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Treatment and management A nerve biopsy (removal of a small piece of the nerve) may be performed to look for changes character- There is no cure for CMT purchase 17.5mg zestoretic with mastercard blood pressure 40. However trusted 17.5 mg zestoretic heart attack iglesias, this testing is not diagnostic of occupational therapy are an important part of CMT treat- GALE ENCYCLOPEDIA OF GENETIC DISORDERS 221 ment. Voice-activated software HNPP—Hereditary Neuropathy with liability to Pressure can also help people who have problems with fine motor Palsies. It is very important that people with CMT avoid OMIM—Online Mendelian Inheritance in Man. It is often difficult for people with CMT to return to their original strength after injury. Krajewski, MS, CGC There is a long list of medications that should be avoided if possible by people diagnosed with CMT such as hydralazine (Apresoline), megadoses of vitamin A, B6, and D, Taxol, and large intravenous doses of penicillin. People considering taking any of these medica- Definition tions should weigh the risks and benefits with their physician. CHARGE syndrome, also known as CHARGE asso- ciation, is a group of major and minor malformations that have been observed to occur together more frequently Prognosis than expected by chance. The name of the syndrome is an The symptoms of CMT usually progress slowly over acronym for some of its features, and each letter stands many years, but do not usually shorten life expectancy. Most people with CMT • H—Heart defects are able to lead full and productive lives despite their • A—Atresia choanae, physical challenges. Charcot-Marie-Tooth Disorders: A Handbook While these features have classically been used for iden- for Primary Care Physicians. Available from the CMT tification of affected individuals, many other malforma- Association, 1995. A magazine for patients available from the Muscular CHARGE syndrome was first described in 1979 as Dystrophy Association. Soon ORGANIZATIONS after, several other papers were published describing sim- Charcot Marie Tooth Association (CMTA). Due to the 222 GALE ENCYCLOPEDIA OF GENETIC DISORDERS large number of patients described since 1979, many physicians now regard CHARGE association as a recog- KEY TERMS nizable syndrome. It is believed that perhaps a new domi- Cryptorchidism—A condition in which one or nant change in a gene is the cause for many cases. Crucial development of the choanoa, heart, ear and when one parent carries an altered gene mutation other organs occurs 35-45 days after conception and any that affects his or her germ line cells (either the egg disruption in development during this time is believed to or sperm cells) but is not found in the somatic lead to many of the features of the syndrome. Infants with CHARGE syndrome generally have dif- ficulty with feeding and most of those affected have men- Phenotype—The physical expression of an indi- tal retardation. Genetic profile Most cases of CHARGE syndrome are sporadic, with CHARGE syndrome also have features of another meaning that they occur in a random or isolated way. There have also been cases in which a parent with George sequence have a missing chromosome 22q11. These families may demon- drome should have chromosome studies as well as strate variable expressivity of a dominant gene. Therefore, the recurrence risk for healthy par- The incidence of CHARGE syndrome is approxi- ents of an affected child would be low, but not negligible. However, this is probably an Twin studies are often used to determine if the occur- underestimate of the true number of people affected. One incidence is likely to increase as the diagnostic features such study compared a pair of monozygotic twins, mean- of the condition are refined and milder cases are diag- ing identical twins resulting from a single zygote (fertil- nosed. CHARGE syndrome affects males more seriously ized egg that leads to the birth of two individuals), who than females, resulting in a higher number of females were both affected with CHARGE syndrome and a pair who survive. The syndrome of dizygotic twins, meaning twins that result from fertil- has not been reported more often in any particular race or ization of two different eggs, of whom only one had the geographic area. Since monozygotic twins are roughly 100% genetically identical, this supports the idea that there is a Signs and symptoms strong genetic factor involved in CHARGE syndrome. Other interesting observations include slightly increased CHARGE syndrome is believed to be caused by a paternal age in sporadic cases. The mean paternal age in disruption of fetal growth during the first three months of one study was 34 years as opposed to 30 years in a con- pregnancy and affecting many different organ systems trol group. Choanal atresia Several patients with various chromosome defects Choanal atresia, the narrowing passages from the have been diagnosed with CHARGE syndrome, again back of the nose to the throat, may occur on one or both pointing to genetic factors as a cause. This condition usually leads chromosomal abnormalities point to particular genes to breathing difficulties shortly after birth. In addition, some patients choanal atresia may result in early death and surgery is GALE ENCYCLOPEDIA OF GENETIC DISORDERS 223 often required to open up the nasal passages.

However buy zestoretic 17.5mg low price blood pressure medication xanax, this category of schemes does not make use of knowledge of the organ structure and also the registration computation is not very efficient 17.5mg zestoretic with mastercard heart attack treatment. The well-established intensity-based similarity measures used in the biomedical image registration area include minimizing the intensity differences, correla- tion-based techniques, and entropy-based techniques. Similarity measures by minimizing the intensity differences include the Sum of Squared Differences (SSD) and the Sum of Absolute Differences (SAD), which exhibit a minimum in the case of perfect matching. Although they are efficient to calculate, these methods are sensitive to intensity changes. N 2 SSD = ∑ R(i) − T(S(i)) (2) i 1 N SAD = ∑ R(i) −T(S(i)) (3) N i Where R(i) is the intensity value at position i of reference image R and S(i) is the corresponding intensity value in study image S; T is geometric transformation. Correlation techniques were proposed to aim at multimodal biomedical image registra- tion, for example, Maintz, van den Elsen, and Viergeve (1996). The cross-correlation technique has also been used for rigid motion correction of SPECT cardiac images, for example, Mäkelä et al. However, because usually the geometric deformations of the image modalities are not likely to be linear, these correlation methods, which require a linear dependence between the intensity of the images, cannot always achieve reliable registration results. The normalized cross correlation is defined as: ∑(IiR () IR )(IiS () IS) CR = i 2 2 (4) ∑ (IiR () IR ) (IiS () IS ) i i Where IR(i) is the intensity value at position i of reference image R and IS(i) is the corresponding intensity value in study image S; IR and IS are the mean intensity value of reference and study image respectively. Information theoretic techniques play an essential role in multimodality medical image registration. The Shannon entropy is widely used as a measure of information in many branches of engineering. It was originally developed as a part of information theory in the 1940s and describes the average information supplied by a set of symbols whose probabilities are given by {p(x)}. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Biomedical Image Registration 169 H = −∑ p(x)log p(x) (5) x In image registration area, when the images are correctly aligned, the joint histograms have tight clusters and the joint entropy is minimized. These clusters disperse as the images become less well registered, and correspondingly, the joint entropy is increased. Because minimizing the entropy does not require that the histograms are unimodal, the joint entropy is generally applicable to multimodality registration and obviates the need of segmentation of images. The mutual information I of the reference image R and study image S measures the degree of dependence of R and S by measuring distance between the joint distribution PRS(r,s) and the distribution associated to PR(r) and PS(s). MI can be defined as: PRS (r, s) IR,S = ∑ PRS (r, s)log( ) (6) (r,s) PR(r)PS (s) With H(R) and H(s) being the entropy of R and S, respectively, H(R,S) is their joint entropy. H (R) = −∑ PR (r)log PR (r) (7) r H(S) = −∑ PS (s)log PS (s) (8) s H(R,S) = −∑ PRS (r,s)log PRS (r, s) (9) r,s MI is related to entropy by the equation: IR,s = H(R) + H(S) − H(R,S) (10) Under the assumption that the mutual information of the two images is maximum when the images are in registration, registration can be performed by maximizing the mutual information as a function of a geometric transformation T of the study image S: Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Mutual information registration does not assume a linear relationship among intensity values of the images to be registered and is one of the few intensity-based measures that are well suited to the multimodality image registration. Feature-Based Medical Image Registration In feature-based registration approaches, transformations often can be stated in analytic form, hence efficient computational schemes can be achieved. However, in most of these methods, the preprocess step is needed and the registration results are highly dependent on the result of this preprocess. Because registration algorithms using landmarks often require users to specify corresponding landmarks from the two images manually or semi- automatically, such methods cannot always provide very accurate registration. The feature-based medical image registration methods can be classified into point-based approaches, for example, Fitzpatrick, West, and Maurer (1998), curve-based algorithms, for example, Maintz et al. Point-based registration involves identifying the corresponding points, matching the points, and inferring the image transformation. The corresponding points are also called homologous landmarks to emphasize that they should present the same feature in the different images. These points can either be anatomical features or markers attached to the patient, which can be identified in both images modalities. Anatomical landmark based registration methods have the drawback of user interaction being required. Registration algorithms based on extrinsic landmarks which maybe invasive or non-invasive, are comparatively easy to implement, fast, and can be automated, but they may have drawbacks of invasiveness and less accurate results.

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Lavender is an adju- Lavender vinegar: Fresh leaves and blossoms may vant and may be used in combination with other herbs to be steeped in white vinegar for seven days trusted 17.5mg zestoretic heart attack 8 months pregnant, then strained make a tonic cordial to strengthen the nervous system zestoretic 17.5 mg free shipping heart attack 18. A 2002 report from Korea showed that aromather- Precautions apy massage with lavender oil and tea tree oil on pa- tients undergoing hemodialysis for kidney failure re- Lavender has a long history of use as an essential oil ceived relief from the itching the treatment often causes. It is important to note that, as with all es- sential oils, high or chronic doses of lavender essential Preparations oil are toxic to the kidney and liver. Infants are even The medicinal properties of lavender are extracted more easily overdosed than adults. The Interestingly, lavenderís relaxant effects were put to plant contains volatile oil, tannins, coumarins, flavonoids, the test in a 2002 study on aromatherapyís effects on im- and triterpenoids as active chemical components. It seems that phytochemicals are the plant constituents responsible for study subjects who smelled lavender actually did worse the medicinal properties. So when extracted from flowers picked before they reach those choosing to use lavenderís soothing effects should maximum bloom and following a long period of hot and perhaps choose the timing carefully. The flower spikes dry quickly when spread on a mat in an airy place away from direct sun. Side effects Distilled oil: The essential oil of lavender is extract- No known side effects. Commercial dis- Interactions tillations of this essential oil are readily available. As an adjuvant, lavender can enhance the helpful Lavender tea: An infusion of the fresh or dried flow- properties of other herbs when used in combination. It can be fusion of lavender and valerian (Valeriana officinalis) steeped (covered) for about ten minutes, strained and makes a soothing tea. A tonic cordial can be made by combin- ful at a time, or warm, by the cup, up to three cups per ing fresh rosemary (Rosmarinus officinalis) leaves, cinna- day. Lavender works well in combination with other mon, nutmeg, and sandlewood with the lavender blos- medicinal herbs in infusion. Lavender oil extract: In a glass container, one ounce of freshly harvested lavender flowers can be combined Resources with 1-1/2 pints of olive oil, sufficient to cover the herb. After three days, the mixture graphs, Therapeutic Guide to Herbal Medicines Massachu- should be strained through muslin or cheesecloth. Definition Adjuvant—A characteristic of an herb that en- hances the benefits of other ingredients when Lazy eye, or amblyopia, is an eye condition in added to a mixture. If not corrected before age eight, amblyopia will cause sig- Coumarins—These blood-thinning plant chemi- nificant loss of stereoscopic vision, the ability to per- cals break down red blood cells. Most exert a pharmacological In some children, one eye functions better than the effect, depending on their type. If Sessile—A botanical term to describe a leaf that left untreated beyond the early child-development years emerges from the plant stem without a stalk. In the first (suspension) phase, the brain Volatile or essential oils—Simple molecules that turns the weaker eye on and off. When applied to the skin, sion) phase, the brain turns off the lazy eye indefinitely. In the last (ambly- opia) phase, which occurs after age seven, the eye loses all the sensitivity that is essential for good vision be- Bown, Deni. The Herb Society of America, Encyclopedia of cause it has not been used for so long. Because of Press, 1987 loss of vision in one eye, these children cannot see three- Lust, John B. Ap- PERIODICALS proximately half of all children with crossed eyes will Carlson, Mike, et al. Odle there is difference in image quality between the two GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1187 not replacements for conventional treatments. Orthoptic exercises are designed to help the eyes move together and assist the fusing of the two images seen by the eyes.

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This in- Albendazole appears to cause cytoplasmic microtubu- hibits microtubule assembly buy 17.5mg zestoretic mastercard blood pressure instruments, which is important in a lar degeneration buy zestoretic 17.5 mg with mastercard hypertension 90, which in turn impairs vital cellular number of helminth cellular processes, such as mitosis, processes and leads to parasite death. The drug is metabolized ably absorbed ( 5%) because of its poor water solubil- in the liver and excreted in urine within 24 to 48 hours ity. Concurrent treatment with corti- Thiabendazole shows a broad spectrum of activity costeroids increases plasma concentrations of albenda- against the following nematodes: A. Albendazole has a broad spectrum of activity against At present, thiabendazole is the drug of choice for the intestinal nematodes and cestodes, as well as the liver treatment of cutaneous larva migrans (creeping erup- flukes Opisthorchis sinensis, Opisthorchis viverrini, and tion), strongyloidiasis, trichostrongyliasis, and trichinosis. It also has been used successfully Anorexia, nausea, vomiting, drowsiness, and vertigo against Giardia lamblia. Diarrhea, pruritus, ment of hydatid cyst disease (echinococcosis), especially 54 Anthelmintic Drugs 625 when accompanied with praziquantel. It also is effective Clinical Use in treating cerebral and spinal neurocysticercosis, particu- Niclosamide has been used extensively in the treatment larly when given with dexamethasone. Albendazole is rec- of tapeworm infections caused by Taenia saginata, Taenia ommended for treatment of gnathostomiasis. It is absorbed by intestinal cestodes but Cestodes, or tapeworms, are flattened dorsoventrally not nematodes. This Niclosamide is administered orally after the patient has head, or scolex (also referred to as the hold-fast organ), fasted overnight and may be followed in 2 hours by purg- is used by the worm to attach to tissues. Drugs that affect ing (magnesium sulfate 15–30 g) to encourage complete the scolex permit expulsion of the organisms from the expulsion of the cestode, especially T. With the a number of segments, called proglottids, each of which availability of other agents, niclosamide is no longer contains both male and female reproductive units. The most widely employed agents are praz- segments, after filling with fertilized eggs, are released iquantel and the benzimidazoles. Cestodes that parasitize humans have complex life cycles, usually requiring development in a second or in- Adverse Effects termediate host. Following their ingestion, the infected No serious side effects are associated with niclosamide larvae develop into adults in the small intestine. In some cestode infections, eggs containing lar- TREATMENT FOR INFECTIONS CAUSED vae are ingested; the larvae invade the intestinal wall, BY TREMATODES enter a blood vessel, and lodge in such tissues as muscle, liver, and eye. Symptoms are associated with the partic- Trematodes (flukes) are nonsegmented flattened ular organ affected. The eggs, which are passed out of the host Mechanism of Action in sputum, urine, or feces, undergo several stages of For many years, niclosamide (Niclocide) was widely maturation in other hosts before the larvae enter hu- used to treat infestations of cestodes. The larvae are acquired either through ingestion chlorinated salicylamide that inhibits the production of of food (aquatic vegetation, fish, crayfish) or by direct energy derived from anaerobic metabolism. After ingestion, most trema- have adenosine triphosphatase (ATPase) stimulating todes mature in the intestinal tract (intestinal flukes); properties. Inhibition of anaerobic incorporation of in- others migrate and mature in the liver and bile duct organic phosphate into ATP is detrimental to the para- (liver flukes), whereas still others penetrate the intes- site. Niclosamide can uncouple oxidative phosphoryla- tinal wall and migrate through the abdominal cavity to tion in mammalian mitochondria, but this action the lung (lung flukes). Diarrhea, abdominal pain, and requires dosages that are higher than those commonly anorexia are common symptoms associated with trema- used in treating worm infections. Liver flukes may cause bile duct block- The drug affects the scolex and proximal segments of age, liver enlargement, upper right quadrant pain, and the cestodes, resulting in detachment of the scolex from diarrhea. Lung the intestinal wall and eventual evacuation of the ces- flukes produce pulmonary symptoms such as cough, he- todes from the intestine by the normal peristaltic action moptysis, and chest pain. Because niclosamide is not absorbed The schistosomes (blood flukes) are a distinct group from the intestinal tract, high concentrations can be of trematodes. The larvae penetrate skin that is in Adverse reactions tend to occur within a few hours of contact with contaminated water and then migrate administration. This After maturing, schistosomes migrate into the mesen- may be due to the liberation of helminth proteins from teric or vesicular vein, where the adults mate and re- dead worms rather than any direct effect of the drug. The eggs secrete enzymes that enable them to pass through the wall of the intestine (Schistosoma Oxamniquine mansoni and Schistosoma japonicum) or bladder (Schistosoma haematobium). In addition, some eggs Oxamniquine (Vansil) is a tetrahydroquinoline that stimulates parasite muscular activity at low concentra- may be carried to the liver or the lung by the circula- tions but causes paralysis at higher concentrations. Penetration of the skin is associated with petechial hemorrhage, some edema, and pruritus that disappears drug may act by esterification and binding of DNA, leading to the death of the schistosome by interruption after about 4 days. With the laying of eggs, esterify oxamniquine to produce a reactive metabolite that alkylates parasite DNA.

Clinical treatments for acute lesions of the cerebral cortex and hippocampus such as head injury and stroke have focused almost exclusively on cytoprotection and prevention of secondary damage within the early period after the lesion buy 17.5 mg zestoretic amex pulse pressure. Moreover buy 17.5 mg zestoretic mastercard heart attack romance, the spontaneous neuronal replacement that transpires via proliferation of endogenous stem/progenitor cells after injury appears to be very restricted, ephemeral, and nonfunctional. Exogenous transplants of multipotent progenitor or stem cells may play a role not only in epilepsy, but also in head injury, stroke, and degenerative disease. Late after a lesion, when the damage is stable, neural grafts may be competent to enhance actual appropriate circuitry reconstruction. Inducing withdrawal of aberrantly formed synaptic contacts © 2005 by CRC Press LLC These events together may suppress hyperexcitability and restore afferent control in autonomous regions. Embryonic neural grafts have the dual advantage of surviving the transplantation trauma and anoxia and possessing competence for considerable axonal growth into the adult host CNS. Many other possible goals and mechanisms can be achieved by neural transplantation including release of neurotrophic factors or neu- rotransmitters and replacement of glial cells. Adequate survival of the transplanted neurons within the host environment (at least 20% of grafted neurons) 2. Appropriate dispersion or migration of the transplanted cells to restore host neuronal cell layers (leaving few cells at the transplant site) 3. Normal cellular development including acquisition of region-specific den- dritic complexity, synapses and intrinsic characteristics 4. Appropriate elaboration of both local circuit and long-distance axons for synaptic connectivity into the host 5. Attraction of a significant number of specific afferent axons from the host While these requirements are rigorous, the quantitative measurement of these characteristics may lend credence to exertion by the graft of a specific, defined role in the host, as opposed to a nonspecific or non-neuronal effect. For example, grafts into the striatum of dopamine-enriched tissue are intentionally ectopic, and do not appear to develop long-distance axonal growth despite the fact that embryonic dopaminergic axons are inherently capable of such growth. Thus, only some parallels may be noted between the two different regions, but issues of graft tissue survival and integration remain paramount for both. Second, the clinical situations to which hippocampal or cortical neural grafting may be applicable will be analyzed, in addition to potential graft sources and their © 2005 by CRC Press LLC limitations. Finally, the bridge between preclinical research and clinical usefulness and applicability will be discussed. Our hypothesis of cellular integration applies primarily to the goal of making a graft an integral part of synaptic circuitry within the brain. Cell survival, directly comparing the number of cells transplanted and those recovered in vivo at different postgrafting time points 2. Graft cell afferent connectivity with appropriate host axons Graft integration may be differentially analyzed for various cell types, including embryonic neurons and immature stem cells. Because the cells are postmitotic and committed after embryonic harvesting, the neurons retain the BrdU label permanently. For analysis purposes, the placement of micrografts (10,000 to 30,000 cells) is much more definitive than the use of larger but more therapeutic macrografts of >1 × 106 cells. The smaller number of cells within micrografts can be explicitly counted and tracked using © 2005 by CRC Press LLC Human Cell Sources Human Stem Cells Embryonic Allograft or Xenograft Cortex Neural Cell Cultured Lines Sterile Therapeutic Graft Effects Dissociation on Host Brain Host mossy fiber axons can innervate grafted neurons and form functional Transplantation synapses onto grafted cells. Graft axonal processes innervate host pyramidal cells and interneurons, leading to circuitry reconstruction and restoration of interneuron cell counts. Mossy fiber terminals can densely innervate graft and prevent aberrant mossy fiber sprouting Can grafts treat epilepsy in humans? First, cell sources include human or porcine embryonic cortex or hippocampus, various types of pro- genitor or stem cells, or cultured cell lines, most derived from neuronal tumors. After disso- ciation and transplantation, the fate of the transplanted cells can be assessed for synaptic integration within the host. In rodent models, therapeutic graft effects on the host include the formation of mossy fiber synapses onto grafted neurons, amelioration of postlesion interneu- ron loss, and prevention of aberrant mossy fiber sprouting. Whether grafts can ameliorate epilepsy remains to be analyzed in rodents and humans although the framework has been established.

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