Gastroenterology
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Clinical Trial
Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension.
It has been suggested that beta-blockers might be harmful in pulmonary arterial hypertension. However, no study has evaluated the effect of beta-blockers in these patients. The aim of this study was to investigate the effect of beta-blockers on exercise capacity and pulmonary hemodynamics in patients with portopulmonary hypertension receiving beta-blockers for the prophylaxis of variceal bleeding. ⋯ In patients with moderate to severe portopulmonary hypertension, beta-blockers are associated with significant worsening in exercise capacity and pulmonary hemodynamics. These deleterious effects support the contraindication of beta-blockers in patients with portopulmonary hypertension.
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Case Reports
Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution.
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is typically characterized by episodic fever, myalgia, skin rash, conjunctivitis, and abdominal cramps. Recently, mutations in the TNFRSF1A gene on chromosome 12p13 encoding tumor necrosis factor receptor type 1 have been linked to this autoinflammatory syndrome. We report the case of a 29-year-old white woman who experienced periodic inflammatory manifestations with fever up to 40 degrees C, leukocytosis, and elevation of C-reactive protein level (>100 mg/L) in conjunction with acute peritonitis of unknown origin since the age of 19 years. ⋯ Upon the next flare, the patient started corticosteroid therapy, resulting in complete relief and normalization of elevated C-reactive protein levels. To the best of our knowledge, we report the first case of compound heterozygosity for 2 TNFRSF1A gene mutations, including a novel one that causes a severe form of TRAPS that responds to anti-inflammatory treatment. A history of recurrent sterile peritonitis should prompt genotyping for periodic fever syndromes.
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The most common form of the disease-causing cystic fibrosis transmembrane conductance regulator mutation, DeltaF508, leads to a misfolded protein that undergoes endoplasmic reticulum-associated degradation. Retrieval of misfolded protein from the cis-Golgi or pre-Golgi intermediate compartment is a critical factor in endoplasmic reticulum retention and degradation of DeltaF508 protein. Therefore, the inhibition of retrograde Golgi-to-endoplasmic reticulum traffic by the alkalinization of Golgi lumen may permit functional DeltaF508 protein to reach the cell surface. ⋯ We found that base treatments correct misfolded cystic fibrosis transmembrane conductance regulator-induced defects in vitro and in vivo. These results imply that the alkalization of intracellular compartments, in particular, Golgi or pre-Golgi intermediate compartments, can be a potential therapeutic target for the loss-of-function type of conformational diseases.
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Comment Letter
Stool DNA: a viable option for colorectal cancer screening.