Post-synthetic modification in vivo of the major hemoglobin beta chain in the rat

Rat hemoglobins are unusually heterogeneous among mammals. This heterogeneity provides multiple opportunities for asynchronies in synthesis and degradation. We have examined rat hemoglobin turnover after an intravenous injection of 2-14C-glycine. After analyzing incorporation into the seven nonallelic globin chains of adult rats, we found the percentage of the major beta chain decreases over the red cell lifespan while the percentage of one of the minor beta chains increases. This suggests that a post-synthetic modification event converts a portion of the latter into the former.     

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase

Summary Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.     

Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems

Recent progress and evolution in device engineering, surgical implantation practices, and periprocedural management have advanced the promise of durable support with left ventricular assist systems (LVAS) in patients with stage D heart failure. With greater uptake of LVAS globally, a growing population of LVAS recipients have pre-existing cardiac implantable electronic devices (CIEDs). Strategies for optimal clinical management of CIEDs in patients with durable LVAS are evolving, and clinicians will increasingly face complex decisions regarding implantation, programming, deactivation, and removal of CIEDs. Traditional decision-making pathways for CIEDs may not apply to LVAS-supported patients, as few patients die of arrhythmic causes and many arrhythmias may be well tolerated. Given limited data, treatment decisions must be individualized and made collaboratively among electrophysiologists, advanced heart failure specialists, and patients and their caregivers. Large, prospective, well-conducted studies are needed to better understand the contemporary utility of CIEDs in patients with newer-generation LVAS.     

Incontinence,Voiding Dysfunction,and Other Urologic Complications After Radiotherapy for Gynecologic Malignancies

Women with newly diagnosed gynecologic cancer will undergo treatment with surgery, radiation, or combination therapy. A considerable proportion of these women will develop urologic complications including urinary incontinence, urinary retention, radiation cystitis, ureteral stricture, or genitourinary fistula. Diagnosis is typically made with a careful history, physical exam, endoscopy, urodynamics, and imaging. Non-surgical and surgical management of urologic complications following radiotherapy is complicated by local tissue damage resulting in inferior success rates when compared to the general population. It is imperative that the patient and physician understand the complexity of treatment and manage expectations accordingly.     

Predictors of mortality and cost among surgical patients requiring rapid response team activation

BackgroundPrior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation.MethodsWe analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors.ResultsWe included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96–6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25–5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17–3.75), emergent surgery (OR 2.04, 95% CI 1.37–3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21–2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44–2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity.ConclusionRRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives.