RESUMEN
Acute carpal tunnel syndrome is an uncommon diagnosis most often related to blunt trauma requiring immediate surgical decompression to avoid serious sequelae. Patients who present with bleeding-related acute carpal tunnel syndrome tend to have severe pain, rapid onset of swelling, and neurologic symptoms that appear early and progress rapidly secondary to mass effect. Acute carpal tunnel syndrome can occur in anticoagulated patients spontaneously or after minor trauma. This article describes a case of a 57-year-old man with progressive pain and paresthesias in the median nerve distribution after reaching for a picture frame. He was taking dabigatran, a direct thrombin inhibitor, for atrial fibrillation. He developed acute carpal tunnel syndrome secondary to spontaneous bleeding into the carpal canal and flexor tenosynovium with hematoma formation requiring surgical decompression. He reported immediate pain relief postoperatively, had no further bleeding complications, and regained full median nerve function within 2 months.Dabigatran has gained recent popularity for the treatment of atrial fibrillation. Unlike warfarin, its use does not involve regular laboratory monitoring or dose titration. The risks and benefits of dabigatran should be considered carefully by the prescriber, particularly in patients taking medications that may alter its metabolism. Aspirin and nonsteroidal anti-inflammatory drugs may have effects similar to dabigatran and may increase the risk of bleeding problems. Should acute carpal tunnel syndrome occur, the authors recommend prompt surgical decompression rather than conservative management. The modification of anticoagulant therapy should be considered on a case-by-case basis.
Asunto(s)
Antitrombinas/efectos adversos , Bencimidazoles/efectos adversos , Síndrome del Túnel Carpiano/inducido químicamente , Hematoma/inducido químicamente , beta-Alanina/análogos & derivados , Enfermedad Aguda , Síndrome del Túnel Carpiano/etiología , Síndrome del Túnel Carpiano/cirugía , Dabigatrán , Descompresión Quirúrgica , Hematoma/etiología , Hematoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , beta-Alanina/efectos adversosRESUMEN
Frailty is a new and emerging syndrome in the field of geriatrics. The study of frailty may provide an explanation for the downward spiral of many elderly patients after an acute illness and hospitalization. The fact that frailty is not present in all elderly persons suggests that it is associated with aging but not an inevitable process of aging and may be prevented or treated. The purpose of this article is to review what is known about frailty, including the definition, epidemiology, and pathophysiology, and to examine potential areas of future research.
Asunto(s)
Anciano Frágil , Anciano de 80 o más Años , Comorbilidad , Evaluación Geriátrica , Geriatría , Humanos , SíndromeRESUMEN
We rank the reactivity of the adenyl residues (A) of model DNA and RNA molecules with electropositive subnano size [Ag]n+ sites as a function of nucleic acid primary sequences and secondary structures and in the presence of biological amounts of Cl- and Na+ or Mg2+ ions. In these conditions A is markedly more reactive than any other nucleic acid bases. A reactivity is higher in ribo (r) than in deoxyribo (d) species [pA>pdA and (pA)n>>(pdA)n]. Base pairing decreases A reactivity in corresponding duplexes but much less in r than in d. In linear single and paired dCAG or dGAC loci, base stacking inhibits A reactivity even if A is bulged or mispaired (A.A). dA tracts are highly reactive only when dilution prevents self-association and duplex structures. In d hairpins the solvent-exposed A residues are reactive in CAG and GAC triloops and even more in ATC loops. Among the eight rG1N2R3A4 loops, those bearing a single A (A4) are the least reactive. The solvent-exposed A2 is reactive, but synergistic structural transitions make the initially stacked A residues of any rGNAA loop much more reactive. Mg2+ cross-bridging single strands via phosphates may screen A reactivity. In contrast d duplexes cross-bridging enables "A flipping" much more in rA.U pairs than in dA.T. Mg2+ promotes A reactivity in unpaired strands. For hairpins Mg2+ binding stabilizes the stems, but according to A position in the loops, A reactivity may be abolished, reduced, or enhanced. It is emphasized that not only accessibility but also local flexibility, concerted docking, and cation and anion binding control A reactivity.
Asunto(s)
Adenina/química , ADN/química , ARN/química , Espectrometría Raman , Resonancia por Plasmón de Superficie , Emparejamiento Base , Secuencia de Bases , Cloruros/farmacología , Magnesio/farmacología , Modelos Moleculares , Conformación de Ácido Nucleico , Sodio/farmacologíaRESUMEN
We previously reported that monoclonal antibodies to protein-disulfide isomerase (PDI) and other membrane-impermeant PDI inhibitors prevented HIV-1 infection. PDI is present at the surface of HIV-1 target cells and reduces disulfide bonds in a model peptide attached to the cell membrane. Here we show that soluble PDI cleaves disulfide bonds in recombinant envelope glycoprotein gp120 and that gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors. Concentrations of inhibitors that prevent this reduction and inhibit the cleavage of surface-bound disulfide conjugate prevent infection at the level of HIV-1 entry. The entry of HIV-1 strains differing in their coreceptor specificities is similarly inhibited, and so is the reduction of gp120 bound to CD4 of coreceptor-negative cells. PDI inhibitors also prevent HIV envelope-mediated cell-cell fusion but have no effect on the entry of HIV-1 pseudo-typed with murine leukemia virus envelope. Importantly, PDI coprecipitates with both soluble and cellular CD4. We propose that a PDI.CD4 association at the cell surface enables PDI to reach CD4-bound virus and to reduce disulfide bonds present in the domain of gp120 that binds to CD4. Conformational changes resulting from the opening of gp120-disulfide loops may drive the processes of virus-cell and cell-cell fusion. The biochemical events described identify new potential targets for anti-HIV agents.