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Spastic—A condition in which the muscles are Approximately 500 cheap 50 mg naltrexone treatment hypercalcemia,000 children and adults in the rigid buy naltrexone 50mg low cost medicine examples, posture may be abnormal cheap naltrexone 50mg line medications 1-z, and fine motor United States have CP, and it is newly diagnosed in about control is impaired. Spasticity—Increased muscle tone, or stiffness, Ironically, advances in medicine have decreased the inci- which leads to uncontrolled, awkward move- dence from some causes, Rh disease for example, but ments. However, people of disadvan- Tenotomy—A surgical procedure that cuts the ten- taged background are at higher risk due to poorer access don of a contracted muscle to allow lengthening. Signs and symptoms review, CP is categorized first by the type of move- By definition, the defect in cerebral function causing ment/postural disturbance(s) present, then by a descrip- CP is nonprogressive. However, the symptoms of CP tion of which limbs are affected, and finally by the often change over time. For example, spastic diple- relate in some way to the aberrant control of muscles. To gia refers to continuously tight muscles that have no vol- GALE ENCYCLOPEDIA OF GENETIC DISORDERS 215 untary control in both legs, while athetoid quadraparesis Diagnosis describes uncontrolled writhing movements and muscle The signs of CP are not usually noticeable at birth. These three-part descriptions Children normally progress through a predictable set of are helpful in providing a general picture, but cannot give developmental milestones through the first 18 months of a complete description of any one person with CP. Children with CP, however, tend to develop these addition, the various “forms” of CP do not occur with skills more slowly because of their motor impairments, equal frequency—spastic diplegia is seen in more indi- and delays in reaching milestones are usually the first viduals than is athetoid quadraparesis. Babies with more severe cases of CP loosely categorized as mild, moderate, or severe, but are normally diagnosed earlier than others. Selected developmental milestones, and the ages for A muscle that is tensed and contracted is hypertonic, normally acquiring them, are given below. Spastic, not acquire the skill by the age shown in parentheses, hypertonic muscles can cause serious orthopedic prob- there is some cause for concern. A contracture is shortening of a • Babbles—6 months (8 months) muscle, aided sometimes by a weak-opposing force from a neighboring muscle. Contractures may become perma- • Crawls—9 months (12 months) nent, or “fixed,” without some sort of intervention. Fixed • Finger feeds, holds bottle—9 months (12 months) contractures may cause postural abnormalities in the • Walks alone—12 months (15–18 months) affected limbs. Clenched fists and contracted feet (equi- nus or equinovarus) are common in people with CP. This CP” refers not only to the number of symptoms present, same preference for one side of the body may show up as but also to the level of involvement of any particular class asymmetric crawling or, later on, favoring one leg while of symptoms. Mechanisms that can cause CP are not always It must be remembered that children normally restricted to motor-control areas of the brain. Other neu- progress at somewhat different rates, and slow beginning rologically–based symptoms may include: accomplishment is often followed by normal develop- ment. Other causes for developmental delay—some • mental retardation/learning disabilities benign, some serious—should be excluded before con- • behavioral disorders sidering CP as the answer. CP is nonprogressive, so con- • seizure disorders tinued loss of previously acquired milestones indicates • visual impairment that CP is not the cause of the problem. Babies that have low • abnormal sensation and perception Apgar scores are at increased risk for CP. About one-third of individuals with CP have mod- associated with CP include scarring, cysts, expansion of erate-to-severe mental retardation, one-third have mild the cerebral ventricles (hydrocephalus), periventricular mental retardation, and one-third have normal intelli- leukomalacia (an abnormality of the area surrounding the gence. Blood and urine biochemical tests, as well as genetic tests, may be used to rule out other possible causes, including muscle and peripheral nerve diseases, mitochondrial and meta- bolic diseases, and other inherited disorders. Evaluations by a pediatric developmental specialist and a geneticist may be of benefit. Cerebral palsy cannot be cured, but many of the dis- abilities it causes can be managed through planning and timely care. Treatment for a child with CP depends on the severity, nature, and location of the primary muscular symptoms, as well as any associated problems that might be present. Optimal care of a child with mild CP may involve regular interaction with only a physical therapist and occupational therapist, whereas care for a more severely affected child may include visits to multiple medical specialists throughout life. With proper treat- ment and an effective plan, most people with CP can lead productive, happy lives.

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Active Research Areas and Open Issues Although an enormous number of biomedical image registration methods have been proposed buy cheap naltrexone 50 mg treatment writing, researchers are still facing challenges of producing registration approaches Copyright © 2005 cheap naltrexone 50 mg otc medicine effects, Idea Group Inc discount naltrexone 50 mg on line treatment bee sting. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Biomedical Image Registration 175 with high precision, efficiency, and validity, which can be used in clinical practice. Hierarchical biomedical image registration and hybrid biomedical image registration are two registration schemes that have advantages of both increased computation efficiency and the ability to find better solutions. In the hierarchical registration methods, the images are first registered at coarse, lower- resolution scales, and then the transformation solution obtained at this resolution scale is used as the initial estimation for the registration at a higher-resolution scale. The advantages of the hierarchical biomedical image registration approaches include accel- erating computation efficiency and avoiding local minima, and therefore, improving the registration performance (Lester & Addridge, 1999). The challenges created by inter-subject variations in the organ structures promote researchers to explore the hybrid approaches for biomedical image registration. Hybrid registration approaches, combining the intensity-based algorithms with landmark-based methods and making use of the merits of both these methods, have potential to achieve automatic and high performance biomedical registration results. Hence, objective criteria can be defined to identify how organ structure is altered by aging, gender, disease, and genetic factors. Deformable organ registration remains a challenge because of the differences in organ shape and volume, complex motion sources, and specific character- istics of different imaging modalities. Mental integration of image information from different modalities is subjective, less accurate, and time-consuming. Therefore, in order to benefit clinical safety and facilitate clinical decision making, automatic registration, especially for the deformable organs such as heart, lung, and liver, is highly desired. Elastic registration approaches are particularly promising for the integration of deformable organ information from multiple imaging modalities. Currently, there is still no general automatic approach for the registration of heart images, lung images, and liver images. Hybrid methods, combining similarity measures with morphological information may provide possibilities for elastic registration. Although a wide variety of registration approaches have been proposed, objective validation of these methods is not well established. Image databases may in the future provide a source for the objective comparison of different registration methods. Future Trends Precise and efficient biomedical image registration is not only a big challenge, but also provides exciting opportunities to improve the quality and safety of diagnostic and medical decision making, treatment monitoring, and healthcare support. Although the more advanced imaging system, the PET scanner containing a CT scanner, has been developed, there is still a need for multi-dimensional, multimodality image registration techniques to assist the analysis of temporal changes and the integration of necessary information from different imaging modalities. With ever-increasing growth of medical datasets with higher resolution, higher dimensionality, and wider range of scanned areas, the demand for more efficient biomedical image registration will increase. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. As an important component and technique of telemedicine and e-health, accurate and efficient biomedical image registration will play a more and more important role in remote diagnosis, patient monitoring, teleradiology, and overcoming the barriers of distance in healthcare service. Although the existing image-based virtual human can provide the healthcare profession- als with a quality of anatomical information and knowledge, there is a need to produce virtual humans with both anatomical and functional information and knowledge. Hence, whole-body multimodality image registration needs further efforts to support the virtual human projects which are essential in surgery simulation and virtual and augmented reality in medicine. As an active research area, biomedical image registration will continue attracting researchers to develop automatic, non-rigid registration methods, which will facilitate clinical decision making, treatment monitoring, and surgical planning. The research of biomedical image registration will greatly promote the development and advance of medical imaging techniques, patient care service, and medical education. The multimodality biomedical image registration will be more and more important in medical diagnosis, surgery planning as well as intraoperative navigation, and in the future, biomedical image registration will play a more essential role in helping people to discover the mysteries of the human body and its complicated functions. Conclusions Biomedical image registration of different medical images, which aims to extract and combine the complementary and useful information and knowledge provided by the individual images, is an important step to a more comprehensive and accurate analysis of the organ functions and pathologies.

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PPCA forms a very large multi- Canadian Society for Mucopolysaccharide and Related Diseases generic 50 mg naltrexone otc treatment definition. Mutations in the gene encoding beta-galactosidase can result in the Margaret Alic discount 50 mg naltrexone mastercard treatment internal hemorrhoids, PhD disorders known as GM1 gangliosidosis (beta-galactosi- dosis) or Morquio B disease buy cheap naltrexone 50mg online medications 44 175. Galactosialidosis is subdivided into three types, depending on the age of onset: severe, neonatal or early- infantile; milder, late-infantile; and juvenile/adult. The type and severity of the disorder depends on the specific mutation(s) pres- deficiency ent in the genes encoding PPCA. Definition Lysosomal storage diseases Neuraminidase deficiency with beta-galactosidase deficiency, commonly-known as galactosialidosis, is a Neuraminidase, beta-galactosidase, PPCA, and rare inherited metabolic disorder with multiple symp- GALNS are all enzymes that function inside lysosomes. Lysosomes contain more than 50 different enzymes that are responsible for digesting, or hydrolyzing, large mole- Description cules and cellular components. These include proteins, Neuraminidase deficiency with beta-galactosidase polysaccharides (long, linear or branched chains of sug- deficiency, or galactosialidosis, is a very rare genetic dis- ars), and lipids, which are large, insoluble biomolecules order with progressive signs and symptoms that are that are usually built from fatty acids. The smaller break- almost identical to those of neuraminidase deficiency down products from the lysosome are recycled back to alone, a disorder that is often called sialidosis. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 807 Galactosialidosis is one of at least 41 genetically dis- develop with galactosialidosis may be due to the loss of tinct lysosomal storage diseases. In these disorders, some this activity, particularly PPCAs ability to cleave endothe- of the macromolecules in the lysosome cannot be lin-1. Instead, these large molecules, or their partial- tributed in the neurons and glial cells of the brain and breakdown products, accumulate, and the lysosomes spinal cord of individuals with galactosialidosis. Genetic profile Neuraminidase deficiency Galactosialidosis is an autosomal recessive disorder Neuraminidase removes sialic acid from the ends of that can be caused by any one of a number of different oligosaccharides, which are relatively short chains of mutations in the gene encoding PPCA. Sialic acid, also known as N-acetylneuraminic known as PPGB, for beta-galactosidase protective pro- acid, is a type of sugar molecule that often is at an end of tein. These oligosaccharides with terminal located on chromosome 20, rather than on the X or Y sex sialic acid residues may be attached to proteins, called chromosomes. However, the two defec- of oligosaccharides and glycoproteins that contain sialic tive genes do not need to carry the same mutations. If the acid and leads to the accumulation and excretion of these two mutations are identical, the individual is a homozy- substances. Following protein synthesis, some lysosomal vidual is called a compound heterozygote. One such pro- PPCA mutations cessing step is the neuraminidase-catalyzed removal of The type of galactosialidosis and the severity of the sialic acid residues from oligosaccharides on enzymes. In general, the higher the level of PPCA activity in other lysosomal enzymes may not behave properly. Protective protein/cathepsin A With some mutations of the PPGB gene, very little PPCA is required for the transport of neuraminidase of the precursor protein to PPCA is produced and there is to the lysosome. With other mutations, matic activity of PPCA may be involved in the activation the precursor protein may not be correctly processed into of neuraminidase. Some individuals with severe early- ciation of multiple molecules of neuraminidase and beta- infantile galactosialidosis carry mutations that prevent galactosidase, as well as GALNS. PPCA, all three enzymes are rapidly degraded in the The lysosomes of these individuals have no PPCA. Thus, PPCA protects and stabilizes these In contrast, individuals with the late-infantile form enzyme activities. In the absence of PPCA, substrates for of galactosialidosis carry at least one mutant PPGB gene these enzymes may accumulate to dangerous levels. However, there Gangliosides are very complex components of cell may be only a small amount of PPCA in the lysosome; membranes. They are made up of a long-chain amino the PPCA may lack enzymatic activity; the PPCA chains alcohol called sphingosine, a long-chain fatty acid, and a may be unable to combine to form the normal two- very complex oligosaccharide that contains sialic acid. The lysosomal beta-galactosidase is responsible for Nevertheless, with these mutations, the symptoms of hydrolyzing gangliosides. Both gangliosides and keratan sulfate may accumu- cules from folding properly or shorten the PPCA protein late in galactosialidosis. In addition to its protective functions, PPCA has at Compound heterozygotes, with different mutations least three enzymatic activities of its own, including the in their PPGB genes, usually have symptoms that are ability to cleave (break apart), or hydrolyze, other pro- intermediate in severity between those of homozygotes teins. Demographics Fibroblast—Cells that form connective tissue As an autosomal recessive disorder, neuraminidase fibers like skin. Since it as neuraminidase deficiency with beta-galactosi- requires two defective copies of the PPGB gene, one dase deficiency.

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