tbuckley/cabot-search huggingface dataset:
Quantitative intra-operative RT-PCR assay predicts size of sentinel node metastases.
Authors: P Blumencranz, M Pieretti, H Asad, A Zanchi
Journal: Cancer Research (2009)

Abstract Abstract #1002 The GeneSearch™ Breast Lymph Node (BLN) Assay (Veridex, LLC) has been FDA approved to detect metastases &amp;gt; 0.2 mm in the sentinel lymph nodes (SLNs) of breast cancer patients and has been in clinical use in our institute for 11 months. This assay gives a qualitative (negative/positive) result by applying cutoff values to the cycle times (Ct) of the two mRNA markers analyzed: mammaglobin (MG) (cutoff value = 31 Cts) and cytokeratin 19 (CK19) (cutoff value = 30 Cts). This is the first study to evaluate if the quantitative Ct values of MG and CK19 can be used to estimate probable size of nodal metastases.&amp;#x2028; To date 184 patients have been tested using the BLN Assay during its clinical use at Morton Plant Hospital. An additional 172 patients were tested with the BLN Assay at our institute during investigational studies. In both cases, the SLNs of breast cancer patients were divided into ∼2 mm pieces. Alternating pieces were homogenized and were processed intra-operatively. The other pieces of the SLN were used for permanent section H&amp;E analysis. The patient was considered H&amp;E positive when a metastasis &amp;gt; 0.2 mm was identified. During clinical use, same-surgery complete axillary dissection was performed when the assay was positive (n = 34).&amp;#x2028; Performance of the assay's qualitative result against permanent section H&amp;E on adjacent node pieces was similar for the two groups (total N = 356), for a total sensitivity of 96% (81/84), specificity of 93% (254/272), and overall agreement of 94%. The marker Ct values correlated with metastases size as determined by H&amp;E in adjacent node pieces (r = 0.74 for MG and 0.72 for CK19, p &amp;lt; .0001). The lower the Ct values, the greater the likelihood of macrometastases reported by H&amp;E, as described in Table 1. For example if CK19 is &amp;lt;21.0 and MG is &amp;lt; 25.0, there is 100% chance for H&amp;E positivity in the SLNs, with the majority being macrometastases.&amp;#x2028; &amp;#x2028; Additionally, BLN Assay Ct values in the SLN were predictive of metastases in the non-SLN nodes. For example, of the 12 patients who had a SLN with CK19 &amp;lt; 24 Cts, 9 (75%) had H&amp;E positive non-SLNs. For the same 12 patients, SLNs were H&amp;E positive (5 macrometastases, 5 micrometastases, and 2 reported as &amp;gt; 0.2 mm).&amp;#x2028; The BLN Assay's high intra-operative qualitative performance minimizes the need for second surgeries for complete axillary dissections. Results from this investigational study examining the marker Ct values suggest that the assay may provide valuable individual tumor volume data intra-operatively or post-operatively. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1002.
Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.
Authors: A Ohnishi, Y Orita, R Okahara, H Fujihara, T Inoue, Y Yamamura, Y Yabuuchi, T Tanaka
Journal: Journal of Clinical Investigation (1993)

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men.
Erythrocyte webb‐type glycophorin C variant lacks N‐glycosylation due to an asparagine to serine substitution
Authors: Marilyn J. Telen, Caroline Le Van Kim, Mary Lou Guizzo, Jean‐Pierre Cartron, Yves Colin
Journal: American Journal of Hematology (1991)

Abstract We have analyzed part of the sequence of the human glycophorin C (GPC) gene carried by a Webb blood‐group positive donor. Our results indicate that the lack of N‐glycosylation of the variant GPC associated with the Webb phenotype is due to a point mutation resulting in an asparagine to serine substitution at amino acid position 8.
Chimeric 7e3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angioplasty
Authors: Judith K Mickelson, M.Nadir Ali, Neal S Kleiman, Nasser M Lakkis, Thomas W Chow, Bonnie J Hughes, C.Wayne Smith
Journal: Journal of the American College of Cardiology (1999)
A quantitative assessment of protoporphyrin IX metabolism and phototoxicity in human skin following dose-controlled delivery of the prodrugs 5-aminolaevulinic acid and 5-aminolaevulinic acid-n-pentylester
Authors: S. Gerscher, J.P. Connelly, G.M.J. Beijersbergen Van Henegouwen, A.J. Macrobert, P. Watt, L.E. Rhodes
Journal: British Journal of Dermatology (2001)

Background Topical 5-aminolaevulinic acid (ALA) is widely used in photodynamic therapy (PDT) to generate protoporphyrin IX (PpIX) in the skin. However, other prodrugs may be more effective. Objectives The pharmacokinetics of ALA- and ALA-n-pentylester-induced PpIX, together with the phototoxicity after PDT, were compared in human skin in vivo, using iontophoresis as a quantitative drug delivery system. Methods A series of six increasing doses of equimolar prodrug solutions was iontophoresed into normal skin of the upper inner arms of 20 healthy subjects. The kinetics of PpIX metabolism in skin (n = 4) and the response to light exposure, performed at 4·5 h (n = 6) and 6 h (n = 10) after application, were assessed by skin surface PpIX fluorescence and postirradiation erythema. Results ALA and ALA-n-pentylester showed a linear correlation between logarithm of dose and PpIX fluorescence (P < 0·005), and logarithm of dose and skin phototoxicity with irradiation at 4·5 h (P < 0·001 and P < 0·005, respectively) and 6 h (P < 0·05 and P < 0·0001, respectively) after iontophoresis. Higher phototoxicity was observed with ALA-n-pentylester than with ALA when sites were irradiated at 6 h, as indicated by the significantly lower theoretical threshold dose for erythema (P < 0·05) and the shift of the PpIX fluorescence/phototoxicity curve towards greater skin erythema at equal PpIX fluorescence levels. Depth of PpIX fluorescence in skin, as determined by fluorescence microscopy, was similar for both prodrugs, but a more homogeneous distribution of PpIX was seen with the more lipophilic ALA-n-pentylester. Conclusions The observed greater phototoxicity of ALA-n-pentylester relative to ALA may be attributable to a more favourable PpIX localization in tissue and/or greater intrinsic toxicity.
A Typology of Shared Decision Making, Informed Consent, and Simple Consent
Authors: Simon N. Whitney, Amy L. McGuire, Laurence B. McCullough
Journal: Annals of Internal Medicine (2004)

Enhancing patient choice is a central theme of medical ethics and law. Informed consent is the legal process used to promote patient autonomy; shared decision making is a widely promoted ethical approach. These processes may most usefully be seen as distinct in clinically and ethically important respects. The approach outlined in this article uses a model that arrays all medical decisions along 2 axes: risk and certainty. At the extremes of these continua, 4 decision types are produced, each of which constrains the principal actors in predictable ways. Shared decision making is most appropriate in situations of uncertainty, in which 2 or more clinically reasonable alternatives exist. When there is only 1 realistic choice, patient and physician may gather and exchange information; however, the patient cannot be empowered to make choices that do not exist. In contrast, informed consent does not require the presence of clinical choice; it is appropriate for all decisions of significant risk, even if there is only one option. When a clinical decision contains both risk and uncertainty, shared decision making and informed consent are both appropriate. For decisions of lower risk, consent should still be present, but it can be simple rather than informed. Clinicians may use this analysis as a guide to their own interactions with patients. In the continuing effort to provide patients with appropriate decisional authority over their own medical choices, shared decision making, informed consent, and simple consent each has a distinct role to play.
The influence of verapamil on serum digoxin concentration.
Authors: H O Klein, R Lang, E Weiss, E Di Segni, C Libhaber, J Guerrero, E Kaplinsky
Journal: Circulation (1982)

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.
Somatic Mutations — Not Just for Cancer Anymore
Authors: Jennifer M. Puck, Stephen E. Straus
Journal: New England Journal of Medicine (2004)

Opportunities for genetic errors during reproduction are so frequent that one wonders how any of us turn out healthy. Although many of these errors are inconsequential, and some can beneficially increase human diversity, germ-line mutations underlie risks for thousands of diseases. Genetic diseases, however, need not be inherited through the germ line: somatic mutations can arise in discrete cell lineages early in embryonic development or during postnatal life. The implications of somatic mutations are best known in the field of oncology. As predicted by Robert Weinberg two decades ago, and elegantly elucidated with regard to colon cancer by Bert Vogelstein, . . .
1204 PHARMACOKINETICS, SAFETY AND TOLERABILITY OF THE HCV NS5A INHIBITOR ABT-267 FOLLOWING SINGLE AND MULTIPLE DOSES IN HEALTHY ADULT VOLUNTEERS
Authors: E.O. Dumas, A. Lawal, R.M. Menon, T. Podsadecki, W. Awni, S. Dutta, L. Williams
Journal: Journal of Hepatology (2011)
Retirement: the four year itch
Authors: James Owen Drife
Journal: BMJ (2013)

Retirement is one of those sensitive topics, like politics and religion, to be avoided when talking to doctors who are still working. It risks provoking a diatribe on the new NHS pension arrangements, their children’s university tuition fees, and, for comparison, bankers’ bonuses. We of the boomer generation have learnt to keep our mouths shut and our heads down.

If it’s any comfort, young doctors, let me reassure you that retirement is rather a disappointment. Yes, there is the …
Tuberculous peritonitis and laparotomy.
Authors: F P Antia
Journal: BMJ (1973)

be traced.Thus the work of Bernstein and others in Britain and America on the importance of early language stimulation, with which we are fully familiar, is not applicable to the present group of children.May we suggest that all of us who are genuinely concerned with language develop- ment in young children join together in tackling this important problem rather than widening divisions of opinion by criticizing large-scale screening procedures in a national survey which, though inevitably crude, did produce useful information hitherto unavail- able.-Weare, etc.
Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells.
Authors: D D Von Hoff, B Forseth, C N Clare, K L Hansen, D VanDevanter
Journal: Journal of Clinical Investigation (1990)

Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63-72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5;17)(q11.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients' tumors.
Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era
Authors: Cristina Ripoll, Rafael Bañares, Diego Rincón, María-Vega Catalina, Oreste Lo Iacono, Magdalena Salcedo, Gerardo Clemente, Oscar Núñez, Ana Matilla, Luis-Miguel Molinero
Journal: Hepatology (2005)

Abstract Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00-1.06; P = .05) so that each 1-mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion , HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved. (Hepatology 2005;42:793–801.)
Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B
Authors: Arvind K. Jain, Amit K. Goyal, Prem N. Gupta, Kapil Khatri, Neeraj Mishra, Abhinav Mehta, Sharad Mangal, Suresh P. Vyas
Journal: Journal of Controlled Release (2009)
B1-04: DN-101-004: a multicenter, open label, dose ranging study of DN-101 (ASENTAR”) and docetaxel in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) after platinum-based chemotherapy
Authors: Howard West, Leonard Reyno, Stella Lee, Louis Fehrenbacher, Allen L. Cohn, Judith O. Hopkins, David H. Irwin, David A. Smith, Thomas E. Boyd, Mark R. Olsen
Journal: Journal of Thoracic Oncology (2007)
AUTOMATIC HYPODERMIC SYRINGE FOR SELF ADMINISTRATION OF INSULIN AND OTHER USES
Authors: Herbert Busher
Journal: JAMA (1934)

The greatest drawback in the treatment of diabetes with insulin, encountered in active practice, is the necessity of the patient to administer this medication himself with a hypodermic needle. The instinct of self preservation creates in every human being a fear to inflict pain on himself. Many a sufferer from diabetes struggles along on diet, to his own detriment and to the chagrin of his physician, simply because he lacks the will power necessary to overcome this natural inhibition. To overcome this difficulty I have devised an automatic hypodermic syringe. The device holds the syringe under tension by means of a spring. After the syringe has been filled with the required amount of insulin, it is drawn back and cocked. The device is then placed firmly against the skin, and by touching a trigger the needle is thrust through the skin with lightning rapidity, very much as the modern spring
E1B-55 kDa-Defective Adenoviruses Activate p53 in Mesothelioma and Enhance Cytotoxicity of Anticancer Agents
Authors: Makako Yamanaka, Yuji Tada, Kiyoko Kawamura, Quanhai Li, Shinya Okamoto, Kuan Chai, Sana Yokoi, Min Liang, Toshihiko Fukamachi, Hiroshi Kobayashi, Naoto Yamaguchi, Atsushi Kitamura, Hideaki Shimada, Kenzo Hiroshima, Yuichi Takiguchi, Koichiro Tatsumi, Masatoshi Tagawa
Journal: Journal of Thoracic Oncology (2012)
Re: Ricardo L. Favaretto, Shahrokh F. Shariat, Daher C. Chade et al. The Effect of Tumor Location on Prognosis in Patients Treated with Radical Nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol 2010;58:574–80
Authors: Pascal Mouracade
Journal: European Urology (2011)
The first international standard for antibodies to double stranded DNA.
Authors: T E Feltkamp, T B Kirkwood, R N Maini, L A Aarden
Journal: Annals of the Rheumatic Diseases (1988)

This paper announces the availability of the first international standard for anti-double-stranded DNA (anti-dsDNA). The material, coded Wo/80, was obtained after recalcification of plasma taken from a patient with systemic lupus erythematosus. Vials were filled with 500 microliters serum and freeze dried. The serum contains no other autoantibodies in measurable quantities. The vials should be stored at -20 degrees C. The standard should be used for establishing national, regional, or local standards. In eight laboratories satisfactory results with the immunofluorescence technique on Crithidia luciliae were obtained; the titres varied between 1/20 and 1/640 (mean 1/160). In seven laboratories the Farr assay, with the so called 9Amersham kit9, was performed. At a dilution of 1:40 a mean binding percentage of about 50% was observed. After reconstitution with 500 microliters of distilled water, the vial contains 100 IU/500 microliters or 200 IU/ml. The standard can be obtained from the custodian of WHO: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, PO Box 9190 1006 AD Amsterdam, The Netherlands.
Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings
Authors: José Garnacho-Montero, C. Ortiz-Leyba, Esteban Fernández-Hinojosa, Teresa Aldabó-Pallás, Aurelio Cayuela, Juan A. Marquez-Vácaro, Andrés Garcia-Curiel, F. J. Jiménez-Jiménez
Journal: Intensive Care Medicine (2005)
Age-Related Dementia
Authors: Tracy Hampton
Journal: JAMA (2006)

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Carcinoid of the breast.
Authors: T F Warner
Journal: BMJ (1978)

heart size decreased after discontinuation of digoxin, contrary to expectations.These observations underline the inherent dangers of digitalis therapy, especially in coronary heart disease and respiratory in- sufficiency.It seems important to make sure that the only patients who are allowed to go on taking digoxin are those who otherwise would deteriorate clinically.At the moment the only way to achieve this goal is to discontinue the drug under conditions enabling close observation of the patients.
1031–33 Intravenous Triiodothyronine in Patients with Advanced Heart Failure
Authors: Michele A. Hamilton, Lynne W. Stevenson, Gregg C. Fonarow, Anthony E. Steimle, Jaime D. Moriguchi, Antoine Hage, Michael Gleason, Susan M. Kaiser, Kim A. Scheibly, Julie A. Walden
Journal: Journal of the American College of Cardiology (1995)