By W. Gembak. Potomac College. 2018.
Deficiencies of different enzymes in the pathway result in chronic accumulation of this pigment in car- phenylketonuria discount alli 60 mg without prescription weight loss questionnaire, tyrosinemia buy cheap alli 60mg weight loss 80 diet, and alcaptonuria. Phenylalanine is hydroxylated to form tyrosine by a mixed function oxidase, phenylalanine hydroxylase (PAH), which requires molecular oxygen and tetrahy- Transient tyrosinemia is frequently drobiopterin (Fig. The cofactor tetrahydrobiopterin is converted to quininoid observed in newborn infants, espe- dihydrobiopterin by this reaction. Tetrahydrobiopterin is not synthesized from a cially those that are premature. For vitamin; it can be synthesized in the body from GTP. However, as is the case with the most part, the condition appears to be other cofactors, the body contains limited amounts. Therefore, dihydrobiopterin benign, and dietary restriction of protein must be reconverted to tetrahydrobiopterin for the reaction to continue to produce returns plasma tyrosine levels to normal. The biochemical defect is most likely a low level, tyrosine. Because this Phenylalanine enzyme requires ascorbate, ascorbate sup- plementation also aids in reducing circulat- ing tyrosine levels. Other types of tyrosinemia are related to Tyrosine specific enzyme defects (see Fig. Tyrosinemia II is caused by a genetic defi- Tryptophan ciency of tyrosine aminotransferase (TAT) and may lead to lesions of the eye and skin as well Homogentisic acid as neurologic problems. Patients are treated Formate with a low-tyrosine, low-phenylalanine diet. Tyrosinemia I (also called tyrosinosis) is Fumarate TCA caused by a genetic deficiency of fumary- Alanine Threonine lacetoacetate hydrolase. The acute form is Glucose associated with liver failure, a cabbagelike Pyruvate odor, and death within the first year of life. Glucose Acetyl CoA Acetoacetate Nicotinamide moiety of Lysine Leucine NAD, NADP Isoleucine Succinyl CoA In addition to methionine, threo- Glucose nine, isoleucine, and valine (see Fig. Some of these amino acids (tryptophan, phenylalanine, the -end of odd-chain fatty acids, and tyrosine) also contain carbons that can form glucose. Leucine and lysine are strictly keto- form succinyl CoA by this route (see Chapter genic; they do not form glucose. These infants exhibit CO2 normal phenylalanine hydroxylase (PAH) OH activity but have a deficiency in dihy- dropteridine reductase (DHPR), an enzyme C – CH2 COO required for the regeneration of tetrahydro- C biopterin (BH4), a cofactor of PAH (see Fig. Less frequently, DHPR activity is nor- mal but a defect in the biosynthesis of BH4 Alcaptonuria homogentisate oxidase exists. In either case, dietary therapy cor- rects the hyperphenylalaninemia. However, BH4 is also a cofactor for two other hydroxy- lations required in the synthesis of neuro- Tyrosinemia I fumarylacetoacetate hydrolase transmitters in the brain: the hydroxylation of tryptophan to 5-hydroxytryptophan and O of tyrosine to L-dopa (see Chapter 48). It has –OO COO– CH C CH OO– 3 2 been suggested that the resulting deficit in Fumarate Acetoacetate central nervous system neurotransmitter activity is, at least in part, responsible for the Fig. The carboxyl carbon forms CO2, and neurologic manifestations and eventual the other carbons form fumarate or acetoacetate as indicated. Deficiencies of enzymes (gray death of these patients. Tryptophan tryptophan are insufficient, the Tryptophan is oxidized to produce alanine (from the non-ring carbons), formate, and condition known as pellagra acetyl CoA. Tryptophan is, therefore, both glucogenic and ketogenic (Fig. The symptoms of pellagra are der- matitis, diarrhea, dementia, and, finally, NAD and NADP can be produced from the ring structure of tryptophan. In addition, abnormal metabolism of fore, tryptophan “spares” the dietary requirement for niacin. The higher the dietary tryptophan occurs in a vitamin B6 deficiency. Threonine, Isoleucine, Leucine, and Lysine vitamin B6.
Contrac- ture is a poor word because it leaves the impression that a muscle has some- how pulled into itself such that it could be pulled out of its contracted posi- tion discount alli 60mg fast delivery weight loss percentage calculator. This concept is wrong order 60 mg alli with mastercard weight loss pills jillian michaels, and what the term really means is that the muscle fibers are too short and have a decreased level of excursion. The stimulus for in vivo growth of muscle is poorly defined, but it is some combination of stretching to the maximum over a frequency or time period. This stimulus is almost exclusively a mechanical factor that is altered by an increase in muscle tone. The increase in muscle tone probably prevents children from stretching the muscle in a relaxed state during activities such as position changes in bed during sleep. If a joint is immobilized, the muscle will shorten, but it will lengthen again after release of joint immobility if the joint has a good range of motion. The length growth of a muscle occurs by muscle fibers adding sarcomeres at the muscle–tendon junction, very similar to the growth plate in bone. Increasing Excursion The clinical treatment of shortened muscles known as contractures has tra- ditionally focused on stretching range-of-motion exercises done with passive and active stretching. There is no doubt that children with no ability to do self-movement need to have their joints moved and these muscles stretched. For ambulatory children who are active ambulators and are growing fast, the goal of trying to avoid the muscles getting shorter and shorter by stimu- lating muscle growth through stretching is reasonable; however, the objec- tive data to support the efficacy of this are minimal. Based on our exami- nation of children in patterning therapy where they receive many hours of passive range-of-motion exercises, we believe it is possible to make muscles grow. However, the amount of passive range-of-motion stretching required is so disruptive to the lives of families and the other activities of these chil- dren that muscle contractures are far less disabling than the therapy to pre- vent the contractures. Stretching is like many exercise programs done for general health, meaning a little is better than none; however, there is an amount that makes a significant difference. We do not know how much stretching in the relaxed position is required; however, it is probably in the range of 4 to 8 hours per day. Other treatments to make muscles grow are poorly documented. There are reports in the literature that claim that muscle growth occurred based on increased range of motion after Botox injections17; however, others, with careful assessment, have not found this to be the case. In an unpublished study, we tried to stretch ham- string muscles in children with the use of knee immobilizer splints. A splint was used every night on one leg but not the other. There was a measurable improvement in the popliteal angle, suggesting increased length in the muscle. However, the major problem was that only 30% of the children could fol- low through a 12-week wearing time on one leg only, which suggests that nighttime splinting does not have good acceptance with families or children. When the goal is to stretch the gastrocnemius, it is very important to realize that this cannot be done without also keep- ing the knee extended. This means nighttime ankle bracing without bracing the knee into extension is worse than not bracing because it only stretches the soleus, which is usually not contracted, and allows the gastrocnemius to further contract because the child will sleep with severe knee flexion. Many therapists believe children should wear ankle-foot orthotics (AFO) at night to stretch the contracted gastrocnemius. However, if only AFOs are used, children will flex the knee and only the soleus gets stretched, further increasing the length difference many children already have between the gastrocnemius and soleus muscles (Figure 7. Stretching the gastrocnemius requires the use of a knee exten- sion splint and a dorsiflexion splint, a combination that is bulky and adds to the poor acceptance. The use of casting adds other problems, especially mus- cle atrophy. One of the most efficient ways to shrink the size of a muscle is to rigidly immobilize the joint in a cast so the muscle has no motion possible. No documentation is available to show that a muscle grows longer if im- mobilized under tension in a cast; however, based on knowledge of how muscle grows, it probably does grow longer in addition to developing severe atrophy. The severe atrophy and temporary nature of the clinical length gain make the use of casting for chronic management of short muscles in children with CP a poor choice.
INTRODUCTION AND HISTORY Parkinson’s disease (PD) alli 60 mg mastercard weight loss pills xenadrine, like other neurodegenerative disorders 60mg alli amex weight loss pills 2013, is clinically heterogeneous (1). Age of onset, the relative prominence of certain signs and symptoms, course and rate of progression, and the responsiveness to therapy are variable but still assist in differentiating it from atypical forms of parkinsonism (2). Mainly described by its cardinal motor manifestations (bradykinesia/akinesia, rigidity, resting tremor, and postural instability), progression is inevitable, as there is a continuous loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNpc) (3). Before 1918, treatment was primarily supportive (4). However, the encephalitis epidemic of 1917–1926 and the emergence of the postencepha- litic form of parkinsonism led to a more aggressive pursuit of effective therapies. The pursuit initially focused on the development of an effective vaccine, and then necessarily toward symptomatic therapy (5,6). As we cannot, at this time, halt the progression of PD, symptomatic relief remains Copyright 2003 by Marcel Dekker, Inc. While this is at times inadequate, the available symptomatic therapies for PD are far more effective than those available for any other neurodegenerative disease (3). A number of natural remedies have been tried to treat the symptoms of PD over the last century and a half. Charcot, in the latter half of the nineteenth century, described the use of potato plant extracts, such as Bulgarian belladonna and atropine, to treat PD. These were initially received with great promise, but fell short of expectations. In the decade following the emergence of postencephalitic parkinsonism, many studies were published comparing the various plant extracts, evaluating the effectiveness of certain agents for speciﬁc symptoms; for example, stramonium was felt to be effective for rigidity and hyoscine for tremor (4). By the early 1950s, synthetic drugs became available to treat the symptoms of PD. Trihexyphenidyl hydrochloride, a synthetic anticholiner- gic, was highly touted for its effectiveness for relieving rigidity, tremor, akinesia, and oculogyric crisis. It was heralded as more effective than the plant extracts and better tolerated than other early synthetic preparations (4,7,8). While still used today, its limitations in treating all the symptoms of PD were recognized even then. Levodopa (LD) has become the cornerstone of symptomatic therapy. It is a metabolic precursor of the neurotransmitter dopamine (see below). Guggenhiem, in 1913, isolated LD from the broad bean plant (10). Its use in PD only emerged after the important works of various researchers in the late 1950s and early 1960s that demonstrated that dopamine depletion was characteristic of PD. Carrlson in 1957 and 1958 (11,12) demonstrated in animal models that the akinetic effects of reserpine (an agent known to deplete dopamine) could be reversed by LD. In addition, Carrlson reported that the striatum was a site of dopamine concentration (11,12). Hornykiewicz in 1960 showed that the striatum of parkinsonian brains were depleted of dopamine and 2 years later that intravenous doses of LD (50 mg) had anti-parkinsonian effects (13). However, studies in the early and mid-1960s showed variable results, and, in fact, treatment with LD was almost abandoned. It was the seminal work of Cotzias, who examined the role of high-dose oral LD in modifying parkinsonism, that dramatically changed the landscape of PD treatment (14,15). Food and Drug Administration (FDA) for use in PD in 1970, 60 years after its discovery and more than 10 years after the realization that dopamine depletion was the key abnormality in PD (16). In 1973, the combined use of a peripheral aromatic amino acid decarboxylase inhibitor (AADI) with LD was reported. Its use resulted in a decrease in peripheral metabolism of LD to dopamine and fewer peripheral side effects such as hypotension and nausea Copyright 2003 by Marcel Dekker, Inc. Controlled-release formulations were tested in the 1980s to treat ﬂuctuations (see below), and one was approved in the United States in 1991 (3). Still regarded as the most potent symptomatic therapy for PD, LD has its drawbacks.
This study is somewhat limited by the relatively small size purchase alli 60 mg mastercard weight loss pills khloe, lack of controls buy alli 60mg without prescription weight loss pills alli, and the reliance upon plain radiography for assessment of healing. Blanda, et al5 reported on a similar study of 82 athletes with spondylolysis and/or spondylolisthesis. The diagnosis in their study was based upon plain radiography or bone scan with plain radiography for follow up, and treatment consisted of activity restriction, bracing, and physical therapy. Unlike Steiner and Micheli,62 however, they used a brace to maintain lordosis, worn full-time for two to six months until the patient was pain free with daily activity and spinal extension. The results of this study were similar to those of Steiner and Micheli,62 with 96% of the patients with only spondylolysis having good or excellent clinical results and 37% of these patients showing radiographic union, although these numbers include 15 patients who underwent surgery after failing non-operative 251 Spondylolysis in the athlete treatment. This study is again limited by the lack of controls, size, and reliance upon plain radiography and bone scan. Morita, et al63,64 and Katoh, et al65 have attempted to assess the relationship between bony healing and the radiographic stage of the pars lesion. These authors classified the pars lesions into early, progressive, and terminal stages based upon either plain radiography (Figures 1A–C) or CT. These studies have shown much higher rates of healing in early stage lesions with essentially no healing in terminal stage defects. Plain radiography or CT was used for diagnosis and follow up and treatment consisted of activity restriction, bracing with a non-specified “conventional lumbar corset” for three to six weeks followed by the use of an extension limiting corset for three to six months with rehabilitation once healing occurred. Healing was noted in 73% of the early stage, 38·5% of the progressive stage, and none of the terminal defects. Katoh, et al65 studied 134 patients ≤ 18 years old who were diagnosed with spondylolysis by plain film. All the patients subsequently underwent CT evaluation pre- and post-treatment and treatment consisted of relative rest only (SK-personal communication). Healing was noted in 62% of the early stage defects while none of the terminal defects healed. Clinical outcome was not reported for these studies. Both of these studies, as well as the study by Blanda, et al5 found much higher healing rates for unilateral pars defects than for bilateral lesions. The use of bracing in the treatment of spondylolysis has been controversial. There are many authors who advocate the routine use of rigid brace use,5,25,62 and there are reports by others who do not routinely use a rigid brace in the management of these patients. As with other aspects of care for athletes with spondylolysis, this issue warrants further study. Surgical treatment for spondylolysis has generally been reserved for patients that fail conservative care. Surgery is reported to be necessary in about 9–15% of cases with spondylolysis and/or low grade spondylolisthesis. Current management The preceding review of the literature on spondylolysis still leaves the primary question of this chapter unanswered; namely, how should you treat the adolescent athlete with spondylolysis? The approach that follows is based upon the current medical literature and relies upon an understanding of the natural history, pathophysiology, diagnostic assessment, and treatment options discussed above. The goals of this approach are to accurately identify symptomatic lesions of the pars where present, to minimise exposure to ionising radiation in the diagnostic assessment, to provide appropriate treatment to reduce pain and allow for any potential healing of the lesion when possible, and, ultimately, to optimise the athlete’s functional abilities. We are fully aware that other practitioners may approach the problem quite differently at times, but we have found the approach described here to be consistent with the current evidence and very effective for our patients. In an adolescent athlete in whom the diagnosis of spondylolysis is suspected, initial antero-posterior and lateral plain radiographs of the lumbar spine are obtained. The primary purpose of obtaining the plain films is to identify spondylolisthesis or any other readily apparent bony anomalies. Oblique and coned down views of the lumbosacral junction are not recommended for routine evaluation. The medical evidence is quite strong that plain radiography has very limited sensitivity and specificity in the diagnosis of a painful pars lesion compared with other imaging modalities, and the use of extensive plain radiographs offers little additional information to assist in patient management. Given the currently available literature, SPECT appears to represent the best available screening tool for the identification of a symptomatic pars lesion.