Cognitive effects of mifepristone in overweight, euthymic adults with depressive disorders.

BACKGROUND: Previous studies have shown that individuals with mood disorders have a higher prevalence of both hypercortisolemia and insulin resistance. Insulin resistance is posited to contribute to the cognitive deficits observed in individuals who have depression. However, the mechanistic relationship between cortisol and insulin within the central nervous system remains to be further elucidated. This study aimed to evaluate the effects of the antiglucocorticoid agent, mifepristone, on metabolic function and cognitive performance in individuals receiving treatment for depressive disorders who were euthymic at baseline. METHODS: Participants were administered a 600 mg/day dose of mifepristone for 28 days. Oral glucose tolerance tests (OGTTs) and cognitive assessments measuring verbal memory and executive functioning were administered at baseline and after 28 days of treatment. RESULTS: Improvements in attention and verbal learning were associated with reduction of fasting plasma glucose (FPG) in response to mifepristone treatment. LIMITATIONS: Limitations include the open-label design of this study and a small sample size. CONCLUSIONS: The findings from this study suggest that improvement in fasting plasma glucose levels, upon administration of mifepristone, is associated with the improvement in early input of verbal information. Further studies are warranted in order to better evaluate the use of mifepristone or other antiglucocorticoid agents in treatment of mood disorders characterized by metabolic dysfunction.

Conservative management of postoperative chylothorax using somatostatin.

Chylothorax is a rare but serious postoperative complication of thoracic surgical procedures. We report the case of a 77-year-old man who underwent a coronary artery bypass procedure using a left internal mammary artery pedicle graft. A permanent pacemaker was required postoperatively. A persistent postoperative chylothorax developed necessitating continuous drainage and conservative management. Somatostatin was instituted when after 1 week this management failed to resolve the chylothorax. This led to rapid cessation of chyle production. Enteral feeding was reinstituted without complication and surgical intervention was avoided.

Effects of left ventricular assist devices on outcomes in patients undergoing heart transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly being used to "bridge" patients to heart transplantation. METHODS: Data from 40 consecutive status 1 heart transplantation patients treated with intravenous inotrope therapy (n = 20) or the HeartMate LVAD (n = 20) were retrospectively analyzed. RESULTS: Baseline clinical characteristics were similar in the two groups. At the time of transplantation, LVAD patients had significantly higher blood pressure and sodium with significantly lower blood urea nitrogen and creatinine. After transplantation, renal failure (52.6% versus 16.7%) and right heart failure (31.6% versus 5.6%) occurred more frequently (p < 0.05) in the inotrope group. Six-month survival after transplantation did not significantly differ in the inotrope or LVAD groups (73.7% versus 88.9%) but event-free survival was significantly (p < 0.05) lower in the inotrope group (15.8% versus 55.6%). Total hospital charges were significantly lower in the inotrope group ($213,860 +/- $107,560 versus $342,620 +/- $104,420), but average daily hospital charges were not different ($3,990 +/- $1,300 versus $4,130 +/- $2,050). CONCLUSIONS: Status 1 heart transplant patients treated with an LVAD as opposed to inotrope therapy have improved clinical and metabolic function at the time of transplant and improved survival to 6 months after transplant without major complications. Total costs are higher in the LVAD patients but average daily costs are similar.

NF-kappaB activation by camptothecin. A linkage between nuclear DNA damage and cytoplasmic signaling events.

Activation of the transcription factor NF-kappaB by extracellular signals involves its release from the inhibitor protein IkappaBalpha in the cytoplasm and subsequent nuclear translocation. NF-kappaB can also be activated by the anticancer agent camptothecin (CPT), which inhibits DNA topoisomerase (Topo) I activity and causes DNA double-strand breaks during DNA replication to induce S phase-dependent cytotoxicity. Here we show that CPT activates NF-kappaB by a mechanism that is dependent on initial nuclear DNA damage followed by cytoplasmic signaling events. NF-kappaB activation by CPT is dramatically diminished in cytoplasts and in CEM/C2 cells expressing a mutant Topo I protein that fails to bind CPT. This response is intensified in S phase cell populations and is prevented by the DNA polymerase inhibitor aphidicolin. In addition, CPT activation of NF-kappaB involves degradation of cytoplasmic IkappaBalpha by the ubiquitin-proteasome pathway in a manner that depends on the IkappaB kinase complex. Finally, inhibition of NF-kappaB activation augments CPT-induced apoptosis. These findings elucidate the progression of signaling events that initiates in the nucleus with CPT-Topo I interaction and continues in the cytoplasm resulting in degradation of IkappaBalpha and nuclear translocation of NF-kappaB to attenuate the apoptotic response.

A comparison of nurse anesthesia practice types.

The present study examined the differences between anesthesia care team (ACT) and non-ACT practice types. Six practice variables were analyzed. We prepared and distributed a 13-item questionnaire to 1,000 practicing Certified Registered Nurse Anesthetists (CRNAs) with a 44.4% response rate. Data analysis revealed that nurse anesthetists in ACT practices had fewer years of experience and were younger than non-ACT nurse anesthetists (alpha = 0.05). Also, a significantly greater percentage of ACT nurse anesthetists were female, held master-level degrees, and practiced in urban and metropolitan locations. This also was true for placement of laryngeal mask airways and arterial lines, and in providing anesthesia for cardiopulmonary bypass, pediatric, intracranial, and trauma cases. However, a significantly greater percentage of non-ACT nurse anesthetists placed epidurals and central lines and were involved in pain management and critical care consultations. Income was significantly greater for non-ACT nurse anesthetists as well, but they worked more hours per week on average. Lastly, evaluation of employment arrangements showed that more than 91% (n = 361) of ACT nurse anesthetists were employees, and only 4% (n = 17) were self-employed. However, only 49% (n = 24) of non-ACT nurse anesthetists were employees, and almost 43% (n = 21) were self-employed. The present study demonstrates that significant differences exist between the 2 nurse anesthesia practice types examined. As nurse anesthesia practice arrangements continue to change and fewer CRNAs are hospital employed, each nurse anesthetist must be aware of current practice trends and understand the alternatives.

The PEST domain of IkappaBalpha is necessary and sufficient for in vitro degradation by mu-calpain.

Polypeptide sequences enriched in proline (P), glutamate (E), serine (S), and threonine (T), dubbed PEST domains, are proposed to expedite the degradation of proteins. The proteolysis of one PEST-containing protein, IkappaBalpha, is prerequisite to the activation of the transcription factor NF-kappaB. Two mechanisms of IkappaBalpha degradation in vivo have been described, one well characterized through the ubiquitin-proteasome pathway, and another less characterized through calpain. In this report, a mutational analysis was done to identify any regions of IkappaBalpha that facilitate its recognition and proteolysis by calpain in vitro. These studies revealed that the PEST sequence of IkappaBalpha is critical for its calpain-dependent degradation. Furthermore, the IkappaBalpha-PEST domain binds to the calmodulin-like domain of the large subunit of mu-calpain (muCaMLD). Transfer of the IkappaBalpha-PEST domain to a protein incapable of either binding to or being degraded by mu-calpain allowed for the interaction of the chimeric protein with muCaMLD and resulted in its susceptibility to calpain proteolysis. Moreover, the muCaMLD of calpain acts as a competitive inhibitor of calpain-dependent IkappaBalpha degradation. Our data demonstrate that the IkappaBalpha-PEST sequence acts as a modular domain to promote the physical association with and subsequent degradation by mu-calpain and suggest a functional role for PEST sequences in other proteins as potential calpain-targeting units.

Management of acute right heart failure after combined heart and kidney transplantation: case report.

Combined heart and kidney transplantation is performed rarely and merits unique fluid-management considerations postoperatively. We present the case of a young man who developed acute right heart failure after combined heart and kidney transplantation and responded to hemofiltration. We believe that the postoperative management of combined heart and kidney transplant recipients should not be different from that of patients receiving a heart transplant only. Intravenous fluids should be administered judiciously, and hemofiltration should be instituted early to remove fluid and reduce preload if right heart failure develops.

Stage I adenocarcinoma presenting in the pneumonectomy specimen at the time of single lung transplantation.

Two patients at our institution underwent single lung transplantation. The procedure and the patient's postoperative course were uncomplicated in each case. Pathological examination of each pneumonectomy specimen revealed a well-differentiated adenocarcinoma; both were less than 1 cm in size. The remainder of each lung showed no evidence of adenocarcinoma and all lymph nodes were negative. Work-ups for an occult malignancy before and after surgery were negative. This is believed to be the first report of a single lung transplant in a patient with a primary adenocarcinoma of the lung. The implications and management of these patients are discussed.