tbuckley/cabot-search huggingface dataset:
Diagnosis of Creutzfeldt-Jakob disease
Authors: M Zeidler, R Knight, G Stewart, J W Ironside, R G Will, A J E Green, M Pocchiari, C W Heizmann
Journal: BMJ (1999)

Editor—Collinge et al recommend that tonsil biopsy be considered in all those in whom new variant Creutzfeldt-Jakob disease is suspected.1 Though the detection of protease resistant prion protein in tonsillar tissue from a young person with a rapidly progressive dementia may have a high specificity for this diagnosis, there are no published data on sensitivity, specificity, or safety; the procedure carries the risk of haemorrhage and infection as well as the risks associated with anaesthesia. Some patients clinically suspected of having new variant Creutzfeldt-Jakob disease, and therefore potential candidates for tonsil biopsy, have subsequently recovered.2 Further information is obviously required, and we concur with the recommendation of a recent WHO consultation that this should come from postmortem studies.3

Brain biopsy has been carried out in 9 of the 27 cases of new variant Creutzfeldt-Jakob disease in the United Kingdom. This procedure has risks but, in contrast to tonsillar biopsy, enables potentially treatable neurological disorders to be identified. New variant Creutzfeldt-Jakob disease is confirmed in about 1 in 7 cases,2 and routine tonsillar biopsy in the population of suspected cases would lead to a high proportion of negative results. A negative result on tonsillar biopsy does not preclude the necessity to proceed to brain biopsy in selected cases. There is clearly a need for a non-invasive diagnostic test for new variant Creutzfeldt-Jakob disease, and preliminary investigation indicates that the presence of posterior thalamic high signal on brain magnetic resonance imaging may be diagnostically useful.4

The accepted clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease have depended on electroencephalography, and an alternative paraclinical criterion would be useful. Cerebrospinal fluid 14-3-3 protein has proved to be a remarkably sensitive and specific marker for sporadic Creutzfeldt-Jakob disease when used appropriately. Protease resistant prion protein has not been detected in palatine tonsillar tissue obtained at necropsy from the small number of patients with sporadic Creutzfeldt-Jakob disease studied to date (unpublished data).5 Unless necropsy studies yield positive results, the clinical use of tonsil biopsy in sporadic Creutzfeldt-Jakob disease is not justified.
Methoserpidine
Authors: M. C. Holt
Journal: BMJ (1961)

Two favourable aspects of guanethidine remain to be stressed.First, the absence of any significant development of drug tolerance, one of the major disappointments of bretylium tosylate therapy; and, secondly, the absence of any toxic drug effects on liver, kidney, or haemopoietic organs.Comparison of guanethidine with the specific sympa- thetic blocker and other anti-adrenergic substance, bretylium tosylate, becomes unavoidable.Although in their main pharmacological action these two drugs appear to be essentially similar, there are certain differences which have an important bearing on their practical use in clinical medicine.
Renal Transplantation between HL-A Identical Donor-Recipient Pairs
Authors: H. F. Seigler, J. C. Gunnells, R. R. Robinson, F. E. Ward, D. B. Amos, D. T. Rowlands, P. M. Burkholder, W. J. Klein, D. L. Stickel
Journal: Journal of Clinical Investigation (1972)

16 patients underwent renal transplantation from a sibling donor who was prospectively determined to be ABO compatible and HL-A identical with the recipient. Unidirectional mixed leukocyte reactions were performed; in each instance, lymphocyte stimulation in either direction was not observed. The plasma creatinine 10-68 months after transplantation in these 16 patients ranged between 0.9 and 1.9 mg/100 ml. The creatinine clearance ranged from 48 to 113 ml/min, and the blood urea nitrogen (BUN) ranged between 12 and 35 mg/100 ml. Urine protein excretion varied from 0.11 to 1.86 g/day. Six patients exhibited no detectable clinical episodes of acute rejection; they were treated with azathioprine alone and each of them demonstrated normal or near normal renal histology when biopsy specimens were obtained more than 6 months after transplantation. Nine patients experienced acute rejection episodes that required the use of steroid therapy. The severity of these rejection episodes was variable; they included a mild reduction in renal function with an immediate steroid-induced restoration of function and eventual discontinuance of steroid therapy to severe reduction in function requiring prolonged and moderate doses of steroids without return to normal renal function. Renal histological observations in this group ranged from mild to marked cellular and structural changes which fit the criteria of the rejection. One patient demonstrated a gradual loss of renal function with heavy proteinuria. Biopsy of this allograft demonstrated the recurrence of original disease, i.e., lobular glomerulonephritis. The marked variability in the clinical course and allograft morphology in these 16 patients could be explained by antigenic differences at non-HL-A loci. The presence of minor histocompatibility loci has been well documented in other mammalian species and they are most certainly present in man. The need for their identification and definition is stressed.
Abstract 3502: Serum Phosphorus Levels are Associated with Incident Fatal and Non-Fatal Coronary Disease in Men but not in Women in the Community
Authors: Francesca Cardarelli, Antonio Bellasi, Stephen J Onufrak, Leslee J Shaw, Charles A Herzog, Emir Veledar, Viola Vaccarino, Paolo Raggi
Journal: Circulation (2007)

Mineral metabolism disorders are associated with coronary atherosclerosis and poor outcomes in chronic kidney disease (CKD) and cardiovascular disease (CVD) patients. A recent study suggested that elevated levels of serum phosphorus are associated with increased risk of CVD in subjects free from CKD and CVD. However, data suggest that the distribution of serum phosphorus differs by gender and it is not known whether phosphorus carries the same prognostic significance in men and in women. We tested the association of baseline serum phosphorus levels with incidence of CHD (myocardial infarction or fatal coronary disease) in 13,998 subjects 45 to 64 years old free of CHD, stroke, or CKD from the Atherosclerosis Risk in Communities (ARIC) study with public use data. The mean follow up was 12.5 years. Serum phosphorus was classified according to quintiles. Elevated phosphorus was significantly associated with age, female gender, smoking, hypercholesterolemia, and fibrinogen levels (p &lt; 0.0001 for each), but was inversely associated with hypertension and not associated with estimated glomerular filtration rate (eGFR). We observed a j-shaped relationship of serum phosphorus with CHD among men but not among women. Compared to men in the 2nd quintile, men in the 1st quintile experienced a 30% increased rate of CHD (multivariable adj. HR: 1.30, 95% CI: 1.01, 1.68) while HRs increased incrementally from 1.17 (95% CI: 0.89, 1.54) to 1.51 (95% CI: 1.09, 2.09) from the 3rd through 5th quintiles. This relationship in men remained significant after adjustment for classic CVD risk factors and estimated GFR (table ). Among women, serum phosphorus was not significantly associated with CHD (table ). In conclusion, this study suggests a j-shaped association of serum phosphorus with CHD risk in men but not women free of CKD and CHD at baseline. Table
NCCN Task Force Report: Positron Emission Tomography (PET)/Computed Tomography (CT) Scanning in Cancer
Authors: Donald A. Podoloff, Ranjana H. Advani, Craig Allred, Al B. Benson, Elizabeth Brown, Harold J. Burstein, Robert W. Carlson, R. Edward Coleman, Myron S. Czuczman, Dominique Delbeke, Stephen B. Edge, David S. Ettinger, Frederic W. Grannis, Bruce E. Hillner, John M. Hoffman, Krystyna Kiel, Ritsuko Komaki, Steven M. Larson, David A. Mankoff, Kenneth E. Rosenzweig, John M. Skibber, Joachim Yahalom, JQ Michael Yu, Andrew D. Zelenetz
Journal: Journal of the National Comprehensive Cancer Network (2007)

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology. ( JNCCN 2007;5(Suppl 1):S1–S22)
What level of risk tips the balance of benefits and harms to favor screening mammography starting at age 40
Authors: Nicolien T. van Ravesteyn, Diana L. Miglioretti, Natasha K. Stout, Sandra J. Lee, Clyde B. Schechter, Diana S.M. Buist, Hui Huang, Eveline A.M. Heijnsdijk, Amy Trentham-Dietz, Oguzhan Alagoz, Aimee M. Near, Karla Kerlikowske, Heidi D. Nelson, Jeanne S. Mandelblatt, Harry J. de Koning
Journal: Annals of Internal Medicine (2012)

Background
In the US biennial screening mammography is recommended for average-risk women aged 50–74 because the benefits outweigh the harms. For women with increased risk starting screening at age 40 may have a similar harm-benefit ratio.
Abstract 40: HB-EGF‑mediated CITED4 signaling in lung cancer
Authors: Cheng-Han Hsieh, Yu-Ting Chou, Cheng-Wen Wu
Journal: Cancer Research (2015)

Abstract Abnormal activation of the EGF receptor (EGFR) signaling is a hallmark of lung cancer. However, the role of heparin-binding EGF-like growth factor (HB-EGF), one of EGFR ligands, in lung tumorigenesis has been unappreciated. In this study, we showed that HB-EGF was highly expressed in a subgroup of lung cancer cells, the proliferation of which was dependent on HB-EGF signaling. Members of CITED family proteins respond to various cytokine signalings, regulating cell proliferation; among them, we identified CITED4 as a downstream effecter of HB-EGF. We revealed that CITED4 was upregulated by HB-EGF through a STAT3 dependent pathway. Moreover, CITED4-silencing attenuated HB-EGF-mediated lung cancer cell proliferation. ChIP analysis and promoter reporter assay showed that STAT3 bound CITED4 promoter, enhancing CITED4 transcription. Co-immunoprecipitation analysis identified MYC as a CITED4-interacting protein. Furthermore, we found that CITED4 expression promoted MYC-mediated transcription of cyclin D1 promoter, leading to increased G1/S cell cycle transition. Thus, our findings support that HB-EGF-CITED4 signaling cascade plays a critical role in aberrant proliferation in lung cancer with potential as a biomarker for lung cancer progression. Citation Format: Cheng-Han Hsieh, Yu-Ting Chou, Cheng-Wen Wu. HB-EGF‑mediated CITED4 signaling in lung cancer. [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 40. doi:10.1158/1538-7445.AM2015-40
Estrogen alone and health outcomes in black women by African ancestry.
Authors: Rowan T. Chlebowski, Wendy Barrington, Aaron K Aragaki, JoAnn E Manson, Gloria Sarto, Mary Jo O'Sullivan, Jane A. Cauley, Lihong Qi, Robert B. Wallace, Ross L Prentice
Journal: Journal of Clinical Oncology (2015)

1502 Background: Disparities are seen in breast cancer outcome in black compared to white women. However, in black women in the Women’s Health Initiative (WHI) randomized trial, estrogen alone significantly reduced breast cancer incidence, but its comprehensive influence on health outcomes in black women in this trial has not been reported. Therefore we examined, in post-hoc analyses, the risks and benefits for estrogen alone use in black women in the WHI randomized trial overall and by African ancestry. Methods: Of 10,729 postmenopausal women with prior hysterectomy randomized at 40 US centers, 1,616 were black, including 1,061 with % African ancestry determined using information from 656,852 single nucleotide polymorphisms. Participants received daily conjugated equine estrogen (CEE 0.625 mg) or placebo for 7.2 years (median intervention) with 13 years cumulative follow-up. Coronary heart disease (CHD) and breast cancer were primary efficacy and safety outcomes. A global index of outcomes under potential hormone influence also included stroke, colorectal cancer, hip fracture, pulmonary embolism and death. Results: At entry, black women had more diabetes, hypertension, and prior myocardial infarctions compared to white women. Black women in the estrogen alone compared to the placebo group had fewer breast cancers (17 vs. 40, hazard ratio [HR] 0.47 95% confidence interval [CI] 0.26-0.82) and somewhat fewer thromboembolism events (23 vs. 40, HR 0.63 95% CI 0.38-1.06, interaction p = 0.049 vs. effect in white women). All other outcomes including CHD, stroke, overall survival and the global index (HR 0.95 95% CI 0.77-1.17) were null without racial differences. In women with > 80% African ancestry, breast cancer HR was lower (0.32 95% CI 0.12-0.86, trend p = 0.04 for effect modification by ancestry). In black women, the estrogen global index effect was more favorable in younger (50-59 years) (HR 0.65 95% CI 0.43-0.98) than in older women. Conclusions: In black postmenopausal women with prior hysterectomy, estrogen alone significantly reduced breast cancers with no apparent adverse influence on CHD, stroke, or mortality. Favorable estrogen alone effects on the global index in younger Black women warrant further study. FUNDING: National Institutes of Health. Clinical trial information: NCT00000611.
Confidentiality dilemmas in group psychotherapy with substance- dependent physicians
Authors: H B Roback, R F Moore, G J Waterhouse, P R Martin
Journal: American Journal of Psychiatry (1996)

The purposes of this article are 1) to review federal and state laws relevant to confidentiality in group therapy with impaired physicians and 2) to provide empirical data concerning the actual confidentiality practices and experiences of group therapists treating chemically impaired physicians.In the clinical research phase, 25 state medical societies identified 45 rehabilitation centers as those to which the societies preferentially referred chemically impaired physicians. Fifty-one group leaders from 33 of these rehabilitation centers completed the survey questionnaire employed in this project.Because of the risk of potentially irreversible social and professional injury, physician patients were exceedingly concerned about breaches of confidentiality. Co-members' infractions most often involved the violator sharing with close friends and family members the name and abuse history of a fellow physician. In contrast, transgressors rarely leaked information about a co-member's drug-related illegal behaviour.Chemically impaired physicians would feel safer in sharing secrets in group therapy if more jurisdictions adopted legislation making co-members liable for violating confidentiality. Currently the pertinent body of law is confusing and inconsistent and provides little protection to impaired physicians who enter group therapy. The authors propose ideas for model legislation.
Lessons in medical school access from America
Authors: J Pip Fisher
Journal: BMJ (2008)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection.patricia de la rosa/stone/getty images screening for type 2 diabetes Screen women with gestational diabetes for type 2 diabetesOne way to reduce type 2 diabetes would be to target women with gestational diabetes. 1Maternity services are increasingly screening women and treating gestational diabetes, after the demonstration of significant perinatal benefits. 2 Within 10 years, 35-60% of women with gestational diabetes will develop type 2 diabetes. 3These women are an already identified high risk group.Their children are also more likely to be obese and share a genetic propensity to type 2 diabetes. 4 Following up women with gestational diabetes allows the targeting of two high risk people without additional screening.Many health service contacts are made in the first year of a child's life, therefore interventions may be easily delivered.Also, many women are receptive to health advice around the time of a birth when new lifestyle patterns are being established.Improved follow-up of these women with promotion of diet, exercise, and pharmacology, together with prolongation of breast feeding and subsequent healthy infant feeding is likely to be effective for mother, child, and the health service.
P0261 : A global risk gene score predicts early and late tumor recurrence after resection of hepatocellular carcinoma
Authors: J. Dekervel, D. Popovic, H. van Malenstein, P. Windmolders, L. Libbrecht, A. Bulle, B. De Moor, E. Van Cutsem, F. Nevens, C. Verslype, J. van Pelt
Journal: Journal of Hepatology (2015)
Cell cycle regulation and radiosensitization of TZT-1027, a novel antimicrotubule agent
Authors: Yusaku Akashi, Taroh Satoh, Isamu Okamoto, Kenji Tamura, Masaaki Terashima, Takafumi Okabe, Minoru Suzuki, Koji Ono, Kazuhiko Nakagawa, Masahiro Fukuoka
Journal: Cancer Research (2006)

589   TZT-1027, a dolastatin 10 derivative, is a novel antimicrotubule agent that inhibits tubulin porimerization. TZT-1027 has demonstrated potent antitumor activity against a variety of murine and human tumor cell lines, and effect on cell cycle progression. Since the exact effect on cell cycle progression was not fully understood, we have evaluated cell cycle regulatory mechanism of TZT-1027 using tsFT210 cells, which express a temperature-sensitive Cdc2 mutant. To determine the phase of the cell cycle at which TZT-1027 exert its growth-inhibitory effect, after synchronized at the G2/M phase, tsFT210 cells were treated with different concentrations of TZT-1027 for 6 hours and analyzed by flow cytometry. We have demonstrated TZT-1027 affected on the G2/M phase specifically, leading to G2/M arrest. These data allowed us to examine the possible synergistic effects of TZT-1027 combined with ionizing radiation. A clonogenic assay indicated that H-460 cells were sensitized to gamma radiation by TZT-1027 with 0.2nM concentration using different combining exposure schedules, concurrent and sequential exposure. The DEFs (dose enhancement factors at a surviving fraction of 0.1) were 1.38, 1.61, concurrent exposure schedule, sequential exposure schedule respectively. Currently in vivo investigation with xenograft models is undergoing. Updated results will be presented in the meeting.
Abstract 136: Evaluation of reversible BTK inhibitors in cell lines with clinically relevant Ibrutinib resistance mutations
Authors: Regina Wai-Yan Choy, Luciana Burton, Wendy Young, James J. Crawford, Elicia Penuel, Lisa D. Belmont
Journal: Cancer Research (2015)

Abstract Background Ibrutinib, a small molecule inhibitor that covalently binds Cys481 of Bruton's Tyrosine Kinase (BTK), has recently been approved in Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Although the majority of patients respond to this drug, eventually resistance develops. Known causes for resistance include the outgrowth of cancer cells with mutations in either the drug binding pocket of BTK or activating mutations in the downstream effector, PLCγ2. Objective To explore mechanisms of resistance to ibrutinib and evaluate the potential of next generation BTK inhibitors on ibrutinib resistant cancer, we selected for resistance in cultured lymphoma cells. We chose TMD8, a cell line model of diffuse large B-cell lymphoma (DLBCL) that has constitutive B-cell receptor signaling, and REC-1, an ibrutinib sensitive MCL line, to model resistance. Methods TMD8 and REC-1 were cultured in increasing concentrations of ibrutinib to generate resistant cell lines. Genetic changes that may account for resistance were evaluated using whole exome sequencing. Resistant cell lines were evaluated for sensitivity to a small panel of BTK inhibitors. Results We generated a TMD8 derived cell line that is 1000-fold resistant to ibrutinib. Whole exome sequencing revealed a C481Y mutation in BTK. Reversible inhibitors that are not reliant on this site may function as alternative inhibitors of C481 mutant BTK. Ibrutinib-resistant TMD8 cells were tested for response to novel, reversible BTK inhibitors. The potency was similar to or modestly reduced (3 to 10 fold) on the ibrutinib-resistant cells compared to the parental line. In addition, we generated ibrutinib-resistant cells derived from the REC-1 line. Unlike resistance generated in TMD8, REC-1 resistant cells harbor a L527W mutation in BTK and are resistant to all BTK inhibitors that we evaluated. Conclusions C481Y and L527W BTK mutations have been identified in CLL patients that have relapsed after response to ibrutinib, and C481S mutations have been identified in ibrutinib relapsed CLL and MCL patients. Our data suggest that reversible, next generation BTK inhibitors have the potential to be efficacious on ibrutinib relapsed patients that harbor mutations at C481 of BTK. Citation Format: Regina Wai-Yan Choy, Luciana Burton, Wendy Young, James J. Crawford, Elicia Penuel, Lisa D. Belmont. Evaluation of reversible BTK inhibitors in cell lines with clinically relevant Ibrutinib resistance mutations. [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 136. doi:10.1158/1538-7445.AM2015-136