Splenectomy for splenomegaly and secondary hypersplenism

Splenomegaly and secondary hypersplenism may be associated with acute and chronic infections, autoimmune states, portal hypertension or splenic vein thrombosis, and a number of infiltrative and neoplastic conditions involving the spleen. Our experience and that of others with these various conditions demonstrates that the decision to perform splenectomy should be based on well-defined and often strictly limited indications. Except for idiopathic splenomegaly, the presence and severity of secondary hypersplenism or severely symptomatic splenomegaly should be well documented. In each case, the potential for palliation and known mean duration of expected response must be weighed against the increased morbidity and mortality of splenectomy (as compared to operation for “primary” hypersplenism) . La splénomégalie avec hypersplénisme secondaire relève de multiples causes: infection aigue ou chronique, états autoimmunologiques, hypertension portale, thrombose de la veine splénique, lésions tumorales spléniques. L'expérience de l'auteur qui rejoint celle de nombreux collègues lui permet d'affirmer que les indications de la splénectomie doivent être bien définies et sont strictement limitées. A l'exception de la splénomégalie idiopathique, l'existence et l'intensité de l'hypersplénisme, l'importance des symptomes provoqués par la splénomégalie doivent être aprréciées avec précision. Dans chaque cas le potentiel de la rémission de l'affection et la durée de la rémission doivent être pris en considération en fonction de l'éventuelle morbidité et de l'éventuelle mortalité de la splénectomie (par comparaison avec la splénectomie pour hypersplénisme primaire). Eplenomegalia e hiperesplenismo secundario pueden estar asociados con infecciones agudas y crónicas, estados autoinmunes (síndrome de Felty, lupus eritematoso sistémico), “esplenomegalia congestiva” por hipertensión portal o trombosis de la vena esplénica y con una variedad de entidades de tipo infiltrativo y neoplásico que afectan al bazo (sarcoidosis, enfermedad de Gaucher, varios desórdenes mieloproliferativos y linfomas). Nuestra experiencia, y aquella de otros autores, con tales condiciones demuestra que la decisión de realizar esplenectomía debe estar fundamentada en indicaciones bien definidas y estrictamente limitadas. Excepto en casos de esplenomegalia idiopática, la presencia y severidad del hiperesplenismo secundario o de esplenomegalia severamente sintomática debe ser bien documentada. En cada caso debe determinarse el potencial de paliación y la duración de la respuesta que se espera obtener frente a la incrementada morbilidad y mortalidad de la esplenectomía (en comparación con la operación que se realiza por hiperesplenismo “primario”).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41318/1/268_2005_Article_BF01655279.pd

Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin

“Two-cysteine” peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus, reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin’s role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here. the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress

Mechanisms That Modulate Peripheral Oxygen Delivery during Exercise in Heart Failure

Oxygen uptake ([Formula: see text]o2) measured at the mouth, which is equal to the cardiac output (CO) times the arterial-venous oxygen content difference [C(a-v)O2], increases more than 10- to 20-fold in normal subjects during exercise. To achieve this substantial increase in oxygen uptake [[Formula: see text]o2\u2009=\u2009CO\u2009 7\u2009C(a-v)O2] both CO and the arterial-venous difference must simultaneously increase. Although this occurs in normal subjects, patients with heart failure cannot achieve significant increases in cardiac output and must rely primarily on changes in the arterial-venous difference to increase [Formula: see text]o2 during exercise. Inadequate oxygen delivery to the tissue during exercise in heart failure results in tissue anaerobiosis, lactic acid accumulation, and reduction in exercise tolerance. H(+) is an important regulatory and feedback mechanism to facilitate additional oxygen delivery to the tissue (Bohr effect) and further aerobic production of ATP when tissue anaerobic metabolism increases the production of lactate (anaerobic threshold). This H(+) production in the muscle capillary promotes the continued unloading of oxygen (oxyhemoglobin desaturation) while maintaining the muscle capillary Po2 (Fick principle) at a sufficient level to facilitate aerobic metabolism and overcome the diffusion barriers from capillary to mitochondria ("critical capillary Po2," 15-20 mm Hg). This mechanism is especially important during exercise in heart failure where cardiac output increase is severely constrained. Several compensatory mechanisms facilitate peripheral oxygen delivery during exercise in both normal persons and patients with heart failure

Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review

Contains fulltext : 200196.pdf (publisher's version ) (Open Access

The role of the clinician in the multi-omics era: Are you ready?

Flatworms of the species Schmidtea mediterranea are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution