondents completed a questionnaire concerning diagnoses, immune/endocrine symptom history, experiences with pain, and seizure history. ASD women with GJH (ASD/GJH) reported more immune- and endocrine-mediated conditions than their non-GJH counterparts (p = 0.001). Autoimmune conditions were especially prominent in the ASD/GJH group (p = 0.027). Presence of immune-mediated symptoms often co-occurred with one another (p < 0.001–0.020), as did endocrine-mediated symptoms (p < 0.001–0.045), irrespective of the group. Finally, the numbers of immune- and endocrine-mediated symptoms shared a strong inter-relationship (p < 0.001), suggesting potential system crosstalk. While our results cannot estimate comorbidity, they reinforce concepts of an etiological relationship between ASD and GJH. Meanwhile, women with ASD/GJH have complex immune/endocrine exophenotypes compared to their non-GJH counterparts. Further, we discuss how connective tissue regulates the immune system and how the immune/endocrine systems in turn may modulate collagen synthesis, potentially leading to higher rates of GJH in this subpopulation. PMID:29562607

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report.

PubMed

Brown, Bradley D; Rais, Theodore

2015-01-01

The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a "zebra" (i.e., an obscure diagnosis that is made when a more common explanation is more likely).

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report

PubMed Central

Rais, Theodore

2015-01-01

The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a “zebra” (i.e., an obscure diagnosis that is made when a more common explanation is more likely). PMID:26634179

Phenotypic variability in developmental coordination disorder: Clustering of generalized joint hypermobility with attention deficit/hyperactivity disorder, atypical swallowing and narrative difficulties.

PubMed

Celletti, Claudia; Mari, Giorgia; Ghibellini, Giulia; Celli, Mauro; Castori, Marco; Camerota, Filippo

2015-03-01

Developmental coordination disorder (DCD) is a recognized childhood disorder mostly characterized by motor coordination difficulties. Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly featuring generalized joint hypermobility (gJHM), musculoskeletal pain, and minor skin features. Although these two conditions seem apparently unrelated, recent evidence highlights a high rate of motor and coordination findings in children with gJHM or JHS/EDS-HT. Here, we investigated the prevalence of gJHM in 41 Italian children with DCD in order to check for the existence of recognizable phenotypic subgroups of DCD in relation to the presence/absence of gJHM. All patients were screened for Beighton score and a set of neuropsychological tests for motor competences (Movement Assessment Battery for Children and Visual-Motor Integration tests), and language and learning difficulties (Linguistic Comprehension Test, Peabody Picture Vocabulary Test, Boston Naming Test, Bus Story Test, and Memoria-Training tests). All patients were also screening for selected JHS/EDS-HT-associated features and swallowing problems. Nineteen (46%) children showed gJHM and 22 (54%) did not. Children with DCD and gJHM showed a significant excess of frequent falls (95 vs. 18%), easy bruising (74 vs. 0%), motor impersistence (89 vs. 23%), sore hands for writing (53 vs. 9%), attention deficit/hyperactivity disorder (89 vs. 36%), constipation (53 vs. 0%), arthralgias/myalgias (58 vs. 4%), narrative difficulties (74 vs. 32%), and atypical swallowing (74 vs. 18%). This study confirms the non-causal association between DCD and gJHM, which, in turn, seems to increase the risk for non-random additional features. The excess of language, learning, and swallowing difficulties in patients with DCD and gJHM suggests a wider effect of lax tissues in the development of the nervous system. © 2015 Wiley Periodicals, Inc.

[Distal soft-tissue procedure in hallux valgus deformity].

PubMed

Arbab, D; Wingenfeld, C; Frank, D; Bouillon, B; König, D P

2016-04-01

Distal, lateral soft tissue release to restore mediolateral balance of the first metatarsophalangeal (MTP) joint in hallux valgus deformity. Incision of the adductor hallucis tendon from the fibular sesamoid, the lateral capsule, the lateral collateral ligament, and the lateral metatarsosesamoid ligament. Hallux valgus deformities or recurrent hallux valgus deformities with an incongruent MTP joint. General medical contraindications to surgical interventions. Painful stiffness of the MTP joint, osteonecrosis, congruent joint. Relative contraindications: connective tissue diseases (Marfan syndrome, Ehler-Danlos syndrome). Longitudinal, dorsal incision in the first intermetatarsal web space between the first and second MTP joint. Blunt dissection and identification of the adductor hallucis tendon. Release of the adductor tendon from the fibular sesamoid. Incision of the lateral capsule, the lateral collateral ligament, and the lateral metatarsosesamoid ligament. Postoperative management depends on bony correction. In joint-preserving procedures, dressing for 3 weeks in corrected position. Subsequently hallux valgus orthosis at night and a toe spreader for a further 3 months. Passive mobilization of the first MTP joint. Postoperative weight-bearing according to the osteotomy. A total of 31 patients with isolated hallux valgus deformity underwent surgery with a Chevron and Akin osteotomy and a distal medial and lateral soft tissue balancing. The mean preoperative intermetatarsal (IMA) angle was 12.3° (range 11-15°); the hallux valgus (HV) angle was 28.2° (25-36°). The mean follow-up was 16.4 months (range 12-22 months). The mean postoperative IMA correction ranged between 2 and 7° (mean 5.2°); the mean HV correction was 15.5° (range 9-21°). In all, 29 patients (93%) were satisfied or very satisfied with the postoperative outcome, while 2 patients (7%) were not satisfied due to one delayed wound healing and one recurrent hallux valgus deformity. There were no infections, clinical and radiological signs of avascular necrosis of the metatarsal head, overcorrection with hallux varus deformity, or significant stiffness of the first MTP joint.

Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome--an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13.

PubMed

Giunta, Cecilia; Elçioglu, Nursel H; Albrecht, Beate; Eich, Georg; Chambaz, Céline; Janecke, Andreas R; Yeowell, Heather; Weis, MaryAnn; Eyre, David R; Kraenzlin, Marius; Steinmann, Beat

2008-06-01

We present clinical, radiological, biochemical, and genetic findings on six patients from two consanguineous families that show EDS-like features and radiological findings of a mild skeletal dysplasia. The EDS-like findings comprise hyperelastic, thin, and bruisable skin, hypermobility of the small joints with a tendency to contractures, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. The skeletal dysplasia comprises platyspondyly with moderate short stature, osteopenia, and widened metaphyses. Patients have an increased ratio of total urinary pyridinolines, lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP), of approximately 1 as opposed to approximately 6 in EDS VI or approximately 0.2 in controls. Lysyl and prolyl residues of collagens were underhydroxylated despite normal lysyl hydroxylase and prolyl 4-hydroxylase activities; underhydroxylation was a generalized process as shown by mass spectrometry of the alpha1(I)- and alpha2(I)-chain-derived peptides of collagen type I and involved at least collagen types I and II. A genome-wide SNP scan and sequence analyses identified in all patients a homozygous c.483_491 del9 SLC39A13 mutation that encodes for a membrane-bound zinc transporter SLC39A13. We hypothesize that an increased Zn(2+) content inside the endoplasmic reticulum competes with Fe(2+), a cofactor that is necessary for hydroxylation of lysyl and prolyl residues, and thus explains the biochemical findings. These data suggest an entity that we have designated "spondylocheiro dysplastic form of EDS (SCD-EDS)" to indicate a generalized skeletal dysplasia involving mainly the spine (spondylo) and striking clinical abnormalities of the hands (cheiro) in addition to the EDS-like features.

Longitudinal Changes in Segmental Aortic Stiffness Determined by Cardiac Magnetic Resonance in Children and Young Adults With Connective Tissue Disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos Syndromes, and Nonspecific Connective Tissue Disorders).

PubMed

Merlocco, Anthony; Lacro, Ronald V; Gauvreau, Kimberlee; Rabideau, Nicole; Singh, Michael N; Prakash, Ashwin

2017-10-01

Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% < 18 years old) with a CTD, and with at least 2 CMR examinations (total 152 examinations) over a median duration of 3.9 (1 to 13.2) years was performed. Aortic stiffness measures (strain, distensibility, and β stiffness index) were calculated on each examination at the aortic root (AoR), ascending aorta, and descending aorta. Longitudinal changes in parameters were analyzed using linear mixed-effects models. Aortic strain and distensibility decreased with age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10 -3  mm Hg -1 per 10-year increase in age) were 0.7, 1.3, and 1 at the AoR, ascending aorta, and descending aorta, respectively. The rates of decline in distensibility were not associated with the rates of AoR dilation or surgical AoR replacement. In conclusion, on serial CMR measurements in children and young adults with CTDs, aortic stiffness progressively increased with age, with rates of change only slightly higher than those previously reported in healthy adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal Structure of the Catalytic Domain of Drosophila [beta]1,4-Galactosyltransferase-7

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

Ramakrishnan, Boopathy; Qasba, Pradman K.

2010-11-03

The {beta}1,4-galactosyltransferase-7 ({beta}4Gal-T7) enzyme, one of seven members of the {beta}4Gal-T family, transfers in the presence of manganese Gal from UDP-Gal to an acceptor sugar (xylose) that is attached to a side chain hydroxyl group of Ser/Thr residues of proteoglycan proteins. It exhibits the least protein sequence similarity with the other family members, including the well studied family member {beta}4Gal-T1, which, in the presence of manganese, transfers Gal from UDP-Gal to GlcNAc. We report here the crystal structure of the catalytic domain of {beta}4Gal-T7 from Drosophila in the presence of manganese and UDP at 1.81 {angstrom} resolution. In the crystalmore » structure, a new manganese ion-binding motif (HXH) has been observed. Superposition of the crystal structures of {beta}4Gal-T7 and {beta}4Gal-T1 shows that the catalytic pocket and the substrate-binding sites in these proteins are similar. Compared with GlcNAc, xylose has a hydroxyl group (instead of an N-acetyl group) at C2 and lacks the CH{sub 2}OH group at C5; thus, these protein structures show significant differences in their acceptor-binding site. Modeling of xylose in the acceptor-binding site of the {beta}4Gal-T7 crystal structure shows that the aromatic side chain of Tyr{sup 177} interacts strongly with the C5 atom of xylose, causing steric hindrance to any additional group at C5. Because Drosophila Cd7 has a 73% protein sequence similarity to human Cd7, the present crystal structure offers a structure-based explanation for the mutations in human Cd7 that have been linked to Ehlers-Danlos syndrome.« less

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

PubMed Central

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Affected twins in the familial intracranial aneurysm study.

PubMed

Mackey, Jason; Brown, Robert D; Sauerbeck, Laura; Hornung, Richard; Moomaw, Charles J; Koller, Daniel L; Foroud, Tatiana; Deka, Ranjan; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L; Meissner, Irene; Anderson, Craig; Rouleau, Guy; Connolly, E Sander; Huston, John; Broderick, Joseph P

2015-01-01

Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs. © 2015 S. Karger AG, Basel.

Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7.

PubMed

Leegwater, Peter A; Vos-Loohuis, Manon; Ducro, Bart J; Boegheim, Iris J; van Steenbeek, Frank G; Nijman, Isaac J; Monroe, Glen R; Bastiaansen, John W M; Dibbits, Bert W; van de Goor, Leanne H; Hellinga, Ids; Back, Willem; Schurink, Anouk

2016-10-28

Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C > T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of the gene. The mutated gene implicates the extracellular matrix in the regular organization of chrondrocyte columns of the growth plate. Conservation of individual amino acids may not be necessary at the protein level but instead may reflect underlying conservation of nucleotide sequence that are required for efficient splicing.

Surgical and medical management of extracranial carotid artery aneurysms.

PubMed

Fankhauser, Grant T; Stone, William M; Fowl, Richard J; O'Donnell, Mark E; Bower, Thomas C; Meyer, Fredric B; Money, Samuel R

2015-02-01

Extracranial carotid artery aneurysms (ECCAs) are extremely rare with limited information about management options. Our purpose was to review our institution's experience with ECCAs during 15 years and to discuss the presentation and treatment of these aneurysms. A retrospective review of patients diagnosed with ECCAs from 1998 to 2012 was performed. Symptoms, risk factors, etiology, diagnostic methods, treatments, and outcomes were reviewed. During the study period, 141 aneurysms were diagnosed in 132 patients (mean age, 61 years; 69 men). There were 116 (82%) pseudoaneurysms and 25 (18%) true aneurysms; 69 (49%) aneurysms were asymptomatic, whereas 72 (52%) had symptoms (28 painless masses; 10 transient ischemic attacks; 10 vision symptoms; 9 ruptures; 8 strokes; 4 painful mass; 1 dysphagia; 1 tongue weakness; 1 bruit). Causes of true aneurysms included fibromuscular dysplasia in 15 patients, Ehlers-Danlos syndrome in three, Marfan syndrome in one, and uncharacterized connective tissue diseases in two. Of 25 true aneurysms, 11 (44%) were symptomatic; 15 (60%) true aneurysms underwent open surgical treatment, whereas 10 (40%) were managed nonoperatively. Postoperative complications included one stroke during a mean follow-up of 31 months (range, 0-166 months). No aneurysms managed nonoperatively required intervention during a mean follow-up of 77 months (range, 1-115 months). Of 116 pseudoaneurysms, 60 (52%) were symptomatic; 33 (29%) pseudoaneurysms underwent open surgery, 18 (15%) underwent endovascular intervention, and 65 (56%) were managed medically. Pseudoaneurysm after endarterectomy (28 patients; 24%) presented at a mean of 82 months from the surgical procedure. Mean follow-up for all aneurysms was 33.9 months. One (0.7%) aneurysm-related death occurred (rupture treated palliatively). No patient undergoing nonoperative management suffered death or major morbidity related to the aneurysm. Nonoperative management was more common in asymptomatic patients (71%) than in symptomatic patients (31%). ECCAs are uncommon and may be manifested with varying symptoms. All segments of the carotid artery are susceptible, although the internal is most commonly affected. Open surgical intervention was more common in patients with symptoms and with true aneurysms. Patients with pseudoaneurysms were more likely to undergo endovascular intervention. Nonoperative treatment is safe in selected patients. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Lumican Deficiency Results In Cardiomyocyte Hypertrophy With Altered Collagen Assembly

PubMed Central

Dupuis, Loren E.; Berger, Matthew G.; Feldman, Samuel; Doucette, Lorna; Fowlkes, Vennece; Chakravarti, Shukti; Thibaudeau, Sarah; Alcala, Nicolas E.; Bradshaw, Amy D.; Kern, Christine B.

2015-01-01

The ability of the heart to adapt to increased stress is dependent on modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest LUM deficient mice (lum−/−) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum−/− hearts have not been evaluated. These studies show LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum−/− neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum−/− hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum−/− hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum−/− hearts. There was also a reduction in the β and γ forms of collagenα1(I) in lum−/− hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum−/− hearts, indicating LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease. PMID:25886697

P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type VIA.

PubMed

Hudson, David M; Weis, MaryAnn; Rai, Jyoti; Joeng, Kyu Sang; Dimori, Milena; Lee, Brendan H; Morello, Roy; Eyre, David R

2017-03-03

Tandem mass spectrometry was applied to tissues from targeted mutant mouse models to explore the collagen substrate specificities of individual members of the prolyl 3-hydroxylase (P3H) gene family. Previous studies revealed that P3h1 preferentially 3-hydroxylates proline at a single site in collagen type I chains, whereas P3h2 is responsible for 3-hydroxylating multiple proline sites in collagen types I, II, IV, and V. In screening for collagen substrate sites for the remaining members of the vertebrate P3H family, P3h3 and Sc65 knock-out mice revealed a common lysine under-hydroxylation effect at helical domain cross-linking sites in skin, bone, tendon, aorta, and cornea. No effect on prolyl 3-hydroxylation was evident on screening the spectrum of known 3-hydroxyproline sites from all major tissue collagen types. However, collagen type I extracted from both Sc65 -/- and P3h3 -/- skin revealed the same abnormal chain pattern on SDS-PAGE with an overabundance of a γ 112 cross-linked trimer. The latter proved to be from native molecules that had intramolecular aldol cross-links at each end. The lysine under-hydroxylation was shown to alter the divalent aldimine cross-link chemistry of mutant skin collagen. Furthermore, the ratio of mature HP/LP cross-links in bone of both P3h3 -/- and Sc65 -/- mice was reversed compared with wild type, consistent with the level of lysine under-hydroxylation seen in individual chains at cross-linking sites. The effect on cross-linking lysines was quantitatively very similar to that previously observed in EDS VIA human and Plod1 -/- mouse tissues, suggesting that P3H3 and/or SC65 mutations may cause as yet undefined EDS variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

PubMed

Watson, Steve P

2009-01-01

The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of atherosclerotic plaques or the disorder Ehler-Danlos syndrome, which is caused by a defect in collagen synthesis and is associated with fragile blood vessels. This review will focus on the role of the subendothelial matrix in haemostasis and thrombosis, highlighting its potential as a target for novel antithrombotics.

Diseases and disorders of muscle.

PubMed

Pearson, A M; Young, R B

1993-01-01

Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.

Two-year outcomes of open shoulder anterior capsular reconstruction for instability from severe capsular deficiency.

PubMed

Dewing, Christopher B; Horan, Marilee P; Millett, Peter J

2012-01-01

To document outcomes after anterior capsulolabral reconstruction for recurrent shoulder instability in 15 patients (20 shoulders) who have had multiple failed stabilizations or collagen disorders. Twenty shoulders with recurrent instability underwent revision stabilization with allograft reconstruction of anterior capsulolabral structures, which re-creates the labrum and capsular ligaments. The patients comprised 3 men and 12 women (mean age, 26 years [range, 18 to 38 years]) in whom multiple prior repairs failed and who had disability from continued pain and instability. Patients could choose to undergo either arthrodesis or salvage allograft reconstruction or to live with permanent disability. Of the patients, 5 had Ehlers-Danlos syndrome whereas 10 had hyperlaxity syndromes without genetic confirmation. Failure was defined as further instability surgery. Pain, shoulder function, instability (dislocations/subluxation), and American Shoulder and Elbow Surgeons scores were documented. At follow-up, 9 of 20 shoulders (45%) remained stable. Recurrent instability was reported in 5 shoulders (25%), but the patients chose not to undergo further surgery. In the 14 shoulders without further stabilization (nonfailures), the mean American Shoulder and Elbow Surgeons score increased 43 points at a mean of 3.8 years (range, 2 to 6 years) postoperatively (P < .05). Mean satisfaction with outcome in nonfailures was 7 of 10 points (range, 1 to 10). Six shoulders failed by progressing to instability surgery at a mean of 8.6 months (range, 2.8 to 24 months). In the 6 shoulders that failed, the mean number of prior surgeries was 8 (range, 3 to 15) compared with a mean of 4 prior surgeries (range, 1 to 16) for the 9 nonfailures. Treating patients in whom multiple stabilizations have failed remains challenging. In our series 9 shoulders (45%) remained completely stable at 3.8 years. Recurrent instability (3 reinjuries) requiring further stabilization occurred in 6 (30%). Subsequent treatment for non-instability reasons was performed in 3 (15%). Instability was reported but revision surgery was not performed in 5 (25%). In 8 nonfailures (64%), the patients were highly satisfied with their surgical outcomes. Our results support this salvage procedure as a viable alternative to arthrodesis in young patients with end-stage shoulder instability or collagen disorders. Level IV, therapeutic case series. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Evaluation of the levels of metalloproteinsase-2 in patients with abdominal aneurysm and abdominal hernias.

PubMed

Antoszewska, Magdalena

2013-05-01

Abdominal aortic aneurysms and abdominal hernias become an important health problems of our times. Abdominal aortic aneurysm and its rupture is one of the most dangerous fact in vascular surgery. There are some theories pointing to a multifactoral genesis of these kinds of diseases, all of them assume the attenuation of abdominal fascia and abdominal aortic wall. The density and continuity of these structures depend on collagen and elastic fibers structure. Reducing the strength of the fibers may be due to changes in the extracellular matrix (ECM) by the proteolytic enzymes-matrix metalloproteinases (MMPs) that degrade extracellular matrix proteins. These enzymes play an important role in the development of many disease: malignant tumors (colon, breast, lung, pancreas), cardiovascular disease (myocardial infarction, ischemia-reperfusion injury), connective tissue diseases (Ehler-Danlos Syndrome, Marfan's Syndrome), complications of diabetes (retinopathy, nephropathy). One of the most important is matrix metalloproteinase-2 (MMP-2). The aim of the study was an estimation of the MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia, and in patients with only abdominal aortic aneurysm. The study involved 88 patients aged 42 to 89 years, including 75 men and 13 women. Patients were divided into two groups: patients with abdominal aortic aneurysm and primary abdominal hernia (45 persons, representing 51.1% of all group) and patients with only abdominal aortic aneurysm (43 persons, representing 48,9% of all group). It was a statistically significant increase in MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia compared to patients with only abdominal aortic aneurysm. It was a statistically significant increase in the prevalence of POCHP in patients with only abdominal aortic aneurysm compared to patients with abdominal aortic aneurysm and primary abdominal hernia. Statistically significant higher MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia seems shows that this enzyme plays a role in the pathogenesis of primary abdominal hernias. The observed distribution of MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia may raise the conclusion that this enzyme determines the presence of multi-organ failure of the connective tissue--the patients with only abdominal aortic aneurysm had significantly lower MMP-2 blood levels.

A cohort of 17 patients with kyphoscoliotic Ehlers–Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history

PubMed Central

Giunta, Cecilia; Baumann, Matthias; Fauth, Christine; Lindert, Uschi; Abdalla, Ebtesam M; Brady, Angela F; Collins, James; Dastgir, Jahannaz; Donkervoort, Sandra; Ghali, Neeti; Johnson, Diana S; Kariminejad, Ariana; Koch, Johannes; Kraenzlin, Marius; Lahiri, Nayana; Lozic, Bernarda; Manzur, Adnan Y; Morton, Jenny E V; Pilch, Jacek; Pollitt, Rebecca C; Schreiber, Gudrun; Shannon, Nora L; Sobey, Glenda; Vandersteen, Anthony; van Dijk, Fleur S; Witsch-Baumgartner, Martina; Zschocke, Johannes; Pope, F Michael; Bönnemann, Carsten G; Rohrbach, Marianne

2018-01-01

Purpose In 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers–Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis–trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date. Methods We report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data. Results Based on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals. Conclusion Our data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS. PMID:28617417

Abnormal brain structure as a potential biomarker for venous erectile dysfunction: evidence from multimodal MRI and machine learning.

PubMed

Li, Lingli; Fan, Wenliang; Li, Jun; Li, Quanlin; Wang, Jin; Fan, Yang; Ye, Tianhe; Guo, Jialun; Li, Sen; Zhang, Youpeng; Cheng, Yongbiao; Tang, Yong; Zeng, Hanqing; Yang, Lian; Zhu, Zhaohui

2018-03-29

To investigate the cerebral structural changes related to venous erectile dysfunction (VED) and the relationship of these changes to clinical symptoms and disorder duration and distinguish patients with VED from healthy controls using a machine learning classification. 45 VED patients and 50 healthy controls were included. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS) and correlation analyses of VED patients and clinical variables were performed. The machine learning classification method was adopted to confirm its effectiveness in distinguishing VED patients from healthy controls. Compared to healthy control subjects, VED patients showed significantly decreased cortical volumes in the left postcentral gyrus and precentral gyrus, while only the right middle temporal gyrus showed a significant increase in cortical volume. Increased axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) values were observed in widespread brain regions. Certain regions of these alterations related to VED patients showed significant correlations with clinical symptoms and disorder durations. Machine learning analyses discriminated patients from controls with overall accuracy 96.7%, sensitivity 93.3% and specificity 99.0%. Cortical volume and white matter (WM) microstructural changes were observed in VED patients, and showed significant correlations with clinical symptoms and dysfunction durations. Various DTI-derived indices of some brain regions could be regarded as reliable discriminating features between VED patients and healthy control subjects, as shown by machine learning analyses. • Multimodal magnetic resonance imaging helps clinicians to assess patients with VED. • VED patients show cerebral structural alterations related to their clinical symptoms. • Machine learning analyses discriminated VED patients from controls with an excellent performance. • Machine learning classification provided a preliminary demonstration of DTI's clinical use.

Musculocontractural Ehlers–Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin

PubMed Central

Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders

2016-01-01

ABSTRACT Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers–Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial–mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo. Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. PMID:27101845

Outcomes following neonatal cardiopulmonary resuscitation.

PubMed

Boldingh, Anne Marthe; Solevåg, Anne Lee; Nakstad, Britt

2018-05-29

Hjerte-lunge-redning av et kritisk sykt barn ved fødsel kan føre til overlevelse eller død. De som overlever kan utvikle komplikasjoner direkte etter fødsel eller senere i småbarns- og skolealder. Hypoksisk iskemisk encefalopati er en tilstand med nevrologiske symptomer hos den nyfødte etter hypoksi ved fødsel. Tilstanden klassifiseres som mild, moderat eller alvorlig. Vi ønsket å gi en oversikt over kort- og langtidsutfall etter hjerte-lunge-redning ved fødsel. Vi søkte i databasen Medline for utfall etter hjerte-lunge-redning ved fødsel. Vi identifiserte 15 indekserte, fagfellevurderte originalartikler og to metaanalyser om utfall etter hjerte-lunge-redning ved fødsel eller fødselsasfyksi. Hypoksisk iskemisk encefalopati rammer generelt 38 % av pasientene i mild til moderat grad og 23 % i alvorlig grad. Dødeligheten varierte fra 10 % i høy- til 28 % i lavinntektsland. Overlevende utvikler ofte motoriske, kognitive og sensoriske utviklingshemninger. I noen tilfeller blir det først avdekket ved skolestart når mer komplekse ferdigheter kreves. Funksjonshemning ved skolealder er sterkt korrelert til tilstanden i småbarnsalder. Endringer i algoritmene ved hjerte-lunge-redning og rutinebehandling med hypotermi har redusert risikoen for alvorlige følgetilstander etter hypoksisk iskemisk encefalopati.

Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?

PubMed

Adib, N; Davies, K; Grahame, R; Woo, P; Murray, K J

2005-06-01

Joint hypermobility (JH) or "ligamentous laxity" is felt to be an underlying risk factor for many types of musculoskeletal presentation in paediatrics, and joint hypermobility syndrome (JHS) describes such disorders where symptoms become chronic, often more generalized and associated with functional impairment. Clinical features are felt to have much in common with more severe disorders, including Ehlers-Danlos syndrome (EDS), osteogenesis imperfecta and Marfan syndrome, although this has not been formally studied in children. We defined the clinical characteristics of all patients with joint hypermobility-related presentations seen from 1999 to 2002 in a tertiary referral paediatric rheumatology unit. Patients were identified and recruited from paediatric rheumatology clinic and ward, and a dedicated paediatric rheumatology hypermobility clinic at Great Ormond Street Hospital. Data were collected retrospectively on the patients from the paediatric rheumatology clinics (1999-2002) and prospectively on patients seen in the hypermobility clinic (2000-2002). Specifically, historical details of developmental milestones, musculoskeletal or soft tissue diagnoses and symptoms, and significant past medical history were recorded. Examination features sought included measurements of joint and soft tissue laxity, and associated conditions such as scoliosis, dysmorphic features, cardiac murmurs and eye problems. One hundred and twenty-five children (64 females) were included on whom sufficient clinical data could be identified and who had clinical problems ascribed to JH present for longer than 3 months. Sixty-four were from the paediatric rheumatology clinic and 61 from the hypermobility clinic. No differences were found in any of the measures between the two populations and results are presented in a combined fashion. Three-quarters of referrals came from paediatricians and general practitioners but in only 10% was hypermobility recognized as a possible cause of joint complaint. The average age at onset of symptoms was 6.2 yr and age at diagnosis 9.0 yr, indicating a 2- to 3-yr delay in diagnosis. The major presenting complaint was arthralgia in 74%, abnormal gait in 10%, apparent joint deformity in 10% and back pain in 6%. Mean age at first walking was 15.0 months; 48% were considered "clumsy" and 36% as having poor coordination in early childhood. Twelve per cent had "clicky" hips at birth and 4% actual congenital dislocatable hip. Urinary tract infections were present in 13 and 6% of the female and male cases, respectively. Thirteen and 14%, respectively, had speech and learning difficulties diagnosed. A history of recurrent joint sprains was seen in 20% and actual subluxation/dislocation of joints in 10%. Forty per cent had experienced problems with handwriting tasks, 48% had major limitations of school-based physical education activities, 67% other physical activities and 41% had missed significant periods of schooling because of symptoms. Forty-three per cent described a history of easy bruising. Examination revealed that 94% scored > or =4/9 on the Beighton scale for generalized hypermobility, with knees (92%), elbows (87%), wrists (82%), hand metacarpophalangeal joints (79%), and ankles (75%) being most frequently involved. JHS is poorly recognized in children with a long delay in the time to diagnosis. Although there is a referral bias towards joint symptoms, a surprisingly large proportion is associated with significant neuromuscular and motor development problems. Our patients with JHS also show many overlap features with genetic disorders such as EDS and Marfan syndrome. The delay in diagnosis results in poor control of pain and disruption of normal home life, schooling and physical activities. Knowledge of the diagnosis and simple interventions are likely to be highly effective in reducing the morbidity and cost to the health and social services.

A Retrospective 2D Morphometric Analysis of Adult Female Chiari Type I Patients with Commonly Reported and Related Conditions

PubMed Central

Eppelheimer, Maggie S.; Houston, James R.; Bapuraj, Jayapalli R.; Labuda, Richard; Loth, Dorothy M.; Braun, Audrey M.; Allen, Natalie J.; Heidari Pahlavian, Soroush; Biswas, Dipankar; Urbizu, Aintzane; Martin, Bryn A.; Maher, Cormac O.; Allen, Philip A.; Loth, Francis

2018-01-01

Purpose: Researchers have sought to better understand Chiari type I malformation (CMI) through morphometric measurements beyond tonsillar position (TP). Soft tissue and bone structures within the brain and craniocervical junction have been shown to be different for CMI patients compared to healthy controls. Yet, several morphological characteristics have not been consistently associated with CMI. CMI is also associated with different prevalent conditions (PCs) such as syringomyelia, pseudotumor, Ehlers-Danlos syndrome (EDS), scoliosis, and craniocervical instability. The goal of this study was two-fold: (1) to identify unique morphological characteristics of PCs, and (2) to better explain inconsistent results from case-control comparisons of CMI. Methods: Image, demographic, and PC information was obtained through the Chiari1000, a self-report web-accessed database. Twenty-eight morphometric measurements (MMs) were performed on the cranial MR images of 236 pre-surgery adult female CMI participants and 140 female healthy control participants. Custom software was used to measure 28 structures within the posterior cranial fossa (PCF) compartment, craniocervical junction, oral cavity, and intracranial area on midsagittal MR images for each participant. Results: Morphometric analysis of adult females indicated a smaller McRae line length in CMI participants with syringomyelia compared to those without syringomyelia. TP was reduced in CMI participants with EDS than those without EDS. Basion to posterior axial line was significantly longer in CMI participants with scoliosis compared to those without scoliosis. No additional MMs were found to differ between CMI participants with and without a specific PC. Four morphometric differences were found to be consistently different between CMI participants and healthy controls regardless of PC: larger TP and a smaller clivus length, fastigium, and corpus callosum height in CMI participants. Conclusion: Syringomyelia, EDS, and scoliosis were the only PCs that showed significant morphometric differences between CMI participants. Additionally, four midsagittal MR-based MMs were found to be significantly different between healthy controls and CMI participants regardless of the presence of one or more PCs. This study suggests that the prevalence of comorbid conditions are not strongly related to CMI morphology, and that inconsistent findings in the radiographic literature cannot be explained by varying prevalence of comorbid conditions in CMI study samples. PMID:29403363

Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans.

PubMed

Lee, Jae-Hong; Choi, Jung-Kyu; Kim, Sang-Hyun; Cho, Kyung-Hyun; Kim, Young-Taek; Choi, Seong-Ho; Jung, Ui-Won

2017-04-01

The National Health Insurance Service-National Sample Cohort and medical checkup data from 2002 to 2013 were used to evaluate the association between periodontal surgery for the treatment of periodontitis (PSTP) and vasculogenic erectile dysfunction (VED). Bivariate and multivariate logistic regression analyses were applied to a longitudinal retrospective database to assess the association between PSTP and VED while adjusting for the potential confounding effects of sociodemographic factors (age, household income, insurance status, health status, residence area, and smoking status) and comorbidities (diabetes mellitus, angina pectoris, cerebral infarction, and myocardial infarction). Among the 7,148 PSTP within the 268,296 recruited subjects, the overall prevalence of VED in PSTP was 1.43% (n=102). The bivariate analysis showed that VED was significantly related to PSTP (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.38-2.06; P <0.001), and this was confirmed in the multivariate analysis after adjusting for sociodemographic factors and comorbidities (OR, 1.29; 95% CI, 1.06-1.58; P =0.002). Subjects with a history of periodontal flap surgery had a significantly higher risk of VED, after adjusting for potential confounding factors. Further studies are required to identify the key mechanisms underlying the association between severe periodontal disease and VED.

Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans

PubMed Central

2017-01-01

Purpose The National Health Insurance Service-National Sample Cohort and medical checkup data from 2002 to 2013 were used to evaluate the association between periodontal surgery for the treatment of periodontitis (PSTP) and vasculogenic erectile dysfunction (VED). Methods Bivariate and multivariate logistic regression analyses were applied to a longitudinal retrospective database to assess the association between PSTP and VED while adjusting for the potential confounding effects of sociodemographic factors (age, household income, insurance status, health status, residence area, and smoking status) and comorbidities (diabetes mellitus, angina pectoris, cerebral infarction, and myocardial infarction). Results Among the 7,148 PSTP within the 268,296 recruited subjects, the overall prevalence of VED in PSTP was 1.43% (n=102). The bivariate analysis showed that VED was significantly related to PSTP (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.38–2.06; P<0.001), and this was confirmed in the multivariate analysis after adjusting for sociodemographic factors and comorbidities (OR, 1.29; 95% CI, 1.06–1.58; P=0.002). Conclusions Subjects with a history of periodontal flap surgery had a significantly higher risk of VED, after adjusting for potential confounding factors. Further studies are required to identify the key mechanisms underlying the association between severe periodontal disease and VED. PMID:28462008

Obliteration of a giant fusiform carotid terminus-M1 aneurysm after distal clip application and extracranial-intracranial bypass. Case report.

PubMed

Ferroli, P; Ciceri, E; Parati, E; Minati, L; Broggi, G

2007-06-01

Giant intracranial aneurysms may not be amenable to direct surgical clipping or endovascular coiling because of three critical factors: 1) lack of clear aneurysmal neck; 2) giant size; 3) involvement with critical perforating or branch vessels. Techniques of flow redirection, however, may offer an alternative treatment strategy for these difficult lesions. In this paper, we report on the use of this alternative strategy in the successful treatment of a left giant fusiform carotid terminus-M1 aneurysm in a 16 year-old boy suffering from Ehler-Danlos disease. This patient was admitted to our Institution because his aneurysm was continuing to be increasing in size, despite a previous ligation of his left cervical ICA which was performed at another institution 2 years earlier after the patient had experienced a hemorrhagic stroke. Upon admission, a neurological examination revealed a slight motor aphasia with mild right hemiparesis, remnant of the ancient stroke. Because of its size and the involvement with M1 perforating arteries, a direct aneurysm attack was deemed inadvisable. After an initial ECA-ICA high flow bypass which spontaneously thrombosed, we performed a repeated high flow bypass with the application of a single clip on M1, right distal to the fusiform dilatation. After an uneventful postoperative course, we were unable to observe any new neurological deficits after surgery. A CT scan on postoperative day 1 revealed that the aneurysm had undergone a spontaneous thrombosis which was completely obliterated at the time of a 6-month follow-up angiogram. At that time, the ECA-ICA bypass was found to be patent. In conclusion the alternative of flow alteration strategies can be successfully used in the treatment of aneurysms that cannot be safely trapped or occluded by traditional neurosurgical methods.

Comparison of the effects of extracorporeal shock wave therapy and a vacuum erectile device on penile erectile dysfunction: a randomized clinical trial.

PubMed

Qi, Tao; Ye, Lei; Wang, Bo; Zhang, Bin; Chen, Jun

2017-11-01

This randomized clinical trial (October 2012-December 2013) compared extracorporeal shock wave therapy (ESWT) and a vacuum erectile device (VED) for management of erectile dysfunction (ED). Consecutive Chinese patients (20-55 years) with ED, abnormal nocturnal penile tumescence and rigidity (NPTR), and international index of erectile function-5 items (IIEF-5) score <22 were randomized to receive ESWT or VED (twice weekly, 4 weeks). Primary outcomes were treatment efficacy and success rate 4 weeks after completion of therapy. Secondary outcomes included changes in IIEF-5 score, sex encounter profile (SEP) score, erection hardness score (EHS) and NPTR assessments 4 weeks post-therapy. All enrolled patients (n = 30 per group) completed the study. At baseline, age, IIEF-5 score, SEP score, EHS, and NPTR assessments were similar between groups. Four weeks post-therapy, IIEF-5 score increased in the ESWT (15.03 ± 3.00 vs. 11.60 ± 2.28) and VED (15.10 ± 3.06 vs. 11.53 ± 2.27) groups, as did SEP score, EHS, and NPTR measures (all P < .05). Efficacy in the ESWT and VED groups was excellent in 10% and 13.3%, respectively, and moderate in 63.3% and 53.3%, respectively. Treatment success rate in the ESWT and VED groups was 73.3% and 67.7%, respectively. VED use and ESWT have comparable efficacies in the treatment of ED in Chinese patients.

Effect of agmatine on experimental vascular endothelial dysfunction.

PubMed

Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

2016-05-01

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

Comparison of the effects of extracorporeal shock wave therapy and a vacuum erectile device on penile erectile dysfunction: a randomized clinical trial

PubMed Central

Qi, Tao; Ye, Lei; Wang, Bo; Zhang, Bin; Chen, Jun

2017-01-01

Abstract Background: This randomized clinical trial (October 2012–December 2013) compared extracorporeal shock wave therapy (ESWT) and a vacuum erectile device (VED) for management of erectile dysfunction (ED). Methods: Consecutive Chinese patients (20–55 years) with ED, abnormal nocturnal penile tumescence and rigidity (NPTR), and international index of erectile function-5 items (IIEF-5) score <22 were randomized to receive ESWT or VED (twice weekly, 4 weeks). Primary outcomes were treatment efficacy and success rate 4 weeks after completion of therapy. Secondary outcomes included changes in IIEF-5 score, sex encounter profile (SEP) score, erection hardness score (EHS) and NPTR assessments 4 weeks post-therapy. All enrolled patients (n = 30 per group) completed the study. At baseline, age, IIEF-5 score, SEP score, EHS, and NPTR assessments were similar between groups. Results: Four weeks post-therapy, IIEF-5 score increased in the ESWT (15.03 ± 3.00 vs. 11.60 ± 2.28) and VED (15.10 ± 3.06 vs. 11.53 ± 2.27) groups, as did SEP score, EHS, and NPTR measures (all P < .05). Efficacy in the ESWT and VED groups was excellent in 10% and 13.3%, respectively, and moderate in 63.3% and 53.3%, respectively. Treatment success rate in the ESWT and VED groups was 73.3% and 67.7%, respectively. Conclusion: VED use and ESWT have comparable efficacies in the treatment of ED in Chinese patients. PMID:29095274

Assessment of vascular and endothelial dysfunction in nutritional studies.

PubMed

Ray, S; Miglio, C; Eden, T; Del Rio, D

2014-09-01

Vascular and endothelial dysfunction (VED) is emerging as a potential set of early markers of cardiovascular disease risk and tests for its measurement have been widely used in clinical research. The aim of this viewpoint is to describe and discuss the current usage of these measures in well-designed nutritional trials, using the potential relationship between fruit juice intake and VED as example. A search was conducted using the NHS evidence portal including studies published in English between January 1980 and October 2013. Only 10 suitable studies were selected, which investigated the effect of fruit juice intake on VED, among which 4 interventions used flow-mediated dilatation, 2 arterial stiffness, 2 a combination of arterial stiffness and flow-mediated dilatation, 2 carotid intimal media thickness and 1 iontophoresis with laser Doppler. Despite minimal effects reported on classical CVD markers, such as lipids, 8 out of the 10 identified studies reported an effect on endothelial function following juice consumption, indicating that VED tests can be effectively used in human dietary interventions to identify relationships between bioactive compounds from fruit and CVD risk. However, paucity of available data, scarcity of compound bioavailability and metabolism information, strong heterogeneity among experimental methodologies and a number of limitations to study designs, still limit the interpretation of the results obtained through these measures. Future, well-designed studies with greater attention to consider use of VED measures are needed to strengthen the utility of VED tests in nutrition research such as those investigating the impact of polyphenol-rich juices and CVD risk. Copyright © 2014 Elsevier B.V. All rights reserved.

Biological functions of iduronic acid in chondroitin/dermatan sulfate

PubMed Central

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-01-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler–Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. PMID:23441919

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

Momeni, D.; Ramazani-Arani, R.; Nouri-Zonoz, M.

Using the Ehlers transformation along with the gravitoelectromagnetic approach to stationary spacetimes we start from the Morgan-Morgan disk spacetime (without radial pressure) as the seed metric and find its corresponding stationary spacetime. As expected from the Ehlers transformation the stationary spacetime obtained suffers from a NUT-type singularity and the new parameter introduced in the stationary case could be interpreted as the gravitomagnetic monopole charge (or the NUT factor). Some of the properties of this spacetime including its particle velocity distribution, gravitational redshift, stability, and energy conditions are discussed.

Micromachined TWTs for THz Radiation Sources

NASA Technical Reports Server (NTRS)

Booske, John H.; vanderWeide, Daniel W.; Kory, Carol L.; Limbach, S.; Downey, Alan (Technical Monitor)

2001-01-01

The Terahertz (THz) region of the electromagnetic spectrum (about 300 - 3000 GHz in frequency or about 0.1 - 1 mm free space wavelength) has enormous potential for high-data-rate communications, spectroscopy, astronomy, space research, medicine, biology, surveillance, remote sensing, industrial process control, etc. It has been characterized as the most scientifically rich, yet under-utilized, region of the electromagnetic spectrum. The most critical roadblock to full exploitation of the THz band is lack of coherent radiation sources that are powerful (0.001 - 1.0 W continuous wave), efficient (> 1%), frequency agile (instantaneously tunable over 1% bandwidths or more), reliable, and comparatively inexpensive. To develop vacuum electron device (VED) radiation sources satisfying these requirements, fabrication and packaging approaches must be heavily considered to minimize costs, in addition to the basic interaction physics and circuit design. To minimize size of the prime power supply, beam voltage must be minimized, preferably 10 kV. Solid state sources satisfy the low voltage requirement, but are many orders of magnitude below power, efficiency, and bandwidth requirements. On the other hand, typical fast-wave VED sources in this regime (e.g., gyrotrons, FELs) tend to be large, expensive, high voltage and very high power devices unsuitable for most of the applications cited above. VEDs based on grating or inter-digital (ID) circuits have been researched and developed. However, achieving forward-wave amplifier operation with instantaneous fractional bandwidths > 1% is problematic for these devices with low-energy (< 15 kV) electron beams. Moreover, the interaction impedance is quite low unless the beam-circuit spacing is kept particularly narrow, often leading to significant beam interception. One solution to satisfy the THz source requirements mentioned above is to develop micromachined VEDs, or "micro-VEDs". Among other benefits, micro-machining technologies provide superior high frequency wall conductivity as a result of superior surface smoothness compared with conventional mechanical or electric discharge machining approaches. Micro-VED technologies are already being applied to the development of millimeter-wave klystrons at Stanford Linear Accelerator Center and submillimeter-wave klystrons at the University of Leeds. We are investigating the use of micro-machining technologies to develop THz regime TWTs, with emphasis on folded-waveguide TWTs. The folded-waveguide TWT (FW-TWT) has several features that make it attractive for THz-regime micro-VED applications. It is a relatively simple circuit to design and fabricate, it is amenable to precision pattern replication by micro-machining, and it is has been demonstrated capable of forward-wave amplification with appreciable bandwidth. We are conducting experimental and computational studies of micro-VED FW-TWTs to examine their feasibility for applications at frequencies from 200 - 1000 GHz.

Interdisciplinary evaluation of dysphagia: clinical swallowing evaluation and videoendoscopy of swallowing.

PubMed

Sordi, Marina de; Mourão, Lucia Figueiredo; Silva, Ariovaldo Armando da; Flosi, Luciana Claudia Leite

2009-01-01

Patients with dysphagia have impairments in many aspects, and an interdisciplinary approach is fundamental to define diagnosis and treatment. A joint approach in the clinical and videoendoscopy evaluation is paramount. To study the correlation between the clinical assessment (ACD) and the videoendoscopic (VED) assessment of swallowing by classifying the degree of severity and the qualitative/descriptive analyses of the procedures. cross-sectional, descriptive and comparative. held from March to December of 2006, at the Otolaryngology/Dysphagia ward of a hospital in the country side of São Paulo. 30 dysphagic patients with different disorders were assessed by ACD and VED. The data was classified by means of severity scales and qualitative/ descriptive analysis. the correlation between severity ACD and VED scales pointed to a statistically significant low agreement (KAPA = 0.4) (p=0,006). The correlation between the qualitative/descriptive analysis pointed to an excellent and statistically significant agreement (KAPA=0.962) (p<0.001) concerning the entire sample. the low agreement between the severity scales point to a need to perform both procedures, reinforcing VED as a doable procedure. The descriptive qualitative analysis pointed to an excellent agreement, and such data reinforces our need to understand swallowing as a process.

Pulsed Artificial Electrojet Generation

NASA Astrophysics Data System (ADS)

Papadopoulos, K.

2008-12-01

Traditional techniques for generating low frequency signals in the ULF/ELF range (.1-100 Hz) and rely on ground based Horizontal Electric Dipole (HED) antennas. It is, furthermore, well known that a Vertical Electric Dipole (VED) is by more than 50 dB more efficient than a HED with the same dipole current moment. However, the prohibitively long length of VED antennas in the ELF/ULF range coupled with voltage limitations due to corona discharge in the atmosphere make them totally impracticable. In this paper we discuss a novel concept, inspired by the physics of the equatorial electrojet, that allows for the conversion of a ground based HED to a VED in the E-region of the equatorial ionosphere with current moment comparable to the driving HED. The paper focuses in locations near the dip-equator, where the earth's magnetic is in predominantly in the horizontal direction. The horizontal electric field associated with a pulsed HED drives a large Hall current in the ionospheric E-region, resulting in a vertical current. It is shown that the pulsed vertical current in the altitude range 80-130 km, driven by a horizontal electric field of, approximately, .1 mV/m at 100 km altitude, is of the order of kA. This results in a pulsed VED larger than 106 A-m. Such a pulsed VED will drive ELF/ULF pulses with amplitude in excess of .1 nT at a lateral range larger than few hundred kilometers. This is by three orders of magnitude larger than the one expected by a HED with comparable current moment. The paper will conclude with the description of a sneak-through technique that allows for creating pulsed electric fields in the ionosphere much larger than expected from steady state oscillatory HED antennas.

Is early measles vaccination better than later measles vaccination?

PubMed

Aaby, Peter; Martins, Cesário L; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2015-01-01

WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies comparing measles-vaccinated and measles-unvaccinated children; however, only 16 studies had specific information that MV had been provided at 4-13 months of age, many before 9 months of age. In the 10 best studies (4 randomized trials and 6 observational studies) control children did not receive MV during follow-up. In eight of these studies the vaccine efficacy against death (VED) was 60% or more. In four studies with information on MV provided both before and after 12 months of age, the all-cause mortality reduction was significantly larger for children vaccinated in infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction in mortality. In five studies with information on measles infection, VED was 67% (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47-77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months of age and found significantly lower all-cause mortality with early vaccination, the difference being 39% (8-60%). Child mortality may be reduced if MV is given earlier than currently recommended by international organizations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predictive modeling of slope deposits and comparisons of two small areas in Northern Germany

NASA Astrophysics Data System (ADS)

Shary, Peter A.; Sharaya, Larisa S.; Mitusov, Andrew V.

2017-08-01

Methods for correct quantitative comparison of several terrains are important in the development and use of quantitative landscape evolution models, and they need to introduce specific modeling parameters. We introduce such parameters and compare two small terrains with respect to the link slope-valley for the description of slope deposits (colluvium) in them. We show that colluvium accumulation in small areas cannot be described by linear models and thus introduce non-linear models. Two small areas, Perdoel (0.29 ha) and Bornhöved (3.2 ha), are studied. Slope deposits in the both are mainly in dry valleys, with a total thickness Mtotal up to 2.0 m in Perdoel and up to 1.2 m in Bornhöved. Parent materials are mainly Pleistocene sands aged 30 kyr BP. Exponential models of multiple regression that use a 1-m LiDAR DEM (digital elevation model) explained 70-93% of spatial variability in Mtotal. Parameters DH12 and DV12 of horizontal and vertical distances are introduced that permit to characterize and compare conditions of colluvium formation for various terrains. The study areas differ 3.7 times by the parameter DH12 that describes a horizontal distance from thalwegs at which Mtotal diminishes 2.72 times. DH12 is greater in Bornhöved (29.7 m) than in Perdoel (8.12 m). We relate this difference in DH12 to the distinction between types of the link slope-valley: a regional type if catchment area of a region outside a given small area plays an important role, and a local type when accumulation of colluvium from valley banks within a small area is of more importance. We argue that the link slope-valley is regional in Perdoel and local in Bornhöved. Peaks of colluvium thickness were found on thalwegs of three studied valleys by both direct measurements in a trench, and model surfaces of Mtotal. A hypothesis on the formation mechanism of such peaks is discussed. The parameter DV12 describes a vertical distance from a peak of colluvium thickness along valley bottom at which Mtotal diminishes 2.72 times; values of this parameter differ 1.4 times for the study areas. DV12 is greater in Perdoel (3.0 m) than in Bornhöved (2.1 m) thus indicating more sharp peaks of Mtotal in Bornhöved. Exponential models allow construction of predictive maps of buried Pleistocene surfaces for both the terrains and calculate colluvium volumes with an error 4.2% for Perdoel and 7.1% for Bornhöved. Comparisons of buried and present surfaces showed that the latter are more smoothed, more strongly in valleys where flow branching is increased.

Terahertz-Regime, Micro-VEDs: Evaluation of Micromachined TWT Conceptual Designs

NASA Technical Reports Server (NTRS)

Booske, John H.; Kory, Carol L.; Gallagher, D.; van der Weide, Daniel W.; Limbach, S; Gustafson, P; Lee, W.-J.; Gallagher, S.; Jain, K.

2001-01-01

Summary form only given. The Terahertz (THz) region of the electromagnetic spectrum (approx.300-3000 GHz) has enormous potential for high-data-rate communications, spectroscopy, astronomy, space research, medicine, biology, surveillance, remote sensing, industrial process control, etc. The most critical roadblock to full exploitation of the THz band is lack of coherent radiation sources that are powerful (0.01-10.0 W continuous wave), efficient (>1 %), frequency agile (instantaneously tunable over 1% bandwidths or more), reliable, and relatively inexpensive. Micro-machined Vacuum Electron Devices (micro-VEDs) represent a promising solution. We describe prospects for miniature, THz-regime TWTs fabricated using micromachining techniques. Several approx.600 GHz conceptual designs are compared. Their expected performance has been analyzed using SD, 2.51), and 3D TWT codes. A folded waveguide (FWG) TWT forward-wave amplifier design is presented based on a Northrop Grumman (NGC) optimized design procedure. This conceptual device is compared to the simulated performance of a novel, micro-VED helix TWT. Conceptual FWG TWT backward-wave amplifiers and oscillators are also discussed. A scaled (100 GHz) FWG TWT operating at a relatively low voltage (-12 kV) is under development at NGC. Also, actual-size micromachining experiments are planned to evaluate the feasibility of arrays of micro-VED TWTs. Progress and results of these efforts are described. This work was supported, in part by AFOSR, ONR, and NSF.

Effects of toothbrush hardness on in vitro wear and roughness of composite resins.

PubMed

Kyoizumi, Hideaki; Yamada, Junji; Suzuki, Toshimitsu; Kanehira, Masafumi; Finger, Werner J; Sasaki, Keiichi

2013-11-01

To investigate and compare the effects of toothbrushes with different hardness on abrasion and surface roughness of composite resins. Toothbrushes (DENT. EX Slimhead II 33, Lion Dental Products Co. Ltd., Tokyo, Japan) marked as soft, medium and hard, were used to brush 10 beam-shaped specimens of each of three composites resins (Venus [VEN], Venus Diamond [VED] and Venus Pearl [VEP]; HeraeusKulzer) with standardized calcium carbonate slurry in a multistation testing machine (2N load, 60 Hz). After each of five cycles with 10k brushing strokes the wear depth and surface roughness of the specimens were determined. After completion of 50k strokes representative samples were inspected by SEM. Data were treated with ANOVA and regression analyses (p < 0.05). Abrasion of the composite resins increased linearly with increasing number of brushing cycles (r² > 0.9). Highest wear was recorded for VEN, lowest for VED. Hard brushes produced significantly higher wear on VEN and VEP, whereas no difference in wear by toothbrush type was detected for VED. Significantly highest surface roughness was found on VED specimens (Ra > 1.5 µm), the lowest one on VEN (Ra < 0.3 µm). VEN specimens showed increased numbers of pinhole defects when brushed with hard toothbrushes, surfaces of VEP were uniformly abraded without level differences between the prepolymerized fillers and the glass filler-loaded matrix, VED showed large glass fillers protruding over the main filler-loaded matrix portion under each condition. Abrasion and surface roughness of composite resins produced by toothbrushing with dentifrice depend mainly on the type of restorative resin. Hardness grades of toothbrushes have minor effects only on abrasion and surface roughness of composite resins. No relationship was found between abrasion and surface roughness. The grade of the toothbrush used has minor effect on wear, texture and roughness of the composite resin.

Molecular, biochemical and functional analysis of a novel and developmentally important fibrillar collagen (Hcol-I) in hydra.

PubMed

Deutzmann, R; Fowler, S; Zhang, X; Boone, K; Dexter, S; Boot-Handford, R P; Rachel, R; Sarras, M P

2000-11-01

The body wall of hydra (a member of the phylum Cnidaria) is structurally reduced to an epithelial bilayer with an intervening extracellular matrix (ECM). Previous studies have established that cell-ECM interactions are important for morphogenesis and cell differentiation in this simple metazoan. The ECM of hydra is particularly interesting because it represents a primordial form of matrix. Despite progress in our understanding of hydra ECM, we still know little about the nature of hydra collagens. In the current study we provide a molecular, biochemical and functional analysis of a hydra fibrillar collagen that has similarity to vertebrate type I and type II collagens. This fibrillar collagen has been named hydra collagen-I (Hcol-I) because of its structure and because it is the first ECM collagen to be identified in hydra. It represents a novel member of the collagen family. Similar to vertebrate type I and II collagens, Hcol-I contains an N-terminal propeptide-like domain, a triple helical domain containing typical Gly-X-Y repeats and a C-terminal propeptide domain. The overall identity to vertebrate fibrillar collagens is about 30%, while the identity of the C-terminal propeptide domain is 50%. Because the N-terminal propeptide domain is retained after post-translational processing, Hcol-I does not form thick fibers as seen in vertebrates. This was confirmed using transmission electron microscopy to study rotary shadow images of purified Hcol-I. In addition, absence of crucial lysine residues and an overall reduction in proline content, results in reduced crosslinking of fibrils and increased flexibility of the molecule, respectively. These structural changes in Hcol-I help to explain the flexible properties of hydra ECM. Immunocytochemical studies indicate that Hcol-I forms the 10 nm fibrils that comprise the majority of molecules in the central fibrous zone of hydra ECM. The central fibrous zone resides between the two subepithelial zones where hydra laminin is localized. While previous studies have shown that basal lamina components like laminin are expressed by the endoderm, in situ hybridisation studies show that Hcol-I mRNA expression is restricted to the ectoderm. Hcol-I expression is upregulated during head regeneration, and antisense studies using thio-oligonucleotides demonstrated that blocking the translation of Hcol-I leads to a reversible inhibition of head morphogenesis during this regenerative process. Taken in total, the data presented in this study indicate that Hcol-I is required for morphogensis in hydra and represents a novel fibrillar collagen whose structural characteristics help to explain the unique biophysical properties of hydra ECM. Interestingly, the structure of Hcol-I mimics what is seen in Ehlers-Danlos syndrome type VII in humans; an inherited pathological condition that leads to joint and skin abnormalities. Hcol-I therefore illustrates an adaptive trait in which the normal physiological situation in hydra translates into a pathological condition in humans.

Photophobia

MedlinePlus

... sensitivity; Vision - light sensitive; Eyes - sensitivity to light Images External and internal eye anatomy References Ehlers W, Suchecki J, Steinemann TL, Donshik P. Contact lens-related complications. ...

Clinical and molecular characterization of 40 patients with classic Ehlers–Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations

PubMed Central

2013-01-01

Background Classic Ehlers–Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. Methods This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. Results We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Conclusions Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS. PMID:23587214

Vessel Enhancement and Segmentation of 4D CT Lung Image Using Stick Tensor Voting

NASA Astrophysics Data System (ADS)

Cong, Tan; Hao, Yang; Jingli, Shi; Xuan, Yang

2016-12-01

Vessel enhancement and segmentation plays a significant role in medical image analysis. This paper proposes a novel vessel enhancement and segmentation method for 4D CT lung image using stick tensor voting algorithm, which focuses on addressing the vessel distortion issue of vessel enhancement diffusion (VED) method. Furthermore, the enhanced results are easily segmented using level-set segmentation. In our method, firstly, vessels are filtered using Frangi's filter to reduce intrapulmonary noises and extract rough blood vessels. Secondly, stick tensor voting algorithm is employed to estimate the correct direction along the vessel. Then the estimated direction along the vessel is used as the anisotropic diffusion direction of vessel in VED algorithm, which makes the intensity diffusion of points locating at the vessel wall be consistent with the directions of vessels and enhance the tubular features of vessels. Finally, vessels can be extracted from the enhanced image by applying level-set segmentation method. A number of experiments results show that our method outperforms traditional VED method in vessel enhancement and results in satisfied segmented vessels.

Consciousness, Cognition and the Cognitive Apparatus in the Vedānta Tradition

PubMed Central

Balasubramanian, R.

2011-01-01

A human being is a complex entity consisting of the Self (also known as Consciousness), mind, senses and the body. The Vedānta tradition holds that the mind, the senses and the body are essentially different from the Self or Consciousness. It is through consciousness that we are able to know the things of the world, making use of the medium of the mind and the senses. Furthermore, the mind, though material, is able to reveal things, borrowing the light from consciousness. From the phenomenological point of view, we have to answer the following questions: how does one know the mind/the mental operations/the cogitations of the mind? Does the mind know itself? Is it possible? There is, again, the problem of the intentionality of consciousness. Is consciousness intentional? According to Vedānta, consciousness by its very nature is not intentional, but it becomes intentional through the mind. The mind or the ego is not part of the consciousness; on the contrary, it is transcendent to consciousness. It is difficult to spell out the relation between consciousness and the mind. How does consciousness, which is totally different from the mind, get related to the mind in such a way that it makes the latter capable of comprehending the things of the world? The Vedānta tradition provides the answer to this question in terms of the knower-known relation. Consciousness is pure light, self-luminous by its very nature, that is, although it reveals other objects, it is not revealed by anything else. When Sartre describes it as nothingness, bereft of even ego, it is to show that it is pure light revealing objects outside it. PMID:21694962

A critical role of Gas6/Axl signal in allergic airway responses during RSV vaccine-enhanced disease.

PubMed

Shibata, Takehiko; Ato, Manabu

2017-11-01

Respiratory syncytial virus (RSV) is a common virus that causes lower respiratory infections across a wide range of ages. A licensed RSV vaccine is not available because vaccination with formalin-inactivated RSV (FI-RSV) and the subsequent RSV infection cause not only insufficient induction of neutralizing antibodies but also severe allergic airway responses, termed FI-RSV vaccine-enhanced disease (FI-RSV VED). However, the underlying mechanism has not been identified, although a Th2-biased immune response is known to be a hallmark of this disease. Our previous studies have shown that growth arrest-specific 6 (Gas6)/Axl signaling leads to Th2-biased immune responses during fungus-induced allergic airway inflammation. Here, we show that Gas6/Axl signaling also leads to FI-RSV VED and partially identify the mechanism in mice. Inhibiting Gas6/Axl signaling using Gas6-deficient mice, neutralizing antibodies, and a specific inhibitor of Axl attenuated allergic airway hyperresponsiveness, including airway inflammation, goblet cell hyperplasia, and Th2 cytokine production, in addition to increasing interferon-γ levels and the production of RSV-neutralizing IgG2a in FI-RSV VED. Gas6 was produced in lymph nodes during immunization with FI-RSV. Lymph node cells derived from immunized mice produced high levels of Gas6 and Th2 cytokines, but not IFN-γ, after restimulation with RSV. Finally, we found that dendritic cells stimulated with RSV-glycoprotein (G protein) produced Gas6 and that Axl signaling suppressed DC maturation and the induction of IL-12 production by the toll-like receptor 4 agonist RSV-fusion protein. Taken together, these results indicate that RSV-G protein-induced Gas6/Axl signaling causes allergic airway responses during FI-RSV VED.

Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats.

PubMed

Si, Lislivia Yiang-Nee; Kamisah, Yusof; Ramalingam, Anand; Lim, Yi Cheng; Budin, Siti Balkis; Zainalabidin, Satirah

2017-07-01

Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) C max = 234.5 ± 3.9%, Endo-(-) C max = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) C max = 264.5 ± 6.9%, Endo-(-) C max = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) R max = 73.2 ± 2.1%, Endo-(-) R max = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) R max = 57.8 ± 1.7%, Endo-(-) R max = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

Verbal Emotional Disclosure of Traumatic Experiences in Adolescents: The Role of Social Risk Factors

PubMed Central

Pérez, Silvia; Peñate, Wenceslao; Bethencourt, Juan M.; Fumero, Ascensión

2017-01-01

It is well-known that traumatic events and adverse life situations are very important in both physical and psychological health. Prevalence studies suggested that adolescents experience at least one potentially traumatic event before reaching age 18. The paradigm of research centered on expressive writing has evidenced the beneficial effects that the emotional disclosure of previous traumas produces on physical health and psychological adjustment. The aims of the study are threefold: determining the prevalence of adverse or traumatic events; examining the extent to which psychopathological symptoms developed in those exposed to traumatic events; and exploring an verbal emotional disclosure (VED) paradigm in which variations on time spent talking about traumatic experiences to others resulted in a reduction of the psychological impact of trauma in a sample of Spanish adolescents. 422 volunteer adolescents participated, 226 boys and 192 girls, from 10 to 19 years old, all of them living in Tenerife. The mean age was 14.8 years (SD = 1.83). All of them completed the instruments used to assess the psychological impact of traumatic experiences and VED. The main results indicated that 77% of the participants had suffered a traumatic situation. The participants who have been exposed to traumatic events scored significantly higher in measures of post-traumatic stress, disorder, intrusive thoughts, avoidance behaviors, anxiety and depression, compared to those without trauma. Furthermore, results show a decrease in symptomatology scores as a function of time spent disclosing emotional experiences to others, particularly when disclosure occurred several times. In conclusion, stressful events or traumatic experiences and their concomitant emotional effects are highly prevalent in adolescents, and repeated VED to others appears to ameliorate their impact. VED shows greater therapeutic benefits when adolescents narrate the experience on several occasions and in an extensive way. PMID:28352242

Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

PubMed

Halper, Jaroslava; Kjaer, Michael

2014-01-01

Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non-elastic extracellular matrixes, and interact closely with tropoelastin and integrins. Not only do microfibrils provide structural integrity of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues. Fibrillin is important for the assembly of elastin into elastic fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan syndrome. Fibulins are tightly connected with basement membranes, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is activation of TGFβ. Increased expression of thrombospondin and TGFβ activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in atherosclerotic plaques as well.

Republication of: Exact solutions of the field equations of the general theory of relativity

NASA Astrophysics Data System (ADS)

Jordan, Pascual; Ehlers, Jürgen; Kundt, Wolfgang

2009-09-01

This is an English translation of a paper by Pascual Jordan, Jürgen Ehlers and Wolfgang Kundt, first published in 1960. The original paper was part 1 of a five-part series of articles containing the first summary of knowledge about exact solutions of Einstein’s equations found until then. (The other parts of the series will be printed as Golden Oldies in the future.) The paper has been selected by the Editors of General Relativity and Gravitation for re-publication in the Golden Oldies series of the journal. It is accompanied by an editorial note written by G. F. R. Ellis, and by the biographies of the authors: P. Jordan (written by A. Krasiński) and W. Kundt (written by himself). The biography of J. Ehlers is contained elsewhere in the same issue of GRG, which is devoted to his memory.

In-situ formation of Ni4Ti3 precipitate and its effect on pseudoelasticity in selective laser melting additive manufactured NiTi-based composites

NASA Astrophysics Data System (ADS)

Gu, Dongdong; Ma, Chenglong

2018-05-01

Selective laser melting (SLM) additive manufacturing technology was applied to synthesize NiTi-based composites via using ball-milled Ti, Ni, and TiC mixed powder. By transmission electron microscope (TEM) characterization, it indicated that the B2 (NiTi) matrix was obtained during SLM processing. In spite of more Ti content (the Ti/Ni ratio >1), a mass of Ni-rich intermetallic compounds containing Ni4Ti3 with nanostructure features and eutectic Ni3Ti around in-situ Ti6C3.75 dendrites were precipitated. Influence of the applied laser volume energy density (VED) on the morphology and content of Ni4Ti3 precipitate was investigated. Besides, nanoindentation test of the matrix was performed in order to assess pseudoelastic recovery behavior of SLM processed NiTi-based composites. At a relatively high VED of 533 J/mm3, the maximum pseudoelastic recovery was obtained due to the lowest content of Ni4Ti3 precipitates. Furthermore, the precipitation mechanism of in-situ Ni4Ti3 was present based on the redistribution of titanium element and thermodynamics analysis, and then the relationship of Ni4Ti3 precipitate, VED and pseudoelastic recovery behavior was also revealed.

Role of Dietary Antioxidants in the Preservation of Vascular Function and the Modulation of Health and Disease

PubMed Central

Varadharaj, Saradhadevi; Kelly, Owen J.; Khayat, Rami N.; Kumar, Purnima S.; Ahmed, Naseer; Zweier, Jay L.

2017-01-01

In vascular diseases, including hypertension and atherosclerosis, vascular endothelial dysfunction (VED) occurs secondary to altered function of endothelial nitric oxide synthase (eNOS). A novel redox regulated pathway was identified through which eNOS is uncoupled due to S-glutathionylation of critical cysteine residues, resulting in superoxide free radical formation instead of the vasodilator molecule, nitric oxide. In addition, the redox sensitive cofactor tetrahydrobiopterin, BH4, is also essential for eNOS coupling. Antioxidants, either individually or combined, can modulate eNOS uncoupling by scavenging free radicals or impairing specific radical generating pathways, thus preventing oxidative stress and ameliorating VED. Epidemiological evidence and dietary guidelines suggest that diets high in antioxidants, or antioxidant supplementation, could preserve vascular health and prevent cardiovascular diseases (CVDs). Therefore, the purpose of this review is to highlight the possible role of dietary antioxidants in regulating eNOS function and uncoupling which is critical for maintenance of vascular health with normal blood flow/circulation and prevention of VED. We hypothesize that a conditioned dietary approach with suitable antioxidants may limit systemic oxidation, maintain a beneficial ratio of reduced to oxidized glutathione, and other redox markers, and minimize eNOS uncoupling serving to prevent CVD and possibly other chronic diseases. PMID:29164133

Modelling Aṣṭādhyāyī: An Approach Based on the Methodology of Ancillary Disciplines (Vedāṅga)

NASA Astrophysics Data System (ADS)

Mishra, Anand

This article proposes a general model based on the common methodological approach of the ancillary disciplines (Vedāṅga) associated with the Vedas taking examples from Śikṣā, Chandas, Vyākaraṇa and Prātiśā khya texts. It develops and elaborates this model further to represent the contents and processes of Aṣṭādhyāyī. Certain key features are added to my earlier modelling of Pāṇinian system of Sanskrit grammar. This includes broader coverage of the Pāṇinian meta-language, mechanism for automatic application of rules and positioning the grammatical system within the procedural complexes of ancillary disciplines.

Estimation of skin concentrations of topically applied lidocaine at each depth profile.

PubMed

Oshizaka, Takeshi; Kikuchi, Keisuke; Kadhum, Wesam R; Todo, Hiroaki; Hatanaka, Tomomi; Wierzba, Konstanty; Sugibayashi, Kenji

2014-11-20

Skin concentrations of topically administered compounds need to be considered in order to evaluate their efficacies and toxicities. This study investigated the relationship between the skin permeation and concentrations of compounds, and also predicted the skin concentrations of these compounds using their permeation parameters. Full-thickness skin or stripped skin from pig ears was set on a vertical-type diffusion cell, and lidocaine (LID) solution was applied to the stratum corneum (SC) in order to determine in vitro skin permeability. Permeation parameters were obtained based on Fick's second law of diffusion. LID concentrations at each depth of the SC were measured using tape-stripping. Concentration-depth profiles were obtained from viable epidermis and dermis (VED) by analyzing horizontal sections. The corresponding skin concentration at each depth was calculated based on Fick's law using permeation parameters and then compared with the observed value. The steady state LID concentrations decreased linearly as the site became deeper in SC or VED. The calculated concentration-depth profiles of the SC and VED were almost identical to the observed profiles. The compound concentration at each depth could be easily predicted in the skin using diffusion equations and skin permeation data. Thus, this method was considered to be useful for promoting the efficient preparation of topically applied drugs and cosmetics. Copyright © 2014 Elsevier B.V. All rights reserved.

Medical abortions performed by specialists in private practice.

PubMed

Pay, Aase Serine Devold; Aabø, Runa Sigrid; Økland, Inger; Janbu, Torunn; Iversen, Ole-Erik; Løkeland, Mette

2018-05-29

I Norge utføres abort kun i offentlige sykehus. I 2010 besluttet Helse- og omsorgsdepartementet å iverksette et toårig prøveprosjekt som ga avtalespesialister i fødselshjelp og kvinnesykdommer adgang til å tilby medikamentell abort før utgangen av 9. svangerskapsuke. Prøveprosjektet ble igangsatt 1.3.2015 og varte til 31.3.2017. I denne artikkelen presenterer vi de første erfaringene, herunder hvordan behandlingstilbudet ble mottatt av kvinnene. Gravide med en svangerskapsvarighet < 63 dager ultrasonografisk vurdert, som oppsøkte avtalespesialist for medikamentell abort, ble fortløpende inkludert i prosjektet (n = 476). Kvinnene inntok 200 mg mifepriston peroralt på legekontoret, 36-48 timer senere satte de selv 800 µg misoprostol vaginalt hjemme. Informasjon ble innhentet ved spørreskjema på den første konsultasjonen, under aborten og ved etterkontrollen 2-4 uker etter aborten. Under aborten rapporterte 66 % (296/450) moderat eller sterk smerte og 79 % (358/451) moderat eller sterk blødning. De fleste opplevde det som trygt å være hjemme. 96 % (390/406) ville valgt medikamentell abort hos avtalespesialist ved en eventuell senere abort, og 97 % (392/405) ville anbefalt behandlingstilbudet til andre i samme situasjon. Kvinnene i studien opplevde abortbehandling hos avtalespesialist som trygt. Tilbudet gir større valgfrihet til gravide som ønsker abort, og pasientene er tilfredse.

Implications of Neuroscientific Evidence for the Cognitive Models of Post-Traumatic Stress Disorder

ERIC Educational Resources Information Center

Cruwys, Tegan; O'Kearney, Richard

2008-01-01

Brewin's dual representation theory, Ehlers and Clark's cognitive appraisal model, and Dalgleish's schematic, propositional, analogue and associative representational systems model are considered in the light of recent evidence on the neural substrates of post-traumatic stress disorder (PTSD). The models' proposals about the cognitive mechanism of…

DIVERGENCE BETWEEN POPULATIONS OF A MONOGAMOUS POLYCHAETE WITH MALE PARENTAL CARE: PREMATING ISOLATION AND CHROMOSOME VARIATION

EPA Science Inventory

Low dispersal and sexual selection are characteristic of the coastal polychaete Nereis acuminata Ehlers 1868 [also known as Nereis arenaceodentata Moore 1903 and Nereis (Neanthes) caudata elle Chiaje 1841]. e assessed levels of premating isolation between populations of this poly...

Introducing cholera vaccination in Asia, Africa and Haiti: a meeting report.

PubMed

Hall, Robert H; Sack, David A

2015-01-15

Orally-administered cholera vaccine (OCV) has been increasingly examined as an additional tool to intervene against endemic and epidemic cholera. In 2013, short- and long-term field experience with OCV under nine distinctive field settings was reported from India, Bangladesh, Vietnam, Guinea, Haiti, and Thailand. Lead investigators from each of these projects presented their findings at a symposium chaired by Drs. David A. Sack and Robert H. Hall at the Vaccines for Enteric Diseases (VED) Conference in Bangkok on November 7, 2013. The objective of the symposium was to describe the unique features of each setting and project, share field experience of implementing cholera vaccination, discuss results, and identify constraints to the wider use of OCV. The VED provided a forum where >200 attendees engaged with this exciting and potentially decisive new development in the cholera field. Copyright © 2014. Published by Elsevier Ltd.. All rights reserved.

78 FR 74046 - Gray's Reef National Marine Sanctuary Regulations and Management Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-10

... or viewed on the internet at www.regulations.gov (search for docket NOAA-NOS-2013-0160) or at http... operators occasionally taking people out to the sanctuary. A 2008 survey (Ehler 2010) identified 15 charter boats that utilize GRNMS as one of their fishing locations. The survey found that approximately 40...

Fiscal Year 2007 House Budget Hearing

NASA Image and Video Library

2006-02-16

U.S. Rep. Vernon J. Ehlers , R-Mich., left, talks with NASA Administrator Michael Griffin, right, as NASA Deputy Administrator Shana Dale looks on prior to the start of a hearing before the House Science & Technology Committee regarding NASA's FY 2007 budget request, Thursday, Feb., 16, 2006, in Washington. Photo Credit: (NASA/Bill Ingalls)

Psychometric Qualities of the German Version of the Posttraumatic Diagnostic Scale (PTDS)

ERIC Educational Resources Information Center

Griesel, Dorothee; Wessa, Michele; Flor, Herta

2006-01-01

In the present study, the psychometric properties of the German version of the Posttraumatic Diagnostic Scale (PTDS; A. Ehlers, R. Steil, H. Winter, & E. B. Foa, 1996) were evaluated in a sample of 143 trauma survivors. To investigate convergent and discriminant validity of this questionnaire, the authors assessed posttraumatic stress disorder…

Impact of cultural differences in self on cognitive appraisals in posttraumatic stress disorder.

PubMed

Jobson, Laura; O'Kearney, Richard T

2009-05-01

Accumulating research indicates posttraumatic stress disorder (PTSD) is a universal phenomenon. However, it remains substantially unknown as to whether the processes implicated in the aetiology and maintenance of PTSD are culturally similar. This study investigated the impact of cultural differences in self on negative cognitive appraisals in those with and without PTSD. Trauma survivors with PTSD and without PTSD from independent and interdependent cultures (N = 106) provided trauma narratives. Narratives were coded for negative cognitive appraisals (mental defeat, control strategies, alienation and permanent change) as in Ehlers and colleagues' previous work. Replicating Ehlers and colleagues' work, trauma survivors with PTSD from independent cultures reported more mental defeat, alienation, permanent change and less control strategies than non-PTSD trauma survivors from independent cultures. In contrast, for those from interdependent cultures, only alienation appraisals differentiated between trauma survivors with and without PTSD. Those with PTSD had more alienation appraisals than those without PTSD. The findings suggest cultural differences in self impact on the relationship between appraisals and posttraumatic psychological adjustment. Theoretical and clinical implications are discussed.

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

PubMed

Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

2016-01-01

Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

Phylogenetic conservatism in plant phenology

USGS Publications Warehouse

Davies, T. Jonathan; Wolkovich, Elizabeth M.; Kraft, Nathan J. B.; Salamin, Nicolas; Allen, Jenica M.; Ault, Toby R.; Betancourt, Julio L.; Bolmgren, Kjell; Cleland, Elsa E.; Cook, Benjamin I.; Crimmins, Theresa M.; Mazer, Susan J.; McCabe, Gregory J.; Pau, Stephanie; Regetz, Jim; Schwartz, Mark D.; Travers, Steven E.

2013-01-01

Synthesis. Closely related species tend to resemble each other in the timing of their life-history events, a likely product of evolutionarily conser ved responses to environmental cues. The search for the underlying drivers of phenology must therefore account for species’ shared evolutionary histories.

Community College Journal for Research and Planning.

ERIC Educational Resources Information Center

Carter, Edith H., Ed.

1981-01-01

This journal, designed as a forum for the exchange of ideas among research and planning professionals, offers articles of research studies and practices. After Timothy Lightfield highlights upcoming professional association events, Janice S. Ancarrow's article, "The National Vocational Education Data Reporting and Accounting System (VEDS): Its…

Astronaut Terry J. Hart in training session RMS for STS-2 bldg 29

NASA Technical Reports Server (NTRS)

1981-01-01

Astronaut Terry J. Hart in training session with the Remote Manipulator System (RMS) for STS-2 bldg 29. Views show Truly working at the command console while watching out the windows. Karen Ehlers, an RMS procedures specialist, can be seen at left side of frame while Astronaut Sally Ride waits on right for her time at the RMS.

Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Bancelin, Stéphane; Lynch, Barbara; Bonod-Bidaud, Christelle; Ducourthial, Guillaume; Psilodimitrakopoulos, Sotiris; Dokládal, Petr; Allain, Jean-Marc; Schanne-Klein, Marie-Claire; Ruggiero, Florence

2015-12-01

Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.

Astronaut Richard H. Truly in training session RMS for STS-2 bldg 9A

NASA Technical Reports Server (NTRS)

1981-01-01

Astronaut Richard H. Truly in training session with the Remote Manipulator System (RMS) for STS-2 bldg 9A. Views show Truly working at the command console while watching out the windows. Karen Ehlers, an RMS procedures specialist, can be seen at left side of frame (34314); view from behind Truly as he trains at the RMS console (34315).

Extended Theories of Gravitation. Observation Protocols and Experimental Tests

NASA Astrophysics Data System (ADS)

Fatibene, Lorenzo; Ferraris, Marco; Francaviglia, Mauro; Magnano, Guido

2013-09-01

Within the framework of extended theories of gravitation we shall discuss physical equivalences among different formalisms and classical tests. As suggested by the Ehlers-Pirani-Schild framework, the conformal invariance will be preserved and its effect on observational protocols discussed. Accordingly, we shall review standard tests showing how Palatini f(R)-theories naturally passes solar system tests. Observation protocols will be discussed in this wider framework.

Sea Grant: Review and Authorization. Hearing Before the Subcommittee on Environment, Technology, and Standards, Committee on Science, House of Representatives, 107th Congress, First Session (February 28, 2002).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House.

The hearing reported in this document focuses on the Sea Grant College Program and evaluates the President's fiscal year 2003 budget proposal for the transfer of the Sea Grant program to the National Science Foundation (NSF). The hearing includes opening statements by Representative Vernon J. Ehlers, Chairman, Subcommittee on Environment,…

The Worried Well Response to CBRN Events: Analysis and Solutions

DTIC Science & Technology

2007-06-01

Megivan, Meena Vythilingam, Elizabeth T . Westerhaus, Gregory J . Martin, and Barry A. Hong, “Concerns of Capitol Hill Staff Workers After...options Postal staff want advice on vaccine vs. Antibiotics,” Atlanta Journal-Constitution, 22 December 2001, A10. 62. Rick Hampson and Martha T ...131. Noriko, “Psycho-Physiological Effects,” 25. 132. Richard J . McNally, Richard A. Bryant, and Anke Ehlers, “Does Early Psychological

A Culture-Based Model for Strategic Implementation of Virtual Education Delivery

ERIC Educational Resources Information Center

Burn, Janice; Thongprasert, Nalinee

2005-01-01

This study was designed to examine the critical success factors for implementing Virtual Education Delivery (VED) in Thailand, and to identify ways to facilitate such adoption and lead to effective outcomes. The study incorporated an analysis of three specific factors related to Thai culture: high power distance "Bhun Khun", uncertainty…

Process Optimization and Microstructure Characterization of Ti6Al4V Manufactured by Selective Laser Melting

NASA Astrophysics Data System (ADS)

junfeng, Li; zhengying, Wei

2017-11-01

Process optimization and microstructure characterization of Ti6Al4V manufactured by selective laser melting (SLM) were investigated in this article. The relative density of sampled fabricated by SLM is influenced by the main process parameters, including laser power, scan speed and hatch distance. The volume energy density (VED) was defined to account for the combined effect of the main process parameters on the relative density. The results shown that the relative density changed with the change of VED and the optimized process interval is 55˜60J/mm3. Furthermore, compared with laser power, scan speed and hatch distance by taguchi method, it was found that the scan speed had the greatest effect on the relative density. Compared with the microstructure of the cross-section of the specimen at different scanning speeds, it was found that the microstructures at different speeds had similar characteristics, all of them were needle-like martensite distributed in the β matrix, but with the increase of scanning speed, the microstructure is finer and the lower scan speed leads to coarsening of the microstructure.

Modeling of a viscoelastic damper and its application in structural control.

PubMed

Mehrabi, M H; Suhatril, Meldi; Ibrahim, Zainah; Ghodsi, S S; Khatibi, Hamed

2017-01-01

Conventional seismic rehabilitation methods may not be suitable for some buildings owing to their high cost and time-consuming foundation work. In recent years, viscoelastic dampers (VEDs) have been widely used in many mid- and high-rise buildings. This study introduces a viscoelastic passive control system called rotary rubber braced damper (RRBD). The RRBD is an economical, lightweight, and easy-to-assemble device. A finite element model considering nonlinearity, large deformation, and material damage is developed to conduct a parametric study on different damper sizes under pushover cyclic loading. The fundamental characteristics of this VED system are clarified by analyzing building structures under cyclic loading. The result show excellent energy absorption and stable hysteresis loops in all specimens. Additionally, by using a sinusoidal shaking table test, the effectiveness of the RRBD to manage the response displacement and acceleration of steel frames is considered. The RRBD functioned at early stages of lateral displacement, indicating that the system is effective for all levels of vibration. Moreover, the proposed damper shows significantly better performance in terms of the column compression force resulting from the brace action compared to chevron bracing (CB).

Heart Rate Variability and Cardiovascular Reactivity in Panic Disorder

DTIC Science & Technology

1999-04-01

pharmacological treatment with alprazolam or clonidine (Klein, Cnaani et al., 1995), or paroxetine (Tucker et al., 1997) were found not to differ...of Cardiology, 60, 86-89. Mcleod, D. R., Hoehn-Saric, R., Zimmerli, W.D. De Souza, E. B. & Oliver, L. K. (1990). Treatment effects of alprazolam and...and alprazolam effects on stress test reactivity in panic disorder. Biological Psychiatry. 31, 35-51. Roth, W. T., Margraf, J., Ehlers, A., Taylor

Homogenization and Linear Thermeoelasticity.

DTIC Science & Technology

1981-08-01

this report) UNCLASSIFIED [7F-- D-EASSIFICATION/ OWNGRADING SCHEDU LE 16. DISTRIBUTION STATEMENT (of this Report) APPRO)VED FOR PUBLIC RELEASE...analogues of Yi and G for Xi and as in (1.27), 18 + Y.4’ (def.) (2.14) 11 = 1o 1’ 1+ where denotes the Y-average f dy y1 we introduce A VIand H1 to

The Relationship Between Post Traumatic Stress Disorder (PTSD) Symptoms and Career Outcomes of Army Enlisted Servicemembers

DTIC Science & Technology

2015-01-01

Medicine , Vietnam vets, among other servicemembers, receive the largest share of mental health services, including cognitive processing and prolonged...of Internal Medicine ,167, 476-482. 32 Iversen, A. C., Fear, N. T., Ehlers, A., Hacker Hughes, J., Hull, L., Earnshaw, M., et al. (2008). Risk...factors for post-traumatic stress disorder among UK armed forces personnel. Psychological Medicine , 38, 511-522 33 Ibid. 16 to either parent trauma or

Workforce Training in a Time of Technological Change. Field Hearing before the Subcommittee on Environment, Technology, and Standards, Committee on Science. House of Representatives, One Hundred Seventh Congress, Second Session (June 24, 2002).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Science.

This report presents the testimony and submissions given at a field hearing on workforce training in Michigan. Four expert witness statements follow introductory comments from Vernon J. Ehlers and James A. Barcia, United States Congressmen from Michigan. The statement of Bruce P. Mehlman, the assistant secretary of commerce, assesses the ability…

The effects of the Omagh bomb on adolescent mental health: a school-based study.

PubMed

Duffy, Michael; McDermott, Maura; Percy, Andrew; Ehlers, Anke; Clark, David M; Fitzgerald, Michael; Moriarty, John

2015-02-06

The main objective of this study was to assess psychiatric morbidity among adolescents following the Omagh car bombing in Northern Ireland in 1998. Data was collected within schools from adolescents aged between 14 and 18 years via a self-completion booklet comprised of established predictors of PTSD; type of exposure, initial emotional response, long-term adverse physical problems, predictors derived from Ehlers and Clark's (2000) cognitive model, a PTSD symptoms measure (PDS) and the General Health Questionnaire (GHQ). Those with more direct physical exposure were significantly more likely to meet caseness on the GHQ and the PDS. The combined pre and peri trauma risk factors highlighted in previous meta-analyses accounted for 20% of the variance in PDS scores but the amount of variance accounted for increased to 56% when the variables highlighted in Ehlers and Clark's cognitive model for PTSD were added. High rates of chronic PTSD were observed in adolescents exposed to the bombing. Whilst increased exposure was associated with increased psychiatric morbidity, the best predictors of PTSD were specific aspects of the trauma ('seeing someone you think is dying'), what you are thinking during the event ('think you are going to die') and the cognitive mechanisms employed after the trauma. As these variables are in principle amenable to treatment the results have implications for teams planning treatment interventions after future traumas.

Benchmarking of data fusion algorithms in support of earth observation based Antarctic wildlife monitoring

NASA Astrophysics Data System (ADS)

Witharana, Chandi; LaRue, Michelle A.; Lynch, Heather J.

2016-03-01

Remote sensing is a rapidly developing tool for mapping the abundance and distribution of Antarctic wildlife. While both panchromatic and multispectral imagery have been used in this context, image fusion techniques have received little attention. We tasked seven widely-used fusion algorithms: Ehlers fusion, hyperspherical color space fusion, high-pass fusion, principal component analysis (PCA) fusion, University of New Brunswick fusion, and wavelet-PCA fusion to resolution enhance a series of single-date QuickBird-2 and Worldview-2 image scenes comprising penguin guano, seals, and vegetation. Fused images were assessed for spectral and spatial fidelity using a variety of quantitative quality indicators and visual inspection methods. Our visual evaluation elected the high-pass fusion algorithm and the University of New Brunswick fusion algorithm as best for manual wildlife detection while the quantitative assessment suggested the Gram-Schmidt fusion algorithm and the University of New Brunswick fusion algorithm as best for automated classification. The hyperspherical color space fusion algorithm exhibited mediocre results in terms of spectral and spatial fidelities. The PCA fusion algorithm showed spatial superiority at the expense of spectral inconsistencies. The Ehlers fusion algorithm and the wavelet-PCA algorithm showed the weakest performances. As remote sensing becomes a more routine method of surveying Antarctic wildlife, these benchmarks will provide guidance for image fusion and pave the way for more standardized products for specific types of wildlife surveys.

[The Contribution of Vascular Capacity and Blood Volume to Maintain Stable Blood Circulation during General Anesthesia].

PubMed

Shigemi, Kenji

2016-05-01

To maintain proper cardiac preload is one of the most effective procedures for the systemic circulation remaining stable. In particular, the balance between vascular capacity and total blood volume must be maintained within appropriate range by the administration of fluids, blood and/or vasoactive drugs with mean circulatory filling pressure (Pmcf), central venous pressure (CVP) or stroke volume variation (SVV). End-diastolic left ventricular volume (Ved) is theoretically the best index of cardiac preload; however, without transesophageal echocardbalanceiogram we cannot directly monitor Ved during anesthesia. The infused fluid volume remaining in intravascular space, the vascular capacity controlled by autonomic nervous system and/or vasoactive agents, and the unstressed blood volume properly mobilized to excess blood volume are the crucial factors to maintain cardiac output The knowledge of vascular physiology contribute the decision making to manipulate such factors to control blood circulation during general anesthesia. For example, CVP is usually maintained in the narrow range and seems to be stable; however, it must be changed just after the circulatory disturbances, such as acute bleeding, blood transfusion, and fluid infusion, and followed by gradual returning to initial value, because of the solid mechanism to preserve cardiac output

Modeling of a viscoelastic damper and its application in structural control

PubMed Central

Ibrahim, Zainah; Ghodsi, S. S.; Khatibi, Hamed

2017-01-01

Conventional seismic rehabilitation methods may not be suitable for some buildings owing to their high cost and time-consuming foundation work. In recent years, viscoelastic dampers (VEDs) have been widely used in many mid- and high-rise buildings. This study introduces a viscoelastic passive control system called rotary rubber braced damper (RRBD). The RRBD is an economical, lightweight, and easy-to-assemble device. A finite element model considering nonlinearity, large deformation, and material damage is developed to conduct a parametric study on different damper sizes under pushover cyclic loading. The fundamental characteristics of this VED system are clarified by analyzing building structures under cyclic loading. The result show excellent energy absorption and stable hysteresis loops in all specimens. Additionally, by using a sinusoidal shaking table test, the effectiveness of the RRBD to manage the response displacement and acceleration of steel frames is considered. The RRBD functioned at early stages of lateral displacement, indicating that the system is effective for all levels of vibration. Moreover, the proposed damper shows significantly better performance in terms of the column compression force resulting from the brace action compared to chevron bracing (CB). PMID:28570657

Design Methodology and Experimental Verification of Serpentine/Folded Waveguide TWTs

DTIC Science & Technology

2016-03-17

FW), oscillation, serpentine, stopband, traveling -wave tube (TWT), vacuum electronics. I. INTRODUCTION DEVELOPMENT of high-power broadband vacuum elec...tron devices (VEDs) beyond Ka-band using conventional coupled-cavity and helix traveling -wave tube (TWT) RF cir- cuit fabrication techniques is...between the two positions is simply ks times the relative distance along the waveguide axis. However, from the beam–wave interaction standpoint, the

Abstracts of AF Materials Laboratory Reports

DTIC Science & Technology

1975-09-01

NO: TITLE: AUTHOR(S): CONTRACT NO; CONTRACTOR: AFML-TR-73-307 200,397 IMPROVED AUTOMATED TAPE LAYING MACHINE M. Poullos, W. J. Murray, D.L...AUTOMATED IMPROVED AUTOMATED TAPE LAYING MACHINE AUTOMATION AUTOMATION OF COATING PROCESSES FOR GAS TURBINE DLADcS AND VANES 203222/111 203072...IMP90VE0 TAPE LAYING MACHINE IMPP)VED AUTOMATED TAPE LAYING MACHINE A STUDY O^ THE STRESS-STRAIN TEHAVIOR OF GRAPHITE

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration

PubMed Central

Ogawa, Rei; Hsu, Chao-Kai

2013-01-01

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers–Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases. PMID:23672502

Assessment of Ganga river ecosystem at Haridwar, Uttarakhand, India with reference to water quality indices

NASA Astrophysics Data System (ADS)

Bhutiani, R.; Khanna, D. R.; Kulkarni, Dipali Bhaskar; Ruhela, Mukesh

2016-06-01

The river Ganges is regarded as one of the most holy and sacred rivers of the world from time immemorial. The evaluation of river water quality is a critical element in the assessment of water resources. The quality/potability of water that is consumed defines the base line of protection against many diseases and infections. The present study aimed to calculate Water Quality Index (WQI) by the analysis of sixteen physico-chemical parameters on the basis of River Ganga index of Ved Prakash, weighted arithmetic index and WQI by National sanitation foundation (NSF) to assess the suitability of water for drinking, irrigation purposes and other human uses. These three water quality indices have been used to assess variation in the quality of the River Ganga at monitored locations over an 11-year period. Application of three different indexes to assess the water quality over a period of 11 years shows minor variations in water quality. Index values as per River Ganga Index by Ved Prakash et al. from 2000 to 2010 ranged between medium to good, Index values as per NSF Index for years 2000-2010 indicate good water quality, while Index values as per the weighted arithmetic index method for the study period indicate poor water quality.

Republication of: On the general relativity theory

NASA Astrophysics Data System (ADS)

Weyl, H.

2009-07-01

This English translation of the paper by H. Weyl, "Zur allgemeinen Relativitätstheorie", Physikalische Zeitschrift 24, 230-232 (1923), in which he formulated the geometrical foundations of a model of an expanding Universe, has been selected by the Editors of General Relativity and Gravitation for publication in the Golden Oldies series of the journal. The paper is accompanied by an editorial note written by Juergen Ehlers and by Weyl's brief biography compiled by Andrzej Krasiński from internet sources, with corrections provided by Weyl's son and grandson.

A Program for Clinical Care in Physical Trauma.

DTIC Science & Technology

1981-03-01

effects obser- ved in intravenous feeding after injury;(2) The use of isotopes of nitrogen and hydrogen in substrate research in man;(3) The patho...Tactical Problems Addressed and Summary of Findings 1. Caloric Support for Protein Synthesis and Intravenous Feeding Findings: The addition of calorie...12, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24) 2. Peripheral versus Central Vein Infusion Sites for Intravenous Feeding in the Wounded, Starved, or

A comparative assessment of endogenous water institutional change

NASA Astrophysics Data System (ADS)

Pande, Saket; Ersten, Maurits

2013-04-01

This paper builds the theory of endogenous institutional change, first proposed by Greif and Laitin (2004), for water scarce regions in context of water institutions. The current emphasis on environmental change, including hydrological change, largely ignores the adaptation of human societies to change. Humans have mostly been considered as boundary conditions or parameters of the dynamics of hydrological change and are not considered as conduits of feedbacks. Nonetheless, the dynamical representation of hydrological change with feedbacks between various components of a system is assuring since it is reminiscent of processual ecological anthropology(Orlove, 1980), except that individual decision making is absent. This paper proposes to consider selected dryland basins of the world, to conceptualize proxies of water relevant socio-economic organisation, such as spatial scales of upstream-downstream cooperation in water use, synthesized over time and then proposes a comparative assessment to test regularities predicted by an extension of river game theory (Ambec and Ehlers, 2008; van der Brink et al, 2012) to endogenous institutional change. References: Orlove, B. S. (1980). Ecological Anthropology. Annual Review of Anthropology, Vol. 9 (1980), pp. 235-273. Greif. A. and D. D. Laitin (2004). A Theory of Endogenous Institutional Change. American Political Science Review, Vol. 98, No. 4 November 2004. Ambec, S. and L. Ehlers (2008). Sharing a river amongst satiable agents. Games and Economic Behavior, 64, 35-50. Van der Brink, G. van der Laan and N. Moes (2012). Fair agreements for sharing international rivers with multiple springs and externalities. Journal of Environmental Economics and Management, 63, 388-403.

Detroit River group in the Michigan basin

USGS Publications Warehouse

Landes, Kenneth K.

1951-01-01

This report attempts to correlate the outcropping rocks in the type locality of the Detroit River group with the thick sequence of rocks that has been explored by many drilled wells in the Michigan Basin during the last twenty years. The surface nomenclature as recently revised (Ehlers, 1950) is suggested for the subsurface section in place of the heterogeneous collection of names now used. The present work revises earlier reports by the writer (1945, a, b, c).During the preparation of this report the samples have been examined from more than 300 wells and cores from 9 wells. The writer has also drawn upon the work of Enyert (1949) who wrote a Doctoral thesis on the sandstones of the Detroit River group, and upon Master's theses on various phases of Detroit River stratigraphy written by Cooley (1947), Saunders .(1948), and Tharp (1944). Finally the writer has had the advantage of many consultations in office and field with George V. Cohee of the U. S. Geological Survey, Professors G. M. Ehlers and E. C. Stumm of the University of Michigan, and with other geologists of Michigan and Ontario, especially George D. Lindberg (Sun Oil Company, Toledo), E. J. Baltrusaitis and K. A. Gravelle (Gulf Refining Company, Saginaw), Willard A. Sanger (Pure Oil Company, Clare), Joseph Lindsay and George WinSton (Carter Oil Co. , Grand Rapids), and Charles S. Evans (Union Gas Co. , Chatham, Ontario). It is a pleasure to acknowledge the help received from these geologists and to thank them for it.The surface and subsurface sections through the Detroit River group in Canada are not included in this report.

Life and consciousness – The Vedāntic view

PubMed Central

Shanta, Bhakti Niskama

2015-01-01

In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter — and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself – omne vivum ex vivo – life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all sentient and insentient nature. In contrast to the idea of objective evolution of bodies, as envisioned by Darwin and followers, Vedānta advocates the idea of subjective evolution of consciousness as the developing principle of the world. In this paper, an attempt has been made to highlight a few relevant developments supporting a sentient view of life in scientific research, which has caused a paradigm shift in our understanding of life and its origin. PMID:27066168

Life and consciousness - The Vedāntic view.

PubMed

Shanta, Bhakti Niskama

2015-01-01

In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter - and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself - omne vivum ex vivo - life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all sentient and insentient nature. In contrast to the idea of objective evolution of bodies, as envisioned by Darwin and followers, Vedānta advocates the idea of subjective evolution of consciousness as the developing principle of the world. In this paper, an attempt has been made to highlight a few relevant developments supporting a sentient view of life in scientific research, which has caused a paradigm shift in our understanding of life and its origin.

Extending color primary set in spectral vector error diffusion by multilevel halftoning

NASA Astrophysics Data System (ADS)

Norberg, Ole; Nyström, Daniel

2013-02-01

Ever since its origin in the late 19th century, a color reproduction technology has relied on a trichromatic color reproduction approach. This has been a very successful method and also fundamental for the development of color reproduction devices. Trichromatic color reproduction is sufficient to approximate the range of colors perceived by the human visual system. However, tricromatic systems only have the ability to match colors when the viewing illumination for the reproduction matches that of the original. Furthermore, the advancement of digital printing technology has introduced printing systems with additional color channels. These additional color channels are used to extend the tonal range capabilities in light and dark regions and to increase color gamut. By an alternative approach the addition color channels can also be used to reproduce the spectral information of the original color. A reproduced spectral match will always correspond to original independent of lighting situation. On the other hand, spectral color reproductions also introduce a more complex color processing by spectral color transfer functions and spectral gamut mapping algorithms. In that perspective, spectral vector error diffusion (sVED) look like a tempting approach with a simple workflow where the inverse color transfer function and halftoning is performed simultaneously in one single operation. Essential for the sVED method are the available color primaries, created by mixing process colors. Increased numbers of as well as optimal spectral characteristics of color primaries are expected to significantly improve the color accuracy of the spectral reproduction. In this study, sVED in combination with multilevel halftoning has been applied on a ten channel inkjet system. The print resolution has been reduced and the underlying physical high resolution of the printer has been used to mix additional primaries. With ten ink channels and halfton cells built-up by 2x2 micro dots where each micro dot can be a combination of all ten inks the number of possible ink combinations gets huge. Therefore, the initial study has been focused on including lighter colors to the intrinsic primary set. Results from this study shows that by this approach the color reproduction accuracy increases significantly. The RMS spectral difference to target color for multilevel halftoning is less than 1/6 of the difference achieved by binary halftoning.

Comparison of vessel enhancement algorithms applied to time-of-flight MRA images for cerebrovascular segmentation.

PubMed

Phellan, Renzo; Forkert, Nils D

2017-11-01

Vessel enhancement algorithms are often used as a preprocessing step for vessel segmentation in medical images to improve the overall segmentation accuracy. Each algorithm uses different characteristics to enhance vessels, such that the most suitable algorithm may vary for different applications. This paper presents a comparative analysis of the accuracy gains in vessel segmentation generated by the use of nine vessel enhancement algorithms: Multiscale vesselness using the formulas described by Erdt (MSE), Frangi (MSF), and Sato (MSS), optimally oriented flux (OOF), ranking orientations responses path operator (RORPO), the regularized Perona-Malik approach (RPM), vessel enhanced diffusion (VED), hybrid diffusion with continuous switch (HDCS), and the white top hat algorithm (WTH). The filters were evaluated and compared based on time-of-flight MRA datasets and corresponding manual segmentations from 5 healthy subjects and 10 patients with an arteriovenous malformation. Additionally, five synthetic angiographic datasets with corresponding ground truth segmentation were generated with three different noise levels (low, medium, and high) and also used for comparison. The parameters for each algorithm and subsequent segmentation were optimized using leave-one-out cross evaluation. The Dice coefficient, Matthews correlation coefficient, area under the ROC curve, number of connected components, and true positives were used for comparison. The results of this study suggest that vessel enhancement algorithms do not always lead to more accurate segmentation results compared to segmenting nonenhanced images directly. Multiscale vesselness algorithms, such as MSE, MSF, and MSS proved to be robust to noise, while diffusion-based filters, such as RPM, VED, and HDCS ranked in the top of the list in scenarios with medium or no noise. Filters that assume tubular-shapes, such as MSE, MSF, MSS, OOF, RORPO, and VED show a decrease in accuracy when considering patients with an AVM, because vessels may vary from its tubular-shape in this case. Vessel enhancement algorithms can help to improve the accuracy of the segmentation of the vascular system. However, their contribution to accuracy has to be evaluated as it depends on the specific applications, and in some cases it can lead to a reduction of the overall accuracy. No specific filter was suitable for all tested scenarios. © 2017 American Association of Physicists in Medicine.

Optical properties of soot particles: measurement - model comparison

NASA Astrophysics Data System (ADS)

Forestieri, S.; Lambe, A. T.; Lack, D.; Massoli, P.; Cross, E. S.; Dubey, M.; Mazzoleni, C.; Olfert, J.; Freedman, A.; Davidovits, P.; Onasch, T. B.; Cappa, C. D.

2013-12-01

Soot, a product of incomplete combustion, plays an important role in the earth's climate system through the absorption and scattering of solar radiation. In order to accurately model the direct radiative impact of black carbon (BC), the refractive index and shape dependent scattering and absorption characteristics must be known. At present, the assumed shape remains highly uncertain because BC particles are fractal-like, being agglomerates of smaller (20-40 nm) spherules, yet traditional optical models such as Mie theory typically assume a spherical particle morphology. To investigate the ability of various optical models to reproduce observed BC optical properties, we measured light absorption and extinction coefficients of methane and ethylene flame soot particles. Optical properties were measured by multiple instruments: absorption by a dual cavity ringdown photoacoustic spectrometer (CRD-PAS), absorption and scattering by a 3-wavelength photoacoustic/nephelometer spectrometer (PASS-3) and extinction and scattering by a cavity attenuated phase shift spectrometer (CAPS). Soot particle mass was quantified using a centrifugal particle mass analyzer (CPMA) and mobility size was measured with a scanning mobility particle sizer (SMPS). Measurements were made for nascent soot particles and for collapsed soot particles following coating with dioctyl sebacate or sulfuric acid and thermal denuding to remove the coating. Wavelength-dependent refractive indices for the sampled particles were derived by fitting the observed absorption and extinction cross-sections to spherical particle Mie theory and Rayleigh-Debye-Gans theory. The Rayleigh-Debye-Gans approximation assumes that the absorption properties of soot are dictated by the individual spherules and neglects interaction between them. In general, Mie theory reproduces the observed absorption and extinction cross-sections for particles with volume equivalent diameters (VED) < ~160 nm, but systematically predicts lower absorption cross-sections relative to observations for larger particles with VED > ~160 nm. The discrepancy is most pronounced for measurements made at shorter wavelengths. In contrast, Rayleigh-Debye-Gans theory, which does not assume spherical particle morphology, exhibited good agreement with the observations for all particle diameters and wavelengths. These results indicate that the use of Mie theory to describe the absorption behavior of particles >160 nm VED will underestimate the absorption by these particles. Concurrent measurements of the absorption Angstrom exponent and the single scattering albedo, and their dependence on particle size, will also be discussed.

The Effect of Consolidating Two-Level Reparable Inventories on Aggregate Inventory Requirements and Mission Capability.

DTIC Science & Technology

1995-09-01

Wright-Patterson Air Force_Ejase, Ohio "DISTRIBUTION STATMENT A Appr°ved for P0^ relea80; Distribution unlimited Accesion For AFTT/GLM/LAL/95S-2...Two-Level Maintenance is one element in the LL architecture . Other elements that address the need for the reliable, high velocity transportation of...of these studies has changed to reflect the [Defense] Department’s increasing concern with readiness and sustainability . Their recommendations

Systems to Detect Bacterial Contamination of Banked Blood in a Rapid, Non-Invasive Low Technology Manner. Phase 1.

DTIC Science & Technology

1994-08-25

Department of the Army position, policy or decision unless so designated by other documentation. 94-30800 IIV III !111 IiI I ’ I foron Appr •vedREPORT...copyrighted material is quoted, permission has been obtained to use such material. Where material from documents designated for limited distribution is...Laser Scanning Densitometry for quantitation of the color changes. (6) Narrative: a. Eperimental Methods: 1. Bacteria: Ten bacterial species

Towards Tailored Interphase Formation Utilizing Surface-Active Benzylsulfonium Salts as Cationic Initiators

DTIC Science & Technology

1994-07-15

34,AR V3 APR edrtion may be ved until eha uv’ed. CURITY" Sf ’’ NO F G .. Towsrds Talared lnterphae F .- wmon qjdM to 0 Surfzce-Actlve BenzyWM*irn Sa, -l...min with nltrog, purge. Solution "C NMR were preformed on a Bruker AC-200 wle so state ’C CPMAS, A b f • and "Sl CPMAS were run on a Bnker \\4SL.-400

Missile Manufacturing Technology Conference Held at Hilton Head Island, South Carolina on 22-26 September 1975. Panel Presentations: Guidance

DTIC Science & Technology

1975-01-01

Instead of the current three. Some de - tail on each component follows. II. POTENTIAL MANUFACTURING TECHNOLOGY PROJECTS Gyro Because of the...ranges of environment. With Imbedded microprocessors. It Is possible that parameters, once de - fined, can be placed within the microprocessor memory...Project cost: $53,000 Estimated duration of the project Is nine months. Benefits: Benefits to be de :ved from this project are a reduction

Exploration of resistive targets within shallow marine environments using the circular electrical dipole and the differential electrical dipole methods: a time-domain modelling study

NASA Astrophysics Data System (ADS)

Haroon, Amir; Mogilatov, Vladimir; Goldman, Mark; Bergers, Rainer; Tezkan, Bülent

2016-05-01

Two novel transient controlled source electromagnetic methods called circular electrical dipole (CED) and differential electrical dipole (DED) are theoretically analysed for applications in shallow marine environments. 1-D and 3-D time-domain modelling studies are used to investigate the detectability and applicability of the methods when investigating resistive layers/targets representing hydrocarbon-saturated formations. The results are compared to the conventional time-domain horizontal electrical dipole (HED) and vertical electrical dipole (VED) sources. The applied theoretical modelling studies demonstrate that CED and DED have higher signal detectability towards resistive targets compared to TD-CSEM, but demonstrate significantly poorer signal amplitudes. Future CED/DED applications will have to solve this issue prior to measuring. Furthermore, the two novel methods have very similar detectability characteristics towards 3-D resistive targets embedded in marine sediments as VED while being less susceptible towards non-verticality. Due to the complex transmitter design of CED/DED the systems are prone to geometrical errors. Modelling studies show that even small transmitter inaccuracies have strong effects on the signal characteristics of CED making an actual marine application difficult at the present time. In contrast, the DED signal is less affected by geometrical errors in comparison to CED and may therefore be more adequate for marine applications.

Design of Visco-Elastic Dampers for RC Frame for Site-Specific Earthquake

NASA Astrophysics Data System (ADS)

Kamatchi, P.; Rama Raju, K.; Ravisankar, K.; Iyer, Nagesh R.

2016-12-01

Number of Reinforced Concrete (RC) framed buildings have got damaged at Ahmedabad city, India located at about 240 km away from epicenter during January 2001, 7.6 moment magnitude (Mw) Bhuj earthquake. In the present study, two dimensional nonlinear time history dynamic analyses of a typical 13 storey frame assumed to be located at Ahmedabad is carried out with the rock level and surface level site-specific ground motion for scenario earthquake of Mw 7.6 from Bhuj. Artificial ground motions are generated using extended finite source stochastic model with seismological parameters reported in literature for 2001 Bhuj earthquake. Surface level ground motions are obtained for a typical soil profile of 100 m depth reported in literature through one dimensional equivalent linear wave propagation analyses. From the analyses, failure of frame is observed for surface level ground motions which indicates that, in addition to the in-adequacy of the cross sections and reinforcement of the RC members of the frame chosen, the rich energy content of the surface level ground motion near the fundamental time period of the frame has also contributed for the failure of frame. As a part of retrofitting measure, five Visco-elastic Dampers (VED) in chevron bracing are added to frame. For the frame considered in the present study, provision of VED is found to be effective to mitigate damage for the soil site considered.

Grasping at ontological straws: overcoming reductionism in the Advaita Vedānta-Neuroscience dialogue.

PubMed

Kaplan, Stephen

2009-01-01

Contemporary neuropsychology reveals that the parietal lobe contains neurons that are specifically attuned to the act of grasping and this act may be fundamental to the establishment of the phenomenal boundaries between subject and object. Furthermore, alterations to this process, such as the hypoactivation of this region during meditation or the hyperactivation associated with schizophrenia, may eliminate or confuse, respectively, the phenomenal boundaries between subject and object. Traversing disciplines, the Advaita Vedānta school of Hinduism traces some of its key terms for subject and object to the verbal root grah, to grasp. The subject is literally the grasper. Furthermore, the practice of asparśa yoga, the yoga of no-touch, is aimed at stopping, hypoactivating, the grasping process in order to transcend all subject-object boundaries. This paper will argue that while we have not uncovered an identity of thought, we have uncovered a confluence of ideas between these two disciplines. We will see that this confluence of ideas has not pitted the believer against the critic-not forced us into the great reductionism debate that has dominated so much of the interchange between religious studies and the sciences. This case study will illuminate some of the methodological ways around this reductionism battle and also the boundaries of both disciplines for the intellectual benefit of each.

Determinants of the development of mitral regurgitation in pacing-induced heart failure.

PubMed

Takagaki, Masami; McCarthy, Patrick M; Goormastic, Marlene; Ochiai, Yoshie; Doi, Kazuyoshi; Kopcak, Michael W; Tabata, Tomotsugu; Cardon, Lisa A; Thomas, James D; Fukamachi, Kiyotaka

2003-01-01

The pacing-induced heart failure model provides an opportunity to assess the structural and functional determinants of mitral regurgitation (MR) in dilated cardiomyopathy. This study aimed to evaluate MR to better understand the multitude of factors contributing to its development. Heart failure was induced by rapid ventricular pacing (230 beats/min) in 40 mongrel dogs. Left ventricular (LV) size and MR were evaluated echocardiographically. LV contractility was analyzed using a conductance catheter. MR increased to mild in 12 animals (regurgitant orifice area, 0.06+/-0.05 cm(2)), moderate in 15 (0.14+/-0.07 cm(2)), and severe in 13 (0.34+/-0.16 cm(2)). The grade of MR had an inverse relationships with E(max) (the slope of the end-systolic pressure-volume relationship, p<0.01) and dE/dt (the slope of the maximum rate of change of pressure-end-diastolic volume [V(ED)] relationship, p<0.01) and positive relationships with V(ED) and end-diastolic cross-sectional areas and lengths (p<0.05) by univariate analysis. The dE/dt had an independently significant (p<0.01) relationship by multivariable logistic regression. Many factors influence the development of MR and because of its similarity to the clinical situation, this model can be used to investigate MR and heart failure, as well as new surgical therapies.

Evaluation of characteristics, associations and clinical course of isolated spontaneous renal artery dissection

PubMed Central

Afshinnia, Farsad; Sundaram, Baskaran; Rao, Panduranga; Stanley, James; Bitzer, Markus

2013-01-01

Background Spontaneous renal artery dissection (SRAD) is a rare entity of unknown etiology. We aimed to study the clinical course and outcomes and compare the characteristics of patients with SRAD with those of the general population. Methods All cases of isolated renal artery dissection diagnosed at the University of Michigan Hospitals between January 2000 and July 2012 were identified by the ICD-9 code. Cases were matched by age, gender and race with individuals from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). Characteristics and awareness of comorbid conditions were compared. Information about the clinical course after diagnosis was retrieved from the case group to ascertain their outcomes. Results Overall, 17 patients with SRAD with a mean age of 38.6 years (SD = 8.3) were identified. Eleven patients were male and 14 were white. The most common presenting symptom was excruciating sudden-onset flank pain ipsilateral to the site of dissection. Fibromuscular dysplasia, Ehlers–Danlos and polyarteritis nodosa were present in 4, 4 and 1 patients, respectively. After adjusting in a multivariable model, the case group was more likely to report history of hypertension, cancer and connective tissue disorders (P < 0.001), and less likely to have obesity (BMI ≥30 kg/m2) compared with the general population. Supportive medical treatment, endovascular intervention and surgery were required in 8, 5 and 4 cases, respectively. After discharge from the hospital, hypertension was adequately controlled in all the patients but one. Conclusion SRAD may be part of a syndrome having multi-organ involvement. With appropriate medical or surgical management, long-term clinical outcome appears favorable. PMID:23563282

Long-Lived Digital Data Collections Enabling Research and Education in the 21st Century

DTIC Science & Technology

2005-09-01

Collections: Enabling Research and Education in the 21st Century40 LoNG-LiVED DiGiTAL DATA CoLLECTioNS AND LARGE FACiLiTiES Workshop participants drew...Long-Lived Digital Data Collections: Enabling Research and Education in the 21st Century NSB-05-40 Report Documentation Page Form...COVERED - 4. TITLE AND SUBTITLE Long-Lived Digital Data Collections Enabling Research and Education in the 21st Century 5a. CONTRACT NUMBER 5b

Operational Test Director Guide. Change 4.

DTIC Science & Technology

1982-09-20

usable by the people invol - ved; the testers, the data collectors, and the evaluators. Sample formats are available to the OTD in (Change 1) 10-4 4 a...to & educe the e6jeetA o the timiting 6aetoxA. FoL exampte, "Avai- * abte ta/getA do not tepiteaent iteaLL~tic thkeatA. Howevek, 3-3 CLASSIFICATION...related test equipment and special tools. (e) (*) Completed NAVSUP Form 1250, with part number and APL number (or nomenclature of parent equipment), for

Visual Electricity Demonstrator

NASA Astrophysics Data System (ADS)

Lincoln, James

2017-09-01

The Visual Electricity Demonstrator (VED) is a linear diode array that serves as a dynamic alternative to an ammeter. A string of 48 red light-emitting diodes (LEDs) blink one after another to create the illusion of a moving current. Having the current represented visually builds an intuitive and qualitative understanding about what is happening in a circuit. In this article, I describe several activities for this device and explain how using this technology in the classroom can enhance the understanding and appreciation of physics.

A Multidisciplinary Study of Ciguatoxin and Related Low Molecular Weight Toxins from Marine Source

DTIC Science & Technology

1986-08-01

viscera (liver and intestines) of guinea pigs, and the fruit of the avocado . Authentic ClX ws not available at the time the experiments outlined below...iully Treatmet of the tissues with attract~s from tilapiao, kale,. guines, pig viscera and avocado produced respnes slimilar to those ctain’ved with...all ultimately caused death. Avocado extract differad only in the anmumt necessary to procduce these effects, 80 - 100 ug/kg in two animals. Copy .c

Development and Validation of Methods for Applying Pharmacokinetic Data in Risk Assessment. Volume 3. Tetrachloroethylene

DTIC Science & Technology

1990-12-01

Armstrong Aerospace Medical Research Laboratory, Wright Paterson Air Force Base, and Drs. Melvin Andersen and Michael Cargas , formerly with the Harry G...based on the arterial blood concentration surrogate were more III-1-10 similar to those de ’!ved in the traditional manner than were the estimates based on...pharmacokinetic modeling. Prepared by Office of Risk Analysis, Oak Ridge National L-ioratory, Oak Pidge, Tenn.zsee. Prepared under Contract No. DE -ACO5-84

Medical Store Management: An Integrated Economic Analysis of a Tertiary Care Hospital in Central India

PubMed Central

Mahatme, MS; Dakhale, GN; Hiware, SK; Shinde, AT; Salve, AM

2012-01-01

Economic analysis plays a pivotal role in the management of medical store. The main objectives of this study were to consider always better control-vital, essential and desirable (ABC-VED) analysis with economic order quantity (EOQ), comparison of indexed cost and the actual cost, and to assess the expenditure for the forthcoming years. Based on cost and criticality, a matrix of nine groups by combining ABC and VED analysis was formulated. Drug categories were narrowed down for prioritization to direct supervisory monitoring. The subgroups AE and AV of the categories category I and II should be ordered based on EOQ. The difference between the actual annual drug expenditure (ADE) and the derived indexed cost using the cost inflation index (CII) was calculated. Linear regression was used to assess the expenditure for the forth coming years. The total ADE for the financial year of 2010–2011 was Rs. 1,91,44,253 which was only 7.68% of annual hospital expenditure. Using the inflation index, the indexed cost of acquisition of ADE for year 2010–2011 was Rs. 1,95,10,387. The difference between the two was estimated to be 2.11%. Thus, the CII justifies the demand of increased budget for next year and prompts us for cautious use of drugs. By taking into consideration the ADE of last 10 years, we have forecasted the budget for forthcoming years which will help significantly for making policies according to the available budget. PMID:22754264

Medical store management: an integrated economic analysis of a tertiary care hospital in central India.

PubMed

Mahatme, Ms; Dakhale, Gn; Hiware, Sk; Shinde, At; Salve, Am

2012-04-01

Economic analysis plays a pivotal role in the management of medical store. The main objectives of this study were to consider always better control-vital, essential and desirable (ABC-VED) analysis with economic order quantity (EOQ), comparison of indexed cost and the actual cost, and to assess the expenditure for the forthcoming years. Based on cost and criticality, a matrix of nine groups by combining ABC and VED analysis was formulated. Drug categories were narrowed down for prioritization to direct supervisory monitoring. The subgroups AE and AV of the categories category I and II should be ordered based on EOQ. The difference between the actual annual drug expenditure (ADE) and the derived indexed cost using the cost inflation index (CII) was calculated. Linear regression was used to assess the expenditure for the forth coming years. The total ADE for the financial year of 2010-2011 was Rs. 1,91,44,253 which was only 7.68% of annual hospital expenditure. Using the inflation index, the indexed cost of acquisition of ADE for year 2010-2011 was Rs. 1,95,10,387. The difference between the two was estimated to be 2.11%. Thus, the CII justifies the demand of increased budget for next year and prompts us for cautious use of drugs. By taking into consideration the ADE of last 10 years, we have forecasted the budget for forthcoming years which will help significantly for making policies according to the available budget.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

PubMed

Ferrari, Gianfranco; Khir, Ashraf W; Fresiello, Libera; Di Molfetta, Arianna; Kozarski, Maciej

2011-09-01

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Ein Blick ins Licht. Einblicke in die Natur des Lichts und des Sehens, in Farbe und Fotografie.

NASA Astrophysics Data System (ADS)

Falk, D. S.; Brill, D. R.; Stork, D. G.

This book is a German translation, by A. Ehlers, of the American original "Seeing the light. Optics in nature, photography, color, vision, and holography", published in 1986. Contents: 1. Die Haupteigenschaften des Lichts. 2. Grundlagen der geometrischen Optik. 3. Spiegel und Linsen. 4. Kamera und Fotografie. 5. Das menschliche Auge und sein Sehvermögen. I: Wie das Bild erzeugt wird. 6. Optische Instrumente. 7. Das menschliche Auge und sein Sehvermögen. II: Bildverarbeitung. 8. Räumliches Sehen und Tiefenwahrnehmung. 9. Farbe. 10. Farbwahrnehmung. 11. Farbfotografie. 12. Wellenoptik. 13. Streuung und Polarisation. 14. Holografie. 15. Ein Blick in die moderne Physik.

Administration and Stenographic Career Ladders, AFS 702x0/A/B/C and 702X1.

DTIC Science & Technology

1980-04-01

MEN mIIIIIIIII hhhllllhlhhl UNITED STATES AIR FORCE _Si -j𔃽.- 0 ADMINISTRATION AND5$TENOGRAPHIC -CAREER LADDERS AIS 702XO/ A /B/C AND 702X1 -J AFPT- 9...7J2-389 ( ,/ " ’ _ LA. -IAPRI 180 This document has n a :’.-pro+ved1 + ,for pil s’ s ;i - , OqCUPATIONAL ANALYSIS PROGRAM USAF OCCUPATIONAL...79 APPENDIX A O--------------------------------------------- 80 Acc22~C~For 1 -* ii L PREFACE This report presents the results of a detailed Air

Controlled Growth of Parallel Oriented ZnO Nanostructural Arrays on Ga2O3 Nanowires

DTIC Science & Technology

2008-11-01

Controlled Growth of Parallel Oriented ZnO Nanostructural Arrays on Ga2O3 Nanowires Lena Mazeina,* Yoosuf N. Picard, and Sharka M. Prokes Electronics...Manuscript ReceiVed NoVember 6, 2008 ABSTRACT: Novel hierarchical ZnO- Ga2O3 nanostructures were fabricated via a two stage growth process. Nanowires of Ga2O3 ...nanobrushes (NBs) with Ga2O3 as the core and ZnO as the branches self-assembling symmetrically in six equiangular directions around the core

Compendium of the ULF/ELF Electromagnetic Fields Generated above a Sea of Finite Depth by Submerged Harmonic Dipoles

DTIC Science & Technology

1980-01-01

CATALOG NUMBER Tech. Report No. E715-1 4. TTE (ln tlitts LTYPE RPOT’ QcOIJj. Compendium of the ULF/ELF Electromagnetic Fields nccnicat Generated above...sidi if noeess’ry arid Identify hy bulock mriifi.rnb) ULF/ELF Electromagnetic Fields VMD, VED, HED, HMD Submerged Dipoles Undersea /Air Communication...a whole, it appears that the vertical electric component produced by th HED in the plane of the dipole (• =0) should be the most useful for undersea

A Model for the Management of Technical Risk in New Technology Development Programs

DTIC Science & Technology

1989-09-01

Heppenheimer , T. A . "Requiem for a Heavy-weight," Air and Snace/Smithsonian, 4: 50-55-- June/July 1989). 91. Jane’s Information Group, Inc. Jane’s...8217-- A MODEL FOR THE MANAGEMENT OF TECHNICAL RISK IN NEW TECHNOLOGY DEVELOPMENT PROGRAMS THESIS Peter B. King Captain, USA~F A FIT /G SM /L SR /89...S-22 1 DISI~1UT0N TAEMEN𔃻 A , S’o11 _44110h, eea;EL ECTE EApproVed 0 ulcrl~;DC2 0 1989 Dis-,irbuticf Unlimited D DEPARTMENT OF THE AIR FORCE-- - AIR

Characterization of CTLA-4 Structure and Expression on Human T Cells

DTIC Science & Technology

1993-10-01

prevents induction of anergy in T-cell plastic B cells. J. Immunol. 143:2714. clones. Nature 356:607. 7. Selvakumar , A., B. K. Mohanraj, R . L. Eddy, T... r ~n~~1 Form Approved ,, "൘ rmi OCUMENTATION PAGE orm Ap.r•ved Onorraoe is estimated Ic Ae.C.. I e 1C.;W fp$ei . ý’~t.cr.cenq Ile Urn* fo 1’ e...associated antigen," CTLA-4 (13). The genes for the geninterestid to the r 5 iacids o both human and mouse CI’IA-4 share a similar exon and J3

Women, Peace And Security: A Diverse Future In The USAF Is A Better Future

DTIC Science & Technology

2016-02-16

development of recruiting, such as to ensure millennials consider military service a viable option. The third recommendation suggests the development...strong leaders have knowledge of history, politics, cultures, religion , economics, and much more. But key to this mix of “smarts” is a drive for...continues+to+decline &source=bl&ots=bF5rXk2Lrh&sig=-GYN4htwJqzA1ac6C23cLFfB-- Y &hl=en&sa=X&ved=0ahUKEwjexaz7zfXKAhXMKyYKHXSTBfYQ6AEIIDAB#v=onepage&q

Hazardous Materials Management System. A Guide for Local Emergency Managers.

DTIC Science & Technology

1981-07-01

UDE OIL OCA EM~GENY ~A~iGRS𔄀. PERFORMING ORG. REPORT NUMBER F O . . . S . C O N T R A T l C R .Y N U BE R ) (i MYRAJ/LEE a&PENELOPE G./ROE *OCP41-79...out of, through, and within the area. Estimate the frequencies of shipments and the types and quanti ti es of ma teri al s i nvol ved. F (NOTE: Rer...reactions 4. Double- replacement reactions S . Oxidation- reduction reactions - Page 44 - B. Rate of Chemical Reactions I. Nature of material 2. Subdivision of

Flying Qualities of Relaxed Static Stability Aircraft. Volume 2. Ramifications of Flight-Essential/Critical Heavily-Augmented Airplane Characteristics on Flying Qualities

DTIC Science & Technology

1982-09-01

root variation am is perwltte4 to becout sort uaatlvs ( eeg ., cog. Wereeeixuly w~ved further fotowrd of the neutral potat). % w~a e t-period dh~a~a fs Cc...deg-sec) unit impulse. For sueh an input the pit~ch att.It~ tdc responses in !A’gure 11 appear with the same response shapes as those deacribed...this pair approaches the clewaical tm -degree-of-froedo. phugoid mode dwereint Z’ V/gZuAT &rglo I n this classic phugoid (Ref erence 22) the angle of

Axisymmetric charge-conservative electromagnetic particle simulation algorithm on unstructured grids: Application to microwave vacuum electronic devices

NASA Astrophysics Data System (ADS)

Na, Dong-Yeop; Omelchenko, Yuri A.; Moon, Haksu; Borges, Ben-Hur V.; Teixeira, Fernando L.

2017-10-01

We present a charge-conservative electromagnetic particle-in-cell (EM-PIC) algorithm optimized for the analysis of vacuum electronic devices (VEDs) with cylindrical symmetry (axisymmetry). We exploit the axisymmetry present in the device geometry, fields, and sources to reduce the dimensionality of the problem from 3D to 2D. Further, we employ 'transformation optics' principles to map the original problem in polar coordinates with metric tensor diag (1 ,ρ2 , 1) to an equivalent problem on a Cartesian metric tensor diag (1 , 1 , 1) with an effective (artificial) inhomogeneous medium introduced. The resulting problem in the meridian (ρz) plane is discretized using an unstructured 2D mesh considering TEϕ-polarized fields. Electromagnetic field and source (node-based charges and edge-based currents) variables are expressed as differential forms of various degrees, and discretized using Whitney forms. Using leapfrog time integration, we obtain a mixed E - B finite-element time-domain scheme for the full-discrete Maxwell's equations. We achieve a local and explicit time update for the field equations by employing the sparse approximate inverse (SPAI) algorithm. Interpolating field values to particles' positions for solving Newton-Lorentz equations of motion is also done via Whitney forms. Particles are advanced using the Boris algorithm with relativistic correction. A recently introduced charge-conserving scatter scheme tailored for 2D unstructured grids is used in the scatter step. The algorithm is validated considering cylindrical cavity and space-charge-limited cylindrical diode problems. We use the algorithm to investigate the physical performance of VEDs designed to harness particle bunching effects arising from the coherent (resonance) Cerenkov electron beam interactions within micro-machined slow wave structures.

Probabilities for gravitational lensing by point masses in a locally inhomogeneous universe

NASA Technical Reports Server (NTRS)

Isaacson, Jeffrey A.; Canizares, Claude R.

1989-01-01

Probability functions for gravitational lensing by point masses that incorporate Poisson statistics and flux conservation are formulated in the Dyer-Roeder construction. Optical depths to lensing for distant sources are calculated using both the method of Press and Gunn (1973) which counts lenses in an otherwise empty cone, and the method of Ehlers and Schneider (1986) which projects lensing cross sections onto the source sphere. These are then used as parameters of the probability density for lensing in the case of a critical (q0 = 1/2) Friedmann universe. A comparison of the probability functions indicates that the effects of angle-averaging can be well approximated by adjusting the average magnification along a random line of sight so as to conserve flux.

Finsler-type modification of the Coulomb law

NASA Astrophysics Data System (ADS)

Itin, Yakov; Lämmerzahl, Claus; Perlick, Volker

2014-12-01

Finsler geometry is a natural generalization of pseudo-Riemannian geometry. It can be motivated e.g. by a modified version of the Ehlers-Pirani-Schild axiomatic approach to space-time theory. Also, some scenarios of quantum gravity suggest a modified dispersion relation which could be phrased in terms of Finsler geometry. On a Finslerian space-time, the universality of free fall is still satisfied but local Lorentz invariance is violated in a way not covered by standard Lorentz invariance violation schemes. In this paper we consider a Finslerian modification of Maxwell's equations. The corrections to the Coulomb potential and to the hydrogen energy levels are computed. We find that the Finsler metric corrections yield a splitting of the energy levels. Experimental data provide bounds for the Finsler parameters.

[The relevance of multiple sclerosis drugs in private health insurance (PHI)].

PubMed

Wild, F

2015-06-01

The development of expenses and prescriptions in the pharmacotherapy for multiple sclerosis (MS) is examined on the basis of prescription data of 14 PHI firms. The drugs for the treatment of MS are among the most top-selling drugs in the PHI. From 2007 to 2012, the expenses increase 2.33-fold. The main cause is the increas of the prescription figures. In 2012, about 8,400 privately insured persons receive an MS drug. The prevalence of MS is 2.3 times higher in women than in men Impro ved diagnostic possibilities and expensive new drugs will lead to a dynamic cost de velopment in the next years.

New directions: Future approaches to the standardized assessment of airborne pollutants affecting environmental quality

NASA Astrophysics Data System (ADS)

Nehr, Sascha; Franzen-Reuter, Isabelle; Kucejko, Catharina

2017-10-01

Man-made activities have caused unexampled changes of our environment during the last two centuries. Due to emissions of a vast number of pollutants the composition of the Earth's atmosphere is continuously changing, and the consequences for humans and for ecosystems are only partly understood at present. Once released to the atmosphere, the emitted substances undergo physical and chemical degradation. Many of the substances detected in ambient air are toxic or carcinogenic and might cause respiratory and cardiovascular diseases. Furthermore, air pollutants are influencing acidification, eutrophication, global warming, and biodiversity. Therefore soil quality, water quality, air quality, ecosystem exposure to pollutant deposition, biodiversity, and climate change are coupled problems (Schlesinger, 1997; Steffen et al., 2005; Ehlers et al., 2006; Rockström et al., 2009).

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

PubMed

Duque, Gustavo Salgado; Silva, Dayse Aparecida da; Albuquerque, Felipe Neves de; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; Albuquerque, Denilson Campos de

2016-11-01

Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Avaliar a frequência dos polimorfismos genéticos da ECA em pacientes com IC de etiologia isquêmica de uma população do Rio de Janeiro e sua associação com achados ecocardiográficos. Avaliação genética do polimorfismo I/D da ECA associada a análise de dados clínicos, laboratoriais e ecocardiográficos de 99 pacientes. Foram encontrados 53 alelos I, 145 alelos D, quanto aos genótipos da ECA: 49,5% DD, 47,48% DI, 3,02% II. O tratamento medicamentoso foi otimizado com 98% usando betabloqueadores e 84,8%, IECA ou bloqueador do receptor de angiotensina. Achados ecocardiográficos: diferença entre os diâmetros diastólicos do ventrículo esquerdo (ΔVED): 2,98±8,94 (DD) vs. 0,68±8,12 (DI) vs. -11,0±7,00 (II), p=0,018; piora evolutiva do diâmetro sistólico do VE (VES): 65,3 % DD vs. 19,0 % DI vs. 0,0 % II, p=0,01; do diâmetro diastólico do VE (VED): 65,3 % DD vs. 46,8 % DI vs. 0,0 % II, p=0,03; e da fração de ejeção do VE (FEVE): 67,3 % DD vs. 40,4 % DI vs. 33,3 % II, p=0,024. Correlação com alelo D: ΔFEVE, ΔVES, ΔVED. Foram identificados mais pacientes com piora evolutiva da FEVE e dos diâmetros cavitários do VE no genótipo DD, seguido do DI, sendo o II o de melhor evolução. O mesmo padrão foi observado na ΔVED.

NASA Tech Helps Better Understand Our Home Planet

NASA Image and Video Library

2018-04-20

NASA’s Earth observations are critical for understanding our home planet and how it is changing. For Earth Day NASA is spotlighting some of the agency’s work with the latest technologies that have the potential to transform how we see our Blue Marble. Join us as we speak with NASA Ames scientist Ved Chirayath, who has developed cameras that can image marine environments below the ocean’s surface; Shayna Skolnik, founder and CEO of Navteca, a company that’s working to bring NASA Earth data to life through virtual reality; and Brian Campbell, senior education and outreach specialist for ICESat-2 satellite, which is set to launch this fall to measure polar ice and other important Earth features.

[Adult hepatoblastoma. A case report].

PubMed

Goikoetxea Urdiain, A; Sánchez Acedo, P; Mateo Retuerta, J; Tarifa Castilla, A; Zazpe Ripa, C; Herrera Cabezón, J

2016-01-01

Adult hepatoblastoma is a rare pathology. Its pathogeny is not well understood and prognosis is very bad. We pre-sent a case of adult hepatoblastoma treated in our centre. A 65 year-old male, without previous hepatopathy, who consulted due to right hypochondrial pain with a subacute evolution. The pathological diagnosis was adult epithelial hepatoblastoma, with free surgical margins. The patient recei-ved a second surgical intervention 5 months later due to early recurrence and died 10 months after the diagnosis due to a new massive recurrence. His definitive diagnosis is histological. Radical surgery is the only treatment that increases survival, but recurrence is frequent. There are no well-defined patterns of adjuvant chemotherapy nor is there any trans-plant experience.

Continued Development and Implementation of the Universal Network Interface Device (UNID) II in the Digital Engineering Laboratory Network (DELNET). Volume 2.

DTIC Science & Technology

1984-12-01

PACKET LO-ATED IN TABLE LCNTTB. INPUT < THE INDUT IS A TWO CHARACTER ASCII VALUE INDICATING THE TABLE REQUIRING EVALUATION . > PROCESSING THIS PROCEDURE...INTO OHANYE A (2). I NPUT THE INPUT IS AN INTEGER VA UE INDICATING’ THE TAlN’LE LOCATI’ OF THE FRAmE TO BE EVALUATED . PROC--SSING THIS PROCEDURE LOU-S AT...GOOD AEXICdLFCL ~N IS NuT rC:L I VED LY THE END OF THE WAIT PER ICOH, I r I S fx>Sit-..) ACAI N UPION IriL NE.XT CflLL THRJOH THIS IRROCEDURE. A [ RAMC OF

The natural and social-economic resourses of the Republic of Komi

NASA Astrophysics Data System (ADS)

Fridman, Anton; Yakovleva, Maya; Kuchkina, Ekaterina; Lyaskovskiy, Sergey; Ievlev, Nikolay

2013-04-01

North-West of Russian Federation, include 11 subjects of Russian Federation. One of the most interesting regions is republic of Komi.. The native population of North - korely, rusichi, komi, ved', permyaki and other peoples are living here. Main characteristics of region are pollution-free territory, low population concentration, material wealth and huge forest and water resources. Flora and fauna are also interesting. Successful fishing and hunting are possible because of great variety of animals and fish. There are 240 protected natural areas in Republic of Komi (information on the 1st January 2010). All these features let organize scientific expeditions, tourists' routes helping to know unique nature and ethnical culture of North.

Glaucoma Progression and its Relationship with Corrected and Uncorrected Intraocular Pressure in Eyes with History of Refractive Corneal Surgery.

PubMed

Kwon, Junki; Sung, Kyung Rim; Jo, Jaehyuck; Yang, Sung Ho

2018-04-20

To investigate glaucoma progression and its relationship with corrected and uncorrected intraocular pressure (IOP) in patients with a history of refractive corneal surgery (RCS). Totally, 56 eyes of 56 primary open-angle glaucoma patients who had a history of RCS were included. Mean keratometry and central corneal thickness were measured at the time of glaucoma diagnosis. Three IOP measurements, i.e., uncorrected IOP ( UC IOP) and corrected IOP calculated by applying the Kohlhaas ( CK IOP) and Ehlers ( CE IOP) formulas, were used. Participants were categorized into two groups (low-teen [<15 mmHg] and high-teen [≥15 mmHg] groups) according to the mean follow-up IOP, in each of the three IOP measurements. Glaucoma progression was determined based on either structurally or functionally by stereoscopic optic disc/retinal nerve fiber layer photographs or visual field tests. Kaplan-Meier survival curves were compared between the low-teens group and high-teens group for each IOP measurement. Risk factors for glaucoma progression, including uncorrected and corrected IOP measurements, were analyzed using a Cox proportional-hazards model. Among total eyes, glaucoma progression was found in 19 (34%) eyes during 4.3 years of mean follow-up period. Individual values of uncorrected IOP and corrected IOP showed significant differences (p < 0.001). Incidence of glaucoma progression was higher in high-teens group than in low-teens group by corrected IOP values (both Kohlhaas and Ehlers, p = 0.006, 0.003), but not by uncorrected IOP values (p = 0.749). The cumulative probability of glaucoma progression was significantly greater in the high-teens group than in the low-teens group using the Elhers formula determined by Kaplan-Meier analysis (p = 0.030). For glaucoma eyes with history of RCS, high-teen group by corrected mean follow-up IOP showed more glaucoma progression than low-teen group. More intensive IOP-lowering treatment will be required for patient with high-teen follow-up corrected IOP to prevent glaucoma progression.

On an algebraic structure of dimensionally reduced magical supergravity theories

NASA Astrophysics Data System (ADS)

Fukuchi, Shin; Mizoguchi, Shun'ya

2018-06-01

We study an algebraic structure of magical supergravities in three dimensions. We show that if the commutation relations among the generators of the quasi-conformal group in the super-Ehlers decomposition are in a particular form, then one can always find a parameterization of the group element in terms of various 3d bosonic fields that reproduces the 3d reduced Lagrangian of the corresponding magical supergravity. This provides a unified treatment of all the magical supergravity theories in finding explicit relations between the 3d dimensionally reduced Lagrangians and particular coset nonlinear sigma models. We also verify that the commutation relations of E 6 (+ 2), the quasi-conformal group for A = C, indeed satisfy this property, allowing the algebraic interpretation of the structure constants and scalar field functions as was done in the F 4 (+ 4) magical supergravity.

Legislation may support STaRS

NASA Astrophysics Data System (ADS)

Congressman Vernon Ehlers (R, MI) has offered three bills in the House of Representatives that support K-12 science, math, engineering, and technology (SMET) education (Eos, April 18, 2000). Although no dollar amounts are mentioned, the three bills contain numerous provisions for improving and expanding SMET education activities at the Department of Education and the National Science Foundation, and for tax incentives for pre-service teacher education and in-service professional development. Of particular interest is Section 15 of H.R. 4271, the National Science Education Act, which directs the NSF to provide scholarships for K-12 teachers to participate in research programs in government agencies, colleges and universities, or private research establishments. Such scholarships could support AGU's Science Teacher and Research Scientist (STaRS) effort, which is intended to provide opportunities for teachers to participate in research under the direction of AGU scientists, and for those same scientists to participate in science teaching under the teachers' direction.

Bill would bolster science at EPA

NASA Astrophysics Data System (ADS)

Showstack, Randy

Since its establishment in 1970, the U.S. Environmental Protection Agency (EPA) has primarily served as a regulatory agency with a significant science component. However, the agency's scientific practices and performance at times have been criticized by the U.S. General Accounting Office, the National Academies of Science (NAS), Congress, and EPA's own science advisory board, as well as in a number of lawsuits.New legislation introduced by Rep. Vernon Ehlers (R-Mich.), chair of the House of Representatives' Science Subcommittee on Environment, Technology, and Standards, includes measures meant to improve the agency's science component. The legislation, H.R. 64, would require the president to appoint an EPA deputy administrator for science and technology This deputy administrator, who would rank higher than existing assistant administrators (AAs), would be responsible for the overall scientific and technical foundation of the agency's decisions, including ensuring that the agency's scientific endeavors use the best possible peer review and research planning practices.

The first international leprosy conference, Berlin, 1897: the politics of segregation.

PubMed

Pandya, S S

2004-01-01

The present paper examines the first attempts to internationalise the problem of leprosy, a subject hitherto overlooked by historians of imperialism and disease. The last decade of the nineteenth century saw many in the civilised countries of the imperialist West gripped by a paranoia about an invasion of leprosy via germ-laden immigrants and returning expatriates who had acquired the infection in leprosy endemic colonial possessions. Such alarmists clamoured for the adoption of vigorous leper segregation policies in such colonies. But the contagiousness of leprosy did not go unquestioned by other westerners. The convocation in Berlin of the first international meeting on leprosy revealed the interplay of differing and sometimes incompatible views about the containment of leprosy by segregation. The roles of officials from several countries, as well as the roles of five protagonists (Albert Ashmead, Jules Goldschmidt, Edvard Ehlers. Armauer Hansen, and Phineas Abraham) in the shaping of the Berlin Conference are here examined.

The first international leprosy conference, Berlin, 1897: the politics of segregation.

PubMed

Pandya, Shubhada S

2003-01-01

The present paper examines the first attempts to internationalize the problem of leprosy, a subject hitherto overlooked by historians of imperialism and disease. The last decade of the nineteenth century saw many in the 'civilized countries' of the imperialist West gripped by a paranoia about an invasion of leprosy via germ-laden immigrants and returning expatriates who had acquired the infection in leprosy-endemic colonial possessions. Such alarmists clamoured for the adoption of vigorous leper segregation policies in such colonies. But the contagiousness of leprosy did not go unquestioned by other westerners. The convocation in Berlin of the first international meeting on leprosy revealed the interplay of differing and sometimes incompatible views about the containment of leprosy by segregation. The roles of officials from several countries, as well as the roles of five protagonists (Albert Ashmead, Jules Goldschmidt, Edvard Ehlers, Armauer Hansen, and Phineas Abraham) in the shaping of the Berlin Conference are here examined.

Homeostatic control of neural activity: from phenomenology to molecular design.

PubMed

Davis, Graeme W

2006-01-01

Homeostasis is a specialized form of regulation that precisely maintains the function of a system at a set point level of activity. Recently, homeostatic signaling has been suggested to control neural activity through the modulation of synaptic efficacy and membrane excitability ( Davis & Goodman 1998a, Turrigiano & Nelson 2000, Marder & Prinz 2002, Perez-Otano & Ehlers 2005 ). In this way, homeostatic signaling is thought to constrain neural plasticity and contribute to the stability of neural function over time. Using a restrictive definition of homeostasis, this review first evaluates the phenomenological and molecular evidence for homeostatic signaling in the nervous system. Then, basic principles underlying the design and molecular implementation of homeostatic signaling are reviewed on the basis of work in other, simplified biological systems such as bacterial chemotaxis and the heat shock response. Data from these systems are then discussed in the context of homeostatic signaling in the nervous system.

Geoscience and Public Policy

NASA Astrophysics Data System (ADS)

White, K. S.

2013-12-01

Many current public policy issues have a geoscience component: climate change, natural hazards, energy, and mineral resources to name just a few. In addition, Congress makes decisions that directly affect scientists, such as funding allocations and visa and travel policy. Yet few geoscientists are engaged in the policy-making process. Members of Congress have called on scientists to become more active, including Ph.D. physicist and former-Representative Vernon Ehlers (R-MI). In an address at the 2010 AAAS Forum on Science and Technology Policy, he told scientists, "The gulf between the scientifically minded and those who are not scientifically minded is still tremendous. I think we are keeping far too quiet about what we know and how we would go about solving problems. We have so much to offer this country à solutions to various difficulties." This talk will provide information on avenues for geoscientists to more effectively engage in the public policy arena.

Predicting participation in and successful outcome of a penile rehabilitation programme using a phosphodiesterase type 5 inhibitor with a vacuum erection device after radical prostatectomy.

PubMed

Kimura, Masaki; Caso, Jorge R; Bañez, Lionel L; Koontz, Bridget F; Gerber, Leah; Senocak, Cagri; Donatucci, Craig F; Vujaskovic, Zeljko; Moul, Judd W; Polascik, Thomas J

2012-12-01

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The role of the vacuum erection device (VED) has increased with its use in combined therapy with a phosphodiesterase type 5 inhibitor (PDE5i) for penile rehabilitation after radical prostatectomy (RP) and radiotherapy. The advantages of the VED are non-invasive, cost-effective, and a possibility of preventing shrinkage of penis length. Albeit current widespread use of penile rehabilitation programmes for post-RP erectile dysfunction, independent predictors for the rehabilitation participants, as well as for its treatment success have not been fully investigated. In the present study, we have added several new predictors for rehabilitation participation, e.g. African-Americans and higher preoperative sexual function. Conversely, higher preoperative PSA concentrations and the presence of positive surgical margins were predictors for avoidance of rehabilitation. Notably, there was a primary surgeon difference, which had a trend for predicting outcome of the rehabilitation among the participants, implying their surgical technique and follow-up might influence success of the rehabilitation. • To investigate baseline demographic and clinicopathological characteristics of men who participate in our penile rehabilitation programme after radical prostatectomy (RP). • To determine predictors for participation in rehabilitation, as well as successful rehabilitation outcome using multivariable logistic regression analyses. • We analysed data on 2345 consecutive patients who underwent RP between 2001 and 2009 in our institution. • The decision to participate in penile rehabilitation using phosphodiesterase type 5 inhibitor (PDE5i) with a vacuum erection device (VED) was based on the patient's choice after post-RP discussions. • Rehabilitation success was defined using the following criteria: (i) patients who continued the penile rehabilitation programme and did not switch treatment from PDE5i to other erectile aids, (ii) success was noted in men who had an Expanded Prostate Cancer Index Composite (EPIC) sexual function (SF) score of >75% of the patient's baseline EPIC score, and (iii) patients who answered that they achieved adequate erections with a PDE5i. • Logistic regression analysis was used to identify factors associated with treatment participation and its success. • Of 676 patients, 354 (53.2%) men participated in a penile rehabilitation programme. Among 329 rehabilitation participants with available data, 96 (29.2%) had treatment success. • In multivariable regression analysis, African-Americans (odds ratio [OR] 3.47, P < 0.001), and higher preoperative SF (OR 1.02, P < 0.001) were associated with participation in rehabilitation. • Higher preoperative PSA concentration (OR 0.50, P = 0.004) and presence of positive surgical margins (OR 0.68, P = 0.042) were found to be independent predictors for non-participation in the rehabilitation. • For rehabilitation outcomes, being older at surgery (OR 0.93, P = 0.001) and adjuvant therapy (OR 0.34, P = 0.047) had a negative association with successful outcome. • There was a trend in the relationship between primary surgeon and rehabilitation success (OR 1.05, P = 0.053) • Those patients who have risk factors, e.g. adverse prostate cancer features, need to be carefully counselled and encouraged to participate in the penile rehabilitation programme. • Clinicians could lead patients toward successful outcomes if appropriate surgical techniques and rehabilitation are provided. © 2012 BJU INTERNATIONAL.

Training healthcare personnel for mass-casualty incidents in a virtual emergency department: VED II.

PubMed

Heinrichs, Wm Leroy; Youngblood, Patricia; Harter, Phillip; Kusumoto, Laura; Dev, Parvati

2010-01-01

Training emergency personnel on the clinical management of a mass-casualty incident (MCI) with prior chemical, biological, radioactive, nuclear, or explosives (CBRNE) -exposed patients is a component of hospital preparedness procedures. The objective of this research was to determine whether a Virtual Emergency Department (VED), designed after the Stanford University Medical Center's Emergency Department (ED) and populated with 10 virtual patient victims who suffered from a dirty bomb blast (radiological) and 10 who suffered from exposure to a nerve toxin (chemical), is an effective clinical environment for training ED physicians and nurses for such MCIs. Ten physicians with an average of four years of post-training experience, and 12 nurses with an average of 9.5 years of post-graduate experience at Stanford University Medical Center and San Mateo County Medical Center participated in this IRB-approved study. All individuals were provided electronic information about the clinical features of patients exposed to a nerve toxin or radioactive blast before the study date and an orientation to the "game" interface, including an opportunity to practice using it immediately prior to the study. An exit questionnaire was conducted using a Likert Scale test instrument. Among these 22 trainees, two-thirds of whom had prior Code Triage (multiple casualty incident) training, and one-half had prior CBRNE training, about two-thirds felt immersed in the virtual world much or all of the time. Prior to the training, only four trainees (18%) were confident about managing CBRNE MCIs. After the training, 19 (86%) felt either "confident" or "very confident", with 13 (59%) attributing this change to practicing in the virtual ED. Twenty-one (95%) of the trainees reported that the scenarios were useful for improving healthcare team skills training, the primary objective for creating them. Eighteen trainees (82%) believed that the cases also were instructive in learning about clinical skills management of such incidents. These data suggest that training healthcare teams in online, virtual environments with dynamic virtual patients is an effective method of training for management of MCIs, particularly for uncommonly occurring incidents.

A Low Cost Traveling Wave Tube for Wireless Communications

NASA Technical Reports Server (NTRS)

Vancil, Bernard Kenneth; Wintucky, Edwin G.; Williams, W. D. (Technical Monitor)

2002-01-01

Demand for high data rate wireless communications is pushing up amplifier power, bandwidth and frequency requirements. Some systems are using vacuum electron devices again because solid-state power amplifiers are not able to efficiently meet the new requirements. The traveling wave tube is the VED of choice because of its excellent broadband capability as well as high power efficiency and frequency. But TWTs are very expensive on a per watt basis below about 200 watts of output power. We propose a new traveling wave tube that utilizes cathode ray tube construction technology and electrostatic focusing. We believe the tube can be built in quantity for under $1,000 each. We discuss several traveling wave tube slow wave circuits that lend themselves to the new construction. We will present modeling results and data on prototype devices.

An evaluation of the accuracy of some radar wind profiling techniques

NASA Technical Reports Server (NTRS)

Koscielny, A. J.; Doviak, R. J.

1983-01-01

Major advances in Doppler radar measurement in optically clear air have made it feasible to monitor radial velocities in the troposphere and lower stratosphere. For most applications the three dimensional wind vector is monitored rather than the radial velocity. Measurement of the wind vector with a single radar can be made assuming a spatially linear, time invariant wind field. The components and derivatives of the wind are estimated by the parameters of a linear regression of the radial velocities on functions of their spatial locations. The accuracy of the wind measurement thus depends on the locations of the radial velocities. The suitability is evaluated of some of the common retrieval techniques for simultaneous measurement of both the vertical and horizontal wind components. The techniques considered for study are fixed beam, azimuthal scanning (VAD) and elevation scanning (VED).

The two NUT-like solutions of Ernst equation

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

Wu Yabo; Dong Peng; Deng Xuemei

By applying Ehlers transformation to Schwarzschild and Kerr solutions of Ernst equation and choosing the suitable coordinate transformations, the two NUT-like solutions, i.e., the so called NUT-Taub-like and the Kerr-NUT-like solutions are obtained which not only can, respectively, reduce to Schwarzschild and Kerr solutions when the parameter l{sup '}=0, but also can also reduce to the NUT-Taub metric and Kerr-NUT metric, respectively, when l{sup '} satisfies the some approximation. Meanwhile it is shown that in the NUT-Taub and Kerr-NUT solutions the range of value for the parameter l interpreted as the gravomagnetic monopole cannot be arbitrary and should be confinedmore » by mass of the source to vertical bar l vertical bar<

Republication of: Contributions to the theory of pure gravitational radiation. Exact solutions of the field equations of the general theory of relativity II

NASA Astrophysics Data System (ADS)

Jordan, Pascual; Ehlers, Jürgen; Sachs, Rainer K.

2013-12-01

This is an English translation of a paper by Pascual Jordan, Juergen Ehlers and Rainer Sachs, first published in 1961 in the proceedings of the Academy of Sciences and Literature in Mainz (Germany). The original paper was part 2 of a five-part series of articles containing the first summary of knowledge about exact solutions of Einstein's equations found until then. (Parts 1 and 4 of the series have already been reprinted, parts 3 and 5 will be printed as Golden Oldies in near future.) This second paper discusses the geometry of geodesic null congruences, the algebraic classification of the Weyl tensor by spinor methods, and applies these to a study of the propagation of gravitational and electromagnetic radiation. It has been selected by the Editors of General Relativity and Gravitation for republication in the Golden Oldies series of the journal. The republication is accompanied by an editorial note written by Malcolm A. H. MacCallum and Wolfgang Kundt.

Net photosynthesis in Sphagnum mosses has increased in response to the last century's 100 ppm increase in atmospheric CO2

NASA Astrophysics Data System (ADS)

Serk, Henrik; Nilsson, Mats; Schleucher, Jurgen

2017-04-01

Peatlands store >25% of the global soil C pool, corresponding to 1/3 of the contemporary CO2-C in the atmosphere. The majority of the accumulated peat is made up by remains of Sphagnum peat mosses. Thus, understanding how various Sphagnum functional groups respond, and have responded, to increasing atmospheric CO2 and temperature constitutes a major challenge for our understanding of the role of peatlands under a changing climate. We have recently demonstrated (Ehlers et al., 2015, PNAS) that the abundance ratio of two deuterium isotopomers (molecules carrying D at specific intramolecular positions, here D6R/S) of photosynthetic glucose reflects the ratio of oxygenation to carboxylation metabolic fluxes at Rubisco. The photosynthetic glucose is prepared from various plant carbohydrates including cellulose. This finding has been established in CO2 manipulation experiments and observed in carbohydrate derived glucose isolated from herbarium samples of all investigated C-3 species. The isotopomer ratio is connected to specific enzymatic processes thus allowing for mechanistic implicit interpretations. Here we demonstrate a clear increase in net photosynthesis of Sphagnum fuscum in response to the increase of 100 ppm CO2 during the last century as deduced from analysis on S. fuscum remains from peat cores. The D6R/S ratio declines from bottom to top in peat cores, indicating CO2-driven reduction of photorespiration in contemporary moss biomass. In contrast to the hummock-forming S. fuscum, hollow-growing species, e.g. S. majus did not show this response or gave significantly weaker response, suggesting important ecological consequences of rising CO2 on peatland ecosystem services. We hypothesize that photosynthesis in hollow-growing species under water saturation is fully or partly disconnected from the atmospheric CO2 partial pressure and thus showing weaker or no response to increased atmospheric CO2. To further test the field observations we grow both hummock and hollow Sphagnum species in controlled green-house experiments under varying combinations of water table, CO2 and temperature. Preliminary results confirm our interpretations of data from field peat cores. Ehlers, I., Augusti, A., Betson, T.R., Nilsson, M.B., Marshall, J.D. and J. Schleucher (2015) Detecting long-term metabolic shifts using isotopomers: CO2-driven suppression of photorespiration in C3 plants over the 20th century, Proceedings National Academy of Sciences (PNAS), doi: 10.1073/pnas.1504493112

Cross-sectional and prospective associations between cognitive appraisals and posttraumatic stress disorder symptoms following stroke.

PubMed

Field, Emma Louise; Norman, Paul; Barton, Jane

2008-01-01

This study examined cross-sectional and prospective associations between cognitive appraisals and posttraumatic stress disorder (PTSD) symptoms following stroke. While in hospital, stroke patients (n=81) completed questionnaires assessing cognitive appraisals (i.e., negative cognitions about the self, negative cognitions about the world, and self-blame) and PTSD symptoms. PTSD symptoms were assessed again 3 months later when all patients had been discharged from hospital (n=70). Significant correlations were found between the time 1 measures of negative cognitions about the self and the world, but not self-blame, and the severity of PTSD symptoms measured at time 1 and at time 2. Regression analyses revealed that cognitive appraisals explained a significant amount of variance in the severity of PTSD symptoms at time 1, with negative cognitions about the self-emerging as a significant predictor. In contrast, time 1 cognitive appraisals were unable to explain additional variance in time 2 PTSD severity over and above that explained by time 1 PTSD severity. The findings therefore provide only weak support for Ehlers and Clark's cognitive model of PTSD.

Evaluation of commercial available fusion algorithms for Geoeye data

NASA Astrophysics Data System (ADS)

Vaiopoulos, Aristides D.; Nikolakopoulos, Konstantinos G.

2013-10-01

In this study ten commercial available fusion techniques and more especially the Ehlers, Gram-Schmidt, High Pass Filter, Local Mean Matching (LMM), Local Mean and Variance Matching (LMVM), Modified IHS (ModIHS), Pansharp, PCA, HCS (Hyperspherical Color Space) and Wavelet were used for the fusion of Geoeye panchromatic and multispectral data. The panchromatic data have a spatial resolution of 0.5m while the multispectral data have a spatial resolution of 2.0m. The optical result, the statistical parameters and different quality indexes such as ERGAS, Q, entropy were examined and the results are presented. The broader area of Pendeli mountain near to the city of Athens Greece and more especially two sub areas with different characteristics were chosen for the comparison. The first sub area is located at the edge of the urban fabric and combines at the same time the characteristics of an urban and a rural area. The second sub area comprises a large open quarry and it is suitable to examine which fused product is more suitable for mine monitoring.

The influence of data-driven versus conceptually-driven processing on the development of PTSD-like symptoms.

PubMed

Kindt, Merel; van den Hout, Marcel; Arntz, Arnoud; Drost, Jolijn

2008-12-01

Ehlers and Clark [(2000). A cognitive model of posttraumatic stress disorder. Behaviour Research and Therapy, 38, 319-345] propose that a predominance of data-driven processing during the trauma predicts subsequent PTSD. We wondered whether, apart from data-driven encoding, sustained data-driven processing after the trauma is also crucial for the development of PTSD. Both hypotheses were tested in two analogue experiments. Experiment 1 demonstrated that relative to conceptually-driven processing (n=20), data-driven processing after the film (n=14), resulted in more intrusions. Experiment 2 demonstrated that relative to the neutral condition (n=24) and the data-driven encoding condition (n=24), conceptual encoding (n=25) reduced suppression of intrusions and a trend emerged for memory fragmentation. The difference between the two encoding styles was due to the beneficial effect of induced conceptual encoding and not to the detrimental effect of data-driven encoding. The data support the viability of the distinction between data-driven/conceptually-driven processing for the understanding of the development of PTSD.

Bridging the timescales between thermochronological and cosmogenic nuclide data

NASA Astrophysics Data System (ADS)

Glotzbach, Christoph

2015-04-01

Reconstructing the evolution of Earth's landscape is a key to understand its future evolution and to identify the driving forces that shape Earth's surface. Cosmogenic nuclide and thermochronological methods are routinely used to quantify Earth surface processes over 102-104 yr and 106-107 yr, respectively (e.g. Lal 1991; Reiners and Ehlers 2005; von Blanckenburg 2006). A comparison of the rates of surface processes derived from these methods is, however, hampered by the large difference in their timescales. For instance, a constant erosion rate of 0.1 mm/yr yield an apatite (U-Th)/He age of ~24 Ma and a 10Be age of ~6 ka, respectively. Analytical methods that bridge this time gap are on the way, but are not yet fully established (e.g. Herman et al. 2010). A ready to use alternative are river profiles, which record the regional uplift history over 102-107 yr (e.g. Pritchard et al. 2009). Changes in uplift are retained in knickzones that propagate with a distinct velocity upstream, and therefore the time of an uplift event can be estimated. Here I present an integrative inverse modelling approach to simultaneously reconstruct river profiles, model thermochronological and cosmogenic nuclide data and to derive robust information about landscape evolution over thousands to millions of years. An efficient inversion routine is used to solve the forward problem and find the best uplift history and erosional parameters that reproduce the observed data. I test the performance of the algorithm by inverting a synthetic dataset and a dataset from the Sila massif (Italy). Results show that even complicated uplift histories can be reliably retrieved by the combined interpretation of river profiles, thermochronological and cosmogenic nuclide data. References Gallagher, K., Brown, R. & Johnson, C. (1998): Fission track analysis and its applications to geological problems. - Annu. Rev. Earth Planet., 26: 519-572. Herman, F., Rhodes, E.J., Braun, J. & Heiniger, L. (2010): Uniform erosion rates and relief amplitude during glacial cycles in the Southern Alps of New Zealand, as revealed from OSL-thermochronology. - Earth Planet. Sci. Lett., 297: 183-189. Lal, D. (1991): Cosmic ray labeling of erosion surfaces: in situ nuclide production rates and erosion models. - Earth Planet. Sci. Lett. 104: 424-439. Pritchard, D., Roberts, G.G., White, N.J. & Richardson, C.N. (2009): Uplift histories from river profiles. - Geophys. Res. Lett., 36, L24301, doi:10.1029/2009GL040928. Reiners, P.W. & Ehlers, T.A. (2005): Low-temperature Thermochronology: Techniques, Interpretations, and Applications. - Rev. Mineral. Geochem., 58. Von Blanckenburg, F. (2006): The control mechanisms of erosion and weathering at basin scale from cosmogenic nuclides in river sediment. - Earth Planet. Sci. Lett., 242: 462-479.

Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

2017-11-02

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Implications of Weak Link Effects on Thermal Characteristics of Transition-Edge Sensors

NASA Technical Reports Server (NTRS)

Bailey, C. N.; Adams, J. S.; Bandler, S. R.; Brekosky, R. P.; Chevenak, J. A.; Eckart, M. E.; Finkbeiner, F. M.; Kelley, R. L.; Kally, D. P.; Kilbourne, C. A.;

[Cognitive therapy of trauma related guilt in patients with PTSD].

PubMed

Popiel, Agnieszka

2014-01-01

Various aspects of guilt are frequent problems of patients suffering from PTSD, though they have been included into the diagnostic criteria for PTSD just in the present version DSM-5. Some studies indicate limitation of effectiveness of exposure therapy in PTSD patients with predominant emotions of anger or guilt. The aim of this paper is to present cognitive conceptualization of guilt in PTSD proposed by Kubany, and a treatment protocol resulting from this conceptualization. The clinical application of the protocol is illustrated with preliminary results of systematic observation of 8 patients with moderate to severe PTSD who were treated with cognitive therapy for guilt followed by a standard prolonged exposure protocol. The cognitive therapy of guilt can be a valuable supplement for treatment of PTSD. This protocol can also be an inspiration for therapists working with patients with dysfunctional guilt as a problem in other than PTSD disorders--like depression or adjustment disorders. In discussion the place of guilt in treatment according to different (PE-Foa et al.; CPT-Resick et al.; CT-Ehlers and Clark) trauma focused therapy approaches is addressed, and the need for further studies is underlined.

The associations between adult attachment, posttraumatic symptoms, and posttraumatic growth.

PubMed

Arikan, Gizem; Stopa, Lusia; Carnelley, Katherine B; Karl, Anke

2016-01-01

Individual differences after trauma vary considerably and can range from posttraumatic stress disorder (PTSD) to posttraumatic growth (PTG). Current theoretical models cannot fully explain this variability. Therefore, we integrated attachment theory with Ehlers and Clark's model of PTSD to understand whether attachment style is associated with negative appraisals of a traumatic event(s), posttraumatic stress symptoms (PTS), and PTG. Our aim was to test this integrated model PTSD in an analog sample who had experienced at least one traumatic event. We used structural equation modeling to test the association of adult attachment and posttraumatic cognitions (self and world/others) with PTS and PTG using a cross-sectional, correlational design. The sample comprised 393 university staff and students (RangeAge= 18-49, 85% females) who completed online measures. Attachment anxiety and negative posttraumatic self-cognitions were positively associated. Negative posttraumatic self-cognitions were positively associated with PTS. Attachment anxiety had an indirect effect (via negative posttraumatic self-cognitions) on PTS, whereas attachment avoidance predicted more negative posttraumatic world cognitions and lower perceived PTG. The study highlights the importance of considering how attachment styles influence posttraumatic emotion regulation and cognitive processing of the trauma to determine posttraumatic mental health.

PREFACE: The Sixth International Conference on Gravitation & Cosmology

NASA Astrophysics Data System (ADS)

Date, Ghanashyam; Souradeep, Tarun

2008-07-01

The sixth International Conference on Gravitation & Cosmology (ICGC-2007) was organized at IUCAA, Pune, 17-21 December 2007. This series of international meetings, held every four years under the auspices of the Indian Association for General Relativity and Gravitation (IAGRG), has now spanned two decades. Previous ICGC meetings were held at Cochin University of Science and Technology (2004), Indian Institute of Technology, Kharagpur (2000), IUCAA, Pune (1995), Physical Research Laboratory, Ahmedabad (1991) & Goa (1987). These meetings have broad international participation and feature leading experts in the field of Cosmology, gravitational waves and quantum gravity. The frontier of research in Gravitation and Cosmology has seen remarkable progress in the past decades. On the theoretical front, black holes and cosmological singularities continue to challenge and attract quantum gravity researchers. The quest for the detection of Gravitational waves and the promise of gravitational wave astronomy continues to grow and breakthroughs of the past couple of years indicate that numerical relativity is catching up too. The past few years have also seen very ambitious experimental efforts to verify general relativity as the theory of gravitation. Cosmology has been veritably transformed into a precision science with the tremendous improvement in the quantity and quality of cosmological observations. The exquisite measurements not only allow refinement of the cosmological model parameters but have begun to allow observational tests of underlying fundamental assumptions and hunt for subtle deviations that could be the key to understanding the early universe. The sixth meeting brought together active scientists from all over the globe to present the state of the art at the frontiers of research. It also offered younger Indian researchers an opportunity for interaction with experts from within India and abroad. The meeting was attended by over 160 participants. The scientific programme had 21 plenary talks on current theoretical, observational and experimental topics in Cosmology, General Relativity, detection of gravitational waves, and various approaches to Quantum gravity. The meeting also included three intensive parallel workshops focused on Cosmology, Classical General Relativity & Gravitational waves and Quantum Gravity, respectively. The workshops had around 75 oral presentations. The immensely rich and diverse scientific programme was highlighted in the concluding remarks by the late Professor Juergen Ehlers. A public lecture on `Oldest light in the Universe' by NASA scientist, Professor Gary Hinshaw, who is a member of the WMAP team (formerly, also a member of the COBE-DMR team that won the Nobel prize in 2006) was also organized as part of ICGC-07 and drew sizable audience from the public in Pune. The proceedings contains articles by the plenary speakers, the concluding remarks and a summary of each of the three workshops. We also include an obituary for Professor Juergen Ehlers, who passed away on 20 May 2008. The sentiments expressed in the obituary are shared by the editors and members of IAGRG. Professor Ehlers had participated very actively during the meeting and delivered an excellent concluding talk on the conference. We are indeed fortunate to able to include in this volume, what is perhaps, his last article. A possible reflection of the tight schedule of researchers in the booming period of research in Cosmology and Gravitation is the number of missing articles by plenary speakers. Due to various reasons, we were able to get only 11 of the 21 plenary talks for publication in this volume. In order to ensure that the volume is published within a year of the conference, we decided to publish the proceedings with the available articles. The meeting was financially supported by generous contribution from Indian organizations: ISRO, CSIR, DST, BNRS and IAGRG; and from Indian institutes: HRI (Allahabad), IIA (Bangalore), IMSc (Chennai), RRI (Bangalore), SINP (Kolkata) and IUCAA. The conference banquet was sponsored by Hewlett-Packard and the reception dinner was sponsored by the Bank of Baroda. We thank them all. It is a pleasure to thank Professor Naresh Dadhich, Director, IUCAA, members of the IAGRG council, members of the SOC and members of the LOC for their pivotal role in the organization of the conference, and the speakers, the participants, and the IUCAA staff for their efforts which made the sixth ICGC a very successful meeting. Ghanashyam Date Institute for Mathematical Science, Chennai Tarun Souradeep Inter-University Centre for Astronomy & Astrophysics, Pune Scientific Organizing Committee Ghanashyam Date (Chairman, SOC, IMSc, India) Abhay Ashtekar (Pennsylvania State Univ., US) Bhuvnesh Jain (Univ. of Pennsylvania, US) Carlo Rovelli (CPT, Marseille, France) Clifford M. Will (Washington Univ., US) Gabriela Gonza'lez (Lousiana State Univ., US) Hideo Kodama (Kyoto Univ. Japan) John Ellis (CERN, Switzerland) Luc Blanchet (IAP, France) Madhavan Varadarajan (RRI, India) Masaru Shibata (Univ. of Tokyo, Japan) Narayan Banerjee (Jadavpur Univ. India) Parthasarathi Mitra (SINP, India) Rajesh Gopakumar (HRI, India) Sanjeev Dhurandhar (IUCAA, India) Somnath Bharadwaj (IITKGP, India) Subhendra Mohanty (PRL, India) Subir Sarkar (Univ. of Oxford, UK) Tarun Souradeep (IUCAA, India) T. P. Singh (TIFR, India) Local Organizing Committee Tarun Souradeep (Chairman, LOC) Biswajit Pandey Gaurang Mahajan Manjiri Mahabal Maulik Parikh Minu Joy Moumita Aich Niranjan Abhyankar Nirupama Bawdekar Ratna Rao Saugata Chatterjee Savita Dalvi Sharanya Sur Snehlata Shankar Subharthi Ray Sudhanshu Barway Tuhin Ghosh Plenary Speakers and Talks The Plenary Talks are available at http://meghnad.iucaa.ernet.in/~icgc07/ Gary Hinshaw Status of WMAP Data Andrew Jaffe The Future of CMB Studies Subir Sarkar Cosmology beyond the Standard Model HongSheng Zhao Dark Matter and Dark Energy: Puzzles and an Alternative Solution Subhabrata Majumdar Cosmology with Clusters David Langlois Cosmological Perturbations from Inflation John Conklin The Gravity Probe B Experiment and Results B. Sathyaprakash Physics, Astrophysics and Cosmology with Gravitational Waves Rana Adhikari Survey of Gravitational Waves Experiments John Baker Survey of Numerical Relativity Results Maria Alessandra Papa Data Analysis for Gravitational Wave Detectors Alessandra Buonanno Interfacing analytical and numerical relativity in modeling binary black hole coalescences Andy Fabian X-ray detection of spinning black hole Alejandro Corichi Black Holes in Loop Quantum Gravity Madhavan Varadarajan Black Hole Information Loss Puzzle in LQG Parampreet Singh Big Bang Singularity Resolution in Loop Quantum Cosmology Sumit Das Cosmological Singularities in String Theory and Gauge-Gravity Duality Samir Mathur What do black holes tell us about the state of the early Universe? Martin Reuter Asymptotic Safety in Quantum Gravity Keiichi Maeda Beyond the Einstein-Hilbert Action Jurgen Ehlers Concluding Remarks

A new species of the rare endoparasitic copepod Entobius (Copepoda: Entobiidae) from Mexico with a key to the species of the genus.

PubMed

Suárez-Morales, Eduardo; Carrera-Parra, Luis F

2012-09-01

Abstract: In a study of the benthic polychaete fauna of the southern Gulf of Mexico and the Caribbean Sea, several specimens of the terebellid polychaete Scionides reticulata (Ehlers) were found to host endoparasitic copepods that represent an undescribed species of the rare cyclopoid genus Entobius Dogiel, 1948. The new species, E. scionides sp. n., can be distinguished from its congeners by a combination of characters including a genital region without constrictions, three-segmented antennules, a reduced antenna with a blunt terminal process, reduced ornamentation of endopods of legs 1-4 and its relatively small size (2.3-2.7 mm). It is the smallest species of the genus. Comments on immature females are also provided, but males of this species remain unknown. It has a high prevalence (53%) in populations of the terebellid S. reticulata in the southern Gulf of Mexico, but it is absent from the Caribbean. This is the first occurrence of this copepod genus in the Americas. The finding of the new species of Entobius in S. reticulata confirms the strict specificity of most members of the genus and expands the host range of this copepod genus. A key for the identification of the species of Entobius is provided.

Posttraumatic stress disorder and fear of emotions: the role of attentional control.

PubMed

Sippel, Lauren M; Marshall, Amy D

2013-06-01

Individuals with posttraumatic stress disorder (PTSD) experience elevated concerns about their capacity to control, and the consequences of, strong emotions that occur in response to trauma reminders. Anxiety is theorized to compromise attentional control (Eysenck, Derakshan, Santos, & Calvo, 2007). In turn, diminished attentional control may increase vulnerability to threat cues and emotional reactivity (Ehlers & Clark, 2001). Consequently, attentional control may play a role in the fear of emotions frequently experienced by individuals with PTSD. Study participants included 64 men and 64 women with a mean age of 37 years, 86% of whom were White, non-Hispanic. Participants experienced an average of 7.68 types of traumatic events, most commonly including motor vehicle accidents and intimate partner violence. PTSD symptoms positively correlated with fear of emotions (r = .53) and negatively correlated with attentional control (r = -.38). Attentional control was negatively correlated with fear emotions (r = -.77) and partially mediated the link between PTSD and fear of emotions (R(2) = .22). Given the findings regarding top-down attentional control, these results have implications for cognitive and emotional processing theories of PTSD and emphasize the importance of clinical consideration of fear of emotions and attentional control in the treatment of PTSD. Copyright © 2013 International Society for Traumatic Stress Studies.

On Einstein's Path, essays in honor of Engelbert Schucking

NASA Astrophysics Data System (ADS)

Harvey, Alex

This collection of essays in honor of Engelbert Schucking spans the gamut of research in general relativity and presents a lively and personal account of current work in the field. Contributions include: E.L. Schucking: Jordan, Pauli, Politics, Brecht... and a Variable Gravitational Constant J.L. Anderson: Thomson Scattering in an Expanding Universe A. Ashtekar & T.A. Schilling: Geometrical Formulation of Quantum Mechanics J. Baugh, D.R. Finkelstein, H. Saller, and Zhong Tang: General Covariance is Bose-Einstein Statistics S.L. Bazanski: The Split and Propagation of Light Rays in Relativity L. Bel: How to Define a Unique Vacuum in Cosmology P.G. Bergmann: EIH Theory and Noether's Theorem W.B. Bonnor: The Static Cylinder in General Relativity C.H. Brahns: Gravity and the Tenacious Scalar Field D. Brill: The Cavendish Experiment in General Relativity Y. Choquet-Bruhat: Wave Maps in General Relativity T. Damour: General Relativty and Experiment J. Ehlers: Some Developments in Newtonian Cosmology G.F.R. Ellis & H. van Elst: Deviation of Geodesics in FLRW Spacetime Geometries S. Frittelli & E.T. Newman: Poincar Pseudo-symmetries in Asymptotically Flat Spacetimes E.N. Glass: Taub Numbers and Asymptotic Invariants J.N. Goldberg: Second Class Constraints F.W. Hehl, A. Macias, E.W. Mielke, & Yu.N. Obukhov: On the Structure of the Energy-momentum and the Spin Currents in Dirac's Electron

Climate-sensitive feedbacks between hillslope processes and fluvial erosion in sediment-driven incision models

NASA Astrophysics Data System (ADS)

Skov, Daniel S.; Egholm, David L.

2016-04-01

Surface erosion and sediment production seem to have accelerated globally as climate cooled in the Late Cenozoic, [Molnar, P. 2004, Herman et al 2013]. Glaciers emerged in many high mountain ranges during the Quaternary, and glaciation therefore represents a likely explanation for faster erosion in such places. Still, observations and measurements point to increases in erosion rates also in landscapes where erosion is driven mainly by fluvial processes [Lease and Ehlers (2013), Reusser (2004)]. Flume experiments and fieldwork have shown that rates of incision are to a large degree controlled by the sediment load of streams [e.g. Sklar and Dietrich (2001), Beer and Turowski (2015)]. This realization led to the formulation of sediment-flux dependent incision models [Sklar and Dietrich (2004)]. The sediment-flux dependence links incision in the channels to hillslope processes that supply sediment to the channels. The rates of weathering and soil transport on the hillslopes are processes that are likely to respond to changing temperatures, e.g. because of vegetation changes or the occurrence of frost. In this study, we perform computational landscape evolution experiments, where the coupling between fluvial incision and hillslope processes is accounted for by coupling a sediment-flux-dependent model for fluvial incision to a climate-dependent model for weathering and hillslope sediment transport. The computational experiments first of all demonstrate a strong positive feedback between channel and hillslope processes. In general, faster weathering leads to higher rates of channel incision, which further increases the weathering rates, mainly because of hillslope steepening. Slower weathering leads to the opposite result. The experiments also demonstrate, however, that the feedbacks vary significantly between different parts of a drainage network. For example, increasing hillslope sediment production may accelerate incision in the upper parts of the catchment, while at the same time the channel bed in the lower parts become shielded from incision by a perpetual sediment cover and incision stalls. These differences cause transients of erosion to migrate through the drainage network. Beer, Alexander R., and J. M. Turowski. "Bedload transport controls bedrock erosion under sediment-starved conditions." Earth Surface Dynamics 3.3 (2015): 291-309. Herman, Frédéric, et al. "Worldwide acceleration of mountain erosion under a cooling climate." Nature 504.7480 (2013): 423-426. Lease, Richard O., and Todd A. Ehlers. "Incision into the Eastern Andean plateau during Pliocene cooling." Science 341.6147 (2013): 774-776. Molnar, Peter. "Late Cenozoic increase in accumulation rates of terrestrial sediment: how might climate change have affected erosion rates?." Annu. Rev. Earth Planet. Sci. 32 (2004): 67-89. Reusser, Luke J., et al. "Rapid Late Pleistocene incision of Atlantic passive-margin river gorges." Science 305.5683 (2004): 499-502. Sklar, Leonard S., and William E. Dietrich. "Sediment and rock strength controls on river incision into bedrock." Geology 29.12 (2001): 1087-1090. Sklar, Leonard S., and William E. Dietrich. "A mechanistic model for river incision into bedrock by saltating bed load." Water Resources Research 40.6 (2004).

Brain Enhancing Ingredients from Āyurvedic Medicine: Quintessential Example of Bacopa monniera, a Narrative Review

PubMed Central

Singh, Hemant K.

2013-01-01

Āyurveda, the science (ved) of life (ayu), owing its origin to Veda, the oldest recorded wisdom of human civilization written in 3500 BCE, contains extensive knowledge of various diseases and their therapeutic approaches. It essentially relied on nature and the immune system of an individual, and therapeutic interventions were introduced only to augment the immune system. Āyurveda had eight specialties, including psycho-neuroscience (a combination of psychology, clinical psychology and psychiatry) and a unique promotive therapy encompassing nutrition, rejuvenation and geriatrics. The symptoms of various brain disorders, including memory disorder, were well defined. The goal of Āyurveda was to help an individual to achieve his cherished goal of leading a healthy life of 100 years. To achieve this, great emphasis was laid on nutrition, diet and a good conduct by the two great exponents of Āyurveda viz. Carak and Suśruta. By following these regimens, an individual could lead a less stressful life free from emotional disturbances. Both Carak and Suśruta had believed that these in combination with rasayana (rejuvenating) plants could enable an individual to lead a healthy life of 100 years. PMID:23389306

Two models of inventory control with supplier selection in case of multiple sourcing: a case of Isfahan Steel Company

NASA Astrophysics Data System (ADS)

Rabieh, Masood; Soukhakian, Mohammad Ali; Mosleh Shirazi, Ali Naghi

2016-06-01

Selecting the best suppliers is crucial for a company's success. Since competition is a determining factor nowadays, reducing cost and increasing quality of products are two key criteria for appropriate supplier selection. In the study, first the inventories of agglomeration plant of Isfahan Steel Company were categorized through VED and ABC methods. Then the models to supply two important kinds of raw materials (inventories) were developed, considering the following items: (1) the optimal consumption composite of the materials, (2) the total cost of logistics, (3) each supplier's terms and conditions, (4) the buyer's limitations and (5) the consumption behavior of the buyers. Among diverse developed and tested models—using the company's actual data within three pervious years—the two new innovative models of mixed-integer non-linear programming type were found to be most suitable. The results of solving two models by lingo software (based on company's data in this particular case) were equaled. Comparing the results of the new models to the actual performance of the company revealed 10.9 and 7.1 % reduction in total procurement costs of the company in two consecutive years.

Brain enhancing ingredients from Āyurvedic medicine: quintessential example of Bacopa monniera, a narrative review.

PubMed

Singh, Hemant K

2013-02-06

Āyurveda, the science (ved) of life (ayu), owing its origin to Veda, the oldest recorded wisdom of human civilization written in 3500 BCE, contains extensive knowledge of various diseases and their therapeutic approaches. It essentially relied on nature and the immune system of an individual, and therapeutic interventions were introduced only to augment the immune system. Āyurveda had eight specialties, including psycho-neuroscience (a combination of psychology, clinical psychology and psychiatry) and a unique promotive therapy encompassing nutrition, rejuvenation and geriatrics. The symptoms of various brain disorders, including memory disorder, were well defined. The goal of Āyurveda was to help an individual to achieve his cherished goal of leading a healthy life of 100 years. To achieve this, great emphasis was laid on nutrition, diet and a good conduct by the two great exponents of Āyurveda viz. Carak and Suśruta. By following these regimens, an individual could lead a less stressful life free from emotional disturbances. Both Carak and Suśruta had believed that these in combination with rasayana (rejuvenating) plants could enable an individual to lead a healthy life of 100 years.

The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy

ClinicalTrials.gov

2018-01-10

Klinefelter Syndrome; Trisomy X; XYY Syndrome; XXXY and XXXXY Syndrome; Xxyy Syndrome; Xyyy Syndrome; Xxxx Syndrome; Xxxxx Syndrome; Xxxyy Syndrome; Xxyyy Syndrome; Xyyyy Syndrome; Male With Sex Chromosome Mosaicism

Familial Investigations of Childhood Cancer Predisposition

ClinicalTrials.gov

2018-01-03

Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease

Fluency Disorders in Genetic Syndromes

ERIC Educational Resources Information Center

Van Borsel, John; Tetnowski, John A.

2007-01-01

The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of…

Syndromes, disorders and maternal risk factors associated with neural tube defects (VII).

PubMed

Chen, Chih-Ping

2008-09-01

Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Clinical and Molecular Investigations Into Ciliopathies

ClinicalTrials.gov

2018-03-27

Autosomal Recessive Polycystic Kidney Disease; Congenital Hepatic Fibrosis; Caroli's Disease; Polycystic Kidney Disease; Joubert Syndrome; Cerebro-Oculo-Renal Syndromes; COACH Syndrome; Senior-Loken Syndrome; Dekaban-Arima Syndrome; Cogan Oculomotor Apraxia; Nephronophthisis; Bardet-Biedl Syndrome; Alstrom Syndrome; Oral-Facial-Digital Syndrome

Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

PubMed

Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Understanding HIV-related posttraumatic stress disorder in South Africa: a review and conceptual framework.

PubMed

Young, Charles

2011-06-01

A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic review of the literature identified eight relevant studies that put current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%. Even the lower estimates suggest that PTSD in response to the trauma of being diagnosed and living with HIV is a significant mental health burden. However, a conceptual framework to advance our understanding of the prevalence and phenomenology of HIV-related PTSD is lacking. This article argues that the Ehlers & Clark (2000) cognitive model of PTSD provides a useful conceptual framework for understanding HIV-related PTSD in South Africa. The model emphasises the role of trauma appraisals in the development and maintenance of PTSD, which can also be usefully applied to some of the other psychological disorders associated with HIV infection. The model appears to fit some of the important research findings, and it offers insights into the relationships between HIV-related PTSD and other psychological disorders, HIV stigma, the high prevalence of non-HIV traumatic events, occasional problems with the delivery of antiretroviral drugs in the South African public health service, the unpredictable course of HIV illness, and the quality of HIV testing and counselling. Implications for individual treatment strategies and broader public health interventions are briefly discussed.

Narrative Characteristics of Genocide Testimonies Predict Posttraumatic Stress Disorder Symptoms Years Later

PubMed Central

Ng, Lauren C.; Ahishakiye, Naphtal; Miller, Donald E.; Meyerowitz, Beth E.

2015-01-01

Cognitive theories of posttraumatic stress disorder (PTSD) suggest that trauma narratives that make greater use of somatosensory, perceptual, and negative emotion words may be indicators of greater risk of PTSD symptoms (Ehlers & Clark, 2000). The purpose of this study was to analyze whether the way that survivors of the 1994 Rwandan Genocide against the Tutsi naturally construct genocide testimonies predicts PTSD symptoms six years later. One hundred orphaned heads of household (OHH) who were members of a community association gave testimonies about their genocide experiences in 2002. In 2008, PTSD symptoms of 61 of the original OHH were assessed using a genocide specific version of the Impact of Events Scale-Revised (Weiss & Marmar, 2004). Experienced genocide events were coded from the genocide testimonies, and the types of words used in the testimonies were analyzed using the Linguistic Inquiry and Word Count program (Pennebaker, Chung, Ireland, Gonzales, & Booth, 2007). Pearson correlations and path analyses assessed the relationships between variables. After accounting for genocide events, touching positively predicted avoidance, and sadness negatively predicted hyperarousal. Sensory descriptions of traumatic experiences in trauma narratives may signify higher risk for mental health problems, while expressions of sadness may indicate emotional processing and better mental health. Analyzing genocide testimonies may help identify survivors at the highest risk of developing PTSD symptoms, even among a group of survivors who have arguably suffered some of the most severe genocide experiences. PMID:25793398

What Is Antiphospholipid Antibody Syndrome?

MedlinePlus

... or rheumatic (ru-MAT-ik) disorders, such as lupus . ("Rheumatic" refers to disorders that affect the joints, ... aCL syndrome Antiphospholipid syndrome aPL syndrome Hughes syndrome Lupus anticoagulant syndrome Causes Antiphospholipid antibody syndrome (APS) occurs ...

Brief Report: Repetitive Behaviour Profiles in Williams syndrome: Cross Syndrome Comparisons with Prader-Willi and Down syndromes.

PubMed

Royston, R; Oliver, C; Moss, J; Adams, D; Berg, K; Burbidge, C; Howlin, P; Nelson, L; Stinton, C; Waite, J

2018-01-01

This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were few group differences, although participants with Williams syndrome were more likely to show body stereotypies. Individuals with Williams syndrome also showed more hoarding and less tidying behaviours than those with Down syndrome. IQ and adaptive ability were negatively associated with repetitive questioning in people with Williams syndrome. The profile of repetitive behaviour amongst individuals with Williams syndrome was similar to the comparison syndromes. The cognitive mechanisms underlying these behaviours in genetic syndromes warrant further investigation.

A Rare Variant of Wallenberg’s Syndrome: Opalski syndrome

PubMed Central

KK, Parathan; P, Chitrambalam; Aiyappan, Senthil Kumar; N, Deepthi

2014-01-01

Lateral Medullary Syndrome (LMS) is a well-documented vascular syndrome of the posterior circulation territory. This syndrome is easily localised because of characteristic presentation, unique territory of blood supply and very small area of involvement. We present a case of Wallenberg’s syndrome which did not have all the classical components of the syndrome, like Horner’s syndrome. Opalski syndrome is a rare variant of Wallenberg syndrome, where lateral medullary syndrome is associated with ipsilateral hemiparesis. This case report highlights how differential involvement of the lateral part of medulla can result in varied presentation. PMID:25177595

Nevoid basal cell carcinoma syndrome

MedlinePlus

NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

Fluency disorders in genetic syndromes.

PubMed

Van Borsel, John; Tetnowski, John A

2007-01-01

The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of these syndromes indicated clients diagnosed with these syndromes do show evidence of nonfluency patterns, but not all would be considered stuttering. Many of the syndromes are marked by degrees of mental retardation that probably contribute to a higher than average prevalence of stuttering, as well as a higher than average prevalence of other fluency disorders (when compared to the population at large). An in-depth analysis of the available data indicates that some of these genetic syndromes show patterns of stuttering that may be indicative of only that syndrome (or similar syndromes) that can be differentially diagnosed from developmental stuttering. Among these patterns are the word-final nonfluencies noted in Prader-Willi syndrome; the presence of stuttering in the absence of secondary behaviors noted in Prader-Willi syndrome and; the presence of palilalia, word-final and word-medial nonfluencies, and word-medial and word-final nonfluencies in Tourette syndrome. Implications for future research are discussed in light of these findings. The reader will be able to: (1) describe the various different genetic syndromes that are associated with fluency disorders; (2) describe the types of nonfluencies that are associated with the major types of genetic syndromes that have fluency disorders; (3) describe the behaviors that may assist in differentially diagnosing different types of speech characteristics associated with various genetic syndromes.

[Clinical study of area of Jiangsu province of polycystic ovarian syndrome correlation distribution of traditional Chinese medicine syndrome type and improper diet].

PubMed

Feng, Yu; Gao, Yue-Ping

2014-05-01

Polycystic ovary syndrome (PCOS) is one of the most popular diseases in obstetrics and gynecology research at internal and abroad at present, traditional Chinese medicine(TCM)in the clinical treatment of the disease have the advantage. Clinical epidemiological study of descriptive research method this research adopts investigation, observation of TCM syndromes and improper diet through 401 cases in Jiangsu Province confirmed PCOS patients, to explore the relationship between TCM syndrome type distribution and improper diet factors, and to provide the clinical basis for further etiology of this disease research. TCM syndrome type distribution of the disease is kidney deficiency, phlegm stagnation syndrome, qi stagnation and blood stasis syndrome, syndrome of dampness heat of liver channel and is composed of 4 basic syndromes and formed complex syndrome, and the composite and syndrome type (60.85%); combined with the analysis of traditional Chinese medicine dialectical, Pure empirical syndrome this disease (46.88%), followed by the actual card (45.39%), pure deficiency is rare. Improper diet factors associated with the disease, in which improper diet with different TCM syndrome type distribution significantly related. Stagnation of phlegm dampness syndrome is the main syndrome of the disease type, improper diet factors and every syndrome PCOS type distribution is as follows: the partial eclipse fatness greasy with basic syndromes of phlegm dampness stagnation of kidney deficiency syndrome, the nephrasthenia syndrome is less; eating spicy stimulation by basic syndromes of stagnation of Qi and blood stasis; eating cold people the basic certificate type of qi stagnation and blood stasis; The diet of patients are more prone to stagnation of phlegm dampness syndrome.

[Distribution characteristics of basic syndromes of chronic functional constipation and its related factors analysis].

PubMed

Zhao, Lei; Liao, Xiu-jun; Yang, Guan-gen; Mao, Wei-ming; Zhang, Xiu-feng; Deng, Qun; Wu, Wen-jing

2014-10-01

To explore the distribution characteristics of basic syndromes and its related factors in patients with chronic functional constipation (CFC). The complete data of 538 patients with CFC were collected and initial database was established with Epidata 3. 0. TCM syndrome typing was performed. The distribution characteristics of basic syndromes were analyzed using SPSS 17. 0 Software. The univariate and multivariate Logistic regression analyses were performed with SPSS 17. 0 Software to determine basic syndrome related factors such as age, engaged professionals, sleep quality, depression, mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation, and so on. The TCM syndrome frequency of CFC patients was sequenced from high to low as qi deficiency syndrome (380 cases, 70.6%), qi stagnation syndrome (337 cases, 62.6%), blood deficiency syndrome (234 cases, 43.5%), yin deficiency syndrome (220 cases, 40.9%), yang deficiency syndrome (197 cases, 36.6%), and others(58 cases, 10. 8%) . Most patients were complicated with complex syndromes, and the most common complex syndromes were qi deficiency complicated qi stagnation syndrome (275 cases, 51.1%) and qi deficiency complicated blood deficiency syndrome (222 cases, 41.3%). Aging, work fatigue, and exercise conditions were main related factors for qi deficiency syndrome (P <0. 01, P <0. 05). Poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, defecation barriers constipation were main related factors for qi stagnation syndrome (P <0.01). Sleep quality and poor emotional (depression and anxiety tendencies) were main related factors for blood deficiency syndrome (P <0. 01, P < 0.05). Stimulating beverages were main related factor for yin deficiency syndrome (P <0.05). Engaged in mental work and slow transit constipation were main related factors for yang deficiency syndrome (P < 0. 01, P <0. 05). CFC is featured as complex syndromes. The most common complex syndromes were qi deficiency complicated qi stagnation syndrome and qi deficiency complicated blood deficiency syndrome. Basic syndrome related factors such as age, engaged professionals, sleep quality, poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation were associated with the distribution of CFC syndromes.

Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome

DTIC Science & Technology

2016-09-01

Syndrome of the Acute Radiation Syndrome PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome 5b. GRANT NUMBER W81XWH-15...protective role against hematopoietic syndrome of the acute radiation syndrome (H-ARS) and is able to attenuate the effect of residual bone marrow

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

ClinicalTrials.gov

2018-06-08

Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7

[Study on qi deficiency syndrome distribution and quality of life in patients with advanced non-small cell lung cancer].

PubMed

Yuan, Lin; Zhang, Pei-tong; Yang, Zong-yan

2011-07-01

To study the qi deficiency syndrome distribution and quality of life (QOL) of patients with advanced non-small cell lung cancer (NSCLC). A questionnaire survey was conducted in 120 patients with advanced NSCLC using the QOL scale "Functional Assessment of Cancer Therapy" (FACT-L) (Version 4.0). Meanwhile, syndrome typing was performed. On the basis of results of syndrome typing, patients of different syndrome types were grouped and compared, thus studying the distribution of advanced NSCLC patients of qi deficiency syndrome and qi deficiency syndrome correlated QOL features. Qi deficiency, blood stasis, yin deficiency, phlegm and dampness dominated in syndrome types of the 120 patients with advanced NSCLC. Of syndrome types accounting for larger ratios in 112 patients, pure qi deficiency syndrome accounted for 30.36% (34 cases), qi deficiency and blood stasis syndrome for 18. 75% (21 cases), both qi and yin deficiency syndrome for 10. 71% (12 cases). There was no correlation between the appearance of qi deficiency syndrome and patients' age, sex, pathological typing (adenocarcinoma/squamous carcinoma), or the disease duration. NSCLC patients in phase IV were mostly complicated with qi deficiency syndrome (P<0.05). Scores of physical states, emotional states, functional states, and total scores in the FACT-L scale were lower in those complicated with qi deficiency syndrome (89 cases) than in those without complicated qi deficiency syndrome (31 cases), showing statistical difference (P<0.01, P<0.05). The scores of the lung cancer specific module (additional concerns) in the FACT-L scale showed statistical difference, sequenced as qi deficiency and blood stasis syndrome > pure qi deficiency syndrome > both qi and yin deficiency syndrome (P<0.05). Qi deficiency syndrome is the main syndrome of advanced NSCLC. The QOL of advanced NSCLC patients complicated with qi deficiency syndrome was poorer than those without complicated qi deficiency syndrome. Besides, along with the aggravation of qi deficiency syndrome, the QOL decreased somewhat. It suggested that symptomatic treatment of qi deficiency syndrome could improve advanced NSCLC patients' QOL.

Comparison of metabolic syndrome with growing epidemic syndrome Z in terms of risk factors and gender differences.

PubMed

Uyar, Meral; Davutoğlu, Vedat; Aydın, Neriman; Filiz, Ayten

2013-05-01

The aim of this study is to compare metabolic syndrome with syndrome Z growing epidemic in terms of risk factors, demographic variables, and gender differences in our large cohort at southeastern area in Turkey. Data of patients admitted to sleep clinic in University of Gaziantep from January 2006 to January 2011 were retrospectively evaluated. ATP III and JNC 7 were used for defining metabolic syndrome and hypertension. Data of 761 patients were evaluated. Hypertension, diabetes mellitus, coronary artery disease, pulmonary hypertension, and left ventricular hypertrophy were more common in patients with syndrome Z than in patients without metabolic syndrome. Age, waist/neck circumferences, BMI, triglyceride, glucose, and Epworth sleepiness scale score were detected higher, whereas the minimum oxygen saturation during sleep was lower in patients with syndrome Z. Metabolic syndrome was more common in sleep apneic subjects than in controls (58 versus 30 %). Female sleep apneics showed higher rate of metabolic syndrome than those of males (74 versus 52 %). Hypertension, diabetes mellitus, coronary artery disease, and left ventricular hypertrophy were detected higher in males with syndrome Z than in males without metabolic syndrome. Snoring and excessive daytime sleepiness were detected higher in females with syndrome Z than in females without metabolic syndrome. Systemic/pulmonary hypertension, diabetes mellitus, and left ventricular hypertrophy were more common in females with syndrome Z than in females without metabolic syndrome. Complaints of headache and systemic/pulmonary hypertension were more common among females than males with syndrome Z. Female syndrome Z patients had lower minimum oxygen saturation than male patients with syndrome Z. Metabolic syndrome in sleep apneic patients is more prevalent than in controls. All metabolic syndrome parameters were significantly different among obstructive sleep apneic patients with respect to gender with more severe coronary risk factors in males.

Correlation Analysis between Traditional Chinese Medicine Syndromes and Gastrointestinal Bleeding after Percutaneous Coronary Intervention

PubMed Central

Huang, Chaolian; Wang, Mingming; Kong, Xiaolin; Liu, Guannan

2018-01-01

Objective To explore the characters of traditional Chinese medicine (TCM) syndromes after percutaneous coronary intervention (PCI) and to provide syndrome study theoretical evidence for TCM differentiation treatment after PCI through retrospective study. Methods Patients with coronary heart disease (CHD) who underwent PCI in Cardiovascular Intervention Center of Wangjing Hospital during Dec. 2012 to Dec. 2014 and met the inclusion criteria were enrolled. Retrospective study was then conducted based on patients' clinical document and angiography data to explore the distribution pattern of TCM syndromes. Results 801 patients were recruited in the study. TCM syndromes in descending order of their incidence were Qi deficiency and blood stasis syndrome, heart blood stasis syndrome, Qi and Yin deficiency syndrome, phlegm and blood stasis syndrome, Qi stagnation and blood stasis syndrome, Yang asthenia syndrome, heart and kidney yin deficiency syndrome to cold congeal, and blood stasis syndrome in a more to less order. Qi deficiency and blood stasis syndrome was in the most (occurring in 298 patients, 37.20%); Qi and Yin deficiency syndrome occurred in 163 patients (20.35%); heart blood stasis syndrome was shown in 126 patients (15.73%); phlegm and blood stasis syndrome was shown in 95 patients (11.86%). Conclusion Qi deficiency and blood stasis syndrome was closely associated with post-PCI bleeding, implying that this syndrome might serve as a powerful predictor of GI bleeding as well as a potential supplement to the current predicting and scoring system of bleeding such as CRUSADE.

The Thermal History of Enstatite Chondrites

NASA Astrophysics Data System (ADS)

Zhang, Y.; Benoit, P. H.; Sears, D. W. G.

1992-07-01

In an attempt to decipher the complicated thermal history of the enstatite chondrites, the CaS enstatite (Larimer and Buseck, 1974; Fogel et al., 1989), cubic sulfide (Skinner and Luce, 1971) and sphalerite (Kissin, 1989; El Goresy and Ehlers, 1989) systems have been applied, but the results have not been straightforward. The CaS-En thermometer gives metamorphic temperatures which appear reasonable, but which do not correlate well with petrologic type. The cubic sulfides yield reasonable temperatures for the EH chondrites, but the values for EL chondrites are very low. To some extent, the problem has been the lack of low petrologic type EL chondrites. Here we discuss data for the recently discovered EL3 chondrites (Chang et al., 1992) and we examine the applicability of the Fe-Ni-P system for thermometry. The CaS-En thermometer uses three reactions including equilibria between metal, CaS, SiO2, enstatite and FeS. The method is crucially dependent on the activity coefficients for Si and CaSiO3 which are in solid solutions with metal and enstatite, respectively. The cubic sulfide thermometer uses the solubility of FeS in MgS and MnS, while the ZnS thermometer (which is pressure-dependent) uses the solubility of FeS in ZnS. Current equilibration temperature estimates for enstatite chondrites including the EL3 chondrites are listed in Table 1. Table 1. Estimates of equilibration temperatures (degrees C) for enstatite chondrites.* Petrologic type EH EL System 3 4 5 6 3 4 5 6 En-CaS 1030 950 830 - 830 - - 1025 Cubic sulf 400 680 600 - <<400 - - <400 ZnS 410 (1859)+ - - 500 - - 550 Fe-Ni-P <450 500 550 - <<450 - - <450 *Literature data (see text), present data (bold type). +Heavily shocked. In an attempt to use the Fe-Ni-P system as a thermometer for enstatite chondrites, we used the phase diagram of Doan and Goldstein (1970). Like the other systems, this required extrapolation to lower temperatures (Fig. 1). The temperatures calculated from this system mirror those of the sulfides, suggesting major differences in the thermal history of the EL and EH chondrites. Two points may be made from the data in Table 1. The EH3 and EL3 chondrites have similar En-CaS equilibration temperatures to those of the higher petrologic types which we suspect reflect pre-metamorphic equilibria. Second, both the cubic sulfides and the phosphides yield metamorphic temperatures for the EH chondrites which are similar to those for ordinary chondrites, while EL chondrites yield very low temperatures. The EL chondrite parent body must have cooled at especially slow rates, perhaps because it was much larger than the EH parent body, or maybe the cooling rate on EL body was governed by the attenuation of the heat source rather than burial depth. Chang Y., Benoit P.H. and Sears D.W.G. (1992) Lunar and Planet. Sci. 23, 217-218. Doan A.S. and Goldstein J.I. (1970) Met. Trans. 1, 1759-1767. El Goresy A. and Ehlers K (1989) Geochim. Cosmochim. Acta 53, 1657-1668. Fogel R.A., Hess P.C. and Rutherford M.C. (1989) Geochim. Cosmochim. Acta 53, 2735-2746. Kissin S.A.(1989) Geochim. Cosmochim. Acta 53, 1649-1655. Larimer J.W. and Buseck P.R. (1974) Geochim. Cosmochim. Acta 38, 471-477. Skinner B.J. and Luce F.D. (1971) Amer. Min. 56, 1269-1296. Figure 1, which in the hard copy appears here, shows isotherm from the Fe-Ni-P phase diagram with data for enstatite chondrites superimposed.

Duane Syndrome

MedlinePlus

... is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), is a congenital and non-progressive ... Is Duane syndrome congenital (present from birth)? Duane retraction syndrome is present from birth, even if it ...

Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study.

PubMed

Krieger, John N; Stephens, Alisa J; Landis, J Richard; Clemens, J Quentin; Kreder, Karl; Lai, H Henry; Afari, Niloofar; Rodríguez, Larissa; Schaeffer, Anthony; Mackey, Sean; Andriole, Gerald L; Williams, David A

2015-04-01

We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria. Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors. Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p < 0.001). Nonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

ClinicalTrials.gov

2009-10-14

Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome