Novel approaches for diagnosing inherited platelet disorders.

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Bastida Bermejo, José María; Hernández-Rivas, Jesús María; González-Porras, José Ramón

2017-01-20

Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are involved in reducing the samples' volume, and faster and more helpful analysis. Moreover, there are no widely available and standardised global tests. High throughput genetic testing such as next-generation sequencing has revolutionised DNA sequencing technologies as it allows the simultaneous and faster investigation of multiple genes at a manageable cost. This technology has improved the molecular characterisation of inherited platelet disorders and has been implemented in the research studies and the clinical routine practice. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

[The hip joint in neuromuscular disorders].

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Strobl, W M

2009-07-01

Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

Role of TGF-β signaling in inherited and acquired myopathies

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Burks Tyesha N

2011-05-01

Full Text Available Abstract The transforming growth factor-beta (TGF-β superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs, and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders.

Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

DEFF Research Database (Denmark)

Dahlqvist, Julia Rebecka; Vissing, John

2016-01-01

There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...

Comparing targeted exome and whole exome approaches for genetic diagnosis of neuromuscular disorders

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Svetlana Gorokhova

2015-12-01

Full Text Available Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by a given patient, while avoiding false negative and false positive results. We developed a targeted exome approach (MyoPanel2 in order to optimize genetic diagnosis of neuromuscular disorders. Using this approach, we were able to analyse 306 genes known to be mutated in myopathies as well as in related disorders, obtaining 98.8% target sequence coverage at 20×. Moreover, MyoPanel2 was able to detect 99.7% of 11,467 known mutations responsible for neuromuscular disorders. We have then used several quality control parameters to compare performance of the targeted exome approach with that of whole exome sequencing. The results of this pilot study of 140 DNA samples suggest that targeted exome sequencing approach is an efficient genetic diagnostic test for most neuromuscular diseases.

Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences.

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Kohei Fujikura

Full Text Available Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI. I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA. The population exome-based epidemiology of SCA [African (allele frequency (AF = 0.0454, N = 2447, Asian (AF = 0, N = 286, European (AF = 0.000214, N = 4677, and Hispanic (AF = 0.0111, N = 362] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05. I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders.

Mitochondrial DNA triplication and punctual mutations in patients with mitochondrial neuromuscular disorders

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Mkaouar-Rebai, Emna, E-mail: emna.mkaouar@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Felhi, Rahma; Tabebi, Mouna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Alila-Fersi, Olfa; Chamkha, Imen [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Maalej, Marwa; Ammar, Marwa [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Kammoun, Fatma [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Keskes, Leila [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Hachicha, Mongia [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh02@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia)

2016-04-29

Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. As brain and muscle are highly dependent on OXPHOS, consequently, neurological disorders and myopathy are common features of mtDNA mutations. Mutations in mtDNA can be classified into three categories: large-scale rearrangements, point mutations in tRNA or rRNA genes and point mutations in protein coding genes. In the present report, we screened mitochondrial genes of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the second patient with mitochondrial neuromuscular disorder. - Highlights: • We reported 2 patients with mitochondrial neuromuscular disorders. • The heteroplasmic MT-ATP6 9157G>A variation was reported. • A triplication of 9 bp in the mitochondrial NC7 region was detected. • The m.14924T>C transition (S60P) in the MT-CYB gene was found.

The use of an online support group for neuromuscular disorders: a thematic analysis of message postings.

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Meade, Oonagh; Buchanan, Heather; Coulson, Neil

2017-06-08

People affected by neuromuscular disorders can experience adverse psychosocial consequences and difficulties accessing information and support. Online support groups provide new opportunities for peer support. The aim of this study was to understand how contributors used the message board function of a newly available neuromuscular disorders online support group. Message postings (n = 1951) from the first five months of the message board of a newly formed online support group for neuromuscular disorders hosted by a charitable organization were analyzed using inductive thematic analysis. Members created a sense of community through disclosing personal information, connecting with people with similar illness experiences or interests, welcoming others and sharing aspirations for the development of a resourceful community. Experiences, emotional reactions and support were shared in relation to: delayed diagnosis; symptom interpretation; illness management and progression; the isolating impact of rare disorders; and the influence of social and political factors on illness experiences. This study provided a novel insight into individuals' experiences of accessing a newly available online support group for rare conditions hosted by a charitable organization. The findings highlight how the online support group provided an important peer support environment for members to connect with others, exchange information and support and engender discussion on political and social issues unique to living with often-rare neuromuscular disorders. Online support groups may therefore provide an important and easily accessible support outlet for people with neuromuscular disorders as well as a platform for empowering members to raise awareness about the impact of living with these conditions. Further research is needed to examine member motivations for using such groups and any effects of participation in greater detail. Implications for rehabilitation Online support groups may

Motor neuron, nerve, and neuromuscular junction disease.

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Finsterer, Josef; Papić, Lea; Auer-Grumbach, Michaela

2011-10-01

The aim is to review the most relevant findings published during the last year concerning clinical, genetic, pathogenic, and therapeutic advances in motor neuron disease, neuropathies, and neuromuscular junction disorders. Studies on animal and cell models have improved the understanding of how mutated survival motor neuron protein in spinal muscular atrophy governs the pathogenetic processes. New phenotypes of SOD1 mutations have been described. Moreover, animal models enhanced the insight into the pathogenetic background of sporadic and familial amyotrophic lateral sclerosis. Novel treatment options for motor neuron disease have been described in humans and animal models. Considerable progress has been achieved also in elucidating the genetic background of many forms of inherited neuropathies and high clinical and genetic heterogeneity has been demonstrated. Mutations in MuSK and GFTP1 have been shown to cause new types of congenital myasthenic syndromes. A third type of autoantibodies (Lrp4) has been detected to cause myasthenia gravis. Advances in the clinical and genetic characterization of motor neuron diseases, neuropathies, and neuromuscular transmission defects have important implications on the fundamental understanding, diagnosis, and management of these disorders. Identification of crucial steps of the pathogenetic process may provide the basis for the development of novel therapeutic strategies.

A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

NARCIS (Netherlands)

Mullender, M.G.; Blom, N.; de Kleuver, M.; Fock, J.; Hitters, W.; Horemans, A.; Kalkman, C.; Pruijs, J.; Timmer, R.; Titarsolej, P.; van Haasteren, N.; Jager, M.V.; van Vught, A.; van Royen, B.J.

2008-01-01

Background: Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is

Ultrastructural findings in noncompaction prevail with neuromuscular disorders.

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Finsterer, Josef; Stöllberger, Claudia

2013-01-01

Little is known about the ultrastructural abnormalities of left ventricular hypertrabeculation/noncompaction (LVHT). This literature review aimed to summarize and discuss ultrastructural abnormalities described in LVHT so far. The literature search was conducted via MEDLINE using the search terms 'non-compaction', 'noncompaction', 'left ventricular hypertrabeculation', 'spongy myocardium' in combination with the terms 'ultra-structural', or 'electron microscopy'. Altogether, 11 studies reporting ultrastructural investigations of LVHT were retrieved. In these 11 studies, data on 13 patients with LVHT were presented. Ultrastructural abnormalities found in these study patients were generally nonspecific and included an increase in the number of mitochondria (n = 3), abnormally shaped mitochondria (n = 2), distorted cristae (n = 3), sarcomeric derangement (n = 3), immature cardiomyocytes (n = 1), lipid-like inclusions (n = 1), enlarged interstitial spaces (n = 1), increased interstitial collagen (n = 1), or increased glycogen (n = 1). The morphological abnormalities were most prominent in patients with a neuromuscular disorder like Barth syndrome or mitochondrial myopathy. Only in few patients with LVHT, ultrastructural investigations have been performed so far. Ultrastructural abnormalities in LVHT are nonspecific and most prominent in patients with a neuromuscular disorder. There is a strong need to carry out thorough ultrastructural investigations of LVHT to contribute to the understanding of this still unexplained myocardial abnormality.

Gynaecological and obstetric management of women with inherited bleeding disorders.

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Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2006-10-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen

Optimizing referral of patients with neuromuscular disorders to allied health care.

NARCIS (Netherlands)

Pieterse, A.J.; Cup, E.H.C.; Akkermans, R.P.; Hendricks, H.T.; Engelen, B.G.M. van; Wilt, G.J. van der; Oostendorp, R.A.B.

2009-01-01

BACKGROUND AND PURPOSE: To report the predictive validity of the perceived limitations in activities and need questionnaire (PLAN-Q), a screening instrument to support neurologists to select patients with neuromuscular disorders (NMD) for referral for a one-off consultation by occupational therapist

Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

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Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

2017-12-01

Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the

Inherited Disorders of Bilirubin Clearance

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Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

2016-01-01

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

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Aboussouan, Loutfi S; Mireles-Cabodevila, Eduardo

2017-10-01

Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Neuromuscular complications of thyrotoxicosis.

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Kung, Annie W C

2007-11-01

Thyroid hormones exert multiple effects on the neuromuscular system and the brain, with the most important being their role in stimulating the development and differentiation of the neuromuscular system and brain in foetal and neonatal life. In the presence of hyperthyroidism, muscular and neurological symptoms may be the presenting clinical features of the disease. The frequency and severity of neuromuscular complications vary considerably and are probably related to the degree of hyperthyroidism, although in some patients the neuromuscular dysfunction is caused by associated disorders rather than by hyperthyroidism per se. This update focuses on the most common neurological and muscular disorders that occur in patients with thyrotoxicosis. It is beyond the scope of this paper to discuss thyroid eye disease and cardiac complications, in themselves separate complications of specific myocytes.

Inborn Errors of Metabolism with Hypoglycemia Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis : Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis

NARCIS (Netherlands)

Weinstein, David A.; Steuerwald, Ulrike; De Souza, Carolina F. M.; Derks, Terry G. J.

Although hyperinsulinism is the predominant inherited cause of hypoglycemia in the newborn period, inborn errors of metabolism are the primary etiologies after 1 month of age. Disorders of carbohydrate metabolism often present with hypoglycemia when fasting occurs. The presentation, diagnosis, and

Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

DEFF Research Database (Denmark)

Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo

2013-01-01

Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exo...... quality control systems in place, and participate in established external quality assessment programs....... the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal...

Genotype-Phenotype Correlation of Maternally Inherited Disorders due to Mutations in Mitochondrial DNA

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Peterus Thajeb

2006-09-01

Full Text Available Mitochondrial disorders are heterogeneous systemic ailments that are most often caused by maternal inheritance of a variety of mutations of the mitochondrial (mt DNA. Paternal inheritance and somatic mutation are rare. The disorders are well recognized not only for the genotypic heterogeneity, but also the phenotypic variation among the affected members of a single family. The genotype-phenotype correlation of the diversity of the syndromic and non-syndromic features of mitochondrial disorders are discussed. Some aspects of the molecular mechanisms of this heterogeneity, and the histopathologic findings are highlighted.

Learning disabilities in neuromuscular disorders: a springboard for adult life.

Science.gov (United States)

Astrea, Guja; Battini, Roberta; Lenzi, Sara; Frosini, Silvia; Bonetti, Silvia; Moretti, Elena; Perazza, Silvia; Santorelli, Filippo M; Pecini, Chiara

2016-10-01

Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

Diagnosis and management of adult hereditary cardio-neuromuscular disorders: A model for the multidisciplinary care of complex genetic disorders.

Science.gov (United States)

Sommerville, R Brian; Vincenti, Margherita Guzzi; Winborn, Kathleen; Casey, Anne; Stitziel, Nathan O; Connolly, Anne M; Mann, Douglas L

2017-01-01

Genetic disorders that disrupt the structure and function of the cardiovascular system and the peripheral nervous system are common enough to be encountered in routine cardiovascular practice. Although often these patients are diagnosed in childhood and come to the cardiologist fully characterized, some patients with hereditary neuromuscular disease may not manifest until adulthood and will present initially to the adult cardiologist for an evaluation of an abnormal ECG, unexplained syncope, LV hypertrophy, and or a dilated cardiomyopathy of unknown cause. Cardiologists are often ill-equipped to manage these patients due to lack of training and exposure as well as the complete absence of practice guidelines to aid in the diagnosis and management of these disorders. Here, we review three key neuromuscular diseases that affect the cardiovascular system in adults (myotonic dystrophy type 1, Friedreich ataxia, and Emery-Dreifuss muscular dystrophy), with an emphasis on their clinical presentation, genetic and molecular pathogenesis, and recent important research on medical and interventional treatments. We also advocate the development of interdisciplinary cardio-neuromuscular clinics to optimize the care for these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

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CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

Neuromuscular complications of immune checkpoint inhibitor therapy.

Science.gov (United States)

Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

2018-01-17

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Clinical audit of inherited bleeding disorders in a developing country

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Sajid Raihan

2010-01-01

Full Text Available Objective: We did a clinical audit to determine the status of coagulation disorders in a hemophilia care center in Pakistan. Setting: Fatimid foundation blood bank and hematological diseases center, Lahore. Study Design: This is a retrospective descriptive study. Materials and Methods: All patients registered at Lahore center were included. Data was collected using a questionnaire including age, gender, diagnosis, hepatitis and human immune deficiency virus (HIV status, number of episodes of bleeding, most common site of bleeding, severity of disorder and number of transfusions required to treat the episode. Results: During the study period, a total of 923 registered patients were reviewed at Lahore center and of these, 408 patients (44.2% were on regular follow-up. Inherited bleeding disorders identified in these patients included hemophilia A, hemophilia B, vWD, factor VII deficiency, factor V deficiency, factor X deficiency, dysfibrinogenemia, afibrinogenemia, factor XIII deficiency; and platelet function defects. Median age was 17 years with a range of three to 57 years. Median age at diagnosis was one year. There were 329 (80.6% males and 79 (19.3% females. The products used in these patients included factor VIII concentrate, fresh frozen plasma, cryoprecipitate, cryosupernatant and platelets. Testing for transmission of viral infections was also done in these patients and one patient (0.2% was found hepatitis B positive, six patients (1.4% were hepatitis C positive and two patients (0.49% were HIV positive. Conclusion: Hemophilia A, hemophilia B and vWD are the commonly encountered inherited bleeding disorders in our patients followed by other recessively transmitted disorders with a median age of 17 years and male to female ratio of 4: 1. Most of the patients utilized services available at Fatimid foundation with good clinical results. In Pakistan, non-governmental organizations (NGOs are trying their best for providing optimal treatment

Stability and migration across femoral varus derotation osteotomies in children with neuromuscular disorders

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Buxbom, Peter; Sonne-Holm, Stig; Ellitsgaard, Niels

2017-01-01

), and acetabuloplasty. Relapse is observed in one-fifth of cases during adolescence. In this prospective cohort study, we performed a descriptive evaluation of translation and rotation across VDROs in children with neuromuscular disorders and syndromes by radiostereometric analysis (RSA). We assessed "RSA stability......" and migration across the VDROs. Patients and methods - Children with a neuromuscular disorder were set up for skeletal corrective surgery of the hip. RSA follow-ups were performed postoperatively, at 5 weeks, and 3, 6, and 12 months after surgery. Results - 27 femoral VDROs were included; 2 patients were...... excluded during the study period. RSA data showed stability across the VDRO in the majority of cases within the first 5 weeks. At the 1-year follow-up, the mean translations (SD) of the femoral shaft distal to the VDRO were 0.51 (1.12) mm medial, 0.69 (1.61) mm superior, and 0.21 (1.28) mm posterior...

MRI in neuromuscular disorders; MRT bei neuromuskulaeren Erkrankungen

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Fischmann, Arne [Klinik St. Anna, Luzern (Switzerland). Inst. fuer Radiologie und Nuklearmedizin; Fischer, Dirk [Kantonsspital Bruderholz (Switzerland)

2014-03-15

Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.

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Hsieh, J-T; Klein, K; Batstone, M

2017-09-01

Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012. Patients with inherited bleeding disorders such as haemophilia A, haemophilia B, and von Willebrand's disease were included. Retrospective chart review was conducted. The result showed 53 extraction events occurred in 45 patients over the 10-year period. Ten out of 53 extraction events (18.9%) had postoperative bleeding requiring further factor replacement or ddAVP. Postoperative bleeding in one patient with mild haemophilia A was complicated by the development of inhibitors. Type and severity of bleeding disorder, bone removal, and use of a local haemostatic agent did not have any significant effect on postoperative bleeding. Despite the use of perioperative factors and desmopressin, the postoperative bleeding rates remain high for patients with inherited bleeding disorders. More studies are required to assess the safety and effectiveness of using local haemostatic control to achieve haemostasis following extractions. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Do Psychosocial Interventions Improve Quality of Life and Wellbeing in Adults with Neuromuscular Disorders? A Systematic Review and Narrative Synthesis.

Science.gov (United States)

Walklet, Elaine; Muse, Kate; Meyrick, Jane; Moss, Tim

2016-08-30

Quality of life and well-being are frequently restricted in adults with neuromuscular disorders. As such, identification of appropriate interventions is imperative. The objective of this paper was to systematically review and critically appraise quantitative studies (RCTs, controlled trials and cohort studies) of psychosocial interventions designed to improve quality of life and well-being in adults with neuromuscular disorders. A systematic review of the published and unpublished literature was conducted. Studies meeting inclusion criteria were appraised using a validated quality assessment tool and results presented in a narrative synthesis. Out of 3,136 studies identified, ten studies met criteria for inclusion within the review. Included studies comprised a range of interventions including: cognitive behavioural therapy, dignity therapy, hypnosis, expressive disclosure, gratitude lists, group psychoeducation and psychologically informed rehabilitation. Five of the interventions were for patients with Amyotrophic Lateral Sclerosis (ALS). The remainder were for patients with post-polio syndrome, muscular dystrophies and mixed disorders, such as Charcot-Marie-Tooth disease, myasthenia gravis and myotonic dystrophy. Across varied interventions and neuromuscular disorders, seven studies reported a short-term beneficial effect of intervention on quality of life and well-being. Whilst such findings are encouraging, widespread issues with the methodological quality of these studies significantly compromised the results. There is no strong evidence that psychosocial interventions improve quality of life and well-being in adults with neuromuscular disorders, due to a paucity of high quality research in this field. Multi-site, randomised controlled trials with active controls, standardised outcome measurement and longer term follow-ups are urgently required.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

Science.gov (United States)

Camacho, A; Esteban, J; Paradas, C

A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Spectrum Of Inherited Metabolic Disorders In Pakistani Children Presenting At A Tertiary Care Centre

International Nuclear Information System (INIS)

Cheema, H. A.; Malik, H. S.; Parkash, A.; Fayyaz, Z.

2016-01-01

Objective: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. Study Design: An observational study. Place and Duration of Study: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. Methodology: All children aged < 14 years with high suspicion of a metabolic disorder were inducted. Routine and radiological investigation were carried out at the study place. Comprehensive diagnostic testing of particular metabolic disorder was sent abroad. Those with a specific metabolic disorder were included in the study while those with normal metabolic work-up were excluded. All data was collected on preformed proforma. Result: A total of 239 patients were enrolled. Nineteen different types of inherited metabolic disorders were diagnosed in 180 patients; age ranged from 8 days to 14 years. Consanguinity was positive in 175 (97 percentage) among the parents of the affected children, with previously affected siblings in 64 (35.5 percentage). The most frequent disorders were inherited disorders of carbohydrate metabolism (92, 51 percentage), lipid storage disease (59, 32.7 percentage), organic acidemia and energy defects (18, 10 percentage), amino acid disorder (6, 3.3 percentage), and miscellaneous (4, 2.2 percentage). Fifty-eight (32.2 percentage) presented with acute metabolic crisis, 28 (15.5 percentage) patients presented with early onset liver failure, and 24 (13.3 percentage) with mental retardation. Out of these, 16 (8.8 percentage) expired. Conclusion: Glycogen storage disorders being the commonest followed by Gaucher disease and Galactosemia. The associated complications resulted in high morbidity and mortality. (author)

The assisted 6-minute cycling test to assess endurance in children with a neuromuscular disorder

NARCIS (Netherlands)

Jansen, M.; Jong, M. de; Coes, H.M.; Eggermont, F.; Alfen, N. van; de Groot, I.J.

2012-01-01

Introduction: For late- or non-ambulant children with a neuromuscular disorder no suitable endurance tests are currently available. We developed the assisted 6-minute cycling test (A6MCT) for the legs and arms and investigated its psychometric properties in healthy boys and boys with Duchenne

Hereditary neuromuscular diseases

Energy Technology Data Exchange (ETDEWEB)

Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

2001-12-01

This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders

Directory of Open Access Journals (Sweden)

Pilar eMartinez-Martinez

2013-09-01

Full Text Available Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the CNS, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand–activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.

Identification and Simulation as Tools for Measurement of Neuromuscular Properties

National Research Council Canada - National Science Library

Kearney, R

2001-01-01

Quantitative, objective methods for the evaluation of neuromuscular properties are required for the diagnosis of neuromuscular disorders and the evaluation of the effectiveness of treatment and rehabilitation...

Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

Science.gov (United States)

Aiello, Lisa B; Chiatti, Beth Desaretz

2017-07-01

Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.

Airway clearance techniques in neuromuscular disorders: A state of the art review.

Science.gov (United States)

Chatwin, Michelle; Toussaint, Michel; Gonçalves, Miguel R; Sheers, Nicole; Mellies, Uwe; Gonzales-Bermejo, Jesus; Sancho, Jesus; Fauroux, Brigitte; Andersen, Tiina; Hov, Brit; Nygren-Bonnier, Malin; Lacombe, Matthieu; Pernet, Kurt; Kampelmacher, Mike; Devaux, Christian; Kinnett, Kathy; Sheehan, Daniel; Rao, Fabrizio; Villanova, Marcello; Berlowitz, David; Morrow, Brenda M

2018-03-01

This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electrophysiological study in neuromuscular junction disorders

Directory of Open Access Journals (Sweden)

Ajith Cherian

2013-01-01

Full Text Available This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS, congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS. SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

Palliative care in neuromuscular diseases

NARCIS (Netherlands)

de Visser, Marianne; Oliver, David J.

2017-01-01

Purpose of review Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness. Neuromuscular disorders (NMDs) are characterized by progressive muscle weakness, leading to pronounced and incapacitating

Neuromuscular Bandage: Neurophysiological Effects and the Role of Fascias

Directory of Open Access Journals (Sweden)

Ximena María Villota Chicaíza

2014-05-01

Full Text Available During the last years, neuromuscular bandage, a therapeutic application created in 1979 by doctor Kenzo Kase has been introduced in the management of many disorders of the musculo-skeletal system and even more so in the treatment of neurological disorders; This therapeutic tool which consists of a self adhesive elastic bandage allows recovery of the injured party without diminishing its bodily function. According to the existing literature on the physiological effects of this therapeutic application in the body, you could say that there is consensus. However in this article the author wants to highlight the significant although little highlighted role played by the fas¬cias on the therapeutic effects of neuromuscular bandage, analyzing from a reflective perspective the analgesic, neuromechanical and circulatory effects, as fundamental effects of neuromuscular bandage and fascias in the same function, trying to bring a global understanding on the way they relate to all connective tissues, aspects that are of great importance for the proper evaluation of alterations and prescription of neuromuscular bandage

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

Midterm outcome of valve-sparing aortic root replacement in inherited connective tissue disorders.

Science.gov (United States)

Tanaka, Hiroshi; Ogino, Hitoshi; Matsuda, Hitoshi; Minatoya, Kenji; Sasaki, Hiroaki; Iba, Yutaka

2011-11-01

This study determined the midterm outcome of valve-sparing aortic root replacement for patients with inherited connective tissue disorders. From 1993 to 2008, 94 patients underwent valve-sparing aortic root replacement. Sixty patients (64%), average age 33 years (range, 15 to 61 years), had inherited connective tissue disorders: Marfan syndrome, 54 (92%); Loeys-Dietz syndrome, 5 (8%); and smooth muscle α-actin (ACTA2) mutation in 1. Median preoperative sinus diameter was 52 mm (range, 42 to 76 mm), and moderate/severe aortic regurgitation was present in 14 (23%). Seven (12%, 1993 to 1999) underwent remodeling procedures, and 53 had reimplantation procedures. Cusp repair was performed in 4. Median follow-up was 55 months (range, 1 to 149 months). There were 15 patients in the early term (1993 to 2000) and 45 in the late term (2001 to 2008). Four late deaths occurred (cardiac, 3; aortic, 1), with 10-year survival of 86%. Rates of freedom from aortic valve replacement at 5 and 10 years were 85% and 58% in remodeling and 96% and 58% in reimplantation. Risk factors for reoperations were postprocedure intraoperative aortic insufficiency greater than mild (p = 0.046), remodeling procedure (p = 0.016), and early term (p = 0.0002). One patient (2%) with none/trivial postprocedure aortic insufficiency required aortic valve replacement. Freedom from reoperation in patients with none/trivial postprocedure aortic insufficiency at 5 and 10 years was 100% and 67%. Meticulous control of aortic insufficiency during operation would bring favorable midterm durability in valve-sparing aortic root replacement using a reimplantation technique, even in patients with inherited connective tissue disorders. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Evaluation of skeletal muscular involvement in neuromuscular disorders with thallium-201 whole body scintigraphy

International Nuclear Information System (INIS)

Yamamoto, Shuhei; Sotobata, Iwao; Indo, Toshikatsu; Matsuoka, Yukihiko; Matsushima, Hideo; Suzuki, Akio; Abe, Tetsutaro; Sakuma, Sadayuki

1986-01-01

The extent as well as severity of pathologic changes of skeletal muscles were analyzed with thallium-201 whole body scintigraphy (WBS) in 29 cases of various types of neuromuscular diseases (18 cases of myogenic and 11 cases of neurogenic muscular diseases) and 14 cases of normal controls. After intravenous injection of 2 mCi of thallium-201 chloride, WBS was performed for 15 minutes using a gamma camera with twin-opposed large rectangular detectors. Counts at brachia, forearms, thighs, and calves were assessed after reconstruction of the scintigram of the whole body by taking the geometric mean of the anterior and posterior data. WBS showed uniform tracer activities in the 4 extremities in 12 cases among 14 controls. Laterality in distribution of counts of both legs and arms was noted in the remaining 2 controls. WBS revealed decrease of perfusion in the extremities with muscular atrophy and/or weakness in neuromuscular diseases. The overall diagnostic accuracy of WBS for evaluation of skeletal muscle involvement was 75 to 80 % except for the bilateral brachia for which it decreased to 65 %. All of the three cases of muscular dystrophy with pseudohypertrophy of the calves or thighs showed unequivocal decrease of perfusion of those regions in WBS. In conclusion, thallium-201 WBS was considered to be a useful clinical means in evaluating the extent and severity of muscular involvement of various types of neuromuscular disorders. (author)

Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

OpenAIRE

Güngör, Deniz

2013-01-01

textabstractPompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents with (progressive) muscle weakness and can hence be categorized as a lysosomal storage disorder, a glycogen storage disorder and also a neuromuscular disorder. Pompe disease was the first neuromuscular disorde...

Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

Directory of Open Access Journals (Sweden)

Andreas Totzeck

2016-09-01

Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

Science.gov (United States)

Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

1998-01-01

VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

Clinical validation of targeted next-generation sequencing for inherited disorders.

Science.gov (United States)

Yohe, Sophia; Hauge, Adam; Bunjer, Kari; Kemmer, Teresa; Bower, Matthew; Schomaker, Matthew; Onsongo, Getiria; Wilson, Jon; Erdmann, Jesse; Zhou, Yi; Deshpande, Archana; Spears, Michael D; Beckman, Kenneth; Silverstein, Kevin A T; Thyagarajan, Bharat

2015-02-01

Although next-generation sequencing (NGS) can revolutionize molecular diagnostics, several hurdles remain in the implementation of this technology in clinical laboratories. To validate and implement an NGS panel for genetic diagnosis of more than 100 inherited diseases, such as neurologic conditions, congenital hearing loss and eye disorders, developmental disorders, nonmalignant diseases treated by hematopoietic cell transplantation, familial cancers, connective tissue disorders, metabolic disorders, disorders of sexual development, and cardiac disorders. The diagnostic gene panels ranged from 1 to 54 genes with most of panels containing 10 genes or fewer. We used a liquid hybridization-based, target-enrichment strategy to enrich 10 067 exons in 568 genes, followed by NGS with a HiSeq 2000 sequencing system (Illumina, San Diego, California). We successfully sequenced 97.6% (9825 of 10 067) of the targeted exons to obtain a minimum coverage of 20× at all bases. We demonstrated 100% concordance in detecting 19 pathogenic single-nucleotide variations and 11 pathogenic insertion-deletion mutations ranging in size from 1 to 18 base pairs across 18 samples that were previously characterized by Sanger sequencing. Using 4 pairs of blinded, duplicate samples, we demonstrated a high degree of concordance (>99%) among the blinded, duplicate pairs. We have successfully demonstrated the feasibility of using the NGS platform to multiplex genetic tests for several rare diseases and the use of cloud computing for bioinformatics analysis as a relatively low-cost solution for implementing NGS in clinical laboratories.

Neuromuscular ultrasound of cranial nerves.

Science.gov (United States)

Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Communication of genetic information to families with inherited rhythm disorders.

Science.gov (United States)

Burns, Charlotte; James, Cynthia; Ingles, Jodie

2017-11-23

Given the dynamic nature of the electrical activity of the heart and ongoing challenges in the diagnostics of inherited heart rhythm disorders, genetic information can be a vital aspect of family management. Communication of genetic information is complex, and the responsibility to convey this information to the family lies with the proband. Current practice falls short, requiring additional support from the clinician and multidisciplinary team. Communication is a 2-part iterative process, reliant on both the understanding of the probands and their ability to effectively communicate with relatives. With the surge of high-throughput genetic testing, results generated are increasingly complex, making the task of communication more challenging. Here we discuss 3 key issues. First, the probabilistic nature of genetic test results means uncertainty is inherent to the practice. Second, secondary findings may arise. Third, personal preferences, values, and family dynamics also come into play and must be acknowledged when considering how best to support effective communication. Here we provide insight into the challenges and provide practical advice for clinicians to support effective family communication. These strategies include acknowledging and managing genetic uncertainty, genetic counseling and informed consent, and consideration of personal and familial barriers to effective communication. We will explore the potential for developing resources to assist clinicians in providing patients with sufficient knowledge and support to communicate complex information to their at-risk relatives. Specialized multidisciplinary clinics remain the best equipped to manage patients and families with inherited heart rhythm disorders given the need for a high level of information and support. Copyright © 2017 Heart Rhythm Society. All rights reserved.

Objective neuromuscular monitoring of neuromuscular blockade in Denmark

DEFF Research Database (Denmark)

Söderström, C M; Eskildsen, K Z; Gätke, M R

2017-01-01

BACKGROUND: Neuromuscular blocking agents are commonly used during general anaesthesia but can lead to postoperative residual neuromuscular blockade and associated morbidity. With appropriate objective neuromuscular monitoring (objNMM) residual blockade can be avoided. In this survey, we investig...

Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure

International Nuclear Information System (INIS)

Lombó, Marta; Fernández-Díez, Cristina; González-Rojo, Silvia; Navarro, Claudia; Robles, Vanesa; Herráez, María Paz

2015-01-01

Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. - Highlights: • We examine the effects of adult male exposure to BPA on the progeny (F1 and F2). • Paternal exposure promotes similar cardiac malformations to those caused by direct exposure. • BPA applied during spermatogenesis decrease the insra and insrb transcripts in spermatozoa. • Sperm insrb transcript controls embryonic expression being the downregulation inherited by F1. • Paternal BPA exposure impairs heart development in F1 and F2 disrupting insulin signaling pathway. - Paternal bisphenol A exposure impairs cardiac development throughout generations.

Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

Science.gov (United States)

Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

2016-05-01

Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

Science.gov (United States)

Duyff, R.; Van den Bosch, J.; Laman, D; van Loon, B.-J. P.; Linssen, W.

2000-01-01

OBJECTIVES—To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism.
METHODS—A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment.
RESULTS—In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6months).
CONCLUSIONS—Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

 PMID:10811699

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

Science.gov (United States)

Højlund, Kurt

2014-07-01

Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

Science.gov (United States)

Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

2005-01-01

Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

[Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

Science.gov (United States)

Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies

NARCIS (Netherlands)

Slater, CR; Young, C; Wood, SJ; Bewick, GS; Anderson, LVB; Baxter, P; Fawcett, PRW; Roberts, M; Jacobson, L; Kuks, J; Vincent, A; NewsomDavis, J

Congenital myasthenic syndromes are a heterogenous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

Science.gov (United States)

Elgadi, Aziz; Arvidsson, C-G; Janson, Annika; Marcus, Claude; Costagliola, Sabine; Norgren, Svante

2005-08-01

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

The burden and consequences of inherited blood disorders among young children in western Kenya

OpenAIRE

Suchdev, Parminder S; Ruth, Laird J; Earley, Marie; Macharia, Alex; Williams, Thomas N

2012-01-01

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6–35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, −3.7 kb al...

Cardiomyopathy in neurological disorders.

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Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

2013-01-01

According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

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Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

2015-12-01

[Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

Impact of presymptomatic genetic testing for hereditary ataxia and neuromuscular disorders.

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Smith, Corrine O; Lipe, Hillary P; Bird, Thomas D

2004-06-01

With the exception of Huntington disease, the psychological and psychosocial impact of DNA testing for neurogenetic disorders has not been well studied. To evaluate the psychosocial impact of genetic testing for autosomal dominant forms of hereditary ataxia and neuromuscular disorders. Patients Fifty subjects at risk for autosomal dominant forms of spinocerebellar ataxia (n = 11), muscular dystrophy (n = 28), and hereditary neuropathy (n = 12). A prospective, descriptive, observational study in a university setting of individuals who underwent genetic counseling and DNA testing. Participants completed 3 questionnaires before testing and at regular intervals after testing. The questionnaire set included the Revised Impact of Event Scale, the Hospital Anxiety and Depression Scale, demographic information, and an assessment of attitudes and feelings about genetic testing. Thirty-nine subjects (78%) completed 6 months to 5 years of posttest follow-up. Common reasons for pursuing genetic testing were to provide an explanation for symptoms, emotional relief, and information for future planning. Thirty-four (68%) had positive and 16 (32%) had negative genetic results. In those with a positive result, 26 (76%) had nonspecific signs or symptoms of the relevant disorder. Forty-two participants (84%) felt genetic testing was beneficial. Groups with positive and negative test results coped well with results. However, 13 subjects (10 with positive and 3 with negative results) reported elevated anxiety levels, and 3 (1 with positive and 2 with negative results) expressed feelings of depression during the follow-up period. The test result was not predictive of anxiety or depression. Most individuals find neurogenetic testing to be beneficial, regardless of the result. Anxiety or depression may persist in some persons with positive or negative test results. Testing can have a demonstrable impact on family planning and interpersonal relationships. Further studies are needed to

Genitourinary complications as initial presentation of inherited ...

African Journals Online (AJOL)

Epidermolysis bullosa (EB) is a rare disorder that presents with urological complications. We present a 6-year-old boy admitted with urological symptoms that revealed an inherited EB misdiagnosed. We also review the literature on this disorder and management of the common urological complications.

Experimental Models of Inherited PrP Prion Diseases.

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Watts, Joel C; Prusiner, Stanley B

2017-11-01

The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Neurologic and neuromuscular functional disorders of the pharynx and esophagus

International Nuclear Information System (INIS)

Wuttge-Hannig, A.; Hannig, C.

2007-01-01

Neurologic swallowing disorders are an increasing diagnostic problem in our overaged population. Undiagnosed chronic aspiration pneumonia is the cause of death in 20-40% of all inhabitants of nursing homes. In neurologic diseases of the pharynx, the physiologic interaction of pharyngeal contraction, closure of the pharynx, and esophageal motility are frequently disturbed. This may be due to cortical, bulbar, or cerebellar brain damage of ischemic or traumatic origin. Furthermore diseases or peripheral nerves, muscles, and synapses cause disturbances. The most life-threatening complication of these disturbances is tracheal aspiration, which requires an iso-osmolar contrast medium for imaging studies that cause no or minimal pulmonary problems. Utilizing fast dynamic documentation we can analyze the swallowing act in 35 images within the passage time of 0.7 s. This requires digital frame sequences from 15-50 images/s, which can be provided by DSI or videofluoroscopy. Neurologic and neuromuscular patterns are demonstrated with and without tracheal aspiration. The differentiation of aspiration in a so-called pre-, intra-, and postdeglutitive form is possible. We distinguish four grades of severity of aspiration, which is also of great clinical impact for the differential rehabilitation therapy. The efficiency of the rehabilitation protocol can be assessed by the dynamic swallowing studies. (orig.) [de

Neuromuscular blockade in children Bloqueadores neuromusculares em crianças

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João Fernando Lourenço de Almeida

2000-06-01

Full Text Available Neuromuscular blocking agents (NMBAs have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000 and active search of articles were the mechanisms used in this review.Os bloqueadores neuromusculares têm sido amplamente utilizados para controlar pacientes que necessitem imobilidade para algum tipo de intervenção médica, desde a realização de procedimentos invasivos até a obtenção de sincronismo com a ventilação mecânica. O objetivo básico desta monografia é revisar a farmacologia dos principais bloqueadores neuromusculares, analisar as diferenças existentes na junção neuromuscular de neonatos, lactentes, pré-escolares e adultos, além de discutir suas indicações em pacientes criticamente enfermos internados em unidade de terapia intensiva pediátrica. Revisão computadorizada da literatura (Medline 1990-2000 associado a busca ativa de artigos compuseram o mecanismo de busca dos dados desta revisão.

Feeding and Swallowing Disorders in Pediatric Neuromuscular Diseases: An Overview.

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van den Engel-Hoek, Lenie; de Groot, Imelda J M; de Swart, Bert J M; Erasmus, Corrie E

2015-11-20

Feeding and swallowing problems in infants and children have a great impact on health and wellbeing. The aim of this study was to provide an overview of recognized feeding and swallowing problems in different groups of children with neuromuscular diseases, based on relevant literature and expert opinion, and to propose recommendations for the assessment and treatment of these problems. Almost all pediatric neuromuscular diseases are accompanied by feeding and swallowing problems during the different phases of deglutition, problems that give rise to a wide variety of signs and symptoms, which emphasizes the importance of a comprehensive feeding and swallowing assessment by a speech and language therapist.

[Inherited primitive and secondary polycythemia].

Science.gov (United States)

Barba, T; Boileau, J-C; Pasquet, F; Hot, A; Pavic, M

2016-07-01

Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

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Ohlendieck, Kay

2002-01-01

This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

Deconstructing Black Swans: An Introductory Approach to Inherited Metabolic Disorders in the Neonate.

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Mew, Nicholas Ah; Viall, Sarah; Kirmse, Brian; Chapman, Kimberly A

2015-08-01

Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve.

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

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Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

2011-03-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

The experience of girls and young women with inherited bleeding disorders.

Science.gov (United States)

Khair, K; Holland, M; Pollard, D

2013-09-01

Haemophilia carriers and women with inherited bleeding disorders (IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers. © 2013 John Wiley & Sons Ltd.

Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

Science.gov (United States)

2012-04-06

Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn

New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

Institute of Scientific and Technical Information of China (English)

Charles H Knowles; Joanne E Martin

2009-01-01

Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

Science.gov (United States)

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Conservative management of neuromuscular scoliosis: personal experience and review of literature.

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Kotwicki, Tomasz; Jozwiak, Marek

2008-01-01

The principles of conservative management of neuromuscular scoliosis in childhood and adolescence are presented. Analysis of personal experience and literature review. The topic is discussed separately for patients with flaccid or spastic paresis. These demonstrate that conservative management might be proposed for patients with neuromuscular scoliosis in many clinical situations. In spastic disorders, it maintains the symmetry around the hip joints. Bracing is technically difficult and often is not tolerated well by cerebral palsy children. In patients with flaccid paresis, the fitting and the use of brace is easier than in spastic patients. The flexibility of the spinal curvature is more important. Functional benefits of conservative management of neuromuscular scoliosis comprise stable sitting, easier use of upper limbs, discharge of the abdomen from the collapsing trunk, increased diaphragm excursion, and, not always, prevention of curve progression. Specific natural history and multiple medical problems associated with the disease make the treatment of children with neuromuscular scoliosis an extremely complex issue, best addressed when a team approach is applied. Continuously improving techniques of conservative management, comprising bracing and physiotherapy, together with correctly timed surgery incorporated in the process of rehabilitation, provide the optimal care for patients.

Inherited coagulation factor VII and X deficiencies associated with severe bleeding diathesis: Molecular genetics and pathophysiology

NARCIS (Netherlands)

Borensztajn, K.; Spek, C. A.

2005-01-01

The rare inherited coagulation disorders are a fascinating group of diseases that have provided us with important insights into the structure and functions of their respective deficient proteins. Factor (F)VII deficiency is the commonest of these inherited disorders of coagulation, whereas FX

The usefulness of electrodiagnostic studies in the diagnosis and management of neuromuscular disorders.

Science.gov (United States)

Lindstrom, Heather; Ashworth, Nigel L

2018-03-13

This study seeks to evaluate the usefulness of electrodiagnostic (EDX) studies in terms of the patient's diagnosis and subsequent management and to identify patient groups in which EDX is particularly useful. The records of new patients referred to a single tertiary hospital EDX laboratory during 1 calendar year were reviewed to determine whether results of EDX studies led to a changed diagnosis and/or management plan. Logistic regression was used to determine whether any factors were associated with changed diagnosis or management. Results of EDX studies led to a change in diagnosis and a confirmation in diagnosis in 51.5% and 46.5% of the cases, respectively. Results of EDX studies led to a change in the management plan in 63.4% of all cases. The diagnosis and management plan were more likely to be changed in older patients and patients referred in hospital. EDX studies seem useful for confirming or changing the diagnosis and in guiding management in patients with suspected neuromuscular disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

[Neuromuscular disease: respiratory clinical assessment and follow-up].

Science.gov (United States)

Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

2014-10-01

Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

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Paulo Victor Sgobbi de Souza

2014-12-01

Full Text Available During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg. IVIg has been tried in a variety of immune-mediated neurological diseases, being target of widespread use in central and peripheral nervous systems diseases. Objective To give an overview of the main topics regarding the mechanism of action and different therapeutic uses of IVIg in neurological practice, mainly in neuromuscular diseases.

TEACHING NEUROMUSCULAR RELAXATION.

Science.gov (United States)

NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

The neuromuscular differential diagnosis of joint hypermobility

NARCIS (Netherlands)

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

2015-01-01

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

Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future

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G. Scaturro

2013-04-01

Full Text Available Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children’s healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn’s place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

Is there any relationship between orthotic usage and functional activities in children with neuromuscular disorders?

Science.gov (United States)

Alemdaroğlu, İpek; Gür, Gozde; Bek, Nilgün; Yilmaz, Öznur T; Yakut, Yavuz; Uygur, Fatma; Karaduman, Ayşe

2014-02-01

Contractures of Achilles tendons and gastrocnemius muscle deteriorate the performance in daily living activities of patients with neuromuscular diseases. Ankle-foot orthoses help to prevent the progression of deformities and to obtain optimal position of the joints to support standing and walking. To investigate the relationship between orthotic usage and functional activities in pediatric patients with different neuromuscular diseases. Retrospective study. A total of 127 subjects' physical assessment forms were analyzed. Functional level, type of orthoses, falling frequencies, ankle joint range of motion, and timed performance tests were examined in two consecutive dates with an interval of 3 months. A total of 91 patients were using orthoses while 36 patients were not within assessment dates. A total of 64 of 91 (70.3%) patients were diagnosed with Duchenne muscular dystrophy. A total of 81 (89.0%) subjects were using plastic ankle-foot orthoses for positioning at nights and 10 (11%) were using different types of the orthoses (knee-ankle-foot orthoses, dynamic ankle-foot orthoses, and so on) for gait in the study group. Night ankle-foot orthoses were not found to be effective directly on functional performance in children with neuromuscular diseases, although they protect ankle from contractures and may help to correct gait and balance. This retrospective study shows that the positive effects of using an ankle-foot orthosis at night are not reflected in the functional performance of children with neuromuscular diseases. This may be due to the progressive deteriorating nature of the disease.

Effects of aquatic balance training and detraining on neuromuscular performance and balance in healthy middle aged male

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Ali Abbasi

2012-04-01

Full Text Available Introduction: Since disorders in neuromuscular performance and imbalance are the main cause of fallingamong the middle aged, their aspects including rehabilitation of balance are the main concern theresearchers attend to them. The aim of this study was to determine the effects of eight weeks aquaticbalance training (ABT and detraining on neuromuscular performance and balance in healthy middle agedmale.Materials and Methods: Thirty adult male subjects were randomized into two groups of ABT and control(n=15 per group. Berg balance scale, Timed Up and Go and 5-Chair stand tests, as they are indicators ofbalance and neuromuscular performance in older subjects, were taken as pretest and post-test and after four,six, and eight weeks of detraining as well. The ABT consisted of the sessions that lasted one hour, threetimes a week, for eight weeks.Results: Results showed that neuromuscular performance and balance improved significantly in ABTgroup (P 0.05.Conclusion: ABT can affect neuromuscular performance and balance in healthy middle aged male, andreduce the probability of falling among them. Moreover, the effects of these training are persistent afterdetraining periods. Hence, ABT can be recommended as an effective neuromuscular and balance training inhealthy middle aged male

The importance of studying inherited hematological disorders in ancient Anatolian populations

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Yeşim Doğan Alakoç

2011-12-01

Full Text Available Before analysis of DNA from ancient remains was possible, anthropologists studied evolution and migration patterns using data obtained from population genetic studies on modern populations combined with data obtained from morphological evaluations of ancient remains. Currently, DNA analysis of ancient populations is making a valuable contribution to these efforts. Researchers that perform ancient DNA analysis prefer to study polymorphisms on the Y chromosome or mitochondrial DNA because the results are easier to statistically evaluate. To evaluate polymorphisms on diploid genomes, which are more informative, only mutations that have been extensively examined in modern populations should be chosen. The most extensively evaluated mutations are those related to prevalent inherited disorders. As such, beta-thalassemia, sickle cell anemia, FVL mutation of globin and the factor V genes are good candidates for DNA studies in ancient populations. These mutations are common in Anatolia, host to many civilizations since the Paleolithic period. This history makes Anatolia a good place for conducting research that could enhance our understanding of human evolution and migration patterns.

Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

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Fauroux, Brigitte; Khirani, Sonia

2014-08-01

Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

The Mode of Inheritance of Scheuermann’s Disease

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A. M. Zaidman

2013-01-01

Full Text Available The mode of Scheuermann’s disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives. The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies’ anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann’s disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene probably indicates posttranscriptional genetic disorders. The study is under way.

Reliability and validity of the Turkish version of ABILHAND-Kids' questionnaire in a group of patients with neuromuscular disorders.

Science.gov (United States)

Öksüz, Çigdem; Alemdaroglu, Ipek; Kilinç, Muhammed; Abaoğlu, Hatice; Demirci, Cevher; Karahan, Sevilay; Yilmaz, Oznur; Yildirim, Sibel Aksu

2017-10-01

This study was performed to examine the reliability and validity of the Turkish version of ABILHAND-Kids questionnaire which assesses manual functions of children with neuromuscular diseases (NMDs). A cross sectional survey study design and Rasch analysis were used to assess the reliability and validity of the Turkish version of scale. Ninety-three children with different neuromuscular disorders and their parents were included in the study. The scale was applied to the parents with face-to-face interview twice; on their first visit and after an interval of 15 days. The test-retest reliability was assessed with intraclass correlation coefficient (ICC), and internal consistency of the multi-item subscales by calculating Cronbach alpha values. Brooke Upper Extremity Functional Classification (BUEFC) and Wee-Functional Independency Measurement (Wee-FIM) were correlated to determine the construct validity. The ICC value for the test/retest reliability was 0.94. The internal consistency was 0.81. Floor (1.1%) and ceiling (11.8%) effects were not significant. There were moderate correlations between the Turkish version of ABILHAND-Kids and Wee-FIM (0.67) and BUEFC (-0.37). Rasch analysis indicated good item fit, unidimensionality, and model fit. The Turkish version of ABILHAND-Kids questionnaire was found to be a reliable and valid scale for the assessment of the manual ability of children with NMDs.

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

DEFF Research Database (Denmark)

Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

2017-01-01

neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia...... and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel...... practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit...

The undesirable effects of neuromuscular blocking drugs

DEFF Research Database (Denmark)

Claudius, C; Garvey, L H; Viby-Mogensen, J

2009-01-01

Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

Practical approach to management of respiratory complications in neurological disorders

Directory of Open Access Journals (Sweden)

Mangera Z

2012-03-01

Full Text Available Zaheer Mangera, Kirat Panesar, Himender MakkerRespiratory Medicine, North Middlesex University Hospital, London, UKAbstract: Patients with certain neurological diseases are at increased risk of developing chest infections as well as respiratory failure due to muscular weakness. In particular, patients with certain neuromuscular disorders are at higher risk. These conditions are often associated with sleep disordered breathing. It is important to identify patients at risk of respiratory complications early in the course of their disease, although patients with neuromuscular disorders often present in the acute setting with respiratory involvement. This review of the respiratory complications of neurological disorders, with a particular focus on neuromuscular disorders, explores why this happens and looks at how to recognize, investigate, and manage these patients effectively.Keywords: respiratory failure, respiratory muscle weakness

[Traditional Chinese medicine inheritance system analysis of professor Ding Yuanqing in treating tic disorder medication based on experience].

Science.gov (United States)

Sun, Lu-yan; Li, Qing-peng; Zhao, Li-li; Ding, Yuan-qing

2015-08-01

In recent years, the incidence of tic disorders has increased, and it is not uncommon for the patients to treat the disease. The pathogenesis and pathogenesis of Western medicine are not yet clear, the clinical commonly used western medicine has many adverse reactions, traditional Chinese medicine (TCM) research is increasingly valued. Based on the software of TCM inheritance assistant system, this paper discusses Ding Yuanqing's experience in treating tic disorder with Professor. Collect yuan Qing Ding professor in treating tic disorder of medical records by association rules Apriori algorithm, complex system entropy clustering without supervision and data mining method, carries on the analysis to the selected 800 prescriptions, to determine the frequency of use of prescription drugs, the association rules between the drug and digging out the 12 core combination and the first six new prescription, medication transferred to the liver and extinguish wind, cooling blood and relieving convulsion, Qingxin soothe the nerves, with the card cut, flexible application, strict compatibility.

GOLGA2, encoding a master regulator of golgi apparatus, is mutated in a patient with a neuromuscular disorder.

Science.gov (United States)

Shamseldin, Hanan E; Bennett, Alexis H; Alfadhel, Majid; Gupta, Vandana; Alkuraya, Fowzan S

2016-02-01

Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2. The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy. Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype. Our data suggest an important developmental role of GM130 in humans and zebrafish.

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

Science.gov (United States)

Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases

Management of neuromuscular diseases and spinal muscular atrophy in Latin America.

Science.gov (United States)

Monges, S; Rosa, A L

2017-09-01

Latin America (LA) has a population of ~645 million people distributed over 33 countries with marked political, cultural and economic differences. In LA, patients with inherited neuromuscular diseases (NMDs) often do not have access to specialized medical centers and many of them go undiagnosed. General management and care of spinal muscular dystrophy (SMA) patients in the region varies due to heterogeneous health care. An active generation of young clinical neurologists is being trained for the specialized care of SMA and other neuromuscular (NM) patients, both in the private and public sectors. The Euro-Latin-American Summer School of Myology (EVELAM) as well as efforts of professionals at large public centers in the major cities of LA have a leading role in this development. Different regional academic-scientific organizations as well as the expanding number of telethon centers and the creation of parent organizations, mostly concerning SMA, all together are contributing to the increased quality of the management of NMD patients. Over the past years, academic and clinical research, as well as the establishment of qualified centers for the molecular testing of NMD are pushing forward the creation of patient registries and the development of specific clinical trials, with Argentina and Brazil having a major role in this field. Nevertheless, increased awareness and further training of specialized health professionals are necessary to reach patients that are currently lacking care throughout the region.

Rare inherited kidney diseases: challenges, opportunities, and perspectives.

NARCIS (Netherlands)

Devuyst, O.; Knoers, N.V.A.M.; Remuzzi, G.; Schaefer, F.; Bindels, R.J.; et al.,

2014-01-01

At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

DEFF Research Database (Denmark)

Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

2017-01-01

BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an......-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x)....

Clinical approach to inherited peroxisomal disorders

NARCIS (Netherlands)

Poggi-Travert, F.; Fournier, B.; Poll-The, B. T.; Saudubray, J. M.

1995-01-01

At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction. Whatever the genetic defect might be, peroxisomal disorders should be considered in various clinical conditions, dependent on the age of onset. The prototype of peroxisomal disorders is represented by

Bloqueio neuromuscular residual após o uso de rocurônio ou cisatracúrio Bloqueo neuromuscular residual después del uso de rocuronio o cisatracúrio Residual neuromuscular block after rocuronium or cisatracurium

Directory of Open Access Journals (Sweden)

Bruno Salomé de Morais

2005-12-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio neuromuscular residual na sala de recuperação pós-anestésica (SRPA é um fenômeno que pode aumentar a morbidade pós-operatória, com incidência variando entre 0% e 93%. O objetivo deste estudo foi avaliar a incidência do bloqueio neuromuscular residual na SRPA. MÉTODO: Foram estudados 93 pacientes submetidos à cirurgia geral com o uso de cisatracúrio ou rocurônio. Após a admissão na SRPA foi realizada a monitorização objetiva da função neuromuscular (aceleromiografia - TOF GUARD. O bloqueio neuromuscular residual foi definido como SQE JUSTIFICATIVA Y OBJETIVOS: El bloqueo neuromuscular residual en la sala de recuperación posanestésica (SRPA es un fenómeno que puede aumentar la morbidez posoperatoria, con incidencia variando entre 0% y 93%. La finalidad de este estudio fue evaluar la incidencia del bloqueo neuromuscular residual en la SRPA. MÉTODO: Fueron estudiados 93 pacientes sometidos a cirugía general con el uso de cisatracúrio o rocuronio. Después de la admisión en la SRPA fue realizada la monitorización objetiva de la función neuromuscular (aceleromiografia - TOF-GUARD. El bloqueo neuromuscular residual fue definido como TOF BACKGROUND AND OBJECTIVES: Residual neuromuscular block in the post-anesthetic recovery unit (PACU may increase postoperative morbidity from 0% to 93%. This study aimed at evaluating the incidence of residual neuromuscular block in the PACU. METHODS: Participated in this study 93 patients submitted to general anesthesia with cisatracurium or rocuronium. After PACU admission, neuromuscular function was objectively monitored (acceleromyography - TOF GUARD. Residual neuromuscular block was defined as TOF < 0.9. RESULTS: From 93 patients, 53 received cisatracurium and 40 rocuronium. Demographics, procedure length and the use of antagonists were comparable between groups. Residual neuromuscular block was 32% in subgroup C (cisatracurium and 30% in subgroup R

Sugammadex: A Review of Neuromuscular Blockade Reversal.

Science.gov (United States)

Keating, Gillian M

2016-07-01

Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

Effectiveness of Neuromuscular Training Based on the Neuromuscular Risk Profile.

Science.gov (United States)

Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

2017-07-01

The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Controlled laboratory study. Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

To inherit heritage or to inherit inheritance?

Directory of Open Access Journals (Sweden)

Vladimir Krivošejev

2016-02-01

Full Text Available The Republic of Serbia is one of the few, if not the only country in the world that, at ratification and translation of the term „baština“– heritage which appears in two significant and related international conventions of UNESCO, used different terms: „baština“– „heritage“, with regard to the Convention Concerning the Protection of the World Cultural and Natural Heritage, and „nasledje“ –inheritance in the Convention for the Safeguarding of the Intangible Cultural Heritage. One of the reasons for the subsequent rejection of the term heritage could lay in the opinion that it was the case of (end of 20th and beginning of the 21st century political bureaucratic introduction of an old, forgotten word, which also contains the notion of gender incorrectness based on pointing out the inheritance through the male line, which could be in conflict with international law. The views expressed in this paper suggest the unsustainability of these claims, as well as greater suitability of the term „baština“– heritage. Namely, the ratification of the Convention Concerning the Protection of the World Cultural and Natural Heritage was done as early as in 1974, and since then the term „baština“– heritage was used, its new introduction into use on the basis of recent daily political aspirations cannot be the case. At the same time inheritance through the male line is encountered with the use of the Latin word „patrimonium“, which is the basis for the terms used in the official translation of the UNESCO-listed conventions in French and Spanish: „patrimoine“ and „patrimonio“ (and other Roman languages so that the use of the term „baština“ –heritage cannot be a violation of international legal norms. Finally, bearing in mind the fact that, in general, use of languages is impossible to achieve complete gender purism, it is necessary to emphasize that in contrast to the term „nasledje“ – inheritance, the

Neuromuscular control and ankle instability.

Science.gov (United States)

Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

2009-04-01

Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

The inherited basis of human radiosensitivity

International Nuclear Information System (INIS)

Gatti, R.A.

2001-01-01

Certain individuals cannot tolerate 'conventional' doses of radiation therapy. This is known to be true of patients with ataxia-telangiectasia and ligase IV deficiency. Although in vitro testing may not correlate completely with clinical radiosensitivity, fibroblasts and lymphoblasts from patients with both of these disorders have been clearly shown to be radiosensitive. Using a colony survival assay (CSA) to test lymphoblastoid cells after irradiation with 1 Gy, a variety of other genetic disorders have been identified as strong candidates for clinical radiosensitivity, such as Nijmegen breakage syndrome, Mre11 deficiency, and Fanconi's anemia. These data are presented and considered as a starting-point for the inherited basis of human radiosensitivity

Classification of EMG signals using PSO optimized SVM for diagnosis of neuromuscular disorders.

Science.gov (United States)

Subasi, Abdulhamit

2013-06-01

Support vector machine (SVM) is an extensively used machine learning method with many biomedical signal classification applications. In this study, a novel PSO-SVM model has been proposed that hybridized the particle swarm optimization (PSO) and SVM to improve the EMG signal classification accuracy. This optimization mechanism involves kernel parameter setting in the SVM training procedure, which significantly influences the classification accuracy. The experiments were conducted on the basis of EMG signal to classify into normal, neurogenic or myopathic. In the proposed method the EMG signals were decomposed into the frequency sub-bands using discrete wavelet transform (DWT) and a set of statistical features were extracted from these sub-bands to represent the distribution of wavelet coefficients. The obtained results obviously validate the superiority of the SVM method compared to conventional machine learning methods, and suggest that further significant enhancements in terms of classification accuracy can be achieved by the proposed PSO-SVM classification system. The PSO-SVM yielded an overall accuracy of 97.41% on 1200 EMG signals selected from 27 subject records against 96.75%, 95.17% and 94.08% for the SVM, the k-NN and the RBF classifiers, respectively. PSO-SVM is developed as an efficient tool so that various SVMs can be used conveniently as the core of PSO-SVM for diagnosis of neuromuscular disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Muscle MRI / whole-body MRI in diagnosis and dynamic evaluation of neuro-muscular disorders

Directory of Open Access Journals (Sweden)

Robert Carlier

2014-01-01

Full Text Available The use of MRI in myopathies dates back to more than 20 years. The first investigations were slow and only allowed segmental and limited studies. Whole-body MRI has emerged over the past twelve years and became a useful diagnostic tool in the etiological diagnosis of myopathies and muscular dystrophies. This study must always be confronted with clinical and whichever other paraclinical data without being able to replace them. Indications to perform such an investigation are getting better and better defined and the diagnostic efficacy has progressed with the increasing number of cases, communications, publications and discussions within multidisciplinary working groups. Its noninvasive nature, the radiation-free exposure and its reasonable cost also enable this technique to be easily accepted by the patient. It also provides a valuable tool for monitoring the natural disease progression or the effectiveness of therapies. The radiology team must be acquainted with the management of neuromuscular patients. Interpreting muscle whole-body MRI requires an excellent knowledge of muscle anatomy whichever body part is examined. The radiologist performing these studies is ideally a specialist of musculoskeletal disorders or a neuroradiologist well trained in muscle anatomy.

Familial epilepsy in Algeria: Clinical features and inheritance profiles.

Science.gov (United States)

Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

2015-09-01

To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neuromuscular blockade in the elderly patient

Directory of Open Access Journals (Sweden)

Lee LA

2016-06-01

Full Text Available Luis A Lee, Vassilis Athanassoglou, Jaideep J Pandit Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Abstract: Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids. Other drugs (atracurium, cisatracurium have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. Keywords: anesthesia, elderly, drugs, pharmacokinetics, pharmacodynamics 

Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders

Directory of Open Access Journals (Sweden)

Derek W. Stouth

2017-11-01

Full Text Available Protein arginine methyltransferases (PRMTs are a family of enzymes that catalyze the methylation of arginine residues on target proteins, thereby mediating a diverse set of intracellular functions that are indispensable for survival. Indeed, full-body knockouts of specific PRMTs are lethal and PRMT dysregulation has been implicated in the most prevalent chronic disorders, such as cancers and cardiovascular disease (CVD. PRMTs are now emerging as important mediators of skeletal muscle phenotype and plasticity. Since their first description in muscle in 2002, a number of studies employing wide varieties of experimental models support the hypothesis that PRMTs regulate multiple aspects of skeletal muscle biology, including development and regeneration, glucose metabolism, as well as oxidative metabolism. Furthermore, investigations in non-muscle cell types strongly suggest that proteins, such as peroxisome proliferator-activated receptor-γ coactivator-1α, E2F transcription factor 1, receptor interacting protein 140, and the tumor suppressor protein p53, are putative downstream targets of PRMTs that regulate muscle phenotype determination and remodeling. Recent studies demonstrating that PRMT function is dysregulated in Duchenne muscular dystrophy (DMD, spinal muscular atrophy (SMA, and amyotrophic lateral sclerosis (ALS suggests that altering PRMT expression and/or activity may have therapeutic value for neuromuscular disorders (NMDs. This review summarizes our understanding of PRMT biology in skeletal muscle, and identifies uncharted areas that warrant further investigation in this rapidly expanding field of research.

Dominant inheritance of cerebral gigantism.

Science.gov (United States)

Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

Emerging modalities in dysphagia rehabilitation: neuromuscular electrical stimulation.

Science.gov (United States)

Huckabee, Maggie-Lee; Doeltgen, Sebastian

2007-10-12

The aim of this review article is to advise the New Zealand medical community about the application of neuromuscular electrical stimulation (NMES) as a treatment for pharyngeal swallowing impairment (dysphagia). NMES in this field of rehabilitation medicine has quickly emerged as a widely used method overseas but has been accompanied by significant controversy. Basic information is provided about the physiologic background of electrical stimulation. The literature reviewed in this manuscript was derived through a computer-assisted search using the biomedical database Medline to identify all relevant articles published until from the initiation of the databases up to January 2007. The reviewers used the following search strategy: [(deglutition disorders OR dysphagia) AND (neuromuscular electrical stimulation OR NMES)]. In addition, the technique of reference tracing was used and very recently published studies known to the authors but not yet included in the database systems were included. This review elucidates not only the substantive potential benefit of this treatment, but also potential key concerns for patient safety and long term outcome. The discussion within the clinical and research communities, especially around the commercially available VitalStim stimulator, is objectively explained.

The inherited basis of human radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Gatti, R.A. [Univ. of California, School of Medicine, Los Angeles, CA (United States). Experimental Pathology

2001-11-01

Certain individuals cannot tolerate 'conventional' doses of radiation therapy. This is known to be true of patients with ataxia-telangiectasia and ligase IV deficiency. Although in vitro testing may not correlate completely with clinical radiosensitivity, fibroblasts and lymphoblasts from patients with both of these disorders have been clearly shown to be radiosensitive. Using a colony survival assay (CSA) to test lymphoblastoid cells after irradiation with 1 Gy, a variety of other genetic disorders have been identified as strong candidates for clinical radiosensitivity, such as Nijmegen breakage syndrome, Mre11 deficiency, and Fanconi's anemia. These data are presented and considered as a starting-point for the inherited basis of human radiosensitivity.

[Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

Science.gov (United States)

Bachmann, H

1987-11-01

Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

Science.gov (United States)

Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

2015-11-01

Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

Challenges identified in the management of patients with inherited ...

African Journals Online (AJOL)

Background: Pakistan is the sixth most populous country in the World. High rates of consanguinity and inter caste marriages have resulted in a substantial burden of inherited metabolic disorders (IMDs). Despite this load, there is a dearth of both medical genetic and clinical metabolic services in Pakistan. There are ...

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

Science.gov (United States)

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

Science.gov (United States)

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

Kinship and interaction in neuromuscular pharmacology

NARCIS (Netherlands)

Schiere, Sjouke

2006-01-01

The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

Online Mendelian Inheritance in Man (OMIM).

Science.gov (United States)

Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

2000-01-01

Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

Translation and validation of the Life Satisfaction Index for Adolescents scale with neuromuscular disorders: LSI-A Brazil

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Valdecir Antonio Simon

Full Text Available ABSTRACT Objective To validate the Life Satisfaction Index for Adolescents (LSI-A scale, parent version and patient version, for Duchenne muscular dystrophy (DMD, spinal muscular atrophy (SMA and limb-girdle muscular dystrophy (LGMD. Methods The parent version of the instrument was divided into Groups A, B, C and D; and the patient version, divided into B, C and D. For the statistical calculation, the following tests were used: Cronbach’s α, ICC, Pearson and the ROC Curve. Results The parent and patient versions of the instrument are presented, with the following results in the overall score, respectively: Cronbach’s α, 0.87 and 0.89; reliability, r 0.98 and 0.97; reproducibility, ICC 0.69 and 0.80; sensitivity, 0.78 and 0.72; specificity, 0.5 and 0.69; and accuracy, 64% and 70.4%. Conclusion According to the validity and reproducibility values, the LSI-A Brazil parent and patient versions, are clinically useful to assess quality of life in DMD, SMA or LGMD and may also be useful for other neuromuscular disorders.

Translation and validation of the Life Satisfaction Index for Adolescents scale with neuromuscular disorders: LSI-A Brazil.

Science.gov (United States)

Simon, Valdecir Antonio; Zanoteli, Edmar; Simon, Margarete Andreozzi Vaz Pereira; Resende, Maria Bernadete Dutra de; Reed, Umbertina Conti

2017-08-01

To validate the Life Satisfaction Index for Adolescents (LSI-A) scale, parent version and patient version, for Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA) and limb-girdle muscular dystrophy (LGMD). The parent version of the instrument was divided into Groups A, B, C and D; and the patient version, divided into B, C and D. For the statistical calculation, the following tests were used: Cronbach's α, ICC, Pearson and the ROC Curve. The parent and patient versions of the instrument are presented, with the following results in the overall score, respectively: Cronbach's α, 0.87 and 0.89; reliability, r 0.98 and 0.97; reproducibility, ICC 0.69 and 0.80; sensitivity, 0.78 and 0.72; specificity, 0.5 and 0.69; and accuracy, 64% and 70.4%. According to the validity and reproducibility values, the LSI-A Brazil parent and patient versions, are clinically useful to assess quality of life in DMD, SMA or LGMD and may also be useful for other neuromuscular disorders.

Schwann Cells in Neuromuscular Junction Formation and Maintenance.

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Barik, Arnab; Li, Lei; Sathyamurthy, Anupama; Xiong, Wen-Cheng; Mei, Lin

2016-09-21

The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation. Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences

Neuromuscular Control and Coordination during Cycling

Science.gov (United States)

Li, Li

2004-01-01

The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

Reduced serum myostatin concentrations associated with genetic muscle disease progression.

Science.gov (United States)

Burch, Peter M; Pogoryelova, Oksana; Palandra, Joe; Goldstein, Richard; Bennett, Donald; Fitz, Lori; Guglieri, Michela; Bettolo, Chiara Marini; Straub, Volker; Evangelista, Teresinha; Neubert, Hendrik; Lochmüller, Hanns; Morris, Carl

2017-03-01

Myostatin is a highly conserved protein secreted primarily from skeletal muscle that can potently suppress muscle growth. This ability to regulate skeletal muscle mass has sparked intense interest in the development of anti-myostatin therapies for a wide array of muscle disorders including sarcopenia, cachexia and genetic neuromuscular diseases. While a number of studies have examined the circulating myostatin concentrations in healthy and sarcopenic populations, very little data are available from inherited muscle disease patients. Here, we have measured the myostatin concentration in serum from seven genetic neuromuscular disorder patient populations using immunoaffinity LC-MS/MS. Average serum concentrations of myostatin in all seven muscle disease patient groups were significantly less than those measured in healthy controls. Furthermore, circulating myostatin concentrations correlated with clinical measures of disease progression for five of the muscle disease patient populations. These findings greatly expand the understanding of myostatin in neuromuscular disease and suggest its potential utility as a biomarker of disease progression.

New clinical molecular diagnostic methods for congenital and inherited heart disease

NARCIS (Netherlands)

Jongbloed, Jan Dh; Pósafalvi, Anna; Kerstjens-Frederikse, Wilhelmina S.; Sinke, Richard J.; van Tintelen, J. Peter

2011-01-01

For patients with congenital and inherited heart disorders, causative mutations are often not identified owing to limitations of current screening techniques. Identifying the mutation is of major importance for genetic counseling of patients and families, facilitating the diagnosis in people at risk

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

Science.gov (United States)

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Ten inherited disorders in purebred dogs by functional breed groupings

OpenAIRE

Oberbauer, A. M.; Belanger, J. M.; Bellumori, T.; Bannasch, D. L.; Famula, T. R.

2015-01-01

Background Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic po...

FUNCTIONS OF A NEUROMUSCULAR CENTRE

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Janez Zidar

2004-12-01

Full Text Available Main functions of a neuromuscular (NM centre are making diagnosis, treatment and counselling. Some other functions, e. g. forming a register and epidemiological endeavours, could be added. All these activities are expected to be achieved by multidisciplinary approach with the idea that members use the same guidelines and share the same knowledge.NM diseases affect lower levels of the nervous system that is motor units (motor cells in the brainstem and spinal cord, nerve roots, cranial and peripheral nerves, neuromuscular junction, and muscles. There are many such diseases; a few are more common others are rare.Rational approach in making a diagnosis can be divided into several steps. The process begins with a person with clinical symptoms and signs which raise the suspicion of NM disease. The first step is the description of the predominant pattern of muscular wasting and weakness (e. g. limb-girdle, distal, ocular, facio-scapulo-humeral. Each of these syndromes require a differential diagnosis within the motor unit territory what is achieved by means of EMG and muscle biopsy. The latter is even more important to define the nature of the abnormality. Disease nature can also be determined biochemically and, as NM disorders are commonly genetically determined, at the molecular genetic level. Treatment modalities include drugs (causative and symptomatic and other measures such as promoting and maintaining good general health, preventing skeletal deformities, physiotherapy, orthoses, surgery, and prevention of respiratory and cardiac functions. Counselling is mainly by social workers that focus on the practical aspects of coping with illness and disability and by genetic counsellors who gave advise on family planning.

Molecular genetics of inherited eye disorders.

Science.gov (United States)

MacDonald, I M; Sasi, R

1994-10-01

In the past 10 y, there have been considerable advances in the mapping, isolation, and characterization of many genes for important ocular conditions: retinitis pigmentosa, Norrie disease, Waardenburg syndrome, choroideremia, aniridia, retinoblastoma, and others. The candidate gene approach has now supplemented classical linkage studies and positional cloning in the investigation of ocular disorders. Developmentally expressed genes and animal models have provided insights as to the etiology of other disorders. With this knowledge at hand, genetic counselling for heritable eye diseases has been greatly improved.

Exploring digenic inheritance in arrhythmogenic cardiomyopathy.

Science.gov (United States)

König, Eva; Volpato, Claudia Béu; Motta, Benedetta Maria; Blankenburg, Hagen; Picard, Anne; Pramstaller, Peter; Casella, Michela; Rauhe, Werner; Pompilio, Giulio; Meraviglia, Viviana; Domingues, Francisco S; Sommariva, Elena; Rossini, Alessandra

2017-12-08

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

Waardinburg syndrome — inherited deafness with pigmentary involvement

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M.F. Macrae

1979-09-01

Full Text Available The Waardenburg syndrome was first clearly defined in 1951. The major clinical importance lies in the fact that about 20% of affected individuals are deaf. Furthermore, because the condition is inherited autosomal dominantly, there is a risk of the disorder being handed down from generation to generation. The syndrome consists of six major features which may appear in any combination and to any degree in the affected individual.

Constraints of behavioural inheritance

NARCIS (Netherlands)

Roubtsova, E.E.; Roubtsov, S.A.; Oquendo, F.; Warboys, B.; Morrison, R.

2004-01-01

We present an approach to component inheritance and reuse which closes the gap between architectural design and process-oriented approaches. To apply inheritance checks in design and verification of a system, one should consider an inheritance relation as a property of the system and specify it as

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

Science.gov (United States)

Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

2015-03-01

Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

Ethics of Inheritance

OpenAIRE

Guibet Lafaye , Caroline

2008-01-01

International audience; Both in the U.S. and in France, inheritance is probably the main factor of wealth concentration among the richest part of the population, and of its intergenerational reproduction. In so far as wealth is an opportunity, a reform of inheritance tax could be a mean to ensure a fairer distribution of opportunities in the society. Many reforms of inheritance systems have been conceived at least since Bentham. The identification and the analysis of ethical properties of ref...

Elucidation of the Molecular Genetic Basis of Inherited Hearing Impairment.

NARCIS (Netherlands)

Luijendijk, M.W.J.

2006-01-01

Hearing loss is the most common sensory disorder in the human population. It affects 0.1% of all young children and by the age of 70, 30% of the population suffers from hearing loss greater than 40 dB. When early onset hearing loss is inherited, 70% is classified as nonsyndromic and 30% as

Inherited disorders of HDL metabolism and atherosclerosis

NARCIS (Netherlands)

Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

Inherited disorders of HDL metabolism and atherosclerosis

NARCIS (Netherlands)

Hovingh, G. Kees; de Groot, Eric; van der Steeg, Wim; Boekholdt, S. Matthijs; Hutten, Barbara A.; Kuivenhoven, Jan Albert; Kastelein, John J. P.

2005-01-01

Purpose of review Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

Effect of long-term non-invasive ventilation on quality of life and cardiac function of children's neuromuscular disorders with chronic respiratory failure: a clinical trial

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Saeed Sadr

2018-04-01

Full Text Available Background: Use of long-term non-invasive positive pressure ventilation is increasing greatly worldwide in children with chronic respiratory failure (CRF of all ages. This treatment requires delivery of ventilation through a non-invasive interface. Cardiac function in majority of these children is impaired. The aim of this study was to assess the effect of institution of non-invasive ventilation (NIV on quality of life (QOL and cardiac function in children with CRF related to neuromuscular disorders. Methods: Information obtained from all of the children under 16 years old with CRF due to neuromuscular disorders who were on NIV for at least six months and that were referred to Mofid children's hospital, Tehran, Iran between September 1, 2013, to September 1, 2017.Based on previous studies they were assessed from the year prior to starting NIV and annually thereafter. Data obtained included diagnosis, pulmonary function test, echocardiographic data, length of hospitalizations, and health care costs. Patients and parents completed questionnaires assessing QOL with NIV and recalling QOL one year before commencing NIV. All results were recorded in information forms and data were analyzed with chi square and entered in SPSS 21. Results: Follow-up ranged from 6 to 36 months (median 18. Before and after NIV hospitalization rates (P<0.001, PICU admission (P<0.001 and health care costs decreased respectively. QOL remained stable after NIV despite disease progression (P<0.001. Systolic pulmonary arterial pressure (P=0.009 is diminished. Symptoms of daytime sleepiness (P<0.001 and headache (P<0.001 improved after initiation of NIV. Conclusions: This study revealed that use of NIV results in a reduction in PAH without adverse effects on quality of life and pulmonary function.

Telomere length is highly inherited and associated with hyperactivity-impulsivity in children with attention deficit/hyperactivity disorder

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Danielle Souza Costa

2015-07-01

Full Text Available Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Additionally, a shorter TL may represent a biomarker of chronic stress and has been associated with psychiatric disorders. However, no study has explored whether there is an association between TL and the symptoms of one of the most common neurodevelopmental disorders in childhood: Attention Deficit/Hyperactive Disorder (ADHD. We evaluated 61 (range, 6-16 years ADHD children and their parents between 2012 and 2014. Telomere length was measured with a quantitative polymerase chain reaction method with telomere signal normalized to the signal from a single copy gene (36B4 to generate a T/S ratio. Family data was processed through a GEE model to determine the effect of parental TL on children TL. Inattentive and hyperactive-impulsive symptoms were also evaluated in relation to TL. For the first time, we found general heritability to be the major mechanism explaining interindividual telomere length variation in ADHD (father-child: 95%CI=0.35/0.91, p0.05. The ADHD inattentive dimension was not significant associated with TL in this study (p>0.05. TL was shown to be a potential biomarker of the ADHD symptoms burden in families affected by this neurodevelopmental disorder. However, it is crucial that future studies investigating the rate of telomere attrition in relation to psychiatric problems to consider the strong determination of telomere length at birth by inheritance.

Compiler generation based on grammar inheritance

NARCIS (Netherlands)

Aksit, Mehmet; Mostert, Rene; Haverkort, Boudewijn R.H.M.

1990-01-01

The concept of grammar inheritance is introduced. Grammar inheritance is a structural organization of grammar rules by which a grammar inherits rules from ancestor grammars or may have its own rules inherited by descendant grammars. Grammar inheritance supports reusability and extensibility of

Protein defects in neuromuscular diseases

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Vainzof M.

2003-01-01

Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

Neuromuscular blockade in cardiac surgery: An update for clinicians

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Hemmerling Thomas

2008-01-01

Full Text Available There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

SWJ:39-42 Inheritance of Pod Colour in Cowpea INHERITANCE

African Journals Online (AJOL)

Dr. Ahmed

Mustapha & Singh (2008) SWJ:39-42. Inheritance of Pod Colour in Cowpea. INHERITANCE OF POD COLOUR IN. COWPEA (Vigna unguiculata (L.) WALP). * MUSTAPHA, Y1. & SINGH, B. B2. 1 Department of Biological Sciences. Bayero University, Kano Nigeria. 2 Department of Genetics and Plant breeding,. G.B. Pant ...

The role of patient advocacy organisations in neuromuscular disease R&D - The case of the Dutch neuromuscular disease association VSN

NARCIS (Netherlands)

Boon, W.P.C.; Broekgaarden, R.

2010-01-01

This article investigates to what extent patient advocacy organisations play a role in influencing R&D and policymaking for rare neuromuscular diseases. The Dutch neuromuscular disease organisation VSN is studied in depth. A brief history of the VSN is sketched along with the international

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

Science.gov (United States)

Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

2017-10-06

Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. The e

Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation

OpenAIRE

Ng, Yi Shiau; Hardy, Steven A.; Shrier, Venice; Quaghebeur, Gerardine; Mole, David R.; Daniels, Matthew J.; Downes, Susan M.; Freebody, Jane; Fratter, Carl; Hofer, Monika; Nemeth, Andrea H.; Poulton, Joanna; Taylor, Robert W.

2016-01-01

Mitochondrial DNA disease is one of the most common groups of inherited neuromuscular disorders and frequently associated with marked phenotypic and genotypic heterogeneity. We describe an adult patient who initially presented with childhood-onset ataxia without a family history and an unremarkable diagnostic muscle biopsy. Subsequent multi-system manifestations included basal ganglia calcification, proteinuria, cataract and retinitis pigmentosa, prompting a repeat muscle biopsy that showed f...

Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

Science.gov (United States)

Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

2015-07-01

Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Medical back belt with integrated neuromuscular electrical stimulation

NARCIS (Netherlands)

Bottenberg, E. (Eliza); Brinks, G.J. (Ger); Hesse, J. (Jenny)

2014-01-01

The medical back belt with integrated neuromuscular electrical stimulation is anorthopedic device, which has two main functions. The first function is to stimulate the backmuscles by using a neuromuscular electrical stimulation device that releases regular,electrical impulses. The second function of

Inheritance versus parameterization

DEFF Research Database (Denmark)

Ernst, Erik

2013-01-01

This position paper argues that inheritance and parameterization differ in their fundamental structure, even though they may emulate each other in many ways. Based on this, we claim that certain mechanisms, e.g., final classes, are in conflict with the nature of inheritance, and hence causes...

Diagnosis of rare inherited glyoxalate metabolic disorders through in-situ analysis of renal stones

Science.gov (United States)

Jacob, D. E.; Grohe, B.; Hoppe, B.; Beck, B. B.; Tessadri, R.

2012-04-01

The primary hyperoxalurias type I - III constitute rare autosomal-recessive inherited disorders of the human glyoxylate metabolism. By mechanisms that are ill understood progressive nephrocalcinosis and recurrent urolithiasis (kidney stone formation) often starting in early childhood, along with their secondary complications results in loss of nephron mass which progresses to end-stage renal failure over time. In the most frequent form, end-stage renal failure (ESRF) is the rule and combined liver/kidney transplantation respectively pre-emptive liver transplantation are the only causative treatment today. Hence, this contributes significantly to healthcare costs and early diagnosis is extremely important for a positive outcome for the patient. We are developing a stone-based diagnostic method by in-detail multi-methods investigation of the crystalline moiety in concert with urine and stone proteomics. Stone analysis will allow faster analysis at low-impact for the patients in the early stages of the disease. First results from combined spectroscopic (Raman, FTIR)and geochemical micro-analyses (Electron Microprobe and Laser Ablation ICP-MS) are presented here that show significant differences between stones from hyperoxaluria patients and those formed by patients without this disorder (idiopathic stones). Major differences exist in chemistry as well as in morphology and phase composition of the stones. Ca/P ratios and Mg contents differentiate between oxalate-stones from hyperoxaluria patients and idiopathic stones. Results show that also within the different subtypes of primary hyperoxaluria significant differences can be found in stone composition. These imply differences in stone formation which could be exploited for new therapeutic pathways. Furthermore, the results provide important feedback for suspected but yet unconfirmed cases of primary hyperoxaluria when used in concert with the genetic methods routinely applied.

Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

Science.gov (United States)

Sloan, Paul A; Rasul, Mazhar

2002-01-01

We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

Noninvasive Respiratory Management of Patients With Neuromuscular Disease.

Science.gov (United States)

Bach, John R

2017-08-01

This review article describes definitive noninvasive respiratory management of respiratory muscle dysfunction to eliminate need to resort to tracheotomy. In 2010 clinicians from 22 centers in 18 countries reported 1,623 spinal muscular atrophy type 1 (SMA1), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis users of noninvasive ventilatory support (NVS) of whom 760 required it continuously (CNVS). The CNVS sustained their lives by over 3,000 patient-years without resort to indwelling tracheostomy tubes. These centers have now extubated at least 74 consecutive ventilator unweanable patients with DMD, over 95% of CNVS-dependent patients with SMA1, and hundreds of others with advanced neuromuscular disorders (NMDs) without resort to tracheotomy. Two centers reported a 99% success rate at extubating 258 ventilator unweanable patients without resort to tracheotomy. Patients with myopathic or lower motor neuron disorders can be managed noninvasively by up to CNVS, indefinitely, despite having little or no measurable vital capacity, with the use of physical medicine respiratory muscle aids. Ventilator-dependent patients can be decannulated of their tracheostomy tubes.

Effects of napping on neuromuscular fatigue in myasthenia gravis.

Science.gov (United States)

Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

2013-11-01

The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

Thyroid-related neurological disorders and complications in children.

Science.gov (United States)

Nandi-Munshi, Debika; Taplin, Craig E

2015-04-01

Thyroid hormones exert critical roles throughout the body and play an important and permissive role in neuroendocrine, neurological, and neuromuscular function. We performed a PubMed search through June 2014 with search terms including "hypothyroidism," "hyperthyroidism," "neurological complications," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy." Relevant publications reviewed included case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials. The neurological outcomes of congenital hypothyroidism were reviewed, along with the clinical features of associated neuromuscular syndromes of both hypothyroidism and hyperthyroidism, including other autoimmune conditions. Evidence for, and pathophysiological controversies surrounding, Hashimoto encephalopathy was also reviewed. The establishment of widespread newborn screening programs has been highly successful in attenuating or preventing early and irreversible neurological harm resulting from congenital thyroid hormone deficiency, but some children continue to display neuromuscular, sensory, and cognitive defects in later life. Acquired disorders of thyroid function such as Hashimoto thyroiditis and Graves' disease are associated with a spectrum of central nervous system and/or neuromuscular dysfunction. However, considerable variation in clinical phenotype is described, and much of our knowledge of the role of thyroid disease in childhood neurological disorders is derived from adult case series. Early and aggressive normalization of thyroxine levels in newborn infants with congenital hypothyroidism is important in minimizing neurological sequelae, but maternal thyroid hormone sources are also critically important to the early developing brain. A spectrum of neurological disorders has been reported in older children with acquired thyroid disease, but the frequency with which these occur remains poorly defined in the literature, and

The heart and cardiac pacing in Steinert disease

OpenAIRE

NIGRO, GERARDO; PAPA, ANDREA ANTONIO; POLITANO, LUISA

2012-01-01

Myotonic dystrophy (Dystrophia Myotonica, DM) is the most frequently inherited neuromuscular disease of adult life. It is a multisystemic disease with major cardiac involvement. Core features of myotonic dystrophy are myotonia, muscle weakness, cataract, respiratory failure and cardiac conduction abnormalities. Classical DM, first described by Steinert and called Steinert's disease or DM1 (Dystrophia Myotonica type 1) has been identified as an autosomal dominant disorder associated with the p...

Epidemiology of ocular disorders presumed to be inherited in three large Italian dog breeds in Italy.

Science.gov (United States)

Guandalini, Adolfo; Di Girolamo, Nicola; Santillo, Daniele; Andreani, Valentina; Corvi, Roberta; Bandini, Marina; Peruccio, Claudio

2017-09-01

To describe the epidemiology and the types of eye disorders that are presumed to be inherited (PIED) in three large Italian dog breeds. Three large Italian dog breeds: Neapolitan Mastiff (FCI code: 197), Maremma Sheepdog (FCI code: 201), and Italian Corso dog (FCI code: 343). All dogs that underwent a complete ophthalmic examination between 1992 and 2012 were included in this prospective observational study. The prevalence of eye disorders with 95% confidence intervals was reported for presumed healthy dogs and for dogs referred to a veterinary center for an ophthalmic consultation. Univariate and multivariate logistic regression techniques were used to generate odds ratios. Of 605 dogs examined during the study period, 351 dogs were affected by at least one PIED (58%; 95% CI: 54-62%). The prevalence of PIED was significantly lower in dogs presented for ophthalmic examination (53.8%) as compared to presumed healthy dogs (62.2%)(OR: 1.4; 95% CI: 1.02-1.9; P = 0.037). Also after multivariate adjustment for the period of observation, the odds of Neapolitan Mastiff (92.1%; OR: 21.4; 95% CI: 11.1-41.4) and of Cane Corso (57.7%; OR: 2.5; 95% CI: 1.7-3.6) suffering a PIED were greater than the Maremma Sheepdog (35.4%). The most common PIED in each breed were entropion (24.3% of all the PIED) in the Neapolitan Mastiff, ectropion (36.6%) in the Corso dog, and cataract (27.9%) in the Maremma Sheepdog. Clinicians should be aware that three large Italian dog breeds frequently suffer PIED. Breed standards should be reconsidered, and breeding programs should be directed at limiting such disorders. © 2016 American College of Veterinary Ophthalmologists.

Neuromuscular control of prey capture in frogs.

OpenAIRE

Nishikawa, K C

1999-01-01

While retaining a feeding apparatus that is surprisingly conservative morphologically, frogs as a group exhibit great variability in the biomechanics of tongue protraction during prey capture, which in turn is related to differences in neuromuscular control. In this paper, I address the following three questions. (1) How do frog tongues differ biomechanically? (2) What anatomical and physiological differences are responsible? (3) How is biomechanics related to mechanisms of neuromuscular cont...

Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.

Science.gov (United States)

Tenforde, Adam S; Shull, Pete B; Fredericson, Michael

2012-05-01

Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

[Characteristics of neuromuscular scoliosis].

Science.gov (United States)

Putzier, M; Groß, C; Zahn, R K; Pumberger, M; Strube, P

2016-06-01

Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research.

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

Science.gov (United States)

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

Psychosocial impact of inherited and autoimmune blistering diseases

Directory of Open Access Journals (Sweden)

Swaranjali V. Jain, B Med Sci (Hons MD

2018-03-01

Full Text Available Inherited and autoimmune blistering diseases are rare, chronic, and often severe disorders that have the potential to significantly affect patients’ quality of life. The effective management of these conditions requires consideration of the physical, emotional, and social aspects of the disease. Self-esteem is integral to patients’ ability to cope with their illness, participate in treatment, and function in society. This article discusses quality-of-life studies of patients with blistering diseases with a particular focus on self-esteem issues that patients may face.

"Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

Directory of Open Access Journals (Sweden)

Hai-peng Huang

2016-01-01

Full Text Available Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10, Zusanli (ST36, Pishu (BL20, and Shenshu (BL23 once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

Atypical mitochondrial inheritance patterns in eukaryotes.

Science.gov (United States)

Breton, Sophie; Stewart, Donald T

2015-10-01

Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

Síndrome de Tako-Tsubo em decorrência de bloqueio neuromuscular residual: relato de caso Síndrome de Tako-Tsubo como consecuencia de bloqueo neuromuscular residual: relato de caso Tako-Tsubo syndrome secondary to residual neuromuscular blockade: case report

Directory of Open Access Journals (Sweden)

Marcos Guilherme Cunha Cruvinel

2008-12-01

neuromuscular residual. RELATO DEL CASO: Paciente del sexo femenino, 61 años, estado físico ASA I, sometida a la anestesia general asociada al bloqueo paravertebral cervical para la reparación artroscópica de lesión de manguito de los rotadores. Después de la extubación, quedó demostrado el bloqueo neuromuscular residual a través del examen clínico. En la sala de recuperación postanestésica, evolucionó con somnolencia, taquicardia, hipertensión arterial y acidosis respiratoria grave. Después de la reintubación evolucionó con parada cardíaca en actividad eléctrica sin pulso, revertida con adrenalina y masaje cardíaco externo. En el postoperatorio presentó una elevación de segmento ST, aumento de troponina y acinesia de segmento medio-apical del ventrículo izquierdo, con fracción de eyección estimada en un 30%. La cineangiocoronariografía mostró coronarias exentas de ateromatosis significativa y un grave comprometimiento de la función sistólica con acinesia inferior y ántero-septo-apical, con hipercontratilidad compensatoria de sus porciones basales. Con el tratamiento iniciado, hubo una recuperación funcional completa. CONCLUSIONES: El bloqueo neuromuscular residual asociado a la parálisis diafragmática y la posible atelectasia pulmonar, que conlleva a la insuficiencia respiratoria, hipercapnia y descarga adrenérgica, fueron los factores desencadenantes del síndrome de Tako-Tsubo con su grave repercusión clínica.BACKGROUND AND OBJECTIVES: Tako-Tsubo syndrome is a rare postoperative complication with a 5% mortality rate. The objective of this report was to present residual neuromuscular blockade as a trigger for this syndrome, discuss this disorder, and call attention to the risks of residual neuromuscular blockade. CASE REPORT: A 61-year old female, physical status ASA I, who underwent general anesthesia associated with paravertebral cervical block for arthroscopic repair of a rotator cuff lesion. Physical exam after extubation detected

Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

Directory of Open Access Journals (Sweden)

Stefan Hettwer

Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance

DEFF Research Database (Denmark)

Dibbens, Leanne M; Mullen, Saul; Helbig, Ingo

2009-01-01

Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We...... then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%) unrelated cases of IGE using quantitative PCR or SNP arrays...... and confirmed by array comparative genomic hybridization analysis using probes specific to the 15q13.3 region. The inheritance of this lesion was tracked using family studies. Of the seven microdeletions identified in probands, three were de novo, two were transmitted from an unaffected parent and in two cases...

The RNAi Inheritance Machinery of Caenorhabditis elegans.

Science.gov (United States)

Spracklin, George; Fields, Brandon; Wan, Gang; Becker, Diveena; Wallig, Ashley; Shukla, Aditi; Kennedy, Scott

2017-07-01

Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in Caenorhabditis elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4 The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1 Together, our results identify additional components of the RNAi inheritance machinery whose conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality. Copyright © 2017 by the Genetics Society of America.

Safe Dynamic Multiple Inheritance

DEFF Research Database (Denmark)

Ernst, Erik

2002-01-01

Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

Science.gov (United States)

Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

2016-06-01

Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent advances in neuromuscular block during anesthesia [version 1; referees: 4 approved

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Martijn Boon

2018-02-01

Full Text Available Muscle relaxation is a routine part of anesthesia and has important advantages. However, the lingering effects of muscle relaxants in the postoperative period have historically been associated with postoperative adverse events. Neuromuscular reversal, together with neuromuscular monitoring, is a recognized strategy to reduce the rate of postoperative residual relaxation but has only marginally improved outcome in the past few decades. Sugammadex, a novel reversal agent with unique encapsulating properties, has changed the landscape of neuromuscular reversal and opened up new opportunities to improve patient care. By quickly and completely reversing any depth of neuromuscular block, it may reduce the rate of residual relaxation and improve respiratory recovery. In addition, sugammadex has made the use of deep neuromuscular block possible during surgery. Deep neuromuscular block may improve surgical working conditions and allow for a reduction in insufflation pressures during selected laparoscopic procedures. However, whether and how this may impact outcomes is not well established.

Recent achievements in restorative neurology: Progressive neuromuscular diseases

International Nuclear Information System (INIS)

Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

1986-01-01

This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report

Directory of Open Access Journals (Sweden)

Parker Stephen W

2005-02-01

gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders.

Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

Science.gov (United States)

de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

1993-01-01

To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

The relative frequency of common neuromuscular diagnoses in a reference center

OpenAIRE

Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista Junior, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

2017-01-01

ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded confir...

Inheritance is Specialisation

DEFF Research Database (Denmark)

Torgersen, Mads

2002-01-01

How can we get a simpler but much more general subclass construct? This position paper takes a "specialisationist" approach to inheritance. Old SIMULA virtues are restored to prominence, but boiled with new unificational ingredients to obtain a substrate of specialisation. Ever since the advent...... of Smalltalk there has been a strong tension in the object-oriented community between two opposing views of the role of inheritance: as an incremental modification mechanism or as a vehicle for conceptual modelling. Madsen [5] and many others characterise the two approaches as the “American ” and “Scandinavian......” schools, respectively. Nowadays, such a geographical terminology hardly remains valid (if ever it was), but the tension remains: should we strive for maximal flexibility of inheritance, to improve the possibilities for later unanticipated reuse, or should we attend above all to the conceptual integrity...

A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

Science.gov (United States)

Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

2016-06-01

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

Directory of Open Access Journals (Sweden)

Peter C Rowe

Full Text Available Chronic fatigue syndrome (CFS is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04 and concentration difficulties (P = 0.02 as well as increased composite symptom scores (all P = 0.03 during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001 and for the composite symptom score (P = 0.005. During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical

Neurologic disorders of mineral metabolism and parathyroid disease.

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Agrawal, Lily; Habib, Zeina; Emanuele, Nicholas V

2014-01-01

Disorders of mineral metabolism may cause neurologic manifestations of the central and peripheral nervous systems. This is because plasma calcium stabilizes excitable membranes in the nerve and muscle tissue, magnesium is predominantly intracellular and is required for activation of many intracellular enzymes, and extracellular magnesium affects synaptic transmission. This chapter reviews abnormalities in electrolytes and minerals which can be associated with several neuromuscular symptoms including neuromuscular irritability, mental status changes, cardiac and smooth muscle changes, etc. © 2014 Elsevier B.V. All rights reserved.

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

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Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

Imaging of respiratory muscles in neuromuscular disease: A review.

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Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

2018-03-01

Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

Total hip arthroplasty in patients with neuromuscular imbalance.

Science.gov (United States)

Konan, S; Duncan, C P

2018-01-01

Patients with neuromuscular imbalance who require total hip arthroplasty (THA) present particular technical problems due to altered anatomy, abnormal bone stock, muscular imbalance and problems of rehabilitation. In this systematic review, we studied articles dealing with THA in patients with neuromuscular imbalance, published before April 2017. We recorded the demographics of the patients and the type of neuromuscular pathology, the indication for surgery, surgical approach, concomitant soft-tissue releases, the type of implant and bearing, pain and functional outcome as well as complications and survival. Recent advances in THA technology allow for successful outcomes in these patients. Our review suggests excellent benefits for pain relief and good functional outcome might be expected with a modest risk of complication. Cite this article: Bone Joint J 2018;100-B(1 Supple A):17-21. ©2018 The British Editorial Society of Bone & Joint Surgery.

Neuromuscular function during a forward lunge in meniscectomized patients

DEFF Research Database (Denmark)

Thorlund, Jonas Bloch; Damgaard, Jacob; Roos, Ewa M.

2012-01-01

This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients....... Such differences may represent early changes in neuromuscular function potentially contributing to the development of knee osteoarthritis....

Neuromuscular dentistry: Occlusal diseases and posture.

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Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

2013-01-01

Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture.

Inherited and predisposing factors in the development of gastric dilatation volvulus in dogs.

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Bell, Jerold S

2014-09-01

This review article summarizes what is known as well as what is undetermined concerning the inherited and environmental pathogenesis of gastric dilatation volvulus in dogs. The disorder primarily affects large and giant, deep-chested breeds. A concise description of a typical dog affected with gastric dilatation volvulus is presented. Copyright © 2014 Elsevier Inc. All rights reserved.

Inherited renal tubular defects with hypokalemia

Directory of Open Access Journals (Sweden)

Muthukrishnan J

2009-01-01

Full Text Available Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter′s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman′s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Reilly, Mary M

2011-03-01

Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder affecting at least 1 in 2,500. Over the last two decades, there have been rapid advances in understanding the molecular basis for many forms of CMT with more than 30 causative genes now described. This has made obtaining an accurate genetic diagnosis possible but at times challenging for clinicians. This review aims to provide a simple, pragmatic approach to diagnosing CMT from a clinician\\'s perspective.

Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

DEFF Research Database (Denmark)

Viby-Mogensen, J.; Østergaard, D.; Donati, F.

2000-01-01

Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

The role of proprioception and neuromuscular stability in carpal instabilities.

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Hagert, E; Lluch, A; Rein, S

2016-01-01

Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

Old diseases and contemporary crisis. Inherited blood disorders in the Sultanate of Oman.

Science.gov (United States)

Beaudevin, Claire

2013-01-01

This contribution draws on ethnographic research conducted in Oman on inherited blood disorders (IBD). By interpreting results from population genomics studies that trace mutation processes over centuries of human activities, lay-representations of IBD often consider them historical evidence. The perceived spread of IBD in Oman may thus provide unusual historical depth in a country where past conflicts have been erased from historiography and representations of time are politically prescribed. Through the notions of crisis and diversification, this contribution shows how IBD's chronicity challenges the healthcare system and became a national issue, politically labelled as urgent. The paper casts light on several aspects of contemporary Omani society: it first addresses the dynamics of disease taxonomies - although biomedically described in the early twentieth century, IBD were not individualized within local nosologies until the 1970s. Secondly, it shows how biomedical knowledge about IBD led to diversification within the healthcare system, through the introduction of clinical genetics, genomics, and community genetics. Thirdly, it attempts to broach modalities of the biopower exerted by the Omani regime over its citizens: IBD are targeted by various public health measures that jeopardize patients' autonomy by aiming to control their bodies through their matrimonial behaviour. In addition, two aspects of the intersections between Omani social hierarchy and IBD are noteworthy: the creation of a patients' association that constitutes a potential disturbance of the social order; and the way IBD mutations traced by genomics are considered direct historical documents that challenge representations of the recently crafted 'Omanity' in a context of regional concern regarding national identities' durability.

Spinal Muscular Atrophy: From Defective Chaperoning of snRNP Assembly to Neuromuscular Dysfunction

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Maia Lanfranco

2017-06-01

Full Text Available Spinal Muscular Atrophy (SMA is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN protein. SMN is part of a multiprotein complex that also includes Gemins 2–8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5 complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs to generate small nuclear ribonucleoproteins (snRNPs, which are the operating components of the spliceosome. Molecular and structural studies have refined our knowledge of the key events taking place within the crowded environment of cells and the numerous precautions undertaken to ensure the faithful assembly of snRNPs. Nonetheless, it remains unclear whether a loss of chaperoning in snRNP assembly, considered as a “housekeeping” activity, is responsible for the selective neuromuscular phenotype in SMA. This review thus shines light on in vivo studies that point toward disturbances in snRNP assembly and the consequential transcriptome abnormalities as the primary drivers of the progressive neuromuscular degeneration underpinning the disease. Disruption of U1 snRNP or snRNP assembly factors other than SMN induces phenotypes that mirror aspects of SMN deficiency, and splicing defects, described in numerous SMA models, can lead to a DNA damage and stress response that compromises the survival of the motor system. Restoring the correct chaperoning of snRNP assembly is therefore predicted to enhance the benefit of SMA therapeutic modalities based on augmenting SMN expression.

The evolutionary implications of epigenetic inheritance.

Science.gov (United States)

Jablonka, Eva

2017-10-06

The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

Treatment strategies for inherited optic neuropathies: past, present and future

OpenAIRE

Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

2014-01-01

Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain...

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

Science.gov (United States)

Choi, Chang Soon; Gonzales, Edson Luck; Kim, Ki Chan; Yang, Sung Min; Kim, Ji-Woon; Mabunga, Darine Froy; Cheong, Jae Hoon; Han, Seol-Heui; Bahn, Geon Ho; Shin, Chan Young

2016-11-07

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

Science.gov (United States)

Zarrei, Mehdi; Fehlings, Darcy L; Mawjee, Karizma; Switzer, Lauren; Thiruvahindrapuram, Bhooma; Walker, Susan; Merico, Daniele; Casallo, Guillermo; Uddin, Mohammed; MacDonald, Jeffrey R; Gazzellone, Matthew J; Higginbotham, Edward J; Campbell, Craig; deVeber, Gabrielle; Frid, Pam; Gorter, Jan Willem; Hunt, Carolyn; Kawamura, Anne; Kim, Marie; McCormick, Anna; Mesterman, Ronit; Samdup, Dawa; Marshall, Christian R; Stavropoulos, Dimitri J; Wintle, Richard F; Scherer, Stephen W

2018-02-01

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

Surgical Space Conditions During Low-Pressure Laparoscopic Cholecystectomy with Deep Versus Moderate Neuromuscular Blockade

DEFF Research Database (Denmark)

Staehr-Rye, Anne K; Rasmussen, Lars S.; Rosenberg, Jacob

2014-01-01

: In this assessor-blinded study, 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade (rocuronium bolus plus infusion maintaining a posttetanic count 0-1) or moderate neuromuscular blockade...... (rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function). Patients received anesthesia with propofol, remifentanil, and rocuronium. The primary outcome was the proportion of procedures with optimal surgical space conditions (assessed by the surgeon...

Neuromuscular exercise as treatment of degenerative knee disease

DEFF Research Database (Denmark)

Ageberg, Eva; Roos, Ewa M.

2015-01-01

Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional...... instability associated with the degenerative knee disease than traditionally used training methods.SUMMARY FOR TABLE OF CONTENTS PAGECurrent data suggests that the effect from neuromuscular exercise on pain and function is comparable to the effects seen from other forms of exercise....

MAPPIN: a method for annotating, predicting pathogenicity and mode of inheritance for nonsynonymous variants.

Science.gov (United States)

Gosalia, Nehal; Economides, Aris N; Dewey, Frederick E; Balasubramanian, Suganthi

2017-10-13

Nonsynonymous single nucleotide variants (nsSNVs) constitute about 50% of known disease-causing mutations and understanding their functional impact is an area of active research. Existing algorithms predict pathogenicity of nsSNVs; however, they are unable to differentiate heterozygous, dominant disease-causing variants from heterozygous carrier variants that lead to disease only in the homozygous state. Here, we present MAPPIN (Method for Annotating, Predicting Pathogenicity, and mode of Inheritance for Nonsynonymous variants), a prediction method which utilizes a random forest algorithm to distinguish between nsSNVs with dominant, recessive, and benign effects. We apply MAPPIN to a set of Mendelian disease-causing mutations and accurately predict pathogenicity for all mutations. Furthermore, MAPPIN predicts mode of inheritance correctly for 70.3% of nsSNVs. MAPPIN also correctly predicts pathogenicity for 87.3% of mutations from the Deciphering Developmental Disorders Study with a 78.5% accuracy for mode of inheritance. When tested on a larger collection of mutations from the Human Gene Mutation Database, MAPPIN is able to significantly discriminate between mutations in known dominant and recessive genes. Finally, we demonstrate that MAPPIN outperforms CADD and Eigen in predicting disease inheritance modes for all validation datasets. To our knowledge, MAPPIN is the first nsSNV pathogenicity prediction algorithm that provides mode of inheritance predictions, adding another layer of information for variant prioritization. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Inheritance conditions for object life cycle diagrams

NARCIS (Netherlands)

Lipeck, U.W.; Saake, Gunter; Hartel, Peter; Vossen, G.; Jungclaus, Ralf; Wieringa, Roelf J.; Feenstra, Remco

Inheritance is the main principle in object-oriented design methods to support structuring and reuse of object behaviour descriptions. Most proposals restrict the formal use of inheritance to method interfaces and method effect specifcations. We propose to extend the inheritance relation to cover

A three-generation family with idiopathic facial palsy suggesting an autosomal dominant inheritance with high penetrance

DEFF Research Database (Denmark)

Larsen, Christian Grønhøj; Gyldenløve, Mette; Jønch, Aia Elise

2015-01-01

Idiopathic facial palsy (IFP), also known as Bell's palsy, is a common neurologic disorder, but recurrent and familial forms are rare. This case series presents a three-generation family with idiopathic facial palsy. The mode of inheritance of IFP has previously been suggested as autosomal dominant...

Current perspectives on mitochondrial inheritance in fungi

Directory of Open Access Journals (Sweden)

Xu J

2015-08-01

Full Text Available Jianping Xu,1,2 He Li2 1Department of Biology, McMaster University, Hamilton, Canada; 2The Key Laboratory for Non-Wood Forest Cultivation and Conservation of the Federal Ministry of Education, Central South University of Forestry and Technology, Changsha, People’s Republic of China Abstract: The mitochondrion is an essential organelle of eukaryotes, generating the universal energy currency, adenosine triphosphate, through oxidative phosphorylation. However, aside from generation of adenosine triphosphate, mitochondria have also been found to impact a diversity of cellular functions and organ system health in humans and other eukaryotes. Thus, inheriting and maintaining functional mitochondria are essential for cell health. Due to the relative ease of conducting genetic and molecular biological experiments using fungi, they (especially the budding yeast Saccharomyces cerevisiae have been used as model organisms for investigating the patterns of inheritance and intracellular dynamics of mitochondria and mitochondrial DNA. Indeed, the diversity of mitochondrial inheritance patterns in fungi has contributed to our broad understanding of the genetic, cellular, and molecular controls of mitochondrial inheritance and their evolutionary implications. In this review, we briefly summarize the patterns of mitochondrial inheritance in fungi, describe the genes and processes involved in controlling uniparental mitochondrial DNA inheritance in sexual crosses in basidiomycete yeasts, and provide an overview of the molecular and cellular processes governing mitochondrial inheritance during asexual budding in S. cerevisiae. Together, these studies reveal that complex regulatory networks and molecular processes are involved in ensuring the transmission of healthy mitochondria to the progeny. Keywords: uniparental inheritance, biparental inheritance, mating type, actin cable, mitochore, mitochondrial partition 

Neuromuscular adaptations to training, injury and passive interventions: implications for running economy.

Science.gov (United States)

Bonacci, Jason; Chapman, Andrew; Blanch, Peter; Vicenzino, Bill

2009-01-01

Performance in endurance sports such as running, cycling and triathlon has long been investigated from a physiological perspective. A strong relationship between running economy and distance running performance is well established in the literature. From this established base, improvements in running economy have traditionally been achieved through endurance training. More recently, research has demonstrated short-term resistance and plyometric training has resulted in enhanced running economy. This improvement in running economy has been hypothesized to be a result of enhanced neuromuscular characteristics such as improved muscle power development and more efficient use of stored elastic energy during running. Changes in indirect measures of neuromuscular control (i.e. stance phase contact times, maximal forward jumps) have been used to support this hypothesis. These results suggest that neuromuscular adaptations in response to training (i.e. neuromuscular learning effects) are an important contributor to enhancements in running economy. However, there is no direct evidence to suggest that these adaptations translate into more efficient muscle recruitment patterns during running. Optimization of training and run performance may be facilitated through direct investigation of muscle recruitment patterns before and after training interventions. There is emerging evidence that demonstrates neuromuscular adaptations during running and cycling vary with training status. Highly trained runners and cyclists display more refined patterns of muscle recruitment than their novice counterparts. In contrast, interference with motor learning and neuromuscular adaptation may occur as a result of ongoing multidiscipline training (e.g. triathlon). In the sport of triathlon, impairments in running economy are frequently observed after cycling. This impairment is related mainly to physiological stress, but an alteration in lower limb muscle coordination during running after cycling

Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

Directory of Open Access Journals (Sweden)

Ximena Paez-Colasante

Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

Robotic assessment of neuromuscular characteristics using musculoskeletal models: A pilot study.

Science.gov (United States)

Jayaneththi, V R; Viloria, J; Wiedemann, L G; Jarrett, C; McDaid, A J

2017-07-01

Non-invasive neuromuscular characterization aims to provide greater insight into the effectiveness of existing and emerging rehabilitation therapies by quantifying neuromuscular characteristics relating to force production, muscle viscoelasticity and voluntary neural activation. In this paper, we propose a novel approach to evaluate neuromuscular characteristics, such as muscle fiber stiffness and viscosity, by combining robotic and HD-sEMG measurements with computational musculoskeletal modeling. This pilot study investigates the efficacy of this approach on a healthy population and provides new insight on potential limitations of conventional musculoskeletal models for this application. Subject-specific neuromuscular characteristics of the biceps and triceps brachii were evaluated using robot-measured kinetics, kinematics and EMG activity as inputs to a musculoskeletal model. Repeatability experiments in five participants revealed large variability within each subjects evaluated characteristics, with almost all experiencing variation greater than 50% of full scale when repeating the same task. The use of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to quantify neuromuscular characteristics has been explored. Despite the ability to predict joint kinematics with relatively high accuracy, parameter characterization was inconsistent i.e. many parameter combinations gave rise to minimal kinematic error. The proposed technique is a novel approach for in vivo neuromuscular characterization and is a step towards the realization of objective in-home robot-assisted rehabilitation. Importantly, the results have confirmed the technical (robot and HD-sEMG) feasibility while highlighting the need to develop new musculoskeletal models and optimization techniques capable of achieving consistent results across a range of dynamic tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Respiratory treatments in neuromuscular disease].

Science.gov (United States)

Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

2014-10-01

In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

The maturational theory of brain development and cerebral excitability in the multifactorially inherited manic-depressive psychosis and schizophrenia.

Science.gov (United States)

Saugstad, L F

1994-12-01

An association has been established between the multifactorially inherited rate of physical maturation and the final step in brain development, when some 40% of synapses are eliminated. This may imply that similarly to endocrine disease entities, we have cerebral disease entities at the extremes of the maturational rate continuum. The restriction of prepubertal pruning to excitatory synapses leaving the number of inhibitory ones fairly constant, implies changes in cerebral excitability as a function of rate of maturation (age at puberty). In early maturation there will be an excess in excitatory drive due to prematurely abridged pruning, which compounds a synchronization tendency inherent in excessive synaptic density. Lowering excitatory level with antiepileptics is hypothesized to be a logical treatment in this type of brain dysfunction. In late maturation, a deficit in excitatory drive due to failure to shut down the pruning process associated with a tendency to the breakdown of circuitry and desynchronization, adds to a similar adversity inherent in reduced synaptic density. Raising the excitatory level with convulsants is hypothesized to be the treatment for this type of CNS dysfunction. The maturational theory of Kraepelin's psychoses holds that they are naturally occurring contrasting chemical signaling disorders in the brain at the extremes of the maturational rate continuum: manic depressive psychosis is a disorder of the early maturer and comprises raised cerebral excitability and a raised density of synapses. This is successfully treated with anti-epileptics like sodium valproate and carbamazepin. Schizophrenia is a disorder in late maturation with reduced cerebral excitability and reduced synaptic density. This is accordingly treated with convulsants such as typical and atypical neuroleptics. However, the conventional effective treatments in both disorders act on inhibition only by either lowering or raising inhibitory level. While the neuroleptics

DNA mutation motifs in the genes associated with inherited diseases.

Directory of Open Access Journals (Sweden)

Michal Růžička

Full Text Available Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs rarely associated with mutations (coldspots and frequently associated with mutations (hotspots exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

Neuromuscular Exercise Post Partial Medial Meniscectomy

DEFF Research Database (Denmark)

Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

2015-01-01

PURPOSE: To evaluate the effects of a 12-week, home-based, physiotherapist-guided neuromuscular exercise program on the knee adduction moment (an indicator of mediolateral knee load distribution) in people with a medial arthroscopic partial meniscectomy within the past 3-12 months. METHODS......: An assessor-blinded, randomised controlled trial including people aged 30-50 years with no to mild pain following medial arthroscopic partial meniscectomy was conducted. Participants were randomly allocated to either a 12-week neuromuscular exercise program that targeted neutral lower limb alignment...... or a control group with no exercise. The exercise program included eight individual sessions with one of seven physiotherapists in private clinics, together with home exercises. Primary outcomes were the peak external knee adduction moment during normal pace walking and during a one-leg sit-to-stand. Secondary...

Effect of Early Physical Activity Programs on Motor Performance and Neuromuscular Development in Infants Born Preterm: A Randomized Clinical Trial

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Leila Valizadeh

2017-03-01

Full Text Available Introduction: Although the survival rate of infants born preterm has increased, the prevalence of developmental problems and motor disorders among this population of infants remains the same. This study investigated the effect of physical activity programs in and out of water on motor performance and neuromuscular development of infants born preterm and had induced immobility by mechanical ventilation.Methods: This study was carried out in Al-Zahra hospital, Tabriz. 76 premature infants were randomly assigned into four groups. One group received daily passive range of motion to all extremities based on the Moyer-Mileur protocol. Hydrotherapy group received exercises for shoulders and pelvic area in water every other day. A combination group received physical activity programs in and out of water on alternating days. Infants in a containment group were held in a fetal position. Duration of study was two weeks ‘from 32 through 33 weeks post menstrual age (PMA. Motor outcomes were measured by the Test of Infant Motor Performance. Neuromuscular developmental was assessed by New Ballard scale and leg recoil and Ankle dorsiflexion items from Dubowitz scale. Data were analyzed using SPSS version 13.Results: TIMP and neuromuscular scores improved in all groups. Motor performance did not differ between groups at 34 weeks PMA. Postural tone of leg recoil was significantly higher in physical activity groups post intervention.Conclusion: Physical activities and containment didn’t have different effects on motor performance in infants born preterm. Leg recoil of neuromuscular development items was affected by physical activity programs.

Accuracy of a Custom Physical Activity and Knee Angle Measurement Sensor System for Patients with Neuromuscular Disorders and Gait Abnormalities

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Frank Feldhege

2015-05-01

Full Text Available Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.

Classification of neuromuscular blocking agents in a new neuromuscular preparation of the chick in vitro

NARCIS (Netherlands)

Riezen, H. van

1968-01-01

A neuromuscular preparation of the chick is described: 1. 1. The sciatic nerve-tibilis anterior muscle preparation of the 2–10 days old chick fulfils all criteria of an assay preparation and differentiates between curare-like and decamethonium-like agents. 2. 2. The preparation responds to

Effects of sugammadex on incidence of postoperative residual neuromuscular blockade

DEFF Research Database (Denmark)

Brueckmann, B; Sasaki, N; Grobara, P

2015-01-01

BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed...... by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual...... measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch® SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P

25 CFR 91.9 - Inheritance of improvements.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in accordance...

Biparental chloroplast inheritance leads to rescue from cytonuclear incompatibility.

Science.gov (United States)

Barnard-Kubow, Karen B; McCoy, Morgan A; Galloway, Laura F

2017-02-01

Although organelle inheritance is predominantly maternal across animals and plants, biparental chloroplast inheritance has arisen multiple times in the angiosperms. Biparental inheritance has the potential to impact the evolutionary dynamics of cytonuclear incompatibility, interactions between nuclear and organelle genomes that are proposed to be among the earliest types of genetic incompatibility to arise in speciation. We examine the interplay between biparental inheritance and cytonuclear incompatibility in Campanulastrum americanum, a plant species exhibiting both traits. We first determine patterns of chloroplast inheritance in genetically similar and divergent crosses, and then associate inheritance with hybrid survival across multiple generations. There is substantial biparental inheritance in C. americanum. The frequency of biparental inheritance is greater in divergent crosses and in the presence of cytonuclear incompatibility. Biparental inheritance helps to mitigate cytonuclear incompatibility, leading to increased fitness of F 1 hybrids and recovery in the F 2 generation. This study demonstrates the potential for biparental chloroplast inheritance to rescue cytonuclear compatibility, reducing cytonuclear incompatibility's contribution to reproductive isolation and potentially slowing speciation. The efficacy of rescue depended upon the strength of incompatibility, with a greater persistence of weak incompatibilities in later generations. These findings suggest that incompatible plastids may lead to selection for biparental inheritance. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

Dengue-associated neuromuscular complications

OpenAIRE

Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

2015-01-01

Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives

Directory of Open Access Journals (Sweden)

Carron M

2017-12-01

Full Text Available Michele Carron, Francesco Bertoncello, Giovanna Ieppariello Department of Medicine, Anesthesiology, and Intensive Care, University of Padova, Padua, Italy Abstract: The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed. Keywords: sugammadex, aging, elderly, neuromuscular blockade, rocuronium, anesthesia, safety

Characterization of cervical neuromuscular response to head-neck perturbation in active young adults.

Science.gov (United States)

Alsalaheen, Bara; Bean, Ryan; Almeida, Andrea; Eckner, James; Lorincz, Matthew

2018-04-01

The majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response. Nineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: (1) Anticipated perturbation with no preload (A-NP), (2) Unanticipated perturbation with no preload (U-NP), (3) Anticipated perturbation with preload (A-P), and (4) Unanticipated perturbation with preload (U-P). None of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM. The findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ação neuro-muscular do veneno crotálico: dados preliminares Neuromuscular action of crotalid venom: preliminar data

Directory of Open Access Journals (Sweden)

Maria Dorvalina Silva

1996-03-01

Full Text Available Estudamos 6 pacientes, 2 cães e um coelho com intoxicação crotálica. Avaliamos a condução nervosa periférica sensitiva e motora, a transmissão neuromuscular e eletromiografias. As biópsias de músculo foram processadas por histoquímica. Os 6 pacientes apresentaram mononeuropatia sensitiva no nervo periférico adjacente ao local da inoculação do veneno e encontramos evidências histoquímicas de miopatia mitocondrial. Os defeitos da transmissão neuromuscular foram mínimos. A maioria dos autores admite que veneno crotálico determina síndrome miastênica. Nossos achados indicam que ptose palpebral, facies miastênico e fraqueza muscular observados após acidente crotálico, correspondem provavelmente a miopatia mitocondrial, muitas vezes transitória e reversível.We studied 6 patients and 2 dogs that have been bitten by South American rattlesnake Crotalus durissus terrificus and one rabbit inoculated with crotalid venom. We analized sensory and motor peripheral nerve conduction, repetitive stimulation for studying neuromuscular transmission and electromyographies. Muscle biopsies were processed by histochemistry. All patients had peripheral mononeuropathy of the closest sensitive nerve to the area of snakebite. The neuromuscular transmission alterations were minimal. Muscle histochemistry of 4 patients, 2 dogs and 1 rabbit showed findings of mitochondrial myopathy. The majority of authors admit that crotalid venom causes myastenic syndrome. Our findings suggest that palpebral ptosis, myastenic facies and muscular weakness observed after crotalid poisoning are, probably, due to transient and reversible mitochondrial myopathy. As far as we know, this is the first report on the ability of the venom of this rattlesnake to cause local sensitive mononeuropathy and the first muscle histochemistry showing mitochondrial myopathy in humans poisoned by crotalid venom.

Differentiating views of inheritance : The free association task as a method to assess social representations of wealth, inherit, and bequeath

NARCIS (Netherlands)

Stark, Jennifer; Kogler, C.; Gaisbauer, Helmut; Sedmak, Clemens; Kirchler, Erich

2016-01-01

Inheritance and in particular inheritance taxes have emerged as topics of steadily increasing interest in public as well as scientific discourse and debate. The present study investigates laypeople’s differentiated social representations of inheritance with the aim of shedding light on distinct

Cancer resistance as an acquired and inheritable trait

DEFF Research Database (Denmark)

Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

2014-01-01

AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer c...... of the resistance is unknown but may involve epigenetic mechanisms. Other examples of inheritability of acquired phenotypic changes exist but, to our knowledge, this is the first demonstration of acquired, inherited cancer resistance.......AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer...... cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype...

Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block

Neuromuscular transmission: new concepts and agents.

NARCIS (Netherlands)

Boer, H.D. de

2009-01-01

Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

The relative frequency of common neuromuscular diagnoses in a reference center.

Science.gov (United States)

Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

2017-11-01

The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. To report the relative frequency of common neuromuscular diagnoses in a reference center. A 17-year chart review of patients with suspicion of myopathy. Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

The relative frequency of common neuromuscular diagnoses in a reference center

Directory of Open Access Journals (Sweden)

Ana Cotta

Full Text Available ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98% yielded confirmatory results: 782 (48.78% underwent molecular studies, and 821 (51.21% had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%, mitochondriopathy 330 (20.59%, spinal muscular atrophy 158 (9.86%, limb girdle muscular dystrophy 157 (9.79%, Steinert myotonic dystrophy 138 (8.61%, facioscapulohumeral muscular dystrophy 99 (6.17%, and other diagnoses 261 (16.28%. Conclusion: Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives.

Science.gov (United States)

Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

2018-01-01

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed.

Neuromuscular fatigue and recovery profiles in individuals with intellectual disability

OpenAIRE

Borji , Rihab; Zghal , Firas; Zarrouk , Nidhal; Martin , Vincent; Sahli , Sonia; Rebai , Haithem

2017-01-01

International audience; Purpose: This study aimed to explore neuromuscular fatigue and recovery profiles in individuals with intellectual disability (ID) after exhausting submaximal contraction.Methods: Ten men with ID were compared to 10 men without ID. The evaluation of neuromuscular function consisted in brief (3 s) isometric maximal voluntary contraction (IMVC) of the knee extension superimposed with electrical nerve stimulation before, immediately after, and during 33 min after an exhaus...

Inheritance of tristyly in Oxalis tuberosa (Oxalidaceae).

Science.gov (United States)

Trognitz, B R; Hermann, M

2001-05-01

Frequencies of floral morphs in progenies obtained from a complete set of diallelic crosses among three accessions of tristylous, octoploid oca (Oxalis tuberosa) were used for a Mendelian analysis of floral morph inheritance. The frequencies observed had the best fit to a model of tetrasomic inheritance with two diallelic factors, S, s and M, m, with S being epistatic over M. No explanation could be found for the unexpected formation of a small percentage of short-styled individuals in crosses between the mid-styled and the long-styled parent. For the acceptance of models of disomic and octosomic inheritance several additional assumptions would have to be made and therefore these modes of inheritance are less likely. Dosage-dependent inheritance of floral morph was rejected. Only a small frequency (36%) of the cross progenies flowered, in contrast to the greater propensity for flowering of O. tuberosa accessions held at gene banks.

Sonographically guided percutaneous muscle biopsy in diagnosis of neuromuscular disease: a useful alternative to open surgical biopsy.

Science.gov (United States)

O'Sullivan, Paul J; Gorman, Grainne M; Hardiman, Orla M; Farrell, Michael J; Logan, P Mark

2006-01-01

The purpose of this study was to evaluate the feasibility of sonographically guided percutaneous muscle biopsy in the investigation of neuromuscular disorders. Sonographically guided percutaneous needle biopsy of skeletal muscle was performed with a 14-gauge core biopsy system in 40 patients over a 24-month period. Patients were referred from the Department of Neurology under investigation for neuromuscular disorders. Sonography was used to find suitable tissue and to avoid major vascular structures. A local anesthetic was applied below skin only. A 3- to 4-mm incision was made. Three 14-gauge samples were obtained from each patient. All samples were placed on saline-dampened gauze and sent for neuropathologic analysis. As a control, we retrospectively assessed results of the 40 most recent muscle samples acquired via open surgical biopsy. With the use of sonography, 32 (80%) of 40 patients had a histologic diagnosis made via percutaneous needle biopsy. This included 26 (93%) of 28 patients with acute muscular disease and 6 (50%) of 12 patients with chronic disease. In the surgical group (all acute disease), 38 (95%) of 40 patients had diagnostic tissue attained. Sonographically guided percutaneous 14-gauge core skeletal muscle biopsy is a useful procedure, facilitating diagnosis in acute muscular disease. It provides results comparable with those of open surgical biopsy in acute muscular disease. It may also be used in chronic muscular disease but repeated or open biopsy may be needed.

Childhood versus adulthood-onset autoinflammatory disorders: myths and truths intertwined

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L. Cantarini

2013-06-01

Full Text Available Autoinflammatory disorders are characterized by spontaneous episodes of systemic inflammation deriving from inherited defects of the innate immune system. Childhood is usually the lifetime involved in most inherited autoinflammatory disorders, but a moderate number of patients may experience disease onset during adulthood. Herein we report our experience in the clinical and genetic approach to the diagnosis of autoinflammatory disorders in regard of the first 500 pediatric and adult patients evaluated during the period 2007-2012 in our Center, due to histories of periodically-recurring inflammatory attacks, giving emphasis to the differences observed according to patients’age and to the most relevant data differentiating child and adult-onset autoinflammatory disorders in the medical literature.

SWJ:39-42 Inheritance of Pod Colour in Cowpea INHERITANCE

African Journals Online (AJOL)

Dr. Ahmed

two additional pod pigmentation genes; one conditions green pods ... Hybridization experiments were conducted in the screen house to study the pattern of inheritance of ... to breeders because its understanding could lead to the development.

Genetic reversion of inherited skin disorders

Energy Technology Data Exchange (ETDEWEB)

Magnaldo, Thierry; Sarasin, Alain

2002-11-30

Human epidermis is a squamous stratified epithelium whose integrity relies on balanced processes of cell attachment, proliferation, and differentiation. In monogenic skin dermatoses, such as mecano-bullous diseases, or DNA repair deficiencies such as the xeroderma pigmentosum (XP), alterations of skin integrity may have devastating consequences as illustrated by the extremely high epidermal cancer proneness of XP patients. The lack of efficient pharmacological treatments, the easy accessibility of skin, and the possibility of long term culture and genetic manipulations ex vivo of epidermal keratinocytes, have encouraged approaches toward gene transfer and skin therapy prospects. We review here some of the human genetic disorders that exhibit major traits in skin, as well as requirements and difficulties inherent to approaches aimed at stable phenotypic correction.

Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults

DEFF Research Database (Denmark)

Hristovska, Ana-Marija; Duch, Patricia; Allingstrup, Mikkel

2017-01-01

, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety......, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. OBJECTIVES: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents......-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. DATA...

Inheritance

OpenAIRE

Lippert, Sandra

2013-01-01

In ancient Egypt inheritance was conveyed either through the legal order of succession, favoring sonsover daughters, children over siblings, and older over younger, or through written declarations thatallowed for individualized arrangements. Adoption was the common means by which a childlessperson could acquire an heir. The initial tendency towards a sole heir (preferably the eldest son) wasreplaced by the division of parental property among all children, although the eldest son continued top...

Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

Directory of Open Access Journals (Sweden)

Alejandro Carbajal-Saucedo

2014-01-01

Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

Stunted PFC activity during neuromuscular control under stress with obesity.

Science.gov (United States)

Mehta, Ranjana K

2016-02-01

Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

Sugammadex Improves Neuromuscular Function in Patients ...

African Journals Online (AJOL)

2018-02-23

Feb 23, 2018 ... aminoglycosides), history of allergy to neuromuscular blocking agents, opioids or other drugs, and alcohol and drug dependence. Patients were divided into two ... titration microcalorimetry investigated the likelihood of the formation of complexes between sugammadex and other steroidal and nonsteroidal ...

Joint angle affects volitional and magnetically-evoked neuromuscular performance differentially.

Science.gov (United States)

Minshull, C; Rees, D; Gleeson, N P

2011-08-01

This study examined the volitional and magnetically-evoked neuromuscular performance of the quadriceps femoris at functional knee joint angles adjacent to full extension. Indices of volitional and magnetically-evoked neuromuscular performance (N=15 healthy males, 23.5 ± 2.9 years, 71.5 ± 5.4 kg, 176.5 ± 5.5 cm) were obtained at 25°, 35° and 45° of knee flexion. Results showed that volitional and magnetically-evoked peak force (PF(V) and P(T)F(E), respectively) and electromechanical delay (EMD(V) and EMD(E), respectively) were enhanced by increased knee flexion. However, greater relative improvements in volitional compared to evoked indices of neuromuscular performance were observed with increasing flexion from 25° to 45° (e.g. EMD(V), EMD(E): 36% vs. 11% improvement, respectively; F([2,14])=6.8, pjoint positions. These findings suggest that the extent of the relative differential between volitional and evoked neuromuscular performance capabilities is joint angle-specific and not correlated with performance capabilities at adjacent angles, but tends to be smaller with increased flexion. As such, effective prediction of volitional from evoked performance capabilities at both analogous and adjacent knee joint positions would lack robustness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Report on Adaptive Force, a specific neuromuscular function

Directory of Open Access Journals (Sweden)

Marko Hoff

2015-08-01

Full Text Available In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1 What is the peculiarity of this neuromuscular function, introduced as AF? 2 Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3 It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects’ option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso, the maximal isometric Adaptive Force (AFisomax and the maximal eccentric Adaptive Force (AFeccmax. Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities.

A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections.

Science.gov (United States)

Xu, Xiu; Xu, Qiong; Zhang, Ying; Zhang, Xiaodi; Cheng, Tianlin; Wu, Bingbing; Ding, Yanhua; Lu, Ping; Zheng, Jingjing; Zhang, Min; Qiu, Zilong; Yu, Xiang

2012-08-21

Autistic spectrum disorders (ASDs) are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Here, we identified a Chinese family with two brothers both inheriting a 2.2 Mb MECP2-containing duplication (151,369,305 - 153,589,577) from their mother. In addition, both brothers also had a 213.7 kb duplication on Chromosome 2, inherited from their father. The older brother also carried a 48.4 kb duplication on Chromosome 2 inherited from the mother, and a 8.2 kb deletion at 11q13.5 inherited from the father. Based on the published literature, MECP2 is the most autism-associated gene among the identified CNVs. Consistently, the boys displayed clinical features in common with other patients carrying MECP2 duplications, including intellectual disability, autism, lack of speech, slight hypotonia and unsteadiness of movement. They also had slight dysmorphic features including a depressed nose bridge, large ears and midface hypoplasia. Interestingly, they did not exhibit other clinical features commonly observed in American-European patients with MECP2 duplication, including recurrent respiratory infections and epilepsy. To our knowledge, this is the first identification and characterization of Chinese Han patients with MECP2-containing duplications. Further cases are required to determine if the above described clinical differences are due to individual variations or related to the genetic background of the patients.

Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome.

Science.gov (United States)

Rohena, Luis; Kuehn, Devon; Marchegiani, Shannon; Higginson, Jason D

2011-04-01

Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal genitalia, and developmental delay in two-thirds of the reported patients. Additional anomalies include dry skin, growth retardation, hearing loss, camptodactyly, hypertelorism, absent zygomatic arches, and umbilical abnormalities. We present the second familial case of ablepharon-macrostomia syndrome in a newborn female and her 22-year-old father making autosomal dominant inheritance more likely than the previously proposed autosomal recessive transmission for this disorder. These cases likely represent the 16th and 17th reported cases of AMS and the first case suspected on prenatal ultrasound. Additionally, the child shows more prominent features of the disorder when compared to her father documenting variable expression and possible anticipation. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2011 Wiley-Liss, Inc.

Non-traditional inheritance

International Nuclear Information System (INIS)

Hall, J.G.

1992-01-01

In the last few years, several non-traditional forms of inheritance have been recognized. These include mosaicism, cytoplasmic inheritance, uniparental disomy, imprinting, amplification/anticipation, and somatic recombination. Genomic imprinting (GI) is the dependence of the phenotype on the sex of the transmitting parent. GI in humans seems to involve growth, behaviour, and survival in utero. The detailed mechanism of genomic imprinting is not known, but it seems that some process is involved in turning a gene off; this probably involves two genes, one of which produces a product that turns a gene off, and the gene that is itself turned off. The process of imprinting (turning off) may be associated with methylation. Erasure of imprinting can occur, and seems to be associated with meiosis. 10 refs

Postoperative effects of neuromuscular exercise prior to hip or knee arthroplasty

DEFF Research Database (Denmark)

Villadsen, Allan; Overgaard, Søren; Holsgaard-Larsen, Anders

2014-01-01

neuromuscular exercise prior to total joint arthroplasty (TJA) of the hip or knee did not confer additional benefits 3 months postoperatively compared with TJA alone. However, the intervention group experienced a statistically significant short-term benefit in ADL and pain, suggesting an earlier onset......OBJECTIVE: To investigate the postoperative efficacy of a supervised programme of neuromuscular exercise prior to hip or knee arthroplasty. METHODS: In this assessor-blinded randomised controlled trial, we included 165 patients scheduled for hip or knee arthroplasty due to severe osteoarthritis (OA......). An 8-week preoperative neuromuscular supervised exercise programme was delivered twice a week for 1 h as adjunct treatment to the standard arthroplasty procedure and compared with the standard arthroplasty procedure alone. The primary outcome was self-reported physical function measured...

The impact of visual media to encourage low protein cooking in inherited metabolic disorders.

Science.gov (United States)

Evans, S; Daly, A; Hopkins, V; Davies, P; MacDonald, A

2009-10-01

The use of educational visual aids is one way to help children with inherited metabolic disorders (IMD) understand and develop a positive attitude towards their low protein diet. However, it is difficult to establish their effectiveness in the clinical setting. The present study aimed to evaluate the impact of a low protein recipe book and accompanying DVD for children with IMD. One hundred and five children (53% female; median age = 6-8 years) with IMD on low protein diets were each given a low protein recipe book and DVD. After 6 months, children and carers were posted a questionnaire asking whether they used these resources; identifying any change in frequency of low protein cooking; and the outcome when preparing recipes. One hundred and two questionnaires were returned, representing 105 patients. Seventy percent (n = 71) of questionnaires were from carers. Ninety-three percent (n = 66) of carers acknowledged receipt of the resource; one-third (n = 22) had not watched the DVD and 23% (n = 15) had not opened the recipe book; 55% (n = 36) had tried the recipes; and 71% (n = 47) said the recipe book and/or DVD motivated them to try new recipes. Children were more likely to have watched the DVD (75%; n = 21/28) and read the recipe book (86%; n = 24/28) than carers. Although a helpful educational tool, just over one-half of respondents had used the resource. Identifying visual media that, by itself, will motivate most families of children with IMD to prepare low protein recipes may be unrealistic. The combined approach of visual aids and 'hands-on' practical experience, such as low protein cooking workshops and individual counselling, may be more beneficial.

Utilization of ACL Injury Biomechanical and Neuromuscular Risk Profile Analysis to Determine the Effectiveness of Neuromuscular Training.

Science.gov (United States)

Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

2016-12-01

The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).

Inherited renal tubulopathies associated with metabolic alkalosis: effects on blood pressure.

Science.gov (United States)

Ariceta, Gema; Rodríguez-Soriano, Juan

2006-11-01

Inherited tubular disorders associated with metabolic alkalosis are caused by several gene mutations encoding different tubular transporters responsible for NaCl renal handling. Body volume and renin-angiotensin-aldosterone system status are determined by NaCl reabsorption in the distal nephron. Two common hallmarks in affected individuals: hypokalemia and normal / high blood pressure, support the differential diagnosis. Bartter's syndrome, characterized by hypokalemia and normal blood pressure, is a heterogenic disease caused by the loss of function of SLC12A1 (type 1), KCNJ1 (type 2), CLCNKB (type 3), or BSND genes (type 4). As a result, patients present with renal salt wasting and hypercalciuria. Gitelman's syndrome is caused by the loss of funcion of the SLC12A3 gene and may resemble Bartter's syndrome, though is associated with the very low urinary calcium. Liddle's syndrome, also with similar phenotype but with hypertension, is produced by the gain of function of the SNCC1B or SNCC1G genes, and must be distinguished from other entities of inherited hypertension such as Apparently Mineralocorticoid Excess, of glucocorticoid remediable hypertension.

Hepatitis A and B immunization for individuals with inherited bleeding disorders.

Science.gov (United States)

Steele, M; Cochrane, A; Wakefield, C; Stain, A-M; Ling, S; Blanchette, V; Gold, R; Ford-Jones, L

2009-03-01

Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

Science.gov (United States)

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

S-nitrosoglutathione reductase deficiency-induced S-nitrosylation results in neuromuscular dysfunction.

Science.gov (United States)

Montagna, Costanza; Di Giacomo, Giuseppina; Rizza, Salvatore; Cardaci, Simone; Ferraro, Elisabetta; Grumati, Paolo; De Zio, Daniela; Maiani, Emiliano; Muscoli, Carolina; Lauro, Filomena; Ilari, Sara; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare; Ciriolo, Maria R; Cecconi, Francesco; Bonaldo, Paolo; Filomeni, Giuseppe

2014-08-01

Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. We demonstrate that, without any sign of protein nitration, young GSNOR-KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant decrease in nerve axon number, with the myelin sheath appearing disorganized and reduced, leading to a dramatic development of a neuropathic phenotype. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, conditions that are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. Our study provides the first evidence that GSNOR deficiency, which affects exclusively SNOs reduction without altering nitrotyrosine levels, results in a clinically relevant neuromuscular phenotype. These findings provide novel insights into the involvement of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that are associated with pathological states; for example, diabetes and cancer.

Testamental inheritance: Just a legal osmosis?

Directory of Open Access Journals (Sweden)

Đorđević-Crnobrnja Jadranka

2011-01-01

Full Text Available Bequeath, a dispose of personal property by the last will is an example of intervention of legislation within the complex of customary law. This influence is not unusual but certainly is less frequent than the influence of customary into civil law, especially so in their interaction within inheritance. This paper therefore tries to explain this example of legal osmosis in practice. In addition, the practice in testament inheritance shows also an influence of customary law into legislation. Hence, the paper will also try to discuss a relationship between customary and civil laws and succeeding problems in inheritance at the levels of individual and that of the society.

Risk of cancer in relatives of patients with myotonic dystrophy

DEFF Research Database (Denmark)

Lund, M; Diaz, L J; Gørtz, S

2014-01-01

BACKGROUND AND PURPOSE: Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM...... genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. METHODS: DM was identified using the National Danish Patient Registry...

Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Pitceathly, Robert D S

2012-09-11

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

Genetic disorders of thyroid metabolism and brain development

Science.gov (United States)

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

[Motility disorders of the esophagus].

Science.gov (United States)

Bruder, E; Rougemont, A-L; Furlano, R I; Schneider, J F; Mayr, J; Haecker, F-M; Beier, K; Schneider, J; Weber, P; Berberich, T; Cathomas, G; Meier-Ruge, W A

2013-03-01

Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

Towards unifying inheritance and automatic program specialization

DEFF Research Database (Denmark)

Schultz, Ulrik Pagh

2002-01-01

and specialization of classes (inheritance) are considered different abstractions. We present a new programming language, Lapis, that unifies inheritance and program specialization at the conceptual, syntactic, and semantic levels. This paper presents the initial development of Lapis, which uses inheritance...... with covariant specialization to control the automatic application of program specialization to class members. Lapis integrates object-oriented concepts, block structure, and techniques from automatic program specialization to provide both a language where object-oriented designs can be e#ciently implemented...

The relative importance of inheritances in Norway

OpenAIRE

Johansson, Marianne Lefsaker

2014-01-01

In a very influential paper, Piketty (2011) finds that inherited wealth is of increasing importance in France. He describes a U-shaped pattern in the long-run development of inheritance flows. Two driving factors in this development are the relative ratio of wealth of the deceased to wealth of the living, and the wealth-income ratio. In periods with high economic growth, wealth of the past is weakened and inheritances as share of national income decreases. As soon as growth declines, however,...

Neuromuscular Activity and Knee Kinematics in Adolescents with Patellofemoral Pain

DEFF Research Database (Denmark)

Rathleff, Michael Skovdal; Samani, Afshin; Olesen, Jens L

2013-01-01

This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS).......This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)....

Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

DEFF Research Database (Denmark)

Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

2017-01-01

INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys...

Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

2009-01-01

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

The immediate effect of neuromuscular joint facilitation on the rotation of the tibia during walking.

Science.gov (United States)

Li, Desheng; Huang, Qiuchen; Huo, Ming; Hiiragi, Yukinobu; Maruyama, Hitoshi

2017-01-01

[Purpose] The aim of this study was to investigate the change in tibial rotation during walking among young adults after neuromuscular joint facilitation therapy. [Subjects and Methods] The subjects were twelve healthy young people (6 males, 6 females). A neuromuscular joint facilitation intervention and nonintervention were performed. The interventions were performed one after the other, separated by a 1-week interval. The order of the interventions was completely randomized. The rotation of the tibia during walking was evaluated before and after treatment. [Results] The neuromuscular joint facilitation group demonstrated increased lateral rotation of the tibia in the overall gait cycle and stance phase, and decreased medial rotation of the tibia in the overall gait cycle, stance phase, and swing phase after the neuromuscular joint facilitation intervention. In the control group, there were no significant differences. [Conclusion] These results suggest neuromuscular joint facilitation intervention has an immediate effect on the rotational function of the knee.

A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections

Directory of Open Access Journals (Sweden)

Xu Xiu

2012-08-01

Full Text Available Abstract Background Autistic spectrum disorders (ASDs are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Case presentation Here, we identified a Chinese family with two brothers both inheriting a 2.2 Mb MECP2-containing duplication (151,369,305 – 153,589,577 from their mother. In addition, both brothers also had a 213.7 kb duplication on Chromosome 2, inherited from their father. The older brother also carried a 48.4 kb duplication on Chromosome 2 inherited from the mother, and a 8.2 kb deletion at 11q13.5 inherited from the father. Based on the published literature, MECP2 is the most autism-associated gene among the identified CNVs. Consistently, the boys displayed clinical features in common with other patients carrying MECP2 duplications, including intellectual disability, autism, lack of speech, slight hypotonia and unsteadiness of movement. They also had slight dysmorphic features including a depressed nose bridge, large ears and midface hypoplasia. Interestingly, they did not exhibit other clinical features commonly observed in American-European patients with MECP2 duplication, including recurrent respiratory infections and epilepsy. Conclusions To our knowledge, this is the first identification and characterization of Chinese Han patients with MECP2-containing duplications. Further cases are required to determine if the above described clinical differences are due to individual variations or related to the genetic background of the patients.

Inherited Bone Marrow Failure Syndromes (IBMFS)

Science.gov (United States)

The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

Hypoglycaemia related to inherited metabolic diseases in adults

Directory of Open Access Journals (Sweden)

Douillard Claire

2012-05-01

Full Text Available Abstract In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family. Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD, ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency].

Neuromuscular dose-response studies: determining sample size.

Science.gov (United States)

Kopman, A F; Lien, C A; Naguib, M

2011-02-01

Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

Conformal symmetry inheritance in null fluid spacetimes

International Nuclear Information System (INIS)

Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

2003-01-01

We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis.

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van der Bent, M Leontien; Paulino da Silva Filho, Omar; van Luijk, Judith; Brock, Roland; Wansink, Derick G

2018-03-08

Antisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and patients. Success in the clinic is nevertheless still limited, due to unfavourable biodistribution and poor cellular uptake of AONs. Extensive research is currently being conducted into the formulation of AONs to improve delivery, but thus far there is no consensus on which of those strategies will be the most effective. This systematic review was designed to answer in an unbiased manner which delivery strategies most strongly enhance the efficacy of AONs in animal models of heritable neurodegenerative and neuromuscular diseases. In total, 95 primary studies met the predefined inclusion criteria. Study characteristics and data on biodistribution and toxicity were extracted and reporting quality and risk of bias were assessed. Twenty studies were eligible for meta-analysis. We found that even though the use of delivery systems provides an advantage over naked AONs, it is not yet possible to select the most promising strategies. Importantly, standardisation of experimental procedures is warranted in order to reach conclusions about the most efficient delivery strategies. Our best practice guidelines for future experiments serve as a step in that direction.

Proprioceptive Neuromuscular Facilitation (PNF): Its Mechanisms and Effects on Range of Motion and Muscular Function

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Hindle, Kayla B.; Whitcomb, Tyler J.; Briggs, Wyatt O.; Hong, Junggi

2012-01-01

Proprioceptive neuromuscular facilitation (PNF) is common practice for increasing range of motion, though little research has been done to evaluate theories behind it. The purpose of this study was to review possible mechanisms, proposed theories, and physiological changes that occur due to proprioceptive neuromuscular facilitation techniques. Four theoretical mechanisms were identified: autogenic inhibition, reciprocal inhibition, stress relaxation, and the gate control theory. The studies suggest that a combination of these four mechanisms enhance range of motion. When completed prior to exercise, proprioceptive neuromuscular facilitation decreases performance in maximal effort exercises. When this stretching technique is performed consistently and post exercise, it increases athletic performance, along with range of motion. Little investigation has been done regarding the theoretical mechanisms of proprioceptive neuromuscular facilitation, though four mechanisms were identified from the literature. As stated, the main goal of proprioceptive neuromuscular facilitation is to increase range of motion and performance. Studies found both of these to be true when completed under the correct conditions. These mechanisms were found to be plausible; however, further investigation needs to be conducted. All four mechanisms behind the stretching technique explain the reasoning behind the increase in range of motion, as well as in strength and athletic performance. Proprioceptive neuromuscular facilitation shows potential benefits if performed correctly and consistently. PMID:23487249

Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models

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James J. Dowling

2012-11-01

Myotubular myopathy (MTM is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ transmission is an important and potentially treatable aspect of the disease pathogenesis. We tested this hypothesis in two murine models of MTM. In both models we uncovered evidence of a disorder of NMJ transmission: fatigable weakness, improved strength with neostigmine, and electrodecrement with repetitive nerve stimulation. Histopathological analysis revealed abnormalities in the organization, appearance and size of individual NMJs, abnormalities that correlated with changes in acetylcholine receptor gene expression and subcellular localization. We additionally determined the ability of pyridostigmine, an acetylcholinesterase inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ dysfunction. Pyridostigmine treatment resulted in significant improvement in fatigable weakness and treadmill endurance. In all, these results describe a newly identified pathological abnormality in MTM, and uncover a potential disease-modifying therapy for this devastating disorder.

Legal Portion in Russian Inheritance Law

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Inshina, Roza; Murzalimova, Lyudmila

2013-01-01

In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

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Kim, Ji Eun; Chun, Hea Rim

2017-01-01

Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

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Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

The role of inheritance in structuring hyperextended rift systems

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Manatschal, Gianreto; Lavier, Luc; Chenin, Pauline

2015-04-01

A long-standing question in Earth Sciences is related to the importance of inheritance in controlling tectonic processes. In contrast to physical processes that are generally applicable, assessing the role of inheritance suffers from two major problems: firstly, it is difficult to appraise without having insights into the history of a geological system; and secondly all inherited features are not reactivated during subsequent deformation phases. Therefore, the aim of our presentation is to give some conceptual framework about how inheritance may control the architecture and evolution of hyperextended rift systems. We use the term inheritance to refer to the difference between an "ideal" layer-cake type lithosphere and a "real" lithosphere containing heterogeneities and we define 3 types of inheritance, namely structural, compositional and thermal inheritance. Moreover, we assume that the evolution of hyperextended rift systems reflects the interplay between their inheritance (innate/"genetic code") and the physical processes at play (acquired/external factors). Thus, by observing the architecture and evolution of hyperextended rift systems and integrating the physical processes, one my get hints on what may have been the original inheritance of a system. Using this approach, we focus on 3 well-studied rift systems that are the Alpine Tethys, Pyrenean-Bay of Biscay and Iberia-Newfoundland rift systems. For the studied examples we can show that: 1) strain localization on a local scale and during early stages of rifting is controlled by inherited structures and weaknesses 2) the architecture of the necking zone seems to be influenced by the distribution and importance of ductile layers during decoupled deformation and is consequently controlled by the thermal structure and/or the inherited composition of the curst 3) the location of breakup in the 3 examples is not significantly controlled by the inherited structures 4) inherited mantle composition and rift

Inherited epidermolysis bullosa

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Fine Jo-David

2010-05-01

Full Text Available Abstract Inherited epidermolysis bullosa (EB encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

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Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial

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Giannasi Lilian

2012-05-01

Full Text Available Abstract Background Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP, given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm and LED (= 660 nm irradiation in CP patients. Methods/design 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. Discussion This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. Trial registration The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS Descriptors Cerebral Palsy

Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

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Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

2016-12-01

To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.

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Wang, Zixuan; Wilson, Amanda; Xu, Jianping

2015-02-01

The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most sexual eukaryotes. In this study, we examined the mitochondrial inheritance pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the US Pacific Northwest and British Columbia (especially Vancouver Island) in Canada. Using molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between strains within and between divergent lineages in C. gattii. Consistent with results from recent studies, our analyses identified significant variations in mtDNA inheritance patterns among strains and crosses, ranging from strictly uniparental to biparental. For two of the crosses that showed uniparental mitochondrial inheritance in standard laboratory conditions, we further investigated the effects of the following environmental variables on mtDNA inheritance: UV exposure, temperature, and treatments with the methylation inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium chloride. Interestingly, one of these crosses showed no response to these environmental variables while the other exhibited diverse patterns ranging from complete uniparental inheritance of the MATa parent mtDNA, to biparental inheritance, and to a significant bias toward inheritance of the MATα parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs from that in its closely related species Cryptococcus neoformans. Copyright © 2015 Elsevier Inc. All rights reserved.

Does Customary Law Discriminate Balinese Women’s Inheritance Rights?

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Hanna Christine Ndun

2018-05-01

Full Text Available There is a stereotype with regard to the rights of the Balinese women on inheriting under the Balinese tradi-tional customary law. It is generally assumed that the law discriminates Balinese women as well as against the human rights principle of equality. This article analyzes the contemporary problems of such issue and would demonstrate the actual principles, rules and practices, including the essential concept of the rights under the Balinese traditional customary law of inheritance. This issue has been explored under a normative legal approach where the resources are primarily taken from the relevant national legal instruments and court decisions, instead of textbooks and journals. An interview has also been commenced for clarifying some aspects of the issue. This article concludes that there has been a generally misleading on viewing the Balinese customary law as discriminating women on an inheritance issue, as in fact, the law also provides rules for supporting women’s rights for inheriting. The law in a certain way has properly preserved the right of women for inheriting in which women under the law have also enjoyed rights for inheriting, especially the daughter and widow. In contrast, the Balinese men that are generally perceived as the ultimate gender enjoying privileges rights to inherit, in the practice of inheritance in the traditional community are also subject to some discrimination. The law has provided a set of rule of inheritance both for men and women where they are subject to certain equal rule and condition. The law also clarifies that both genders are enjoying equal rights on inheritance in a certain portion and situation binding under the principle of balancing between rights and obligation for each side.

Elbow joint position sense after neuromuscular training with handheld vibration.

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Tripp, Brady L; Faust, Donald; Jacobs, Patrick

2009-01-01

Clinicians use neuromuscular control exercises to enhance joint position sense (JPS); however, because standardizing such exercises is difficult, validations of their use are limited. To evaluate the acute effects of a neuromuscular training exercise with a handheld vibrating dumbbell on elbow JPS acuity. Crossover study. University athletic training research laboratory. Thirty-one healthy, college-aged volunteers (16 men, 15 women, age = 23 + or - 3 years, height = 173 + or - 8 cm, mass = 76 + or - 14 kg). We measured and trained elbow JPS using an electromagnetic tracking device that provided auditory and visual biofeedback. For JPS testing, participants held a dumbbell and actively identified the target elbow flexion angle (90 degrees ) using the software-generated biofeedback, followed by 3 repositioning trials without feedback. Each neuromuscular training protocol included 3 exercises during which participants held a 2.55-kg dumbbell vibrating at 15, 5, or 0 Hz and used software-generated biofeedback to locate and maintain the target elbow flexion angle for 15 seconds. We calculated absolute (accuracy) and variable (variability) errors using the differences between target and reproduced angles. Training protocols using 15-Hz vibration enhanced accuracy and decreased variability of elbow JPS (P or = .200). Our results suggest these neuromuscular control exercises, which included low-magnitude, low-frequency handheld vibration, may enhance elbow JPS. Future researchers should examine vibration of various durations and frequencies, should include injured participants and functional multijoint and multiplanar measures, and should examine long-term effects of training protocols on JPS and injury.

Inherited cardiomyopathies and sports participation.

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Zorzi, A; Pelliccia, A; Corrado, D

2018-03-01

Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients.

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Awater, Carina; Zerres, Klaus; Rudnik-Schöneborn, Sabine

2012-06-01

Information about pregnancy and delivery in hereditary neuromuscular disorders (NMD) is limited and largely restricted to small case series and single case reports. Further data of obstetric histories in clinically and genetically defined subgroups are required. We reviewed the obstetric histories of 178 patients with myotonic dystrophy type 1 (DM1) and 2 (DM2), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), and congenital myopathy (CM) by means of questionnaires and medical reports. Patients were recruited in the period 1992-2010 after they had at least completed one pregnancy. A total of 380 pregnancies resulting in 315 children were documented. Compared to the normal German population, the number of miscarriages and hypertensive diseases in pregnancy was not increased in the cohort. Patients with NMD delivered more frequently by vaginal operations (8.9-18.2%) and by cesarean births with significantly high rates in DM1 (36.7%) and SMA (42.4%). Preterm deliveries were recorded in 30.7% of DM1, 12.6% of DM2, and 29.4% of SMA gestations. Abnormal fetal presentation occurred significantly more frequently in DM1 (34.6%) and LGMD (26.7%) deliveries and was a feature of chairbound patients. Considering a possible influence of pregnancy on the disease course, about half of LGMD, one-third of SMA, and one fifth of CMT patients reported a deterioration of symptoms in pregnancy. Neonatal outcome was favorable in all NMD but DM1, where infantile morbidity and mortality is often but not exclusively related to congenitally affected children. Our data are important for obstetric care and genetic counseling of women with NMD who are contemplating pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Private inherited microdeletion/microduplications: implications in clinical practice.

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Mencarelli, Maria Antonietta; Katzaki, Eleni; Papa, Filomena Tiziana; Sampieri, Katia; Caselli, Rossella; Uliana, Vera; Pollazzon, Marzia; Canitano, Roberto; Mostardini, Rosa; Grosso, Salvatore; Longo, Ilaria; Ariani, Francesca; Meloni, Ilaria; Hayek, Josef; Balestri, Paolo; Mari, Francesca; Renieri, Alessandra

2008-01-01

The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.

Why does biparental plastid inheritance revive in angiosperms?

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Zhang, Quan; Sodmergen

2010-03-01

It is widely believed that plastid and mitochondrial genomes are inherited through the maternal parent. In plants, however, paternal transmission of these genomes is frequently observed, especially for the plastid genome. A male gametic trait, called potential biparental plastid inheritance (PBPI), occurs in up to 20% of angiosperm genera, implying a strong tendency for plastid transmission from the male lineage. Why do plants receive organelles from the male parents? Are there clues in plastids that will help to elucidate the evolution of plants? Reconstruction of the ancestral state of plastid inheritance patterns in a phylogenetic context provides insights into these questions. In particular, a recent report demonstrated the unilateral occurrence of PBPI in angiosperms. This result implies that nuclear cytoplasmic conflicts, a basic driving force for altering the mode of organelle inheritance, might have arisen specifically in angiosperms. Based on existing evidence, it is likely that biparental inheritance may have occurred to rescue angiosperm species with defective plastids.

Influência do lítio no bloqueio neuromuscular produzido pelo atracúrio e pelo cisatracúrio: estudo em preparações nervo frênico-diafragma de rato Influencia del litio en el bloqueo neuromuscular producido por el atracurio y por el cisatracurio: estudio en preparo nervio frénico-diafragma del ratón Influence of lithium on the neuromuscular blockade produced by atracurium and cisatracurium: study on rat phrenic nerve-diaphragm preparations

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Samanta Cristina Antoniassi Fernandes

2007-06-01

alteraciones en los potenciales de placa terminal en miniatura mostraron una acción presináptica.BACKGROUND AND OBJECTIVES: Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS: Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1; atracurium (20 µg.mL-1, and cisatracurium (3 µg.mL-1; the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 µg.mL-1 and cisatracurium (5 µg.mL-1. The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP and miniature end-plate potentials (MEPP were also evaluated. RESULTS: Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS: Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders.

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Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M; Di Minno, Giovanni; Grazzini, Giuliano

2014-04-01

Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.

Widow inheritance and HIV/AIDS in rural Uganda.

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Mabumba, E D; Mugyenyi, P; Batwala, V; Mulogo, E M; Mirembe, J; Khan, F A; Liljestrand, J

2007-10-01

Despite current efforts to combat HIV/AIDS through behavioural change, ingrained socio-cultural practices such as widow inheritance in south-western Uganda has not changed. Low education, unemployment, dowry, widows' socioeconomic demands and the inheritor's greed for the deceased's wealth, influence widow inheritance. Voluntary counselling and testing is needed for the widows and their inheritors; formal dowry should be removed from marriage and widow inheritance stripped of its sexual component.

Does the mode of plastid inheritance influence plastid genome architecture?

Directory of Open Access Journals (Sweden)

Kate Crosby

Full Text Available Plastid genomes show an impressive array of sizes and compactnesses, but the forces responsible for this variation are unknown. It has been argued that species with small effective genetic population sizes are less efficient at purging excess DNA from their genomes than those with large effective population sizes. If true, one may expect the primary mode of plastid inheritance to influence plastid DNA (ptDNA architecture. All else being equal, biparentally inherited ptDNAs should have a two-fold greater effective population size than those that are uniparentally inherited, and thus should also be more compact. Here, we explore the relationship between plastid inheritance pattern and ptDNA architecture, and consider the role of phylogeny in shaping our observations. Contrary to our expectations, we found no significant difference in plastid genome size or compactness between ptDNAs that are biparentally inherited relative to those that are uniparentally inherited. However, we also found that there was significant phylogenetic signal for the trait of mode of plastid inheritance. We also found that paternally inherited ptDNAs are significantly smaller (n = 19, p = 0.000001 than those that are maternally, uniparentally (when isogamous, or biparentally inherited. Potential explanations for this observation are discussed.

A self-controlled comparative clinical trial to explore the effectiveness of three topical hemostatic agents for stopping severe epistaxis in pediatrics with inherited coagulopathies.

Science.gov (United States)

Eshghi, P; Jenabzade, A; Habibpanah, B

2014-09-01

The aim of this study was to assess the effectiveness of localized treatments to persistently stop epistaxis in patients with inherited bleeding disorders. In a self-controlled comparative clinical trial, to offer the best solution to stop epistaxis at home (within 10 minutes), patients with inherited bleeding disorders were treated using three different topical hemostatic agents, including Tranexamic acid impregnated tampon, EpiCell tampon prepared from oxidized regenerated cellulose pad, and ChitoHem tampon (reinforced with chitosan). The results of using these different products on three groups of randomly selected patients were ultimately compared using the χ(2) and Fisher's exact test statistics. A total of 31 patients, 5 females and 26 males with a mean age of 5.6 years, were included in the study. Twenty-three patients had Glanzmann disease, four had von-Willebrand disease, two had Bernard soulier syndrome, two had activated factor VII deficiency, and one patient had impaired secretion of adenosine deaminase. The study exhibited that statistically there was no significant difference between EpiCell tampon and Tranexamic acid impregnated tampon treatments with respect to the hemostasis duration. However, ChitoHem tampon was more efficient than Tranexamic acid impregnated tampon (P value stop epistaxis. We recommend further research on the use of other hemostatic agents for localized bleeding in patients with inherited bleeding disorders.

The inheritance of groin hernia

DEFF Research Database (Denmark)

Burcharth, J; Pommergaard, H C; Rosenberg, Jacob

2013-01-01

Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.......Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias....

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review

Science.gov (United States)

Schaller, Stefan Josef; Fink, Heidrun

2013-01-01

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing. PMID:24098155

De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder.

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Reijnders, Margot R F; Miller, Kerry A; Alvi, Mohsan; Goos, Jacqueline A C; Lees, Melissa M; de Burca, Anna; Henderson, Alex; Kraus, Alison; Mikat, Barbara; de Vries, Bert B A; Isidor, Bertrand; Kerr, Bronwyn; Marcelis, Carlo; Schluth-Bolard, Caroline; Deshpande, Charu; Ruivenkamp, Claudia A L; Wieczorek, Dagmar; Baralle, Diana; Blair, Edward M; Engels, Hartmut; Lüdecke, Hermann-Josef; Eason, Jacqueline; Santen, Gijs W E; Clayton-Smith, Jill; Chandler, Kate; Tatton-Brown, Katrina; Payne, Katelyn; Helbig, Katherine; Radtke, Kelly; Nugent, Kimberly M; Cremer, Kirsten; Strom, Tim M; Bird, Lynne M; Sinnema, Margje; Bitner-Glindzicz, Maria; van Dooren, Marieke F; Alders, Marielle; Koopmans, Marije; Brick, Lauren; Kozenko, Mariya; Harline, Megan L; Klaassens, Merel; Steinraths, Michelle; Cooper, Nicola S; Edery, Patrick; Yap, Patrick; Terhal, Paulien A; van der Spek, Peter J; Lakeman, Phillis; Taylor, Rachel L; Littlejohn, Rebecca O; Pfundt, Rolph; Mercimek-Andrews, Saadet; Stegmann, Alexander P A; Kant, Sarina G; McLean, Scott; Joss, Shelagh; Swagemakers, Sigrid M A; Douzgou, Sofia; Wall, Steven A; Küry, Sébastien; Calpena, Eduardo; Koelling, Nils; McGowan, Simon J; Twigg, Stephen R F; Mathijssen, Irene M J; Nellaker, Christoffer; Brunner, Han G; Wilkie, Andrew O M

2018-06-07

Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles.

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Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

2014-07-01

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm(2)), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm(2)). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18-0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the 'design' of their

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles

Science.gov (United States)

Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

2014-01-01

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm2), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm2). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18–0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the ‘design’ of their

Evaluation of a web-based registry of inherited bleeding disorders: a descriptive study of the Brazilian experience with HEMOVIDAweb Coagulopatias.

Science.gov (United States)

Rezende, Suely Meireles; Rodrigues, Silvia Helena Lacerda; Brito, Kelly Neves Pinheiro; da Silva, Diego Lima Quintino; Santo, Marcos Lázaro; Simões, Bárbara de Jesus; Genovez, Guilherme; Melo, Helder Teixeira; Araújo, João Paulo Baccara; Barca, Danila Augusta Accioly Varella

2017-02-10

Inherited bleeding disorders (IBD) consist of a group of rare heterogeneous diseases, which require treatment for life. Management of these disorders is complex and costly. Therefore, good quality data of the affected population is crucial to guide policy planning. The aim of this manuscript is to describe the impact of a national, web-based registry - the Hemovidaweb Coagulopatias (HWC) - in the management of the IBD in Brazil. The system was developed in PHP 5.0 language and is available on the internet at http://coagulopatiasweb.datasus.gov.br . The system was validated in September 2008 and launched nationally with input from January 1, 2009. HWC collects variables related to socio-demographic, clinical, laboratory and treatment data of patients with IBD. Within 7 years, there was an increment of 90.8% on the diagnosis of IBD altogether, which increased from 11,040 in December 2007 to 21,066 in December 2014. This is now the fourth and third largest world population of patients with haemophilia and von Willebrand's disease (vWD), respectively, according to the most recent (2015) Annual Global Survey of the World Federation of Hemophilia. The data collected provided the basis for planning and implementing home therapy, prophylaxis and immune tolerance induction (ITI), recently initiated in Brazil. HWC was an effective tool in the increment of registration of patients with IBD in Brazil. Furthermore, it was essential to support policy planning, monitoring, evaluation and treatment. Future development should focus on surveillance, health outcomes and research. Every country should implement a national registry on IBD.

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort.

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Salvado, Maria; Canela, Merce; Ponseti, Jose Maria; Lorenzo, Laura; Garcia, Cecilia; Cazorla, Sonia; Gili, Gisela; Raguer, Nuria; Gamez, Josep

2016-01-15

Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. We investigated the presence of familial cases in 462 MG patients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23–82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.

[Impact of a quality assurance program on the use of neuromuscular monitoring and reversal of muscle relaxants].

Science.gov (United States)

Motamed, C; Bourgain, J-L

2009-04-01

As part of a quality assurance in the anaesthesia department, this study was designed to enhance the rate of neuromuscular blockade monitoring for patients receiving muscle relaxant during anaesthesia. After approval of our local ethical committee, we assessed 200 computerized anaesthesia records in which neuromuscular relaxants were used. The following data were collected: demographic characteristics, durations of anaesthesia and surgery, use of neuromuscular monitoring, reversal agents and the quality of neuromuscular monitoring. The results were discussed with all anaesthesia providers of the department and an internal guideline was elaborated with the endpoint that all patients having muscle relaxants should have quantitative neuromuscular monitoring. Six months later, another assessment of 200 consecutive records collected the same data to check the efficiency of the elaborated guideline. The monitoring rate was of 67% at the first assessment and increased to 94% (passessment and was stable at the second assessment (50%). The rate of patients not monitored and not reversed decreased from 5 to 2% (pquality assurance program systematic quantitative monitoring of neuromuscular blockade can be significantly increased.

Dietary management of urea cycle disorders : European practice

NARCIS (Netherlands)

Adam, S.; Almeida, M. F.; Assoun, M.; Baruteau, J.; Bernabei, S. M.; Bigot, S.; Champion, H.; Daly, A.; Dassy, M.; Dawson, S.; Dixon, M.; Dokoupil, K.; Dubois, S.; Dunlop, C.; Evans, S.; Eyskens, F.; Faria, A.; Favre, E.; Ferguson, C.; Goncalves, C.; Gribben, J.; Heddrich-Ellerbrok, M.; Jankowski, C.; Janssen-Regelink, R.; Jouault, C.; Laguerre, C.; Le Verge, S.; Link, R.; Lowry, S.; Luyten, K.; MacDonald, A.; Maritz, C.; McDowell, S.; Meyer, U.; Micciche, A.; Robertson, L. V.; Rocha, J. C.; Rohde, C.; Saruggia, I.; Sjoqvist, E.; Stafford, J.; Terry, A.; Thom, R.; Vande Kerckhove, K.; van Rijn, M.; van Teeffelen-Heithoff, A.; van Wegberg, A.; van Wyk, K.; Vasconcelos, C.; Vestergaard, H.; Webster, D.; White, F. J.; Wildgoose, J.; Zweers, H.; Robert, M.

2013-01-01

Background: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. Methods: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1

Dietary management of urea cycle disorders: European practice.

NARCIS (Netherlands)

Adam, S.; Almeida, M.F.; Assoun, M.; Baruteau, J.; Bernabei, S.M.; Bigot, S.; Champion, H.; Daly, A.; Dassy, M.; Dawson, S.; Dixon, M.; Dokoupil, K.; Dubois, S.; Dunlop, C.; Evans, S.; Eyskens, F.; Faria, A.; Favre, E.; Ferguson, C.; Goncalves, C.; Gribben, J.; Heddrich-Ellerbrok, M.; Jankowski, C.; Janssen-Regelink, R.G.; Jouault, C.; Laguerre, C.; Verge, S. Le; Link, R.; Lowry, S.; Luyten, K.; Macdonald, A.; Maritz, C.; McDowell, S.; Meyer, U.; Micciche, A.; Robert, M.; Robertson, L.V.; Rocha, J.C.; Rohde, C.; Saruggia, I.; Sjoqvist, E.; Stafford, J.; Terry, A.; Thom, R.; nde Kerckhove, K. Va; Rijn, M. van de; Teeffelen-Heithoff, A. van; Wegberg, A.M.J. van; Wyk, K. van; Vasconcelos, C.; Vestergaard, H.; Webster, D.; White, F.J.; Wildgoose, J.; Zweers, H.

2013-01-01

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1

Law & psychiatry: Murder, inheritance, and mental illness.

Science.gov (United States)

Gold, Azgad; Appelbaum, Paul S

2011-07-01

Should a murderer be allowed to inherit the victim's estate? The question dates from biblical times, but most jurisdictions today have statutes in place that bar inheritance by convicted murderers. However, a special problem arises when the killer has a severe mental illness and has been found not guilty by reason of insanity. Should such people, who have not been convicted of a crime, be permitted to collect their inheritance? Jurisdictions vary in their responses, with the rules reflecting a mix of practical and moral considerations influenced by different perspectives about what determines the behavior of persons with mental illness.

Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

Science.gov (United States)

Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

2015-05-01

[Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

Bloqueio neuromuscular prolongado após administração de mivacúrio: relato de caso Bloqueo neuromuscular prolongado después de administración de mivacúrio: relato de caso Prolonged neuromuscular block after mivacurium: case report

Directory of Open Access Journals (Sweden)

Karina Bernardi Pimenta

2005-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Com a introdução de novos fármacos com ação de curta duração, houve aumento do número de procedimentos realizados em caráter ambulatorial. O mivacúrio com duração de ação entre 15 e 30 minutos e metabolismo enzimático tornou-se opção de bloqueador neuromuscular para estes procedimentos. O relato de caso tem como objetivo chamar a atenção para a ocorrência de bloqueio neuromuscular prolongado após administração do mivacúrio e as condutas que foram adotadas. RELATO DO CASO: Descreve-se um caso de paciente programado para procedimento de curta duração em regime ambulatorial e que apresentou bloqueio neuromuscular prolongado após administração do mivacúrio. O diagnóstico foi posteriormente confirmado pela demonstração de níveis reduzidos de atividade da colinestesterase plasmática. CONCLUSÕES: A investigação laboratorial pré-operatória, mesmo incluindo a dosagem da atividade da colinesterase, não previne a possibilidade do bloqueio neuromuscular prolongado devido à possibilidade de alteração qualitativa da atividade da enzima, não existindo recomendação para investigação sistemática. Ocorrendo esta complicação, deve-se sedar o paciente e manter ventilação mecânica até a completa recuperação da força muscular e realizar exames laboratoriais para o diagnóstico definitivo. É de responsabilidade do anestesiologista a coleta de amostra sangüínea para realização de testes quantitativos e qualitativos da colinesterase plasmática. Paciente e familiares devem ser orientados quanto à importância da investigação para classificação da variante atípica da colinesterase plasmática e suas implicações anestésicas.JUSTIFICATIVA Y OBJETIVOS: Con la introducción de nuevos fármacos con acción de corta duración, hubo aumento del número de procedimientos realizados en carácter ambulatorial. El mivacúrio con duración de acción entre 15 y 30 minutos y

The Role of Neuromuscular Changes in Aging and Knee Osteoarthritis on Dynamic Postural Control

Science.gov (United States)

Takacs, Judit; Carpenter, Mark G.; Garland, S. Jayne; Hunt, Michael A.

2013-01-01

Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA. PMID:23696951

Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

Science.gov (United States)

Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

2015-05-15

Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin

2018-02-22

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin; Howells, Emily J.; Wang, Xin; Michell, Craig; Burt, John A.; Idaghdour, Youssef; Aranda, Manuel

2018-01-01

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study.

Science.gov (United States)

Brueckmann, B; Sasaki, N; Grobara, P; Li, M K; Woo, T; de Bie, J; Maktabi, M; Lee, J; Kwo, J; Pino, R; Sabouri, A S; McGovern, F; Staehr-Rye, A K; Eikermann, M

2015-11-01

This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], Psugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02). After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. Clinicaltrials.gov:NCT01479764. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Inheritance and wealth inequality: Evidence from population registers

OpenAIRE

Elinder, Mikael; Erixson, Oscar; Waldenström, Daniel

2016-01-01

We use new population-wide register data on inheritances and wealth in Sweden to estimate the causal impact of inheritances on wealth inequality. We find that inheritances reduce relative wealth inequality (e.g., the Gini coefficient falls by 5–10 percent) but that absolute dispersion increases. Examining different parts of the wealth distribution, we find that the top decile's wealth share decreases substantially, whereas the wealth share of the bottom half increases from a negative to a pos...

Genetics and Neuromuscular Diseases

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... Testing that reveals a young child’s genet- ic destiny may affect relationships within the family or may ... linked inheritance don’t apply at all. An embryo receives its mitochondria from the mother’s egg cell, ...

Role of analgesics, sedatives, neuromuscular blockers, and delirium.

Science.gov (United States)

Hall, Jesse B; Schweickert, William; Kress, John P

2009-10-01

A major focus on critical care medicine concerns the institution of life-support therapies, such as mechanical ventilation, during periods of organ failure to permit a window of opportunity to diagnose and treat underlying disorders so that patients may be returned to their prior functional status upon recovery. With the growing success of these intensive care unit-based therapies and longer-term follow-up of patients, severe weakness involving the peripheral nervous system and muscles has been identified in many recovering patients, often confounding the time course or magnitude of recovery. Mechanical ventilation is often accompanied by pharmacologic treatments including analgesics, sedatives, and neuromuscular blockers. These drugs and the encephalopathies accompanying some forms of critical illness result in a high prevalence of delirium in mechanically ventilated patients. These drug effects likely contribute to an impaired ability to assess the magnitude of intensive care unit-acquired weakness, to additional time spent immobilized and mechanically ventilated, and to additional weakness from the patient's relative immobility and bedridden state. This review surveys recent literature documenting these relationships and identifying approaches to minimize pharmacologic contributions to intensive care unit-acquired weakness.

Organelle Genome Inheritance in Deparia Ferns (Athyriaceae, Aspleniineae, Polypodiales

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Li-Yaung Kuo

2018-04-01

Full Text Available Organelle genomes of land plants are predominately inherited maternally but in some cases can also be transmitted paternally or biparentally. Compared to seed plants (>83% genera of angiosperms and >12% genera of gymnosperms, plastid genome (plastome inheritance has only been investigated in fewer than 2% of fern genera, and mitochondrial genome (mitogenome from only one fern genus. We developed a new and efficient method to examine plastome and mitogenome inheritance in a fern species—Deparia lancea (Athyriaceae, Aspleniineae, Polypodiales, and found that plastid and mitochondrial DNAs were transmitted from only the maternal parentage to a next generation. To further examine whether both organelle genomes have the same manner of inheritance in other Deparia ferns, we sequenced both plastid and mitochondrial DNA regions of inter-species hybrids, and performed phylogenetic analyses to identify the origins of organellar DNA. Evidence from our experiments and phylogenetic analyses support that both organelle genomes in Deparia are uniparentally and maternally inherited. Most importantly, our study provides the first report of mitogenome inheritance in eupolypod ferns, and the second one among all ferns.

Ricci inheritance symmetry in general relativity

International Nuclear Information System (INIS)

Bokhari, A.H.; Al-Dweik, A.; Zaman, F.D.; Karim, M.; Kubel, D.

2010-01-01

In an earlier paper (see Nuovo Cimento B, 19 (2004) 1187) it was conjectured that none of the well-known spherically symmetric static space-time solutions of the Einstein equations admit non-trivial Ricci inheritance symmetry. In this paper we discuss Ricci inheritance (R I) symmetry in three well-known non static spherically symmetric space-time metrics and show that our conjecture is also valid in non-static space-time metrics.

The rapid evolution of molecular genetic diagnostics in neuromuscular diseases.

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Volk, Alexander E; Kubisch, Christian

2017-10-01

The development of massively parallel sequencing (MPS) has revolutionized molecular genetic diagnostics in monogenic disorders. The present review gives a brief overview of different MPS-based approaches used in clinical diagnostics of neuromuscular disorders (NMDs) and highlights their advantages and limitations. MPS-based approaches like gene panel sequencing, (whole) exome sequencing, (whole) genome sequencing, and RNA sequencing have been used to identify the genetic cause in NMDs. Although gene panel sequencing has evolved as a standard test for heterogeneous diseases, it is still debated, mainly because of financial issues and unsolved problems of variant interpretation, whether genome sequencing (and to a lesser extent also exome sequencing) of single patients can already be regarded as routine diagnostics. However, it has been shown that the inclusion of parents and additional family members often leads to a substantial increase in the diagnostic yield in exome-wide/genome-wide MPS approaches. In addition, MPS-based RNA sequencing just enters the research and diagnostic scene. Next-generation sequencing increasingly enables the detection of the genetic cause in highly heterogeneous diseases like NMDs in an efficient and affordable way. Gene panel sequencing and family-based exome sequencing have been proven as potent and cost-efficient diagnostic tools. Although clinical validation and interpretation of genome sequencing is still challenging, diagnostic RNA sequencing represents a promising tool to bypass some hurdles of diagnostics using genomic DNA.

A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.

Science.gov (United States)

Bluteau, Olivier; Sebert, Marie; Leblanc, Thierry; Peffault de Latour, Régis; Quentin, Samuel; Lainey, Elodie; Hernandez, Lucie; Dalle, Jean-Hugues; Sicre de Fontbrune, Flore; Lengline, Etienne; Itzykson, Raphael; Clappier, Emmanuelle; Boissel, Nicolas; Vasquez, Nadia; Da Costa, Mélanie; Masliah-Planchon, Julien; Cuccuini, Wendy; Raimbault, Anna; De Jaegere, Louis; Adès, Lionel; Fenaux, Pierre; Maury, Sébastien; Schmitt, Claudine; Muller, Marc; Domenech, Carine; Blin, Nicolas; Bruno, Bénédicte; Pellier, Isabelle; Hunault, Mathilde; Blanche, Stéphane; Petit, Arnaud; Leverger, Guy; Michel, Gérard; Bertrand, Yves; Baruchel, André; Socié, Gérard; Soulier, Jean

2018-02-15

Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders ( GATA2 , RUNX1 ), telomeropathies ( TERC , TERT , RTEL1 ), ribosome disorders ( SBDS , DNAJC21 , RPL5 ), and DNA repair deficiency ( LIG4 ). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling. © 2018 by The American Society of Hematology.

Schwartz–jampel syndrome: Clinical and diagnostic phenotype of a rare genetic disorder

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Bhaskara P Shelley

2016-01-01

Full Text Available The distinctive phenotypic, clinical, skeletal characteristics with the typical electrophysiological features of an 11-year-old male child who presented to the neurology outpatient service are described, with the objective of emphasizing the diagnostic awareness of chondrodystrophic myotonia or Schwartz–Jampel syndrome, a very rare genetic disorder. This autosomal recessive disorder due to mutations in the gene Perlecan leads to abnormal cartilage development and anomalous neuromuscular activity.

Neuromuscular signs associated with acute hypophosphatemia in a dog.

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Claus, Kimberly N; Day, Thomas K; Wolf, Christina

2015-01-01

The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

Science.gov (United States)

Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

2013-11-01

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

Epigenetic Inheritance Across the Landscape

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Amy Vaughn Whipple

2016-10-01

Full Text Available The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

Epigenetic Inheritance across the Landscape.

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Whipple, Amy V; Holeski, Liza M

2016-01-01

The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

A theoretical framework for understanding neuromuscular response to lower extremity joint injury.

Science.gov (United States)

Pietrosimone, Brian G; McLeod, Michelle M; Lepley, Adam S

2012-01-01

Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

Science.gov (United States)

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Dynamic Inheritance and Static Analysis can be Reconciled

DEFF Research Database (Denmark)

Ernst, Erik

1998-01-01

the exibility and expressivity of staticlanguages while preserving the safety properties. It is an inheritancemechanism, with standard single inheritance as a special case. It al-lows both compile-time and run-time construction of new classes. More-over, it supports specialization of existing objects at run......-time. This helpsavoiding the combinatorial explosion in the number of classes associatedwith multiple inheritance, and it supports a better separation of con-cerns in large systems. Pre-methoding|inheritance applied to behavioraldescriptors|has been used for the construction of control structures formany years, in Beta....... With dynamic inheritance, pre-methoding becomesmore expressive, supporting control structures as rst class values whichmay be constructed and combined dynamically. Even though the conceptof pre-methoding is missing from most other languages, the basic ideacould be applied to any statically typed object...

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

Science.gov (United States)

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.

2010-01-01

A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs

Neuromuscular Manifestations of West Nile Virus Infection

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A. Arturo eLeis

2012-03-01

Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

Acute neuromuscular weakness associated with dengue infection

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Harmanjit Singh Hira

2012-01-01

Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

Effects of intensive physical rehabilitation on neuromuscular adaptations in adults with poststroke hemiparesis

DEFF Research Database (Denmark)

Andersen, Lars L; Zeeman, Peter; Jørgensen, Jørgen R

2011-01-01

consisting of isokinetic muscle strength, neuromuscular activation measured with electromyography (EMG), electrically evoked muscle twitch contractile properties, and gait performance (10-m Walk Test and 6-min Walk Test). After the 12-week conditioning program, knee extensor and flexor strength increased...... the effect of intensive physical rehabilitation on neuromuscular and functional adaptations in outpatients suffering from hemiparesis after stroke. A within-subject repeated-measures design with the paretic leg as the experimental leg and the nonparetic leg as the control leg was used. Eleven outpatients...... observed in the nonparetic control leg. Gait performance increased 52-68%. In conclusion, intensive physical rehabilitation after stroke leads to clinically relevant neuromuscular improvements, leading to increased voluntary strength during a wide range of contraction modes and velocities, and improved...

Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

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Corrêa da Silva Bruno Victor

2014-12-01

Full Text Available The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest. Neuromuscular performance was measured by the bench press throw (BPT and vertical counter movement jump (VCMJ tests, assessed before the 1st fight (Pre and after the last one (Post. Blood lactate (LA was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05 increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post, but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post were observed. LA concentration increased significantly (p < 0.05 at Post, both in the 1st min and the 15th min of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power was observed.

The effects of neuromuscular training on knee joint motor control during sidecutting in female elite soccer and handball players.

Science.gov (United States)

Zebis, Mette K; Bencke, Jesper; Andersen, Lars L; Døssing, Simon; Alkjaer, Tine; Magnusson, S Peter; Kjaer, Michael; Aagaard, Per

2008-07-01

The project aimed to implement neuromuscular training during a full soccer and handball league season and to experimentally analyze the neuromuscular adaptation mechanisms elicited by this training during a standardized sidecutting maneuver known to be associated with non-contact anterior cruciate ligament (ACL) injury. The players were tested before and after 1 season without implementation of the prophylactic training and subsequently before and after a full season with the implementation of prophylactic training. A total of 12 female elite soccer players and 8 female elite team handball players aged 26 +/- 3 years at the start of the study. The subjects participated in a specific neuromuscular training program previously shown to reduce non-contact ACL injury. Neuromuscular activity at the knee joint, joint angles at the hip and knee, and ground reaction forces were recorded during a sidecutting maneuver. Neuromuscular activity in the prelanding phase was obtained 10 and 50 ms before foot strike on a force plate and at 10 and 50 ms after foot strike on a force plate. Neuromuscular training markedly increased before activity and landing activity electromyography (EMG) of the semitendinosus (P Neuromuscular training increased EMG activity for the medial hamstring muscles, thereby decreasing the risk of dynamic valgus. This observed neuromuscular adaptation during sidecutting could potentially reduce the risk for non-contact ACL injury.

Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

DEFF Research Database (Denmark)

Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

2014-01-01

High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

Application of an Image Cytometry Protocol for Cellular and Mitochondrial Phenotyping on Fibroblasts from Patients with Inherited Disorders

DEFF Research Database (Denmark)

Fernandez-Guerra, Paula; Lund, Martin; Corydon, T J

2015-01-01

Cellular phenotyping of human dermal fibroblasts (HDFs) from patients with inherited diseases provides invaluable information for diagnosis, disease aetiology, prognosis and assessing of treatment options. Here we present a cell phenotyping protocol using image cytometry that combines measurements...... on a parallel one. We analysed HDFs from healthy individuals after treatment with various concentrations of hydrogen peroxide (H2O2) for different intervals, to mimic the physiological effects of oxidative stress. Our results show that cell number, viability, TRS and MMP decreased, while MSL increased both...... in a time- and concentration-dependent manner. To assess the use of our protocol for analysis of HDFs from patients with inherited diseases, we analysed HDFs from two patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD), one with a severe clinical phenotype and one with a mild...

Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

Science.gov (United States)

Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

2014-08-01

Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, ppain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective sweeps of mitochondrial DNA can drive the evolution of uniparental inheritance.

Science.gov (United States)

Christie, Joshua R; Beekman, Madeleine

2017-08-01

Although the uniparental (or maternal) inheritance of mitochondrial DNA (mtDNA) is widespread, the reasons for its evolution remain unclear. Two main hypotheses have been proposed: selection against individuals containing different mtDNAs (heteroplasmy) and selection against "selfish" mtDNA mutations. Recently, uniparental inheritance was shown to promote adaptive evolution in mtDNA, potentially providing a third hypothesis for its evolution. Here, we explore this hypothesis theoretically and ask if the accumulation of beneficial mutations provides a sufficient fitness advantage for uniparental inheritance to invade a population in which mtDNA is inherited biparentally. In a deterministic model, uniparental inheritance increases in frequency but cannot replace biparental inheritance if only a single beneficial mtDNA mutation sweeps through the population. When we allow successive selective sweeps of mtDNA, however, uniparental inheritance can replace biparental inheritance. Using a stochastic model, we show that a combination of selection and drift facilitates the fixation of uniparental inheritance (compared to a neutral trait) when there is only a single selective mtDNA sweep. When we consider multiple mtDNA sweeps in a stochastic model, uniparental inheritance becomes even more likely to replace biparental inheritance. Our findings thus suggest that selective sweeps of beneficial mtDNA haplotypes can drive the evolution of uniparental inheritance. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia : the FRUIT-RCT

NARCIS (Netherlands)

De Vries, J. I. P.; Van Pampus, M. G.; Hague, W. M.; Bezemer, P. D.; Joosten, J. H.

Background: Early-onset hypertensive disorders (HD) of pregnancy and small-for-gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding

Inherited Wealth

OpenAIRE

Beckert, J.

2008-01-01

How to regulate the transfer of wealth from one generation to the next has been hotly debated among politicians, legal scholars, sociologists, economists, and philosophers for centuries. Bequeathing wealth is a vital ingredient of family solidarity. But does the reproduction of social inequality through inheritance square with the principle of equal opportunity? Does democracy suffer when family wealth becomes political power? The first in-depth, comparative study of the development of inheri...

Molecular mechanisms for protein-encoded inheritance

Science.gov (United States)

Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

Science.gov (United States)

2015-08-24

Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

Propiocepción y control neuromuscular en el fútblo infantil

OpenAIRE

Zarza, Cristían

2014-01-01

En el fútbol profesional la escasa utilización de la pierna no hábil hace que muchas situaciones de juego no se resuelvan eficazmente, además de predisponer a la aparición de lesiones. El presente estudio se concentró en determinar la influencia del entrenamiento propioceptivo y del control neuromuscular en las cualidades físicas y técnicas del miembro no hábil. Objetivo: Indagar el nivel propioceptivo y de control neuromuscular del miembro inferior no hábil en chicos que re...

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

Science.gov (United States)

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Neuromuscular interactions around the knee in children, adults and elderly

Science.gov (United States)

Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

2014-01-01

Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

Directory of Open Access Journals (Sweden)

Ashok Verma

2018-01-01

Full Text Available Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

Magnetic resonance imaging (MRI) in the diagnosis of neuromuscular diseases

International Nuclear Information System (INIS)

Schalke, B.C.G.; Rohkamm, R.; Kaiser, W.

1990-01-01

In the last few years imaging procedures became also important in the diagnosis of neuromuscular diseases. We examined more than 150 patients with different neuromuscular diseases with MRI. Conventional diagnostic procedures like EMG, muscle biopsy can not be replaced by imaging procedures. MRI gives the chance to get additional diagnostic informations. It is possible to determine exact distribution and intensity of pathological changes in the muscle. Inflammatory muscle diseases can be differrentiated by T1/T2 values from atrophic/dystrophic diseases. The resolving power is very high and allows the exact detection of affected areas even in a single muscle. This can help to reduce false negative muscle biopsies. This is very useful in children and young adults. MRI can be used for the early detection of genetic myopathies and neuropathies. MRI allows to examine all muscles, including the heart, bone artefacts are absent. Heart muscle involvement in neuromuscular diseases can directly be shown by this method without any risk for the patient. In addition P-spectroscopy can be done for better understanding of pathogenesis, especially if the exact distribution of pathological changes is known. (author)

Neuromuscular deficits after peripheral joint injury: a neurophysiological hypothesis.

Science.gov (United States)

Ward, Sarah; Pearce, Alan J; Pietrosimone, Brian; Bennell, Kim; Clark, Ross; Bryant, Adam L

2015-03-01

In addition to biomechanical disturbances, peripheral joint injuries (PJIs) can also result in chronic neuromuscular alterations due in part to loss of mechanoreceptor-mediated afferent feedback. An emerging perspective is that PJI should be viewed as a neurophysiological dysfunction, not simply a local injury. Neurophysiological and neuroimaging studies have provided some evidence for central nervous system (CNS) reorganization at both the cortical and spinal levels after PJI. The novel hypothesis proposed is that CNS reorganization is the underlying mechanism for persisting neuromuscular deficits after injury, particularly muscle weakness. There is a lack of direct evidence to support this hypothesis, but future studies utilizing force-matching tasks with superimposed transcranial magnetic stimulation may be help clarify this notion. © 2014 Wiley Periodicals, Inc.

Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

Science.gov (United States)

Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

1999-06-01

Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

Science.gov (United States)

Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

2018-01-15

Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

Skeletal Muscle Na+ Channel Disorders

Directory of Open Access Journals (Sweden)

Dina eSimkin

2011-10-01

Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

A human model for multigenic inheritance : Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus

NARCIS (Netherlands)

Bolk, S; Pelet, A; Hofstra, RMW; Angrist, M; Salomon, R; Croaker, D; Buys, CHCM; Lyonnet, S; Chakravarti, A

2000-01-01

Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with approximate to 50% of familial cases being heterozygous for mutations in the receptor tyrosine

Unexplained infertility: association with inherited thrombophilia.

Science.gov (United States)

Fatini, Cinzia; Conti, Lucia; Turillazzi, Valentina; Sticchi, Elena; Romagnuolo, Ilaria; Milanini, Maria Novella; Cozzi, Cinzia; Abbate, Rosanna; Noci, Ivo

2012-05-01

Unexplained infertility represents one of the most common diagnoses in fertility care. Attention is being paid to the association between inherited thrombophilia and infertility causes. In this study we investigated the prevalence of inherited thrombophilia according to infertility causes. We studied Prothrombin gene G20210A mutation, Factor V Leiden, deficiencies in protein S and C and antithrombin in 930 Caucasian infertile women referred to Fertility Center of the Department of Sciences for Woman and Child's Health, University of Florence, of whom 230 with unexplained, 195 female and 283 male infertility, and in 240 women who have conceived naturally without hormonal stimulation therapy. A significant relationship between inherited thrombophilia [OR 95%CI 1.97 (1.05-3.68), p = 0.03] and unexplained infertility was observed, whereas no association between thrombophilia and female and male infertility was found. Significantly higher prevalence of prothrombin gene mutation in unexplained infertile women in comparison to that observed in fertile women was observed (5.7% vs 2.1% p = 0.04); the prevalence of the other thrombophilia determinants was higher, even if not significantly, in the unexplained infertile group. This study demonstrates the relationship between inherited thrombophilia and unexplained infertility, thus suggesting the contribution of genetic components in modulating unexplained infertility, behind anovulation, male and tubal factor. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neuromuscular performance in the hip joint of elderly fallers and non-fallers.

Science.gov (United States)

Morcelli, Mary Hellen; LaRoche, Dain Patrick; Crozara, Luciano Fernandes; Marques, Nise Ribeiro; Hallal, Camilla Zamfolini; Rossi, Denise Martineli; Gonçalves, Mauro; Navega, Marcelo Tavella

2016-06-01

Low strength and neuromuscular activation of the lower limbs have been associated with falls making it an important predictor of functional status in the elderly. To compare the rate of neuromuscular activation, rate of torque development, peak torque and reaction time between young and elderly fallers and non-fallers for hip flexion and extension. We evaluated 44 elderly people who were divided into two groups: elderly fallers (n = 20) and elderly non-fallers (n = 24); and 18 young people. The subjects performed three isometric hip flexion and extension contractions. Electromyography data were collected for the rectus femoris, gluteus maximus and biceps femoris muscles. The elderly had 49 % lower peak torque and 68 % lower rate of torque development for hip extension, 28 % lower rate of neuromuscular activation for gluteus maximus and 38 % lower rate of neuromuscular activation for biceps femoris than the young (p neuromuscular for rectus femoris than the young (p < 0.05). The elderly fallers showed consistent trend toward a lower rate of torque development than elderly non-fallers for hip extension at 50 ms (29 %, p = 0.298, d = 0.76) and 100 ms (26 %, p = 0.452, d = 0.68).The motor time was 30 % slower for gluteus maximus, 42 % slower for rectus femoris and 50 % slower for biceps femoris in the elderly than in the young. Impaired capacity of the elderly, especially fallers, may be explained by neural and morphological aspects of the muscles. The process of senescence affects the muscle function of the hip flexion and extension, and falls may be related to lower rate of torque development and slower motor time of biceps femoris.

Effects of Neuromuscular Electrical Stimulation During Hemodialysis on Peripheral Muscle Strength and Exercise Capacity: A Randomized Clinical Trial.

Science.gov (United States)

Brüggemann, Ana Karla; Mello, Carolina Luana; Dal Pont, Tarcila; Hizume Kunzler, Deborah; Martins, Daniel Fernandes; Bobinski, Franciane; Pereira Yamaguti, Wellington; Paulin, Elaine

2017-05-01

To evaluate the effects of neuromuscular electrical stimulation of high and low frequency and intensity, performed during hemodialysis, on physical function and inflammation markers in patients with chronic kidney disease (CKD). Randomized clinical trial. Hemodialysis clinic. Patients with CKD (N=51) were randomized into blocks of 4 using opaque sealed envelopes. They were divided into a group of high frequency and intensity neuromuscular electrical stimulation and a group of low frequency and intensity neuromuscular electrical stimulation. The high frequency and intensity neuromuscular electrical stimulation group was submitted to neuromuscular electrical stimulation at a frequency of 50Hz and a medium intensity of 72.90mA, and the low frequency and intensity neuromuscular electrical stimulation group used a frequency of 5Hz and a medium intensity of 13.85mA, 3 times per week for 1 hour, during 12 sessions. Peripheral muscle strength, exercise capacity, levels of muscle trophism marker (insulin growth factor 1) and levels of proinflammatory (tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines. The high frequency and intensity neuromuscular electrical stimulation group showed a significant increase in right peripheral muscle strength (155.35±65.32Nm initial vs 161.60±68.73Nm final; P=.01) and left peripheral muscle strength (156.60±66.51Nm initial vs 164.10±69.76Nm final; P=.02) after the training, which did not occur in the low frequency and intensity neuromuscular electrical stimulation group for both right muscle strength (109.40±32.08Nm initial vs 112.65±38.44Nm final; P=.50) and left muscle strength (113.65±37.79Nm initial vs 116.15±43.01Nm final; P=.61). The 6-minute walk test distance (6MWTD) increased in both groups: high frequency and intensity neuromuscular electrical stimulation group (435.55±95.81m initial vs 457.25±90.64m final; P=.02) and low frequency and intensity neuromuscular electrical stimulation group (403.80�

Inheritance tax revenue low despite surge in inheritances

OpenAIRE

Bach, Stefan; Thiemann, Andreas

2016-01-01

Every year in Germany, an estimated 200 to 300 billion euros is gifted or inherited. Due to the extremely unequal distribution of wealth, these capital transfers are also highly concentrated. Approximately half of all transfers are less worth than 50,000 euros. Transfers of over 500,000 euros were received by one and a half percent of beneficiaries, accounting for one-third of the total transfer volume. The 0.08 percent of cases with transfers of over five million euros received 14 percent of...

Assessment of bone density in patients with scoliosis neuromuscular secondary to cerebral palsy

Directory of Open Access Journals (Sweden)

Charbel Jacob Júnior

2014-09-01

Full Text Available OBJECTIVE: To evaluate bone mineral density in patients with neuromuscular scoliosis secondary to spastic quadriplegic cerebral palsy. METHODS: A prospective descriptive study in which, in addition to bone densitometry, the anthropometric data of the patients were assessed. As inclusion criterion we adopted patients with spastic quadriplegic cerebral palsy, wheelchair users, aged between 10 and 20 years and with neuromuscular scoliosis. RESULTS: We evaluated 31 patients, 20 female, whose average age was 14.2 years. The mean bone density was -3.2 standard deviation (Z-score, with mean biceps circumference of 19.4 cm, calf circumference 18.6 cm and BMI of 13.6 kg/m². CONCLUSION: There is a high incidence of osteoporosis in patients with neuromuscular scoliosis secondary to spastic quadriplegic cerebral palsy.

Constitutional delay of puberty: presentation and inheritance pattern in 48 familial cases.

Science.gov (United States)

Winter, Sarah; Ousidhoum, Aldjia; McElreavey, Kenneth; Brauner, Raja

2016-03-12

The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. Familial forms of constitutional delay of puberty (CDP) suggest the involvement of genetic factors. The purpose of this study is to describe the presentation and the mode of inheritance of CDP in a series of familial cases. A retrospective, single center study was carried out over 10 years on 48 probands (14 girls and 34 boys) from 48 families seen for CDP with a familial component. Of the 48 probands, 46 (96 %) had at least one affected 1(st) degree relatives and 2 (4 %, 2 boys) had only 2(nd) degree relatives affected. In girls, 11 families (79 %) exhibited exclusive maternal inheritance, 1 (7 %) paternal inheritance and 2 (14 %) both maternal and paternal inheritance. In boys, 14 families (41 %) exhibited exclusive maternal inheritance, 12 (35 %) paternal inheritance and 8 (24 %) both maternal and paternal inheritance. In the boys with bilineal inheritance, the ages at onset of puberty (16 ± 1.41 years) and at evaluation (16.05 ± 2.47 years) were higher than in those with unilineal inheritance (15.25 ± 0.35 and 15.1 ± 0.42 years respectively), but the difference was not significant. In girls exclusive maternal inheritance seems to be the major mode of inheritance whereas for boys the mode of inheritance was almost equally maternal, paternal or bilineal. Clinical phenotype of boys with bilineal inheritance seems to be more severe, but the difference did not reach statistical significance, perhaps because of the small sample size. This greater severity of the phenotype in boys with bilineal inheritance is likely due to inheriting different puberty timing genes from each parent. Future research should be directed at identifying such genes.

Whole-body vibration does not influence knee joint neuromuscular function or proprioception.

Science.gov (United States)

Hannah, R; Minshull, C; Folland, J P

2013-02-01

This study examined the acute effects of whole-body vibration (WBV) on knee joint position sense and indices of neuromuscular function, specifically strength, electromechanical delay and the rate of force development. Electromyography and electrically evoked contractions were used to investigate neural and contractile responses to WBV. Fourteen healthy males completed two treatment conditions on separate occasions: (1) 5 × 1 min of unilateral isometric squat exercise on a synchronous vibrating platform [30 Hz, 4 mm peak-to-peak amplitude] (WBV) and (2) a control condition (CON) of the same exercise without WBV. Knee joint position sense (joint angle replication task) and quadriceps neuromuscular function were assessed pre-, immediately-post and 1 h post-exercise. During maximum voluntary knee extensions, the peak force (PF(V)), electromechanical delay (EMD(V)), rate of force development (RFD(V)) and EMG of the quadriceps were measured. Twitch contractions of the knee extensors were electrically evoked to assess EMD(E) and RFD(E). The results showed no influence of WBV on knee joint position, EMD(V), PF(V) and RFD(V) during the initial 50, 100 or 150 ms of contraction. Similarly, electrically evoked neuromuscular function and neural activation remained unchanged following the vibration exercise. A single session of unilateral WBV did not influence any indices of thigh muscle neuromuscular performance or knee joint proprioception. © 2011 John Wiley & Sons A/S.

Family Intervention with a Case of Bipolar I Disorder with Family Conflict

Science.gov (United States)

Sahu, Kamlesh Kumar

2013-01-01

Bipolar disorder is a major mental illness. Inherited treatment of bipolar disorder has been focused on pharmacological treatments. Though, psychosocial variables appear to be important antecedents of bipolar disorder, poor drug compliance, expressed emotion or faulty communication and life events play a vital role in relapse. Conflict is commonly…

Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.

Science.gov (United States)

Kazuo Ikeda, K I; Masaki Matsuda, M M; Daisuke Yamauchi, D Y; Katsuro Tomita, K T; Shigenori Tanaka, S T

2005-07-01

The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

Bilateral neuromuscular and force differences during a plyometric task.

Science.gov (United States)

Ball, Nick B; Scurr, Joanna C

2009-08-01

The purpose of this article is to compare the bilateral neuromuscular and force contribution during a plyometric bounce drop jump task and to assess the affects of nonsimultaneous foot placement. Sixteen male participants performed bounce drop jumps from a height of 0.4 m. Mean peak electromyography activity of the soleus, medial, and lateral gastrocnemius of both legs was recorded from each phase of the drop jump and normalized to a reference dynamic muscle action. Resultant ground reaction force, ground contact time, and duration of the drop jumps were recorded from each leg. Multivariate analysis of variance was used to compare bilateral electromyographic activity, resultant peak ground reaction force, and contact duration. Pearson's correlations (r) ascertained relationships between normalized electromyographic activity and contact time. Significant differences were shown between left and right triceps surae normalized electromyography during precontact and contact40ms (p 0.01). Significant differences were found between normalized soleus electromyography and both gastrocnemii for both legs during precontact (p 0.01). Weak relationships were found between normalized electromyographic activity and nonsimultaneous foot contact (r < 0.2). This study showed differences between left and right triceps surae in neuromuscular strategies engaged in the early stages of a drop jump task. Differences in contact time initiation were present; however, they are not significant enough to cause neuromuscular differences in the plantar flexor muscles.

Neuromuscular adaptations induced by adjacent joint training.

Science.gov (United States)

Ema, R; Saito, I; Akagi, R

2018-03-01

Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training. © 2017 The Authors. Scandinavian Journal of Medicine & Science In Sports Published by John Wiley & Sons Ltd.

Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

Science.gov (United States)

Ramsay, D A; Drachman, D B; Pestronk, A

1988-10-11

The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients

OpenAIRE

Serrano Mercedes L.; Martins Cecilia E.; Pérez-Dueñas Belén; Gómez-López Lilian; Murgui Empar; Fons Carmen; García-Cazorla Ángels; Artuch Rafael M D; Jara Fernando; Arranz José Antonio; Häberle Johannes; Briones Paz; Campistol Jaume M D; Pineda Mercè; Vilaseca María Antònia Antonia

2010-01-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation attention deficit hyper...

Inherited Retinal Degenerative Clinical Trial Network. Addendum

Science.gov (United States)

2013-10-01

inherited orphan retinal degenerative diseases and dry age-related macular degeneration (AMD) through the conduct of clinical trials and other...design and conduct of effective and efficient clinical trials for inherited orphan retinal degenerative diseases and dry AMD; • Limited number and...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa, and the ProgSTAR studies for Stargardt disease ) . As new interventions b

Regulation, cell differentiation and protein-based inheritance.

Science.gov (United States)

Malagnac, Fabienne; Silar, Philippe

2006-11-01

Recent research using fungi as models provide new insight into the ability of regulatory networks to generate cellular states that are sufficiently stable to be faithfully transmitted to daughter cells, thereby generating epigenetic inheritance. Such protein-based inheritance is driven by infectious factors endowed with properties usually displayed by prions. We emphasize the contribution of regulatory networks to the emerging properties displayed by cells.

Statutory Law, Patriarchy and Inheritance: Home ownership among ...

African Journals Online (AJOL)

inheritance customs, which in many cases discriminate against women. While one would expect the inheritance statutory law to protect the widow, instead it supports the cultural image ideology that encourages male dominance. The intestate succession law guarantees the widow only the user rights to the matrimonial ...

Partial neuromuscular blockade in humans enhances muscle blood flow during exercise independently of muscle oxygen uptake and acetylcholine receptor blockade

DEFF Research Database (Denmark)

Hellsten, Ylva; Krustrup, Peter; Iaia, F Marcello

2009-01-01

This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one-legged k......This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one...... conductance during exercise, events that are not associated with either acetylcholine or an increased oxygen demand. The results do not support an essential role for acetylcholine, released form the neuromuscular junction, in exercise hyperaemia or for the enhanced blood flow during neuromuscular blockade....... The enhanced exercise hyperemia during partial neuromuscular blockade may be related to a greater recruitment of fast-twitch muscle fibres. Key words: blood flow, neuromuscular blockade, exercise, skeletal muscle....

Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

Science.gov (United States)

Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

2012-11-13

Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

Legal Inheritance in the Republic of Kosovo

Directory of Open Access Journals (Sweden)

Dr.Sc. Hamdi Podvorica

2011-06-01

Full Text Available Legal inheritance is one of the most important institutions of inheritance law which regulates the process of legal transition of property of the decedent to one or several heirs. The establish-ment of the legal framework has brought about new reforms to the Inheritance Law. This has enabled the enrichment and functio-ning of the law. A particularly important step was taken towards regulation of legal procedures regarding to how courts, other or-gans and other persons should act regarding inheritance issues. Concretization of the legal authorizations of bodies authorized to enforce the procedure of processing hereditary property has estab-lished the legal basis for realization of the iso jure principle, accor-ding to which, at the moment of death of the person, the heirs gain the right of inheritance and the hereditary property is never left without a titleholder. This is a great advantage that we have noted in undertaking this analysis of the norms in this work, because leaving hereditary property for a longer period of time without a titleholder would render the property vulnerable to des-truction, theft and extermination. The goal of this paper is to avoid focusing only on finding the positive sides of the normative regulation of the legal inheritance process, but also in finding practical deficiencies that are weighing down at the moment on this important process in Kosovo, and in proposing measures for overcoming them. The dark side of the legal inheritance process is linked to the inefficiency of courts and the still fragile legal system in Kosovo. By implementing empirical methods, we have come to the con-clusion that the low number of judges in proportion with the huge number of cases has become a key liability for practical implemen-tation of the principle of initiating the legal procedure ex officio. The failure in enforcing this principle and initiating the procedu-res for processing of hereditary property by courts, even though they

Phenobarbital influence on neuromuscular block produced by rocuronium in rats Influência do fenobarbital no bloqueio neuromuscular produzido pelo rocurônio em ratos

Directory of Open Access Journals (Sweden)

Angélica de Fátima de Assunção Braga

2008-08-01

Full Text Available PURPOSE: To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS: Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg and the following parameters were evaluated: 1 the amplitude of muscle response in the preparation of rats exposed to phenobarbital; 2 rocuronium effect on rat preparation exposed or not to phenobarbital; 3 concentrations of cytochrome P450 and cytochrome b5 in hepatic microsomes isolated from rats exposed or not to phenobarbital. The concentration and dose of rocuronium used in vitro and in vivo experiments were 4 µg/mL and 0,6 mg/kg, respectively. RESULTS: Phenobarbital in vitro and in vivo did not alter the amplitude of muscle response. The neuromuscular blockade in vitro produced by rocuronium was significantly different (p=0.019 between exposed (20% and not exposed (60% rats; the blockade in vivo was significantly greater (p=0.0081 in treated rats (93.4%. The enzymatic concentrations were significantly greater in rats exposed to phenobarbital. CONCLUSIONS: Phenobarbital alone did not compromise neuromuscular transmission. It produced enzymatic induction, and neuromuscular blockade in vivo produced by rocuronium was potentiated by phenobarbital.OBJETIVO: Avaliar in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio em ratos tratados com fenobarbital e determinar as concentrações de citocromo P450 e b5 em microssomos hepáticos. MÉTODOS: Trinta ratos foram incluídos no estudo e distribuídos em seis grupos de cinco animais cada. Ratos foram tratados por sete dias com fenobarbital (20 mg/kg e avaliou-se: 1 amplitude das respostas musculares em preparação de ratos expostos ao fenobarbital; 2 o efeito do rocurônio em preparações de ratos expostos ou n

Assessment of Motor Units in Neuromuscular Disease.

Science.gov (United States)

Henderson, Robert D; McCombe, Pamela A

2017-01-01

The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an effective biomarker for assessing disease progression and for use in clinical trials in amyotrophic lateral sclerosis has stimulated the study of methods to measure the number of motor units. Since 1970 a number of different methods, including the incremental, F-wave, multipoint, and statistical methods, have been developed but none has achieved widespread applicability. Two methods (MUNIX and the multipoint incremental method) are in current use across multiple centres and are discussed in detail in this review, together with other recently published methods. Imaging with magnetic resonance and ultrasound is increasingly being applied to this area. Motor unit number estimates have also been applied to other neuromuscular diseases such as spinal muscular atrophy, compression neuropathies, and prior poliomyelitis. The need for an objective measure for the assessment of motor units remains tantalizingly close but unfulfilled in 2016.

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

Science.gov (United States)

Ishigaki, Sayaka; Ogura, Takahiro; Kanaya, Ayana; Miyake, Yu; Masui, Kenichi; Kazama, Tomiei

2017-01-01

The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. Randomised, single-blinded study. A secondary hospital from October 2013 to July 2014. In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. Arterial plasma rocuronium concentrations. Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. Umin identifier: UMIN000011981.

Proceedings of the Inheritance Workshop at ECOOP 2002

DEFF Research Database (Denmark)

2002-01-01

The Inheritance Workshop at ECOOP 2002, which took place on Tuesday, 11 June, was the first ECOOP workshop focusing on inheritance after the successful workshops in 1991 and 1992. The workshop was intended as a forum for designers and implementers of object-oriented languages, and for software de...

Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder

OpenAIRE

Mahmood, Tashfeen; Nugent, Kenneth

2015-01-01

Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting.

Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder.

Science.gov (United States)

Mahmood, Tashfeen; Nugent, Kenneth

2015-07-01

Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting.

Symmetry inheritance of scalar fields

International Nuclear Information System (INIS)

Ivica Smolić

2015-01-01

Matter fields do not necessarily have to share the symmetries with the spacetime they live in. When this happens, we speak of the symmetry inheritance of fields. In this paper we classify the obstructions of symmetry inheritance by the scalar fields, both real and complex, and look more closely at the special cases of stationary and axially symmetric spacetimes. Since the symmetry noninheritance is present in the scalar fields of boson stars and may enable the existence of the black hole scalar hair, our results narrow the possible classes of such solutions. Finally, we define and analyse the symmetry noninheritance contributions to the Komar mass and angular momentum of the black hole scalar hair. (paper)

Residual neuromuscular block as a risk factor for critical respiratory events in the post anesthesia care unit.

Science.gov (United States)

Norton, M; Xará, D; Parente, D; Barbosa, M; Abelha, F J

2013-04-01

Residual neuromuscular block is an important postoperative complication associated to the use of neuromuscular blocking drugs. The purpose of this study was to access the incidence of residual neuromuscular block in a post-anesthesia care unit and to evaluate its association with critical respiratory events. Prospective cohort study was conducted in a Post Anesthetic Care Unit (PACU) for a period of 3 weeks. Two hundred two adult patients who submitted to scheduled non-cardiac and non-intracranial surgery were eligible to the study. The primary outcome variable was residual neuromuscular block after arrival to PACU that was defined as train-of-four ratio <0.9 and objectively quantified using acceleromyography. Demographic data, perioperative variables, lengths of hospital and recovery room stay and critical respiratory events were recorded. Inadequate emergence was classified in its different forms according to the Richmond agitation and sedation scale 10 min after admission to the recovery room. Residual neuromuscular block incidence in the post-anesthesia care unit was 29.7% (95% confidence interval: 23.4, 36.1). Patients with residual neuromuscular block had more frequently overall critical respiratory events (51% versus 16%, P<0.001), airway obstruction (10% versus 2%, P=0.029), mild-moderate hypoxemia (23% versus 4%, P<0.001), severe hypoxemia (7% versus 1%, P=0.033), respiratory failure (8% versus 1%, P=0.031), inability to breathe deeply (38% versus 12%, P<0.001) and muscular weakness (16% versus 1%, P<0.001). Residual neuromuscular block was more common after high-risk surgery (53% versus 33%, P=0.011) and was more often associated with post-operative hypoactive emergence as defined by the Richmond Agitation and Sedation Scale (21% versus 6%, P=0.001). This study suggests that residual neuromuscular block is common in the PACU and is associated with more frequent critical respiratory events. Copyright © 2012 Sociedad Española de Anestesiología, Reanimaci

Diagnostic value of CT scanning in neuromuscular diseases

International Nuclear Information System (INIS)

Bulcke, J.A.L.; Leuven Univ.; Herpels, V.

1983-01-01

The diagnosis of myopathies has become easier since the CT technique is available. In this article the possibilities of CT for diagnostic procedures of neuromuscular diseases are pointed out. Density measurements increase differentiation of atrophy or hypertrophy of muscles as well as other pathological changes. (orig.)

Comparison of the Effect of Neuromuscular Electrical Stimulation ...

African Journals Online (AJOL)

Children with cerebral palsy (CP) often demonstrate poor hand function due to spasticity. Thus spasticity in the wrist and finger flexors poses a great deal of functional limitations. This study was therefore designed to compare the effectiveness of Cryotherapy and Neuromuscular Electrical Stimulation (NMES) on spasticity ...

Occupational Inheritance in Service Academy Cadets and Midshipmen

Science.gov (United States)

Roller, Brain; Doerries, Lee E.

2008-01-01

Occupational inheritance refers to the phenomenon where sons and daughters follow in the career paths of their parents. Historically this has been documented in the areas of engineering, medicine and education. This study investigated the phenomenon of occupational inheritance as it pertains to military service. Archival data provided by the…

26 CFR 1.102-1 - Gifts and inheritances.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Gifts and inheritances. 1.102-1 Section 1.102-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Items Specifically Excluded from Gross Income § 1.102-1 Gifts and inheritances...

Adherence issues in inherited metabolic disorders treated by low natural protein diets

DEFF Research Database (Denmark)

MaCdonald, A; van Rijn, M; Feillet, F

2012-01-01

Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor......-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

Cross Border Inheritances and European Community Law : Juridical double taxation of inheritances and the free movement of capital

OpenAIRE

Wiberg, Caroline

2009-01-01

Double taxation is known as restricting the free flow of capital and accordingly results in a limited access of the internal market. Although, not many Member States have entered into double taxation conventions in order to avoid juridical double taxation of inheritances. The question then arises whether this failure to eliminate juridical double taxation is restricting the free movement of capital. The ECJ‟s case law regarding inheritance taxes are very varying. In its initial case law, the ...

Intracranial hemorrhage in congenital bleeding disorders.

Science.gov (United States)

Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

2018-01-01

: Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

Targeted massively parallel sequencing and histological assessment of skeletal muscles for the molecular diagnosis of inherited muscle disorders.

Science.gov (United States)

Nishikawa, Atsuko; Mitsuhashi, Satomi; Miyata, Naomasa; Nishino, Ichizo

2017-02-01

Inherited skeletal muscle diseases are genetically heterogeneous diseases caused by mutations in more than 150 genes. This has made it challenging to establish a high-throughput screening method for identifying causative gene mutations in clinical practice. In the present study, we developed a useful method for screening gene mutations associated with the pathogenesis of skeletal muscle diseases. We established four target gene panels, each covering all exonic and flanking regions of genes involved in the pathogenesis of the following muscle diseases: (1) muscular dystrophy (MD), (2) congenital myopathy/congenital myasthenic syndrome, (3) metabolic myopathy and (4) myopathy with protein aggregations/rimmed vacuoles. We assigned one panel to each patient based on the results of clinical and histological analyses of biopsied muscle samples and performed high-throughput sequencing by using Ion PGM next-generation sequencer. We also performed protein analysis to confirm defective proteins in patients with major muscular dystrophies. Further, we performed muscle-derived cDNA analysis to identify splice-site mutations. We identified possible causative gene mutations in 33% of patients (62/188) included in this study. Our results showed that the MD panel was the most useful, with a diagnostic rate of 46.2%. Thus, we developed a high-throughput sequencing technique for diagnosing inherited muscle diseases. The use of this technique along with histological and protein analyses may be useful and cost-effective for screening mutations in patients with inherited skeletal muscle diseases. 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/.

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

Science.gov (United States)

Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

2008-11-15

We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

Science.gov (United States)

Nijssen, Jik; Frost‐Nylen, Johanna

2015-01-01

Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26502195

Effects of Short- and Long-Duration Space Flight on Neuromuscular Function

Science.gov (United States)

Buxton, Roxanne E.; Spiering, Barry A.; Ryder, Jeffrey W.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

2010-01-01

The Functional Task Tests (FTT) is an interdisciplinary study designed to correlate the changes in functional tasks (such as emergency egress, ladder climbing, and hatch opening) with changes in neuromuscular, cardiovascular, and sensorimotor function. One aspect of the FTT, the neuromuscular function test, is used to investigate the neuromuscular component underlying changes in the ability of astronauts to perform functional tasks (representative of critical mission tasks) safely and quickly after flight. PURPOSE: To describe neuromuscular function after short- and long-duration space flight. METHODS: To date, 5 crewmembers on short-duration (10- to 15-day) missions and 3 on long-duration missions have participated. Crewmembers were assessed 30 days before flight, on landing day (short-duration subjects only) and 1, 6, and 30 days after landing. The interpolated twitch technique, which utilizes a combination of maximal voluntary contractions and electrically evoked contractions, was used to assess the maximal voluntary isometric force (MIF) and central activation capacity of the knee extensors. Leg-press and bench-press devices were used to assess MIF and maximal dynamic power of the lower and upper body respectively. Specifically, power was measured during concentric-only ballistic throws of the leg-press sled and bench-press bar loaded to 40% and 30% of MIF respectively. RESULTS: Data are currently being collected from both Shuttle and ISS crewmembers. Emerging data indicate that measures of knee extensor muscle function are decreased with long-duration flight. DISCUSSION: The relationships between flight duration, neural drive, and muscle performance are of particular interest. Ongoing research will add to the current sample size and will focus on defining changes in muscle performance measures after long-duration space flight.

Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia.

Science.gov (United States)

Sweet, Laurene A; OʼNeill, Lindsey M; Dobbs, Matthew B

2014-01-01

The purpose of this report is to explore assessment and serial casting intervention for painful rigid flatfoot deformities with vertical talus in an adolescent girl with hereditary spastic paraplegia who was nonambulatory. The participant's right foot underwent 2 phases of casting with correction first toward hindfoot inversion and then dorsiflexion. Because of a vertical talus, her left foot required an intermediate casting toward plantar flexion, inversion, and forefoot adduction prior to casting toward dorsiflexion. The patient improved despite the underlying progressive neuromuscular disorder. Pain ameliorated and she returned to supported standing and transfers. Spasticity decreased bilaterally and the flexibility of her foot deformities improved to allow orthotic fabrication in subtalar neutral. Results were maintained at 12 and 16 months. Individualized multiphase serial casting requires further investigation with patients such as those with hereditary spastic paraplegia.

Inheritance for software reuse: The good, the bad, and the ugly

Science.gov (United States)

Sitaraman, Murali; Eichmann, David A.

1992-01-01

Inheritance is a powerful mechanism supported by object-oriented programming languages to facilitate modifications and extensions of reusable software components. This paper presents a taxonomy of the various purposes for which an inheritance mechanism can be used. While some uses of inheritance significantly enhance software reuse, some others are not as useful and in fact, may even be detrimental to reuse. The paper discusses several examples, and argues for a programming language design that is selective in its support for inheritance.

Early appearance and possible roles of non-neuromuscular cholinesterases.

Directory of Open Access Journals (Sweden)

Carla eFalugi

2012-04-01

Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

Survey of how different groups of veterinarians manage the use of neuromuscular blocking agents in anesthetized dogs.

Science.gov (United States)

Martin-Flores, Manuel; Sakai, Daniel M; Campoy, Luis; Gleed, Robin D

2018-03-23

To analyze practice habits associated with the use, reversal and monitoring of nondepolarizing neuromuscular blocking agents (NMBAs) in dogs by different groups of veterinarians. Online anonymous survey to veterinarians. Data from 390 answered surveys. A questionnaire was sent to e-mail list servers of the American College of Veterinary Anesthesia and Analgesia (ACVAA-list), Sociedad Española de Anestesia y Analgesia Veterinaria (SEEAV-list), Colégio Brasileiro de Anestesiologia Veterinária (Brazilian College of Veterinary Anesthesiology; CBAV-list) and American College of Veterinary Ophthalmologists (ACVO-list) to elicit information regarding use of NMBAs and reversal agents, monitoring techniques, criteria for redosing, reversing and assessing adequacy of recovery of neuromuscular function. Binomial logistic regression was used to test for association between responses and group of veterinarians in selected questions. Veterinarians of the ACVO-list use NMBAs on a higher fraction of their caseload than other groups (all p < 0.0001). Subjective assessment (observation) of spontaneous movement, including spontaneous breathing, is the most common method for assessing neuromuscular function (43% of pooled responses); 18% of participants always reverse NMBAs, whereas 16% never reverse them. Restoration of neuromuscular function is assessed subjectively by 35% of respondents. Residual neuromuscular block is the most common concern regarding the use of NMBAs for all groups of veterinarians. Side effects of reversal agents (anticholinesterases) were of least concern for all groups. While most veterinarians are concerned about residual neuromuscular block, relatively few steps are implemented to reduce the risks of this complication, such as routine use of quantitative neuromuscular monitoring or routine reversal of NMBAs. These results suggest a limitation in transferring information among groups of veterinarians, or in implementing techniques suggested by scientific

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability

DEFF Research Database (Denmark)

Eshoj, Henrik; Rasmussen, Sten; Frich, Lars Henrik

2017-01-01

BACKGROUND: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence......-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme...... dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status...

Genetic hearing impairment : a clinical study of various dominant inherited types

NARCIS (Netherlands)

Ensink, Robbert Jan Herman

2000-01-01

In this thesis a presentation is given of different patterns of inheritance, present in the cochlea or in the auditory chain of ossicles. Presentation and diagnosis of hereditary hearing loss is reviewed. A rare pattern of inheritance is the so called mitochondrial or maternal inheritance. In this

Alport syndrome: impact of digenic inheritance in patients management.

Science.gov (United States)

Fallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, A R; Garosi, G; Frullanti, E; Pinto, A M; Mencarelli, M A; Mari, F; Renieri, A; Ariani, F

2017-07-01

Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

Science.gov (United States)

Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

2015-01-01

The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Population thinking and natural selection in dual-inheritance theory

NARCIS (Netherlands)

Houkes, W.N.

2012-01-01

A deflationary perspective on theories of cultural evolution, in particular dual-inheritance theory, has recently been proposed by Lewens. On this ‘pop-culture’ analysis, dual-inheritance theorists apply population thinking to cultural phenomena, without claiming that cultural items evolve by

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report.

Science.gov (United States)

O'Driscoll, Jeremiah; Kerin, Fearghal; Delahunt, Eamonn

2011-06-09

Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: 1 Cumberland Ankle Instability Tool (CAIT) scores, 2 Star Excursion Balance Test (SEBT) reach distances, 3 ankle joint plantar flexion during drop landing and drop vertical jumping, and 4 ground reaction forces (GRFs) during walking. CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.

Autosomal recessive mode of inheritance of a Coffin-Siris like syndrome.

Science.gov (United States)

Bonioli, E; Palmieri, A; Bertola, A; Bellini, C

1995-01-01

Autosomal recessive mode of inheritance of a Coffin-Siris like syndrome: Coffin-Siris syndrome is a rare mental retardation/multiple congenital anomalies syndrome; so far its pattern of inheritance is under debate. We report a child affected by this syndrome, the pedigree of which is consistent with autosomal recessive inheritance.

Maternal telomere length inheritance in the king penguin.

Science.gov (United States)

Reichert, S; Rojas, E R; Zahn, S; Robin, J-P; Criscuolo, F; Massemin, S

2015-01-01

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Gene panel testing for inherited cancer risk.

Science.gov (United States)

Hall, Michael J; Forman, Andrea D; Pilarski, Robert; Wiesner, Georgia; Giri, Veda N

2014-09-01

Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process. Copyright © 2014 by the National Comprehensive Cancer Network.

Endangering of Businesses by the German Inheritance Tax? – An Empirical Analysis

Directory of Open Access Journals (Sweden)

Henriette Houben

2011-04-01

Full Text Available This contribution addresses the substantial tax privilege for businesses introduced by the German Inheritance Tax Act 2009. Advocates of the vast or even entire tax exemption for businesses stress the potential damage of the inheritance tax on businesses, as those often lack liquidity to meet tax liability. This submission tackles this issue empirically based on data of the German Inheritance Tax Statistics and the SOEP. The results indicate that former German inheritance tax law has not endangered transferred businesses. Hence, there is no need for the tremendous tax privilege for businesses in current German inheritance tax law. An alternative flat inheritance tax without tax privileges, which meets revenue neutrality per tax class according to current tax law, provokes in some cases relative high tax loads which might trouble businesses.

Channelopathies - emerging trends in the management of inherited arrhythmias

NARCIS (Netherlands)

Chockalingam, Priya; Mizusawa, Yuka; Wilde, Arthur A. M.

2015-01-01

In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and

The Legal Position and Factual Situation of Women Participation to Inheritance in Kosovo

OpenAIRE

LL.M. Egzonis Hajdari

2014-01-01

The right to inheritance represents one of the basic human rights. As such this right is regulated by the law. The Law on Inheritance in Kosovo regulates substantially, all the issues related to inheritance. In this context, this Law contains numerous rules that proclaim full equality of women with men to inheritance. Regardless of equality proclaimed by law practical reality of life indicates a different situation. This reality proves that women participation to inheritance nevertheless ...

Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

International Nuclear Information System (INIS)

Kang, E.; Jung, J.W.

2015-01-01

A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

Effects of heavy metals on the neuromuscular transmission of the mouse diaphragm

Energy Technology Data Exchange (ETDEWEB)

Fu, W M; Shiau, S Y.L.

1978-04-01

Effects of heavy metals including Mn, Co, Ni, Cd, Zn, Cu, Sr, Ba, and UO/sub 2//sup +/ ions on the neuromuscular transmission of the mouse diaphragm were studied and compared. From the dose-inhibition curves, the concentrations (mM) required to inhibit 50% of the contraction (ID/sub 50/) for Cd, Mn, Co, Ni, Zn and Sr are 0.03, 0.8, 0.75, 0.82, 1.2 and >20 respectively. In addition to the potent neuromuscular blocking action, both Cd and Zn induce a contracture of the mouse diaphram. Among the cations tested, Cu is the most potent in inducing the contracture. Mn does not cause a contracture, while Co and Ni induce a contracture only after a prolonged incubation for 3 hours. The neuromuscular blocking action of most of the cations tested can be completely or partially reversed by either high Ca or cysteine except the irreversible action of Zn and Cu. These findings suggest that most divalent cations block the neuromuscular transmission by binding to the -SH group of the cell membrane and inhibiting Ca influx. On the other hand, both Ba and UO/sub 2/ at low concentration increase but at high concentration inhibit the twitch response. Sine Ba increases the twitch response of the mouse diaphragm stimulated directly in the presence of d-tubocurarine as well as that stimulated indirectly, Ba/sup + +/ acts mainly directly on the muscle. In contrast, UO/sub 2//sup +/ ions at low concentration increases the twitch response possibly by releasing acetylcholine from the nerve endings.

Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABHD5 mutation.

Science.gov (United States)

Ronchetti, Anna; Prati, Daniele; Pezzotta, Maria Grazia; Tavian, Daniela; Colombo, Roberto; Callea, Francesco; Colli, Agostino

2008-09-01

Fatty liver disease is mainly caused by alcohol consumption, excessive body weight, dyslipidemia and impaired glucose tolerance, but inherited disorders can sometimes be involved. We report the case of a 40-year-old woman with steatohepatitis and severe portal hypertension, associated with ichthyosis, cataract and hypoacusia. The clinical, pathological and genetic findings were consistent with a diagnosis of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive inherited neutral lipid storage disorder, and genetic analysis showed that a novel ABHD5 mutation is responsible.

Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes.

Science.gov (United States)

Zech, Astrid; Klahn, Philipp; Hoeft, Jon; zu Eulenburg, Christine; Steib, Simon

2014-02-01

Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular training effects on functional, dynamic and static balance measures. Thirty youth (14.9 ± 3 years) field hockey athletes were randomised to an intervention or control group. The intervention included a 20-min neuromuscular warm-up program performed twice weekly for 10 weeks. Balance assessments were performed at baseline, week three, week six and post-intervention. They included the star excursion balance test (SEBT), balance error scoring system (BESS), jump-landing time to stabilization (TTS) and center of pressure (COP) sway velocity during single-leg standing. No baseline differences were found between groups in demographic data and balance measures. Adherence was at 86%. All balance measures except the medial-lateral TTS improved significantly over time (p controls (31.8 ± 22.1%). There were no significant group by time interactions in the SEBT, TTS and COP sway velocity. Neuromuscular training was effective in improving postural control in youth team athletes. However, this effect was not reflected in all balance measures suggesting that the neuromuscular training did not influence all dimensions of postural control. Further studies are needed to confirm the potential of specific warm-up programs to improve postural control.

Estimulação elétrica neuromuscular na disfunção patelofemoral: revisão de literatura Neuromuscular electric stimulation in patellofemoral dysfunction: riterature review

Directory of Open Access Journals (Sweden)

Ricardo Lucas dos Santos

2013-02-01

Full Text Available A disfunção femoropatelar é uma deficiência bastante comum entre indivíduos jovens que acomete, principalmente, o sexo feminino e pode ser caracterizada por dor, edema e creptação retropatelar. Sistematizar o conhecimento em relação ao aumento da força muscular do quadríceps e alívio de dor em pacientes com disfunção femoropatelar, através da utilização da estimulação elétrica neuromuscular e exercícios resistidos. Trata se de um estudo de revisão narrativa da literatura no período de 2005 a 2011. Os critérios de inclusão foram artigos de intervenção, dos últimos seis anos, nos idiomas inglês, espanhol e português, que utilizaram o fortalecimento muscular e a eletroestimulação neuromuscular para reabilitação obtidos através de buscas nos bancos de dados eletrônicos Medline, Lilacs e na biblioteca Bireme. A busca bibliográfica resultou em 28 referências, destes foram excluídos nove de acordo com os objetivos e critérios de inclusão e foram selecionados 16 artigos para leitura dos resumos e posterior análise. A Estimulação Elétrica Neuromuscular (EENM de média frequência pode ser utilizada associada a exercícios resistidos como coadjuvante no tratamento da disfunção femoropatelar (DFP, tanto para se obter um reequilíbrio muscular quanto para o alívio da dor.Patellofemoral dysfunction is a fairly common deficiency among young individuals that primarily affects females and may be characterized by pain, swelling and retropatellar crepitation. The purpose of this review of literature from the period between 2005 and 2011 was to systematize knowledge in relation to the increase in quadriceps muscle strength and pain relief in patients with patellofemoral dysfunction, using neuromuscular electrical stimulation and resistance exercises. The inclusion criteria were intervention articles from the past six years, in English, Spanish and Portuguese, which used muscle strengthening and neuromuscular

COLQ-mutant congenital myasthenic syndrome with microcephaly: A unique case with literature review

Directory of Open Access Journals (Sweden)

Al-Mobarak Sulaiman Bazee

2017-07-01

Full Text Available Congenital Myasthenic Syndrome (CMS is a group of inherited neuromuscular junction disorders caused by defects in several genes. Clinical features include delayed motor milestones, recurrent respiratory illnesses and variable fatigable weakness. The central nervous system involvement is typically not part of the CMS. We report here a Saudi girl with genetically proven Collagen Like Tail Subunit Of Asymmetric Acetylcholinesterase (COLQ mutation type CMS who has global developmental delay, microcephaly and respiratory failure. We have reviewed the literature regarding COLQ-type CMS and to the best of our knowledge this is the first ever reported association of congenital myasthenia syndrome with microcephaly.

Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

Science.gov (United States)

Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

2011-08-15

A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of temperature on spontaneous release of transmitter at the mammalian neuromuscular junction

Energy Technology Data Exchange (ETDEWEB)

Duncan, C J; Statham, H E

1977-01-01

Temperature has a multifactorial effect on miniature endplate potential (MEPP) frequency at the mammalian neuromuscular junction, with a negative Q/sub 10/ at 14--28/sup 0/C. The results are explained in terms of the effect of temperature on the various factors that control (Ca/sup 2/+sub i/ at the presynaptic terminals. The temperature-sensitivity of the Ca/sup 2 +/-transport enzyme is believed to be of particular significance and accounts for the observed differences between the amphibian and mammalian neuromuscular junctions.

Use/disuse paradigms are ubiquitous concepts in characterizing the process of inheritance.

Science.gov (United States)

Veigl, Sophie Juliane

2017-12-02

In recent years, a Lamarckian theme has found its way back into academic discourse on evolution and inheritance. Especially the emerging field of transgenerational small RNAs has provided at least a proof of concept for the inheritance of acquired traits. Yet it remains unclear whether the Lamarckian concept of inheritance will in fact have its rennaisance or whether it will remain the rallying cry for the outlaws, heretics and enfants terribles of molecular biology. As unclear as the future of Lamarckian theory is its content and reference. Since the formulation of the Philosophie Zoologique, Lamarckian thought has been de- and reconfiguring in and out of the scientific literature and become an umbrella-term for all kinds of unconventional modes of inheritance. This essay will argue that heritable small RNAs might in fact provide a case of genuine Lamarckian inheritance. Moreover, it will be claimed that not only the very broad concept of "inheritance of acquired traits" applies, but also that Lamarck's mechanistic insight into a use/disuse relation might help to explain a specific mode of transgenerational inheritance.

Fractional populations in multiple gene inheritance.

Science.gov (United States)

Chung, Myung-Hoon; Kim, Chul Koo; Nahm, Kyun

2003-01-22

With complete knowledge of the human genome sequence, one of the most interesting tasks remaining is to understand the functions of individual genes and how they communicate. Using the information about genes (locus, allele, mutation rate, fitness, etc.), we attempt to explain population demographic data. This population evolution study could complement and enhance biologists' understanding about genes. We present a general approach to study population genetics in complex situations. In the present approach, multiple allele inheritance, multiple loci inheritance, natural selection and mutations are allowed simultaneously in order to consider a more realistic situation. A simulation program is presented so that readers can readily carry out studies with their own parameters. It is shown that the multiplicity of the loci greatly affects the demographic results of fractional population ratios. Furthermore, the study indicates that some high infant mortality rates due to congenital anomalies can be attributed to multiple loci inheritance. The simulation program can be downloaded from http://won.hongik.ac.kr/~mhchung/index_files/yapop.htm. In order to run this program, one needs Visual Studio.NET platform, which can be downloaded from http://msdn.microsoft.com/netframework/downloads/default.asp.

Defeasible inheritance-based description logics

CSIR Research Space (South Africa)

Casini, G

2013-01-01

Full Text Available of Artificial Intelligence Research 2013 Defeasible Inheritance-based Description Logics Giovanni Casini GCASINI@CSIR.CO.ZA Centre for Artificial Intelligence Research (CAIR), CSIR Meraka Institute and UKZN, South Africa Umberto Straccia UMBERTO...

Certain peculiarities of structural inheritance in phase recrystallization of steel

International Nuclear Information System (INIS)

Mukhamedov, A.A.

1978-01-01

The structural inheritance in phase recrystallization of previously overheated to various temperatures industrially melted 40Kh steel and of Armco-iron has been investigated. The steels have been heated to 100O, 11O0, 1200 and 1260 deg C and cooled in the air, and in some instances, hardened (quenched) in water. The physical broadening of X-ray lines points to a nonmonotonous variation of fine structure parameters as a function of the temperature and the heating time. The inheritance effect of fine structure defects affects the steel properties obtained in a final heat treatment. The structural inheritance effect has an important bearing upon the wear resistance of steel. A purpose-oriented use of the structural inheritance effect can enhance service properties of steel parts

Effect of heterogeneity and assumed mode of inheritance on lod scores.

Science.gov (United States)

Durner, M; Greenberg, D A

1992-02-01

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical neurogenetics: autism spectrum disorders.

Science.gov (United States)

Mehta, Sunil Q; Golshani, Peyman

2013-11-01

Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social interactions, communication, and repetitive or restricted interests. There is strong evidence that de novo or inherited genetic alterations play a critical role in causing Autism Spectrum Disorders, but non-genetic causes, such as in utero infections, may also play a role. Magnetic resonance imaging based and autopsy studies indicate that early rapid increase in brain size during infancy could underlie the deficits in a large subset of subjects. Clinical studies show benefits for both behavioral and pharmacological treatment strategies. Genotype-specific treatments have the potential for improving outcome in the future. Published by Elsevier Inc.

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report

Directory of Open Access Journals (Sweden)

O'Driscoll Jeremiah

2011-06-01

Full Text Available Abstract Background Ankle joint sprain and the subsequent development of chronic ankle instability (CAI are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. Methods The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: 1 Cumberland Ankle Instability Tool (CAIT scores, 2 Star Excursion Balance Test (SEBT reach distances, 3 ankle joint plantar flexion during drop landing and drop vertical jumping, and 4 ground reaction forces (GRFs during walking. Results CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. Conclusions The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report

LENUS (Irish Health Repository)

O'Driscoll, Jeremiah

2011-06-09

Abstract Background Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. Methods The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed\\/agility drills. The outcome measures chosen to assess for interventional efficacy were: 1 Cumberland Ankle Instability Tool (CAIT) scores, 2 Star Excursion Balance Test (SEBT) reach distances, 3 ankle joint plantar flexion during drop landing and drop vertical jumping, and 4 ground reaction forces (GRFs) during walking. Results CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. Conclusions The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.

Neuromuscular blockade for improvement of surgical conditions during laparotomy

DEFF Research Database (Denmark)

Madsen, Matias Vested; Scheppan, Susanne; Kissmeyer, Peter

2015-01-01

neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS...

Evaluation of Inheritance Pattern in Mentally Retarded Children

Directory of Open Access Journals (Sweden)

F Behnaz

2011-07-01

Full Text Available Introduction: Mental retardation is one of the most important problems of general health. The purpose of this study was to evaluate inheritance pattern of mentally retarded patients in Yazd city. Methods: In a descriptive cross- sectional study, all medical records and pedigrees of 320 mentally retarded children whose parents had referred for genetic consultation to the Welfare center of Yazd city were reviewed. Results: Of the total, 62.8% of the parents had consanguineous marriage. Mean inbreeding coefficient of offsprings was 0.0713 in third degree related parents versus 0.0156 in non-related parents. Mental retardation was seen in 43.4% of first– degree relatives of children (6.6% of parents and 36.8% of siblings, respectively. Frequency of mental retardation did not differ significantly in both sexes. Pedigree showed inheritance pattern in 43.4% of patients (autosomal recessive, autosomal dominant and x-linked inheritance pattern were seen in 33.75%, 6.9% and 2.8%, respectively, while 37% of patients had no definite inheritance pattern. Abnormal karyotype were seen in 19.4% of patients, 28 of whom(8.75% of all patients had Down syndrome. The prevalence of autosomal recessive inheritance in patients with consanguineous marriages and non family marriages was 62.8 % and 10%, respectively (P=0. 002. Conclusion: Since multiple cases of mental retardation were seen in families and rate of consanguineous marriage was more in parents of mentally retarded children, genetic counseling in consanguinity marriages and families of mentally retarded children can prevent incidence of mental retardation in these families.

Neuroimaging of Lipid Storage Disorders

Science.gov (United States)

Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

2013-01-01

Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

The information value of non-genetic inheritance in plants and animals.

Directory of Open Access Journals (Sweden)

Sinead English

Full Text Available Parents influence the development of their offspring in many ways beyond the transmission of DNA. This includes transfer of epigenetic states, nutrients, antibodies and hormones, and behavioural interactions after birth. While the evolutionary consequences of such non-genetic inheritance are increasingly well understood, less is known about how inheritance mechanisms evolve. Here, we present a simple but versatile model to explore the adaptive evolution of non-genetic inheritance. Our model is based on a switch mechanism that produces alternative phenotypes in response to different inputs, including genes and non-genetic factors transmitted from parents and the environment experienced during development. This framework shows how genetic and non-genetic inheritance mechanisms and environmental conditions can act as cues by carrying correlational information about future selective conditions. Differential use of these cues is manifested as different degrees of genetic, parental or environmental morph determination. We use this framework to evaluate the conditions favouring non-genetic inheritance, as opposed to genetic determination of phenotype or within-generation plasticity, by applying it to two putative examples of adaptive non-genetic inheritance: maternal effects on seed germination in plants and transgenerational phase shift in desert locusts. Our simulation models show how the adaptive value of non-genetic inheritance depends on its mechanism, the pace of environmental change, and life history characteristics.

Genetic and neurobiological aspects of attention deficit hyperactive disorder: a review.

OpenAIRE

Hechtman, L

1994-01-01

This paper reviews key studies that have addressed genetic and neurobiological aspects in attention deficit hyperactive disorder. Genetic studies can be divided into three distinct types: twin, adoption, and family studies. Evidence for a particular mode of inheritance and the possible specific genetic abnormalities are also explored. There is strong evidence of genetic involvement in this condition, although a clear-cut mode of inheritance and specific genetic abnormalities are yet to be det...

Endangering of Businesses by the German Inheritance Tax? – An Empirical Analysis

OpenAIRE

Houben, Henriette; Maiterth, Ralf

2011-01-01

This contribution addresses the substantial tax privilege for businesses introduced by the German Inheritance Tax Act 2009. Advocates of the vast or even entire tax exemption for businesses stress the potential damage of the inheritance tax on businesses, as those often lack liquidity to meet tax liability. This submission tackles this issue empirically based on data of the German Inheritance Tax Statistics and the SOEP. The results indicate that former German inheritance tax law has not enda...

Congenital diarrheal disorders: an updated diagnostic approach.

Science.gov (United States)

Terrin, Gianluca; Tomaiuolo, Rossella; Passariello, Annalisa; Elce, Ausilia; Amato, Felice; Di Costanzo, Margherita; Castaldo, Giuseppe; Canani, Roberto Berni

2012-01-01

Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.

What Programmers do with Inheritance in Java and C#

NARCIS (Netherlands)

B. Brekelmans

2014-01-01

htmlabstractInheritance is a widely used concept in modern object oriented software engineering. Previous studies show that inheritance is widely used in practice yet empirical data about how it is used in practice is scarce. An empirical study into this subject has been done by Tempero, Yang and

The Influence of Robotic Assistance on Reducing Neuromuscular Effort and Fatigue during Extravehicular Activity Glove Use

Science.gov (United States)

Madden, Kaci E.; Deshpande, Ashish D.; Peters, Benjamin J.; Rogers, Jonathan M.; Laske, Evan A.; McBryan, Emily R.

2017-01-01

The three-layered, pressurized space suit glove worn by Extravehicular Activity (EVA) crew members during missions commonly causes hand and forearm fatigue. The Spacesuit RoboGlove (SSRG), a Phase VI EVA space suit glove modified with robotic grasp-assist capabilities, has been developed to augment grip strength in order to improve endurance and reduce the risk of injury in astronauts. The overall goals of this study were to i) quantify the neuromuscular modulations that occur in response to wearing a conventional Phase VI space suit glove (SSG) during a fatiguing task, and ii) determine the efficacy of Spacesuit RoboGlove (SSRG) in reversing the adverse neuromuscular modulations and restoring altered muscular activity to barehanded levels. Six subjects performed a fatigue sequence consisting of repetitive dynamic-gripping interspersed with isometric grip-holds under three conditions: barehanded, wearing pressurized SSG, and wearing pressurized SSRG. Surface electromyography (sEMG) from six forearm muscles (flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), extensor digitorum (ED), extensor carpi radialis longus (ECRL), and extensor carpi ulnaris (ECU)) and subjective fatigue ratings were collected during each condition. Trends in amplitude and spectral distributions of the sEMG signals were used to derive metrics quantifying neuromuscular effort and fatigue that were compared across the glove conditions. Results showed that by augmenting finger flexion, the SSRG successfully reduced the neuromuscular effort needed to close the fingers of the space suit glove in more than half of subjects during two types of tasks. However, the SSRG required more neuromuscular effort to extend the fingers compared to a conventional SSG in many subjects. Psychologically, the SSRG aided subjects in feeling less fatigued during short periods of intense work compared to the SSG. The results of this study reveal the promise of the SSRG as a

Utilizing inheritance in requirements engineering

Science.gov (United States)

Kaindl, Hermann

1994-01-01

The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

Neuromuscular stimulation after stroke: from technology to clinical deployment

NARCIS (Netherlands)

IJzerman, Maarten Joost; Renzenbrink, Gerbert J.; Geurts, Alexander C.H.

2009-01-01

Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades

Roles of neuro-exocytotic proteins at the neuromuscular junction

NARCIS (Netherlands)

Sons-Michel, Michèle S.

2011-01-01

The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

The Social Meaning of Inherited Financial Assets. Moral Ambivalences of Intergenerational Transfers

Directory of Open Access Journals (Sweden)

Merlin Schaeffer

2013-11-01

Full Text Available What do inherited financial assets signify to heirs and testators and how does this shape their conduct? Based on grounded theory methodology and twenty open, thematically structured interviews with US heirs, future heirs and testators, this article explicates a theoretical account that proposes a moral ambivalence as the core category to understand the social meaning of inherited financial assets. In particular, the analysis reveals that the social meaning of inherited assets is a contingent, individual compromise between seeing inherited assets as unachieved wealth and seeing them as family means of support. Being the lifetime achievement of another person, inheritances are, on the one hand, morally dubious and thus difficult to appropriate. Yet in terms of family solidarity, inheritances are "family money," which is used when need arises. Taken from this angle, inheriting is not the transfer of one individual's privately held property to another person, but rather the succession of the social status as support-giver along with the resources that belong to this status to the family's next generation. Heirs need to find a personal compromise between these poles, which always leaves room for interpretation. http://nbn-resolving.de/urn:nbn:de:0114-fqs1401131

Distal mdx muscle groups exhibiting up-regulation of utrophin and rescue of dystrophin-associated glycoproteins exemplify a protected phenotype in muscular dystrophy

Science.gov (United States)

Dowling, Paul; Culligan, Kevin; Ohlendieck, Kay

2002-02-01

Unique unaffected skeletal muscle fibres, unlike necrotic torso and limb muscles, may pave the way for a more detailed understanding of the molecular pathogenesis of inherited neuromuscular disorders and help to develop new treatment strategies for muscular dystrophies. The sparing of extraocular muscle in Duchenne muscular dystrophy is mostly attributed to the special protective properties of extremely fast-twitching small-diameter fibres, but here we show that distal muscles also represent a particular phenotype that is more resistant to necrosis. Immunoblot analysis of membranes isolated from the well established dystrophic animal model mdx shows that, in contrast to dystrophic limb muscles, the toe musculature exhibits an up-regulation of the autosomal dystrophin homologue utrophin and a concomitant rescue of dystrophin-associated glycoproteins. Thus distal mdx muscle groups provide a cellular system that naturally avoids myofibre degeneration which might be useful in the search for naturally occurring compensatory mechanisms in inherited skeletal muscle diseases.

Combined gait disorder: a diagnostic challenge –a case report

Directory of Open Access Journals (Sweden)

Ioana Stanescu

2017-02-01

Full Text Available Gait disorders are a major cause of functional impairment and morbidity, especially in the elderly population. Prevalence of gait disorders is higher in persons over 60: is estimated to be around 15% at 60 years of age and more than 50% in people > 80 years. Most gait disorders are multifactorial and have both neurologic and non-neurologic components. Neurological gait abnormalities result from focal or diffuse lesions occurring in the neural pathways linking the cortical motor centers to the peripheral neuromuscular systems. Nonneurological gait abnormalities include gait limitations caused by musculoskeletal, cardiac, or respiratory diseases. Assessment of a gait abnormality should include history, clinical presentation and additional diagnostic tests. Finding the ethiology of a gait disorder could be a challenge for the practitioners in many cases, requiring interdisciplinary cooperation.

Inheritance tax - an equitable tax no longer: time for abolition?

OpenAIRE

Lee, Natalie

2007-01-01

Statistics from HM Revenue & Customs predict that receipts from inheritance tax will amount to some £3.56 billion in the tax year 2006/07. This compares to £1.68 billion in 1997/98. This paper explores the reason for the large increase in inheritance tax revenues and, in the light of those findings, together with a consideration of the recent public reaction to the changes to the inheritance taxation of trusts announced in the Budget 2006 and incorporated in the Finance Act 2006, argues t...

Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency

DEFF Research Database (Denmark)

Thomsen, J L; Nielsen, C V; Palmqvist, D F

2015-01-01

, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation prematurely awakened if anaesthesia had been terminated while the patient was still...... paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored...

Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

Science.gov (United States)

Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

2014-01-01

The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

Friedreich's Ataxia: a review from a cardiology perspective.

LENUS (Irish Health Repository)

Bourke, T

2011-12-01

Neuromuscular disorders are not among the common causes of cardiomyopathy in the general population; however, cardiomyopathy is known to occur in several neuromuscular disorders including Friedreich\\'s Ataxia (FA). In patients with neuromuscular disorders, concomitant cardiac involvement contributes significantly to morbidity and mortality and often leads to premature death.

A designated centre for people with disabilities operated by North West Parents and Friends Association, Sligo

LENUS (Irish Health Repository)

Bourke, T

2011-12-01

Neuromuscular disorders are not among the common causes of cardiomyopathy in the general population; however, cardiomyopathy is known to occur in several neuromuscular disorders including Friedreich\\'s Ataxia (FA). In patients with neuromuscular disorders, concomitant cardiac involvement contributes significantly to morbidity and mortality and often leads to premature death.

Does perioperative tactile evaluation of the train-of-four response influence the frequency of postoperative residual neuromuscular blockade?

DEFF Research Database (Denmark)

Pedersen, T; Viby-Mogensen, J; Bang, U

1990-01-01

pancuronium), the anesthetists assessed the degree of neuromuscular blockade during operation and during recovery from neuromuscular blockade by manual evaluation of the response to TOF nerve stimulation. In the other two groups, one of which received vecuronium and the other pancuronium, the anesthetists...... evaluated the degree of neuromuscular blockade solely by clinical criteria. The use of a nerve stimulator was found to have no effect on the dose of relaxant given during anesthesia, on the need for supplementary doses of anticholinesterase in the recovery room, on the time from end of surgery to end...... of anesthesia, or on the incidence of postoperative residual neuromuscular blockade evaluated clinically. The median (and range of) TOF ratios recorded in the recovery room were 0.75 (0.33-0.96) and 0.79 (0.10-0.97) in the vecuronium groups monitored with and without a nerve stimulator, respectively...

C-terminal agrin fragment is inversely related to neuromuscular fatigue in older men.

Science.gov (United States)

Stout, Jeffrey R; Fragala, Maren S; Hoffman, Jay R; Robinson, Edward H; Mccormack, William P; Townsend, Jeremy R; Jatjner, Adam R; Emerson, Nadia S; Oliveira, Leonardo P; Fukuda, David H

2015-01-01

The aim of this study was to examine the relationship between serum C-terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. Twenty-two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWCFT ) test. A significant inverse correlation for men was observed between CAF and PWCFT (r = -0.602; P = 0.05), but not for women (r = 0.208; P = 0.54). After controlling for age and body mass index, significant correlations (r = -0.69; P = 0.042) remained for men, but not for women (r = 0.12; P = 0.76). These data suggest that serum CAF concentrations were significantly related to the onset of neuromuscular fatigue independent of age and BMI in men only. © 2014 Wiley Periodicals, Inc.

Influence of intense neuromuscular blockade on surgical conditions during laparotomy

DEFF Research Database (Denmark)

Madsen, Matias Vested; Donatsky, Anders Meller; Jensen, Bente Rona

2015-01-01

endotracheally intubated, mechanically ventilated, anesthetized with propofol and fentanyl, and randomized into two groups in a cross-over assessor-blinded design. Neuromuscular block was established with rocuronium. Artificial laparotomy for ileus was performed. We investigated the influence of intense...

Fatiguing exercise intensity influences the relationship between parameters reflecting neuromuscular function and postural control variables.

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Sébastien Boyas

Full Text Available The purpose of this study was to investigate the influence of fatiguing exercise intensity on the nature and extent of fatigue-induced changes in neuromuscular function and postural stability in quiet standing. We also explored the contribution of selected neuromuscular mechanisms involved in force production to postural stability impairment observed following fatigue using an approach based on multivariate regressions. Eighteen young subjects performed 30-s postural trials on one leg with their eyes closed. Postural trials were performed before and after fatiguing exercises of different intensities: 25, 50 and 75% of maximal isometric plantarflexor torque. Fatiguing exercises consisted of sustaining a plantarflexor isometric contraction at the target intensity until task failure. Maximal isometric plantarflexor torque, electromyographic activity of plantarflexor and dorsiflexor muscles, activation level (twitch interpolation technique and twitch contractile properties of plantarflexors were used to characterize neuromuscular function. The 25% exercise was associated with greater central fatigue whereas the 50 and 75% exercises involved mostly peripheral fatigue. However, all fatiguing exercises induced similar alterations in postural stability, which was unexpected considering previous literature. Stepwise multiple regression analyses showed that fatigue-related changes in selected parameters related to neuromuscular function could explain more than half (0.51≤R(2≤0.82 of the changes in postural variables for the 25% exercise. On the other hand, regression models were less predictive (0.17≤R(2≤0.73 for the 50 and 75% exercises. This study suggests that fatiguing exercise intensity does not influence the extent of postural stability impairment, but does influence the type of fatigue induced and the neuromuscular function predictors explaining changes in postural variables.

Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

DEFF Research Database (Denmark)

Kolte, Astrid M; Nielsen, Henriette S; Steffensen, Rudi

2015-01-01

pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses....... The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. METHODOLOGY: We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA......-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test. RESULTS: We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non...

Inheritance of microsatellite loci in the polyploid lake sturgeon (Acipenser fulvescens)

Science.gov (United States)

Pyatskowit, J.D.; Krueger, C.C.; Kincaid, H.L.; May, B.

2001-01-01

Inheritance in the expression of amplicons for four microsatellite primer pairs was determined using 10 families created from gametes of wild lake sturgeon (Acipenser fulvescens). Loci Afu34 and Afu68 expressed a maximum of two even-intensity bands per individual and had progeny genotype ratios that fit disomic inheritance (P > 0.05). Some variation exhibited at Afu34 and Afu68 was attributable to a null allele. Genotype expression at both loci also indicated that one female parent had transmitted unreduced gametes. Primer Afu39 amplified products that exhibited four gene doses, where genotype counts fit expected ratios for disomic inheritance (P > 0.05) indicating amplification of products from two disomic loci that share alleles. Meiotic drive was evident at the Afu39 loci based on a test for random segregation (P inheritance based on a single progeny potentially produced by a double reduction gamete. No evidence for proposed octoploid inheritance was observed.

Adjustments with running speed reveal neuromuscular adaptations during landing associated with high mileage running training.

Science.gov (United States)

Verheul, Jasper; Clansey, Adam C; Lake, Mark J

2017-03-01

It remains to be determined whether running training influences the amplitude of lower limb muscle activations before and during the first half of stance and whether such changes are associated with joint stiffness regulation and usage of stored energy from tendons. Therefore, the aim of this study was to investigate neuromuscular and movement adaptations before and during landing in response to running training across a range of speeds. Two groups of high mileage (HM; >45 km/wk, n = 13) and low mileage (LM; joint stiffness might predominantly be governed by tendon stiffness rather than muscular activations before landing. Estimated elastic work about the ankle was found to be higher in the HM runners, which might play a role in reducing weight acceptance phase muscle activation levels and improve muscle activation efficiency with running training. NEW & NOTEWORTHY Although neuromuscular factors play a key role during running, the influence of high mileage training on neuromuscular function has been poorly studied, especially in relation to running speed. This study is the first to demonstrate changes in neuromuscular conditioning with high mileage training, mainly characterized by lower thigh muscle activation after touch down, higher initial knee stiffness, and greater estimates of energy return, with adaptations being increasingly evident at faster running speeds. Copyright © 2017 the American Physiological Society.

Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

NARCIS (Netherlands)

Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

VIPER:a visualisation tool for exploring inheritance inconsistencies in genotyped pedigrees

OpenAIRE

Paterson, Trevor; Graham, Martin; Kennedy, Jessie; Law, Andy

2012-01-01

Background Pedigree genotype datasets are used for analysing genetic inheritance and to map genetic markers and traits. Such datasets consist of hundreds of related animals genotyped for thousands of genetic markers and invariably contain multiple errors in both the pedigree structure and in the associated individual genotype data. These errors manifest as apparent inheritance inconsistencies in the pedigree, and invalidate analyses of marker inheritance patterns across the dataset. Cleaning ...

Inheritance-mode specific pathogenicity prioritization (ISPP) for human protein coding genes.

Science.gov (United States)

Hsu, Jacob Shujui; Kwan, Johnny S H; Pan, Zhicheng; Garcia-Barcelo, Maria-Mercè; Sham, Pak Chung; Li, Miaoxin

2016-10-15

Exome sequencing studies have facilitated the detection of causal genetic variants in yet-unsolved Mendelian diseases. However, the identification of disease causal genes among a list of candidates in an exome sequencing study is still not fully settled, and it is often difficult to prioritize candidate genes for follow-up studies. The inheritance mode provides crucial information for understanding Mendelian diseases, but none of the existing gene prioritization tools fully utilize this information. We examined the characteristics of Mendelian disease genes under different inheritance modes. The results suggest that Mendelian disease genes with autosomal dominant (AD) inheritance mode are more haploinsufficiency and de novo mutation sensitive, whereas those autosomal recessive (AR) genes have significantly more non-synonymous variants and regulatory transcript isoforms. In addition, the X-linked (XL) Mendelian disease genes have fewer non-synonymous and synonymous variants. As a result, we derived a new scoring system for prioritizing candidate genes for Mendelian diseases according to the inheritance mode. Our scoring system assigned to each annotated protein-coding gene (N = 18 859) three pathogenic scores according to the inheritance mode (AD, AR and XL). This inheritance mode-specific framework achieved higher accuracy (area under curve  = 0.84) in XL mode. The inheritance-mode specific pathogenicity prioritization (ISPP) outperformed other well-known methods including Haploinsufficiency, Recessive, Network centrality, Genic Intolerance, Gene Damage Index and Gene Constraint scores. This systematic study suggests that genes manifesting disease inheritance modes tend to have unique characteristics. ISPP is included in KGGSeq v1.0 (http://grass.cgs.hku.hk/limx/kggseq/), and source code is available from (https://github.com/jacobhsu35/ISPP.git). mxli@hku.hkSupplementary information: Supplementary data are available at Bioinformatics online. © The Author

Swedish Inheritance and Gift Taxation (1885–2004)

OpenAIRE

Henrekson, Magnus; Du Rietz, Gunnar; Waldenström, Daniel

2012-01-01

This paper studies the evolution of the modern Swedish inheritance taxation from its introduction in 1885 to its abolishment in 2004. A thorough description is offered of the basic principles of the tax, including underlying ideas and ambitions, tax schedules, and rules concerning valuation of assets, liability matters and deduction opportunities. Using these rules, we calculate inheritance tax rates for the whole period for a number of differently endowed family firms and individuals. The ov...

Neuromuscular Control of Rapid Linear Accelerations in Fish

Science.gov (United States)

2016-06-22

sunfish, Lepomis macrochirus. Animals with flexible bodies, like fishes , face a tradeoff for rapid movements. To produce high forces, they must...2014 30-Apr-2015 Approved for Public Release; Distribution Unlimited Final Report: Neuromuscular Control of Rapid Linear Accelerations in Fish The...Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 swimming, acceleration, fish , muscle, stiffness REPORT DOCUMENTATION PAGE 11. SPONSOR

Congenital Diarrheal Disorders: An Updated Diagnostic Approach

Directory of Open Access Journals (Sweden)

Giuseppe Castaldo

2012-03-01

Full Text Available Congenital diarrheal disorders (CDDs are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.

Inherited myopathies and muscular dystrophies

NARCIS (Netherlands)

Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

Mitochondrial genome inheritance and replacement in the human germline.

Science.gov (United States)

Wolf, Don P; Hayama, Tomonari; Mitalipov, Shoukhrat

2017-08-01

Mitochondria, the ubiquitous power packs in nearly every eukaryotic cell, contain their own DNA, known as mtDNA, which is inherited exclusively from the mother. The number of mitochondrial genomes varies depending on the cell's energy needs. The mature oocyte contains the highest number of mitochondria of any cell type, although there is little if any mtDNA replication after fertilization until the embryo implants. This has potential repercussions for mitochondrial replacement therapy (MRT; see description of currently employed methods below) used to prevent the transmission of mtDNA-based disorders. If only a few mitochondria with defective mtDNA are left in the embryo and undergo extensive replication, it might therefore thwart the purpose of MRT In order to improve the safety and efficacy of this experimental therapy, we need a better understanding of how and which mtDNA is tagged for replication versus transcription after fertilization of the oocyte. © 2017 The Authors.

Inheritance of craniofacial features in Colombian families with class III malocclusion

Directory of Open Access Journals (Sweden)

L Otero

2010-02-01

Full Text Available L Otero, L Quintero, D Champsaur, E SimancaPontificia Universidad Javeriana, Bogotá, ColombiaIntroduction: The inheritance of class III malocclusion has been well documented, but the inheritance of craniofacial structures in Colombian families with this malocclusion has been not yet reported.Patients and methods: The study sample of 25 families comprised 186 untreated orthodontic individuals from 8 to 60 years old. Pedigrees were drawn using Cyrillic software. Complete family histories for each proband were ascertained and the affection status of relatives was confirmed by lateral cephalograms and facial and dental photographs. Analysis of variance and odds ratio test for each parameter was performed to estimate inheritance from parents to offspring and to determine similar phenotypic features in relatives.Results: The analysis of the pedigrees suggests autosomal dominant inheritance. The craniofacial characteristics that showed more resemblance between parents and offspring were middle facial height, shorter anterior cranial base and mandibular prognathism. In contrast the protrusion of upper lip and maxillary retrusion were the phenotypic features that contributed to class III in the majority of families.Conclusion: Knowledge of the inheritance of craniofacial phenotypes in class III malocclusion will enable the design of new therapies to treat this malocclusion.Keywords: inheritance, craniofacial, phenotype, class III malocclusion

Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

Directory of Open Access Journals (Sweden)

Karen K Y Ling

2010-11-01

Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

TUBULAR DISORDERS WITH RICKETS-LIKE SYNDROME

Directory of Open Access Journals (Sweden)

N.N. Kartamysheva

2011-01-01

Full Text Available Often under the guise of «ordinary» Rickets are more severe kidney diseases, developing as a result of inherited or acquired, primary or secondary defects in the renal tubules. Incorrect diagnosis leads to an inadequate therapy, rapid progression of disease and renal failure. The article describes the main approaches to the diagnosis and treatment of disorders of tubular rachitis similar syndrome, presents a number of clinical cases in author's practice.Key words: tubulopathy, acidosis, electrolyte disorders, rickets, rickets-like syndrome, diagnostics, treatment, children.

Sugammadex to reverse neuromuscular blockade and provide optimal conditions for motor-evoked potential monitoring

Directory of Open Access Journals (Sweden)

Mehdi Trifa

2017-01-01

Full Text Available Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade (NMB via a mechanism that differs completely from acetylcholinesterase inhibitors. By encapsulating rocuronium, sugammadex can provide recovery of neuromuscular function even when there is a profound degree of NMB. We report anecdotal experience with the use of sugammadex to reverse NMB to facilitate intraoperative neurophysiological monitoring (motor evoked potentials in an adolescent with scoliosis during posterior spinal fusion. Its potential application in this unique clinical scenario is discussed, and potential dosing schemes are reviewed.

"You're saying something by giving things to them:" communication and family inheritance.

Science.gov (United States)

de Witt, Lorna; Campbell, Lori; Ploeg, Jenny; Kemp, Candace L; Rosenthal, Carolyn

2013-09-01

The study purpose was to contribute to a more complete understanding of the experience and meaning of family inheritance. The aim of this article is to describe and discuss the meaning of communication in inheritance experiences among Canadian families. A constructivist/interpretive methodological approach guided this research. Participants were recruited through purposive, convenience sampling from two cities and one town in southern and southwestern Ontario, Canada. Fifty face-to-face, semi-structured, audio-taped, in-depth interviews were conducted between June 2006 and April 2007. NVivo software was used to organize and analyze the data. A content analysis method guided data analysis. Participants interpreted the meaning of family structure, relationships, feelings, and past inheritance experiences to construct their family inheritance communication. Analysis of the findings revealed four themes regarding the role of communication in family inheritance including: (a) avoiding conflict and preserving biological ties , (b) resisting conversations about possessions , (c) achieving confidence with possession communication , and (d) lasting effects. Participants from non-blended and blended families experienced similar inheritance communication challenges related to past experience with their parents' wills and distribution of their own possessions. Participants with past positive inheritance experiences with parents adopted similar strategies when communicating their own inheritance wishes. Negative messages conveyed to participants by their parent's wills inspired participants to communicate in opposite ways in their own inheritance planning. The study findings are useful for gerontologists, lawyers, family counselors, and estate planners.

Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

Directory of Open Access Journals (Sweden)

Stéphane Mathis

2016-01-01

Full Text Available Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies. For each patient, we carried out a pathological analysis (nerve and muscle and an electrophysiological study (and follow-up. To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders.

Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance.

Science.gov (United States)

Day, Troy

2016-04-01

Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance. © 2016 John Wiley & Sons Ltd.

Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial.

Science.gov (United States)

Giannasi, Lilian Chrystiane; Matsui, Miriam Yumi; de Freitas Batista, Sandra Regina; Hardt, Camila Teixeira; Gomes, Carla Paes; Amorim, José Benedito Oliveira; de Carvalho Aguiar, Isabella; Collange, Luanda; Dos Reis Dos Santos, Israel; Dias, Ismael Souza; de Oliveira, Cláudia Santos; de Oliveira, Luis Vicente Franco; Gomes, Mônica Fernandes

2012-05-15

Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP), given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm) and LED (= 660 nm) irradiation in CP patients. 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS.

Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular Influencia de la procainamida sobre el bloqueo neuromuscular producido por el rocuronio e investigación sobre el mecanismo de acción de la procainamida en la junción neuromuscular Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction

Directory of Open Access Journals (Sweden)

Thalita Duque Martins

2007-02-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada: procainamida - 20 µg.mL-1 (Grupo I; rocurônio - 4 µg.mL-1 (Grupo II e rocurônio - 4 µg.mL-1 e procainamida - 20 µg.mL-1 (Grupo III. Avaliaram-se: 1 a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2 os potenciais de placa terminal em miniatura (PPTM; 3 a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5 e diafragma de rato desnervado (n = 5, observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067 em relação ao Grupo II (10,4% ± 4,5%, revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida.JUSTIFICATIVA Y OBJETIVOS: La potenciación de la procainamida sobre

Alterations in neuromuscular function in girls with generalized joint hypermobility

DEFF Research Database (Denmark)

Jensen, Bente Rona; Melcher, Jesper Sandfeld; Melcher, Pia Grethe Sandfeld

2016-01-01

BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions...

The Effect of Proprioceptive Neuromuscular Facilitation on Learning Fine Motor Skills: A Preliminary Study

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Mohammad Reza Shahabi Kaseb

2016-09-01

Full Text Available Introduction: Preparation of neuromuscular system prior to performing motor skills affects the learning of motor skills. The present study was conducted to investigate the effects of Proprioceptive Neuromuscular Facilitation (PNF on limb coordination and accuracy in dart throwing skill. Methods: Thirty two male students were randomly selected as study sample. Based on the pretest scores, the participants were divided into three groups: experimental (proprioceptive neuromuscular facilitation, first control (without warm-up, and second control (specific warm-up. During the acquisition phase, the participants first performed the preparation training related to their own group, then all groups performed the exercise program of dart throwing consisting of 6 blocks of 9 trials in 4 training sessions. Finally, 20 days following the last exercise session, the subjects took the retention and transfer tests. Results: The results of one-way ANOVA test for coordination variable in acquisition test showed no significant difference between the groups, while there was a statistically significant difference between groups regarding coordination variable in retention and transfer tests. Furthermore, the results of one-way ANOVA for the accuracy variable in acquisition and retention tests showed no statistically significant difference between the three groups, while there was a statistically significant difference between groups for accuracy variable in transfer test. Conclusion: It seems that proprioceptive neuromuscular facilitation, as a preparation method before performance, can enhance the efficacy of training to better learn the coordination pattern of fine motor skills.

Effect of a neuromuscular training program on the kinetics and kinematics of jumping tasks.

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Chappell, Jonathan D; Limpisvasti, Orr

2008-06-01

Altered motor control strategies are a proposed cause of the female athlete's increased risk for noncontact anterior cruciate ligament injury. Injury prevention programs have shown promising results in decreasing the incidence of anterior cruciate ligament injury. To evaluate the effect of the Kerlan-Jobe Orthopaedic Clinic Modified Neuromuscular Training Program on the biomechanics of select jumping tasks in the female collegiate athlete. Controlled laboratory study. Thirty female National Collegiate Athletic Association Division I soccer and basketball players performed vertical jump, hopping tests, and 2 jumping tasks (drop jump and stop jump). All subjects completed a 6-week neuromuscular training program with core strengthening and plyometric training. Three-dimensional motion analysis and force plate data were used to compare the kinetics and kinematics of jumping tasks before and after training. Dynamic knee valgus moment during the stance phase of stop jump tasks decreased after completion of the neuromuscular training program (P = .04), but differences were not observed for the drop jump. Initial knee flexion (P = .003) and maximum knee flexion (P = .006) angles increased during the stance phase of drop jumps after training, but differences were not observed for the stop jump. The athletes showed improved performance in vertical jump (P training program improved select athletic performance measures and changed movement patterns during jumping tasks in the subject population. The use of this neuromuscular training program could potentially modify the collegiate athlete's motion strategies, improve performance, and lower the athlete's risk for injury.

Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

OpenAIRE

O'Connor, Joanne; McCaughan, Dorothy; McDaid, Catriona; Booth, Alison; Fayter, Debra; Rodriguez-Lopez, Roccio; Bowers, Roy; Dyson, Lisa; Iglesias, Cynthia P; Lalor, Simon; O'Connor, Rory J; Phillips, Margaret; Ramdharry, Gita

2016-01-01

BACKGROUND: \\ud \\ud Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs).\\ud \\ud OBJECTIVES: \\ud \\ud To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs.\\ud \\ud METHODS: \\ud \\ud Qualitative study of views of orthoses users - a qualitative in-...

Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin ligase, mysterin/RNF213

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Kotani, Yuri; Morito, Daisuke; Yamazaki, Satoru; Ogino, Kazutoyo; Kawakami, Koichi; Takashima, Seiji; Hirata, Hiromi; Nagata, Kazuhiro

2015-01-01

Mysterin (also known as RNF213) is a huge intracellular protein with two AAA+ ATPase modules and a RING finger ubiquitin ligase domain. Mysterin was originally isolated as a significant risk factor for the cryptogenic cerebrovascular disorder moyamoya disease, and was found to be involved in physiological angiogenesis in zebrafish. However, the function and the physiological significance of mysterin in other than blood vessels remain largely unknown, although mysterin is ubiquitously expressed in animal tissues. In this study, we performed antisense-mediated suppression of a mysterin orthologue in zebrafish larvae and revealed that mysterin-deficient larvae showed significant reduction in fast myofibrils and immature projection of primary motoneurons, leading to severe motor deficits. Fast muscle-specific restoration of mysterin expression cancelled these phenotypes, and interestingly both AAA+ ATPase and ubiquitin ligase activities of mysterin were indispensable for proper fast muscle formation, demonstrating an essential role of mysterin and its enzymatic activities in the neuromuscular regulation in zebrafish. PMID:26530008

Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass

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Lara Maris Nápolis

2011-01-01

Full Text Available BACKGROUND: High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients. However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. OBJECTIVE: To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study. METHODS: Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim were assessed. RESULTS: Thirteen (46.4% patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation. Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6% non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01. Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05. CONCLUSIONS: We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD.

A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking.

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Mills, Kathryn; Hunt, Michael A; Leigh, Ryan; Ferber, Reed

2013-08-01

Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA) during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals and how these may be influenced by osteoarthritis severity, varus alignment and/or joint laxity. Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude of observed differences. Where studies were homogenous, effect sizes were pooled using a fixed-effects model. Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular activity was prevalent for those exhibiting varus alignment and medial knee joint laxity. Interpretation Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease, varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efficacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation of medial and lateral knee muscles on disease progression. © 2013.

Inherited sterility in insects

International Nuclear Information System (INIS)

Carpenter, J.E.; Marec, F.; Bloem, S.

2005-01-01

The unique genetic phenomena responsible for inherited sterility (IS) in Lepidoptera and some other arthropods, as compared with full sterility, provide advantages for pest control. Lepidopteran females are usually more sensitive to radiation than males of the same species. This allows the radiation dose to be adjusted to suit programme requirements. When partially sterile males mate with wild females, the radiation-induced deleterious effects are inherited by the F 1 generation. As a result, egg hatch is reduced and the resulting offspring are both highly sterile and predominately male. Compared with the high radiation required to achieve full sterility in Lepidoptera, the lower dose of radiation used to induce F 1 sterility increases the quality and competitiveness of the released insects as measured by improved dispersal after release, increased mating ability, and superior sperm competition. F 1 sterile progeny produced in the field enhance the efficacy of released partially sterile males, and improve compatibility with other pest control strategies. In addition, F 1 sterile progeny can be used to increase the production of natural enemies, and to study the potential host and geographical ranges of exotic lepidopteran pests. (author)