tbuckley/cabot-search huggingface dataset:
Learning From Caregivers About the End of Life in Patients With a Left Ventricular Assist Device
Authors: Sue Wingate
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Measuring racial bias in inpatient treatment
Authors: J A Flaherty, R Meagher
Journal: American Journal of Psychiatry (1980)

In a retrospective chart audit of 66 black and 36 white male schizophrenic inpatients, the authors found that black patients spent less time in the hospital, obtained a lower privilege level, were given more p.r.n. medications, and were less likely to receive recreation therapy and occupational therapy. Seclusion and restraints were more likely to be used with black patients. The authors ruled out the possibility of more severe pathology in the black patients by global rating of an additional 15 white and 15 black patients. Concluding that there was racial bias, they attribute it to subtle stereotyping and the staff's greater familiarity with white patients; they suggest increased recruitment of black professionals and the inclusion of blacks in each treatment team.
Abstract 17301: AMP-Dependent Protein Kinase Regulates Mitochondrial Reprogramming and Differentiation Potential of Cardiac Progenitor Cells
Authors: Amabel M Orogo, Sang-Bing Ong, Xiaoxue Zhang, Anne N Murphy, Mark A Sussman, Asa B Gustafsson
Journal: Circulation (2012)

Activation and participation of cardiac progenitor cells (CPCs) in regeneration are critical for effective repair in the wake of pathologic injury. The process of stem cell activation and commitment involves increased energy demand and mitochondrial biogenesis. However, significant gaps exist in our knowledge of CPC differentiation, and little attention has been paid to alterations in mitochondria during differentiation. In this study, we have investigated the mechanisms of mitochondrial maturation integral to the execution of a cardiac differentiation program. We found that uncommitted c-kit+ CPCs contain an under-developed network of few mitochondria that localize in the perinuclear region. In contrast, after incubation in differentiation medium, mitochondria displayed a dramatic change with increased mitochondrial mass and formation of a large network as the CPCs grew in size. Expansion of the mitochondrial network correlated with cardiac lineage commitment as detected by real time PCR for GATA4, MEF2C and Actinin. Moreover, differentiation induced expression of mitochondrial biogenesis proteins PGC-1α, NRF-1 and Tfam, which correlated with an increase in the number of mitochondria as well as enhanced oxidative capacity and cellular ATP levels. AMP-dependent protein kinase (AMPK) is an energy sensor that is activated in response to increased energy demand in cells. Since differentiation requires energy and PGC-1α is a known downstream target of AMPK, we examined the role of AMPK in regulating mitochondrial expansion and differentiation in CPCs in vivo and in vitro. We found that AMPK protein levels and phosphorylation drastically increased during differentiation of CPCs in vitro. Moreover, CPCs are known to migrate to the border zone after myocardial infarction (MI), where they proliferate and differentiate into distinct cardiac lineages. We found that a majority of the c-kit+ cells in the border zone were positive for p-AMPK after MI. Inhibiting AMPK with Compound C prevented both expansion of the mitochondrial network and differentiation in CPCs in vitro. These data suggest that mitochondrial expansion by AMPK and PGC-1α play an essential role in CPC differentiation and defects in this process will impair their repair capacity.
Retrospective claims database analysis of elderly compared with nonelderly patients (pts) with newly diagnosed hepatocellular carcinoma (HCC)
Authors: A. J. Sanyal, E. Moyneur, V. Barghout
Journal: Journal of Clinical Oncology (2009)

9552 Background: HCC is the most common type of liver cancer in the US and its incidence has been rising. We assessed whether differences existed in risk factors and treatment practices in pts with HCC by age. Methods: De-identified, individual-level healthcare claims data from a database (MarketScan MedStat) covering all US census regions for ≥18 million lives in 2002–2008 were retrospectively analyzed. Pts had ≥2 claims for primary HCC (ICD9 155.0), continuous healthcare coverage, &gt;180 days of coverage before HCC, and no prior claims for secondary liver cancer (ICD9 197.7). Pts were followed longitudinally from HCC diagnosis until end of healthcare coverage or 3/31/08. Pts were stratified by age (&lt;65 or ≥65 y), and treatment was analyzed using prevalence and time to initiation. Results: Of 4,153 pts with HCC identified, 46.3% were ≥65 y. Risk factors in the groups were nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH, 59% for &lt;65 vs 50% for ≥65), hepatitis C (32% vs 11%), diabetes (29% vs 40%), alcoholic cirrhosis (16% vs 7%), and hepatitis B (9% vs 3%). Treatments were similar between groups; however, more pts in the younger group received transplantation, IV chemotherapy, and hospice care ( Table ). Twice as many older pts did not receive any of the considered treatment compared with younger pts. Sorafenib, approved for unresectable HCC in 11/07, was used in a limited number of pts in the groups. Most noncurative treatment options were initiated sooner in pts ≥65 y than those &lt;65 y, whereas the opposite holds for the 2 main curative treatments (transplantation and cancer removal surgery). Conclusions: Regardless of age, principal risk factors associated with HCC were NAFLD/NASH, diabetes, and hepatitis C. Based on this retrospective claims analysis, variations between treatment options and time to initiation did differ between the groups, suggesting that underlying comorbidities and practice patterns affect treatment options in elderly and nonelderly pts with HCC. [Table: see text] [Table: see text]
Inhibition of Carcinogenic Effects of Polycyclic Hydrocarbons by Benzyl Isothiocyanate and Related Compounds2
Authors: Lee W. Wattenberg
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Inhibition of Carcinogenic Effects of Polycyclic Hydrocarbons by Benzyl Isothiocyanate and Related Compounds Get access Lee W. Wattenberg Lee W. Wattenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 395–398, https://doi.org/10.1093/jnci/58.2.395 Published: 01 February 1977 Article history Received: 30 April 1976 Accepted: 28 June 1976 Published: 01 February 1977
Allopurinol-induced severe cutaneous adverse reactions
Authors: Corrado Campochiaro
Journal: Annals of the Rheumatic Diseases (2016)

Allopurinol-induced severe cutaneous adverse reactionsIn their article entitled 'Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin', 1 Chung and colleagues elegantly investigated the factors associated with severe cutaneous adverse reactions (SCAR) in patients taking allopurinol as antihyperuricaemic agent and found that impaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol SCAR.In their results section, the authors stated that they did not find any difference in patients with renal impairment in the values of initial dose/estimated glomerular filtration rate (eGFR) between allopurinol SCAR and tolerant controls.This result seems in contrast to what reported by Stamp et al 2 because these authors found that there was an increase in the risk of allopurinol SCAR as the starting dose of allopurinol corrected for the estimated GFR increased.The main difference between these two studies is that the mean baseline eGFR was frankly lower in the cohort studied by Chung (34 mL/min/1.73m 2 ) compared with the cohort studied by Stamp (50.2 mL/min/1.73m 2 ).In both studies, the Modification Diet Renal Disease (MDRD) study equation was used to calculate eGFR.Two important questions should then be answered.(1) Is the initial dose/eGFR negligible in terms of risk of SCAR in patients with more severe renal impairment?(2) Was the group of patients studied by Chung dialysis-free?Unfortunately in the text it is not specified whether the patients were dialysisfree and as plasma oxypurinol concentrations are reduced by 50% by dialysis, 3 this could be of great importance in the final results.
Temperature Gradients and Local Perfusion in a Mammary Carcinoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P M Gullino, R K Jain, F H Grantham
Journal: JNCI Journal of the National Cancer Institute (1982)

Temperature gradients of mammary tumors in randombred Sprague-Dawley rats under normothermia, hypothermia, and hyperthermia were determined, and their experimental modifications were utilized to assess differences in perfusion rates within the neoplastic tissue. Normothermic tumors showed a circadian rhythm with zenith at midnight and nadir at midday. Differences between highest and lowest temperatures recorded during the 24-hour period reached up to 3 degrees C. Similar oscillations were observed in subcutaneous tissue without tumor. An average temperature increment of 0.5-1.0 degrees C was observed when a tumor was transferred from the subcutaneous to the abdominal location. Gradients larger than 1 degrees C were observed within the same tumor in locations only a few millimeters distance from each other. The nonuniformity in temperature within normothermic tumors was exaggerated during hyperthermia. No appreciable change in temperature gradients was seen within a normothermic tumor when tumor blood flow was doubled or reduced to one-third of the basal level. Hyperthermia increased both volume and temperature of tumor efferent blood. As expected, decrease or increase in blood flow during hyperthermia increased or decreased tumor temperature, respectively, but substantial temperature gradients up to 2 degrees C still persisted within adjacent regions. The extent of temperature changes in the tumor could not be correlated with a known change in blood supply. A pulse of cold serum into the tumor afferent artery produced a substantial reduction of tumor blood flow, but only a small depression in tumor temperatures, and a very small change in tumor temperature gradients. No appreciable modification could be brought about in tumor temperature levels and temperature gradients within the tumor by pulses of cold serum in the afferent artery during hyperthermia. After external cooling of the tumor, the time necessary to compensate for temperature depression did not correlate with either the reduction of temperature or with the thickness of the tumor tissue separating the thermistor from the cold source. The results indicate extensive anisotropy of temperature and blood distribution within growing neoplastic tissue and suggest that heat transfer by convection within the tumor is much less effective than it is commonly assumed.
Factors Associated With Cancer of the Esophagus, Mouth, and Pharynx in Puerto Rico&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Isidro Martìnez, M.D.
Journal: JNCI Journal of the National Cancer Institute (1969)

A case-control, community-based study of 400 patients with cancer of the esophagus, mouth, and pharynx was undertaken to explore the association of environmental and dietary factors and familial aggregation. Twelve hundred age- and sex-matched controls were interviewed and asked the same questions as were the cancer patients. Both controls and patients had diets deficient in fresh fruits, vegetables, meat, eggs, and milk, but high in beans and carbohydrates in the form of rice, bread, and such starchy roots as potatoes and sweet potatoes. Patients differed significantly from controls in that they used more alcohol, tobacco, hot beverages (mostly coffee), and spices. Their meals were fewer, scantier, and more irregular, served very hot and without beverage.
Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays
Authors: Apurva K. Srivastava, Melinda G. Hollingshead, Jennifer Weiner, Tony Navas, Yvonne A. Evrard, Sonny A. Khin, Jiuping Jay Ji, Yiping Zhang, Suzanne Borgel, Thomas D. Pfister, Robert J. Kinders, Donald P. Bottaro, W. Marston Linehan, Joseph E. Tomaszewski, James H. Doroshow, Ralph E. Parchment
Journal: Clinical Cancer Research (2016)

Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect.
Biomonitoring of prenatal analgesic intake and correlation with infantile anti-aeroallergens IgE
Authors: H. Hoeke, S. Roeder, A. Mueller, T. Bertsche, M. Borte, U. Rolle-Kampczyk, M. von Bergen, D. K. Wissenbach
Journal: Allergy (2016)

An association between prenatal acetaminophen or ibuprofen intake and an increased risk of asthma and increased IgE level in children is discussed in various epidemiological studies. Although the molecular mechanistic link is still unknown, the question whether or not acetaminophen and/or ibuprofen are safe pain medications during pregnancy arose. In this study, we associate maternal acetaminophen and ibuprofen intake during pregnancy and breastfeeding to infantile asthma phenotypes and elevated IgE level. Therefore, we analysed questionnaires from a local mother-child cohort and monitored drug intake by LC-MS biomonitoring in urine. No association was found between drug intake and any analysed health outcome using questionnaire data. For the information obtained from biomonitoring, no association was found for ibuprofen and acetaminophen intakes during breastfeeding. However, an association between prenatal acetaminophen intake and increased infantile IgEs related to aeroallergens was statistically detected, but not for asthma phenotypes.
Exogenous Estrogens and Other Factors In the Epidemiology of Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Jennifer L. Kelsey, Diana B. Fischer, Theodore R. Holford, Virginia A. LiVolsi, Evelyn D. Mostow, Ira S. Goldenberg, Colin White
Journal: JNCI Journal of the National Cancer Institute (1981)

In a hospital-based case-control study of the epidemiology of breast cancer undertaken in Connecticut from 1977 to 1979, there was no evidence of an increase in risk for breast cancer among women who had used oral contraceptives or estrogen-replacement therapy. In fact, there was some suggestion of a decrease in risk for breast cancer with increasing length of use of oral contraceptives. Higher than average risks were found among women who had never given birth to a child, women with a late age at menopause, women with an early age at menarche, women who had given birth to their first child at a relatively late age, women with previous benign breast disease, and women with a history of breast cancer in a sister or mother. Heavy women were at high risk for postmenopausal breast cancer, and thin women were at high risk for premenopausal breast cancer. The association between heaviness and postmenopausal breast cancer was strongest among women who had had their last menstrual period more than 5 years before the diagnosis of breast cancer.
Host-Clonal Interactions in the Generation of Proviral Gene Deletion Variants
Authors: B Zbar, Y Tanio
Journal: JNCI Journal of the National Cancer Institute (1987)

A nonproducer clone (clone A1) (from a retrovirus-infected guinea pig fibrosarcoma) has been described that under conditions of in vivo immunologic selection forms variants that lack the proviral gene. One trivial explanation for the apparent loss of the provirus from clone A1 is that clone A1 did not originate from a single cell. For evaluation of this possibility, subclones were derived from clone A1 and tested for tumor recurrence in nonimmune and virus-immune animals. Each of four subclones contained the A1 provirus and exhibited specific viral interference; tumor recurrences formed from each of these four subclones lacked the clone A1 provirus. Possible, when heterogeneous populations of retrovirus-infected cells are injected into nonimmune animals, some clones will elicit immunologic responses to retroviral antigens and subject other clones in the population to immunologic selective pressures. For testing this concept, clone A1 was injected in admixture with a producer clone (clone A4) into nonimmune Sewall Wright strain 2 guinea pigs. Tumors formed in nonimmune guinea pigs inoculated with clone A1 in admixture with clone A4 were shown to lack a detectable clone A1 provirus. The results supported the concept that a somatic mutational event (deletion of the proviral gene) occurs during growth of clone A1. When heterogeneous populations of retrovirus-infected cells are injected into animals, host-clonal interactions may occur leading to outgrowth of proviral gene deletion variants. These results supported the notion that interactions between tumor clones and the host can change the dominant clonal type of the tumor and provide a genetic basis for this change.
Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study
Authors: C.J. Morrow, F. Trapani, R.L. Metcalf, G. Bertolini, C.L. Hodgkinson, G. Khandelwal, P. Kelly, M. Galvin, L. Carter, K.L. Simpson, S. Williamson, C. Wirth, N. Simms, L. Frankliln, K.K. Frese, D.G. Rothwell, D. Nonaka, C.J. Miller, G. Brady, F.H. Blackhall, C. Dive
Journal: Annals of Oncology (2016)

BackgroundOver the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX).Patients and methodsCTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient.ResultsThe NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype.ConclusionsThis study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM+) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.
Abstract 2703: Overcoming Lapatinib resistance by the fatty acid synthase inhibitor HS-106
Authors: Yazan Alwarawrah, Philip Hughes, Rachid Safi, Donald P. McDonnell, Neil L. Spector, Timothy A. Haystead
Journal: Cancer Research (2015)

Abstract Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that is overexpressed in about 20% of breast cancers and most often in the more aggressive inflammatory breast cancer (IBC). Lapatinib is one of the most potent small molecule inhibitors of HER2. Although Lapatinib has shown to be an effective targeted therapy, development of drug resistance stands as a major problem. Here we show that the anti-cancer activity of the novel fatty acid synthase inhibitor HS-106 can re-sensitize resistant cell lines to Lapatinib. Lapatinib resistant SKBR3 and BT474 breast cancer cell lines were treated with increasing concentrations of HS-106 either alone or in combination with Lapatinib and their effects on cell proliferation were assessed using the DNA dye Hoechst 33342. The ability of HS-106 and Lapatinib drug combination to induce apoptosis were measured in Caspase 3/7 activity assay using the fluorogenic Caspase substrate (DEVD)2 R110. Their effect on apoptosis was further confirmed in Lapatinib resistant BT474 cells using flow cytometry based Annexin V assay. In addition, the effect of HS-106 on the expression levels and phosphorylation of the kinases involved in Her2 pathway including Her2, AKT and ERK were determined. The fatty acid synthase inhibitor HS-106 significantly inhibits the proliferation of Lapatinib resistant cell lines with concentrations. Interestingly, when combined with Lapatinib, the drugs synergize to dramatically affect cell growth. This anti-proliferative activity of HS-106 was found to be the result of induction of apoptosis, Caspase 3/7 activity was found to increase in a dose dependent manner following HS-106 treatment. Low concentrations of Lapatinib and HS-106, which does not induce Caspase activity when administrated separately, were found to significantly induce Caspase activity when combined together. These results were confirmed with the Annexin V assay. By examining the expression levels of HER2 pathway proteins we found a decrease in HER2 levels which was reflected on the levels of the downstream kinases AKT and ERK when treating with high concentrations of HS-106. In a previous work, HS-106 showed a good tolerability and anti-cancer activity in the MMTV neu+ mouse model. By showing potent efficacy against Lapatinib resistant breast cancer cell lines, our data suggest that HS-106 is an excellent drug candidate to advance into translational studies for the treatment of Lapatinib resistant breast cancer. Citation Format: Yazan Alwarawrah, Philip Hughes, Rachid Safi, Donald P. McDonnell, Neil L. Spector, Timothy A. Haystead. Overcoming Lapatinib resistance by the fatty acid synthase inhibitor HS-106. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2703. doi:10.1158/1538-7445.AM2015-2703