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Management of large aggressive nonfunctional pituitary tumors: experimental medical options when surgery and radiation fail

Miller, Brandon A; Rutledge, W Caleb; Ioachimescu, Adriana G; Oyesiku, Nelson M
Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors.
PMID: 23040745
ISSN: 1558-1349
CID: 4836992

Cervical tracheal resection: new lessons learned

Mutrie, Christopher J; Eldaif, Shady M; Rutledge, Caleb W; Force, Seth D; Grist, William J; Mansour, Kamal A; Miller, Daniel L
BACKGROUND:Cervical tracheal stenosis can be a difficult condition to manage. Depending on the etiology, location, and extent of the stenosis, tracheal or cricotracheal resection may be required. Intraoperative decisions may predict outcome. METHODS:We performed a retrospective chart review of all patients undergoing cervical tracheal or cricotracheal resection from April 2000 through March 2008. RESULTS:One hundred and five patients underwent 108 tracheal or cricotracheal resections. Median age was 65 years (range, 15 to 78); 68% were women. Indication for operation included postintubation tracheal stenosis (38), idiopathic (31), tracheostomy stenosis (19), invasive thyroid cancer (9), and other (8). Median length of trachea resected was 2.7 cm (range, 1.5 to 6.0 cm); 48 patients (46%) underwent extended cricotracheal resections. Twenty-six patients (25%) had an intraoperative chin stitch placed. Hospital stay was a median of 4 days (range, 2 to 33). Operative mortality was (1%); 1 patient died of myocardial infarction on postoperative day 3. Four patients (4%) had hoarseness or vocal cord immobility. Median follow-up was 36 months (range, 1 to 79). Eighteen patients (17%) required dilation postoperatively. Seven patients (7%) required tracheostomy; 2 (2%) are tracheostomy dependent. Three patients (3%) underwent a re-resection for recurrent stenosis. Multivariate analysis of indication for resection, type of resection, length of resection, anastomotic technique, and use of chin stitch did not predict the need for postoperative dilation, tracheostomy, or reoperation. CONCLUSIONS:Cervical tracheal resection can be performed safely with low morbidity and mortality. Only 5% of patients required a long-term tracheostomy or re-resection for recurrent tracheal stenosis. Specific intraoperative decisions did not predict long-term success.
PMID: 21440131
ISSN: 1552-6259
CID: 4836972

Measurement of both the equilibrium constant and rate constant for electronic energy transfer by control of the limiting kinetic regimes

Vagnini, Michael T; Rutledge, W Caleb; Wagenknecht, Paul S
Electronic energy transfer can fall into two limiting cases. When the rate of the energy transfer back reaction is much faster than relaxation of the acceptor excited state, equilibrium between the donor and acceptor excited states is achieved and only the equilibrium constant for the energy transfer can be measured. When the rate of the back reaction is much slower than relaxation of the acceptor, the energy transfer is irreversible and only the forward rate constant can be measured. Herein, we demonstrate that with trans-[Cr(d(4)-cyclam)(CN)(2)](+) as the donor and either trans-[Cr([15]ane-ane-N(4))(CN)(2)](+) or trans-[Cr(cyclam)(CN)(2)](+) as the acceptor, both limits can be obtained by control of the donor concentration. The equilibrium constant and rate constant for the case in which trans-[Cr([15]ane-ane-N(4))(CN)(2)](+) is the acceptor are 0.66 and 1.7 x 10(7) M(-1) s(-1), respectively. The equilibrium constant is in good agreement with the value of 0.60 determined using the excited state energy gap between the donor and acceptor species. For the thermoneutral case in which trans-[Cr(cyclam)(CN)(2)](+) is the acceptor, an experimental equilibrium constant of 0.99 was reported previously, and the rate constant has now been measured as 4.0 x 10(7) M(-1) s(-1).
PMID: 20038123
ISSN: 1520-510x
CID: 4836962

The risk of esophageal resection after esophagomyotomy for achalasia

Eldaif, Shady M; Mutrie, Christopher J; Rutledge, W Caleb; Lin, Edward; Force, Seth D; Miller, Joseph I; Mansour, Kamal A; Miller, Daniel L
BACKGROUND:Esophagomyotomy is the mainstay of treatment for achalasia with proven long-term success. However, in patients with a significantly dilated esophagus, many advocate esophageal resection thus forgoing an esophagomyotomy. The purpose of this study is to determine the esophagomyotomy failure rate in patients with achalasia. METHODS:A retrospective review of all patients with achalasia who underwent an esophagomyotomy from 1996 to 2006; 272 patients were divided into three groups based on their preoperative degree of esophageal dilation for comparison. The endpoint for esophagomyotomy failure was persistent symptoms requiring any intervention. RESULTS:The preoperative characteristics were comparable except for the severely dilated esophagus patients who had a longer duration of preoperative symptoms. Group I (mild dilatation) had 162 patients with 7 failures requiring intervention. Group II (moderate dilatation) had 74 patients with 4 failures and group III (severe dilatation) had 36 patients with 5 patients requiring intervention. For the entire cohort, median follow-up was 37 months (range, 8 to 144 months). There was no statistically significant difference among the groups in the number of patients requiring reintervention. The overall esophagectomy rate was only 2%. However, there was a significantly higher (p = 0.02) esophagectomy rate in the severely dilated patients. CONCLUSIONS:The degree of esophageal dilatation associated with achalasia does not influence the success of an esophagomyotomy. Of the entire patient population in this study, only 6 patients required an esophagectomy. The majority of patients with the most severely dilated esophagus did not require an esophagectomy. Esophagomyotomy should be the first treatment option for patients with achalasia no matter what the degree of esophageal dilatation.
PMID: 19379905
ISSN: 1552-6259
CID: 4836952

A novel peptide agonist of formyl-peptide receptor-like 1 (ALX) displays anti-inflammatory and cardioprotective effects

Hecht, Iris; Rong, Jiang; Sampaio, André L F; Hermesh, Chen; Rutledge, Caleb; Shemesh, Ronen; Toporik, Amir; Beiman, Merav; Dassa, Liat; Niv, Hagit; Cojocaru, Gady; Zauberman, Arie; Rotman, Galit; Perretti, Mauro; Vinten-Johansen, Jakob; Cohen, Yossi
Activation of the formyl-peptide receptor-like (FPRL) 1 pathway has recently gained high recognition for its significance in therapy of inflammatory diseases. Agonism at FPRL1 affords a beneficial effect in animal models of acute inflammatory conditions, as well as in chronic inflammatory diseases. TIPMFVPESTSKLQKFTSWFM-amide (CGEN-855A) is a novel 21-amino acid peptide agonist for FPRL1 and also activates FPRL2. CGEN-855A was discovered using a computational platform designed to predict novel G protein-coupled receptor peptide agonists cleaved from secreted proteins by convertase proteolysis. In vivo, CGEN-855A displays anti-inflammatory activity manifested as 50% inhibition of polymorphonuclear neutrophil (PMN) recruitment to inflamed air pouch and provides protection against ischemia-reperfusion-mediated injury to the myocardium in both murine and rat models (36 and 25% reduction in infarct size, respectively). Both these activities are accompanied by inhibition of PMN recruitment to the injured organ. The secretion of inflammatory cytokines, including interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha, was not affected upon incubation of human peripheral blood mononuclear cells with CGEN-855A, whereas IL-8 secretion was elevated up to 2-fold upon treatment with the highest CGEN-855A dose only. Collectively, these new data support a potential role for CGEN-855A in the treatment of reperfusion-mediated injury and in other acute and chronic inflammatory conditions.
PMID: 19023040
ISSN: 1521-0103
CID: 4836942