tbuckley/cabot-search huggingface dataset:
Abstract P2-01-01: Establishment and validation of circulating tumor cell-based prognostic nomograms in 497 first-line metastatic breast cancer patients
Authors: A Giordano, JM Reuben, BL Egleston, D Hajage, GN Hortobagyi, M Cristofanilli, J-Y Pierga, F-C Bidard
Journal: Cancer Research (2012)

Abstract Background: Several prognostic clinical and pathological characteristics have been reported to be independently associated with survival in metastatic breast cancer (MBC). Circulating tumor cells (CTCs) isolated by CellSearch® from peripheral blood of MBC patients was shown to be an additional strong independent prognostic factor for survival and progression of disease. The aim of this study was to combine CTC and other predictors in a nomogram that would allow clinicians to assess, on an individual basis, the prognosis of patients starting first-line chemotherapy for MBC. Patients and Methods: CTCs were counted before the start of treatment using the US Food and Drug Administration–cleared CellSearch® technology. We used a training set of 237 MBC patients starting a first line chemotherapy from the MD Anderson Cancer Center (MDACC, Houston, TX, USA), and nomograms were established to calculate the predicted probability of overall survivals (OS) at 1, 2 and 3 years. These nomograms were externally validated using an independent data set of 260 patients starting a first line chemotherapy from the prospective Institut Curie 2006–04 study (Paris, France). Discriminatory ability of the models was assessed using Harrell's c-statistic examining the model in the training sample (U.S. data) and the validation sample (French data). Accuracy of the nomograms was assessed both within the training sample and the validation sample via calibration plots at 1, 2 and 3 years. Covariates computed in the model were: age, subtype of disease, presence of visceral metastasis, bone metastasis, performance status, and CTCs. Results: Table1 describes patient characteristics. Median follow-up was of 24.5 and 29 months, respectively in the MDACC and Institut Curie. The C-statistics for OS was 0.7338 in the training set and 0.7229 in the validation set. For the calibration plots, we averaged Cox predictions at two years within the quintiles of the ordered predictions. Within each quintile, we also estimated the unadjusted probability of death using Kaplan-Meier survival estimators. We then plotted unadjusted versus model average predictions at 1, 2 and 3 years. The nomograms discriminated OS prediction at 1, 2 and 3 years very well. Conclusions: Patients with first-line MBC present a wide range of survival duration, and our ability to assess prognosis and predict risks of progression and death on the basis of clinic-pathologic findings is limited. The validated nomograms represent an important tool for estimating prognosis, support treatment-decisions and clinical trial stratification in MBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-01.
What Is Not Closed Is Open
Authors: J. S. Mill
Journal: JAMA (1965)

<h3>To the Editor:—</h3> I have been struck on many occasions with the misuse of the word "occlusion." Literally, occlusion means closed. It does not mean half closed, partially closed, a little bit closed, or a lot closed. When an artery is narrowed but not closed, it is stenotic. Thus "completely occluded" or "partially occluded" leaves the reader with confusion, as it makes considerable difference in our understanding of cerebral blood flow whether the artery is closed, stenotic, or normal in size. For instance, in a recent article 50 cases of "occlusion of the internal carotid artery" are reported; however, careful review reveals that a number of them are only stenotic or "partially occluded." Thus, when one reads the phrase "completely occluded" in a manuscript one is not certain whether the author is really talking about stenosis but using the single word "occluded." Eccentricity has always abounded when and where strength
Medal of Honor
Authors: Francis J. McDougall
Journal: JAMA (1963)

ABSTRACT To the Editor:— I am impelled to make comment on the article by Dr. Roy J. Popkin, Doctors Who Have Been Awarded the Congressional Medal of  (JAMA182:1319 [Dec 29] 1962).The author states in his final paragraphs that Although no Honor Medals were won by Physicians in World War II or the Korean Campaign, it is understandable as the opportunities to be at the front lines were limited. Due to the nature of modern warfare, physicians are rarely assigned to frontline units under combat conditions.As a former battalion surgeon with the infantry in World War II throughout the European campaigns, I can assure Dr. Popkin that his information is quite erroneous. My battalion aid station was seldom farther than 1,000 yards and more often around 250 yards behind the combat troops. It must be explained that the concept of a front-line or straight-battle line is not
Further Observations on the Effect of Synthetic Thyrotrophin-releasing Hormone in Man
Authors: B. J. Ormston, J. R. Kilborn, R. Garry, J. Amos, R. Hall
Journal: BMJ (1971)

Synthetic thyrotrophin-releasing hormone (TRH) given intravenously in doses of 50 mug or more causes a significant rise in serum thyroid-stimulating hormone (TSH) levels but has no effect on serum growth hormone, plasma luteinizing hormone, or plasma 11-hydroxycorticosteroids under carefully controlled basal conditions.The peak TSH response to intravenous TRH occurs at 20 minutes. The mild and transient side effects, which occur only after intravenous TRH, include nausea, a flushing sensation, a desire to micturate, a peculiar taste, and tightness in the chest. There is considerable variability in response to a given dose of TRH in the same subject on different occasions and in different subjects. Oral administration of TRH in doses of 1 mg and above causes a rise in serum TSH, maximal at two hours, a consistent response being obtained at doses of 20 mg and above. A rise in serum protein-bound iodine (P.B.I.) follows that of TSH, a consistent response being observed at 40-mg doses of TRH orally. Measurements of serum TSH after intravenous administration of TRH or of serum TSH or serum P.B.I. after oral TRH should prove useful tests of pituitary TSH reserve.
Temporal Trends in the Use of Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery in New York State and Ontario
Authors: Dennis T. Ko, Jack V. Tu, Zaza Samadashvili, Helen Guo, David A. Alter, Warren J. Cantor, Edward L. Hannan
Journal: Circulation (2010)

Background— Healthcare reform initiatives in the United States have rekindled debate about the role of government regulation in the healthcare system. Although New York State (NYS) historically has had twice as many coronary revascularizations performed as Ontario, the relative evolution of coronary revascularization patterns in both jurisdictions over time is unknown. Methods and Results— We conducted an observational study comparing the temporal trends of cardiac invasive procedures use in NYS and Ontario using population-based data from 1997 to 2006 stratified by procedure indication. For nonacute myocardial infarction patients, the age- and sex-adjusted rate of percutaneous coronary intervention (PCI) was 2.3 times (95% confidence interval, 2.2 to 2.5) greater in NYS than in Ontario in 2004 to 2006. In contrast, population-based rates of coronary artery bypass grafting among nonacute myocardial infarction patients were not significantly different. For acute myocardial infarction patients, differences in coronary revascularization rates between NYS and Ontario narrowed substantially over time. In 2004 to 2006, the relative ratio was 1.3 times higher for PCI (95% confidence interval, 1.2 to 1.5) and 1.4 times higher (95% confidence interval, 1.1 to 1.8) for coronary artery bypass grafting in NYS relative to Ontario. However, a larger relative gap (relative ratio, 2.0; 95% confidence interval, 1.7 to 2.3) was observed among acute myocardial infarction patients undergoing emergency PCIs in NYS compared with Ontario. Conclusions— The market-oriented financing approach in NYS is associated with markedly higher rates of PCI procedures for both discretionary indications (eg, PCI in nonacute myocardial infarction patients) and emergent indications (eg, primary PCI) compared with the government-funded single-payer system in Ontario.
HLA and thyrotoxic periodic paralysis.
Authors: P P Yeo, S H Chan, K F Lui, G B Wee, P Lim, J S Cheah
Journal: BMJ (1978)

A CAT-scan performed six days after the first symptoms disclosed areas of decreased attenuation with a remarkable specific localisation to the putamens.It is tempting to suggest that the transient difficulties in articulation and swallowing, as well as the pyramidal tract symptoms, were due to the influence of oedema on corticobulbar and corticospinal fibres adjacent to the putamen.The CAT-scan finding (figure) is of special interest in relation to the neuropathological findings in fatal cases of methanol intoxication.1-4Orthner3 found symmetrical areas of necrosis in the putamens in 41 of 42 deaths from methanol.Thus the present case suggests that methanol intoxication should be seriously considered when a CAT- scan shows bilateral low-attenuating areas in the putamens.
High-density lipoprotein cholesterol and premature coronary heart disease in urban Japanese men.
Authors: A Kitamura, H Iso, Y Naito, M Iida, M Konishi, A R Folsom, S Sato, M Kiyama, M Nakamura, T Sankai
Journal: Circulation (1994)

BACKGROUND The objective of this study was to examine the relation of high-density lipoprotein cholesterol (HDL-C) to coronary heart disease in Japanese men whose serum total cholesterol is low by Western standards. METHODS AND RESULTS A prospective, observational study based on 7.7 years of follow-up for incidence of coronary heart disease and stroke was conducted. The subjects were 6408 middle-aged male workers aged 40 to 59 years at baseline in urban companies in Osaka, Japan, whose mean serum total cholesterol was 5.10 mmol/L. Mean HDL-C adjusted for age, total cholesterol, systolic blood pressure, alcohol intake, cigarette smoking, and body mass index was 1.27 to 1.28 mmol/L for men who developed coronary heart disease (n = 46) or definite myocardial infarction (n = 21) compared with 1.46 mmol/L for those free of cardiovascular disease (n = 6256; difference, P &lt; .01). There was no significant difference in mean HDL-C between stroke cases (n = 33) and those free of cardiovascular disease. The incidence rates of coronary heart disease and definite myocardial infarction, adjusted for the other risk factors, were three to four times higher in the lowest HDL-C quartile (&lt; 1.24 mmol/L) than the highest quartile (&gt; or = 1.66 mmol/L), and there was a significant dose response for definite myocardial infarction. Serum total cholesterol was positively and significantly associated with coronary heart disease incidence. Furthermore, the inverse association for HDL-C was apparent among men with total cholesterol &lt; 5.69 mmol/L (mean total cholesterol, 4.76 mmol/L) and men with total cholesterol &gt; or = 5.69 mmol/L (mean total cholesterol, 6.26 mmol/L). CONCLUSIONS Coronary heart disease incidence is inversely related to HDL-C in urban Japanese middle-aged men, whose mean total cholesterol (5.10 mmol/L) is relatively low.
Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes.
Authors: T Hercend, J D Griffin, A Bensussan, R E Schmidt, M A Edson, A Brennan, C Murray, J F Daley, S F Schlossman, J Ritz
Journal: Journal of Clinical Investigation (1985)

The initial characterization of two monoclonal antibodies directed at antigens selectively expressed on large granular lymphocytes (LGL) is reported in the present paper. These two reagents, anti-natural killer (NK) H1A and anti-NKH2, were obtained following immunization of mouse spleen cells with a cloned human NK cell line termed JT3. In fresh human peripheral blood, both anti-NKH1A and anti-NKH2 selectively reacted with cells that appeared morphologically as large granular lymphocytes. However, complement lysis studies and two color fluorescence analysis demonstrated that some LGL express both antigens and other cells express only NKH1A or NKH2. Functional analysis of these subsets indicated that the population of NKH1A+ cells contains the entire pool of NK active lymphocytes, whereas expression of NKH2 antigen appeared to delineate a unique subpopulation of LGL which, in a resting state, display a low degree of spontaneous cytotoxicity. Expression of NKH1A and NKH2 was also investigated using a series of nine well characterized human NK clones. All NK clones were found to be NKH1A+ and four out of nine also expressed NKH2. These results strongly supported the view that NKH1A is a "pan-NK" associated antigen, and indicated that at least a fraction of cloned NKH2 + LGL are strongly cytotoxic. Anti-NKH1A was shown to have the same specificity as the previously described N901 antibody and was found here to precipitate a 200,000-220,000-mol wt molecule in SDS-polyacrylamide gel electrophoresis (PAGE) analysis. Anti-NKH2 was specific for a structure that migrates at 60,000 mol wt in SDS-PAGE analysis under reducing conditions. Two color immunofluorescence analysis of NKH1A, NKH2, and other NK-associated antigens (Leu7 and B73.1) demonstrated variable degrees of coexpression of these antigens, which confirmed that NKH1A and NKH2 define distinct cell surface structures. Anti-NKH1A and anti-NKH2 appear to be useful reagents for characterizing LGL present in human peripheral blood and for identifying functionally relevant subsets within this heterogeneous population of cytotoxic lymphocytes.
A NEW METHOD OF MOLDING WAX BOUGIE BULBS
Authors: B. C. Corbus
Journal: JAMA (1926)

To Guy L. Hunner belongs the credit of establishing ureteral stricture as a clinical entity. After many years of persistent writing and discussion on Hunner's part, American urologists have come to believe that stricture of the ureter is a fairly common lesion, and year by year additional case reports have substantiated Hunner's ideas. Hunner's method of dilating the ureter is by means of wax bulbs molded by hand, and, before the advent of the solid bulb, was the best method available. As all solid bulbs are imported and consequently expensive, I conceived the idea of molding wax bulbs by machine made molds. If one has a set of dies, these bulbs, after a little practice, can be quickly and cheaply made. When the wax bulb is used for ureteral dilation, the McCarthy cysto-urethroscope is preferable, as it has none of the disadvantages of the female air cystoscope of Kelly, the
Diabetes Insipidus and Blindness Caused by a Suprasellar Tumor
Authors: Tero Kivelä, Risto Pelkonen, Matti Oja, Olli Heiskanen
Journal: JAMA (1998)

Tumors in the suprasellar region may cause both visual and endocrinologic symptoms. This association, well known to modern physicians, was established during the 19th century. However, we have identified a 16th-century autopsy report, written by the Dutch professor of anatomy Pieter Pauw (1564-1617), which describes an 18-year-old girl who developed marked polyuria and subsequently became totally blind from a cystic tumor compressing the optic chiasm. Based on prevailing theories on the nature of diabetes, Pauw attributed the disease to the kidneys. Undoubtedly, however, his lucid report is the earliest known account of diabetes insipidus caused by an arachnoid cyst, the Rathke cleft cyst, or craniopharyngioma in the region of the pouch of Rathke. The description also gives insights into the role of anatomic dissections in late 16th-century northern Europe.
Reply to the Letter to the Editor from Fromont
Authors: Shahrokh F. Shariat, Pierre I. Karakiewicz
Journal: Clinical Cancer Research (2008)

In Response: We thank Dr. Fromont for his letter. Whereas postprostatectomy identification of prostate cancer patients at increased risk for biochemical recurrence would allow administration of adjuvant therapy (i.e., radiotherapy or systemic therapy), preprostatectomy identification would allow to
Case 10-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Douglas G. Cole, Bradley R. Buchbinder, Edward P. Richardson
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 67-year-old man was admitted to the hospital because of ataxia and the recent onset of atrial fibrillation.The patient had been well until one month earlier, when he began to experience sweats without documented fever. During the two weeks before entry he lost 3.6 kg in weight. One day before admission he staggered on getting out of bed and was taken to a hospital, where his temperature was 37.4 °C; the heart rhythm was regular; his gait was ataxic, with a broad base and a parkinsonian shuffle; and he repeatedly fell to his left side. Two . . .
Structural Identity of Human Histocompatibility Leukocyte Antigen-B27 Molecules from Patients with Ankylosing Spondylitis and Normal Individuals
Authors: Robert W. Karr, Yaffa Hahn, Benjamin D. Schwartz
Journal: Journal of Clinical Investigation (1982)

Although the association between human histocompatibility leukocyte antigen (HLA) B27 and ankylosing spondylitis is the prototype of HLA-disease association, the mechanism underlying these associations has not been determined. We have investigated the possibility that the B27 molecules from patients with ankylosing spondylitis are different from those of normals, and only the “different” molecules predispose the individual to disease. Biosynthetically radiolabeled HLA-B27 molecules from patients with ankylosing spondylitis and normal individuals were compared by two-dimensional gel electrophoresis and tryptic peptide mapping with high pressure liquid chromatography. Extensive charge heterogeneity in the 45,000-dalton heavy chain was detected when B27 molecules were analyzed by two-dimensional gel electrophoresis; the charge heterogeneity was reduced, but not eliminated, when the B27 molecules were treated with neuraminidase to remove sialic acid residues before analysis. No structural difference in the B27 molecules from an ankylosing spondylitis patient and a normal individual were detected by two-dimensional gel electrophoresis. Analysis of [3H]leucine-labeled and [3H]arginine-labeled tryptic peptides and chymotryptic peptides of the trypsin insoluble material by reverse-phase high pressure liquid chromatography revealed identity of the B27 molecules from ankylosing spondylitis patients and normal individuals. These studies indicate that development of akylosing spondylitis in only some B27 positive individuals is not attributable to those individuals possessing variant B27 molecules.
Sustained Generation of Nitric Oxide and Control of Mycobacterial Infection Requires Argininosuccinate Synthase 1
Authors: Joseph E. Qualls, Chitra Subramanian, Wasiulla Rafi, Amber M. Smith, Liza Balouzian, Ashley A. DeFreitas, Kari Ann Shirey, Benjamin Reutterer, Elisabeth Kernbauer, Silvia Stockinger, Thomas Decker, Isao Miyairi, Stefanie N. Vogel, Padmini Salgame, Charles O. Rock, Peter J. Murray
Journal: Cell Host & Microbe (2012)
Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator.
Authors: H J Rapold, H Kuemmerli, M Weiss, H Baur, A Haeberli
Journal: Circulation (1989)

Fibrinopeptide A (FPA) is a very sensitive marker of fibrin generation in vivo. Because an imbalance between thrombogenic and thrombolytic forces may be responsible for the failure to recanalize and for reocclusion of coronary arteries, such a marker could be of eminent value during thrombolytic treatment of acute myocardial infarction. Thirty-four consecutive patients with acute myocardial infarction (peak creatine kinase level, 1,869 +/- 1,543 IU/l) were treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) 3.1 +/- 1.1 hours after onset of chest pain. Angiography 12.5 +/- 6.1 days later revealed an 81% patency rate of the infarct-related vessel. FPA plasma levels (normal, 1.9 +/- 0.5 ng/ml) were 34 +/- 46 ng/ml on admission and 93 +/- 86 ng/ml (538 +/- 674% with respect to each patient's admission level) after 90 minutes of rt-PA infusion (p less than 0.01). In patients without evidence of reocclusion (including three primary failures), FPA levels fell under continuous heparin infusion to 6.7 +/- 9.7 ng/ml (24 +/- 33%, p less than 0.01) within 30 minutes and were 3.1 +/- 2.2 ng/ml (15 +/- 15%, p less than 0.01), 1.6 +/- 1.1 ng/ml (8 +/- 10%, p less than 0.01), and 2.5 +/- 3.0 ng/ml (12 +/- 16%, p less than 0.01) 30 minutes, 9 hours, and 21 hours, respectively, after completion of rt-PA therapy. Five patients sustained intermittent or permanent coronary reocclusion after primary thrombolytic success. Their early postlytic FPA levels (13-51 ng/ml) remained high or increased again despite adequate anticoagulation. FPA allows the monitoring of fibrin generation during acute myocardial infarction and thrombolytic therapy. Despite successful recanalization, fibrin generation is increased under rt-PA administration before anticoagulation. Patients under anticoagulation with postlytic FPA levels less than 5 ng/ml or below their admission value seem to be at low risk of reocclusion for several days. FPA levels that are persistently high or that increase again despite adequate anticoagulation indicate ongoing fibrin generation. However, whether FPA can indeed be considered a useful marker of reocclusion remains to be confirmed in a larger population of patients with acute myocardial infarction.
Medical treatment for menorrhagia may only delay hysterectomy
Authors: Scott Gottlieb
Journal: BMJ (2004)

Some women with abnormal uterine bleeding may be able to avoid hysterectomy by making the best use of available medical options. But the results of two new studies show that despite aggressive medical management most women with menorrhagia unrelated to pregnancy or malignancy will eventually need surgery and will undergo additional suffering by forestalling more definitive treatment ( JAMA 2004;291:1447-55,1456-63).

The two studies contained some conflicting conclusions and differed with respect to the controls. The first study used “expanded medical therapy” with sex steroid hormones or prostaglandin synthetase inhibitors, or both. The other study used an intrauterine administration of a continuous release progestational hormone that is only available for this indication in Europe (marketed as Mirena by Schering Health).

The …
Healthcare, Guaranteed: A Simple, Secure Solution for America
Authors: Daniel M. Fox
Journal: JAMA (2009)

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