By K. Quadir. University of South Carolina, Beaufort. 2018.

Although it may sound strange after many years of research on MS buy 25 mg dipyridamole fast delivery, what is called the ‘natural history’ of the disease is still not entirely clear dipyridamole 100mg otc, although major studies in Canada have revealed much about the long-term outcome of MS generic dipyridamole 100mg overnight delivery. As we discussed in Chapter 1 order 25 mg dipyridamole free shipping, it is still not really possible to give anyone a clear idea of how their disease will develop over time generic dipyridamole 25mg with amex, so much clinical research is still devoted to assessing people with MS over long periods of time – several decades – to chart as carefully as possible how their disease develops, especially in relation to early symptoms and signs. Such information is very important, in order to judge, for example, whether early inter- vention will affect the later course of the disease. As people with the condition know, the effects of MS appear to be very fickle on a day-to-day basis, let alone a longer term one, so it is one of the most difficult research tasks to determine the specific effects of MS, as against those occurring from other, perhaps unrelated, conditions, and the effects of natural ageing processes. Other clinical research is focused on improving and developing diagnostic techniques to try and ensure that such techniques are both accurate and available as early as possible. RESEARCH 191 Applied research The traditional kind of research on MS has focused on the causes and cures of the disease, and indeed this kind of research is still the most important in terms of size and funding. However, this research generally does not tackle all the everyday problems that people with MS have of living with the condition. To put it another way, whilst waiting for a cure, people with MS have had to live for years with many difficult and annoying problems, and indeed may have to wait many more years before MS and its problems are banished. Thus an area of ‘applied research’ has arisen where the focus is on researching the best ways in which people with MS can live with or manage their current and future symptoms, and their consequences. This research might include: • clinical trial research on drugs and other means of managing everyday symptoms; • the most appropriate forms of equipment that people may need, to live as comfortably as possible; • the most effective ways in which physiotherapy, occupational therapy and speech therapy can help people with MS; • the most appropriate ways in which issues of employment, housing and insurance can be dealt with; • the psychological and social consequences of MS, especially in relation to concerns about the quality of life, and • issues about counselling and support for the family consequences of the condition. In practice, this broad area of ‘applied research’ is one of the most significant of current research areas, and is one which – on reflection – many people with MS find extremely valuable and relevant. Although everyone wishes to find a cure for MS, a realistic view is that this will take some time, and meanwhile research on how people with MS can make the best of their everyday lives is very important. Clinical trials Much of the hugely expensive development work on new (drug) therapies is undertaken by pharmaceutical companies. The commercial return on their investment in these costs, including clinical trials, has to come from patenting and protecting the rights to the therapy involved. Potential medicines that may be freely available, or are not patentable, offer very little incentive for such companies to invest in them, unless they can in some way lay claim to a variant of the medicine concerned 192 MANAGING YOUR MULTIPLE SCLEROSIS or a particular way of administering it. In such cases, other funding agencies, such as the Medical Research Council (MRC), step in to support formal trials on drugs or other substances that are considered promising therapies for MS. A clinical trial is actually a formal scientific means of testing the safety or the effectiveness of a drug or other treatment, either against another drug or treatment, or against what is called a ‘placebo’, i. This way the drug can be tested for efficacy compared to the other drug or substance. In a clinical trial of a potential therapy for MS, usually one group of patients (the experimental group) receives the active drug or the drug being tested, and another group (the control group) receives the drug against which it is to be compared, or the placebo, the inactive substance. The two groups of patients should be as similar as possible at the outset of the trial, so that the drug alone will make the difference between the groups. Various characteristics of the two groups of people will be measured before, during and after the trial – typically these will include measures of disability, the number of MS ‘attacks’ or ‘relapses’ people have had, and other things such as blood cell counts or hormone levels. It is always hoped, of course, that the trial will show that the group who has received the active drug will do better. Thus, for the active drug to be shown to be effective, the trial must finally result in a statistically significant difference between the characteristics of the two groups. However, many trials are relatively inconclusive and, because MS is a complicated condition, statistically significant differences will be observed for some characteristics but not others, or indeed only for certain types of participant. Blinded and randomised clinical trials ‘Blinded’ in this sense means that you do not know which drug – active or inactive – you are taking, and thus you will not be able to exert any psychological impact on the results, or be tempted to take supplements if you know that you are in the control rather than the experimental group. People are also usually ‘randomized’, meaning that they are allocated to either the experimental or control groups randomly, i. If people are allowed to choose which group they go into, biases may arise in the trial, as certain people, for example with milder or more serious forms of MS, may elect to join RESEARCH 193 one of the groups and not the other. The placebo and the active substance must therefore look and taste identical, so they are often provided in coded containers to each person. Only at the end of the trial is the code broken to reveal who received which compound, when the trial is ‘unblinded’. This minimizes the possibility of researchers influencing the outcome, for instance by paying more attention, or giving additional and differential care, to people in the treatment group during the trial.

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Note also that F in Plate 1 is decreasing (with Z increasing time) as the subject’s right foot approaches toe-off order dipyridamole 100 mg overnight delivery. The ground reaction force data may be plotted as a function of time as seen in Figure 3 buy dipyridamole 25 mg fast delivery. There are a few observations that need to be made when studying the F cheap 25mg dipyridamole with mastercard,X F dipyridamole 100 mg without prescription, and F curves in this figure cheap 25mg dipyridamole amex. The range (in newtons) for the vertical forceY Z F is almost three times that of the fore-aft force F. The subject’s weight is a little over Y Z 600N, so F , which has the characteristic double hump, exceeds body weight Z 38 DYNAMICS OF HUMAN GAIT at two different times during the stance phase. It should be pointed out that the male subject in this example was walking slightly slower than his normal pace (stance time is normally a little over 0. Thereafter it becomes positive as the subject pushes off, driving backward on the plate, and, in accordance with Newton’s third law of motion, experiencing a forward force. During most of the stance phase F is positive, which means that the plate is pushing inward (or in aY medial direction) on the subject’s foot. Calculation of Joint Forces and Moments Now that we have the ground reaction force data, we can go on to calculate the resultant forces and moments acting at the joints of the subject’s lower extremities — ankles, knees, and hips. The mathematics to accomplish this is not trivial (Greenwood, 1965), but we provide a simple overview of some of the key steps here in this chapter, leaving the details for Appendix B. An FBD is a diagram in which the segment or body or interest (say, the right foot) is removed (or set free) from its environment and the external forces and mo- ments acting on it are drawn in. For X, a forward force is +ve, backward is -20 -ve; for Y to the left is -40 +ve, to the right is -ve; and for Z, up is +ve, down is -ve. Ankle F reaction FR, and the force of the calf on the foot at the ankle joint FR FR. The external moments acting on the foot are the ground reaction torque about the Z axis TZ, and the moment of the calf on the foot at the ankle joint MR. Note that the torque and moment are W Foot indicated as vectors with double arrow points. Linear: The summation of external forces acting on a segment (or free body) is equal to the rate of change of the linear momentum of the segment. All this means that we now have sufficient information to solve for the resultant force at the right ankle joint FR. It is important to realise that this force is not simply the force of the tibia acting on the talar dome. Rather, it is the resultant of all the forces acting across the ankle, including bone, ligament, and muscular forces. To solve for all these individual forces uniquely is not possible because we do not have enough equations (Vaughan, Hay & Andrews, 1982). The angular form of Newton’s second law of motion may be stated as follows: Angular: The summation of external moments acting on a segment (or free body) about its centre of gravity is equal to the rate of change of the angular momentum of the segment. With this information, we calculate the lever arms and hence the moments due to the proximal force at the ankle and the distal force from the ground. Now, by Newton’s third law of motion (also known as the law of action and reaction), if we know the force and moment exerted by the calf on the foot at the ankle, then the force and moment exerted by the foot on the calf at the ankle has the same magnitude and opposite direction. We repeat the process for the thigh to find the force and moment at the hip joint. Just as this procedure has been applied to the right side, it can be applied to the left side, providing the foot is either airborne (in which case the ground reaction force data are zero) or in contact with a force plate (and the ground reaction force data can be measured). Expression of Joint Forces and Moments The resultant joint forces and moments are three-dimensional vectors. One way of doing this is to use the global reference frame XYZ as the basis for the com- ponents. The drawback of this approach, however, is that it can be difficult to relate these laboratory-based components to human subjects, particularly those who walk at an angle to the X and Y axes instead of walking parallel to the X axis as illustrated in Figure 3. We believe a more sensible approach is to express the forces and moments in terms of body-based coordinate systems that have some anatomical signficance. These are as follows: Forces • A mediolateral force takes place along the mediolateral axis of the proxi mal segment. Moments • A flexion/extension moment takes place about the mediolateral axis of the proximal segment. These curves compare favorably with other data in the literature (Andriacchi & Strickland, 1985; Apkarian et al. You will notice that the ranges (in newton•metres, Nm) for the flexion/extension and abduction/adduction moments are of the same order of magnitude.

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The back- bone to MS management has been and continues to be the man- agement of symptoms cheap dipyridamole 100 mg without a prescription. Everyone with MS should be aware of the many ways that the symptoms of MS can be managed order 25 mg dipyridamole fast delivery, with the goal of improved quality of life cheap dipyridamole 25mg online. Symptoms in MS may be divided into those that are caused directly by demyelination within the brain and spinal cord and those that are not buy cheap dipyridamole 100 mg online. If you lose myelin in the part of the brain or spinal cord that influences strength buy dipyridamole 100mg with visa, you will develop weakness; if you lose myelin in the part that controls coordination, you will become uncoordinated; and if you lose myelin in the part that con- PART II • Managing MS Symptoms trols sensation, you will develop numbness, pain, burning, or itch- ing. Symptoms in MS may be divided into those that are caused directly by demyeli- nation within the brain and spinal cord and those that are not. People who have primary symptoms sometimes also suffer from problems that are only indirectly caused by the disease; these are called secondary symptoms. For example, some people who are weak and stiff develop decreased movement at the joints, which are called contractures, and immobility can lead to osteoporosis or skin breakdown. Chronic disease may lead to changes in how one looks at life and tackles life’s stresses. Thus, to really tackle MS, the disease process should be modi- fied whenever it is possible to do so; the symptoms of the disease should be managed to allow better function; and the person with the disease should be helped to improve his or her quality of life. Part of the reason that fatigue is so common and potentially disabling relates to the fact that many different kinds of fatigue are experienced by people with MS, and it is possi- ble to have none or all of the forms at the same time. Obviously, MS does not protect you from the normal fatigue that anyone else may experience. However, a person with MS some- times may have a "short-circuiting" type of fatigue. The limb will recover when the arm or leg is rested, but it may be both- ersome when activities require its ongoing use. Repeatedly asking the demyelinated nerve to perform when it is repeatedly short-cir- cuiting causes fatigue. The judicious use of aerobic exercise (see Chapter 20) may help build endurance, if not strength, and thus may decease this form of fatigue. However overexercising with weights increases both fatigue and weakness, so a careful balance must be sought. Management strategies include the appropriate use of exercise and rest, with the understanding that "no pain, no gain" is simply 25 PART II • Managing MS Symptoms wrong and that rest should come before short-circuiting fatigue becomes significant. The appropriate management strategy for this type of fatigue is exercise and maintaining of mobility. Depression (see also Chapter 22) may be associated with MS and may cause sig- nificant fatigue. This may result from not eating or sleeping well, or it may be associated with a general feeling of depression. It should be managed by aggressively treating the depression with medica- tion and counseling. This form of fatigue likely is bio- chemical in origin, and medications that modify brain chemistry may be helpful. Amantidine (Symmetrel®) is an example of a med- ication that affects the nervous system and also has antiviral effects. The antidepressants, including fluoxetine (Prozac®), paroxetine (Paxil®), and sertraline (Zoloft®), may be useful for this type of fatigue, even in those who are not depressed. These med- ications may not be interchangeable, with one working better for one person and a different one for another. Lassitude is a bother- some form of fatigue because a person may look well and yet not be able to function. A new, novel medication, modafinil (Provigil®) has been shown to decrease MS fatigue and has become a com- monly used treatment for this problem. Its mode of action is not clear but it does work by altering the brain’s neurochemistry. It has a potential side effect of agitation, which should be reported to your physician immediately. These include pemoline (Cylert®), methylphenidate (Ritalin®), and occa- sionally dextroamphetamine (Dexedrine®). These medications 26 CHAPTER 3 • Fatigue should be used with caution because they may be habit-forming and may lead to agitation. The management strategy for this form of fatigue includes rest and the use of antidepressant and stimulant medications. Even though fatigue is common and potentially disabling, it is clear that people who have MS are not fragile.

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THE PRACTICALITIES OF SETTING TARGET HEART RATES From ETT results discount dipyridamole 25mg overnight delivery, the HRpeak can be used in either the %HRpeak or %HRRpeak (Karvonen HR reserve method) formulas buy dipyridamole 100mg online. If a true maximal HR has been attained 25 mg dipyridamole visa, then the annotation would be %HRmax or %HRRmax safe dipyridamole 25mg, respectively cheap dipyridamole 25mg. When using the age-estimated maximal HR formula of 220 minus age (years) or the formula recommended by Tanaka, et al. The Karovonen heart rate reserve method for determining a target HR, which can be used from either an exercise test peak HR (HRpeak), a maximal HR (HRmax), or from the age estimated HRmax formulas above, is as follows: Target heart rate = %target ¥ (HRpeak/max - HRrest) + HRrest %target = the desired percentage (e. Exercise Physiology and Monitoring of Exercise 59 60 Exercise Leadership in Cardiac Rehabilitation Exercise Physiology and Monitoring of Exercise 61 62 Exercise Leadership in Cardiac Rehabilitation Exercise Physiology and Monitoring of Exercise 63 64 Exercise Leadership in Cardiac Rehabilitation Exercise Physiology and Monitoring of Exercise 65 66 Exercise Leadership in Cardiac Rehabilitation TARGET HEART RATE RESPONSE NUANCES DURING THE EXERCISE SESSION Two factors can alter the theoretical relationship between exercise work rate and HR during an exercise session: 1. Exercises performed using an interval approach, where each station or interval of exercise lasts less than two minutes. Cardiovascular drift The basic premise of cardiovascular drift is that after 10 minutes of exercise, HR will rise in spite of no change in the work rate or oxygen cost of the exer- cise being performed (Coyle and Gonzales-Alonso, 2001). There are a number of factors, which continue to be debated, in this effect (Ajisaka, et al. The agreed fact is that, for a given oxygen uptake, cardiac output must remain constant. What is still debatable is the cause of cardiovascular drift including: •adecrease in peripheral vascular resistance that leads to a drop in blood pressure as a result of an increase in skin blood flow to meet the needs of thermo-regulation, in light of the fact that blood pressure is a function of the stroke volume component of cardiac output and total peripheral resistance; •adecrease in plasma volume, due to either dehydration or a shift of fluid from the vascular to the interstitial tissues of the exercising muscle; •adrop in stroke volume, either as a function of one or both of the factors above, where venous return has decreased and impairs the Frank-Starling mechanism, or possibly, and more simply that a raised HR reduces the time for ventricular filling. From the exercise leader’s perspective, the one undeniable point is that over the duration of an exercise rehabilitation session the target HR should allow for an upward drift in HR by as much as 10 beats·min-1. Heart rate response during interval-type exercise Interval circuit exercise is specifically beneficial to individuals with low func- tional capacity, left ventricular dysfunction or concomitant pulmonary or peripheral circulatory disease exercise limitations (Cachovan, et al. The use of interval circuit exercise is a typical feature in the UK for phase III and IV rehabilitation programmes. Interval training permits the patient to produce a greater amount of work in a training session if the training periods Exercise Physiology and Monitoring of Exercise 67 are spaced between periods of lower intensity work. These lower intensity bouts, called active recovery (AR) periods, are between 30 seconds and 1 minute in duration. A deconditioned patient may only be able to maintain a training intensity exercise for a few minutes before becoming too fatigued to continue. Other practical reasons for using the interval circuit format include the lack of specialist exercise facilities, where rehabilitation gymnasia are multipur- pose, and the area needs to be set up and cleared for a variety of uses. This is addressed by the characteristics of interval training which allows for the use of very basic exercise equipment (hand weights, steps, shuttle walks, callisthenic-type movements, etc. The total duration of exercise, however, is aimed at accumulating the recom- mended minimum of at least 20 minutes of aerobic activity (ACSM, 2000). The progression is to gradually remove the active-rest intervals towards achieving at least 20 minutes of continuous activity. For patients using interval circuit training, the differences in HR response compared to continuous activity need to be acknowledged. It has long been known that it takes at least two minutes for HR to rise and level off, follow- ing the initiation of constant sub-maximal exercise workload (Saltin, et al. This time lag is a function of the response time of the sympathetic neuro-humoral regulation of HR, relative to the required systemic circulatory and metabolic demands. Because interval training often has exercise stations lasting less than two minutes, the theoretical matching of HR to muscular work output will not occur. If patients are attaining their aerobic target HR in this short period (<2mins) they will actually be working at an intensity that would elicit an HR above their target, if the activity were sustained continuously (>2mins). Inadvertently, this is beneficial, because it is metabolically challenging to the skeletal muscle. Before HR begins to approach its critical level, the patient starts to decrease inten- sity as part of AR. However, over the course of a rehabilitation session, there is cardiovascular drift and an increased likelihood of muscular fatigue. This latter point could cause a potential loss of sense of achievement for the patient if the intensity is too high. With too high an intensity, the accumulation of lactic acid will prolong both metabolic recovery and heart rate recovery (McArdle, et al. This is due to both the raised aerobic metabolism needed to clear the lactate from the system and lactate’s sympathetic nervous system stimu- lating properties. The concept of the cool-down is discussed in more depth in Chapter 5 on programme design. In this individual, when the intensity requires greater than 60% HRmax 68 Exercise Leadership in Cardiac Rehabilitation Heart rate at a given MET level for 1 and 3 min durations 200 180 1 1 164 160 150 140 129 120 120 116 111 106 Heart rate 1 min 100 101 Heart rate 3 min 80 1.

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