tbuckley/cabot-search huggingface dataset:
Acral Lentiginous Histologic Subtype and Sentinel Lymph Node Positivity in Thin Melanoma
Authors: Andrew J. Marek, Michael E. Ming, Edmund K. Bartlett, Giorgos C. Karakousis, Emily Y. Chu
Journal: JAMA Dermatology (2016)

Recent analysis of mortality from melanoma has shown that thin melanomas account for 20% and 25% of melanoma deaths in Australia and the United States, respectively, despite an overall survival rate of approximately 95% for patients with these cancers. 1,2Sentinel lymph node (SLN) biopsy is routinely recommended in patients with intermediate-thickness melanomas, but its role in thin melanomas (≤1 mm) is less well defined 3,4 ; moreover, factors predictive of SLN positivity in this latter group have been variably reported.To specifically examine the prognostic significance of histologic subtype of thin melanomas for SLN metastasis, we reanalyzed these lesions in a cohort of patients originally created for a previous study of thin melanomas.
Increased Gluconeogenic Substrates in the Small-for-Gestational-Age Infant
Authors: Morey W. Haymond, Irene E. Karl, Anthony S. Pagliara
Journal: New England Journal of Medicine (1974)

Five normal and 11 small-for-gestational-age infants had blood glucose, lactate, pyruvate, ketone bodies, glycerol, amino acids, cortisol, growth hormone and insulin measured during the first 24 hours of life. At two hours of age, plasma glucose of the small-for-gestational-age infants was significantly lower than that of the normal infants (39.8 ± 5.0 vs. 57 ± 3.5 mg per 100 ml, mean ± S.E.M., p<0.05). Samples of umbilical-cord and venous blood at two and 24 hours contained more lactate and alanine in the small-for-gestational-age than in the normal infants. When all infants were considered, significant inverse correlations were found between glucose and lactate (p<0.01) and glucose and alanine (p<0.05) at two hours of age. In samples of umbilical-cord blood, and those obtained at two hours of age, all potential gluconeogenic amino acids entering at pyruvate were significantly elevated (p<0.05) in small-for-gestational-age infants as compared to normal infants. These data suggest a functional delay in the development of a rate-limiting hepatic gluconeogenic enzyme. (N Engl J Med 291:322–328, 1974)
Chronic Subdural Hematoma
Authors: Albert A. LaLonde, W. James Gardner
Journal: New England Journal of Medicine (1948)

AFTER evacuation of a subdural hematoma the compressed hemisphere may fail to expand spontaneously. This may be a grave prognostic sign. Trotter,1 Coleman,2 Coblentz3 and Voris4 have discussed this aspect of subdural hematoma.We agree with Coleman and Coblentz that failure of the compressed hemisphere to expand is more likely than cerebral edema to cause serious symptoms. Coleman found that the compressed hemisphere may not expand for several days after evacuation of the clot. It has been shown that the hemisphere may still be in a compressed state at autopsy even though the hematoma has been adequately evacuated.5 We have . . .
Smoking and the Risk of LADA: Results From a Swedish Population-Based Case-Control Study
Authors: Bahareh Rasouli, Tomas Andersson, Per-Ola Carlsson, Valdemar Grill, Leif Groop, Mats Martinell, Petter Storm, Tiinamaija Tuomi, Sofia Carlsson
Journal: Diabetes Care (2016)

Smoking is an established risk factor for type 2 diabetes. In contrast, it has been proposed that smoking may reduce the risk of latent autoimmune diabetes in adults (LADA), but studies are scarce. We aimed to study the impact of smoking on LADA and type 2 diabetes risks.We used data from a Swedish case-control study including incident case patients with LADA (GAD antibody [GADA] positive, n = 377) and type 2 diabetes (GADA negative, n = 1,188) and control subjects randomly selected from the population (n = 1,472). We calculated odds ratios (ORs) with 95% CIs by logistic regression, adjusted for age, sex, BMI, family history of diabetes, and alcohol consumption.There was no indication of reduced risk of LADA in smokers; instead, heavy smoking was associated with an increased risk of LADA (OR 1.37, 95% CI 1.02-1.84). Heavy smokers had higher levels of HOMA of insulin resistance (9.89 vs. 4.38, P = 0.0479) and HOMA of β-cell function (55.7 vs. 42.5, P = 0.0204), but lower levels of GADA (75 vs. 250, P = 0.0445), compared with never smokers. Smokers also displayed an increased risk of type 2 diabetes (OR in ever smokers 1.53, 95% CI 1.25-1.88).In this large population of LADA patients, we did not observe a protective effect of smoking on autoimmunity and the risk of LADA. A protective effect could possibly be masked by a smoking-induced aggravation of insulin resistance, akin to the diabetogenic effect seen in individuals with type 2 diabetes.
REM architecture changes in bipolar and unipolar depression
Authors: W C Duncan, K D Pettigrew, J C Gillin
Journal: American Journal of Psychiatry (1979)

The authors compared total night sleep measures and REM sleep architecture values for normal control subjects (N = 36), unipolar depressed patients (N = 36), and bipolar depressed patients (N = 22). The unipolar and bipolar patients had significantly greater fragmentation of REM periods than control subjects, and bipolar patients showed greater fragmentation of REM periods than unipolar patients. In both the unipolar and bipolar samples, the duration of successive REM periods was related to the total number of REM periods during sleep.
Association of long-term survival in pancreatic cancer (PDAC) with increased proliferative and anti-apoptotic protein activation.
Authors: Vincent J. Picozzi, Corinne Ramos, Nicholas N Hoke, Glenn D. Hoke
Journal: Journal of Clinical Oncology (2016)

254 Background: 5 year (yr) overall survival (OS) for resected PDAC is typically 20%. To test the potential for molecular prediction of &gt; 5 yr OS in such patients (pts), we analyzed proteomic activation (phosphorylation) patterns in both cancer and stromal cells from initial surgical specimens prior to adjuvant therapy (Rx). Methods: Formalin-fixed, paraffin-embedded tissue from 40 pts (20 pts each with long-term actual disease-free OS [median 65 mo, range 26-137 mo] [LTS] and with early relapse/death &lt; 2 yrs [STS]) with de novo resected PDAC formed the test cohort. All pts received adjuvant Rx (chemo Rx with/without chemoradiation). Laser Capture Microdissection enabled directed cancer and stromal cell isolation. Retrospective blinded protein activation analysis for both was performed via Reverse Phase Protein Array (RPPA). Differences in baseline protein signaling of LTS vs. STS were evaluated via two-way ANOVA analysis. Results: Analysis of &gt; 50 signal transduction proteins (STPs) for activation (phosphorylation) showed these significant differences for LTS vs. STS in cancer cells: 1) Activation of proliferation markers Sox2/ Ki 67 were higher (p&lt;0.0001). 2) Activation of anti-apoptotic signal transducer and activator of transcription 3 (p-STAT 3) ( p=0.047) and p-SRC kinase (p=0.039) were higher. 3) Activated p-m-TOR expression was higher (p=0.021). 4) Activation of mitotic marker histone H3S10 was lower (p=0.03). In stromal cells, activation of the survival marker Mek S298 was lower (p=0.021). For other STPs, differences for LTS vs. STS (e.g. Livin, PCNA) were not seen. Conclusions: 1) LTS and STS of de novo resected PDAC show clear differences in cancer cell protein activation re key markers of proliferation and apoptosis (Sox2, Ki67, STAT3, SRC kinase, H3S10). 2) For stromal cells, protein activation was largely similar, but a difference in activation of one stromal protein (Mek S298) was seen. 3) For these pts, differences in protein activation prior to adjuvant Rx could enhance current prognostic models and/or identify new pharmacological targets designed to improve OS. 4) These findings require further validation: a second 60 sample validation cohort is now under anaylsis.
Prognostic impact of reduced lymph node yield in lymph-node negative rectal cancer specimens following neoadjuvant treatment.
Authors: Benjamin Garlipp, Patrick Stuebs, Ronny Otto, Hans Lippert, Ingo Gastinger, Christiane Bruns
Journal: Journal of Clinical Oncology (2014)

3626 Background: Pathologic examination of at least 12 lymph nodes (LN) is required as per NCCN and ESMO guidelines to accurately identify pN0 rectal cancer. However, this may not apply to patients undergoing surgery following neoadjuvant treatment because LN may be rendered unrecognizable by preoperative chemoradiation. The prognostic impact of reduced LN yield in rectal cancer specimens following neoadjuvant treatment is unknown. Methods: Data from the prospective German multicenter Quality Assurance in Rectal Cancer observational trial were retrospectively analyzed. Patients undergoing radical surgery for rectal cancer between 01/01/2007 and 12/31/2009 who were staged to have pN0 disease were included. Propensity Score Analysis using factors potentially influencing the decision for or against neoadjuvant treatment was performed to compensate for bias inflicted by factors that affect both the decision on neoadjuvant treatment and survival. Cox regression including age, complicated surgery, pT stage, propensity score for neoadjuvant treatment, LN yield, and interaction between the latter two was then performed to identify factors independently influencing survival. Results: The full data set included 4,154 patients of whom 1,914 (46.1%) underwent neoadjuvant treatment. Significantly fewer LN were retrieved in neoadjuvantly treated patients (median, 13 vs. 15; p<0.001). Complete data were available for 1,394 patients. Only age (p<0.001), advanced pT stage (p=0.001 and p<0.001 for pT3 and pT4, respectively), and complicated surgery (p<0.001) were independently associated with survival. Neither number of LN, propensity for neoadjuvant treatment, nor interaction between these two were identified as factors independently affecting survival. Only when interaction between propensity for neoadjuvant treatment and LN number was removed from the model, number of LN retrieved was found to be an independent prognostic factor (p=0.027). Conclusions: Although neoadjuvant treatment reduces the number of LN retrieved in rectal cancer specimens, our data suggest that this has no influence on the prognostic impact of the number of LN examined in patients with pN0 rectal cancer.
Comparisons of the Chemical and Biologic Properties of Triaziquone and Triaziquone-Protein Conjugates2
Authors: J. H. Linford, G. Froese
Journal: JNCI Journal of the National Cancer Institute (1978)

Prepared with nonimmunospecific proteins were covalent conjugates of triaziquone [2,3,5-tris(1-aziridinyl)-p-benzoquinone] (hereafter referred to by the tradename, Trenimon). The bound Trenimon that absorbs maximally at 350 nm (∈ = 8,200) was assayed by titration of the acid uptake during alkylation of thiosulfate ion and by the color produced during alkylation of 4-(p-nitrobenzyl)pyridine. Conjugates of Trenimon with nonimmune IgG were toxic to cells in culture, although no firm binding of conjugate to cell surface could be measured by fluorescein labeling. Inhibition of cellular pinocytotic activity with cytochalasin B had no effect on the cytotoxic response. Polyoma virus-transformed baby hamster kidney (BHK) cells that were threefold more resistant to the action of a conjugate than was the parent cell line were as sensitive as normal BHK cells when grown in the presence of dibutyryl cyclic AMP or when acted on in suspension by the conjugate. These conditions did not affect the response of the parent BHK line. Cysteine acted to protect both cell lines. The results suggest that Trenimon bound to nonimmune protein reacted primarily with a component of the cell surface. The reaction did not appear to depend on a firm attachment of the conjugate to the cell.
Percutaneous Indwelling Radial-Artery Catheters for Monitoring Cardiovascular Function
Authors: Reed M. Gardner, Rosanne Schwartz, Harry C. Wong, John P. Burke
Journal: New England Journal of Medicine (1974)

Original Article from The New England Journal of Medicine — Percutaneous Indwelling Radial-Artery Catheters for Monitoring Cardiovascular Function — Prospective Study of the Risk of Thrombosis and Infection
Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138−CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis
Authors: M Martello, D Remondini, E Borsi, B Santacroce, M Procacci, A Pezzi, F A Dico, G Martinelli, E Zamagni, P Tacchetti, L Pantani, N Testoni, G Marzocchi, S Rocchi, B A Zannetti, K Mancuso, M Cavo, C Terragna
Journal: Leukemia (2016)
L-Xylulose Metabolism in Diabetes Mellitus
Authors: Albert I. Winegrad, Constance Louise Burden
Journal: New England Journal of Medicine (1966)

THE existence of the glucuronic acid pathway of glucose metabolism was recognized as the result of studies of the biosynthesis of L-ascorbic acid and of L-xylulose, the sugar characteristically found in patients with pentosuria (Fig. 1).1 2 3 4 5 Hollmann1 has estimated that approximately 5 to 15 gm. of glucose per day is utilized by this cycle in patients with pentosuria, but the significance and regulation of this pathway in man, who lacks the ability to synthesize ascorbic acid, remains to be clarified. Our interest in the activity of the glucuronic acid pathway in diabetes mellitus stems in large part from the intimate . . .
Case 34-2001
Authors: Joseph O. Jacobson, Laurence de Leval
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 54-year-old woman was admitted to the hospital with fever of unknown origin of one year's duration.The patient was confined to a bed because of multiple sclerosis of 20 years' duration. Her fever had initially been ascribed to a urinary tract infection caused by an indwelling catheter, but the fever persisted after successful treatment of the infection. Seven months before the current admission, the white-cell count fell to 1300 per cubic millimeter, and chronic anemia developed. Her customary therapy with interferon beta-1a and interferon beta-1b was discontinued, without defervescence. Five months before admission, skin nodules appeared . . .
Gout and Hyperuricemia after Adrenalectomy for Hypertension
Authors: Harold D. Itskovitz, Alfred M. Sellers
Journal: New England Journal of Medicine (1963)

BETWEEN 1950 and 1959, 171 patients with severe hypertensive cardiovascular disease underwent bilateral total or subtotal adrenalectomy and sympathectomy at the Hospital of the University of Pennsylvania in an effort to lower their blood pressure. Most of these patients achieved an excellent hypotensive response at a time when effective anti-hypertensive drugs were not yet available.1 Currently, 105 patients survive. During the course of semiannual examinations performed after adrenalectomy acute gouty arthritis was observed in 11 patients. Study of this group has afforded a unique opportunity to evaluate not only hypertensive cardiovascular disease but also adrenal factors as they may relate . . .
Abstract 2629: High Dose Erythropoietin Improves the Postresuscitation Myocardial Dysfunction and Survival in an Appropriate Therapeutic Time Window
Authors: Chien-Hua Huang, Chiung-Yuan Hsu, Huei-Wen Chen, Wei-Tien Chang, Wen-Jone Chen
Journal: Circulation (2007)

Introduction: The myocardial dysfunction carries high mortality rate in the postresuscitation period. Interventions for improving myocardial dysfunction may improve the outcomes of resuscitated victims. The erythropoietin (EPO) provides protective effects for the myocardium with ischemia-reperfusion injuries. However, its effects on the treatment of cardiopulmonary arrest and post-resuscitation myocardial dysfunction remain unknown. Hypothesis: EPO can improve the postresuscitation myocardial dysfunction in an appropriate therapeutic time window. Methods: Asphyxia-induced cardiac arrest was performed in male adult Wistar rats. Cardiopulmonary resuscitation including chest compressions, mechanical ventilation and epinephrine (0.01 mg/kg) was begun after 6.5 or 9.5 minutes of asphyxia. Animals were randomized to undergo treatment with intravenous EPO (5000 U/kg) or equivalent volume of 0.9% saline placebo. These agents were administrated 3 minutes after the return of spontaneous circulation. Results: The better left ventricular dP/dt 40 (2958±827 vs. 1321±1200 mmHg/s, P&lt;0.05) and maximal -dP/dt (2562±546 vs. 745±877 mmHg/s, P&lt;0.05) at 120 minutes after cardiac arrest, and better left ventricular fraction shortening (32.0 ± 2.0 vs. 24 ± 6.7 %, P&lt;0.05) by echocardiography at 90 minutes after cardiac arrest were noted in the EPO-treated group compared to the control group in the condition of 6.5 minutes of asphyxia. The EPO treated group had better neurological recovery at 24 hours after resuscitation. Survival rate at 72 hours after 6.5 minutes of asphyxia was better in the EPO-treated group (50% vs. 20 %, P=0.02). No animal survived 72 hours after 9.5 minutes of asphyxia either in EPO-treated or control group. More activation of cardiac Akt and ERK 42/44 signaling pathways were noted in the EPO-treated group than the control group. Conclusions: EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest in an appropriate therapeutic time window.
Receptor-independent Effects of Estrogen on the HERG Channel Predispose Women to Drug-induced Arrhythmias
Authors: Junko Kurokawa
Journal: Circulation (2007)

Abstract 289 Junko Kurokawa, Tokyo Medical &amp; Dental University, MRI, Tokyo, Japan; Masaji Tamagawa, Chiba University Graduate School of Medicine, Chiba, Japan; Nobuhiro Harada, Shinichiro Honda, School of Med, Fujita Health University, Toyoake, Japan; Haruaki Nakaya, Chiba University Graduate School of Medicine, Chiba, Japan; Tetsushi Furukawa, Tokyo Medical &amp; Dental University, MRI, Tokyo, Japan Junko Kurokawa, 2007 Finalist and Presenting Author
ACTH Therapy in Ulcerative Colitis and Regional Enteritis
Authors: S. J. Gray, R. W. Reifenstein, J. A. Benson
Journal: New England Journal of Medicine (1951)

THE purpose of this communication is to evaluate the clinical use of ACTH in nonspecific ulcerative colitis and regional enteritis. The immediate and long-term effects of this treatment on the clinical course of 6 patients with ulcerative colitis and 2 patients with regional enteritis have been studied over a period of sixteen months, and the response to ACTH therapy was correlated with the fecal lysozyme titer, which is a measure of the activity of the disease.The rationale of this use of ACTH is based upon its beneficial effect on systemic diseases involving mesenchymal tissue or in which an antigen–antibody . . .
Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) does not increase the incidence of venous thromboembolism when added to first-line chemotherapy to treat metastatic colorectal cancer
Authors: W. F. Novotny, E. Holmgren, B. Nelson, R. Mass, F. Kabbinavar, H. Hurwitz
Journal: Journal of Clinical Oncology (2004)

3529 Background: Venous thromboembolism has been reported as a potential risk of anti-angiogenic and anti-VEGF therapy. To clarify the true risk, studies of bevacizumab [Avastin (BV)] included special case report forms and “real-time” assessment of the incidence and characteristics of thromboembolism. An analysis was performed from two completed randomized, controlled, double-blind trials. Methods: Study AVF2107g was a large, randomized, controlled, double-blinded Phase III trial testing the efficacy and safety of adding BV to bolus-IFL as first-line chemotherapy for metastatic colorectal cancer. The addition of BV to IFL chemotherapy resulted in a prolongation of median survival from 15.6 mos to 20.3 mos (p=0.00004). Study AVF2192g was a randomized, controlled, double-blinded Phase II trial testing the efficacy and safety of adding BV to FU/LV as first-line chemotherapy in CRC for subjects who were not optimal candidates for first-line CPT- II. The addition of BV to FU/LV chemotherapy resulted in prolongation of median progression-free survival from 5.5 to 9.2 months (p=0.0002). Results: The incidences and types of thrombembolic events in the two trials is shown below: Conclusions: The addition of BV to either standard first-line chemotherapy was not associated with an increase in venous thromboembolism in either study AVF2107g or study AVF2192g. There may be a small increase in arterial thromboembolic events. These data emphasize the high background rate of thromboembolism associated with mCRC and standard chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech; Pfizer Genentech, Inc. Genentech, Inc. AstraZeneca; Genentech, Inc.; GlaxoSmithKline
Abstract 10879: Efficacy and Safety of Rivaroxaban in Patients With Venous Thromboembolism and Active Malignancy - A Single Center Registry
Authors: Rayya Saadiq, Dalene Bott-Kitslaar, Charles Loprinzi, Robert McBane, Waldemar Wysokinski
Journal: Circulation (2015)

Background: Active malignancy accounts for 20% of venous thromboembolism (VTE) in the community and is the second leading cause of death among cancer patients. Rivaroxaban offers a convenient alternative to conventional anticoagulation for VTE in cancer patients but its efficacy and safety for this group of patients is not well documented. Patients and Methods: All patients with cancer-associated deep vein thrombosis (DVT) or pulmonary embolism (PE), enrolled into Mayo Rochester Thrombophilia Clinic Direct Oral Anticoagulants Registry between November 1, 2012 and April 30, 2015, were followed prospectively to provide an estimate of the efficacy and safety of this form of therapy. Follow up was obtained in person or by mailed or telephone survey. Results: Out of the 377 patients in the registry, 118 (31%) patients (51% female, mean age 66±10 years) had active malignancy related VTE (62% DVT, 24% PE, and 14% DVT/PE) treated with rivaroxaban. The most common malignancies in this group were: gastrointestinal (20%), lung (13%) and ovary/uterine (13%). Over the follow up period, the VTE recurrence rate was 3.3% (2 DVT and 2 PE; of these, 2 occurred during periprocedural interruptions of anticoagulation); and the major bleeding rate was 3%. There were 26 deaths (22%), none related to VTE or bleeding. The main reasons for choosing rivaroxaban were lower cost compared to LMWH, no need for injections, and the lack of food/drug interactions. Conclusions: These data support that rivaroxaban may provide a safe, effective, and convenient alternative treatment option to standard therapy for cancer related VTE treatment.
Treatment of Venous Thrombosis with Intravenous Unfractionated Heparin Administered in the Hospital as Compared with Subcutaneous Low-Molecular-Weight Heparin Administered at Home
Authors: Maria M.W. Koopman, Paolo Prandoni, Franco Piovella, Paul A. Ockelford, Desiderius P.M. Brandjes, Jan van der Meer, Alexander S. Gallus, Gérald Simonneau, Colin H. Chesterman, Martin H. Prins, Patrick M.M. Bossuyt, Hanneke de Haes, Angelique G.M. van den Belt, Luc Sagnard, Pascal d'Azemar, Harry R. Büller
Journal: New England Journal of Medicine (1996)

An intravenous course of standard (unfractionated) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the standard initial in-hospital treatment for patients with deep-vein thrombosis, but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe. Because the latter treatment can be given on an outpatient basis, we compared the two treatments in symptomatic outpatients with proximal-vein thrombosis but no signs of pulmonary embolism.