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Background. Trypanosoma cruzi infection (i.e., Chagas disease) is an unusual complication that can occur after solid-organ transplantation and that can result in severe illness or death. In 2006, there were 2 heart transplant recipients in Los Angeles, California, reported to have acute trypanosomiasis during the same month. We conducted an investigation to determine the source of these infections. Methods. We reviewed the medical, organ procurement, and donor transfusion and transplantation records of these 2 heart transplant recipients. The 2 heart transplant recipients were interviewed regarding any kind of natural exposure and were screened for parasites by obtaining blood and other tissue samples for buffy coat, culture, and polymerase chain reaction. Serum samples from the heart transplant recipients, organ donors, and blood donors were tested for T. cruzi antibodies by use of immunofluorescence assay and radioimmunoprecipitation assay. Tissue samples from the organ donors were examined by use of polymerase chain reaction and immunohistochemical staining. Other recipients of organs from the same donors were monitored for T. cruzi infection by use of polymerase chain reaction and immunofluorescence assay. Results. Both heart transplant recipients had no apparent risk factors for preexisting T. cruzi infection. Both were seronegative but tested positive for the parasite, indicating recent infection. Both recipients died despite medical treatment. The organ donors tested positive for T. cruzi antibodies by use of radioimmunoprecipitation assay; the blood donors were seronegative. Six other patients had received a liver or kidney from these organ donors. None showed evidence of T. cruzi infection. Conclusions. To our knowledge, this is the first report of T. cruzi transmission associated with heart transplantation. Clinicians and public health authorities should be aware that manifestations of Chagas disease can occur after transplantation, requiring rapid evaluation, diagnosis, and treatment.

The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI).Thirty-six patients (27 males and 9 females, mean +/- SEM age 33 +/- 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured.The AR was impaired (AR index2.8) in 30 (83%) of 36 patients on Days 3-5 after injury, and in 19 individuals (53%) impairments were found on Days 9-11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index1) on postinjury Days 12-14, which eventually recovered on Days 15-23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3-5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury.Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.

Many libraries have been affected by the proliferation and price inflation of serial publications in recent years. Academic libraries have been especially hard‐hit since they are trying to cope with increasing subscription prices while facing budget reductions or very small increases. Although requesting additional funds and freezing new subscriptions help as short‐term measures, some libraries have undertaken serials evaluation and cancellation programs as a more permanent solution. Our university library conducted a comprehensive serials review, which is described here. This article explains the justification for the review and describes the methodology used and the problems encountered in canceling serials subscriptions.

A large-scale field intervention study was undertaken to examine the effects of office ergonomics training coupled with a highly adjustable chair on office workers' knowledge and musculoskeletal risks. Office workers were assigned to one of three study groups: a group receiving the training and adjustable chair (n=96), a training-only group (n=63), and a control group (n=57). The office ergonomics training program was created using an instructional systems design model. A pre/post-training knowledge test was administered to all those who attended the training. Body postures and workstation set-ups were observed before and after the intervention. Perceived control over the physical work environment was higher for both intervention groups as compared to workers in the control group. A significant increase in overall ergonomic knowledge was observed for the intervention groups. Both intervention groups exhibited higher level behavioral translation and had lower musculoskeletal risk than the control group.

OBJECTIVE. We aimed to describe gender differences in blood flow velocity and autoregulation of the anterior and posterior cerebral circulations in prepubertal children. METHODS. A prospective observational cohort study was performed at Harborview Medical Center's Cerebrovascular Laboratory after institutional review board approval, consent, and assent procedures. Children underwent measurement of middle cerebral and basilar artery flow velocities and cerebral autoregulation testing of the middle cerebral and basilar arteries. Cerebral autoregulation was quantified using the autoregulatory index, and estimated cerebrovascular resistance was calculated. Autoregulatory index RESULTS. Forty-eight children (24 boys and 24 girls) 4 to 8 years of age (mean: 6 ± 2 years) were enrolled. Middle cerebral artery flow velocity was higher than basilar artery flow velocity (96 ± 13 vs 65 ± 11 cm/s). Girls had higher middle cerebral artery flow velocity (99 ± 11 vs 91 ± 13 cm/s) and basilar artery flow velocity (70 ± 10 vs 61 ± 9 cm/s) than boys. Cerebral autoregulation was intact in all children. There was no gender difference in autoregulation between the middle cerebral artery (boys: 0.97 ± 0.07; girls: 0.94 ± 0.11) or basilar artery (boys: 0.94 ± 0.13; girls: 0.94 ± 0.11). CONCLUSIONS. Similar to older children and adults, girls between 4 and 8 years of age had higher middle cerebral and basilar artery flow velocity than age-matched boys. This difference may reflect inherent differences in cerebral metabolic rate and/or estimated cerebrovascular resistance between the genders.

11008 Background: Bone marrow derived endothelial progenitor cells (EPCs) and copper-dependent pathways are critical components to remodeling the tumor microenvironment and creating the pre-metasta...

9518 Background: Alopecia is an emotionally traumatic side effect for breast cancer (BC) patients (pts) undergoing adjuvant chemotherapy (CTX). The DigniCap System is the first scalp cooling system...

The aims of this study were to determine the electrogastrographic patterns in children with functional dyspepsia and to investigate the correlations among electrogastrogram (EGG), gastric emptying (GE), and pain severity.We studied 30 children (19 F; mean age 11.4 years) with functional dyspepsia. Electrogastrography was performed for 30 minutes fasting and for 1 hour during a GE test after ingestion of an isotope-labeled solid meal. The percent emptying was measured every 10 minutes for 1 hour after the meal. The dominant frequency of the EGG, the change in the postprandial peak power (deltaP), and percent dysrhythmia during each recording session were calculated. Specific symptoms were graded from 0 (none) to 4 (severe) by the patient.Of 30 patients, 14 (47%) had slow GE, and 15 (50%) had abnormal EGG (dysrhythmiaor = 30% or deltaP0). GE was slow in 73% of patients with an abnormal EGG but was slow in only 20% of patients with normal EGG (P = 0.009). GE was negatively correlated with fasting bradygastria (r = -0.383, P = 0.04). Abdominal pain was the most severe dyspeptic symptom, both during fasting and after the meal. Patients with an abnormal EGG had an increased mean pain severity score (3.5 +/- 0.2 vs. 2.5 +/- 0.2, P = 0.002).Sixty percent of functional dyspepsia subjects had either slow GE or abnormal EGG. Patients with abnormal EGG were more likely to have slow GE. EGG abnormalities were associated with more severe postprandial pain and should be considered a possible mechanism for dyspeptic symptoms.

This study seeks to elucidate the effects of the cycle time of a pick-and-place task on muscle activity, grip force, posture, and perception-based measures (discomfort and difficulty). Six healthy adults (3 males, 3 females) participated. A 4×2 repeated measures design was used with cycle time (1, 2, 5, and 10 s) and grip (power and chuck) as independent variables. The task consists of repetitively picking a 0.7 kg part and placing it into a bin. A reduction in cycle time (CT) resulted in both a decrease of task time and physical rest time (p

We used the hyperinsulinemic normoglycemic clamp technique, i.e., infusion of insulin at a constant rate combined with dextrose titrated to clamp blood glucose at a specific level, to preserve normoglycemia during elective cardiac surgery. Ten nondiabetic and seven diabetic patients entered the clamp protocols. Perioperative glucose control was also assessed in 19 nondiabetic and 11 diabetic patients (control group) receiving a conventional insulin infusion sliding scale. In patients of the clamp group, a priming bolus of insulin (2 U) was started before the induction of anesthesia followed by infusions of insulin at 5 mU. kg(-1). min(-1) and of variable amounts of dextrose. Arterial blood glucose was measured every 5 min in the clamp group and every 20 min in the control group. Control of normoglycemia was defined as > or =95% of the glucose levels within 4.0-6.0 mmol/L. Glucose concentration was recorded before surgery, 15 min before cardiopulmonary bypass (CPB), during early and late CPB, and at sternal closure. Patients of the control group became progressively hyperglycemic during surgery (late CPB; nondiabetics, 9.0 +/- 3.2 mmol/L; diabetics, 10.1 +/- 3.6 mmol/L), whereas normoglycemia was achieved in the study group (late CPB; nondiabetics, 5.5 +/- 0.7 mmol/L; diabetics, 4.9 +/- 0.6 mmol/L; P < 0.05 versus control group). In conclusion, it seems that normal blood glucose concentration during open heart surgery can be reliably maintained in nondiabetic and diabetic patients by using the hyperinsulinemic normoglycemic clamp technique.

Study design Office workers invited and agreeing to participate were assigned to one of three study groups: a group receiving a highly adjustable chair with office ergonomics training, a training-only group, and a control group receiving the training at the end of the study. Objective To examine the effect of office ergonomics intervention in reducing musculoskeletal symptom growth over the workday and, secondarily, pain levels throughout the day. Materials and methods Data collection occurred 2 months and 1 month before the intervention and 2, 6, and 12 months postintervention. During each round, a short daily symptom survey was completed at the beginning, middle, and end of the workday for 5 days during a workweek to measure total bodily pain growth over the workday. Multilevel statistical models were used to test hypotheses. Results The chair-with-training intervention lowered symptom growth over the workday (P = 0.012) after 12 months of follow-up. No evidence suggested that training alone lowered symptom growth over the workday (P = 0.461); however, average pain levels in both intervention groups were reduced over the workday. Conclusion Workers who received a highly adjustable chair and office ergonomics training had reduced symptom growth over the workday. The lack of a training-only group effect supports implementing training in conjunction with highly adjustable office furniture and equipment to reduce symptom growth. The ability to reduce symptom growth has implications for understanding how to prevent musculoskeletal injuries in knowledge workers.

Pre- and post-intervention data on health outcomes, absenteeism, and productivity from a longitudinal, quasi-experimental design field study of office workers was used to evaluate the economic consequences of two ergonomic interventions. Researchers assigned individuals in the study to three groups: a group that received an ergonomically designed chair and office ergonomics training; a group that received office ergonomics training only; and a control group. The results show that while training alone has neither a statistically significant effect on health nor productivity, the chair-with-training intervention substantially reduced pain and improved productivity. Neither intervention affected sick leave hours.

Pre- and post-intervention data on health outcomes, absenteeism, and productivity from a longitudinal, quasi-experimental design field study of office workers was used to evaluate the economic consequences of two ergonomic interventions. Researchers assigned individuals in the study to three groups: a group that received an ergonomically designed chair and office ergonomics training; a group that received office ergonomics training only; and a control group. The results show that while training alone has neither a statistically significant effect on health nor productivity, the chair-with-training intervention substantially reduced pain and improved productivity. Neither intervention affected sick leave hours.

The suppression of forward-propagating stimulated hyper-Raman (SHR) emission is well studied in sodium vapor. Theory predicts that SHR emission to a state linked to the gound state by a one-photon transition is suppressed by an interference with a four-wave-mixing (FWM) emission that links that state to the ground state. Since FWM emission only propagates in the forward direction due to phase-matching considerations, only the forward SHR emission is suppressed. This has been previously demonstrated in sodium. An obvious corollary to this theory is that no suppression occurs if the state is not linked to the ground state by a one-photon transition. A serendipitous arrangement of energy levels in cesium allowed this corollary to be tested and confirmed here.

Background: Bone marrow derived endothelial progenitor cells (EPCs) and copper-dependent angiogenic pathways are critical to the metastatic process. Copper depletion (CD) therapy inhibits tumor metastases in preclinical models. We hypothesized that TM-associated CD would reduce EPCs in pts at high risk for BC recurrence, and we explored the relationship between CD and its effects on the tumor microenvironment in pre-clinical models. Methods: In this single arm, phase II study, BC pts at high risk for recurrence, defined as node positive triple negative (TN), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. We CD’d to maintain ceruloplasmin (Cp) between 5-17 mg/dl for 2 years or until relapse. The primary endpoint was change in EPCs measured before and during treatment with TM. Secondary endpoints included tolerability, safety, and efficacy of CD. Laboratory studies: MDA-LM2-luciferase cells were implanted into CB17-SCID mice gavaged with water or TM. The tumors were quantified by bioluminescence images (BLI). We measured Cp oxidase to determine copper status. Western blots were used to assess LOX activity, and IHC was used to quantify collagen cross-linking and CD11b+ macrophage infiltration. Results: We enrolled 43 pts. Treatment duration was 24 cycles (each cycle is 28 days) for the primary study. A total of 752 cycles were completed in 2 years. The mean age was 49 (range 29-66). Mean Cp level decreased from 29 at baseline to 16 (p Citation Format: Nancy Chan, Naomi Kornhauser, Maureen Ward, Amy Willis, Tessa Cigler, Ellen Chuang, Anne Moore, Diana Donovan, Sarah E. Schneider, Christina Lam, David J. Warren, Anna Rubinchik, Sandra Hurtado Rua, Sharrell Lee, Maureen Lane, Vivek Mittal, Linda Vahdat. Influencing the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT309. doi:10.1158/1538-7445.AM2014-CT309

A key step in the analysis of circadian data is to make an accurate estimate of the underlying period. There are many different techniques and algorithms for determining period, all with different assumptions and with differing levels of complexity. Choosing which algorithm, which implementation and which measures of accuracy to use can offer many pitfalls, especially for the non-expert. We have developed the BioDare system, an online service allowing data-sharing (including public dissemination), data-processing and analysis. Circadian experiments are the main focus of BioDare hence performing period analysis is a major feature of the system. Six methods have been incorporated into BioDare: Enright and Lomb-Scargle periodograms, FFT-NLLS, mFourfit, MESA and Spectrum Resampling. Here we review those six techniques, explain the principles behind each algorithm and evaluate their performance. In order to quantify the methods' accuracy, we examine the algorithms against artificial mathematical test signals and model-generated mRNA data. Our re-implementation of each method in Java allows meaningful comparisons of the computational complexity and computing time associated with each algorithm. Finally, we provide guidelines on which algorithms are most appropriate for which data types, and recommendations on experimental design to extract optimal data for analysis.

PURPOSE: Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS: Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION: Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Object. This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma.Methods. This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy.Conclusions. The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

After a detailed assessment of the College's rapid response and service review mechanism, the professional standards and regulation division has upgraded the service and renamed it the 'invited review mechanism' (IRM). Here we examine the process of the review and the new arrangements in place to support surgeons and hospitals in providing high quality surgical services.

Background: Treatment with trastuzumab prolongs overall survival when given to patients (pts) with Her2/neu+ breast cancer (BC). The primary toxicity of trastuzumab is cardiotoxicity and the incidence is estimated at 2-4% in the adjuvant setting. The mechanism for trastuzumab-induced cardiotoxicity is not known. Although Her2neu expression is usually not seen on cardiac myocytes, its expression has been shown to be upregulated after chemotherapy. Trastuzumab is a monoclonal antibody that binds to the extracellular domain of Her2/neu. We hypothesized that single nucleotide polymorphisms (SNPs) in the Her2/neu receptor may play a role in trastuzumab associated cardiotoxicity. Methods: 140 pts with BC who were treated with chemotherapy and trastuzumab were enrolled into an IRB approved protocol at the Weill Cornell Medical College between July 2008 and March 2013. Cardiotoxicity was defined as either symptomatic CHF, or a decline in LVEF of 15% (or if LVEF Results: 140 subjects (29 with cardiotoxicity and 111 without) had 11 SNPs sequenced. Median age of subjects was 56 years (range: 32-85), mean baseline LVEF was 65% (±6%). 16.4% of subjects had hypertension (HTN). 80% of patients were Caucasian, 10% East Asian, 7.1% African American, 2.9% South Asian. There were two SNPs for which there was variation seen among subjects: rs 1136201 (corresponding to codon 655) and rs61552325 (codon 1170). The frequencies of the codon 655 polymorphisms were: AA (Ile/Ile) 67.9%, AG (Ile/Val) 29.3%, and GG (Val/Val) 2.9%. The frequencies of the codon 1170 polymorphisms were: CC (Pro/Pro) 20.7%, GC (Ala/Pro) 45.7%, and GG (Ala/Ala) 33.6%. There was no association observed between the codon 655 polymorphism and cardiotoxicity (p = 0.96). A significant association between cardiotoxicity and the codon 1170 polymorphism was observed, with subjects having cardiotoxicity being more likely to carry the CC allele compared with subjects without cardiotoxicity (34.5% vs 17.1%, p = 0.04). This association persisted after multivariable adjustment for age, race, and HTN status (adjusted OR = 2.60, 95% CI = 1.02-6.62, p = 0.046). Conclusion: In this study, the Her2/neu 1170 Pro/Pro polymorphism was associated with trastuzumab cardiotoxicity. If confirmed in a larger series, this polymorphism could be used to identify pts who may be at increased risk for cardiotoxicity and who may benefit from treatments associated with less cardiotoxicity. Furthermore, the Her2/neu 1170 SNP has previously been implicated as a minor histocompatibility antigen, and our findings raise the possibility that immune mediated mechanisms may play a role in trastuzumab related cardiotoxicity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-06.

e20641 Background: Chemotherapy induced alopecia (CIA) is a distressing adverse effect of many chemotherapy agents. The TC chemotherapy regimen (four cycles of docetaxel 75mg/m2 and cyclophosphamide 600mg/m2 given every 3 weeks apart) commonly used for aduvant therapy of breast cancer is associated with complete alopecia, with rare reports of permanent alopecia. Scalp cryotherapy has been reported to minimize or prevent CIA. Penguin cold caps are a commercially available scalp cooling product gaining increasing media attention. We conducted a prospective study aimed to assess efficacy of scalp cryotherpy in preventing CIA among women receiving adjuvant TC chemotherapy for early stage breast cancer who independently elected to use Penguin cold caps. Methods: Women at the Weill Cornell Breast Center who elected to use scalp cryotherapy with Penguin cold caps during adjuvant TC chemotherapy were asked to participate in the study. Degree of hair loss was rated by practitioner assessment using Dean’s alopecia scale (poor (>75% hair loss), moderate (50-75%), good (25-50%) or excellent (

When I was working as a neurosurgical registrar, one of my consultants used to describe me as “the vanguard of the monstrous regiment of women that will take over the world”. So, what happened to the “monstrous regiment”? The number of female consultant surgeons has increased over the past few years, but in the context of an increase in the total number of consultant surgeons, the percentage increase is still small. Currently, around 6.5% of consultant surgeons are female. The number of women entering medical school has increased dramatically and the proportion of female medical graduates is now 65%. If all the consultant surgeons of the future are chosen from the remaining 35%, the individuals selected may not necessarily be the ones with the greatest aptitude for the job.

Background: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. Tetrathiomolybdate (TM), a copper-depleting compound inhibits angiogenesis and maintains tumor dormancy. This study explores the effect of TM on EPCs in patients (pts) at high risk for breast cancer (BC) recurrence. Methods: This phase II study enrolled Stage 3, 4 without evidence of disease (NED), and any node-positive triple negative (TN) BC pts. Only concomitant hormonal therapy was allowed. Pts received induction TM 180 mg daily at baseline (with exception of one pt) followed by an equal or lower daily dose (median 100mg, range 0-140) to maintain ceruloplasmin (Cp) level < 17 mg/dl (target for copper depletion). We monitored EPCs (CD45dim/CD133+/VEGFR2+), Cp, CEA and CA15-3 at baseline and monthly. To assess the association between Cp and EPCs over time, 3 independent mixed effects linear models with subject as a random effect were used to account for the correlation between observations on the same subject. All p-values were two-sided with statistical significance evaluated at the 0.10 alpha level. Results: 40 pts (28 adjuvant, 12 Stage 4 NED, 11 TN) were enrolled and 426 cycles of TM (average 10.65 per pt) were administered in the first 12 months on study. Median age was 50 yrs (29-66). Median number of tumor size and positive lymph nodes among adjuvant pts were 3.5 cm (1.2-7) and 9 (0-42), respectively. Of the patients receiving hormone therapy, 10 patients were on tamoxifen and 15 patients were on an aromatase inhibitor. 20% of patients were receiving a proton pump inhibitor (PPI). Median baseline Cp level was 28 mg/dL (20-47). 75% pts adequately copper depleted at month 1. 91% of TN patients copper depleted compared to hormone receptor positive subtypes (38-43%) and HER2/neu positive subtypes (40-67%). EPCs/ml decreased from baseline to last dose by 12 in pts that were copper-depleted (p=0.10) and by −52 in pts that did not achieve the copper depletion target (p=0.95). Multivariable modeling revealed an association of EPCs with Cp over time (p=0.005), with type of hormone therapy administered (p=0.007), and with co-administration of a PPI (p=0.0008). Six pts relapsed while on study in which a 200-fold increase in EPCs preceded an objective clinical relapse and a tumor marker rise by median of 1 month. Only grade 3/4 toxicity was hematologic, occurred in 20 cycles (4.7%) and resolved in 5-13 days with TM held and resumed at lower dose. Conclusions: TM is a well-tolerated oral copper chelator that may contribute to maintaining EPCs below baseline in copper-depleted pts. PPI may facilitate TM absorption. Molecular subtype and hormone therapy may impact on the ability to copper deplete. EPCs may have potential as a surrogate marker for early relapse and as a therapeutic target for interrupting the metastatic progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2699. doi:1538-7445.AM2012-2699

6027 Background: Routine use of treatment plans and summaries has been recommended as an important step in improving the quality of cancer care. However, limited data exist about their impact on qu...

1054 Background: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. Tetrathiomolybdate (TM), an oral copper-depleting compound, inhibits angiogenesis and maintains tumor dormancy. This study explores the effect of TM on EPCs in patients (pts) at high risk for breast cancer recurrence. Methods: This phase II study enrolled pts with stage III, stage IV without evidence of disease (NED) breast cancer, and stage II if triple negative (TN). Only concomitant hormone therapy was allowed. Pts received induction TM 180 mg daily followed by 100 mg daily to maintain ceruloplasmin (Cp) level < 17 mg/dL (target for copper depletion). TM was continued for 24 months (mo), or until relapse or toxicity, with an extension study for additional 24 mo in selected pts. We monitored EPCs (CD45dim/CD133+), Cp, CEA and CA15-3 at baseline (BL) and monthly. EPCs were quantitated from peripheral blood mononuclear cells by flow cytometry. Median BL EPCs was compared to subsequent time poi...

Background: BC can relapse years after initial diagnosis. In animal models, bone marrow (BM)-derived VEGFR1+ cells define the premetatastic niche and VEGFR2+ cells are critical for the transition from micro- to macrometastatic disease. We sought to define the temporal relationship of these circulating hemangiogenic progenitor cells in a cohort of BC patients (pts) that developed recurrent disease and whether quantitative changes in these cells could predict response to therapy in pts with established metastases. Methods: 125 pts with Stages I to IV BC enrolled in 2 studies. In Study #1 circulating VEGFR1+ (CD45+/CD34+/VEGFR1+) hematopoietic progenitor cells (HPCs) and VEGFR2+ (CD45dim/CD133+/ VEGFR2+) endothelial progenitor cells (EPCs) of adjuvant patients were assessed at baseline (BL), every 3 months (mo) for the first year, then every 6 mo. Stage IV pts had levels measured at BL (defined as when initiating new treatment (tx)), with subsequent 1 mo interval blood draws and accompanied by a clinical evaluation. Tx could include chemo-, hormone or biologic therapy. In Study #2, these cells were examined monthly in pts without overt evidence of BC. HPCs/EPCs were quantified from peripheral blood mononuclear cells using flow cytometry with commercially available antibodies. Statistical analysis is by Wilcoxon signed-rank test. Results: Data from both studies were combined to analyze 1) pts without overt BC who relapse and 2) stage IV pts according to response. Seven pts without evidence of BC based on physical exam, labs, and imaging developed recurrence while on study. In all 7 pts, there was a median (med) increase of 1,111% in HPCs preceding overt relapse (range 283% to 5800%). Med HPCs at BL 0.65/ul (range 0.02 to 1.22/ul) increased to 2.90/ul prior to relapse (range 1.18 to 34.94/ul), p=0.016. In 5 of 7 relapsed pts a 433% increase in EPCs occurred as HPCs decreased: med EPCs at BL 0.03/ul (range 0.015 to 0.21/ul) and at relapse 0.16/ul (range 0.03 to 0.27/ul). This pattern was not seen in non-relapsed pts. In 22 stage IV pts, HPCs and EPCs were evaluated over the course of 40 tx. For the 20 tx (16 pts) in which progression of disease (POD) was the outcome, HPCs increased prior to POD (median 7.45/ul, range 0.37 to 77.6/ul) from BL (med 1.70/ul, range 0.01 to 16.47/ul), p=0.001. Similarly, EPCs increased at relapse (med 0.07/ul, range 0 to 0.62/ul) from BL (med 0.03/ul, range 0 to 0.21/ul), p=0.04. For the 12 tx (11 pts) with disease responding to systemic tx, there was a reduction in HPCs (BL med 6.15/ul, range 0.91 to 85.1/ul) to a 3 mo time point (med 0.63/ul, range 0.05 to 18.1/ul), p=0.05. A trend was noted in med EPCs (0.05/ul at BL to 0.02/ul at 3 mo), p=0.37. There was no change in HPCs/EPCs in 8 tx (6 pts) with stable disease. Conclusion: BM-derived progenitor cells are important in the metastatic cascade and may represent a novel biomarker in following disease status and a new target for therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4720. doi:10.1158/1538-7445.AM2011-4720

Analyses the state of the management consultancy industry in Britain, from both a supply and a demand perspective. Aims to help potential clients evaluate and select consultants; to keep academics in business‐related subjects abreast of developments in the field; and to identify growth areas into which consultants might elect to move. Outlines available consulting specialisms, identifies key players in each, and profiles a typical management consultant.

Background: EPCs are critical to tumor angiogenesis, are increased in BC patients (pts) and are probably an early marker for paclitaxel response. Copper is required for angiogenesis, and pre-clinical data suggest that TM, a copper-depleting compound, inhibits angiogenesis and maintains tumor dormancy. We sought to measure the effect of TM on circulating endothelial progenitor cells (EPCs) in pts at high risk of BC recurrence and to evaluate the effect of copper depletion on EPCs. Methods: This analysis is part of an ongoing phase II study of TM in BC pts at high risk of recurrence defined as any node positive triple negative (TN) BC, Stage III or IV with no evidence of disease (NED). All therapy other than hormonal was completed at least 6 weeks prior to study. Treatment: TM 180 mg daily to achieve a target ceruloplasmin (Cp) level of 5-15 mg/dL (copper depletion), and then 100 mg daily. We monitored levels of EPCs (CD45dim, CD133+, VEGFR2+), CEA, CA15-3, and Cp at baseline and monthly. Imaging studies are done every 6 months (mos). Results: 28 pts are enrolled and 304 cycles of TM have been administered. Adjuvant: 20 pts, Stage 4 NED: 8 pts, Triple negative: 8 pts (5 stage IV NED, 3 Adjuvant) The median age is 51 years (range: 29-64), median number of positive lymph nodes among Stage III patients is 7 (4-42). The median baseline Cp level was 28 mg/dL (21-43). Among 21 patients who have reached target Cp, the median time to target is 6 weeks (2-16 weeks). Two pts discontinued treatment before reaching target. The median baseline EPCs is 17.38 cells/ml (0.0-286.1) Although there was a trend toward increased EPCs at month 1, this was not statistically significant (p=0.8964) and the majority of pts EPCs were maintained below baseline over time when Cp levels were below target (ie. copper depleted). Toxicity: Grade 3/4 neutropenia occurred in 3 patients (0.02%) with 1 pt with febrile neutropenia. All resolved 5-13 days later with TM held and resumed at a lower dose in 2 patients. No other grade 3/4 toxicity was observed. Three patients were diagnosed with recurrent breast cancer at 1, 9 and 10 mos. An EPC rise preceded an abnormal marker or overt relapse by 3-5 months in 2 of 3 pts. Conclusions: TM is well tolerated in breast cancer patients. TM might contribute to maintaining EPCs below baseline in pts who are copper depleted. We postulate that the increased EPCs noted in both patients with recurrent disease 2-4 months prior to overt relapse could represent the turning on of an angiogenic switch, resulting in an outpouring of CEPCs to the new site of metastasis. Other studies geared toward understanding the mechanism for metastases are underway. The trial continues to accrue.Supported by the Susan B Komen for the Cure, NY Community Trust, Breast Cancer Alliance of Greenwich and the Madeline and Stephen Anbinder Foundation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6090.

A reduction in waiting lists for in‐patient oral surgery together with an improved service for minor procedures by the use of a day‐bed facility is the proposed solution to the problem studied. The approach used relies on adopting a production/operations management (POM) viewpoint combined with an interfacing methodology based on that of the soft systems school.