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)

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

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

A 69-year-old man with advanced heart failure treated with a continuous-flow left ventricular assist device presented for evaluation of dark urine and severe dysphagia. Because of evidence of ongoing intravascular hemolysis with device dysfunction, there was a clinical suspicion for pump thrombosis. He had progressive end-organ dysfunction and was therefore treated with tissue plasminogen activator with prompt resolution in hemolysis and dysphagia. Although symptoms of smooth muscle dystonia could represent worsening heart failure in the setting of device failure, the observation may also be related to intravascular hemolysis as described in the prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria.
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PMID:Dysphagia in the setting of left ventricular assist device hemolysis. 2364 23

A 41-year-old man with a continuous-flow left ventricular assist device presented for evaluation of dysphagia and dark urine. He was found to have a significantly elevated L-lactate dehydrogenase and an elevated plasma free hemoglobin consistent with intravascular hemolysis. After the hemolysis ceased, both the black urine and dysphagia resolved spontaneously. Transient esophageal dysfunction, as a manifestation of gastrointestinal dysmotility, is known to occur in the setting of hemolysis. Paroxysmal nocturnal hemoglobinuria is another recognized cause of massive hemolysis with gastrointestinal dysmotility occurring in 25%-35% of patients during a paroxysm. Intravascular hemolysis increases plasma free hemoglobin, which scavenges nitric oxide (NO), an important second messenger for smooth muscle cell relaxation. The decrease in NO can lead to esophageal spasm and resultant dysphagia. In our patient the resolution of hemolysis resulted in resolution of dysphagia.
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PMID:Left ventricular assist device hemolysis leading to dysphagia. 2598

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

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis. Real-world experience of PNH management is largely unreported. A retrospective analysis was undertaken based on medical records from six patients with PNH [two with aplastic anemia (AA)] treated at our center, Dicle University, Turkey. Diagnosis was based on granulocyte PNH clones, ranging from 93% to 66%. All patients had symptoms consistent with PNH. One patient was managed adequately with supportive measures only. Five were treated with the complement inhibitor eculizumab. Follow-up data (<1 year) were available in four cases (the fifth had received only three infusions by final follow-up). Hemoglobin level in these four patients increased from 4.1-7.2 g/dL to 8.3-13.0 g/dL. Lactate dehydrogenase, a marker for hemolysis, decreased profoundly in the two non-AA patients, with more minor improvements in the two AA patients. Weakness and fatigue improved in all eculizumab-treated patients. Four of the five treated patients became transfusion independent, including the patient given only three infusions. In the remaining case, a patient with AA, transfusion requirement decreased, and abdominal pain and dysphagia resolved. No adverse events occurred. PNH can be successfully managed in routine practice.
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PMID:Presentation and Management of Paroxysmal Nocturnal Hemoglobinuria: A Single-Center Experience. 2710 81

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