By E. Trano. Gutenberg College. 2018.
A progres- sive alteration in mental status has a broad differential diagnosis buy cymbalta 60mg low cost, but within the context of an individual resuscitation its signifi- cance is often clear order cymbalta 40mg without a prescription. In shock states cheap 40 mg cymbalta free shipping, it may represent worsening cerebral perfusion or hypoxia and the need for more aggressive resuscitative efforts. In patients with intracranial pathology, it may represent brain herniation and the need for lowering intracranial pressure, especially when combined with localizing signs. When toxic, metabolic and endocrinologic derangements are present, worsening electrolyte abnormalities or hypoglycemia may be present and a multitude of interventions, ranging from simple dextrose administration to hemodialysis may be necessary. These may indicate the need to search for an occult injury such as a fracture or penetrating trauma that may change the direction of the resuscitation. Pain can also be used as a guide to the success of resuscitation, as is the case when chest pain and dyspnea resolve with adequate treatment of myocardial ischemia or pulmonary edema. Continuous cardiac Continuous telemetry is essential in any resuscitation to monitor monitor for life-threatening dysrhythmias and responses to treatment. Attention is directed at signs of myocardial infarction and ischemia, electrolyte derangements and clues to other life threatening pathologies such as decreased voltage in cardiac tamponade or signs of acute right-sided heart strain in pulmonary embolus. Bedside laboratory tests Blood glucose Critically low blood glucose results from many different life- threatening processes and must be addressed immediately. The finding of high blood glucose is similarly important and may help tailor early resuscitative efforts. Blood glucose should be measured in all patients with altered mental status and, when abnormal, frequent rechecks are indicated. Continued 1 Hemoglobin or Both of these tests express hemoglobin concentration and, as hematocrit such, can appear misleadingly high in acute hemorrhage before volume resuscitation has occurred. These tests are subject to error, and repeat and serial values should be obtained when they are utilized to guide resuscitation. Pregnancy test A positive serum or urine pregnancy test may lead to a diagnosis of the underlying pathology in a critically ill female. In addition, this finding may affect decisions made during resuscitation with respect to monitoring, emergent procedures, the selection of medications and imaging studies and disposition. Blood type and This is an essential test that must be performed to facilitate crossmatch treatment with blood and blood products in a multitude of resuscitations, both traumatic and non-traumatic. Bedisde electrolytes The availability of blood electrolyte analysis at the bedside is increasing and very helpful. Knowledge of the electrolytes in the first few minutes may enable critical interventions to be started early. In some cases, such therapies should be started even before electrolytes are available (e. The pH and base excess values obtained from blood gases (including venous gases) may also be used as an adjunct to gauge the severity of shock states and response to resuscitative efforts. Pooled venous Requires the placement of central venous line with a special oxygen levels probe. Other bedside assays Although there are many potential pitfalls in their application and interpretation, bedside assays may be extremely helpful. A variety of toxicological tests are now available, and, in the appropriate circumstances, bedside screening assays for various bioterrorism agents. Diagnostic imaging Chest film An early portable chest X-ray is of paramount importance. It may also be helpful in pulmonary embolism—less for the presence of rare signs such as Hampton’s Hump and Westermark’s sign than for the absence of significant findings pointing to alternative diagnoses such as pulmonary edema and pneumonia. Cervical spine films The presence of cervical spine trauma may help explain the findings of shock, neurological deficits and ventilatory failure. Continued Pelvis This is an important film that may identify a source of hemor- 1 rhage and occult trauma. Lateral soft tissue neck This film may identify mechanical airway obstruction, a source of septic shock or foreign bodies. Abdominal films Although rarely helpful in resuscitation, a single abdominal film may show a pattern of calcification of the aorta in the case of a ruptured aortic aneurysm and the presence of radiopaque toxic ingestions such as iron, phenothiazines and enteric release tablets. Ultrasonography Bedside ultrasound is ideal for use in resuscitation because of its availability, repeatability and speed. Bedside echocardiography can be used to reveal the presence of various shock states by identifying cardiac tamponade, global hypokinesis or right ventricular outflow obstruction. In the future, it may be utilized by emergency physicians to evaluate valvular lesions and dyskinesis. It can also assist with the distinction between pulseless electrical activity and cardiac standstill (electromechanical dissociation). Abdominal ultrasound may quickly identify free-fluid (most importantly, hemorrhage) in the peritoneal cavity.
Whilst research shows some positive associations order 30 mg cymbalta with mastercard, the contribution is only part of a multifactorial aetiology purchase 30 mg cymbalta with mastercard, and the effect may be transient in some cases buy 20mg cymbalta. Concern over the influence of media reporting of suicides has led to strong suggestions for more responsible reporting, the avoidance of dramatic portrayal and oversimplification of causes (e. Ganly, 2004) 1517 Räikkönen ea (2007) found increased susceptibility to depressive symptoms at age 60 years in people with shorter length of gestation. Females outnumbered males, rural villagers were over-represented, and victims were older than controls (mean in years: 48 v 43). Negative life events such as economic problems and serious illness or injury did not differentiate the two groups (although both groups had an excess) and other events (childbirth, pregnancy [incl. Nevertheless, even younger children can have suicidal thoughts or even harm themselves deliberately. About 20% of suicides leave a suicide note, the percentage perhaps being higher in the elderly. Nearly half will change the way they practice in various ways such as becoming more structured in their approach to patients or admitting more involuntary patients. Shock, fear of blame, grief, guilt, self-doubt, shame, anger, and a sense of betrayal are common. These allow to learn and to improve our clinical management skills of such cases and to handle the aftermath better. Official suicide figures in Ireland may have underestimated the problem in the past (undereporting may still apply in India: Joseph ea, 2003). However, according to the Irish Minister for Health,(Anonymous, 2004b) Ireland, with 10. He cautions against drawing too many conclusions about trends since numbers are small, especially for females. Also, figures vary because yearly sumaries on vital statistics precede annual reports by 2 years. Hanging accounted for 857 male suicides and 104 female suicides, while drowning was the method used by 376 males and 141 females. Perhaps one percent or more of 1531 parasuicides go on to kill themselves, but which 1%? Risk factors retrospectively identify groups of people who have killed themselves rather than prospectively identifying individuals who may do so. They 1532 have a high sensitivity but low specificity, spewing out many false positives. In a psychological autopsy study of 85 suicides aged over 65 years of age at death, Waern ea (2002) found that 97% (v 18% in living comparators) had at least one Axis I diagnosis, commonly recurrent major depression or substance use disorders. Increased risk was also associated with minor depression, dysthymic disorder, psychosis, single episode major depression, and anxiety disorder. Comorbid Axis I disorders were found in 38% of suicides (15 subjects) with major depression. Questionnaires are most useful for research when used in a population for long-term prediction, but do not replace individual clinical assessment. Beck’s scale for suicidal intent (Beck ea, 1974) is widely used in clinical practice but seems to show poor agreement with clinician’s rating of the same phenomenon. Important in determining suicidal intent at the time of the act of self-harm Premeditation - buying a rope, securing a flat unknown to others, saving up tablets, getting tablets from many sources Secrecy - precautions against discovery Not alerting potential helpers Being alone Final acts - writing a will, insurance cover, a suicide note Violent or aggressive act Low lethality act believed by the person to be lethal It is important to consider suicidal intent even in very young children. Do the adolescent’s peers view their friend as having changed significantly or being ill? Extended suicide Talk about harming someone else who is also believed to suffering e. Feeney ea,(2005) looking at parasuicides seen in a Dublin general hospital emergency department, found that emergency staff had a tendency to overrate suicide risk relative to the evaluations of a liaison psychiatry service. However, extraneous factors may operate between appointments to undermine our best efforts. The Health Services Executive published a strategy for suicide prevention in 2005 (Health Services Executive, National Suicide Review Group, and Department of Health and Children, 2005) which acknowledged that no one group can take on this preventive role on its own. Restriction or removal of one method may be replaced by another,(Ohberg ea, 1995; Isometsa & Lonnqvist, 1998) although efforts in this area (which must be monitored for compliance) are worthwhile. Nevertheless, determined people will most probably find a way to end their lives,(Edwards, 1995b) and car exhaust seems to have been replaced by hanging. We do not know how many ‘parasuicides end up in Heaven’ by accident and how many ‘parasuicides’ are actually failed suicides. It is far from clear what psychosocial and physical interventions prevent repetition of self harm.
Vasodilates Heart block Arrythmogenic Worsens shock Triggers apoptosis Acute kidney injury: an indirect effect of muscle damage K+ Direct renal damage result from the nephrotoxic properties of a Lactic acid Reperfusion Injury −ve inotropic effect Arrythmogenic variety of leaked intracellular substances such as proteases and purines generic cymbalta 60 mg on-line. However generic cymbalta 60mg without a prescription, damage principally occurs indirectly as the kidneys attempt to ﬁlter acidotic plasma and the muscle protein order cymbalta 20 mg without prescription, Phosphate Microvascular impairment myoglobin (Figure 19. Thromboembolic Material 3rd space fluid shift Micro & macro vascular impairment It is very important, from a therapeutic perspective, to appreciate Pulmonary embolism that myoglobin itself causes no renal damage. It is a small protein Fat embolism Disseminated intravascular coagulation that is freely ﬁltered and eliminated by the kidneys with no nephro- toxic properties. This by-product of anaerobic metabolism, together Where tourniquets have been applied, they should remain in with other organic acids being released from cells, lowers the pH of place until the patient is fully resuscitated, potential haemorrhage urine. As the ﬁltered myoglobin combines with urine below a pH of points addressed and in a safe environment. Ferrihaemate in the hospital resuscitation room or operating theatre, with full is both directly nephrotoxic to renal tubules and causes mechanical cardiovascular monitoring and support. There may be cases where obstruction by precipitating within the lumen of nephrons. Inad- there is a long delay to deﬁnitive care and in these cases ‘staged equate circulating volume due to hypovolaemia and third space release’ should be employed. Amputation prior to release will also prevent the sequelae of urine and wash away rapidly accumulating ferrihaemate and other the reperfusion syndrome by removing the source of the problem. Resuscitate the system Management A haemodynamically stable system will handle a reperfusion injury Isolate and move to a place of safety better than a collapsed, shocked system. A great deal of thought By applying arterial tourniquets just proximal to a harness or needs to be applied to preparing the circulation prior to entrapment entrapping force, one can prevent the massive haemorrhage or release. There is a wealth of data from disaster medicine literature to rescue cardioplegia frequently encountered with sudden release support early circulatory resuscitation prior to reperfusion. Spend- of an entrapment on scene; transferring the problem to a safer, ing time optimizing an entrapped person poses signiﬁcant health controlled environment (Box 19. This ethos ﬁts well within the and safety risks, the obvious being the stability of the entrapping establishedphilosophyof‘scoopandrun’. Medical staff casualty, they should be rescued as soon as is safely possible must work in close collaboration with rescue personnel, ideally as and placed in the horizontal recovery position if consciousness an integrated team, to understand differing roles and needs. There is no evidence to support rescue in the semi- Systemic resuscitation prior to extrication in earthquake entrap- recumbent position. An initial Tourniquets must be purposefully designed for prehospital use, 20 mL/kg bolus (10 mL/kg in elderly people) of 0. Ongoing ﬂuid administration should continue at a rate of degree of ischaemic reperfusion injury themselves, but the beneﬁts 5 ml/kg/hour with additional ﬂuid boluses titrated against clin- greatly outweigh this risk, especially where ambulance transit times ical response. Hartmann’s) must be strictly avoided in the ﬁeld to avoid tourniquet and the patient remains stable then delayed application hyperkalaemia. When the patient is collapsed in a conﬁned space, of a tourniquet is not required as ‘washout’ will have already intravenous access maybe challenging and intraosseous infusion occurred. Trauma: Suspension and Crush 101 Forprolongedtransfersthepatientshouldhaveaurinarycatheter gluconate and an enema of sodium or calcium resonium if available. Improving urine output is a good Calcium should only be given under these circumstances, as you indication of end organ perfusion and that preventative manage- run the risk of precipitating metastatic calciﬁcation and further mentisstartingtobecomeeffective. Standard medical management strategies for hyperkalaemia tend to be ineffective, as hyperkalaemia in a crush injury results from muscle wall damage, and not ionic or osmotic shifts. Patients Analgesia must therefore be immediately transferred to an intensive care Pain is often minimal in the early post-crush phase because of environment capable of haemoﬁltration. As limbs become In the event that prehospital anaesthesia is required as part progressively more swollen and the intrinsic analgesic effects of of the resuscitative process, non-depolarizing muscle relaxants endorphins wear off, pain will become more problematic. Regional local anaesthetic blocks may also be useful in providing additional analgesia for the trapped limb, but avoid long acting agents which may mask the onset of compartment Alkaline diuresis syndrome. When evacuation times are prolonged (>4 hours) the use of alkaline diuresis may be considered. Alkaline diuresis will prevent the precipitation of toxic myoglobin metabolites in nephrons and Staged tourniquet release strategy help ameliorate acidosis and hyperkalaemia. This allows for controlled washout and sys- oedema (particularly in the presence of pre-existing renal or heart temic redistribution of ischaemic metabolites during reperfusion. The risk of iatrogenic metabolic alkalosis and sodium It should be employed on one limb at a time and the patient overload is greater in the unmonitored prehospital environment must be monitored closely. If at any point the patient becomes and where possible alkaline diuresis should be left for the hospital unstable, then the tourniquet should be immediately reapplied environment where it can be titrated to urine output, urine pH and and the patient’s cardiovascular state managed prior reinstituting serum pH. Once optimal volume resuscitation has been achievedfurtherhypotensiveepisodesmaybetreatedwithinotropic or vasopressive agent. Tourniquet Released + Re-inflated 30 sec later Tips from the ﬁeld 3 Min • Resuscitate the system prior to release • Consider use of tourniquets to prevent rescue cardioplegia Tourniquet Released • Limb amputation may be considered in the non-viable limb • Prepare for clinical deterioration after release. Introduction Permanent Cavity The term ballistic trauma encompasses any physical trauma sus- tained from the discharge of arms or munitions. The two main types of ballistic trauma likely to be experienced by prehospital practi- Figure 20. The rise in terrorist activity over the last decade and the increased use of ﬁrearms during criminal passage of the projectile the temporary cavity collapses down to acts means such injuries are becoming increasingly common.
In some individ- is presumed cymbalta 60 mg on-line, the cardiac investigation may remain uals buy 60 mg cymbalta otc, 2–10% according to different authors [3 generic cymbalta 30mg free shipping, 4], the limited. Finally, making the correct diagnosis means The anterior circulation can be subdivided into choosing the appropriate secondary prevention. Large-vessel disease suggests an M1 occlusion with or without carotid occlusion and is associated with a rather unfavorable 2. Other etiology intracranial pressure and subsequent subfacial, uncal and transtentorial herniation. Undetermined or multiple possible etiologies ation occurs typically within 48–72 hours, when vigi- lance decreases and initial signs worsen. The artery is subdivided into the M1 segment, leading to an ipsilateral fixed mydriasis and the contra- from which start the deep perforating lenticulostriate lateral cerebral peduncle is compressed against the cere- arteries, the M2 segment, corresponding to the seg- bellar tentorium, leading to ipsilateral corticospinal ment after the bifurcation into superior and inferior signs, such as Babinski’s sign and paresis (Kernohan divisions, and the M3 segment, including the insular notch). Early recognition of frontal, prefrontal, precentral, central sulcus, anterior patients at risk enables the medical team to propose a parietal, posterior parietal, angular and temporal arter- hemicraniectomy for selected patients, a treatment ies, with important variations in their territories. As collateral networks are highly variable, an of the lower limbs are less involved than the face and occlusion of the same artery at the same place may arms. The patient is usually awake or presents mild partial brachiofacial sensitive loss (mainly tactile and drowsiness or agitation, particularly with a right discriminative modalities), transient conjugate ipsilat- infarct. Cognitive signs are always present: in the case eral eye and head deviation and aphasia (aphemia or of a left lesion, aphasia, and most of the time global, Broca aphasia) frequently associated with buccolin- ideomotor apraxia. In the case of a right lesion, gual apraxia in the case of left infarcts and various contralateral multimodal hemineglect (visual, motor, degrees of multimodal hemineglect, anosognosia, 122 sensitive, visual, spatial, auditive), anosognosia (denial anosodiaphoria, confusion and monotone language of illness), anosodiaphoria (indifference to illness), in right lesions. Ischemia in their glect, transcortical motor aphasia and behavioral dis- territory can therefore produce severe deficits with a turbances (with involvement of the supplementary very small-volume lesion. Sensory hemisyndromes affecting mainly minor, except in the case of deafferentation of the cortex the contralateral leg are also described. Clinical function, mutism, anterograde amnesia, grasping, signs include proportional hemiparesis, hemihypesthe- and behavioral disturbances are particularly frequent sia, dysarthria, hypophonia, and occasionally abnormal in ischemia of the deep perforating arteries and the movements in the case of involvement of basal ganglia. Involvement of the corpus callosum can produce The centrum ovale receives its blood supply from the callosal disconnection syndrome, secondary to medullary perforating arteries coming principally interruption of the connection of physical informa- from leptomeningeal arteries. Small infarcts (less than tion from the right hemisphere to cognitive center in 1. Therefore, it is restricted to the deficits are often less proportional than in pontine left hand, which presents ideomotor apraxia, agra- or internal capsule lacunes. A rare but specific visual field defect less severe, with a classic subacute two-phase pre- is a homonymous defect in the upper and lower sentation or even asymptomatic. The two vertebral arteries leave the and repetition but anomia, jargon speech and seman- subclavian arteries, pass through transverse foramina tic paraphasic errors) with left infarct. The manifestations of acute internal carotid occlusion are quite variable, depending on the collateral status Clinical clues to differentiate posterior from and preexisting carotid stenosis. Consciousness is usually more posterior circulation stroke and should be recognized. In contrast, a progressive atherosclerotic occlusion Similarly, headache is more frequent in the posterior is usually less severe, with a classic subacute two- circulation, is typically ipsilateral to the infarct, and phase presentation. Chapter 8: Common stroke syndromes On exam, a disconjugate gaze strongly suggests a eyelid, and hemifacial anhydrosis. It may occur as a fixed misalign- ipsilateral dorsolateral brainstem, upper cervical, or ment of the ocular axis, such as in vertical skew thalamic lesion, but may also occur due to a carotid deviation of the eyes as part of the ocular tilt reaction. If the eyes are deviated toward the hemiparesis, nerves and fascicles that produce ipsilateral signs and i. If somnolence, early anisocoria or vertical A vertical gaze paresis (upwards, downwards, or gaze palsy are present, posterior circulation stroke is both) points to a dorsal mesencephalic lesion and may more probable than carotid territory stroke. The latter structure may also Section 3: Diagnostics and syndromes receive direct (long circumferential) branches from the case, the patient develops paresthesia in the shoulder, vertebral artery. Three classic clinical syndromes are neck stiffness up to opisthotonos, no motor recognized in their territory: the medial medullary responses, small and unreactive pupils, ataxic then stroke (or Déjerine syndrome); the dorsolateral medul- superficial respiratory pattern, Cushing’s triad lary stroke (or Wallenberg syndrome); and the hemi- (hypertension, bradycardia, apnea) and finally cardio- medullary stroke (or Babinski-Nageotte syndrome). With transtentorial herniation, The medial medullary stroke is a rare stroke lethargy and coma are accompanied by central hyper- syndrome and classically includes contralateral hemi- ventilation, upward gaze paralysis, unreactive, mid- paresis sparing the face (corticospinal tract), contra- position pupils and decerebration. The laterodorsal medullary stroke syndrome, leading to contralateral motor and all- is the most common of those three syndromes and modalities sensory deficits, ipsilateral tongue, phar- is named the Wallenberg syndrome, after Adolf ynx and vocal cord weakness and facial thermoalgesic Wallenberg (1862–1946), a German neurologist. Wallenberg syndrome and an infarct in the inferior Dorsolateral medullary stroke (or Wallenberg syn- cerebellum stroke can be seen in isolation or together, drome) is the most common brainstem syndrome the latter being usually the case if the vertebral artery of vertebral artery involvement. It is frequently misdiagnosed as the correct diagnosis is the presence of an unusual Wallenberg syndrome, but the main clinical distinc- nystagmus, which will be purely horizontal or direc- tions are the hearing loss and the peripheral-type tion-changing, and preservation of the vestibulo-ocular facial palsy. Occasionally, horizontal ipsilateral gaze reflex with the head thrust (Halmagyi) maneuver. Nystagmus (middle are nonspecific, such as paresthesias, dysarthria, and/or superior cerebellar peduncle, superior cerebel- (“herald”) hemiparesis or dizziness.
These cells are thin (high surface-to-volume ratio) generic 60mg cymbalta overnight delivery, with a good capillary supply for efﬁcient gas exchange generic 20mg cymbalta visa. They are built for aerobic metabolism and prefer to use fat as a source of energy buy generic cymbalta 20mg line. They are progressively recruited when additional effort is required, but are still very resistant to fatigue. These cells are thin (high surface-to-volume ratio) with a good capillary supply for efﬁcient gas exchange. They are built for aerobic metabolism and can use either glucose or fats as a source of energy. These are general-purpose muscle ﬁbres which give the edge in athletic performance, but they are more expensive to operate than type 1. These cells are large (poor surface-to-volume ratio) and their limited capillary supply slows the delivery of oxygen and removal of waste products. It is here that the initiation of action potentials across the muscle surface ultimately leads to muscle contraction. At each end of the muscle ﬁbre this outer coat of the sarcolemma fuses with a tendon ﬁbre, and the tendon ﬁbres in turn collect into bundles to form the muscle tendons that then insert into bones. The membrane is designed to receive and conduct stimuli, is extensible and encloses the contractile substance of a muscle ﬁbre. It invaginates into the cytoplasm, forming membranous tubules called transverse tubules; sarcoplasmic reticulum (enlarged smooth endoplasmic reticulum) lies either side of the transverse tubules. The transverse tubules and sarcoplasmic reticulum transmit altered membrane permeability down the tubules and into the muscle. Entrance of Ca2+ triggers a biochemical cascade to cause neurotransmitter-containing vesicles to fuse with the cell membrane and release acetylcholine into the synaptic cleft. This allows movement of Na+ into and K+ out of the myocyte, producing a local depolarisation of the motor end plate (the end-plate potential). Diseases of the motor end plate include myasthenia gravis and its related condition Lambert–Eaton myasthenic syndrome. Tetanus and botulism are bacterial infections in which bacterial toxins cause increased or decreased muscle tone, respectively. Myasthenia gravis is an autoimmune reaction against acetylcholine receptors; the end-plate potential fails to activate the muscle ﬁbre, resulting in muscle weakness and fatigue. Anti- bodies directed against this protein are found in those patients with myasthenia gravis who do not demonstrate antibodies to the acetylcholine receptor (sero-negative). Botulinum toxin is both a medication and a neurotoxin, produced by the bacterium Clostridium botulinum. It can be used to treat muscle spasms, and is sold commercially under various names (Botox, Dysport, Myobloc, etc. They are multi-protein complexes composed of three different ﬁlament systems: • The thick ﬁlament system, which comprises myosin protein, connected from the M-line to the Z-disc by titin (connectin), and myosin-binding protein C, which binds at one end to the thick ﬁlament and at the other to actin. Sarcomere Z-line Z-line thin filament thick filament H-zone I-band I-band A-band Figure 17. The relationship between the proteins and the regions of the sarcomere are as follows: • Actin ﬁlaments are the major component of the I-band and extend into the A-band. Titin (along with its splice isoforms) is the biggest single highly elasticated protein found in nature. It provides binding sites for numerous proteins and is thought to play an important role in the assembly of the sarcomere. Focal adhesions (in muscle often referred to as costameres) are regions that are associated with the sarcolemma of skeletal muscle ﬁbres and comprise proteins of the dystrophin–glycoprotein complex and vinculin–talin–integrin system. Focal adhesions play both a mechanical and a signalling role, transmitting force from the contractile apparatus to the extracellular matrix in order to stabilise skeletal-muscle ﬁbres during contraction and relaxation. Several focal adhesion constituent proteins have been shown to be defective in muscular dystrophies and cardiomyopathies. Focal adhesions are large macromolecular assemblies through which both mechanical force and regulatory signals are transmitted. They can be considered as sub-cellular macro- molecules that mediate the regulatory effects (e. Focal adhesions serve as the mechanical linkages to the extra- cellular matrix, and as a biochemical signalling hub to concentrate and direct numerous signalling proteins at sites of integrin binding and clustering. Integrins are cell-surface receptors that interact with the extracellular matrix and mediate various intracellular sig- nals. Vinculin is a membrane-cytoskeletal protein in focal adhesions that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Although dystrophin is not required for the assembly of focal adhesions, its absence in humans and mice leads to a disorganised focal adhesion lattice and disruption of sarcolemmal integrity. Deﬁciency of dystrophin is the main cause of muscular dystrophy; mutation in the gene causes Duchenne muscular dystrophy, a severe recessive X-linked form of muscular dystrophy characterised by rapid progression of muscle degeneration, which eventually leads to loss of ambulation and death.