tbuckley/cabot-search huggingface dataset:
NC-13 * CRANIAL RADIATION ENCOMPASSING THE GENU IS ASSOCIATED WITH NEURO-PSYCHOLOGICAL SEQUELAE IN CHILDREN: A PROSPECTIVE STUDY OF DIFFUSION TENSOR IMAGING (DTI) AND PROTON MR SPECTROSCOPY (MRS)
Authors: K. Redmond, M. Mahone, H. Sair, T. Vannorsdall, S. Terezakis, L. Kleinberg, T. McNutt, M. Wharam, A. Horska
Journal: Neuro-Oncology (2014)

PURPOSE: This study examines white matter integrity as measured by DTI and proton MR spectroscopy (MRS) and their associations with region specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. METHODS: 20 patients and 34 age-& sex-matched controls participated. MRS and DTI and neuropsychological assessment were conducted at baseline, 6, 15, 27 months (times 1-4) following RT and compared to a single visit in controls. Neuro-psychological battery included: motor dexterity, visual attention/processing speed, visual and verbal working memory. White matter regions contoured and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each. Concentrations of neuro-metabolites were expressed as ratios N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr. Linear mixed effects (LME) regression models were used to examine associations among ADC, FA, metabolite ratios, RT dose to contoured structures, and performance on testing, and to compare findings for patients versus controls. RESULTS: Mean prescription dose: 44.2 Gy (range 2-59.4 Gy). LME analyses demonstrated significant differences between patients and controls in NAA/Cr and ADC, with the greatest difference at time 4 (p = <0.01 and <0.0001, respectively). At time 4, the ADC difference was most significant in the temporal lobes (p < 0.0001), genu (p = 0.01) and splenium (p = 0.01). Increasing radiation dose was associated with an increase in ADC at time 3 (p = 0.005), with the most pronounced effects in the genu. There was no significant difference in RT dose to the genu versus splenium. Overall, there was poorer performance on visual working memory with higher ADC in the genu, especially in patients (group by ADC, p = 0.02) and a trend towards poorer performance on motor dexterity with higher ADC in the genu in patients at baseline (p = 0.057). CONCLUSIONS: The genu is a region with increased susceptibility to injury associated with neuro-psychological sequelae. Efforts should be made to limit radiation dose to this region during treatment planning.
INTERLEUKIN-6 AND THE RISK OF ADVERSE OUTCOMES IN PATIENTS AFTER AN ACUTE CORONARY SYNDROME: OBSERVATIONS FROM THE SOLID-TIMI 52 TRIAL
Authors: Christina Fanola, David Morrow, Christopher Cannon, Petr Jarolim, Mary Ann Lukas, Erica Goodrich, Eugene Braunwald, Michelle O'Donoghue
Journal: Journal of the American College of Cardiology (2016)
AB0378 Microarchitecture assessment by trabecular bone score at the spine in patients with rheumatoid arthritis and ankylosing spondylitis. Preliminary results
Authors: E. Toussirot, G. Dumoulin, B. Gaugler, D. Wendling
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Inflammatory rheumatic diseases such as rheumatoid arthritis (RA) or ankylosing spondylitis (AS) are associated with osteoporosis and increased risk of fractures. This bone involvement is related to the inflammatory process, the treatments given such as corticosteroids (CTC) and the menopausal status. Bone mass in RA and AS has been well evaluated by measuring areal bone mineral density (BMD) with DXA. Trabecular bone score (TBS) is a new method evaluating bone microarchitecture by assessing pixel gray- level variations in DXA images from lumbar spine. The clinical usefulness of this method is currently being evaluated in post menopausal osteoporosis. <h3>Objectives</h3> to evaluate TBS in patients with RA or AS and to compare these results with spine BMD measurements. <h3>Methods</h3> 30 patients with RA (ACR criteria, 19 F; 12 post menopausal women; age [mean ± SD]: 56.9±9.7 years; disease duration: 11.7±8.8 years; 26 under low dosage CTC) and 31 patients with AS (modified NY criteria, 28 M, age 43.8±13.4; disease duration: 13.0±11.1; no CTC) were evaluated and compared to 51 healthy subjects (29 F, 12 post menopausal women, age: 46.6±11.1). L2-L4 spine BMD and hip BMD were measured using DXA (Lunar, iDXA). TBS was calculated from L2-L4 BMD images (TBS insight®, Med-Imaps). <h3>Results</h3> compared to healthy subjects, patients with RA and AS had elevated biological markers of inflammation (ESR, CRP, IL-6) (all p&lt;0.0001). RA patients had decreased BMD and T score at the hip (p&lt;0.005) compared to the control group. Hip T score in patients with AS was also decreased (p=0.02). The other BMD measurements (L2-L4 BMD, total body BMD) did not differ between the patients and the controls. TBS was decreased in RA and AS compared to healthy subjects: 1.242±0.16 <i>vs</i> 1.282±0.13 <i>vs</i> 1.365±0.14, respectively (p=0.005). In the whole population, TBS correlated with spine BMD measurements (r=0.29, p=0.002). In AS, we observed no correlation between TBS and biological or clinical indexes of disease activity while in RA, IL-6 correlated with TBS (r =0.44, p=0.02). We also examined TBS results according to male/female distribution in RA and AS and confirmed that TBS was decreased in both women and men with RA while TBS did not differ between male AS and male controls. <h3>Conclusions</h3> in this study, we observed decreased TBS values, mainly in patients with RA, suggesting that bone micro architecture is altered in RA, and this may probably be related to CTC treatment. In addition, TBS analysis may found decreased values whereas areal BMD measurements are normal, suggesting a potential interest of this new method in evaluating bone status in inflammatory rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Abstract 5559: Molecular mechanisms of elesclomol cytotoxicity.
Authors: Brian B. Hasinoff, Jack C. Yalowich, Daywin Patel, Aron Yadav, Xing Wu
Journal: Cancer Research (2013)

Abstract Elesclomol is an anticancer drug that has received both fast track and orphan drug status from the FDA and is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with Cu2+ and may exert its anticancer activity through the induction of oxidative stress or its ability to transport Cu2+ into the cell. The complexes of elesclomol with redox inactive Pt2+ and Ni2+ were much less cytotoxic than its Cu2+ complex which suggests a role for Cu2+-induced oxidative stress. Elesclomol and Cu2+-elesclomol inhibited the growth of human erythroleukemic K562 cells in the low nanomolar concentrations with even a brief 1.5 hr exposure. The cell growth inhibitory effects of elesclomol were decreased with an increase in cell density, likely due to Cu2+ depletion of the medium. Consistent with this, the addition of the Cu2+ chelator Trien to the medium decreased cytotoxicity. Cu2+-elesclomol induced caspase 3/7 in K562 cells, indicating it was apoptosis inducing. The Cu2+-elesclomol complex inhibited topoisomerase I activity and induced topoisomerase I-covalent complexes in K562 cells at a relatively high concentration of 50 μM. It did not, however, inhibit or poison topoisomerase II or produce topoisomerase II-covalent complexes in cells. Cu2+-elesclomol, but not elesclomol, was able to induce γH2AX formation in K562 cells, indicative of DNA double strand breaks. Ascorbic acid, GSH and NADH were all able to slowly reduce the Cu2+-elesclomol complex. However, EPR spin trapping experiments, either in the presence or absence of added H2O2, showed that the reduced copper complex could not directly generate damaging hydroxyl radicals. Depletion of GSH in K562 cells by treatment with BSO sensitized cells to elesclomol and its copper complex, indicating oxidative stress may be responsible for cytotoxicity. In conclusion, these results show that elesclomol may inhibit cell growth through Cu2+-mediated oxidative stress. Support: CIHR, a Canada Research Chair in Drug Development to B.B.H., and a National Institutes of Health grant CA090787 to J.C.Y. Citation Format: Brian B. Hasinoff, Jack C. Yalowich, Daywin Patel, Aron Yadav, Xing Wu. Molecular mechanisms of elesclomol cytotoxicity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5559. doi:10.1158/1538-7445.AM2013-5559
The clip-and-snare method with a pre-looping technique during gastric endoscopic submucosal dissection
Authors: Naohiro Yoshida, Hisashi Doyama, Ryosuke Ota, Kunihiro Tsuji
Journal: Endoscopy (2014)

The effectiveness of the clip-and-snare method, which is a traction method used during gastric endoscopic submucosal dissection (ESD), has been reported previously [1] [2]. In previous reports, an additional forceps was required to deliver the snare to an anchored clip. However, this delivery technique is difficult and risks gastric tissue injury, especially when lesions are located in the upper body. In this report, we describe a newly developed pre-looping technique as an easy and safe delivery method.
The Genetic Basis of the Reduced Expression of Bilirubin UDP-Glucuronosyltransferase 1 in Gilbert's Syndrome
Authors: Piter J. Bosma, Jayanta Roy Chowdhury, Conny Bakker, Shailaja Gantla, Anita de Boer, Ben A. Oostra, Dick Lindhout, Guido N.J. Tytgat, Peter L.M. Jansen, Ronald P.J. Oude Elferink, Namita Roy Chowdhury
Journal: New England Journal of Medicine (1995)

People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal.
Here We Go Again — Another Failure of Postmarketing Device Surveillance
Authors: Robert G. Hauser
Journal: New England Journal of Medicine (2012)

U.S. patients continue to be exposed to underperforming and potentially hazardous medical devices after FDA approval. Most recently, Riata and Riata ST implantable cardioverter–defibrillator leads — currently implanted in more than 75,000 U.S. patients — were recalled.
Clinical and Pathological Studies of Joint Involvement in Sarcoidosis
Authors: Leon Sokoloff, Joseph J. Bunim
Journal: New England Journal of Medicine (1959)

THIS paper deals with a little known form of sarcoidosis in which polyarthritis is a conspicuous or dominant clinical finding. In extensive reviews of the literature on sarcoidosis, articular involvement is either not mentioned or noted as an infrequent finding.1 2 3 4 In three recent studies,5 6 7 however, arthritis was found to occur in 25, 10 and 22 per cent of cases respectively. Although at times sarcoidosis coexists with rheumatoid arthritis,8 this diagnosis, or rheumatic fever9 or the arthritis occurring with erythema nodosum, has been made in patients with sarcoidosis because of the failure to recognize the existence of joint involvement in sarcoidosis. . . .
How Do Health-Maintenance Organizations Achieve Their “Savings”?
Authors: Harold S. Luft
Journal: New England Journal of Medicine (1978)

Health-maintenance organizations have been suggested as a way to stop spiraling medical costs. Although many of the arguments have been largely rhetorical, theoretical considerations suggest that the shift from fee for service to a fixed budget for the providers (physicians and hospitals) will result in substantial savings. Total costs (premium and out-of-pocket) for enrollees are 10 to 40 per cent lower than those for comparable people with health insurance. Enrollees in health-maintenance organizations have about as many ambulatory visits as comparison groups. Most of the cost differences are attributable to hospitalization rates about 30 per cent lower than those of conventionally insured populations. These lower hospitalization rates, in turn, are due almost entirely to lower admission rates; the average lenth of stay shows little difference. There is no evidence that health-maintenance organizations reduce admissions in discretionary or "unnecessary" categories; instead, the data suggest lower admission rates across the board.
Detection of Meningioma Metastasis to Liver and Lung Using Somatostatin Receptor Scintigraphy
Authors: Michael Lanfranchi, Nayer Nikpoor
Journal: Clinical Nuclear Medicine (2013)

Extracranial meningioma metastasis is rare. We report a case of a 74-year-old Caucasian man with intracranial recurrence of atypical meningioma treated with a combination of surgical resection and gamma knife radiotherapy over a 4-year period. Somatostatin receptor scintigraphy using (111)In pentreotide for surveillance of tumor recurrence showed multiple pulmonary and hepatic metastases.
Predictors of the Acquired Immunodeficiency Syndrome Developing in a Cohort of Seropositive Homosexual Men
Authors: B. Frank Polk, Robin Fox, Ron Brookmeyer, Sukon Kanchanaraksa, Richard Kaslow, Barbara Visscher, Charles Rinaldo, John Phair
Journal: New England Journal of Medicine (1987)

In a cohort of 1835 homosexual men who were seropositive for human immunodeficiency virus (HIV) on entry into a prospective study, the acquired immunodeficiency syndrome (AIDS) developed in 59 during a median follow-up of 15 months. We matched 5 seropositive controls to each case according to study center and date of enrollment and performed a case-control analysis to determine factors predictive of AIDS. In a multivariate analysis, a decreased number of T helper lymphocytes, an increased number of T suppressor lymphocytes, a low level of antibody to HIV, a high titer of cytomegalovirus antibody, and a history of sex with someone in whom AIDS developed were independently associated with subsequent AIDS. Separate analyses of risk factors for Kaposi's sarcoma and opportunistic infections failed to support previously reported associations between the use of nitrites or an elevated cytomegalovirus-antibody titer and Kaposi's sarcoma. These variables may be markers rather than determinants of disease progression. A vigorous antibody response to HIV infection may confer at least temporary protection against the progression of immunodeficiency to AIDS, or a low level of antibody to HIV may reflect a later stage of infection. The increased risk associated with a history of sex with someone in whom AIDS developed may indicate earlier infection in cases or infection with a more virulent strain of HIV. These results may be useful in counseling HIV-seropositive persons and in designing studies of clinical interventions. (N Engl J Med 1987; 316:61–6.)
The Circus Disaster and the Hartford Hospital
Authors: Donald B. Wells
Journal: New England Journal of Medicine (1945)

An emergency anticipated and prepared for ceases to be an emergency.IN TERMS of sudden death and human suffering, the circus fire of July 6, 1944, is the worst disaster that has overtaken Hartford in the more than three hundred years of her history. In less than fifteen minutes 125 human beings, more than half of them children under fourteen, were burned to death on the lot. One hundred and eighty-three others, of whom 150 were burned, were admitted to the various hospitals, where 43 subsequently died. Some concept of this terrible disaster can be brought to you today.The . . .
Bioavailability of Digoxin
Authors: Trieste G. Vitti, Daniel Banes, Theodore E. Byers
Journal: New England Journal of Medicine (1971)

A variable or poor response to a therapeutic agent may not have its origin in the patient; it may be due to a formulation defect in the drug product administered. The most commonly recognized formulation defect in a dosage form such as a tablet is a deficiency or excess of the active ingredient. The fact that difficulties of this type were occurring with certain lots of digoxin and digitoxin tablets on the market was discovered by the Food and Drug Administration through a systematic testing program inaugurated in April, 1970, by the Bureau of Drugs with the testing done at . . .
Gangrene of the Hand Following Treatment for Pruritus of Hepatotoxic Origin
Authors: Francis R. Kenney
Journal: New England Journal of Medicine (1946)

THE treatment of severe pruritus is often so difficult that one is prone to seize on any remedy that seems to offer relief. Many patients enter the hospital with badly excoriated skin, traumatized by their attempts to alleviate the itching, and suffering from lack of rest and sleep. In this report we wish to describe our experiences with a patient suffering from acute hepatitis and jaundice who was given ergotamine tartrate for control of itching and who subsequently developed serious constitutional symptoms and gangrene of one hand.A 56-year-old, married woman entered the New England Baptist Hospital on January 28, . . .
Reminder letters for bowel screening tests improve uptake
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Only four in 10 people aged 55 currently accept the offer of a one-off flexible sigmoidoscopy screening test under NHS England’s bowel scope screening programme, but a reminder letter can boost uptake, a study published in the British Journal of Cancer shows.1

The study targeted a randomly selected group of 155 people previously invited for bowel scope screening in the London boroughs of Brent and Harrow, where fewer than the four in 10 national average currently accepted their bowel scope invitation.

A reminder letter, including instructions …
Idiopathic CD4 Lymphocytopenia: Clinical and Immunological Aspects
Authors: Norma de Paula Motta Rubini, Albertina Varandas Capelo, Eliane Miranda da Silva, Mary Jane, Lisboa Valory, Rafael Figueredo Poleshuck, Fernando Samuel Sion, João Negreiros Tebyriçá, Carlos Alberto Morais-de-Sá
Journal: Journal of Allergy and Clinical Immunology (2013)
PWE-075 Association between Thiopurine use and Non-Melanoma Skin Cancers in Patients with Inflammatory Bowel Disease: A Meta-Analysis: Abstract PWE-075 Table
Authors: J Ariyaratnam, V Subramanian
Journal: Gut (2013)

<h3>Introduction</h3> Thiopurines are the mainstay of treatment for patients with inflammatory bowel disease (IBD). Thiopurine therapy increases the risk of non-melanoma skin cancers (NMSC) in solid organ transplant patients. The data on NMSC in patients taking thiopurines for IBD is conflicting. <h3>Methods</h3> We searched electronic databases (PubMed, OVID, the Cochrane library, EMBASE and CINAHL) for full journal articles reporting on the risk of developing NMSC in patients taking thiopurines for IBD and hand searched the reference lists of all retrieved articles. Pooled adjusted hazard ratios and 95% confidence intervals were determined using a random effects model. Publication bias was assessed using Funnel plots or Egger’s test for regression asymmetry. Heterogeneity was assessed using Cochran’s Q and the I2 statistic. <h3>Results</h3> A total of 8 studies involving 60,351 patients provided data on the risk of developing NMSC in patients with IBD on thiopurines. The pooled adjusted hazard ratio of developing NMSC after exposure to thiopurines in patients with IBD was 2.275 (95% CI 1.502 to 3.446). There was significant heterogeneity (I2 76%) between the studies, but no evidence of publication bias (<i>P</i> = 0.15, intercept = –6.7 and 95% CI: –17.2 to 3.7). Meta regression analysis suggested that the population studied (hospital based versus population based) and duration of follow up (&gt; 3 years) were the major contributors to the heterogeneity. Grouping studies according to population studied and also duration suggests that the risk was much higher in hospital based and shorter duration studies (Table). <h3>Conclusion</h3> The risk of developing NMSC in patients with IBD on thiopurines is only modestly elevated. This effect loses significance when studies with less than 3 years follow-up are excluded. The difference in pooled risk between population based and hospital based studies suggests the possibility that ascertainment bias could have contributed to this increased risk. Use of thiopurines to treat IBD should not be limited by this marginally increased risk of NMSC. <h3>Disclosure of Interest</h3> None Declared.
Abstract P5-11-14: Distribution of Tamoxifen and Five Metabolites into Normal and Malignant Human Breast Cancer Tissue during Conventional and Low Dose Treatment
Authors: J Gjerde, S Gandini, A Guerrieri-Gonzaga, Flågeng M Hauglid, B Bonanni, D Macis, G Mellgren, A De Censi, EA. Lien
Journal: Cancer Research (2010)

Abstract Background: Biotransformation of tamoxifen leads to metabolites with different pharmacological and toxicological effects. Profiling and screening for active metabolites are important to assess their contribution to the overall therapeutic and adverse effects. The anticancer effect of tamoxifen is believed to be due to the hydroxylated metabolites 4hydroxytamoxifen (4OHtam) and 4hydroxyNdesmethyltamoxifen (4OHNDtam, endoxifen). Its demethylated metabolites have been related to side effects of the drug, whereas effects of tamoxifenNoxide (tamNoxide) have not been evaluated. In the present study we wanted to examine the distribution of tam and five of its metabolites in serum and normal and malignant breast tissues during normal dose (20 mg/day) and low dose (5 or 1 mg/day) regimens after 28 days of continuous dosing. Methods: Serum and biopsies from 56 patients were available for analysis. The concentrations of tamoxifen and the metabolites 4OHtam, 4OHNDtam, Ndesmethyltamoxifen (NDtam), Ndesdimethyltamoxifen (NDDtam), and tamNoxide in serum and tissues were measured by means of a recently developed highly sensitive liquid chromatography tandem mass spectrometry (LCMSMS) method. Results: Serum and biopsies from 56 patients were available for analysis. All compounds including the potent metabolites 4OHtam and 4OHNDtam were detected and measured in all samples. The tissue levels of tam and its hydroxylated and demethylated metabolites were highly related to the serum levels (p &amp;lt; 0.000 — 0.0069). The tumor tissue to serum concentration ratios of tamNoxide decreased by increasing doses (p &amp;lt; 0.0001) whereas this ratio was unchanged over the dose range 1-20 mg/day for the other compounds measured. Conclusion: Tamoxifen and its metabolites were detected in all samples examined including those sampled during the low dose regimens. The tissue levels of tamoxifen and its hydroxylated and demethylated metabolites were strongly corresponding to the serum concentrations, in contrast to those of tamNoxide. The strong relations between the concentrations of the potent active 4OHtam and 4OHNDtam (endoxifen) in serum and target tissues suggest that implementation of therapeutic drug monitoring may represent a tool to improve tamoxifen therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-14.
Understanding, evaluating, and producing arguments: Training is necessary for reasoning skills
Authors: Maralee Harrell
Journal: Behavioral and Brain Sciences (2011)

Abstract This commentary suggests that the general population has much less reasoning skill than is claimed by Mercier &amp; Sperber (M&amp;S). In particular, many studies suggest that the skills of understanding, evaluating, and producing arguments are generally poor in the population of people who have not had specific training.
The Waterhouse-Friderichsen Syndrome
Authors: Vincent C. D'Agati, Bruno A. Marangoni
Journal: New England Journal of Medicine (1945)

THE Waterhouse-Friderichsen syndrome is a clinical entity first described in 1911 by Waterhouse1 in an eight-month-old child. In 1918, Friderichsen2 reviewed the literature and described a similar case with a fulminating course, characterized clinically by stupor, cyanosis, pallor, vomiting and a rapidly spreading purpuric eruption, and at autopsy by massive bilateral adrenal hemorrhages. This syndrome is associated with a bacteremia, the etiologic agent in the majority of cases being the meningococcus. Although the pneumococcus, hemolytic streptococcus and staphylococcus have also been inculpated, considerable doubt has been cast on the role of any of these organisms as the offending agent.Most . . .