tbuckley/cabot-search huggingface dataset:
S2 The impact of continuous positive airway pressure (CPAP) therapy on cognitive function in older people with sleep disordered breathing (SDB) and co morbidity
Authors: A McMillan, L Paniccia, M Glasser, P Edison, AK Simonds, MJ Morrell
Journal: Thorax (2013)

<h3></h3> The impact of SDB on cognitive function is debatable, with sleepiness and intermittent hypoxia being implicated as potential mechanisms. The purpose of this study was to investigate the relationship between cognitive function and brain structure in older patients with SDB, who may be more vulnerable to cognitive decline, and in whom SDB is more common. A randomised controlled trial was carried out to determine if CPAP therapy could reverse any changes in cognitive function and brain structure. <h3>Methods</h3> Older patients ≥65 years, with SDB [≥4% Oxygenation Desaturation Index (ODI) &gt;7.5 events/hour] were randomised to CPAP therapy or Best Supportive Care (BSC) for 6 months. Cognitive function was assessed at baseline and after 6 months, using a battery of 8 cognitive tests designed to examine attention, executive function and memory. MR brain scans were also completed however analysis is on-going. <h3>Results</h3> The CPAP (n = 17) and BSC (n = 17) groups were well matched for age [mean (SD)] 70.8(4.1) vs. 70.8(3.3) years; BMI: 30.1(6.0) vs. 31.4(3.8) Kg/m<sup>2</sup>; Epworth sleepiness score (ESS): 9.4(4.3) vs. 9.4(4.8) and number of additional co morbidities/patient 2(1) vs. 2(1). ODI was higher in the CPAP group [35(22) vs. 19(15) events/hour p = 0.01]. Baseline cognitive function was similar between groups for all tests. At 6 months the CPAP group had improvements in both of the attention and executive function compared to the BSC group [Trail Making B: 94(56) vs. 83(45) seconds, p = 0.047; STROOP: 33(10) vs. 29(11) correct responses p = 0.03]. Other measures of cognitive function were not statistically improved following 6 months of CPAP therapy. Subjective sleepiness did not improve significantly between groups [Change in ESS: CPAP -2.1(0.8) vs. BSC -0.7(0.7) p = 0.261]; however the ODI was significantly reduced with CPAP: 20(18.3) vs. BSC 3(10.7) events/hour p &lt; 0.01. The mean (SD) daily CPAP usage was: 3.4(2.2) hours. <h3>Conclusion</h3> 6 months of CPAP therapy improved the ODI, attention and executive function but not subjective sleepiness or memory in this small group of older patients with SDB. We speculate the improvements in attention and executive function were due to a reduction in intermittent hypoxia. This may be reflected in changes in brain structure.
S131 Iron chelation reduces lung cancer proliferation in vitro
Authors: J Kay, G McNab, P Newby, M Bedford, A Turner
Journal: Thorax (2013)

<h3>Introduction</h3> There is growing evidence that iron plays an important role within the lung cancer, the leading cause of cancer-related mortality worldwide. As a result of this, iron homeostasis has potential as a new avenue for targeting and treatment of lung cancer. In this study, the effect of iron loading on cellular proliferation and iron homeostasis gene expression was investigated. In addition, the effect of the chelator deferasirox on cellular iron levels and proliferation rates was studied. <h3>Methods</h3> Cellular proliferation was assessed by the BrdU assay and cellular iron levels were assessed using the ferrozine assay. Manipulation of <i>IREB2</i> gene expression was achieved using short interfering RNA (siRNA) and subsequent expression of this and other iron homeostasis genes was assessed using real time PCR. All experiments were carried out on both the A549 adenocarcinoma and QG56 squamous cell carcinoma cell lines in triplicate. Primary bronchial epithelia cells (PBEC) were used as reference of normal behaviour. <h3>Results</h3> A dose of 150uM of iron was seen to cause a significant increase in proliferation in both the A549 (50% increase) and QG56 (40% increase) cell lines (P = 0.002 and 0.03 respectively) whilst no change was seen in the PBECs. A corresponding increase in cellular iron was also seen.When the cancer cell lines were treated with deferasirox, cellular iron loading decreased by roughly 25% in each cell line (P = 0.001 and 0.01 respectively) and cellular proliferation decreased below levels seen in unstimulated cells. Deferasirox was also seen to effect unstimulated cancer cells, reducing their proliferation by 50% (P = 0.02 and 0.03 respectively). <h3>Conclusion</h3> Iron exposure was shown to have a significant effect on cellular proliferation within lung cancer cell lines, although the underlying mechanism is not yet fully understood. This iron mediated cellular proliferation could be reversed using the chelator deferasirox. Down-regulated expression of <i>IREB2</i> may cause the cancer cell lines to exhibit similar behaviour to the PBECs when stimulated with iron. These finding show that iron may provide a potential new target and deferasirox a potential new therapeutic agent for lung cancer.
Tc-99m MIBI Thoracic SPECT for the Detection of Intrathoracic Tumor Masses
Authors: WEI-JEN SHIH, AMITA RASTOGI, VICKI STIPP, KELLY K. GROSS, JOHN J. COUPAL, SYLVIA MAGOUN
Journal: Clinical Nuclear Medicine (1998)

Thirty-one men (age range, 46-76 years; mean age, 64.8 years) with intrathoracic masses suggesting possible malignancy on the basis of chest radiography or CT underwent preoperative Tc-99m MIBI SPECT examinations. Diagnosis was confirmed on pathologic examinations of samples obtained either at thoracotomy, esophagectomy, or by biopsy. Twenty-five patients had primary lung cancer, including squamous cell carcinoma, large cell carcinoma, adenocarcinoma, and small cell carcinoma. Two patients had lymphomas with spread to the mediastinum, and three patients had extrathoracic primary cancers (one squamous cell carcinoma of esophagus, one squamous cell carcinoma originating from a head and neck tumor, and one metastatic mediastinal leiomyosarcoma). One patient with a tuberculoma had negative results of the Tc-99m MIBI examination. Tc-99m MIBI had a 86.7% sensitivity rate, a 0% false-positive rate, and a 100% positive predictive value to detect malignant intrathoracic masses. There was a 13% false-negative rate, however, suggesting that MIBI-SPECT may underdiagnose malignant lesions. SPECT findings of these 31 patients can be classified as 1) mass with increased uptake, n = 23; 2) ring-like appearance of increased uptake, n = 3; 3) mass with absent uptake, n = 4; and 4) photon-deficient mass, n = 1. Absent uptake in patients with mass lesions could be explained by necrosis of the lesion (caseation necrosis or massive tumor necrosis with or without bleeding). Most malignant intrathoracic masses are Tc-99m MIBI avid and may be detected with a high degree of sensitivity and with an excellent positive predictive value. A positive MIBI scan may help in the clinical diagnosis of malignancy. The use of Tc-99m MIBI could serve not only as a tumor imaging agent, but also may be used to determine the extent of spread and potentially the chemotherapeutic responsiveness of a tumor.
Developing a Referral System for Fertility Preservation Among Patients With Newly Diagnosed Cancer
Authors: Gwendolyn P. Quinn, Susan T. Vadaparampil, Clement K. Gwede, Joyce D. Reinecke, Tina M. Mason, Celso Silva
Journal: Journal of the National Comprehensive Cancer Network (2011)

The goal of this project was to develop a referral system to increase the likelihood that patients of childbearing age with newly diagnosed cancer receive timely information about fertility, and reduce the burden oncologists may feel when discussing and exploring fertility preservation options with their patients. The group developed and examined the effectiveness of a fertility preservation referral system through pilot-testing a developed patient education brochure. During the 12-month pilot-testing period, 776 patients of childbearing age (&lt; 40 years) were seen at H. Lee Moffitt Cancer Center and 349 brochures were taken. The reproductive endocrinologist/infertility clinic experienced a 9-fold increase in the number of calls received during the 12-month study period, with 122 calls received compared with 13 the prior year. The large increase in calls illuminates the gap in patient interest and referral, and shows an effective method to transmit this information. Improving the communication of time-sensitive information about fertility and preservation options to patients with cancer is associated with an increased likelihood of improving quality of life, reducing patient distress, and increasing use of ancillary fertility-related health services. Through referring and providing patient information, this referral system allows oncologists to fulfill their obligation and make informed decisions about fertility preservation, thereby improving the full cancer care continuum.
P04.10 * PREDICTIVE VALUE OF MGMT PROMOTER METHYLATION QUANTITATIVE ASSESSMENT IN GLIOBLASTOMA, WHICH OPTIMAL CUT-POINT?
Authors: T. de Saint-Denis, E. Lerhun, C. Ramirez, P. Devos, C. A. Maurage, F. Dubois, N. Reyns, F. Escande
Journal: Neuro-Oncology (2014)

BACKGROUND: The methylation in the promoter region of the MGMT gene encoding the DNA repair protein O6-methyl guanine-DNA methyl transferase is a predictive marker for benefit from alkylating agent therapy and a prognostic factor in glioblastoma. Pyrosequencing-based assessement of MGMT promoter status is of particularly interest, but analytical methods and cut-points may varied from one center to another. We intend to establish a correlation between quantitative methylation of MGMT promoter values and overall survival (OS) or progression-free survival (PFS). METHODS: The clinical and biological data of 159 newly diagnosed glioblastoma recruited in Lille University Hospital between 2008 and 2011 were retrospectively collected. For the patients, the methylation status has been assessed by pyrosequencing on 5 CpG islands. Statistical analyses were performed using SAS software V9.3. RESULTS: Median age of the patients was 61 years. Sixty three patients were male. Of 159 patients, 156 underwent a surgery (40,4% of complete resection), 3 patients were diagnosed only by biopsies. 123 received concomitant radiotherapy and temozolomide and adjuvant temozolomide. The median PFS and the median OS were 9,9 and 15,9. The most significant cut-off methylation determined on 5 sites mean methylaion value was 12% for both predictive and pronostic evaluations. Site 1 methylation status was the best predictive value for both PFS and OS compared to the other CpG islands. On this site 1, a >3% methylation status was a significant predictive factor for reponse to standard treatment for PFS and a >25% site 1 methylation status was a strong pronostic factor for 2 years survival (OS) (47%). CONCLUSIONS: Even a low MGMT methylation (>3%) status on selected CpG site can already be a predictive factor for response to treatment in glioblastoma and allow us to reduce the cut-off values. Highest methylations status are correlated with the longest overall survival and therefore confirm the pronostic value of MGMT methylation. Establishing correlation between clinical data and biological assessment, such as pyrosequencing providing quantitative values for each CpG, would allow to lower and precise useful cut-points and to chose analysed site for a better predictive and pronostic significativity.
Abstract LB-280: Inhibition of SHP2 in basal-like and triple-negative breast cancer cells induces basal-to-luminal transition, suppresses tumorigenesis, and blocks metastasis.
Authors: Fatimah Matalka, Hua Zhao, Yehenew M. Agazie
Journal: Cancer Research (2013)

Abstract One of the factors that contribute to the disproportionately high mortalities in basal-like and triple-negative breast cancer (BTBC) is the lack of targeted therapies. Identifying and characterizing potential targets is therefore critical for future development of such therapies. In the current report, we show that silencing the expression of the Src homology phosphotyrosyl phosphatase 2 (SHP2) in BTBC cell lines (MDA-MB231 and MDA-MB468) suppresses cell proliferation, reverses transformation, and blocks invasiveness. Unexpectedly, we have discovered that inhibition of SHP2 induces basal-to-luminal transition (BLT) in BTBC cells as evidenced by a decrease in the expression of mesenchymal markers and/or drivers (vimentin, ZEB1, Snail, and alpha smooth muscle actin) and an increase in the expression of the luminal marker cytokeratin 18. Furthermore, we have discovered that inhibition of SHP2 induces the expression of the estrogen receptor alpha in otherwise triple-negative breast cancer cells. Intramammary transplantation studies in the NOD/SCID mice demonstrated that inhibition of SHP2 suppresses tumorigenesis and blocks metastasis. Analyses of total cell lysates prepared from cells grown in 3D matrigel cultures demonstrated that SHP2 mediates the activation of the Ras-ERK, the PI3K, and the β-catenin signaling pathways to promote the tumorigenic, invasive, and metastatic potential of BTBC cells. By and large, the results presented in this report suggest that SHP2 plays an essential role in the biology of BTBC. Citation Format: Fatimah Matalka, Hua Zhao, Yehenew M. Agazie. Inhibition of SHP2 in basal-like and triple-negative breast cancer cells induces basal-to-luminal transition, suppresses tumorigenesis, and blocks metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-280. doi:10.1158/1538-7445.AM2013-LB-280
Private insurance website is forced to drop advertisement
Authors: J. Wise
Journal: BMJ (2013)

A private health insurance comparison website has been forced to take down an advertisement claiming that the NHS in England was responsible for 13 000 needless deaths since 2005.

The Advertising Standards Authority said that the claim made by bestmedicalcover.co.uk was misleading and used an “appeal to fear to sell private health insurance and that it was not justified to do so.”1

The company, which compares private health insurance packages, had a web page headed “Your 3-step guide to avoid the NHS crisis.” In the piece it …
“Shoulder Pad” Sign
Authors: Carlos Geraldo Guerreiro de Moura, Sérgio Pinto de Souza
Journal: New England Journal of Medicine (2004)

This 66-year-old man presented with fatigue, paresthesia of the legs, weight loss, and shoulder enlargement, with limitation of movement. Periorbital ecchymoses (the “raccoon” sign) were present. What's the diagnosis?
The psychiatrist's double bind: the right to refuse medication
Authors: M G Ford
Journal: American Journal of Psychiatry (1980)

The assertion of a patient's right to refuse medication places a psychiatrist in a double bind because he or she knows that medication will often greatly relieve mental disturbance. Delaying medication until the patient is formally judged incompetent and a guardian appointed causes discomfort for the patient, the physician, staff, and other patients. On the other hand, forcing medication on a patient undermines the latter's sense of autonomy and may interfere with his or her constitutional rights, as a federal judge has ruled in the famous Boston State Hospital case. The right to refuse medication presents a uniquely intriguing case study of a need for accommodation between abstract constitutional concepts and practical realities and has opened a profound legal and ethical debate about the nature of "true freedom."
RISK FACTORS FOR INFECTIVE ENDOCARDITIS IN SURGICAL PATIENTS WITH BICUSPID AORTIC VALVE DISEASE
Authors: Dillon Schafer, Alexander Taylor, Adin-Cristian Andrei, Zhi Li, Colleen Clennon, Jota Nakano, Patrick McCarthy, S. Chris Malaisrie, Jyothy Puthumana
Journal: Journal of the American College of Cardiology (2016)
Detection of Achlorhydria by Tubeless Gastric Analysis with Betazole Hydrochloride as the Gastric Stimulant
Authors: Harry L. Segal, James C. Rumbold, Bernard L. Friedman, Michael M. Finigan
Journal: New England Journal of Medicine (1959)

THE fact that orally administered betazole hydrochloride is a potent gastric stimulant in man1 provided the opportunity to investigate the possibility of its superiority to caffeine as the gastric stimulant in the detection of achlorhydria∥ by the tubeless gastric-analysis technic.2 This paper describes the results with betazole hydrochloride administered either orally or subcutaneously as the gastric stimulant in a group of persons previously found achlorhydric by tubeless gastric analysis with caffeine sodium benzoate as the gastric stimulant.MethodIndividuals achlorhydric by the azure A tubeless gastric-analysis technic** with 500 mg. of caffeine sodium benzoate (250 mg. of caffeine base) as . . .
Porphyria Cutanea Tarda and Hypertrichosis
Authors: Roger Kapoor, Richard A Johnson
Journal: New England Journal of Medicine (2013)

A 54-year-old woman with hepatitis C infection presented with excess hair on her face, which she had had since the age of 25 years, and new erosions on her hands. Several ulcerations, milia, and thickened skin were noted on the dorsal aspect of her hands.
CLINICAL TRIALS OF A THIRD-GENERATION RECOMBINANT ONCOLYTIC HSV-1 IN RECURRENT GLIOBLASTOMA AND OLFACTORY NEUROBLASTOMA PATIENTS
Authors: T. Todo, M. Tanaka, M. Ito, H. Ito, Y. Ino
Journal: Neuro-Oncology (2014)

BACKGROUND: Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for cancer. We have developed a triple-mutated, third-generation oncolytic HSV-1, G47Δ, by introducing an additional genetic mutation in the viral genome of G207, a second-generation HSV-1 used in multiple clinical trials for glioblastoma in the US. In preclinical studies, G47Δ exhibited better stimulation of human antitumor immune cells, better growth properties leading to higher virus yields and increased cytopathic effect in vitro, better antitumor efficacy in various mouse cancer models, and preserved safety in HSV-1-sensitive mice compared with G207. METHODS: Clinical-grade G47Δ has been manufactured at the GMP Vector Production Facility at the Institute of Medical Science, the University of Tokyo. The first-in-man clinical trial of G47Δ started in 2009. It is an open-label, single-armed, phase I-IIa study in patients with a single lesion of recurrent glioblastoma. For each patient, G47Δ is administered stereotactically into the tumor, twice within 14 days. RESULTS: So far, the treatment has been well tolerated by patients. Clinical observations in some patients hint the efficacy of G47Δ for glioblastoma, which warrants further clinical development for glioblastoma as well as for other cancer. This first trial teaches us that conventional methods for efficacy evaluation such as RECIST and WHO criteria may not be adequate for oncolytic virus therapy. Also, a conventional dose escalation scheme for anti-cancer drugs may not be suited for designing phase I trials for oncolytic virus therapy. Because the extent of viral replication and the strength of immune responses vary considerably among patients, a preferred means of treatment using oncolytic HSV-1 may be repeating local injections until the cancer is cured. In the new clinical trial that started in 2013 for recurrent olfactory neuroblastoma, the patients receive repeated intratumoral G47Δ administration every 4 weeks until the shrinkage of the tumor or the patient is judged to have progressive disease. CONCLUSIONS: G47Δ is considered to be efficacious not only for brain tumors but for a variety of solid cancer. We aim that oncolytic virus therapy using G47Δ become a standard therapeutic option for brain tumor and cancer patients in the near future. SECONDARY CATEGORY: n/a.
California Senate Bill 277’s Grandfather Clause and Nonmedical Vaccine Exemptions in California, 2015-2022
Authors: Paul L. Delamater, Timothy F. Leslie, Y. Tony Yang
Journal: JAMA Pediatrics (2016)

On June 25, 2015, California's governor approved Senate Bill (SB) 277, a state law that substantially narrows exceptions to school-entry vaccination mandates.The law goes into effect on July 1, 2016, and California will join Mississippi and West Virginia as the third state to disallow nonmedical exemptions (NMEs) from vaccination based on religious or philosophical beliefs for
P1035 LIVER (LS) AND SPLEEN STIFFNESS (SS) IN PATIENTS WITH HAEMOGLOBINOPATHIES. DATA FROM TRANSIENT ELASTOGRAPHY (TE)
Authors: C.B. Conti, M. Giunta, M. Fraquelli, L. Zanaboni, G. Graziadei, C. Terrani, R. D'Ambrosio, E. Cassinerio, M. Colombo, M.D. Cappellini, D. Conte
Journal: Journal of Hepatology (2014)
Abstract P4-02-18: Antiprogestins as Possible Therapeutic Agents for Breast Cancer Patients Showing a High Expression of the Progesterone Receptor Isoform A
Authors: PA Rojas, G Sequeira, P Gonzalez, A Bagnati, A Urrutia, J Medel, P Martinez Vazquez, H Gass, C. Lanari
Journal: Cancer Research (2010)

Abstract Near 75 percent of breast cancer patients express progesterone (PR) and estrogen (ER) receptors and are potential candidates to receive an endocrine therapy. Most of the endocrine therapies available have been designed to target ER and there is not much information about PR as a therapeutic target for breast cancer treatment. However, extensive clinical and experimental evidence suggest that progestins are associated with the induction and maintenance of the neoplastic phenotype in the mammary gland. Moreover, different antiprogestins including ZK 98299, ZK 230211 and RU-486 proved to exert excellent therapeutic effects in murine mammary carcinomas from the MPA-breast cancer model which express high levels of PR with an increased PR-isoform A/PR-isoform B ratio (PR-A/PR-B) (Lanari C et al, Endocrine Related Cancer, 2009 Feb, Jun;16(2):333-50). The main goal of this study is to validate these experimental results using human breast cancer samples and to identify breast cancer patients that might benefit from an antiprogestin therapy. In the first part of this study our aim was to set up primary cultures from each breast cancer sample and to evaluate the in vitro response to antiprogestins, correlating this response with the PR-A/PR-B ratio. Tumor samples were obtained at surgery from patients diagnosed with breast cancer at the Magdalena V. de Martinez Hospital from General Pacheco and at the Rivadavia Hospital of Buenos Aires after signing the informed consent (n=70; median age 53.9 years). All tumor samples were processed by mechanical and enzymatic disaggregation and epithelial cells were purified by differential sedimentation techniques. Only 10 percent of the tumor samples succeeded in tissue culture and could be subcultured for further studies in 24 well plates. Cells were grown in culture medium in the presence of 10% fetal calf serum with or without RU-486 (10-8 M) or Tamoxifen (10-8 M). After one week of treatment, the cells were trypsinized and the total number of cells in each well was counted. Treatment with RU-486 or with Tamoxifen induced a decrease in the number of cells as compared to the controls (n=4, P&amp;lt;0.05). In these patients PR-A expression was the same or higher than PR-B as observed by Western Blot. Our results suggest that RU-486 might be an alternative therapy to treat breast carcinomas showing a high expression of PR-A. We still need more successful cultures in order to correlate the in vitro responsiveness with the PR isoform ratio. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-18.