Concomitant off-pump myocardial revascularization and pheochromocytoma resection

Surgical management of patients with coexisting ischemic heart disease and pheochromocytoma remains challenging. We present one such case in which hybrid myocardial revascularization (angioplasty with stenting and off-pump coronary artery bypass grafting) and resection of pheochromocytoma were undertaken. Unusual features included simultaneous coronary artery surgery and tumor resection and, in particular, coronary artery surgery being performed without cardiopulmonary bypass.     

Student quality-of-life declines during third year surgical clerkship

INTRODUCTION: Choosing surgery as a career is declining among U.S. medical students. The 8-wk third year surgery clerkship at our institution can be an intense learning experience, and we hypothesized that during this clerkship medical student quality-of-life would drop significantly from baseline, and that this drop would be greater among certain subgroups, such as women students not interested in pursuing a surgical career, and those who place a high value on a controllable lifestyle. METHODS: At clerkship orientation (baseline), students were asked to complete a survey that measured quality-of-life on an 84-point scale, and depression on a 40-point scale. The quality-of-life scale was composed of select questions from the Medical Outcomes Study, and the Harvard Department of Psychiatry/NDSD brief screening instrument was used to measure depression. Students were also asked the typical number of hours they slept per night. Demographics, attitude toward a controllable lifestyle, and top three specialties of interest were also gathered at baseline. On week 6 of the clerkship, students were surveyed on the same quality-of -life and depression scales, and asked average hours of sleep per night for the previous week. RESULTS: From June 2005 through December 2006, 143 of 177 (81%) students agreed to participate, and after exclusions for missing data, 137 students were included in the analysis. Sixty-nine students were women (51%), and the average age was 25.8 (sd 2.6). Mean quality-of-life at baseline was 57.0 (sd 11.3) and at week 6 was 50.4 (sd 10.1) representing a statistically significant average decline of 6.6 points (P < 0.0001). Mean depression at baseline was 14.4 (sd 3.8) and at week 6 was 15.1 (sd 3.6), representing a small but significant average decline of 0.7 points (P = 0.0155). Mean sleep at baseline was 6.3 h/night (sd 0.9) and at week 6 was 5.7 h/night (sd 1.2), representing a statistically significant average decline of 0.6 h/night (P < 0.0001). Declines were similar on all outcomes between men versus women, those who ranked surgery in their top three career choices versus those who did not, and those who ranked controllable lifestyle as "very important" versus all other categories. CONCLUSION: Quality-of-life and sleep declines and depression increases significantly in third-year medical students from orientation to week 6 of their surgery clerkship at our institution. We look forward to studying quality-of-life on other clerkships for comparison, assessing whether the magnitude of this decline in quality-of-life predicts students avoiding a future career in surgery, and testing interventions to prevent this decline in quality-of-life during the clerkship.     

Inflammation in human brain injury: intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra

Following traumatic brain injury (TBI), cascades of inflammatory processes occur. Laboratory studies implicate the cytokines interleukin-1alpha (IL-1alpha) and IL-1beta in the pathophysiology of TBI and cerebral ischemia, whilst exogenous and endogenous interleukin-1 receptor antagonist (IL-1ra) is neuroprotective. We analyzed IL-1alpha, IL-1beta, and IL-1ra in brain microdialysates (100-kDa membrane) in 15 TBI patients. We also analyzed energy-related molecules (glucose, lactate, pyruvate, glutamate, and the lactate/pyruvate ratio) in these brain microdialysates. Mean of mean (+/-SD) in vitro microdialysis percentage recoveries (extraction efficiencies) were IL-1alpha 19.7+/-7.6%, IL-1beta 23.9+/-10.5%, and IL-1ra 20.9+/-6.3%. In the patients' brain microdialysates, mean of mean cytokine concentrations (not corrected for percentage recovery) were IL-1alpha 5.6+/-14.8 pg/mL, IL-1beta 10.4+/-14.7 pg/mL, and IL-1ra 2796+/-2918 pg/mL. IL-1ra was consistently much higher than IL-1alpha and IL-1beta. There were no significant relationships between IL-1 family cytokines and energy-related molecules. There was a significant correlation between increasing IL-1beta and increasing IL-1ra (Spearman r=0.59, p=0.028). There was also a significant relationship between increasing IL-1ra and decreasing intracranial pressure (Spearman r=-0.57, p=0.041). High concentrations of IL-1ra, and also high IL-1ra/IL-1beta ratio, were associated with better outcome (Mann Whitney, p=0.018 and p=0.0201, respectively), within these 15 patients. It is unclear whether these IL-1ra concentrations are sufficient to antagonize the effects of IL-1beta in vivo. This study demonstrates feasibility of our microdialysis methodology in recovering IL-1 family cytokines for assessing their inter-relationships in the injured human brain, and suggests a neuroprotective role for IL-1ra. It remains to be seen whether exogenous IL-1ra or other agents can be used to manipulate cytokine levels in the brain, for potential therapeutic effect.     

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

Open lung biopsy in immunocompromised patients

From January 1978 through December 1980, ninety-five immunocompromised patients underwent diagnostic open lung biopsy (OLB) at the Mayo Clinic, Rochester, Minn. A specific causative diagnosis was made in 77 patients (81%); 12 patients (13%) had more than one specific causative diagnosis. Of the 77 patients with a specific causative diagnosis, 52 patients (68%) had infections, 19 patients (24%) had malignant pulmonary disease, 12 patients (15%) had cytotoxic lung disease, ten patients (13%) had interstitial fibrosis (not related to cytotoxins), and one patient (1%) had vasculitis. In 36 (47%) of the 77 patients with a specific causative diagnosis, the diagnosis was made, by frozen sections or stains, within three hours of OLB. In 35 additional patients (45%), the diagnosis was established within 24 hours. Twelve patients (13%) had minor complications of OLB; no deaths were attributed to the OLB procedure.     

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m². In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m² higher eGFR at levels below 45 mL/min/1.73 m² was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m². In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.