Characteristics and treatment of elemental mercury intoxication: A case series.

BACKGROUND AND AIMS: Elemental mercury toxicity is a rare condition which can be difficult to diagnose due to its nonspecific signs and symptoms. The purpose of this investigation is to describe the presenting characteristics and treatment of adult and pediatric patients with elemental mercury poisoning. METHODS: A retrospective review was performed in six patients with elemental mercury exposure or intoxication who were treated in an outpatient medical toxicology clinic. Clinical signs and symptoms, laboratory assessments, and public health responses were reviewed. RESULTS: Headache, anorexia, rash, and personality changes were commonly reported symptoms in pediatric patients; the adult patients were asymptomatic or reported signs and symptoms included myalgias, tremors, and hypertension. Delays in diagnosis were common. Symptomatic patients had 24-hour urine mercury concentrations greater than 20 mcg/L. Treatment, including removal from the exposure source as well as chelation with dimercaptosuccinic acid, resulted in resolution of signs and symptoms within 6 months of diagnosis. CONCLUSION: The evaluation and treatment of patients with suspected elemental mercury poisoning frequently require a multidisciplinary approach including medical toxicologists and public health officials. A heightened awareness of the clinical presentations of this condition, as well as early identification and removal of patients from the source of exposure and consideration of chelation therapy, can result in accelerated patient recovery.

Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57 : 01-restricted CD8+ T-cell activation.

OBJECTIVE: Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA)-B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA-B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. DESIGN: An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. METHODS: Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. RESULTS: Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNγ following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. CONCLUSION: These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy.

Ureaplasma parvum prosthetic joint infection detected by PCR.

We describe the first reported case of Ureaplasma parvum prosthetic joint infection (PJI) detected by PCR. Ureaplasma species do not possess a cell wall and are usually associated with colonization and infection of mucosal surfaces (not prosthetic material). U. parvum is a relatively new species name for certain serovars of Ureaplasma urealyticum, and PCR is useful for species determination. Our patient presented with late infection of his right total knee arthroplasty. Intraoperative fluid and tissue cultures and pre- and postoperative synovial fluid cultures were all negative. To discern the pathogen, we employed PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Our patient's failure to respond to empirical antimicrobial treatment and our previous experience with PCR/ESI-MS in culture-negative cases of infection prompted us to use this approach over other diagnostic modalities. PCR/ESI-MS detected U. parvum in all samples. U. parvum-specific PCR testing was performed on all synovial fluid samples to confirm the U. parvum detection.

Reform requires resilience: a holistic model for success.

Ten initiatives associated with healthcare reform may alter the way healthcare organizations operate. Implementing a governance, risk, and compliance (GRC) model can help healthcare leaders deliver performance and compliance and enable enterprise resilience. Implementing GRC effectively requires a vision that's clearly supported by the management team.