Acute Liver Failure due to Non-Hodgkin's Lymphoma

Acute hepatic failure secondary to involvement of the liver by hematologic malignancies is a very uncommon condition, and usually has a fatal prognosis. We describe the case of a woman who developed acute hepatic failure due to infiltration by a non-Hodgkin's lymphoma 18 yr after the initial diagnosis of a nodular-type lymphocytic lymphoma, while she was apparently in remission. Early diagnosis was achieved through liver biopsy; therefore, rapid administration of chemotherapy allowed her complete recovery. Hepatic biopsy may provide a diagnosis in patients in whom the etiology of liver failure is unknown, thus establishing the possible need for specific treatment.     

Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when coligated with the high-affinity Fc receptor for IgE.

Mouse mast cells express gp49B1, a cell-surface member of the Ig superfamily encoded by the gp49B gene. We now report that by ALIGN comparison of the amino acid sequence of gp49B1 with numerous receptors of the Ig superfamily, a newly recognized family has been established that includes gp49B1, the human myeloid cell Fc receptor for IgA, the bovine myeloid cell Fc receptor for IgG2, and the human killer cell inhibitory receptors expressed on natural killer cells and T lymphocyte subsets. Furthermore, the cytoplasmic domain of gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs that are also present in killer cell inhibitory receptors; these motifs downregulate natural killer cell and T-cell activation signals that lead to cytotoxic activity. As assessed by flow cytometry with transfectants that express either gp49B1 or gp49A, which are 89% identical in the amino acid sequences of their extracellular domains, mAb B23.1 was shown to recognize only gp49B1. Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. Thus, gp49B1 is an immunoreceptor tyrosine-based inhibition motif-containing integral cell-surface protein that downregulates the high-affinity Fc receptor for IgE-mediated release of proinflammatory mediators from mast cells. Our findings establish a novel counterregulatory transmembrane pathway by which mast cell activation can be inhibited.     

Bile-Duct Hamartomas Presenting as Multiple Focal Lesions on Hepatic Ultrasonography

Multiple bile-duct hamartomas are usually diagnosed at autopsy as an incidental finding. We report a case of a 50-yr-old male in whom multiple bile-duct hamartomas were suspected in an abdominal ultrasonography and confirmed by an echo-guided needle liver biopsy. The ultrasonography disclosed multiple scattered hyperechoic lesions with a diameter of up to 1 cm, associated with some anechoic lesions of a larger size and a cystic appearance. Computed tomography demonstrated multiple hypodense lesions that were not modified by the administration of contrast. Bile-duct hamartomas should be included in the differential diagnosis of multiple focal hepatic lesions at ultrasonography or computed tomography.     

Life Change Events,Ballistocardiography and Coronary Death

Abstract

Thirty-six men and women who experienced a documented myocardial infarction, half of whom ultimately died from their disease and half of whom survived over a six-year period, provided longitudinal recent life changes and ballistocardiographic data. The 18 patients who died from their coronary disease indicated a significant buildup in life changes which peaked approximately one year prior to death; their serial ballistocardiograms indicated a significant buildup in average force of contraction which was seen to peak approximately six months prior to death. The 18 post-infarction patients who survived the six-year follow-up showed neither a buildup in life change nor a buildup in the ballistocardiographic index of cardiac contraction force. These findings of a life change peak preceding ballistocardiographic evidence of an “overworked” heart are discussed in terms of their possible medical and psychophysiological significances.     

Hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and desensitization

ObjectiveTo review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and its management with drug desensitization.Data SourcesEnglish-language literature on MEDLINE regarding hypersensitivity, anaphylaxis, and checkpoint inhibitor–monoclonal antibodies.Study SelectionsReferences were selected based on relevance, novelty, robustness, and applicability.ResultsThere are well-known tissue toxicities associated to checkpoint inhibitors, but hypersensitivity reactions and anaphylaxis have been underreported. The presentation of these reactions is based on clinical phenotypes with underlying endotypes identified by specific biomarkers. Drug desensitizations have been successfully applied to checkpoint inhibitor drugs to allow patients with cancer to receive first-line therapies. This review provides current best practices for the recognition and diagnosis of hypersensitivity reactions and anaphylaxis to checkpoint inhibitors and their management using drug desensitization.ConclusionHypersensitivity reactions and anaphylaxis have been identified as potential adverse effects induced by checkpoint inhibitor–monoclonal antibodies. Drug desensitization is a safe and effective treatment option for patients who experience hypersensitivity reactions in need of these monoclonal antibodies to improve cancer outcomes.     

Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.