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

Forty-eight men with Parkinson's disease (PD) were interviewed utilizing a questionnaire which evaluated autonomic function. The study population included PD patients (mean age: 65.8 years, mean duration of PD: 8 years) and 32 elderly healthy nonparkinsonian males (mean age: 70.4 years). We found a significantly higher prevalence of the following symptoms of autonomic dysfunction in the parkinsonian patients: erectile dysfunction (60.4 vs. 37.5%), sensation of incomplete bladder emptying (41.6 vs. 15.6%), urgency (45.8 vs. 3.125%), constipation (43.9 vs. 6.25%), dysphagia (22.9 vs. 6.25%) and orthostatic dizziness (21.95 vs. 0%). Eighty-nine percent of parkinsonian patients had at least one of these autonomic symptoms, compared to 43% of control subjects (p less than 0.05). This study is the first comprehensive survey of autonomic symptomatology in PD compared to elderly healthy controls and confirms that autonomic nervous system dysfunction is a pervasive problem in PD. Erectile dysfunction is a significant problem in this patient group and contributes to deterioration in the quality of life.
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PMID:Autonomic dysfunction in men with Parkinson's disease. 159 69

Aberrant smooth muscle dystonia during hemolytic episodes in paroxysmal nocturnal hemoglobinuria (PNH) is implicated in the symptoms of abdominal pain, dysphagia and erectile dysfunction. Here we report two PNH patients treated with the complement inhibitor, eculizumab. Complement inhibition has been sustained for over 2 years and results in resolution of intravascular hemolysis and amelioration of symptoms associated with smooth muscle contractions.
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PMID:Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria. 1646 55

Paroxysmal nocturnal haemoglobinuria (PNH) has been recognised as a discrete disease entity since 1882. Approximately a half of patients will eventually die as a result of having PNH. Many of the symptoms of PNH, including recurrent abdominal pain, dysphagia, severe lethargy and erectile dysfunction, result from intravascular haemolysis with absorption of nitric oxide by free haemoglobin from the plasma. These symptoms, as well as the occurrence of thrombosis and aplasia, significantly affect patients' quality of life; thrombosis is the leading cause of premature mortality. The syndrome of haemolytic-anaemia-associated pulmonary hypertension has been further identified in PNH patients. There is currently an air of excitement surrounding therapies for PNH as recent therapeutic developments, particularly the use of the complement inhibitor eculizumab, promise to radically alter the symptomatology and natural history of haemolytic PNH.
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PMID:Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. 1740 57

Although infectiological stimuli, environmental factors and genotypic features are known to contribute to the initiation and perpetuation of systemic sclerosis (SSc), its etiology still remains to be enigmatic, and less elusive insights are to be achieved by ongoing and future investigations. Being characterized, however, as chronic autoimmune disease with excessive collagen accumulation in skin, synovia and visceral organs such as lung, heart, and digestive tract along with obliterating angiopathy, the pathophysiology of SSc can be summarized as being based on imbalances of the cellular and humoral immune system, vascular dysfunction and activation of resident connective tissue cells. A complex interplay between these major components manages to establish and maintain the inability of the vasculature to adequately react to the need for dilatation, constriction and growth of new vessels, to cause the increased deposition of extracellular matrix constituents as well as to facilitate immunological disarrangement. Despite parallels to the chicken and egg causality dilemma, all of these account for what later clinicians observe in patients suffering from Raynaud's phenomenon, digital ulcers, sclerodactyly, rigidity of the face, microstomia, sicca syndrome, dyspnea, dry cough, pulmonary hypertension, palpitations, syncopes, renal insufficiency, dysphagia, gastroesophageal reflux, dyspepsia, generalized arthralgias, but also dyspareunia, or erectile dysfunction.
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PMID:The pathogenesis of systemic sclerosis revisited. 2008 91

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder characterized by complementmediated hemolytic anemia, thrombophilia and bone marrow failure. The clinical hallmark of PNH is evident chronic hemolysis due to the absence of the complement regulators CD55 and CD59 on PNH erythrocytes. Intravascular hemolysis drives the major clinical features of PNH, including anemia, hemoglobinuria, fatigue and other hemolysisrelated disabling symptoms, such as painful abdominal crises, dysphagia and erectile dysfunction. A peculiar thromboembolic risk has been associated with the hemolysis in PNH, but its pathophysiologic cause remains unclear. The treatment of PNH has remained supportive until a few years ago, when the first complement inhibitor, designated eculizumab, became available. Chronic treatment with eculizumab results in sustained control of intravascular hemolysis, leading to hemoglobin stabilization and transfusion independence in half of the patients. However, residual anemia may persist in a substantial fraction of patients. Recent observations by different groups, including our own, have demonstrated that residual hemolysis may be due to persistent activation of the early phases of the complement cascade, leading to progressive C3-deposition on PNH erythrocytes and possible subsequent extravascular hemolysis through the reticuloendothelial system. Here we critically review the available clinical results of eculizumab treatment for PNH patients, pointing out the recent insights into the pathophysiology of the disease. We discuss the role of the different components of the complement cascade leading to hemolysis, in both the absence and presence of the terminal effector pathway inhibition by eculizumab. Finally, we provide a theoretical rationale for the development of novel strategies of complement inhibition which could in the future further improve on the already substantial efficacy of eculizumab.
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PMID:Achievements and limitations of complement inhibition by eculizumab in paroxysmal nocturnal hemoglobinuria: the role of complement component 3. 2156 3

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haematopoietic progenitor cells due to a somatic mutation in theX-linked phosphatidylinositol glycan class A gene. The disease is characterized by intravascular haemolytic anaemia, propensity to thromboembolic events and bone marrow failure. Other direct complications of haemolysis include dysphagia, erectile dysfunction, abdominal pain, asthenia and chronic renal failure (65% of patients). The disease appears more often in the third decade of life and there is no sex or age preference. Detection of markers associated with glucosyl phosphatidyl inositol deficit by flow cytometry is currently used in the diagnosis of PNH. For years, transfusions have been the mainstay of therapy for PNH. A breakthrough in treatment has been the approval of the humanized monoclonal antibody eculizumab, which works by blocking the C5 complement protein, preventing its activation and therefore haemolysis. Several studies have confirmed that treatment with eculizumab avoids or decreases the need for transfusions, decreases the probability of thrombosis, improves the associated symptomatology and the quality of life in patients with PNH, showing an increase in survival. Because of rapid advances in the knowledge of the disease and its treatment, it may become necessary to adapt and standardize clinical guidelines for the management of patients with PNH.
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PMID:[Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria]. 2689 45

: A 63-year-old male was diagnosed with autoimmune autonomic ganglionopathy based on the finding of plasma antibodies to the nicotinic acetylcholine receptor (nAChR) of autonomic ganglia. He complained of mouth and eye dryness, dysphagia, severe constipation, erectile dysfunction, urgency, frequent urination, habitual orthostatic syncope and presyncope. A remarkable symptomatic orthostatic hypotension without changes in heart rate was present. We here describe the 3-year time course of the changes in spectral indices of cardiovascular autonomic control LF/HF and LFSAP, dysautonomia symptoms intensity and anti-nAChR antibodies following repetitive selective immunoadsorptions. During the follow-up, the reduction of anti-nAChR antibodies produced by immunoadsorption was associated with a diminished orthostatic hypotension, a restored capability to increase LF/HF, LFSAP and norepinephrine in upright position, a decline in the intensity of autonomic symptoms and an improvement of life quality. Spectral parameters LF/HF and LFSAP may represent noninvasive, low-cost biomarkers suitable for autoimmune autonomic ganglionopathy patients' clinical follow-up.
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PMID:Long-term cardiovascular autonomic and clinical changes after immunoglobulin G immunoadsorption therapy in autoimmune autonomic ganglionopathy. 2831 94

The aim of the present study was to clarify the clinical characteristics and quality of life (QOL) of Japanese patients (N=116) enrolled in the International PNH Registry, compared to the whole registry cohort (N=3,457), censored as of March 2015. The proportion of patients treated with eculizumab was comparable between the two cohorts; the Japanese cohort showed higher levels of lactate dehydrogenase and lower hemoglobin values at baseline. Compared to the whole cohort, the Japanese cohort had a greater incidence of bone marrow failure (67.4% vs 56.8%), but fewer episodes of thrombotic events in their medical history (6.4% vs 13.3%), and lower reported rates of abdominal pain (11.9% vs 33.9%), dysphagia (1.7% vs 16.4%), and erectile dysfunction (5.6% vs 25.3%). Additionally, assessment of QOL using FACIT-Fatigue and EORTC QLQ-C30 confirmed that the Japanese cohort had better QOL scores in most of the QOL subscales at baseline. These data are the first report of QOL outcomes for the Japanese cohort in the International PNH Registry; further assessments are ongoing.
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PMID:[Clinical features and quality of life assessment in Japanese PNH patients enrolled in the International PNH Registry]. 2921 79

Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. Generally, it's characterized by of adrenal insufficiency in consequence of adrenocorticotropic hormone (ACTH) resistance, besides of achalasia, and alacrimia. Neurologic features are varied and have been the subject of several case reports and reviews. A few cases of Allgrove syndrome with motor neuron disease have been already described. A 25-year-old white man, at the age of four, presented slowly progressive distal amyotrophy and weakness, autonomic dysfunction, dysphagia and lack of tears. He suffered later of orthostatic hypotension and erectile dysfunction. He presented distal amytrophy in four limbs, tongue myofasiculations, alacrimia, hoarseness and dysphagia due to achalasia. The ENMG showed generalized denervation with normal conduction velocities. Genetic testing revealed 2 known pathogenic variants in the AAAS gene (c.938T>C and c.1144_1147delTCTG). Our case presented a distal spinal amyotrophy with slow evolution and symptoms and signs of AS with a mutation in AAAS gen. Some cases of motor neuron disease, as ours, may be due to AAS. Early diagnosis is extremely important for symptomatic treatment.
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PMID:Allgrove syndrome and motor neuron disease. 3006 87