tbuckley/cabot-search huggingface dataset:
Therapy-associated subclinical cardiac injury in survivors of Hodgkin and non-Hodgkin lymphoma.
Authors: K. Y. Usuki, M. J. Adams, K. Boudadi, M. T. Milano, O. Thomas, R. Tuli, O. Wexler, G. R. Morrow, R. G. Schwartz, L. S. Constine
Journal: Journal of Clinical Oncology (2010)

e19572 Background: Contributions of modern techniques of mediastinal radiation (mRT) and anthracycline chemotherapy (ACT) to cardiotoxicity in survivors of Hodgkin (HL) and Non-Hodgkin lymphoma (NHL) remain incompletely defined. We assessed the effects of mRT and / or ACT on subclinical cardiotoxicity by radionuclide imaging. Methods: 100 HL and NHL survivors without cardiac symptomatology were screened with ECG-gated RN perfusion and ventriculographic scans since 8/91. In this analysis we reviewed the most recent scan (mean 10.9 ± .06 yrs, median 8.1 yrs). Treatment groups included: ACT (n = 10), ACT + mRT (n = 35) and mRT (n = 55). 34 pts. had multiple gated acquisition (MUGA) scans evaluating left ventricular ejection fraction (LVEF), while 66 had ECG-gated single photon emission computed tomography (SPECT) scans evaluating myocardial ischemia, LVEF, end systolic and end diastolic volume indices (ESVI & EDVI). Since sequential blocking of the heart is often employed in modern mRT treatments, mRT dose was determined to the region of the LV (RT lv), base (RT b), and superior heart (RT sup) in addition to maximum mRT dose (maxd). Results: Mean LVEF differed among the treatment groups: ACT = 53%, ACT + mRT = 56% and mRT = 60% (n = 100, p =.015). Mean ESVI was 39, 34, 25 respectively (n = 66, p =.005). Mean EDVI was 75, 72, 59 (n = 66, p =.009). Univariate linear regression individually tested the associations between ACT, RT lv, RT b, RT sup, maxd and the cardiac variables. ACT dose was associated with reduced LVEF (n = 100, p =.04), increased ESVI (n = 66, p =.002) and increased EDVI (n = 66, p =.005). XRT doses showed no correlation. In the ACT + mRT patients, separate multivariate analysis individually tested the maxd, RT lv, RT b, RT sup with ACT dose. The only significant association was between ACT and increased EDVI, ESVI found on all analyses. No associations were seen with myocardial ischemia throughout Conclusions: Radionuclide function variables identify subclinical cardiac changes in HL and NHL survivors treated with ACT. The volume indices ESVI and EDVI appear particularly sensitive indicators of subclinical cardiac damage after ACT. Modern mRT is less correlated with subclinical cardiotoxicity as determined by LVEF, ESVI and EDVI. No significant financial relationships to disclose.
Continuous psychotherapy within an HMO
Authors: M J Bennett, M J Wisneski
Journal: American Journal of Psychiatry (1979)

The authors describe the long-term psychotherapy program developed by the Harvard Community Health Plan, focusing on its planning, implementation, and monitoring. The inclusion of coverage for chronic conditions in an HMO practice led to the development of a range of extended treatment services, exploratory as well as supportive, and to the enhancement of short-term methods. The control of utilization and cost is effected through the willingness of the provider group to adapt treatment methods to patient needs, rather than through the benefit structure. With the broad range of treatment methods available in this plan, only 1%-2% of patients require long-term continuous psychotherapy.
Clinical outcome of triple-negative (TN) breast cancer (BC)
Authors: D. Cabuk, G. Basaran, H. Kaya, B. Gulluoglu, M. Teomete, F. Dane, P. F. Yumuk, N. S. Turhal
Journal: Journal of Clinical Oncology (2008)

11526 Background: Breast cancer is a heterogeneous disease with different biologic characteristics and clinical behaviors. Triple- negative tumors, most of which fall into the basal subgroup of breast cancers based on microarray profiling have been reported to have an aggressive clinical course. Methods: We reviewed the medical records of early breast cancer patients (pts) with known receptor and Her- 2 satus by immunohistochemistry, who have been treated in our institution between 1999–2006. We recorded the clinical/pathologic characteristics of these tumors, analyzed survival outcome. Results: We identified 60 pts with triple negative tumors among 705 early BC cases. 4% pts were <35 years of age, 58% were postmenopausal, 57% had left breast involved, 36% had breast-conserving surgery. The histology was invasive ductal carcinoma in 72% cases, invasive lobular in 8% and medullary in 8% cases. Thirty percent of pts had node- positive disease, 40%/53% had grade 2/3 tms respectively. Twenty percent of the pts had multifocal disease, 40% had lymphovascular invasion. Eighty percent of pts had anthracycline-based, 12% had anthracycline/taxane- based adjuvant chemotherapy. 51% had adjuvant radiotherapy. So far 5 pts had relapse and one patient died because of BC. Eight-year overall survival is 88% and 8-year disease-free survival (DFS) is 75%. Conclusions: Not all of these TN BC pts had poor prognostic features as mentioned in literature. Both the overall survival and DFS are almost similar to those with receptor negative subset in our institution. Effective treatment strategies can only be implemented with increased understanding of the biology of this distinct breast cancer subtype. No significant financial relationships to disclose.
New Concepts about the Mast Cell
Authors: Jeffrey S. Flier, Lisa H. Underhill, Stephen J. Galli
Journal: New England Journal of Medicine (1993)

Most physicians and immunologists, if they think of the mast cell at all, regard it as something of a pariah. Other cells of hematopoietic origin, such as neutrophils, macrophages, and platelets, are clearly important in host defense, hemostasis, or both. In contrast, the contributions of the mast cell to pathologic conditions come to mind much more readily than any role it may have in the maintenance of health. Indeed, some would argue that an entire branch of medicine -- allergy -- deals in large part with the adverse effects produced by activation of the mast cell and the basophil, a . . .
Single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (NOS3) and vascular endothelial growth factor (VEGF) and its relationship to sunitinib-induced hypertension.
Authors: A. A. van der Veldt, K. Eechoute, S. Oosting, M. H. Kappers, J. B. A. G. Haanen, A. K. L. Reyners, H. Gelderblom, H. Guchelaar, C. Van Herpen, E. Boven, R. Mathijssen
Journal: Journal of Clinical Oncology (2011)

4611 Background: Hypertension is a common side-effect in patients treated with sunitinib and is likely associated with inhibition of the VEGF/VEGF receptor(R)-2 pathway. SNPs in VEGF-A, VEGFR-2, but also in NOS3and endothelin-1 (EDN1) have been mentioned as possible candidates associated with a higher risk on development of hypertension. Methods: A retrospective multicenter study was performed in 255 patients with advanced renal cell cancer and gastrointestinal stromal tumor treated with sunitinib 50 mg/day in a 4 weeks on 2 weeks off or 37.5 mg/day continuous schedule. Office systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and on days 14 and 28 of the first treatment cycle. Hypertension was graded according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Seven SNPs in genes encoding for VEGF-A (rs2010963, rs833061, rs3025039, rs699947), VEGFR-2 (rs1870377), EDN1 (rs5370) and NOS3 (rs2070744) were selected. SNPs were univariately tested against hypertension grades according to CTCAE. Results: During the first treatment cycle, sunitinib induced a mean increase of 13 ± 23 mmHg and 10 ± 12 mmHg in SBP and DBP (t-test, P < 0.001), respectively. According to CTCAE, 36.5 % of patients developed hypertension. Among these patients, 10.6%, 12.9% and 12.9% had hypertension grade 1, 2, and 3, respectively. Development of grade 3 hypertension was associated with two copies of the C-allele in VEGF-A (rs833061; Chi-square, P = 0.048), two copies of the A-allele in VEGF-A(rs699947; P = 0.053) and a C-allele in NOS3 (rs2070744; P = 0.051). Conclusions: SNPs in genes of NOS3 and VEGF-A are associated with the development of severe hypertension in patients treated with sunitinib. In particular, the association between the NOS3 pathway and hypertension induced by an inhibitor of the VEGF/VEGFR-2 pathway is a new finding. Hence, SNPs in VEGF-A and NOS3 genes may identify patients predisposed to develop hypertension on sunitinib treatment.
Affective disorder: studies with amine precursors
Authors: D L Dunner, R R Fieve
Journal: American Journal of Psychiatry (1975)

The authors assessed the clinical antidepressant effects of L-tryptophan given alone and in combination with L-dopa in 12 patients with a diagnosis of primary affective disorder; Preliminary results did not demonstrate an antidepressant response when L-dopa was combined with L-tryptophan. Also, the results did not support the catecholamine or biogenic amine hypotheses of affective disorder.
Treatment of acute myeloid meukemia with a mrc aml 10 modified regime in Mexican children
Authors: S. Gallegos Castorena, A. Medina Sanson, M. Zapata Tarres, E. Dorantes Acosta, A. Martinez Avalos
Journal: Journal of Clinical Oncology (2007)

9533 Background: The results of treatment in acute myeloid leukemia had been limited. We have obtained event free survival of 17% in patients treated in our Institution from 1990–2003. The availability of stem cell transplantation is limited in our country. The objective of the present study was to assessed the remission rate, event-free and overall survival obtained with and intense chemotherapy regime. Methods: We designed a prospective study using a MRC AML 10 modified protocol from February 2003 to September 2005 for patients diagnosed with de novo AML 0 to 18 years. Patients were classified as high risk if they presented with M4 or M5 morphology, &gt;100,000 WBC/mm3, positive CSF, t(11;23) or &gt; 1 cycle to achieve remission. Induction consisted on two cycles of daunorubicin 50 mg/m 2 /day 1, 3 and 5; cytarabine 100 mg/m 2 /dose twice days 1–10 and etoposide 100 mg/m 2 /day 1–5; in the second cycle cytarabine was scheduled for 8 days. Consolidation consisted on 4 alternating cycles of etoposide 100 mg/m 2 /day 1–5 and cytarabine 1 gr/m 2 /dose twice day 1–3 alternating with mitoxantrone 10 mg/m 2 /day 1–5 and cytarabine 1 gr/m 2 /dose twice day 1–3. All patients received triple intrathecal chemotherapy every cycle and craniospinal radiation was limited to patients with &gt;100,000 WBC/mm3 o positive CSF at diagnosis. Remission rate, event-free and overall survival were assessed. Kaplan Meier curve for survival was used. Results: We included 37 patients, 21 male and 16 female, mean age was 8.3 years (11 months-16 years), M1, M2 and M4 subtypes were equally frequent with 21.6% each. Mean leukocyte count was 79,000 (2,100- 525,000). CSF was positive in one patient. 56.8% were classified as high risk patients. Remission was achieved in 91.6%, 75% after the first cycle, 13% after the second and 3% needed more than two cycles. An event free survival of 48.6% (50% for low risk and 47% for high risk) and overall survival of 59.4% were achieved. Relapse rate was high with 35% of patients. Conclusions: The evaluated treatment regime improved our results and was well tolerated. No significant financial relationships to disclose.
A Proposal to Provide Health Insurance to All Children and All Pregnant Women
Authors: Birt Harvey
Journal: New England Journal of Medicine (1990)

Currently, about 33 million people in the United States lack health insurance.1 They include the self-employed, those employed part time, seasonal workers, the unemployed, and full-time workers whose employers offer unaffordable insurance or none at all. More than two thirds of the uninsured work full time but either are not offered employer-based health insurance or are offered insurance at a cost too high for their incomes.2 Among the uninsured are 10 to 12 million children.3 Contrary to popular misconceptions, the typical uninsured child has a working parent,4 lives in a two-parent family, and is white.2 Even more children are underinsured; . . .
Unusually High Incidence of Spontaneous Lymphomas in Wild House Mice2
Authors: Murray B. Gardner, Brian E. Henderson, John D. Estes, Herman Menck, John C. Parker, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Unusually High Incidence of Spontaneous Lymphomas in Wild House Mice Get access Murray B. Gardner, Murray B. Gardner Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian E. Henderson, Brian E. Henderson Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Estes, John D. Estes Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Herman Menck, Herman Menck Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar John C. Parker, John C. Parker Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Huebner Robert J. Huebner Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; National Cancer Institute,6Bethesda, Maryland 20014; and Microbiological Associates, Inc., Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 6, June 1973, Pages 1571–1579, https://doi.org/10.1093/jnci/50.6.1571 Published: 01 June 1973 Article history Received: 24 November 1972 Accepted: 14 February 1973 Published: 01 June 1973
P255 Utility of a screening protocol incorporating an interferon-gamma release assay (IGRA) on detection and decision to treat latent tuberculosis infection (LTBI) prior to anti-TNF therapy
Authors: E Zatyka, A Nundoll, RAM Breen, N Price
Journal: Thorax (2015)

<h3>Introduction</h3> Anti-TNFα treatment is associated with a significant risk of LTBI reactivation (median onset 12 weeks for infliximab). Patients are therefore recommended to undergo prior LTBI screening but current NICE and BTS guidance differ in their approach. In particular, the BTS places more emphasis on demographic factors (age, ethnicity, birth outside the UK) in stratifying risk and does not mandate routine IGRA use.<sup>1</sup> We describe the effect of local Trust screening protocol, incorporating IGRA, in the diagnosis and decision to start anti-TB chemoprophylaxis in a large cohort of patients being worked-up for anti-TNFα therapy. <h3>Methods</h3> Data on adult patients undergoing LTBI screening before anti-TNFα commencement were collected prospectively between Jan ‘13 and Dec ‘14. The local screening protocol included clinical assessment, chest X-ray (CXR) and an ELISpot-TB assay. Where required, routine chemoprophylaxis was isoniazid for 6 months (anti-TNFα was started ≥1 month). Clinical follow-up data was obtained for 6 months post anti-TNFα commencement. <h3>Results</h3> 472 patients received anti-TNFα for a minimum of 6 months after LTBI screening. According to the local protocol 21 cases (4.5%) received chemoprophylaxis vs. 66 patients (14%) who would have received chemoprophylaxis if the BTS guideline had been applied (Table 1). Moreover, 5 white, UK born, patients were identified that would not have been risk stratified to receive chemoprophylaxis according to the BTS. 2 cases receiving adalimumab for psoriasis developed active TB during the follow-up period. Both had negative IGRA at screening and were not given chemoprophylaxis however, both would have received treatment according to the BTS protocol. One case resulted from a subsequent TB exposure. The other had an abnormal screening CXR. This result was not appropriately followed up hence the case did not necessarily represent protocol failure <i>per se</i>. <h3>Conclusions</h3> These preliminary data demonstrate the value of an LTBI screening IGRA based protocol by decreasing the need for chemoprophylaxis by 69% if BTS recommendations had been applied. <h3>Reference</h3> 1 Ormerod, <i>et al</i>. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-α. <i>Thorax</i> 2005;<b>60</b>:800–805
Abstract 1170: TTP inhibits insulin receptor signals in cancer cell
Authors: Ji Eun Yoon, VO MAI TRAM, Nal Ae Yoon, Jin Ho Back, Young Joo Min, Wha Ja Cho
Journal: Cancer Research (2015)

Abstract Insulin receptors (IRs) belong to the large class of tyrosine kinase receptors and are activated by insulin, IGF-I, IGF-II and. The binding of ligands to the IR initiates a cascade of events leading to activation of signal transduction pathways, mainly PI3K and AKT pathways, and induce glucose uptake and cell proliferation. IR signaling pathway has been reported to be deregulated in cancer cells resulting in a range of clinical manifestations including cancer. It has been shown that the presence of IR was required for transformation induced by many oncogenes and over-expression or constitutive activation of IR gave rise to transformed phenotypes. Here, we report an unexpected role of a tumor suppressor tristetraprolin (TTP) in inhibiting IR. TTP bound to the AU-rich element (ARE) within the mRNA 3′UTRs of IR, enhanced the decay of their mRNAs and inhibited the metabolism of cancer cells. The ectopic expression of IR without their 3′UTRs blocked the inhibitory effects of TTP on the Warburg effect cancer. Our data propose a new model whereby the TTP down-regulates IR and plays an important role as a negative regulator of both the energy metabolism and proliferation of cancer cells. Citation Format: Ji Eun Yoon, VO MAI TRAM, Nal Ae Yoon, Jin Ho Back, Young Joo Min, Wha Ja Cho. TTP inhibits insulin receptor signals in cancer cell. [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 1170. doi:10.1158/1538-7445.AM2015-1170
Meat and fat intake and colorectal cancer risk: A pooled analysis of 14 prospective studies
Authors: Eunyoung Cho, Stephanie A. Smith-Warner
Journal: Cancer Research (2004)

491  Relatively high red meat and fat intakes have been hypothesized to increase the risk of colorectal cancer. However previous epidemiologic studies on meat and fat intake and colorectal cancer risk have been inconclusive. We therefore examined the association in a pooled analysis of the primary data from 14 prospective follow-up studies from North America and Europe. Meat and fat intake was assessed using a validated food-frequency questionnaire in each study at baseline. We calculated study-specific relative risks and pooled them using a random-effects model. During follow-up of 725,258 women and men over a maximum of 5 to 20 years in the studies, 7,743 incident cases of colorectal cancer were documented. Greater intake of either red meat (excluding processed meat) or processed meat was not related to colorectal cancer risk. The pooled multivariate relative risks (RRs) of colorectal cancer were 1.00 (95% CI 0.92-1.08) for each 90g(approximately 3 oz)/d increase of red meat and 1.05 (95% CI 0.96-1.15) for each 30g/d increase of processed meat. However, intake of poultry and seafood was related to a reduced risk of colorectal cancer (RR= 0.88 [95% CI 0.77-1.00] for each 90g/d increase, P value for heterogeneity=0.04). The RRs for colorectal cancer for each 45g/d increase were 0.92 (95% CI 0.83-1.02) for poultry and 0.91 (95% CI 0.83-0.99) for seafood. Intakes of total, saturated, monounsaturated, and polyunsaturated fats were not appreciably associated with colorectal cancer risk. In conclusion, these prospective data do not support a positive association between higher red meat and fat intake and colorectal cancer risk. Higher intake of poultry and fish may be associated with a lower risk of colorectal cancer.
The Ambiguity of Reduction
Journal: New England Journal of Medicine (1977)

I claim that the question of whether chemistry is reduced to quan- tum mechanics is more ambiguous and multi-faceted than generally supposed. For example, chemistry appears to be both reduced and not reduced at the same time depending on the perspective that one adopts. Similarly, I argue that some conceptual issues in quantum mechanics are ambiguous and can only be laid to rest by embracing paradox and ambiguity rather than regarding them as obstacles to be overcome. Recent work in the reduction of chemistry is also reviewed, including discussions of the ontological reduction of chemis- try and the question of the emergence of chemistry from physics.
Coinfection with<i>Borrelia burgdorferi</i>and the Agent of Human Granulocytic Ehrlichiosis
Authors: Sylvie J. De Martino, Jason A. Carlyon, Erol Fikrig
Journal: New England Journal of Medicine (2001)

To the Editor: Lyme disease and human granulocyte ehrlichiosis are infections carried by the deer tick, Ixodes scapularis. Ticks may harbor both Borrelia burgdorferi and the human granulocytic ehrlichiosis bacterium, the causative agents of these diseases, and dual infections can occur.1 We assessed the risk of exposure to human granulocytic ehrlichiosis among 86 persons with serologic evidence of Lyme disease living in southern Connecticut and Rhode Island — areas in which Lyme disease and human granulocytic ehrlichiosis are relatively common. We used an enzyme-linked immunosorbent assay (ELISA) and immunoblotting (for IgM and IgG antibodies) with B. burgdorferi as the . . .
Cholesterol Reduction in Cardiovascular Disease — Clinical Benefits and Possible Mechanisms
Authors: Glenn N. Levine, John F. Keaney, Joseph A. Vita
Journal: New England Journal of Medicine (1995)

The causal role of an elevated serum cholesterol level in the genesis of atherosclerosis and its clinical sequelae, particularly ischemic heart disease, is now well established. The recognition of this role has been the impetus for numerous trials designed to test the hypothesis that a reduction in the cholesterol level will lead to a reduction in morbidity and mortality from cardiovascular disease. Most of these studies have indeed demonstrated a reduction in the incidence of ischemic cardiac events, and some have also shown a reduction in mortality from cardiovascular disease. Despite this intensive investigation, however, the mechanism (or mechanisms) responsible . . .