tbuckley/cabot-search huggingface dataset:
Evidence of an Altered Pattern of Breathing during Exercise in Recipients of Heart–Lung Transplants
Authors: Frank C. Sciurba, Gregory R. Owens, Mark H. Sanders, Bartley P. Griffith, Robert L. Hardesty, Irvin L. Paradis, Joseph P. Costantino
Journal: New England Journal of Medicine (1988)

Recipients of heart–lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart–lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart–lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart–lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart–lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise. (N Engl J Med 1988;319:1186–92.)
Pseudoprecocious Puberty in Girls as a Result of Estrogen Ingestion
Authors: Charles D. Cook, Janet W. McArthur, William Berenberg
Journal: New England Journal of Medicine (1953)

THE purpose of this paper is to report 2 cases of precocious secondary sexual development resulting from the ingestion of estrogenic substances by young girls, to point out the clinical peculiarities of this type of sexual precocity and to emphasize the importance of including estrogen ingestion in the differential diagnosis of pseudopuberty in females.Case ReportsCase 1. A 4 - 3/12-year-old girl was referred to the hospital because of tenderness and enlargement of both breasts, together with dark pigmentation of the areolae, of 3 weeks' duration. Two days before admission scanty vaginal bleeding had occurred.The family history was . . .
Device regulator is told to improve its safety monitoring after breast implant debacle
Authors: I. Torjesen
Journal: BMJ (2012)

A government review has concluded that the UK regulator of medical devices, the Medicines and Healthcare Products Regulatory Agency (MHRA), acted “reasonably” in communicating to the public safety issues related to breast implants made by the French company Poly Implant Prothese (PIP).

The review was ordered by the health secretary for England, Andrew Lansley, in January, when it became clear that more than 40 000 UK women had been fitted with the defective implants, which had fraudulently been filled with non-medical grade silicone.1

Although the review, conducted by the health minister Earl Howe, exonerates the actions of the MHRA and the Department of Health, it says that both organisations need to learn lessons, particularly in how to communicate information promptly and appropriately to affected individuals, the medical profession, the public, and the press.2

Although the MHRA was found to have …
Is Detection of Additional Lesions in Post–Peptide Receptor Radionuclide Therapy Scans With Respect to Diagnostic Imaging Only Due to Different Affinity of Ligands?
Authors: Fabio Minutoli, Astrid Herberg, Alessandro Sindoni, Davide Cardile, Mariapaola Cucinotta, Sergio Baldari
Journal: Clinical Nuclear Medicine (2012)

It is known that different affinity profiles for somatostatin receptor subtypes among different radiopharmaceuticals result in different organ and tumor uptakes and even in different sensitivities in the detection of lesions. Such differences are considered main factors explaining cases of detecting additional lesions in posttherapy scans with respect to diagnostic imaging. We show a posttherapy scan revealing more lesions—namely, a diffuse bone involvement with many small focal bony uptake areas—than the diagnostic scan using the same radiopharmaceutical (111In-pentetreotide) in a 71-year-old man with metastases from a well-differentiated ileal neuroendocrine tumor.
Hyperandrogenism — What Is Normal?
Authors: Roger S. Rittmaster
Journal: New England Journal of Medicine (1992)

Androgens are part of normal female physiology, although their role in women is not as well defined as it is in men. Hyperandrogenism may be defined socially, clinically, or biochemically. In North America, the only acceptable type of androgen-dependent hair in women is pubic and axillary hair. Hair above the upper lip, around the areolas, over the linea alba, and on the thighs is often unacceptable, although considered normal by physicians. Clinical definitions of hirsutism, such as that of Ferriman and Gallwey,1 are based on scoring the extent of hair growth in several body regions. From a biochemical standpoint, hyperandrogenism . . .
Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing
Authors: Cathelijne H. van der Wouden, Deanna Alexis Carere, Anke H. Maitland-van der Zee, Mack T. Ruffin, J. Scott Roberts, Robert C. Green
Journal: Annals of Internal Medicine (2016)

Background: Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP). Objective: To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP. Design: Longitudinal, prospective cohort study. Setting: Online survey before and 6 months after results. Participants: DTC PGT consumers. Measurements: Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCP's understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses. Results: Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%). Limitation: Participants may not be representative of all DTC PGT consumers. Conclusion: A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve. Primary Funding Source: National Institutes of Health.
Small-Vessel Vasculitis
Authors: J. Charles Jennette, Ronald J. Falk
Journal: New England Journal of Medicine (1997)

Vasculitis is inflammation of vessel walls. It has many causes, although they result in only a few histologic patterns of vascular inflammation. Vessels of any type in any organ can be affected, a fact that results in a wide variety of signs and symptoms. These protean clinical manifestations, combined with the etiologic nonspecificity of the histologic lesions, complicate the diagnosis of specific forms of vasculitis. This is problematic because different vasculitides with indistinguishable clinical presentations have very different prognoses and treatments. For example, a patient with purpura, nephritis, and abdominal pain caused by Henoch–Schönlein purpura usually has a good prognosis . . .
BI-01 * 4EBP1 PARTICIPATES IN CISPLATIN RESISTANCE OF HUMAN GLIOMA CELLS THROUGH PI3K/AKT/mTOR PATHWAY
Authors: L. Bie, C. Hua, L. Liu, H. Yuan
Journal: Neuro-Oncology (2015)

BACKGROUND: The oncogenic activation of mTOR pathway is considered to be crucial for tumorigenesis and tumor progression in glioblastoma (GBM). But GBMs are strikingly resistant to mTOR-targeted therapy. We observed the change of 4EBP1 gene expression is significantly higher in primary GBMs than recurrent GBMs. In this study, we focused on 4EBP1 potential mechanisms of action in PI3K/AKT/mTOR pathway. METHODS: U251 cell lines and U251/BCNU cell lines were treated with rapamycin and LY294002, and the cell growth changes in response to subsequent cisplatin treatment was observed. QPCR was performed to detect 4EBP1 mRNA expression in the cells. RESULTS: Blocking PI3K/AKT/mTOR pathway by rapamycin and LY294002 significantly reduced drug resistance of both U251 and U251/BCNU cells to cisplatin and obviously decreased the expression of 4EBP1 gene mRNA (p <0.05). CONCLUSIONS: 4EBP1 gene is located downstream of the PI3K/AKT/mTOR pathway, which might be one of the mechanisms of 4EBP1 to cause cisplatin resistance in the glioma cells.
Abstract P6-01-04: DDB2 a new regulator of metabolism and cell death in human breast tumor cells
Authors: R Klotz, V Besancenot, E Brunner, P Becuwe, S Grandemange
Journal: Cancer Research (2012)

Abstract The protein Damaged DNA Binding-2 (DDB2) is well known for its role in DNA repair by nucleotide excision repair. Interestingly, DDB2 is differentially expressed in breast cancer expressing the estrogen receptor alpha or not. Recent works performed in our laboratory showed a new role of DDB2 in the control of proliferation and invasive abilities in different breast tumor cells through its involvement in the transcriptional regulation of target genes. Two genes involved in tumorigenic processes, MnSOD (manganese superoxide dismutase) and IκBα (inhibitor alpha of Nuclear Factor-kappa B), have been found to be regulated by DDB2. In addition, transcriptomic analyses on cells that differentially express DDB2 showed that several genes involved in the regulation of cellular metabolism are modulated. Our aim is now to focus on the effects of DDB2 expression on cellular metabolism and glycolysis. The results indicated that the overexpression of DDB2 leads to a respiratory chain dysfunction and an increase of the glycolytic pathway. Moreover, we observed an increased production of reactive oxygen species in these cells, compared to parental cells. As mitochondria are involved in cell death, we performed different experiments to evaluate the impact of DDB2 in the response to anticancer agents (Doxorubicin, and 5-fluorouracile (5-FU)) commonly used in the treatment of breast cancer. Interestingly, the cells exhibit a greater sensitivity to anticancer drugs when DDB2 is overexpressed. As these two agents are related to DNA damaged, we have also used other molecules, the apoptotic inducer, TNFα (Tumor Necrosis Factor alpha), and the Paclitaxel (an antimicrotubule agent) to precise the role of DDB2 on cell death. Similar results were obtained, thus demonstrating the influence of DDB2 overexpression in the response to cell death. The identification of molecular mechanisms responsible for these cellular modifications could place DDB2 and these target genes as predictive markers of sensitivity to anticancer drugs in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-01-04.
Genome Project to Expand Intramural Participation
Authors: S. Kumar
Journal: JNCI Journal of the National Cancer Institute (1989)

Genome Project to Expand Intramural Participation Get access Seema Kumar Seema Kumar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 16, 16 August 1989, Pages 1212–1213, https://doi.org/10.1093/jnci/81.16.1212 Published: 16 August 1989
Prognostic Value of Volumetric Parameters on Staging and Posttreatment FDG PET/CT in Patients With Stage IV Non–Small Cell Lung Cancer
Authors: Jeong Won Lee, Sun Min Lee, Mijin Yun, Arthur Cho
Journal: Clinical Nuclear Medicine (2016)

This study aimed to evaluate the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as SUVmax on initial staging and posttreatment F-FDG PET/CT in patients with stage IV non-small cell lung cancer (NSCLC).Sixty-three NSCLC patients with stage IV who underwent staging and posttreatment FDG PET/CT after completion of the first-line chemotherapy were retrospectively enrolled. SUVmax, MTV, and TLG of primary cancer and all metastatic lesions (lymph node and distant metastases) on both PET/CT images were measured and their association with progression-free survival (PFS) and overall survival (OS) analyzed.Median PFS and OS in the patient population were 5.9 and 23.1 months, respectively. Among the PET/CT parameters, MTV and TLG of primary cancer lesions on initial PET/CT and MTV and TLG of metastatic lesions on posttreatment PET/CT were independent prognostic factors for both PFS and OS (P < 0.05). The median OS in patients who showed low values of those PET/CT parameters was more than 26.0 months, whereas patients with high values of those parameters had a median OS of less than 15.0 months.Metabolic tumor burdens of primary cancer lesions on staging PET/CT and metastatic lesions on posttreatment PET/CT were independent prognostic factors in patients with stage IV NSCLC. Volume-based PET parameters could further stratify the prognosis of stage IV NSCLC patients.
Congress Passes NCI Money Bill
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1991)

Congress Passes NCI Money Bill Get access Dorothy A. Tisevich Dorothy A. Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Page 1619, https://doi.org/10.1093/jnci/83.22.1619 Published: 20 November 1991
A Brief Review of Pharmacotherapies for Smoking Cessation
Authors: Cho Y. Lam, Jennifer A. Minnix, Jason D. Robinson, Paul M. Cinciripini
Journal: Journal of the National Comprehensive Cancer Network (2006)

The U.S. Department of Health and Human Services' Clinical Practice Guidelines have established both nicotine and nonnicotine-based pharmacotherapies as efficacious treatments for smoking cessation. Smokers attempting to quit smoking can significantly increase their chances by using one of several first-line agents, including nicotine transdermal patches, gum, nasal spray, inhalers, tablets, and the antidepressant bupropion. Those who cannot use either bupropion or nicotine replacement therapy because of contraindications or lack of effectiveness may benefit from the second-line treatment nortriptyline. This article also discusses several novel compounds for smoking cessation.
A Randomized Trial of Comprehensive Geriatric Assessment in the Care of Hospitalized Patients
Authors: David B. Reuben, Gerald M. Borok, Girma Wolde-Tsadik, Daniel H. Ershoff, Linda K. Fishman, Virginia L. Ambrosini, Yunbao Liu, Laurence Z. Rubenstein, John C. Beck
Journal: New England Journal of Medicine (1995)

Although many studies describe benefits from the comprehensive assessment of elderly patients by an interdisciplinary team (comprehensive geriatric assessment), the most supportive evidence for the process has come from programs that rely on specialized inpatient units and long hospital stays. We examined whether an inpatient geriatric consultation service might also be beneficial in a trial involving four medical centers of a group-practice health maintenance organization (HMO).We conducted a randomized clinical trial with 2353 hospitalized patients 65 years of age or older in whom at least 1 of 13 screening criteria were present: stroke, immobility, impairment in any basic activity of daily living, malnutrition, incontinence, confusion or dementia, prolonged bed rest, recent falls, depression, social or family problems, an unplanned readmission to the hospital within three months of a previous hospital stay, a new fracture, and age of 80 years or older. Of the 1337 patients assigned to the experimental group, 1261 (94 percent) received a comprehensive geriatric assessment in the form of a consultation, with limited follow-up; the 1016 patients assigned to the control group received usual care. The functional and health status of the patients was measured at base line and 3 and 12 months later; survival was assessed at 12 months. Subgroups of patients who might be presumed to benefit from comprehensive assessment were also studied.The survival rate at 12 months was 74 percent in the experimental group and 75 percent in the control group. At base line, 3 months, and 12 months the scores of the two groups on measures of functional and health status were similar. The analysis of 16 subgroups did not identify any with either clearly improved functional status or improved survival.In this HMO, comprehensive geriatric assessment by a consultation team, with limited follow-up, did not improve the health or survival of hospitalized patients selected on the basis of screening criteria.
Abstract 1694: Warburg effect increases intracellular oxygen concentration and determines membrane localization of Ras and other prenylated proteins.
Authors: Ara Kim, Masahiro Higuchi
Journal: Cancer Research (2013)

Abstract The Warburg effect is a famous cancer-related phenomenon which describes a metabolic shift from oxidative phosphorylation to glycolysis and fermentation in a cancer cell. Many studies suggest that the Warburg effect is in response to changes (mutation, deletion, and depletion) within the mitochondrial genome. We previously showed that poorly differentiated prostate cancer cells have reduced mitochondrial genome content and are more influenced by the Warburg effect than well differentiated prostate cancer cells. The reduction of mitochondrial genome content induced overexpression and activation of proto-oncogenic Ras, which is responsible for the activation of AKT and ERK, leading to advanced phenotypes of prostate cancer. Farnesylation (membrane localization) of Ras was required for Ras activation and was induced by the overexpression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), the rate-limiting enzyme of the mevalonate pathway, through inhibition of hypoxia-dependent degradation of HMGR. We hypothesize that increased intracellular oxygen concentration due to the Warburg effect responding to the reduction of mitochondrial genome content determines membrane localization of Ras via induction of farnesylation mediated by overexpression of HMGR. In the poorly differentiated prostate cancer cells such as LNCaP (intracellularly normoxic cells), Ras localized in both the plasma membrane and Golgi, whereas in well differentiated prostate cancer cells such as PC-3 (intracellularly hypoxic cells), Ras is prominent in the cytosol. Exogenous hypoxic conditions eliminated Ras localization in the membrane in PC-3, possibly through inhibition of the farnesylation of Ras. In contrast, exogenous hyperoxic condition increased membrane localization of Ras in LNCaP. Next, we demonstrated the localization of other prenylated proteins, such as Rab5a and prelamin A. In the PC-3, Rab5a and prelamin A were localized in the early endosomes and the nuclear membrane, respectively. In LNCaP, they were present throughout the cytosol and inside of the nucleus. Similar to Ras, the localization of Rab5a and prelamin A was reversible with changes in exogenous oxygen concentration. Our results revealed a coherent mechanism that directly links changes in intracellular oxygen concentration, determined by the mitochondrial genome, with the progression of prostate cancer. Citation Format: Ara Kim, Masahiro Higuchi. Warburg effect increases intracellular oxygen concentration and determines membrane localization of Ras and other prenylated proteins. [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 1694. doi:10.1158/1538-7445.AM2013-1694
1359 ASSOCIATION BETWEEN LIVER FIBROSIS AND DECREASED APOLIPOPROTEIN-A1 IN A 7-YEARS PROSPECTIVE STUDY. COULD IT EXPLAIN CARDIOVASCULAR-RELATED RISK WITH FIBROSIS PROGRESSION IN TYPE-2 DIABETIC PATIENTS?
Authors: H. Perazzo, Y. Ngo, M. Munteanu, F. Huet, M. Couteau, P. Lebray, S. Jacqueminet, F. Imbert-Bismut, V. Ratziu, A. Hartemann-Heurtier, T. Poynard
Journal: Journal of Hepatology (2013)
P21 Does time of day affect outcomes on an advanced office based driving simulator in patients with obstructive sleep apnoea syndrome (OSAS)?
Authors: D. Ghosh, S. L. Jamson, P. D. Baxter, M. W. Elliott
Journal: Thorax (2011)

<h3>Introduction</h3> Road traffic accidents (RTA) are known to peak at certain times of the day especially early afternoons. OSAS patients are at higher risk of being involved in RTA. Recently we have established that it is possible to identify with high degree of certainty a group of OSAS sufferers who perform significantly worse than others using specific simulator parameters on our advanced office based driving simulator (miniSim). We now explore whether the time of day when the study is performed affects simulator outcomes. <h3>Methods</h3> 205 (52±10 yrs, ESS 12±5, AHI 33±22) patients performed a 90 km motorway driving scenario on the miniSim. Two events were programmed to trigger evasive actions, one subtle (Veer event) where an alert driver should not crash, while with the other (Brake event) even a fully alert driver might crash. There were three possible outcomes of the simulator runs; “fail”, “indeterminate” and “pass”. “Fail” was defined by any crash other than at the brake event and/or inability to complete the test. Comparisons were made between the patient populations performing the test before &amp; after 12:00 in terms of demographics, symptoms &amp; severity of OSAS. Outcomes on the simulator, lane position &amp; reaction times were also compared between these groups. <h3>Results</h3> There were no differences between the patients performing at the different time slots in terms of age, BMI, ESS &amp; AHI (Abstract P21 table 1). The number of “fails”, “indeterminates” &amp; “passes” during morning &amp; afternoon runs were: 16/26/70 (n=112) &amp; 22/30/41 (n=93). Patients performing in the afternoon were no more likely to fail the test than those doing it in the morning (Fisher9s exact test p=0.1). There were no differences in terms of lane position or reaction times (p=0.38, 0.65). <h3>Conclusion</h3> The results indicate that the time of day the study is performed is unlikely to affect outcomes on this driving simulator. It has implications for its clinical use as the test can performed at any time of the day.
P542 STUDY OF THE VENTRICULAR MECHANIC WITH 3D-SPECKLE TRACKING ECHOCARDIOGRAPHY IN CIRRHOTIC PATIENTS: A POSSIBLE TOOL FOR THE DIAGNOSIS OF CIRRHOTIC CARDIOMYOPATHY
Authors: F. Cucchi, G. Iacovone, G. Giura, T. Dominici, A. Calicchia, V. De Gregorio, P.E. Puddu, O. Riggio, C. Torromeo, M. Merli
Journal: Journal of Hepatology (2014)