Syndrome of inappropriate antidiuretic hormone associated with tolterodine therapy.

OBJECTIVE: To present a case of syndrome of inappropriate antidiuretic hormone (SIADH) associated with the use of tolterodine. SETTING: An acute-care unit at a university hospital with a comprehensive program for elders. CASE SUMMARY: In this case report, we present a 99-year-old female who was admitted to our unit for suspected gastrointestinal bleeding who subsequently developed hyponatremia. After the initiation of tolterodine for urinary incontinence, the patient's sodium dropped to 121 mEq/L (from a usual baseline that ranged between 128 mEq/L and 134 mEq/L). Laboratory and urinary findings revealed a serum osmolality of 220 mOsm/kg, a urinary osmolality of 340 mOsm/kg, and a urinary sodium of 101 mmol/L, suggesting a euvolemic hyponatremic state consistent with SIADH. Tolterodine therapy was promptly discontinued, and patient sodium levels normalized. CONCLUSION: Although the etiology of SIADH is often obscure and multifactorial, clinicians should be aware that it is a major cause of hyponatremia among hospitalized elderly patients, and drug therapies must always be evaluated to prevent further complications.

Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons.

Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is critical to NMDA receptor (NMDAR)-dependent synaptic plasticity. Using quantitative high-resolution in situ hybridization, we show that mRNAs encoding the AMPA-type glutamate receptor subunits (GluRs) 1 and 2 are localized to dendrites of hippocampal neurons and are regulated by paradigms that alter synaptic efficacy. A substantial fraction of synaptic sites contain AMPAR mRNA, consistent with strategic positioning and availability for "on-site" protein synthesis. NMDAR activation depletes dendritic levels of AMPAR mRNAs. The decrease in mRNA occurs via rise in intracellular Ca2+, activation of extracellular signal-regulated kinase/mitogen-activated protein kinase signaling, and transcriptional arrest at the level of the nucleus. The decrease in mRNA is accompanied by a long-lasting reduction in synaptic AMPAR number, consistent with reduced synaptic efficacy. In contrast, group I metabotropic GluR signaling promotes microtubule-based trafficking of existing AMPAR mRNAs from the soma to dendrites. Bidirectional regulation of dendritic mRNA abundance represents a potentially powerful means to effect long-lasting changes in synaptic strength.

Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes.

We undertook a retrospective cohort study describing general outcomes and specific factors associated with positive outcomes in bacteremia due to carbapenem-resistant Klebsiella pneumoniae (CRKP). Forty-eight patients were included, of which 42% died at 30 days. Forty-two percent of patients were in septic shock at the time of the first positive blood culture, and 42% were recipients of solid organ transplants. Lack of microbiologic eradication at 7 days was independently associated with 30-day mortality. Adjunctive procedures performed for source control and microbiologic eradication at 7 days were associated with a favorable clinical response at 7 days. Time to initiation and receipt at any time of antimicrobials with in vitro activity against CRKP were not associated with improved survival. Breakthrough bacteremia occurred in 8 cases, all in patients receiving tigecycline. Our data suggest that severity of illness, rapid microbiologic eradication, and source control are crucial factors in the outcomes of patients with CRKP bacteremia.