tbuckley/cabot-search huggingface dataset:
Nutritional Requirement for Taurine in Patients Receiving Long-Term Parenteral Nutrition
Authors: Harry S. Geggel, Marvin E. Ament, John R. Heckenlively, Deidre A. Martin, Joel D. Kopple
Journal: New England Journal of Medicine (1985)

Animals fed diets lacking the amino acid taurine have low plasma and tissue levels of taurine and ultimately have retinal dysfunction. Since parenteral nutrition does not ordinarily provide taurine, we looked for evidence of taurine deficiency in 21 children and 23 adults undergoing long-term parenteral nutrition at home for an average of 27±23 (S.D.) months. The fasting plasma taurine level was reduced in children as compared with controls (26±13 vs. 57±16 μmol per liter, P<0.001). In adults with less than 25 per cent intestinal absorption of the recommended caloric intake, the plasma taurine level was also significantly reduced and correlated inversely with the duration of parenteral nutrition. Electroretinograms were abnormal in each of eight children who were examined. Addition of taurine to the intravenous solutions restored plasma levels to normal in four children; the electroretinograms of three of these children also became normal. The plasma taurine level became abnormally low again in two of three children one year after the intravenous taurine was discontinued. We conclude that children and possibly adults receiving long-term parenteral nutrition have a nutritional requirement for taurine. (N Engl J Med 1985; 312:142–6.)
Cumulative Effects of High Cholesterol Levels, High Blood Pressure, and Cigarette Smoking on Carotid Stenosis
Authors: Peter W.F. Wilson, Jeffrey M. Hoeg, Ralph B. D'Agostino, Halit Silbershatz, Albert M. Belanger, Harold Poehlmann, Daniel O'Leary, Philip A. Wolf
Journal: New England Journal of Medicine (1997)

Single measurements of cardiovascular risk factors may not accurately reflect a person's past exposure to those risk factors. We therefore studied the long-term associations of cardiovascular risk factors such as high serum cholesterol levels, high blood pressure, and cigarette smoking with the prevalence of carotid stenosis.
Screening for Multiple Endocrine Neoplasia Type 2A with DNA-Polymorphism Analysis
Authors: Hagay Sobol, Steven A. Narod, Yusuke Nakamura, Andrée Boneu, Claude Calmettes, Denis Chadenas, Gilles Charpentier, Jean François Chatal, Nicole Delepine, Marie Joëlle Delisle, Jean Louis Dupond, Paule Gardet, Hélène Godefroy, Pierre-Jean Guillausseau, Claudine Guillausseau-Scholer, Chantal Houdent, Jean Daniel Lalau, Geneviève Mace, Claude Parmentier, Florent Soubrier, Jacques Tourniaire, Gilbert M. Lenoir
Journal: New England Journal of Medicine (1989)

Multiple endocrine neoplasia type 2a has been shown to be genetically linked to a locus near the centromere of chromosome 10. The availability of polymorphic DNA probes for the region permits the use of restriction-fragment–length polymorphisms (RFLP) to identify carriers of the gene for this cancer syndrome. As part of a French national program, DNA probes were used in a genetic-linkage study of 130 members of 11 families of European and North African origin. In these families there was no recombination between the mutation causing multiple endocrine neoplasia type 2a and two of the three probes used. All 11 families were informative for at least one of the three markers, and linkage information was adequate to provide genetic counseling to 8 families. We found that RFLP analysis is much more useful in predicting the carrier state than conventional endocrine challenge, especially in younger people, but accuracy is maximal when both methods are employed. We conclude that genetic screening allows the identification of those who are at risk for multiple endocrine neoplasia type 2a at any age with a high level of certainty. After initial screening with DNA, tests for early neoplastic change may be directed toward those determined to be at high risk. (N Engl J Med 1989; 321:996–1001.)
Prognostic and Predictive Value in<i>KRAS</i>in Non–Small-Cell Lung Cancer
Authors: Kevin Wood, Thomas Hensing, Raeva Malik, Ravi Salgia
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Lung cancer is the leading cause of cancer deaths worldwide, with non–small-cell lung cancer (NSCLC) constituting more than 80% of all lung cancers. Non–small-cell lung cancer is a heterogenous disease, with multiple different oncogenic driver mutations representing possible therapeutic targets. The vi-Ki-ras2 Kirsten rat sarcoma viral oncogene (<i>KRAS</i>) represents one of the most common oncogenic driver mutations. Unfortunately, targeted therapies thus far have been unsuccessful. <h3>Objective</h3> To discuss current advancements in understanding the prognostic and predictive value of<i>KRAS</i>in NSCLC and explaining the treatment advancements in both the preclinical and clinical setting. <h3>Evidence Review</h3> PubMed, Cochrane Library, and Google Scholar databases were searched through February 1, 2016. English-language peer-reviewed articles published between 1964 and 2016 were found using the keywords “<i>RAS</i>,” “<i>KRAS</i>,” “NSCLC,” “synthetic lethality,” “oncogenic driver mutations,” “clinical trials,” and “phase 3 clinical trials.” Abstracts at scientific meetings were not excluded. Of 112 records idetified, 61 articles or studies were included in qualitative synthesis for this review. <h3>Findings</h3> The<i>KRAS</i>oncogenic driver mutation is noted in 15% to 25% of patients with NSCLC.While there has been limited success in inhibiting the protein directly, phase 2 and phase 3 clinical trials have demonstrated success in inhibiting downstream effectors, specifically<i>MEK1 </i>and/or<i> MEK2</i>with selumetinib and trametinib (albeit with poor tolerability). Current clinical trials are evaluating inhibiting downstream effector pathways for improved efficacy. In the laboratory, the success of synthetic lethal approaches suggests another possible direction for future clinical trials. <h3>Conclusions and Relevance</h3> <i>KRAS</i>is one of the most common oncogenic driver mutations in NSCLC, with prior attempts at direct inhibition being unsuccessful. In recent years, there has been significant advancement in the understanding of the biology of<i>KRAS</i>and its downstream effectors. This has translated into a multitude of important preclinical studies and clinical trials that are currently underway to find effective therapeutic drugs for<i>KRAS</i>mutant lung cancer. Ultimately, better therapeutics need to be engineered to arrive at<i>RAS</i>-driven precision medicine.
The poor rich: the children of the super-rich
Authors: R R Grinker
Journal: American Journal of Psychiatry (1978)

Because they have little parental contact, many children of the very rich lack self-esteem and clear role models, resulting in shallow values and pathological narcissism. Low self-awareness and the absence of great suffering work against therapeutic progress, as do the efforts of the parents, who may feel threatened, and countertransference feelings of envy or anger by middle-class therapists. A supportive psychotherapeutic relationship is the most likely means of developing trust and self-discipline in these patients.
273P Expression2Kinases (E2K) analysis indentifies potential drugable kinases for targeted treatment of cervical carcinoma
Authors: P.A. van Dam, P.-J. van Dam, C.D. Rolfo, X.B. Trinh, S. Altintas, M.T. Huizing, K. Papadimitriou, W. Tjalma, S. van Laere
Journal: Annals of Oncology (2015)
Final overall survival analysis of EXAM, an international, double-blind, randomized, placebo-controlled phase III trial of cabozantinib (Cabo) in medullary thyroid carcinoma (MTC) patients with documented RECIST progression at baseline.
Authors: Martin Schlumberger, Rossella Elisei, Stefan Müller, Patrick Schöffski, Marcia S. Brose, Manisha H. Shah, Lisa F. Licitra, Barbara Jarzab, Viktor Medvedev, Michael Kreissl, Ezra E. W. Cohen, Lori J. Wirth, Haythem Y. Ali, Colin Hessel, Yifah Yaron, Douglas Wilmot Ball, Barry Nelkin, Steven I. Sherman
Journal: Journal of Clinical Oncology (2015)

6012 Background: Cabo inhibits tyrosine kinases including MET, VEGFR2, and RET. EXAM, a randomized double-blind placebo (P)-controlled study in patients (pts) with progressive, locally advanced, or metastatic MTC (NCT00704730), met its primary end point with a statistically significant improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.28, p < 0.001) (Elisei et al, JCO, 2013). This report contains the final analysis of the secondary endpoint, Overall Survival (OS). Methods: Eligible pts were required to have documented RECIST progression within 14 months (mo) of screening, and were randomized 2:1 to receive Cabo (140 mg qd) or P. Crossover between treatment arms was not allowed. The primary endpoint was PFS assessed by RECIST via independent review. The study was designed with 80% power to detect a HR of 0.667 for the secondary endpoint of OS. Results: At the final analysis, median follow up time was 52.4 mo. 218 events were recorded in the intent-to-treat (ITT) population (N = 330). The estimated median OS was 26.6 mo for Cabo vs 21.1 mo for P (stratified HR = 0.85; 95% CI 0.64-1.12; p = 0.241). For 126 pts with known RET M918T mutations, median OS was 44.3 mo for Cabo vs 18.9 mo for P (HR = 0.60, p = 0.026). 32% of Cabo-treated pts received subsequent systemic anticancer therapy vs 50% for P-treated pts. The median duration of treatment was 10.8 mo for Cabo and 3.5 mo for P. 46% and 26% of Cabo-treated pts remained on study treatment for over 1 year and 2 years, and 10% and 1.8% for P, respectively. The most common serious adverse events ( ≥ 2%) on the Cabo arm were pneumonia (4.2%), pulmonary embolism (3.3%), mucosal inflammation (2.8%), hypocalcemia (2.8%), hypertension, dysphagia, dehydration and lung abscess (2.3% each). Conclusions: The secondary endpoint of improved OS was not met, with a median OS 5.5 mo longer with Cabo compared to P that did not reach significance in the ITT population. OS improvement with Cabo was greatest in patients with RET M918T mutations, with a 25.4-month increase in median OS compared to P. The safety profile of Cabo remained consistent with longer term exposure. Clinical trial information: NCT00704730.
Postsynaptic supersensitivity in schizophrenia
Authors: G N Pandey, D L Garver, C Tamminga, S Ericksen, S I Ali, J M Davis
Journal: American Journal of Psychiatry (1977)

In the context of the dopamine hypothesis of schizophrenia, the authors examined postsynaptic dopamine (DA) receptor sensitivity in schizophrenic patients by means of a neuroendocrine strategy using the DA receptor agonist apomorphine and growth hormone (GH) release as the measurable postsynaptic event. The activity of platelet adenylate cyclase, an enzyme intimately associated with catecholamine receptor activity, was also studied following stimulation by prostaglandin E1 (PGE1). Patients diagnosed as having acute schizophrenia had significantly higher GH responses and adenylate cyclase activity than normal control subjects and patients diagnosed as having chronic schizophrenia. Chronic schizophrenic patients with and without tardive dyskinesia showed GH responses slightly lower than but not significantly different from those of control groups.
NHS may have to pay out £2.8bn in negligence cases
Authors: Clare Dyer
Journal: BMJ (2000)

The House of Commons public accounts committee is “appalled” that the NHS has at least 15 000 cases of clinical negligence on its books, and the total could be much more, according to its report last week on NHS financial management.

The report on the 1997–1998 NHS expenditure for England revealed that £79 million ($126 million) had been paid out that year on negligence cases, with outstanding liabilities estimated at £2.8 billion.

The MPs' watchdog on public spending said that such cases represented a “tragedy” for the people involved and the figure for outstanding …
Lethal Neonatal Multiorgan Deficiency of Carnitine Palmitoyltransferase II
Authors: George Hug, Kevin E. Bove, Shirley Soukup
Journal: New England Journal of Medicine (1991)

IN adults, deficiency of carnitine palmitoyltransferase (CPT) II is a genetic disorder characterized by exercise intolerance and myoglobinuria.1 , 2 In newborns, it is a generalized, lethal disease with reduced CPT II activity in multiple organs, reduced concentrations of total and free carnitine, and increased concentrations of lipids and long-chain acylcarnitines.3 The clinical severity of CPT II deficiency is not determined by the degree of the reduction in CPT II activity, since this reduction is of similar magnitude in adults, young children, and newborns.1 2 3 4 5 However, lethal CPT II deficiency is associated with an accumulation of arrhythmogenic long-chain acylcarnitines,6 , 7 as in the patient . . .
SAT0046 Role of C-Reactive Protein in Osteoclastogenesis in Rheumatoid Arthritis
Authors: H.-R. Kim, S.-H. Lee, S.-H. Lee, H.-Y. Kim
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> C-reactive protein (CRP) is one of the biomarkers for the diagnosis and assessment of disease activity in rheumatoid arthritis (RA). CRP is not only the by-product of inflammatory response, but also plays pro-inflammatory and pro-thrombotic roles. <h3>Objectives</h3> This study aims to determine the role of CRP on bone destruction in RA. <h3>Methods</h3> CRP levels in RA synovial fluid (SF) and serum were measured using the immunoturbidimetric method. The expression of CRP in RA synovium was assessed using immunohistochemical staining. CD14+ monocytes from peripheral blood were cultured with CRP, and RANKL expression and osteoclast differentiation were evaluated by using real-time PCR, counting TRAP-positive multinucleated cells and assessing bone resorbing function. CRP-induced osteoclast differentiation was also examined after inhibition of Fcgamma receptors. <h3>Results</h3> There was a significant correlation between CRP levels serum and SF in RA patients. The SF CRP level was correlated with interleukin (IL)-6 levels, but not with RANKL levels. Immunohistochemical staining revealed that, compared with the osteoarthritis synovium, CRP was more abundantly expressed in the lining and sublining areas of the RA synovium. CRP stimulated RANKL production in monocytes, and it induced osteoclast differentiation from monocytes and bone resorption in the absence of RANKL. <h3>Conclusions</h3> CRP could plays an important role in the bony destructive process in RA through the induction of RANKL expression and direct differentiation of osteoclast precursors into mature osteoclasts. In the treatment of RA, lowering CRP levels is a significant parameter not only for improving disease activity but also for preventing bony destruction. <h3>Acknowledgements</h3> This work was supported by Konkuk University Medical Center Research Grant 2013. <h3>Disclosure of Interest</h3> None declared
Identification of 12 or more lymph nodes in resected colon cancer specimens as an indicator of quality performance
Authors: R. O. Dillman, K. Aaron, F. S. Heinemann, S. E. McClure
Journal: Journal of Clinical Oncology (2008)

15009 Background: The percentage of colon cancer resections, in which 12 or more lymph nodes were identified in pathology reports, was recently endorsed as an indicator of quality performance by various groups. However, who or what is actually being evaluated in such an analysis? Methods: We utilized the Hoag Cancer Center data base to examine several variables potentially associated with the number of nodes identified in colon cancer resections, including pathology procedures, surgeons, anatomic location, tumor stage, and patient age. Patients whose cancers were contained in a polyp were excluded. Statistical comparisons were two-tailed, and included the chi square test for paired or grouped proportions, t-test for means, and log-rank test for survival curves. Results: A change in tissue processing procedures in 1998 was followed by an increase in the number of nodes identified from 8 per specimen during 1989–1997 to 15 during 1998–2005 (p<.0001). For 571 patients who underwent surgical resection of colon adenocarcinoma at Hoag Hospital during 1998–2005, the rates of failure to identify at least 12 nodes varied from 17% to 43% by seven anatomic locations (p<.0001), from 25% to 35% by patient age (p=.027), from 27% to 41% by stage of disease (p=.004) and from 20% to 47% among 12 surgeons who performed at least 15 colon cancer resections (p=.014). Fewer than 12 nodes were identified in 49% of tumors resected by a cohort of 30 surgeons, each of whom performed less than 10 of the colon cancer resections. The greatest number of nodes (mean 19.5) were identified in patients with local extension node-negative (T3 and T4) disease. Identification of 12 or more nodes was associated with better survival for patients with local disease, and T3N0 disease. Conclusion: Analysis of this contemporary data set confirms the prognostic value of identifying at least 12 lymph nodes in resected colon cancer specimens. The variance among surgeons is of concern, but more extensive analysis is warranted before concluding that failure to identify 12 lymph nodes in colon cancer specimens is indicative of inferior quality of surgery. No significant financial relationships to disclose.
Creutzfeldt–Jakob Disease Prion Proteins in Human Brains
Authors: Jeffrey M. Bockman, David T. Kingsbury, Michael P. McKinley, Paul E. Bendheim, Stanley B. Prusiner
Journal: New England Journal of Medicine (1985)

Creutzfeldt-Jakob disease is caused by a slow infectious pathogen, or prion. We found that purified fractions from the brains of two patients with Creutzfeldt-Jakob disease contained protease-resistant proteins ranging in apparent molecular weight from 10,000 to 50,000. These proteins reacted with antibodies raised against the scrapie prion protein PrP 27-30. Rod-shaped particles were found in the brain tissue of the patients that were similar to those isolated from rodents with either scrapie or experimental Creutzfeldt-Jakob disease. After being stained with Congo red dye, the protein polymers from patients with Creutzfeldt-Jakob disease exhibited green birefringence when examined under polarized light. Our findings suggest that the amyloid plaques found in the brains of patients with Creutzfeldt-Jakob disease may be composed of paracrystalline arrays of prions similar to those in prion diseases in laboratory animals.
Update on Safety of ESAs in Cancer-Induced Anemia
Authors: John Glaspy
Journal: Journal of the National Comprehensive Cancer Network (2012)

Patients with cancer frequently develop a multifactorial anemia. The past decade has seen a dramatic improvement in understanding of the biology of the anemia of chronic disease, which has increased interest in studies of parenteral iron or antihepcidin strategies in these patients. Randomized trials have shown that therapy with erythropoiesis-stimulating agents (ESAs) is associated with a reduction in transfusion rates in patients with cancer undergoing chemotherapy. More recently, some studies have suggested that ESA therapy may increase the risk of tumor progression or reduce survival in patients with cancer. This topic was extensively reviewed previously. This update supplements prior reviews with data generated over the past 4 years. During this interval, interest in thrombosis and its role in cancer biology has increased, and concerns about the thrombotic risks of ESAs has moved to the fore-front. Until additional safety data are forthcoming, ESAs should be used only to treat chemotherapy-induced anemia, with the goal of preventing transfusions. Patients and physicians should be aware of the safety data for these products.
Phenomenology and psychopathology of uncontrolled buying
Authors: M Lejoyeux, J Adès, V Tassain, J Solomon
Journal: American Journal of Psychiatry (1996)

Uncontrolled buying, defined by the presence of repetitive impulsive and excessive buying that leads to personal and familial distress, is a psychiatric disorder that has only recently been recognized. This review focuses on the prevalence, clinical features, and etiology of this disorder.All published articles on the topic were collected and reviewed. The literature concerning the typology of normal consumerism was also reviewed.The prevalence of the disorder in the general population is reported to be 1.1%. The main clinical features of uncontrolled buying are impulsivity and repetition of buying, the invasive need to buy, unsuccessful attempts to control spending, and the existence of tangible negative consequences of buying (marked distress, interference with social or occupational functioning, or financial problems). Uncontrolled buying may be related to obsessive-compulsive disorder, depression, addiction, or impulsivity.In most cases, uncontrolled buying can be understood as "compensatory buying" that temporarily alleviates depressive symptoms and can thus be associated with the results of antidepressant treatment in cases in which uncontrolled buying is symptomatically associated with depression.
A Comparative Study of Four Methods for Detecting Fibrinogen Degradation Products in Patients with Various Diseases
Authors: D. P. Thomas, S. Niewiarowski, A. R. Myers, K. J. Bloch, R. W. Colman
Journal: New England Journal of Medicine (1970)

Detection of the products of fibrinogen-fibrin degradation by plasmin constitutes a sensitive method for recognizing consumption coagulopathy or primary fibrinolysis. By this means we compared four assays for fibrinogen and fibrin degradation products (FDP) — staphylococcal clumping, tanned red-cell hemagglutination inhibition, latex agglutination and immunodiffusion — to determine their sensitivity and specificity. Fibrinogen, plasminogen, euglobulin lysis time and thrombin time were measured, in addition to FDP levels, in patients with various diseases and in women on oral contraceptives. In patients with consumption coagulopathy, FDP titers were markedly elevated (p less than 0.01), with good correlations between all three sensitive assays (staphylococcal clumping, hemagglutination inhibition and latex agglutination). Patients with alcoholic cirrhosis had moderate elevation of FDP; lymphoproliferative and renal diseases were characterized by mild elevation of tanned red-cell hemagglutination inhibition alone, whereas those with cancer and rheumatoid arthritis showed mild increases in hemagglutination inhibition and antifibrinogen-antibody-sensitized latex particle titers. In contrast, patients with myocardial infarction and women on oral contraceptives showed no abnormalities.
Antibodies to “Alcalase” after Industrial Exposure
Authors: Solomon A. Berson, Rosalyn S. Yalow, Tokuko Saito, Irving J. Selikoff
Journal: New England Journal of Medicine (1971)

Abstract Nineteen of 22 workers in a detergent factory, exposed to an enzyme additive (Alcalase) derived from Bacillus subtilis cultures, had circulating antibodies to a component of this materia...