Absence of detectable xanthine oxidase in human myocardium

The enzyme xanthine oxidase has been implicated as a generator of toxic oxygen metabolites that contribute to ischemic injury. Because substantial species variability has been demonstrated and because there are minimal human data available, the relevance of xanthine oxidase to human heart damage has been in doubt. We report the absence of xanthine oxidase activity in nine human heart biopsy specimens obtained during cardiac surgery, and in two larger samples obtained during heart transplantation. A sensitive radiochemical assay was used to assess enzyme activity. Our findings imply that oxygen free radicals generated by xanthine oxidase are not relevent in terms of human myocardial injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28034/1/0000473.pd

Absence of xanthine oxidase or xanthine dehydrogenase in the rabbit myocardium

We directly measured the activity of the enzymes xanthine oxidase and xanthine dehydrogenase in rabbit and rat hearts, using a sensitive radio-chemical assay. Neither xanthine oxidase activity nor xanthine dehydrogenase activity was detected in the rabbit heart. In the rat heart, xanthine oxidase activity was 9.1 [plus-or-minus sign] 0.5 mIU per gram wet weight and xanthine dehydrogenase activity was 53.0 [plus-or-minus sign] 1.9 mIU per gram wet weight. These results argue against the involvement of the xanthine oxidase/xanthine dehydrogenase system as a mechanism of tissue injury in the rabbit heart, and suggest that the ability of allopurinol to protect the rabbit heart against hypoxic or ischemic damage must be due to a mechanism other than inhibition of these enzymes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25939/1/0000001.pd

Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome

Oxygen metabolites have been implicated in the pathogenesis of various types of acute tissue injury. One biologic source of oxygen metabolites is the reaction catalyzed by the enzyme xanthine oxidase. Because we previously demonstrated that the substrates for xanthine oxidase (hypoxanthine and xanthine) are elevated in the plasma of critically ill patients, we questioned whether the enzyme itself might also be present. We therefore measured hypoxanthine concentration and xanthine oxidase activity in the plasma of 15 patients with ARDS and in 13 non-ARDS critically ill patients. Plasma xanthine oxidase activity in our ARDS group (1,514 +/- 975 mlU/L, mean +/- SE) was higher than that seen in the non-ARDS group (17 +/- 4 mlU/L, P [pre] .05). Plasma hypoxanthine was elevated in both groups, and there was no difference between the ARDS and non-ARDS groups (22.0 +/- 9.2 [mu]mol/L and 11.8 +/- 4.3 [mu]mol/L, respectively). The presence of both circulating xanthine oxidase and its substrate demonstrates the potential for intravascular oxygen metabolite production. These toxic products may then cause tissue injury in ARDS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26777/1/0000333.pd

Student Evaluation of Faculty Physicians: Gender Differences in Teaching Evaluations

Purpose: To investigate whether there is a difference in medical student teaching evaluations for male and female clinical physician faculty. Methods: The authors examined all teaching evaluations completed by clinical students at one North American medical school in the surgery, obstetrics and gynecology, pediatrics, and internal medicine clinical rotations from 2008 to 2012. The authors focused on how students rated physician faculty on their ?overall quality of teaching? using a 5-point response scale (1?=?Poor to 5?=?Excellent). Linear mixed-effects models provided estimated mean differences in evaluation outcomes by faculty gender. Results: There were 14,107 teaching evaluations of 965 physician faculty. Of these evaluations, 7688 (54%) were for male physician faculty and 6419 (46%) were for female physician faculty. Female physicians received significantly lower mean evaluation scores in all four rotations. The discrepancy was largest in the surgery rotation (males?=?4.23, females?=?4.01, p?=?0.003). Pediatrics showed the next greatest difference (males?=?4.44, females?=?4.29, p?=?0.009), followed by obstetrics and gynecology (males?=?4.38, females?=?4.26, p?=?0.026), and internal medicine (males?=?4.35, females?=?4.27, p?=?0.043). Conclusions: Female physicians received lower teaching evaluations in all four core clinical rotations. This comprehensive examination adds to the medical literature by illuminating subtle differences in evaluations based on physician gender, and provides further evidence of disparities for women in academic medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140140/1/jwh.2015.5475.pd

Weaning from Mechanical Ventilation

For most patients who require mechanical ventilation weaning and extubation is simple. In these patients a variety of strategies can be successful. In addition, sim ple criteria may predict when the patient is ready for extubation. For the small group of patients who require prolonged mechanical ventilation, however, contro versy exists about how best to remove ventilator sup port by weaning, and available data are sparse. Much of the controversy has centered on T-piece weaning ver sus intermittent mandatory ventilation. To date no con trolled study has demonstrated the superiority of either intermittent mandatory ventilation or T-piece weaning in difficult-to-wean patients. In the evolution of this con troversy, concern has developed over the potential for increased inspiratory work and expiratory resistance that may be associated with certain intermittent manda tory ventilation systems. The possibility that significant inspiratory work may occur during assist-control venti lation has also been demonstrated. Respiratory muscle weakness and fatigue is likely important in failure to wean. Other possible causes are failure of the cardiovas cular system and impaired ability of the lung to carry out gas exchange. In this article we first examine criteria and techniques for weaning short-term ventilator pa tients. We then examine criteria to begin the weaning process in prolonged ventilation patients, potential causes of failure to wean, and techniques that can be used to remove ventilator support from patients who are difficult to wean. Much literature has been devoted to techniques and criteria for weaning and extubation of patients from mechanical ventilation. For most patients who require ventilatory support, weaning and extuba tion can be easily accomplished by a variety of tech niques [1-4]. At one referral center 77.2% of all surviving patients were weaned from the ventilator within 72 hours of the onset of mechanical ventila tion, and 91% were weaned within 7 days [1]. Less than 10% of ventilated patients potentially posed problems in weaning from mechanical ventilation. Similarly, at a community hospital, few surviving patients required prolonged ventilatory support [2]. In easy-to-wean patients, Sahn and Lakshminarayan [5] described simple criteria that are predictive of successful discontinuation of ventilator support. For the small group of patients who require pro longed mechanical ventilation, however, minimal data are available. In these patients criteria to deter mine weaning ability or which measurements to follow are not clearly defined. Furthermore, no controlled trials are available to compare the differ ent weaning techniques proposed. In this article we first address routine weaning of the patient who has not required prolonged ventilator support. We then examine the difficult-to-wean patient and dis cuss criteria to begin the weaning process, poten tial causes of failure to wean, and available weaning techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68923/2/10.1177_088506668800300207.pd

Which Internal Medicine Clerkship Characteristics Are Associated With Students’ Performance on the NBME Medicine Subject Exam? A Multi-Institutional Analysis

Purpose To identify which internal medicine clerkship characteristics may relate to NBME Medicine Subject Examination scores, given the growing trend toward earlier clerkship start dates. Method The authors used linear mixed effects models (univariable and multivariable) to determine associations between medicine exam performance and clerkship characteristics (longitudinal status, clerkship length, academic start month, ambulatory clinical experience, presence of a study day, involvement in a combined clerkship, preclinical curriculum type, medicine exam timing). Additional covariates included number of NBME clinical subject exams used, number of didactic hours, use of a criterion score for passing the medicine exam, whether medicine exam performance was used to designate clerkship honors, and United States Medical Licensing Examination Step 1 performance. The sample included 24,542 examinees from 62 medical schools spanning 3 academic years (2011–2014). Results The multivariable analysis found no significant association between clerkship length and medicine exam performance (all pairwise P > .05). However, a small number of examinees beginning their academic term in January scored marginally lower than those starting in July (P < .001). Conversely, examinees scored higher on the medicine exam later in the academic year (all pairwise P < .001). Examinees from schools that used a criterion score for passing the medicine exam also scored higher than those at schools that did not (P < .05). Step 1 performance remained positively associated with medicine exam performance even after controlling for all other variables in the model (P < .001). Conclusions In this sample, the authors found no association between many clerkship variables and medicine exam performance. Instead, Step 1 performance was the most powerful predictor of medicine exam performance. These findings suggest that medicine exam performance reflects the overall medical knowledge students accrue during their education rather than any specific internal medicine clerkship characteristics

Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts

Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37[deg]C), reperfused 5 min with well-oxygenated IPSS containing 1 m CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28797/1/0000631.pd