Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kennedy's disease (spinal and bulbar muscular atrophy) is an X-linked form of motor neuron disease that affects adult men. The syndrome is characterized by progressive atrophy of the limb muscles, pelvic and shoulder girdles and dysphagia and dysarthria, and is caused by the degeneration of spinal and bulbar motor neurons. Kennedy's disease is caused by a trinucleotide repeat expansion of a CAG repeat in exon A of the androgen receptor gene, and is one of a group of neurological diseases caused by trinucleotide repeat expansions in different genes. The mutation in Kennedy's disease involves an increased number of glutamine residues in the amino-terminal domain of the receptor. Point mutations and deletions in the androgen receptor gene cause androgen insensitivity syndrome, however subjects with Kennedy's disease have normal virilization, although progressive gynaecomastia, testicular atrophy and infertility may occur. Androgen receptors are expressed widely in the normal brain, and in the anterior horn cells of the spinal cord; however, their role in neuronal tissue is not known, nor is it known how the androgen receptor gene mutation causes neuronal degeneration. Kennedy's disease is likely to be a 'gain of function' abnormality, so that the presence of the receptor with an increased number of glutamines is toxic to motor neurons. It is possible that the mutation alters interaction of the receptor with other neuronal transcription factors, or neuronotoxicity may occur because of a non-specific effect caused by the presence of a protein with a large homoglutamine domain. Studies of patients with Kennedy's disease have shown that expression of androgen receptor mRNA and protein in spinal cord may be decreased, as can be the affinity of the mutant receptor for androgen. In vitro studies have shown impaired transcription activation ability of the mutant androgen receptor. The age at onset of Kennedy's disease may correlate with the size of the CAG repeat, however there is a large degree of variability of age at onset between subjects with the same number of repeats. Further study of the effect of the Kennedy's disease mutation on androgen receptor function in motor neurons will allow us to increase our understanding of the pathogenesis of this disease.
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PMID:Spinal and bulbar muscular atrophy: androgen receptor dysfunction caused by a trinucleotide repeat expansion. 886 71

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.
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PMID:Enteral nutrition by endoscopic means; I. Techniques, indications, types of enteral feed. 1559 63

Oral mucositis is a common complication in cancer patients receiving chemotherapy and/or radiation therapy. Nearly all patients undergoing myeloablative therapy for stem-cell or bone marrow transplantation experience oral mucositis. Those receiving radiation therapy for head and neck cancer are at especially high risk. However,this toxicity also occurs with standard-dose chemotherapy and can be seen in association with treatment of many other tumor types. Oral mucositis significantly complicates cancer treatment by contributing to pain, dysphagia, weight loss, depression, higher risk of infection, decreased quality of life, and increased healthcare costs. This review summarizes the impact of oral mucositis in patients with cancer, including its pathogenesis, diagnosis, financial implications, and management. Current treatment guidelines are presented, and novel targeted therapies are discussed. Newer agents, such as palifermin (recombinant human keratinocyte growth factor-1), have been shown in clinical trials to reduce the incidence and severity of oral mucositis,and Saforis (an oral glutamine suspension) may also promote recovery from mucosal damage following chemotherapy or radiation therapy. Continued advances in understanding the pathobiology of oral mucositis should lead to the development of additional agents for its effective prevention and treatment in patients undergoing cancer therapy.
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PMID:Diagnosis and management of oral mucositis. 1736 29

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.
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PMID:Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics. 2333 13

Following the new ESPEN Standard Operating Procedures, the previous guidelines to provide best medical nutritional therapy to critically ill patients have been updated. These guidelines define who are the patients at risk, how to assess nutritional status of an ICU patient, how to define the amount of energy to provide, the route to choose and how to adapt according to various clinical conditions. When to start and how to progress in the administration of adequate provision of nutrients is also described. The best determination of amount and nature of carbohydrates, fat and protein are suggested. Special attention is given to glutamine and omega-3 fatty acids. Particular conditions frequently observed in intensive care such as patients with dysphagia, frail patients, multiple trauma patients, abdominal surgery, sepsis, and obesity are discussed to guide the practitioner toward the best evidence based therapy. Monitoring of this nutritional therapy is discussed in a separate document.
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PMID:ESPEN guideline on clinical nutrition in the intensive care unit. 3225 75