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Effects of a 6-month course of tamsulosin for chronic prostatitis/chronic pelvic pain syndrome: a multicenter heart attack telugu movie purchase discount lozol online, randomized trial understanding prehypertension order lozol 2.5mg with visa. Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis arrhythmia and alcohol discount lozol 1.5 mg without prescription. Predictors of patient response to antibiotic therapy for the chronic prostatitis/ chronic pelvic pain syndrome: a prospective multicenter clinical trial blood pressure medications that start with l 1.5 mg lozol mastercard. Prostate biopsy culture findings of men with chronic pelvic pain syndrome do not differ from those of healthy controls blood pressure of 130/80 buy generic lozol 2.5mg on-line. Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial prehypertension systolic normal diastolic cheap lozol 1.5 mg line. Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: a double-blind, placebo-controlled, pilot study. Failure of a monotherapy strategy for difficult chronic prostatitis/chronic pelvic pain syndrome. A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo controlled phase 3 study. Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome. The role of flower pollen extract in managing patients affected by chronic prostatitis/ chronic pelvic pain syndrome: a comprehensive analysis of all published clinical trials. Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study. Transurethral intraprostatic injection of botulinum neurotoxin type A for the treatment of chronic prostatitis/chronic pelvic pain syndrome: Results of a prospective pilot double blind and randomized placebo-controlled study. Preliminary assessment of safety and efficacy in proof-of-concept, randomized clinical trial of tanezumab for chronic prostatitis/chronic pelvic pain syndrome. Effect of allopurinol in chronic nonbacterial prostatitis: a double blind randomized clinical trial. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a meta analysis. Treatment of ulcer and nonulcer interstitial cystitis with sodium pentosanpolysulfate: a multicenter trial. Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo controlled study. Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis. Treatment of interstitial cystitis with immunosuppression and chloroquine derivatives. A systematic review and meta-analysis on the efficacy of intravesical therapy for bladder pain syndrome/interstitial cystitis. Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia. Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis. Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution. Urodynamic results of intravesical heparin therapy for women with frequency urgency syndrome and interstitial cystitis. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double-blind placebo-controlled trial. Clinical response to an oral prostaglandin analogue in patients with interstitial cystitis. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. Improvement in interstitial cystitis symptom scores during treatment with oral L-arginine. Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis. Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis. The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study. Urinary tract infection and inflammation at onset of interstitial cystitis/painful bladder syndrome. Botulinum toxin A for myofascial trigger point injection: a qualitative systematic review. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Pilot study of botulinum toxin type A in the treatment of chronic pelvic pain associated with spasm of the levator ani muscles. Clinical trial: effects of botulinum toxin on Levator ani syndrome-a double-blind, placebo-controlled study. Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions. The pharmacological management of neuropathic pain in adults in non-specialist settings. A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain. Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized controlled pilot study. Faculty of Pain Medicine, Opioids Aware: A resource for patients and healthcare professionals to support prescribing of opioid 2015. Different effects of morphine and oxycodone in experimentally evoked hyperalgesia: a human translational study. Comparison of intravesical botulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis/painful bladder syndrome. Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis. Adverse Events of Intravesical Onabotulinum Toxin A Injection between Patients with Overactive Bladder and Interstitial Cystitis-Different Mechanisms of Action of Botox on Bladder Dysfunction Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response. Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment A prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Long-term efficacy and safety of repeated intravescial onabotulinumtoxin A injections plus hydrodistention in the treatment of interstitial cystitis/bladder pain syndrome. Persistent therapeutic effect of repeated injections of onabotulinum toxin A in refractory bladder pain syndrome/interstitial cystitis. The functional results of partial, subtotal and total cystoplasty with special reference to ureterocaecocystoplasty, selective sphincterotomy and cystocystoplasty. Experiences with colocystoplasties, cecocystoplasties and ileocystoplasties in urologic surgery: 40 patients. Interstitial cystitis: thirteen patients treated operatively with intestinal bladder substitutes. Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution. Urinary conduit formation using a retubularized bowel from continent urinary diversion or intestinal augmentations: ii. Circumcision plus antibiotic, anti-inflammatory, and alpha-blocker therapy for the treatment for chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized, multicenter trial. Prospective double-blind preoperative pain clinic screening before microsurgical denervation of the spermatic cord in patients with testicular pain syndrome. Twelve-year outcomes of laparoscopic adhesiolysis in patients with chronic abdominal pain: A randomized clinical trial. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomised controlled multi-centre trial. Laparoscopic neurolysis of the sacral plexus and the sciatic nerve for extensive endometriosis of the pelvic wall. Decompression and transposition of the pudendal nerve in pudendal neuralgia: a randomized controlled trial and long-term evaluation. A prospective, single-blind, randomized crossover trial of sacral vs pudendal nerve stimulation for interstitial cystitis. The long-term efficacy of sacral neuromodulation in the management of intractable cases of bladder pain syndrome: 14 years of experience in one centre. Pudendal nerve neuromodulation with neurophysiology guidance: a potential treatment option for refractory chronic pelvi-perineal pain. Sacral neuromodulation as a treatment for neuropathic clitoral pain after abdominal hysterectomy. Is sacral nerve stimulation an effective treatment for chronic idiopathic anal pain The efficacy and safety of the ganglion impar block in chronic intractable pelvic and/ or perineal pain: A systematic review and meta-analysis. Management of neuropathic pain with methylprednisolone at the site of nerve injury. Adding corticosteroids to the pudendal nerve block for pudendal neuralgia: a randomised, double-blind, controlled trial. This information is publically accessible through the European Association of Urology website. This document was developed with the financial support of the European Association of Urology. It infuences different daily life aspects, including physical status, academic performance, mood, diet, exercise and sleep pattern. Objective: To determine the impact of the menstrual period on female medical students. Methods: this is a cross sectional study on Arabian Gulf University medical students. It included the following variables: socio-demographic characteristics, menstrual history, academic performance and habits (sleeping, appetite, exercise, mood and social relationships) during the menstrual period. The questionnaires were distributed to two hundred twenty-six female medical students during the academic year 2011-2012. Pain was reported as the most common cause of exercise discontinuation during menstruation (42. Further research should be conducted to study the effect of menstruation on Arab females. Resting, applying heating pads, The menstrual cycle involves many psychological changes, such as drinking tea, eating low-fat diet, intake of herbs and exercising are some irritability, mood liability, depression and anxiety. Women with heavy and painful menstrual periods have more problems afecting their academic and social lives [9]. Moreover, dysmenorrhea is one of the commonest gynecological *Corresponding author: Professor Randah R. Hamadeh, Vice Dean for Graduate problems among female adolescents and is the leading cause of short Studies and Research, College of Medicine & Medical Sciences, Arabian Gulf term school absenteeism, which negatively infuences their social, University, P. Box 22979, Manama, Kingdom of Bahrain, Tel: (+973) 17239423; Fax: (+973) 17239495; E-mail: randah@agu. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits women has shown that they were less likely to be negatively afected by unrestricted use, distribution, and reproduction in any medium, provided the menses [1-4]. The medical curriculum is based on small group tutorials that English class teachers. The average according to the distribution of the student population by academic duration of the menstrual cycle lasted between 2-11 days with a mean year. In addition, the average between two succeeding of the curriculum, tutorial groups for phase 2, and lecture attendees for cycles was 28. Tere were no statistically signifcant nationality and accommodation), menstrual history, academic diferences between medical years except for breast tenderness (0. Female students in two rotations of years 5 and 6 were selected continued to exercise and 62% stopped exercising during their period. Clerkship phase students were identifed from The most reported reasons that stopped students from exercising were: various rotations. They were also told in the study that the researches would clarify any query they Academic performance was afected by menstruation in several had in flling the questionnaire. Ethical approval was obtained for the ways mainly study time (76%), concentration (65. Eat more during my period Eat less during my period No effect No % No % No % Chocolate 133 59.

Syndromes

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Odour-evoked autobiographical memories: psychological investigations of Proustian phenomena prehypertension at 36 weeks pregnant lozol 1.5 mg low price. Cross Reference Amnesia Proximal Limb Weakness Weakness affecting predominantly the proximal musculature (shoulder abduc tors and hip exors) is a pattern frequently observed in myopathic and dystrophic muscle disorders and neuromuscular junction transmission disorders hypertension essential benign order lozol in india, much more so than predominantly distal weakness (the differential diagnosis of which encompasses myotonic dystrophy blood pressure chart 17 year olds purchase lozol now, distal myopathy of Miyoshi type pulse pressure aortic regurgitation buy lozol online now, desmin myopathy blood pressure medication numbness discount lozol 1.5mg with mastercard, and arrhythmia symptoms and treatment discount lozol 2.5 mg overnight delivery, rarely, myasthenia gravis). Age of onset and other clinical features may help to narrow the differential diagnosis: painful muscles may suggest an in ammatory cause (polymyositis, dermatomyositis); fatiguability may suggest myasthenia gravis (although lesser degrees of fatigue may be seen in myopathic disorders); weakness elsewhere may suggest a speci c diagnosis. Investigations (blood creatine kinase, neurophysiology, and muscle biopsy) may be required to determine exact diagnosis. Causes include any interruption to the anatomical pathway mediating proprioception, most often lesions in the dorsal cervical cord. Pseudo Babinski signs may normalize after dopaminergic treatment in dopa-responsive dystonia. These may be observed with lesions anywhere along the proprioceptive pathways, including parietal cortex, thalamus (there may be associated ataxic hemiparesis and hemihypoaesthesia), spinal cord, dorsal root ganglia (neuronopathy), and mononeuropathy. Pseudochoreoathetosis in four patients with hypes thetic ataxic hemiparesis in a thalamic lesion. The pattern of cognitive de cits in individuals with depression most closely resembles that seen in so-called subcortical dementia, with bradyphre nia, attentional, and executive de cits. Memory loss for recent and distant events may be equally severe -293 P Pseudodiplopia (cf. The recognition of pseudodementia is important since the de cits are often at least partially reversible with appropriate treatment with antidepressants. Psychomotor retardation in dementia syndromes may also be mistaken for depression. Longitudinal assessment may be required to differentiate between these diagnostic possibilities. In the European psychopathological tradition, it may refer simply to vivid visual imagery, whereas in the American arena it may refer to hallucinations that are recognized for what they are, i. Some patients with dementia with Lewy bodies certainly realize that their percepts do not correspond to external reality and similar experiences may occur with dopamine agonist treatment. Cross Reference One-and-a-half syndrome Pseudopapilloedema Pseudopapilloedema is the name given to elevation of the optic disc that is not due to oedema. In distinction to oedematous disc swelling, the nerve bre layer is not hazy and the underlying vessels are not obscured; however, spontaneous retinal venous pulsation is usually absent, and haemorrhages may be seen, so these are not reliable distinguishing features. Visual acuity is usually normal, but visual eld defects (most commonly in the inferior nasal eld) may be found. This may result simply from a redundant tarsal skin fold, especially in older patients, or be a functional condition. The term pseudoptosis has also been used in the context of hypotropia; when the non-hypotropic eye xates, the upper lid follows the hypotropic eye and appears ptotic, disappearing when xation is with the hypotropic eye. Cross Reference Ptosis Pseudoradicular Syndrome Thalamic lesions may sometimes cause contralateral sensory symptoms in an apparent radicular. If associated with perioral sensory symptoms this may be known as the cheiro-oral syndrome. Restricted acral sensory syndrome following minor stroke: further observations with special reference to differential severity of symptoms among individual digits. It may be confused with the akinesia of parkinsonism and with states of abulia or catato nia. This may be due to mechanical causes such as aponeurosis dehiscence, or neurological disease, in which case it may be congenital or acquired, partial or complete, unilateral or bilateral, xed or variable, isolated or accompanied by other signs. This is a stereo-illusion result ing from latency disparities in the visual pathways, most commonly seen as a 298 Pupillary Re exes P consequence of conduction slowing in a demyelinated optic nerve following uni lateral optic neuritis. A tinted coloured lens in front of the good eye can alleviate the symptom (or induce it in the normally sighted). Use of the Pulfrich pendulum for detecting abnormal delay in the visual pathways in multiple sclerosis. It is frequently related to previous occupation or hobbies but is seldom pleasurable. It is thought to be related to dopamin ergic stimulation and may be associated with impulse control disorder such as pathological gambling and hypersexuality. The contralat eral (consensual) response results from bres crossing the midline in the optic chiasm and in the posterior commissure at the level of the rostral brainstem. Paradoxical constriction of the pupil in darkness (Flynn phenomenon) has been described. In comatose patients, xed dilated pupils may be observed with central diencephalic herniation, whereas midbrain lesions produce xed midposition pupils. A dissociation between the light and accommodation reactions (light-near pupillary dissociation, q. This disparity arises because pupillomo tor bres run on the outside of the oculomotor nerve and are relatively spared by ischaemia but are vulnerable to external compression. Lip reading may assist in the understanding of others who sometimes seem to the patient as though they are speaking in a foreign language. Patients can copy and write spontaneously, follow written commands, but cannot write to dictation. There may be associated amusia, depending on the precise location of cerebral damage. Pure word deafness has been variously conceptualized as a form of auditory agnosia or a subcortical sensory aphasia. Pure word deafness is most commonly associated with bilateral lesions of the temporal cortex or subcortical lesions whose anatomical effect is to dam age the primary auditory cortex or isolate it. Very rarely pure word deafness has been associated with bilateral brainstem lesions at the level of the inferior colliculi. Pure word deafness after resection of a tectal plate glioma with preservation of wave V of brain stem auditory evoked potentials. Impaired pursuit may result from occipital lobe lesions, and may be abolished by bilateral lesions, and may coexist with some forms of congenital nystagmus. Cross References Nystamgus; Saccades; Saccadic intrusion, Saccadic pursuit Pyramidal Decussation Syndrome Pyramidal decussation syndrome is a rare crossed hemiplegia syndrome, with weakness of one arm and the contralateral leg without involvement of the face, due to a lesion within the pyramid below the decussation of corticospinal bres destined for the arm but above that for bres destined for the leg. Parietal lobe lesions may produce inferior quadrantic defects, usually accompanied by other localiz ing signs. Damage to extrastriate visual cortex (areas V2 and V3) has also been suggested to cause quadrantanopia; concurrent central achromatopsia favours this localization. As with hemiplegia, upper motor neurone quadriplegia may result from lesions of the corticospinal pathways anywhere from motor cortex to cervical cord via the brainstem, but is most commonly seen with brainstem and upper cervi cal cord lesions. Cerebellar hypoplasia and quadrupedal locomotion in humans as a recessive trait mapping to chromosome 17p. No speci c investigations are required, but a drug history, including over the counter medi cation, is crucial. The condition may be confused with edentulous dyskinesia, if there is accompanying tremor of the jaw and/or lip, or with tardive dyskinesia. Radiculopathy A radiculopathy is a disorder of nerve roots, causing pain in a radicular distribution, paraesthesia, sensory diminution or loss in the corresponding der matome, and lower motor neurone type weakness with re ex diminution or loss in the corresponding myotome. There may be concurrent myelopathy, typically of extrinsic or extramedullary type. Recognized causes include connective tissue disease, especially systemic sclerosis: cervical rib or tho racic outlet syndromes; vibration white nger; hypothyroidism; and uraemia. Associated symptoms should be sought to ascertain whether there is an under lying connective tissue disorder. Rebound Phenomenon this is one feature of the impaired checking response seen in cerebellar disease, along with dysdiadochokinesia and macrographia. Although previously attributed to hypotonia, it is more likely a re ection of asynergia between agonist and antagonist muscles. Recruitment Recruitment, or loudness recruitment, is the phenomenon of abnormally rapid growth of loudness with increase in sound intensity, which is encountered in patients with sensorineural (especially cochlear sensory) hearing loss. Cross Reference Re exes Recurrent Utterances the recurrent utterances of global aphasia, sometimes known as verbal stereo typies, stereotyped aphasia, or monophasia, are reiterated words or syllables produced by patients with profound non uent aphasia. Red Ear Syndrome Irritation of the C3 nerve root may cause pain, burning, and redness of the pinna. This may also occur with temporomandibular joint dysfunction and thalamic lesions. Reduplicative Paramnesia Reduplicative paramnesia is a delusion in which patients believe familiar places, objects, individuals, or events to be duplicated. The syndrome is probably het erogeneous and bears some resemblance to the Capgras delusion as described by psychiatrists. Reduplicative paramnesia is more commonly seen with right (non dominant) hemisphere damage; frontal, temporal, and limbic system damage has been implicated.

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Very common symptoms of McArdle disease (seen in almost all McArdle people): Exercise intolerance; muscles becoming tired very quickly and running out of energy (Lucia et al hypertension disorder cheap 2.5mg lozol free shipping. Muscle pain during intense exercise will usually have existed since childhood (Quinlivan and Vissing prehypertension 2016 buy lozol 2.5mg with visa, 2007) blood pressure 0f 165 purchase discount lozol. However blood pressure keeps going down purchase lozol cheap, many McArdle people do not know how to get into a 18 second wind or do not realise that this is occurring unless guided through it by a family doctor or specialist (Quinlivan and Vissing arteria subclavia discount 2.5 mg lozol visa, 2007) arrhythmia consultants greenville sc buy discount lozol 1.5mg. Muscle pain (myalgia), inflammation (myositis) and damage caused by statins (drugs taken to lower cholesterol) can sometimes lead to hospital investigations which result in a diagnosis of McArdle disease (Biller, 2007). A brief description of each, along with the pros and cons, and limitations is given in Table 2. No Use of this test was first described by Dr Brian McArdle and forearm exercise test has been in use for about 50 years. An overview of my opinion of how commonly each method is used, whether it produces a definitive diagnosis, and relevant notes. All three are intended to test whether the body is able to break down glycogen to produce glucose in order to provide the muscles with energy during exercise. What is tested: When a muscle of an unaffected person is exercised vigorously (anaerobic exercise), the free glucose is rapidly used up. Stored glycogen is then broken down by the process of glycogenolysis to produce energy. In McArdle people, the absence of functional muscle glycogen phosphorylase enzyme blocks glycogenolysis. McArdle people therefore do not have the expected increase in lactate and pyruvate levels. However, recent studies have shown that similar results with less risk of muscle damage can be achieved with a non-ischaemic forearm test (Niepel, 2004). Cons of all exercise tests: the level of effort must be below the maximum so that severe complications like rhabdomyolysis and myoglobinuria do not occur (Fernandes, 2006). Following exercise, increased ammonia levels, increased uric acid levels (see section 13. An absence of increase in lactate and pyruvate levels indicates a metabolic disease caused by a block in glycogenolysis. Many other glycogen storage diseases prevent lactate production after anaerobic exercise (Lane, 1996). The exercise test does not distinguish whether the person has McArdle disease or another other metabolic disease, for example, another glycogen storage disease such as Tauri disease (phosphofructokinase deficiency) (Abramsky, 2001). Cori disease and Tauri disease can produce flat (not increasing) lactate levels after the forearm test (Biller, 2007). For this reason, the level of 21 ammonia in the blood (plasma ammonia) is usually measured before and after an ischaemic forearm test (Lane, 1996). The forearm is contracted by squeezing a ball or balloon, or the thigh is contracted at maximum force/strength for one minute or until extreme pain. The blood is analysed to determine whether the expected increase in lactate and pyruvate occurs. It is important that ammonia levels in the blood rise, as this shows that the person has exercised enough, as an incorrect result could be obtained if the person who is being tested does not exercise with enough effort (Lane, 1996). Cramping, muscle pain and contracture of the muscle may occur following the test (Cush, 2005) There is a small risk of the severe problem of compartment syndrome (discussed further in section 12. The risk of compartment syndrome is much lower if the non-ischaemic forearm test is performed. There is also a risk of the test causing severe muscle damage which could lead to kidney failure (see section 5 for further information on rhabdomyolysis and kidney failure). The muscle of the tested forearm was damaged, which resulted in myoglobinuria and raised creatine kinase levels in the blood. The person was placed under medical observation and instructed to drink plenty of fluids. How the non-ischaemic forearm test is carried out: A non-ischaemic forearm test (similar to that described above but without use of a cuff) is now recommended. The non-ischaemic forearm test is much less likely to cause damage (Niepel, 2004). Cons of the non-ischaemic forearm test: I think that it seems possible that muscle damage could also be a side effect of the non-ischaemic forearm test if the person exercises too vigorously (as described by Meinck et al. Pros of both the ischaemic and non-ischaemic forearm exercise tests: It is not very invasive (the only invasive part is taking blood samples). It may produce a positive result in people with other similar diseases which affect glycogenolysis or glycolysis (like some of the other glycogen storage disease). It was suggested by Lane (1996) that false negative results could be seen in the rare cases of McArdle people with low levels of phosphorylase activity, but no experimental data was provided to support this theory. The blood samples must be assayed quickly, so it is essential that the test is performed at a location near to a biochemistry laboratory (Barnes, 2003). The band can be tightened to provide more resistance, making it harder work to pedal and increasing the amount of energy the person needs to move the pedals (energy is measured as Watts (W)). What is tested: this test measures whether exercise leads to an increase in lactate and pyruvate in the blood. How the cycle ergometer test is carried out: McArdle people have very low work capacities, so the cycle ergometer should be precisely adjusted to provide low amount of resistance (0-50W). The person begins to pedal gently, with the amount of resistance being increased by 5-10W every other minute. A blood sample is taken prior to exercise, and after exercise to find out the lactate levels in the blood (Abramsky, 2001). In McArdle people, this level of exercise causes a high heart rate and a high level of perceived exhaustion (it feels like really hard work to pedal) until 8-10minutes into the exercise, when the second wind occurs. At this point (8-10mins into exercise), McArdle people have a dramatic drop in 23 heart rate and it feels much easier to exercise/pedal even though they are pedalling at the same rate as before. It can be further tested by increasing the resistance (making the band tighter so that the person has to pedal even harder). In some experiments, the person is then given intravenous glucose (glucose via a needle and drip in the arm; 50ml of a 50% solution). In Tauri disease, a second wind does not occur, and intravenous glucose makes it harder for the person to exercise (Abramsky, 2001). To ensure that the person exercised is not working at their maximum level, their pulse rate should be kept below 150 beats/min for adults and 150-180 beats/min for children (Fernandes, 2006). Pros of cycle ergometer for exercise tests (pros are not specific to testing for McArdle disease): Keeps person being tested in the same place, so it is easy for them to wear a facemask which is used to monitor the amount of oxygen being breathed in, and amount of carbon dioxide being breathed out. It is also easier to take blood from the person as they are staying in the same place. It is easy to use the cycle machine to accurately quantify the amount of exercise the person is doing (adapted from Cooper and Storer, 2001). For these reasons, a cycle ergometer is often used by scientists testing the effect of diet or exercise on the ability of McArdle people to exercise, for example, Drs Haller and Vissing frequently publish papers using cycle ergometers. Cons of cycle ergometer for exercise tests (cons are not specific to testing for McArdle disease): If people do not cycle regularly, it may feel strange, and may result in premature leg tiredness if it is an unfamiliar form of exercise (adapted from Cooper and Storer, 2001). What is tested: the treadmill test is used to measure presence of second wind, effect of exercise on heart rate, and to test whether exercise leads to muscle pain. How the treadmill test is carried out: the person being tested walks on a treadmill. The speed of the belt and the slope of the belt (level of inclination) can be adapted so that the person is walking at a speed of 3-5km/h with a pulse rate of 150-180beats/min. The length of time that it takes for the person to become exhausted can indicate which disease they may have. Glycogen storage diseases will make people exhausted more rapidly, whereas diseases caused by defects in fatty-acid oxidation will make people feel exhausted later (Fernandes, 2006). Everyone is used to walking around, so it is a very natural and familiar way to test (Cooper and Storer, 2001). Cons of the treadmill test: It can be harder to measure oxygen and carbon dioxide. Unaffected people have a high level of muscle glycogen phosphorylase enzyme in their muscle cells. How is the muscle biopsy test carried out: the McArdle person is placed under either local or general anaesthetic. A surgeon removes a piece of muscle from one of the large muscles such as the upper arm, thigh, or calf. The piece of muscle is sent to a histology department who will preserve it if necessary, and carry out the necessary tests. It should be compared to a sample from someone who is known not to have any muscle disease (a negative control). The family doctor or specialist should then be sent a report from the histology department outlining the results. It should be noted that muscle biopsies can either be taken as a needle biopsy (a hollow needle is used to cut and remove a sample of the muscle), or as an open biopsy (a surgeon cuts and removes a small sample of muscle). A needle biopsy is normally smaller than an open biopsy, is likely to cause less damage to the muscle, and have a quicker healing time. Some textbooks recommended that a muscle biopsy be performed in the most symptomatic area (Cush, 2005). Surgeons usually chose to biopsy the thigh, calf, or bicep because they are large muscles, so it is easier to take a small biopsy without damaging any surrounding tissue. McArdle people are at an increased risk of having malignant hyperthermia-like symptoms which can cause a dangerous reaction to general anaesthetic). Dubowitz and Sewry (2007) recommend muscle biopsy be performed under local anaesthetic, which reduces risk of side effects like malignant hyperthermia. Limitations: An inaccurate result may be obtained if muscle biopsy is performed shortly after a period of rhabdomyolysis and muscle damage. If muscle damage has occurred prior to the biopsy being taken, small (immature/regenerating) muscle fibres may be seen which are positive for the phosphorylase stain due to expression of other isoforms of glycogen phosphorylase enzyme (Lane, 1996). It is not possible to distinguish between the different isoforms of glycogen phosphorylase enzyme in the phosphorylase staining test. Testing a muscle biopsy shortly after rhabdomyolysis has occurred is likely to result in a false negative result; a person who really does have McArdle disease will be told that there is nothing wrong with them. Notes: It should be noted that McArdle disease cannot be diagnosed by skin biopsy. It would be advisable to ask/request that the muscle biopsy is stored by the laboratory carrying out the tests (in liquid nitrogen or -80 freezer as appropriate) until the diagnosis is confirmed. If there are any questions or uncertainty about the diagnosis, the stored muscle biopsy can be used to perform further tests. A chemical reaction is carried out to determine whether there is functional muscle glycogen phosphorylase in the muscle fibres (Amato, 2003). The muscle glycogen phosphorylase enzyme is used to produce a compound which can be stained to produce the purple/brown colour. If the muscle glycogen phosphorylase enzyme is not functional, it will not produce this compound and no colour will be seen. After staining, the slides with slices of muscle will be examined under a microscope. This removes the possibility of a false negative test if some part of the test does not work correctly. Pros of the staining of slides with slices of muscle test: If the phosphorylase staining is carried out correctly, it will provide an accurate and specific diagnosis of McArdle disease. It will work whether the mutation is known or a brand new mutation which has not been identified before. One muscle biopsy can also be used to test for (and exclude) many different muscle diseases. Cons of the staining of slides with slices of muscle test: It should be noted that an accumulation of glycogen will be seen from almost all the glycogen storage diseases, and therefore is not diagnostic of McArdle disease. Instead of making thin slices, the sample is homogenised (mashed up), and a chemical reaction is carried out to measure how much active muscle glycogen phosphorylase is present (if any). It may be easier to quantify a very low level of phosphorylase activity, but with the limitation described below.

Diseases

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