Citations

The synapse is a localized neurohumoral contact between a neuron and an effector cell and may be considered the quantum of fast intercellular communication. Analogously, the postsynaptic neurotransmitter receptor may be considered the quantum of fast chemical to electrical transduction. Our understanding of postsynaptic receptors began to develop about a hundred years ago with the demonstration that electrical stimulation of the vagus nerve released acetylcholine and slowed the heart beat. During the past 50 years, advances in understanding postsynaptic receptors increased at a rapid pace, owing largely to studies of the acetylcholine receptor (AChR) at the motor endplate. The endplate AChR belongs to a large superfamily of neurotransmitter receptors, called Cys-loop receptors, and has served as an exemplar receptor for probing fundamental structures and mechanisms that underlie fast synaptic transmission in the central and peripheral nervous systems. Recent studies provide an increasingly detailed picture of the structure of the AChR and the symphony of molecular motions that underpin its remarkably fast and efficient chemoelectrical transduction.

The long-lived glycoprotein hormone, human chorionic gonadotropin (hCG), downregulates testosterone (T) biosynthesis in vitro and in vivo in animals and humans. The degree to which short-lived pulses of pituitary luteinizing hormone (LH) do so, particularly at physiological concentrations, is not known. We test the hypothesis that continuous LH infusion compared with bolus injections of LH every 1 h or every 2 h overnight downregulates T secretory responses to a subsequent fixed template of three consecutive intravenous pulses of a physiological amount of recombinant human (rh) LH (triple stimulus). Nineteen healthy men ages 18–49 yr each underwent four separate randomly ordered overnight gonadotropin-releasing hormone-receptor antagonist treatments with superimposed intravenous infusions of saline or rhLH (1-h pulses, 2-h pulses, or continuously). Each 12-h infusion protocol was followed by the triple rhLH-pulse stimulus the next morning. During the triple stimulus, basal (nonpulsatile) as well as total (basal plus pulsatile) T secretion was higher after overnight 2- and 1-h rhLH pulses than after continuous rhLH or saline delivery. Approximate entropy, a probabilistic measure of feedforward-induced irregularity of T concentration time series, was higher after 1-h rhLH pulses than after continuous rhLH. Analytical estimation of pulsatile rhLH-T dose-response measures revealed higher T secretory sensitivity and greater rhLH potency (lower EC50) after exposure to 1-h than 2-h rhLH pulses. Collectively, these data indicate that in vivo dynamics of LH-stimulated T secretion under standardized conditions in men depend on the prior time mode of LH delivery in the bloodstream.

Background— Use of the left internal mammary artery (LIMA) in multivessel coronary artery disease improves survival after coronary artery bypass graft surgery; however, the survival benefit of multiple arterial (MultArt) grafts is debated. Methods and Results— We reviewed 8622 Mayo Clinic patients who had isolated primary coronary artery bypass graft surgery for multivessel coronary artery disease from 1993 to 2009. Patients were stratified by number of arterial grafts into the LIMA plus saphenous veins (LIMA/SV) group (n=7435) or the MultArt group (n=1187). Propensity score analysis matched 1153 patients. Operative mortality was 0.8% (n=10) in the MultArt and 2.1% (n=154) in the LIMA/SV ( P =0.005) group, which was not statistically different ( P =0.996) in multivariate analysis or the propensity-matched analysis ( P =0.818). Late survival was greater for MultArt versus LIMA/SV (10- and 15-year survival rates were 84% and 71% versus 61% and 36%, respectively [ P <0.001], in unmatched groups and 83% and 70% versus 80% and 60%, respectively [ P =0.0025], in matched groups). MultArt subgroups with bilateral internal mammary artery/SV (n=589) and bilateral internal mammary artery only (n=271) had improved 15-year survival (86% and 76%; 82% and 75% at 10 and 15 years [ P <0.001]), and patients with bilateral internal mammary artery/radial artery (n=147) and LIMA/radial artery (n=169) had greater 10-year survival (84% and 78%; P <0.001) versus LIMA/SV. In multivariate analysis, MultArt grafts remained a strong independent predictor of survival (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94; P =0.007). Conclusions— In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery, arterial grafting of the non–left anterior descending vessels conferred a survival advantage at 15 years compared with SV grafting. It is still unproven whether these results apply to higher-risk subgroups of patients.

Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control.

Ductal carcinoma in situ (DCIS) of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS) and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve.