tbuckley/cabot-search huggingface dataset:
Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections.
Authors: E P Fox, T D Weathers, S D Williams, P J Loehrer, T M Ulbright, J P Donohue, L H Einhorn
Journal: Journal of Clinical Oncology (1993)

PURPOSE We review the long-term outcome of patients with viable nonteratomatous germ cell tumor (NTGCT) in retroperitoneal lymph node dissection (RPLND) specimens after primary or salvage chemotherapy, and the impact of postoperative therapy with two courses of standard-dose cisplatin-based induction chemotherapy. PATIENTS AND METHODS All patients with viable NTGCT in postchemotherapy RPLND specimens from surgeries performed at Indiana University between July 1975 and March 1991 were retrospectively reviewed. RESULTS Of 580 postchemotherapy RPLNDs performed, 133 had viable NTGCT in their pathology specimens. Of these 580 postchemotherapy RPLNDs, 417 were performed after primary chemotherapy, and 43 (10%) had viable NTGCT in their pathology specimens. There were 163 RPLNDs performed after salvage chemotherapy and 90 (55%) had viable NTGCT in their pathology specimens. After primary chemotherapy, 34 of 43 had complete resections, and 27 of the 34 received postoperative cisplatin-based chemotherapy. Nineteen of 27 (70%) are continuously disease-free (c-NED). All seven who received no postoperative chemotherapy have relapsed. After salvage chemotherapy, 53 of 90 had complete resections. Of those 53, 25 received postoperative chemotherapy, and nine (36%) are c-NED. Twenty-eight received no postoperative chemotherapy, and 12 (43%) are c-NED. Overall, 43 of 133 patients had incomplete resections, and only four are currently disease-free. There were four postoperative deaths (PODs). CONCLUSION (1) Incomplete resection of viable NTGCT after primary or salvage chemotherapy portends a very poor prognosis. (2) For patients with complete resection of viable NTGCT following primary chemotherapy, two additional courses of cisplatin-based chemotherapy appear to be safe and effective therapy for reducing the risk of relapse. (3) Additional standard-dose chemotherapy appears to offer no benefit to patients with viable NTGCT in the resected specimen after salvage chemotherapy.
Subtypes of self-injurious patients with borderline personality disorder
Authors: M J Russ, E N Shearin, J F Clarkin, K Harrison, J W Hull
Journal: American Journal of Psychiatry (1993)

Twenty-seven female inpatients with borderline personality disorder were assigned to two groups on the basis of whether they did (N = 14) or did not (N = 13) report experiencing pain during self-injurious episodes. Ratings of depression, anxiety, impulsiveness, dissociation, and trauma symptoms were higher in the women who did not experience pain while injuring themselves, as were the number of suicide attempts and the prevalence of childhood sexual abuse.
ELK4 neutralization sensitizes high-grade glioma to apoptosis through downregulation of the antiapoptotic protein Mcl-1
Authors: Brett W Stringer, Bryan W Day, Mark D Spanevello, Brent A Reynolds, Jacinta C Carter, Joanne M Cox, Vicky J Ellis, Christopher L Brown, David G Walker, Jason D Lickliter, Andrew W Boyd
Journal: Neuro-Oncology (2009)

Purpose: Bcl-2 family antiapoptotic proteins are elevated in many  human malignancies and are attractive therapeutic targets. The purpose  of this study was to measure antiapoptotic Bcl-2 family expression in highgrade  glioma to investigate potential targets for molecular therapy. Methods:  Gene expression was investigated by QPCR and Western blot in 37  primary high-grade glioma surgical specimens and 12 GBM cell lines. Targeted  reduction of gene expression was performed in GBM cell lines using  transfected siRNAs or plasmid-based shRNAs. Increased gene expression  was achieved using plasmid-based cDNAs. Spontaneous, ABT-737 or  cisplatin-induced apoptosis was measured by FACS analysis of annexin  V-stained cells. Gene promoter function was analyzed by luciferase  reporter assay. Results: We found Mcl-1 to be the highest expressed antiapoptotic  Bcl-2 family member in the majority of malignant gliomas. This  was functionally important as neutralization of Mcl-1 induced apoptosis  and increased sensitivity to the BH3 mimetic ABT-737 or cisplatin treatment  in GBM cells. Sequencing of the Mcl-1 promoter identified a novel  functional single nucleotide polymorphism (SNP) in a previously uncharacterized  consensus ETS transcription factor binding site. We identified  the ETS domain transcription factor ELK4 as a key regulator of Mcl-1 in  glioma, since ELK4 downregulation was shown to reduce Mcl-1 expression.  Importantly the presence of the SNP, which ablated ELK4 binding,  while uncommon in gliomas, was associated with low Mcl-1 levels and  greater susceptibility to apoptosis following chemotherapy treatment. Furthermore,  downregulation of ELK4 by siRNA, resulting in loss of Mcl-1  expression, increased sensitivity to ABT-737 and cisplatin treatment. Conversely,  ELK4 overexpression increased Mcl-1 levels and this was shown  to be protective against higher concentrations of the chemotherapy agent  cisplatin. Conclusions: These findings demonstrate ELK4 to be a critical  regulator of Mcl-1 expression in GBM and highlight both ELK4 and Mcl-1  as molecular therapeutic targets in high-grade glioma.
Corticosteroid Replacement Therapy: Twice Or Thrice Daily?
Authors: R W Groves, G C Toms, B J Houghton, J P Monson
Journal: Journal of the Royal Society of Medicine (1988)

Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma Cortisol by mid-afternoon. This study compared plasma Cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of Cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of ‘well-being’ by visual analogue scale correlated significantly with simultaneous plasma Cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.
Diagnostic value of the bronchoscopy in the focal pulmonary malignant lesions
Authors: Rocio Magdalena Diaz Campos, Ricardo Garcia Lujan, Rodrigo Alonso Moralejo, Eduardo De Miguel Poch
Journal: European Respiratory Journal (2011)

Introduction:  A focal pulmonary lesion (FPL) is defined as an intra-parenchymatous pulmonary lesion that is well circumscribed and completely surrounded by healthy lung.   Objective:  To analyze the diagnostic value of the fiberoptic bronchoscopy (FB) in the malignant FPL in the last 18 months, concurring with a change in the medical staff.   Material and methods:  Cross-sectional study of all the FBs done at our Unit between 02/2008 and 08/2009 in patients with a solitary FPL with a definitive diagnosis of malignancy. The diagnostic value by size and site was analyzed with Pearson9s chi 2  statistics.   Results:  We studied 131 patients of whom 107 (82%) were men. The area around the pulmonary hilum was divided in 3 elliptic areas; considering a central lesion when it was localized in the most internal ellipse and a peripheral lesion when it was localized in the 2 external ellipses. In 24 cases, the size of the FPL was not possible to be determined (23 central and 1 peripheral). The media size of the FPL was 4.8cm (SD 2.7cm). The diagnostic value of the FB in FPL was 0.73.  The diagnostic value of the TBB with radioscopic guide, according to the size and site is showed in the table (in 7 cases, the size was not determined).   Conclusion:  The diagnostic value of the FB was 0.73 and of the TBB with radioscopic guide was 0.53, being a difference by size but not by site.
Fenretinide Therapy in Prostate Cancer: Effects on Tissue and Serum Retinoid Concentration
Authors: Christina Thaller, Moshe Shalev, Anna Frolov, Gregor Eichele, Timothy C. Thompson, Russel H. Williams, Ozdal Dillioglugil, Dov Kadmon
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To examine the feasibility of using fenretinide (4-HPR) for the prevention and treatment of prostate cancer. MATERIALS AND METHODS: We measured the impact of 4-HPR therapy on retinoid concentrations in vivo, in a mouse model of prostate cancer and clinically, in patients with prostate cancer who were given oral 4-HPR (200 mg/d) or placebo for 4 weeks before undergoing a radical prostatectomy. RESULTS: Prostate tumors in mice treated with 4-HPR contained high levels of 4-HPR and of all-trans-retinoic acid (RA) and reduced levels of retinol (ROH). Patients given 4-HPR were found to have significantly higher concentrations of 4-HPR in the cancerous prostate as compared with the serum levels (463 nmol/L v 326 nmol/L; P = .049), but they were only 1/10 the levels found in mice and were far below the concentrations reported in human breast tissue. Serum and tissue ROH levels were reduced to less than half the concentrations found in untreated controls. RA concentrations in human serum and in cancerous prostates were not significantly affected by 4-HPR treatment, in contrast with the findings in mice. CONCLUSION: The standard oral dose of 4-HPR proposed for breast cancer (200 mg/d) achieved only modest drug levels in the prostate and is unlikely to be effective for prostate cancer prevention or treatment. Higher doses need to be explored.
Immunomodulatory function of chemerin and its receptor ChemR23 in the physiopathology of viral pneumonia and acute lung injury
Authors: Benjamin Bondue, Olivier Vosters, Patricia De Nadai, Stephanie Glineur, Olivier De Henau, Souphalone Luangsay, Frederic Van Gool, Daniel Desmecht, Paul De Vuyst, Marc Parmentier
Journal: European Respiratory Journal (2011)

Chemerin, the natural ligand of the ChemR23 receptor, acts as a chemoattractant agent for macrophages, immature dendritic cells, and NK cells. In this study, we investigated the role of the chemerin/ChemR23 system in the physiopathology of inflammatory lung diseases using wild type (WT) and knock-out mice for the receptor (ChemR23 -/- ). Whereas no differences are observed in models of lung fibrosis and asthma, ChemR23 -/-  mice present higher mortality and morbidity in a model of viral pneumonia induced by the pneumonia virus of mice (PVM). ChemR23 -/-  mice display delayed viral clearance, and impaired acquired immunity contrasting with an excessive innate response and recruitment of neutrophils. Lower recruitment of type I interferon-producing plasmacytoid dendritic cells (pDCs) may explain the delayed acquired response and viral clearance in ChemR23 -/-  mice. However, the stronger inflammation observed in these mice is not due to defective pDC recruitment but rather to the loss of an anti-inflammatory role of chemerin on non-leukocytic cells. Indeed, experiments involving adoptive transfer of pDCs and bone marrow transplantation exclude the role of ChemR23-expressing pDCs and more generally leukocytes in the protection against excessive inflammation. Moreover, a strong anti-inflammatory role of chemerin is observed in a model of acute lung injury induced by instillation of lipopolyssacharide (LPS), which is strictly dependent of ChemR23. Altogether, our data suggest a role of the chemerin/ChemR23 system in the modulation of innate immunity and this is likely mediated by non-leukocytic cells, such as lung endothelial or epithelial cells.
Abstract 1694: Combination of Indolizino[6,7-b]indole and Gefitinib synergistically suppresses the growth of EGFR-mutant NSCLC cells
Authors: Chi-Wei Chen, Satishkumar Tala, Tsann-Long Su, Te-Chang Lee
Journal: Cancer Research (2014)

Abstract We have previously revealed that indolizino[6,7-b]indoles are effective antitumor agents against a variety of cancer cells. Indolizino[6,7-b]indoles were shown to induce DNA crosslinks and inhibit the enzymatic activities of topoisomerase I and II. Our recent results demonstrated that the derivatives of indolizino[6,7-b]indoles potently suppressed the cell growth of several non-small cell lung cancer (NSCLC) cells, including H460, PC9, PC9/gef B4, and H1975 cells in in vitro and in vivo systems. We also showed that BO-1978, one of indolizino[6,7-b]indole derivatives, completely suppressed the growth of CL1-5/GFP-Luciferase and PC9/gef B4-Luciferase cells in orthotopic lung cancer models. These results implicated that indolizino[6,7-b]indoles are potential candidate agents against NSCLC. EGFR mutations are frequently occurred in NSCLC. Although targeted agents such as Gefitinib is effectively suppression the growth of NSCLC with EGFR mutations, the resistance to Gefitinib is quickly developed and causes the failure of targeted treatments. Since the combination of targeted agents and cytotoxic drugs is one of strategies to overcome the problem encountered by targeted therapy, we further explore the therapeutic potential of combination of BO-1978 and Gefitinib against EGFR-mutant NSCLC. Our results showed that the combination treatment of PC9 and PC9/gef B4 cells with BO-1978 and Gefitinib resulted in synergistic induction of apoptosis and suppression of cell growth in cultured cells. We also confirmed the therapeutic efficacy of combined treatment of PC9 and PC9/gef B4 cells with BO-1978 and Gefitinib in xenografted tumor models. Since we did not observe severe body weight loss in mice received the combination treatment of BO-1978 and Gefitinib, our present studies apparently support that BO-1978 and its combination with Gefitinib is highly prospective as therapeutic agents against EGFR-mutant NSCLC. Citation Format: Chi-Wei Chen, Satishkumar Tala, Tsann-Long Su, Te-Chang Lee. Combination of Indolizino[6,7-b]indole and Gefitinib synergistically suppresses the growth of EGFR-mutant NSCLC cells. [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 1694. doi:10.1158/1538-7445.AM2014-1694
Skeletal muscle oxygen delivery in COPD: The impact of coexistent heart failure
Authors: Flavio Arbex, Mayron Oliveira, Priscila Sperandio, Maria Clara Alencar, Luiz Medina, Wladimir Medeiros, Luiz Eduardo Nery, Denis O'Donnell, J. Alberto Neder
Journal: European Respiratory Journal (2014)

Heart failure with reduced left ventricular ejection fraction (HFrEF) may impair central hemodynamics in patients with COPD with negative consequences for muscle blood flow and exercise tolerance. Sixteen patients with COPD+HFrEF, 16 with COPD, 15 with HFrEF and 12 age-matched healthy men performed a discontinuous cardiopulmonary exercise test in which the highest work rate (80% peak) was sustained to the limit of tolerance (Tlim, s). Changes (Δ) in cardiac output (QT) by trans-thoracic cardioimpedance and in a leg blood flow index (BFI) by the indocyanine green-near infrared spectroscopy method were related to Δ oxygen consumption (VO2). COPD+HFrEF, COPD (by FEV1) and HFrEF (by EF) groups were well-matched.. The former group showed the lowest Tlim; moreover, they had proportionately blunted ΔQT and ΔBFI responses compared to the other groups ( Table ). Significant relationships between ΔQT and ΔBFI with Tlim were found only in COPD+HFrEF (r= 0.72 and r= 0.68, respectively; p<0.05).

Table. Resting characteristics and exercise responses 

![Figure][1] 



Different letters indicate statistically-significant differences

In conclusion, COPD+HFrEF patients had more pronounced impairments in central and intra-muscular hemodynamic responses to exercise than their counterparts with each disease in isolation. This patient sub-population, therefore, might particularly benefit from interventions aimed at increasing convective O2 delivery during exercise.

 [1]: pending:yes
The Changing Pattern of Thoracic Surgery in the United Kingdom 1963–1982
Authors: J A Paraskevopoulos, A J Gunning, A R Dennison
Journal: Journal of the Royal Society of Medicine (1991)

During the period 1963–1982 a total of 11 459 patients with general surgical and thoracic conditions were admitted to the Churchill and John Radcliffe Hospitals in Oxford under the care of a single thoracic surgeon. 55.1% of the admissions were for general surgical conditions whereas 44.9% were for a thoracic disorder. The total period has been studied by dividing it into three subgroups of 7, 6 and 7 years (1963–1969, 1970–1975, 1976–1982). The percentage of thoracic patients treated during the three periods was found to be 48.86%, 41.73% and 50.11% respectively. The three periods studied have been subdivided into major disease groups and the changes in these groups have been studied in detail. During this 20-year period there has been a dramatic change in the makeup of a typical thoracic surgical practice. This is in part due to the changing pattern and prevalence of many of the diseases treated by thoracic surgeons, but is also due to a change in referral patterns, the distribution of patients between thoracic and general surgeons and also the dichotomy emerging between thoracic and cardiac surgeons.
Effects of using a Charnley-Howorth Enclosure in a District General Hospital
Authors: I W L Bintcliffe
Journal: Journal of the Royal Society of Medicine (1983)

A high rate of infection was found to occur when total hip replacements were performed in an operating theatre used by a variety of surgical specialities. Because of this, a downward displacement laminar flow enclosure was installed to provide ultraclean air operating conditions. Retrospective examination of 419 total hip replacements, carried out over a six-year period during which the enclosure was installed, showed a reduction in the infection rate from 3.2% to 0.4% ( P=0.05) when using the enclosure. The infections were associated with a postoperative wound discharge and with revision surgery but were less frequent when the enclosure was used. Prosthetic loosening was found to be common when metal-to-metal prostheses were used. Working in an enclosure with side panels, wearing body exhaust units, was generally considered to be so noisy as to restrict communication.
Strengthening the Supply of Routinely Recommended Vaccines in the United States
Authors: Jeanne M Santoli, Georges Peter, Ann Margaret Arvin, Jeffrey P Davis, Michael D Decker, Patricia Fast, Fernando A Guerra, Charles M Helms, Alan Richard Hinman, Ruth Katz, Jerome O Klein, Mary Beth Koslap-Petraco, Peter R Paradiso, William Schaffner, Patricia N Whitley-Williams, Donald E Williamson, Bruce Gellin
Journal: JAMA (2003)

Between late 2000 and the spring of 2003, the United States experienced shortages of vaccines against 8 of 11 preventable diseases in children. In response, the Department of Health and Human Services requested that the National Vaccine Advisory Committee (NVAC) make recommendations on strengthening the supply of routinely recommended vaccines. The NVAC appointed a Working Group to identify potential causes of vaccine supply shortages, develop strategies to alleviate or prevent shortages, and enlist stakeholders to consider the applicability and feasibility of these strategies. The NVAC concluded that supply disruptions are likely to continue to occur. Strategies to be implemented in the immediate future include expansion of vaccine stockpiles, increased support for regulatory agencies, maintenance and strengthening of liability protections, improved communication among stakeholders, increased availability of public information, and a campaign to emphasize the benefits of vaccination. Strategies requiring further study include evaluation of appropriate financial incentives to manufacturers and streamlining the regulatory process without compromising safety or efficacy.
Predictors of Treatment (Tx) Response and Progression in Braf V600E Metastatic Melanoma (Mm) Patients (Pts) with Brain Metastases (Bm) Receiving Vemurafenib (Vem) in a Real-World Setting
Authors: G. Gibney, G. Gauthier, C. Ayas, P. Galebach, E. Wu, Y.M. Yim, S.S. Abhyankar, C. Reyes, A. Guerin
Journal: Annals of Oncology (2014)
Impact of a nurse practitioner-staffed, symptom-management clinic on emergency department utilization in a large community oncology cancer institute.
Authors: Shanthi Sivendran, Rachel Holliday, Kristen De la Torre, Kristina Braine Newport
Journal: Journal of Clinical Oncology (2014)

58 Background: Emergency department (ED) utilization among oncology patients is a source of patient distress as well as a financial burden to the health care system. Effective outpatient symptom management can potentially reduce ED utilization. In this analysis, we review ED utilization prior to and post the institution of a nurse practitioner staffed symptom management clinic in a large community oncology practice. Methods: In April 2014 a symptom management clinic staffed by a nurse practitioner five days a week was established at our outpatient cancer institute to increase patient access to acute symptom management. ED utilization 6 months prior to and post starting this clinic was measured. Only patients who received chemotherapy within 30 days of an ED visit were included in this analysis. Results: Between October 2013 and September 2014, a total of 420 visits to the ED were documented. A total of 196 visits occurred in the 6 months prior to establishing the clinic. There was an increase in visits to 224 after instituting the clinic. The median number of monthly visits was 34.5 (range 24-38) prior to the clinic and increased to 38 (range 30-43) after establishing the clinic. Conclusions: In our practice, a nurse practitioner led symptom management clinic did not reduce ED utilization in patients receiving chemotherapy. Based on published studies, other factors may need to be incorporated into our cancer institute to effectively reduce ED utilization. These include standardizing symptom assessment and management, patient and caregiver education on how to effectively manage symptoms at home, and improved coordination with supportive services.
Woman asks court for right to use dead daughter's eggs to produce grandchild
Authors: C. Dyer
Journal: BMJ (2015)

A 59 year old woman has launched a High Court action against the UK’s regulator of infertility treatment for the right to try to become pregnant with her own grandchild by using her dead daughter’s frozen eggs.

The woman, referred to in court as “Mrs M,” wants to take the eggs to New York, where a clinic has agreed to …