Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene leading to progressive muscle weakness. It mainly affects boys and symptoms start between ages 2-3. Affected children become wheelchair bound by age 12 and have life-threatening heart, respiratory, and orthopedic complications if not properly managed. Management involves monitoring for cardiomyopathy, respiratory support, orthopedic care, corticosteroids which can prolong ambulation, and future therapies like gene therapy aim to treat the underlying genetic cause.
Amyotrophic lateral sclerosis (ALS), AKA "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
Amyotrophic lateral sclerosis (ALS), AKA "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
Dystonia is a movement disorder in which a person's muscles contract uncontrollably. The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures. Dystonia can affect one muscle, a muscle group, or the entire body.
achondroplasia is genetic disorder that results in dwarfism
problem is not in forming cartilage but in converting it to bone.
This disorder usually results in the following: An average-size trunk; Short arms and legs, with particularly short upper arms and upper legs; Short fingers.
Mutation in FGFR3 on chromosome 4 is responsible for achondroplasia.
Dystonia is a movement disorder in which a person's muscles contract uncontrollably. The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures. Dystonia can affect one muscle, a muscle group, or the entire body.
achondroplasia is genetic disorder that results in dwarfism
problem is not in forming cartilage but in converting it to bone.
This disorder usually results in the following: An average-size trunk; Short arms and legs, with particularly short upper arms and upper legs; Short fingers.
Mutation in FGFR3 on chromosome 4 is responsible for achondroplasia.
CP is the most common motor disability in childhood. Cerebral means having to do with the brain. Palsy means weakness or problems with using the muscles. CP is caused by abnormal brain development or damage to the developing brain that affects a person's ability to control his or her muscles.
this presentation briefly discus about muscle and its related disorder. some myopathies which are common are cover here in an approach to provide basis of the same disease and treatment. this ppt is basically from chapter 32 zakazewski.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
2. Introduction
•An inherited progressive myopathic disorder
•X-linked recessive form of muscular dystrophy
•Affects 1 in 3600 boys
•Caused by mutations in the dystrophin gene, and hence is termed “dystrophinopathy”
3. Dystrophinopathies
•Duchenne muscular dystrophy (DMD) is associated with the most severe clinical symptoms
•Becker muscular dystrophy (BMD) has a similar presentation to DMD, but typically has a later onset and a milder clinical course
•Patients with an intermediate phenotype may be classified clinically as having either mild DMD or severe BMD
5. Genetics and Pathogenesis
•Caused by mutations of the dystrophin gene located on chromosome Xp21.2
–Deletions
•Around 72% of patients
–Partial gene duplications
•6 – 10% of patients
–Point mutations
•In the coding sequence or the splicing sites
6. Dystrophin
•Dystrophin is located on the cytoplasmic face of the plasma membrane of muscle fibers, functioning as a component of a large, tightly associated glycoprotein complex .
•Provides mechanical reinforcement to the sarcolemma and stabilizes the glycoprotein complex, shielding it from degradation.
–In its absence, the glycoprotein complex is digested by proteases. Loss of these membrane proteins may initiate the degeneration of muscle fibers, resulting in muscle weakness.
Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP. Nature. 1990;345(6273):315.
7.
8. Pathogenesis
•Muscle cell membrane damage related to the loss of dystrophin may permit the pathologic entry of extracellular calcium into muscle fibers.
•The excess cytosolic calcium can activate calpains, which promote muscle proteolysis .
10. Clinical Features
•Clinical onset of muscular weakness usually occurs between 2 and 3 years of age.
•Histologic and laboratory evidence of a myopathy may be observed from birth.
11. Weakness
•Proximal before distal limb muscles
•Lower before upper extremities
•Difficulty running, jumping, and walking up steps
•Waddling gait
•Lumbar lordosis
•Pseudohypertrophy of calf muscles, due to fat infiltration
•Patients are usually wheelchair-bound by the age of 12
12.
13.
14. Gowers Sign
•Patient uses his hands and arms to "walk" up his own body from a squatting position
–due to lack of hip and thigh muscle strength
Gowers WR. Clinical lecture on pseudohypertrophic muscular paralysis. Lancet 1879;ii,73-5.
15. Gowers Sign
•Patient with DMD demonstrating the Gowers maneuver.
–The prone position.
–The bear position.
–Moving the hands up the thighs to help upright the trunk and augment knee extension.
–The upright position.
18. Cardiomyopathy
•Characterized by extensive fibrosis of the posterobasal left ventricular wall
–tall right precordial R waves
–increased R/S ratio
–deep Q waves in leads I, aVL, and V5-6
•As the disease progresses, fibrosis can spread to the lateral free wall of the left ventricle.
•Significant mitral regurgitation due to involvement of posterior papillary muscle
19. Cardiomyopathy
•Incidence
–By 14 years: One-third of patients
–By 18 years: One half of patients
–Older than 18 years: All patients
•Despite the high incidence of DCM, the majority of children with DMD are relatively asymptomatic until late in the disease course, probably because of their inability to exercise
•Heart failure and arrhythmias may develop in the late stages of the disease
The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Nigro G, Comi LI, Politano L, Bain RJ. Int J Cardiol. 1990;26(3):271.
20. Respiratory complications
•Chronic respiratory insufficiency due to restrictive lung disease is inevitable in all patients.
–Vital capacity increases as predicted until around age 10 years; after this time it starts to decrease at a rate of 8-12% per year.
–When vital capacity reaches less than 1 liter the risk of death within the next one to two years is relatively high.
•Obstructive sleep apnea
–1st decade
•Hypoventilation
–2nd decade
21. Intellectual disability
•In around 30% of patients
•Average IQ is 85
–normally distributed one standard deviation below the population norms
–Verbal IQ is more impaired than performance IQ
•Intellectual disability is not correlated with the severity of weakness
•Higher incidence of ADHD
Leibowitz D, Dubowitz V. Intellect and behaviour in Duchenne muscular dystrophy. Dev Med Child Neurol 1981;23:577-90.
22. Orthopedic Complications
•Long bone fractures
•21% of DMD patients had experienced fractures.
–Most common mechanism was falling
–About half of the fractures occurred among patients who were ambulatory
•Osteoporosis is present in most patients. Bone mineral density begins early and continues to diminish with age.
Fracture prevalence in Duchenne muscular dystrophy. McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Dev Med Child Neurol. 2002;44(10):695.
23. Orthopedic Complications
•Progressive scoliosis in nearly all patients
–Scoliosis, in combination with progressive weakness, results in impaired pulmonary function, and eventually, respiratory failure.
Progression of scoliosis in Duchenne muscular dystrophy. Smith AD, Koreska J, Moseley CF. J Bone Joint Surg Am. 1989;71(7):1066.
24. Malignant hyperthermia
•Patients with DMD are thought to have increased risk of malignant hyperthermia, or at least malignant hyperthermia-like reactions if exposed to inhalational anesthetics such as halothane, or succinylcholine.
Wedel DJ. Malignant hyperthermia and neuromuscular disease. Neuromuscul Disord 1992;2:157-64.
Wang JM, Stanley TH. Duchenne muscular dystrophy and malignant hyperthermia-two case reports. Can Anaesth Soc J 1986;33:492-7.
26. Diagnosis
•The diagnosis of a dystrophinopathy is suspected based upon:
–Characteristic age and sex
–Presence of symptoms and signs suggestive of a myopathic process
–Markedly increased serum creatine kinase values
–Myopathic changes on electromyography and muscle biopsy
–A positive family history suggesting X-linked recessive inheritance
27. Serum muscle enzymes
•Markedly raised serum CK level, 10-20 times the upper limit of normal
–Levels peak at 2-3 years of age and then decline with increasing age, due to progressive loss of dystrophic muscle fibres
•Elevated serum ALT, AST, aldolase and LDH
28. Electromyography
•Needle electromyography
–Short duration, low amplitude polyphasic motor unit potentials in proximal muscles
–Over time, some of these areas become electrically silent
29. Muscle biopsy
•Gold standard for diagnosis
•Performed when genetic testing is negative, or the clinical phenotype is atypical
30. Molecular Genetic Testing
•Multiplex polymerase chain reaction (PCR), covering 18 exons at the deletion hotspots detected 90-98% of all deletions
•Multiplex ligation-dependent probe amplification (MLPA) has provided a more sensitive technique for detecting deletions.
•If MLPA testing is negative, the DMD gene can be tested for point mutations.
31. Muscle MRI
•Muscle MRI is usually not performed in DMD for diagnosis, but may be a useful noninvasive tool to evaluate progression of muscle involvement over time.
32. Genetic Analysis
•Molecular genetic testing is indicated for patients with an elevated serum CK level and clinical findings suggestive of a dystrophinopathy.
•The diagnosis is established if a disease-causing mutation of the dystrophin gene (DMD) is identified
–Deletion of one or more exons of DMD gene
–Duplication of one or more exons of DMD
–Small insertions/deletions/point mutations/splicing mutations of DMD gene
34. Cardiac disease
•Cardiac surveillance with ECG and echocardiogram and Holter monitoring, beginning at 10 years and continuing on an annual basis.
•Early treatment of dilated cardiomyopathy with ACE inhibitors and beta blockers
–improvement in LV function
Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, et al . Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 2005;112:2799-804.
35. Respiratory disease
•Baseline pulmonary function tests and respiratory evaluations beginning at age 8 to 9 years.
–Spirometry, early morning and daytime carbondioxide levels monitoring
•Annual polysomnography
–To detect sleep disordered breathing and nocturnal hypoventilation
•Pneumococcal vaccine and annual flu vaccination
36. Respiratory disease
•Acute respiratory deteriorations due to infections require early management with antibiotics, chest physiotherapy and respiratory support.
•Nocturnal noninvasive intermittent positive pressure ventilation (NIPPV) for hypercapnia
–Life expectancy has increased to an average of 25 and even 30 years in patients who receive NIPPV.
Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: Improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 2002;12:926-9.
37. Orthopedic problems
•Passive stretching
•Night splints
•Surveillance radiographs for scoliosis
•Maintenance of bone density
–Monitoring of vitamin D levels and supplementing calcium and vitamin D
38. Corticosteroid Therapy
•Prednisolone, prednisone and deflazacort have been the only drugs shown to be effective to date in DMD.
•Prednisolone/prednisone
–0.75mg/kg/day
•Deflazacort
–0.9mg/kg/day
•A common regimen is to offer corticosteroids at the time of decline of muscle strength and frequent falls, and to cease treatment when the child is no longer ambulant.
•Preservation of respiratory muscle function, cough strength and cardiac function, with a lower incidence of dilated cardiomyopathy.
Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord 2006;16:249-55.
39. Prednisone – Merits and Demerits
•Average muscle strength increased by 11% with prednisone treatment compared with placebo.
–Strength increased significantly by 10 days, reached a maximum at 3 months, and was maintained at 6 and 18 months.
•Forced vital capacity improved significantly (10.5% higher) after 6 months of daily prednisone.
•Weight gain, diabetes, Cushingoid appearance, hypertension, gastrointestinal bleeding and compression fractures.
40. Prednisone Regimen
•Prednisone (0.75mg/kg per day or 10mg/kg per week given over two weekend days) in patients > 5 years of age.
•Optimally, should be maintained at this dose.
•In case of side effects
–A gradual tapering of prednisone to as low as 0.3 mg/kg per day
41. Deflazacort
•In contrast with prednisone, alternate day treatment with deflazacort (2mg/kg every other day) for 2 years was beneficial in one study.
–The mean prolongation of ambulation was 13 months.
Deflazacort in Duchenne dystrophy: study of long-term effect. Angelini C, Pegoraro E, Turella E, Intino MT, Pini A, Costa C. Muscle Nerve. 1994;17(4):386.
42. Other drug therapies
•Oxandrolone, an anabolic steroid has shown some promise in increasing quantitative muscle strength in a randomized prospective trial.
•Cyclosporine therapy showed some improvement in muscle strength.
Fenichel GM, Griggs RC, Kissel J, Kramer TI, Mendell JR, Moxley RT, et al . A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy. Neurology 2001;56:1075-9.
43. Gene Therapy
•Viral vectors
–Recombinant adeno-associated viral (rAAV) vectors that carry critical regions of the DMD gene
•Antisense oligonucleotide exon skipping
–To redirect splicing and induce exon skipping
–Restoring the reading frame and producing a partially functioning dystrophin.
•Utrophin
–A protein homologue of dystrophin in the sarcolemma
–May compensate for dystrophin deficiency if it is upregulated.