tbuckley/cabot-search huggingface dataset:
c-MYC amplification and correlation with patient outcome in early stage HER2+ breast cancer from the NCCTG adjuvant intergroup trial N9831.
Authors: EA Perez, MM Reinholz, AC Dueck, AE Wiktor, WL Lingle, NE Davidson, S Martino, PA Kaufman, LA Kutteh, RB Jenkins
Journal: Cancer Research (2009)

Abstract Abstract #56 Background: Recent findings from NSABP B-31 suggested that breast cancer (BC) patients (pts) with c-MYC (MYC)/HER2 co-amplification in their primary tumors may benefit more in terms of disease-free survival (DFS) from adjuvant trastuzumab (n=471; p&amp;lt;0.0001, HR 0.24; 13 vs. 51 events) than those pts with only HER2 amplification in their primary tumors (n=1078, p=0.007, HR 0.63; 55 vs. 82 events).&amp;#x2028; Purpose: The overall objective of this analysis is to determine the association between MYC/HER2 co-amplification and outcome of pts randomized to receive chemotherapy alone (Arm A) or chemotherapy with concurrent trastuzumab (Arm C) on N9831.&amp;#x2028; Patients/Methods: This analysis included 868 pts from the HER2+ NCCTG N9831 Intergroup adjuvant trastuzumab phase III clinical trial on Arms A or C. Fluorescent in situ hybridization (FISH) was performed at a central laboratory, Mayo Clinic Clinical Cytogenetics Laboratory, using dual probe mixtures for HER2 (17q11.2-12/centromere 17) and for MYC (8q24/centromere 8). The HER2 amplification status in whole tissue sections was evaluated to determine eligibility of pts for N9831. Tissue microarrays containing three cores from each patient's tumor were analyzed for MYC amplification status. The gene and centromere copy number as well as the distribution of the signals for each marker were determined in sixty non-overlapping interphase nuclei.&amp;#x2028; Results: Of 273 pts with completed FISH analyses, 34 (12%) pts had MYC amplification. The rate of MYC amplification was similar across arms (18/135 [13%] vs. 16/138 [12%]; ChiS p=0.66). Co-amplification of MYC/HER2 was observed in 32 (12%) pts with similar co-amplification rates across arms (17/135 [13%] vs. 15/138 [11%]; ChiS p=0.66). Based on preliminary analyses, MYC amplification and MYC/HER2 co-amplification do not appear to be associated with race, menopausal status, hormone receptor status, nodal status, tumor histology, tumor grade, or tumor size (all ChiS p&amp;gt;0.05); however, MYC amplified pts were significantly younger than MYC non-amplified pts (mean 46.4 vs. 51.0, t-test p=0.02) and MYC/HER2 co-amplified pts were significantly younger than MYC/HER2 non-co-amplified pts (mean 45.9 vs. 51.0, t-test p=0.01).&amp;#x2028; Conclusions: In our initial analyses of 239 pts, we observed a lower frequency of MYC/HER2 co-amplification than the previously reported 30% for NSABP B-31. Complete FISH analyses of 868 pts in N9831 and association with DFS will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 56.
Effects of nitric oxide (NO)-donors on activated human hepatic stellate cells (HSC): cellular basis for the treatment of portal hypertension
Authors: R.M.S. DeFranco, A. Caligiuri, P. Failli, A. Gentilini, R. Romanelli, A. Casini, C. Tosti-Guerra, P. Gentilini, G. Laffi, M. Pinzani
Journal: Journal of Hepatology (1998)
Covert Drug Abuse
Authors: Stephen C. Butzer
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The article by Blumberg et al on illicit drug use by young voluntary psychiatric inpatients (<b>217</b>:1659, 1971) aroused our interest considerably. We are currently running a 20-bed inpatient therapeutic community for adolescents and young adults (age range, 15 to 25 years) and thought we might be dealing with a problem of similar magnitude. However, this turned out not to be the case. Following their protocol, we obtained a urine sample from each patient on a Monday morning and found no covert amphetamine or barbiturate use in 20 patients. Like their sample, 51 of 65 patients admitted to our unit from July 1 to Dec 1, 1971, have used illicit drugs extensively before hospitalization; 10% have used opiates in one form or another; 30%, each of barbiturates and amphetamines; 41%, hallucinogens; and 72%, marihuana. In spite of this, drug use or traffic or both on our unit
Discovery and occurrence of the fumonisins: a historical perspective.
Authors: W F Marasas
Journal: Environmental Health Perspectives (2001)

This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.
Drug points: Purpuric rash associated with slow release morphine
Authors: R J Whiston, C D M Griffith, B R Hopkinson
Journal: BMJ (1988)

Digoxin is a widely prescribed drug with narrow therapeutic margins, and intoxication is a common complication.We report a case ofsevere generalised chorea, agitation, and emotional disturbance due to digoxin excess.A 63 year old woman with a dissection of the ascending aorta had been treated conservatively for one month with digoxin 250 ig daily, labetalol 100 mg three times a day, dihydralazine 25 mg twice a day,
Cytomegalovirus Infection in Heart Transplant Recipients Is Associated With Impaired Endothelial Function
Authors: Paraskevi Petrakopoulou, Marion Kübrich, Sinan Pehlivanli, Bruno Meiser, Bruno Reichart, Wolfgang von Scheidt, Michael Weis
Journal: Circulation (2004)

Background— Cardiac allograft vasculopathy (CAV) is initiated by allograft endothelial injury. We hypothesized that a major mechanism by which cytomegalovirus (CMV) could contribute to CAV is by dysregulation of the endothelial vasomotor response. Methods— Coronary endothelial vasomotor function was determined in 183 consecutive patients (24±33 months after transplantation), and was correlated with recipient and donor CMV serological status before transplantation and with documented CMV infection episodes (CMVpp65Ag+). Serial endothelial function measurements were performed in a subgroup of 53 transplant recipients (1 month and 12 months after transplantation). The composite endpoint of cardiovascular related events and death during a follow-up of 66±41 months was analyzed based on the CMV serological status before transplantation. Results— The medium event-free time for CMV-negative recipients of CMV-positive hearts was 8.1 years compared with 13.3 years for the other groups ( P &lt;0.05). Distal epicardial but not microvascular endothelial function was significantly impaired in CMV seronegative recipients of seropositive donor hearts (n=48) compared with all other groups ( P &lt;0.01 versus seronegative recipient/seronegative donor; P &lt;0.05 versus seropositive recipient/seronegative donor; P &lt;0.05 versus seropositive recipient/seropositive donor). Distal epicardial endothelial dysfunction was more pronounced in heart transplant recipients with a history of documented CMV infection compared with patients without any documented CMV infection ( P &lt;0.01). In a longitudinal subgroup analysis, distal epicardial and microcirculatory endothelial vasomotor response deteriorated significantly in recipients with documented CMV infection ( P &lt;0.05 versus baseline) but not in patients without previous CMV infection. Conclusion— Documented CMV infection episodes in heart transplant recipients are associated with impaired coronary endothelial function. CMV-negative recipients of CMV-positive donor hearts have an impaired distal epicardial endothelial function and an increased incidence of cardiovascular-related events and death during follow-up. CMV infection may contribute to allograft failure by accelerating coronary endothelial dysfunction.
Psychiatric disorders and the social brain: Distinguishing mentalizing and empathizing
Authors: Alfonso Troisi
Journal: Behavioral and Brain Sciences (2008)

Abstract Social cognition is a broad term, incorporating all aspects of social functioning from perceiving emotional stimuli to attributional style and theory of mind. Not distinguishing between these different capacities may confound the interpretation of the data deriving from studies of the relationship between psychiatric disorders and the social brain. The distinction between cognitive and affective components of social cognition is clearly exemplified by the abnormalities observed in psychopathy and Williams syndrome.
Toxic-Shock Syndrome
Authors: Jeffrey P. Davis, P. Joan Chesney, Philip J. Wand, Martin LaVenture
Journal: New England Journal of Medicine (1980)

Surveillance for toxic-shock syndrome (TSS) in Wisconsin detected 38 cases with onsets from September 1975 through June 1980. Thirty-seven of the cases occurred after January 1, 1979; 37 of the patients were women, 35 cases occurred during menses; 38 patients were white; and one patient died. Cervical or vaginal cultures were obtained before antibiotic therapy in 23 patients, and 17 cultures were positive for Staphylococcus aureus. Ten patients had at least one recurrent episode during subsequent menstrual periods. The recurrence rate was lower in patients who had been treated with beta-lactamase-resistant antibiotics. Thirty-five patients were matched for age and menstruation to 105 controls: 34 of 35 cases (versus 80 of 105 controls) used tampons during every menstrual period (P < 0.01); nine of 35 cases (versus 64 of 105 controls) practiced contraception (P < 0.001). In Wisconsin the minimum incidence of TSS as defined by clinical criteria is 6.2 cases per 100,000 menstruating women per year. The rate of TSS among menstruating women younger than 30 years was 2.4 to 3.3 times the rate among those who were 30 or older.
Establishment of Diagnostic Validity in Psychiatric Illness: Its Application to Schizophrenia
Authors: ELI ROBINS, SAMUEL B. GUZE
Journal: American Journal of Psychiatry (1970)

A method for achieving diagnostic validity in psychiatric illness is described, consisting of five phases: clinical description, laboratory study, exclusion of other disorders, follow-up study, and family study. The method was applied in this paper to patients with the diagnosis of schizophrenia, and it was shown by follow-up and family studies that poor prognosis cases can be validly separated clinically from good prognosis cases. The authors conclude that good prognosis "schizophrenia" is not mild schizophrenia, but a different illness.
A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection
Authors: S. Gross, A. Buchner, J. Crook, J. Cangemi, M. Picco, H. Wolfsen, K. DeVault, D. Loeb, M. Raimondo, T. Woodward, M. Wallace
Journal: Endoscopy (2011)

Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy.In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates.100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11).Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.
Antiviral Therapy for Human Papillomaviruses: Rationale and Prospects
Authors: William C. Phelps
Journal: Annals of Internal Medicine (1995)

Objective: To review the basic virology of human papillomavirus (HPV) and the natural history of HPV infection and to discuss current and potential therapies. Data Sources: The MEDLINE database (1966 to 1994) was searched to identify English-language articles and abstracts on HPV biology and antiviral chemotherapy. Study Selection: Peer-reviewed basic science and clinical research studies on the molecular, cellular, and human biology of HPV infection. Data Extraction: Summaries of data from research studies on the biology of papillomavirus infection and information from review articles on the basic and applied pharmacology of antiviral agents. Data Synthesis: Papillomavirus infections are very common. Human papillomavirus infections may be asymptomatic or may be manifested in various benign or malignant lesions, most notably anogenital condyloma and anogenital carcinoma. Currently, therapeutic options for HPV infection are limited, expensive, and often ineffective. By understanding the basic virology and natural history of HPV infection, potential sites for pharmacologic intervention can be identified. Although currently available antiviral compounds are inactive against HPV, they serve as models for the rational design of HPV antiviral drugs. Conclusions: Although HPV infection causes substantial morbidity and expense, uniformly effective therapy for HPV infection is not currently available. Several processes in the HPV infection cycle are appropriate targets for the development of antiviral agents. The development of compounds active against HPV could prevent the benign and malignant diseases associated with HPV infection.
Lead poisoning in Nigeria causes "unprecedented" emergency
Authors: P. Moszynski
Journal: BMJ (2010)

International agencies are urgently scaling up their response to help local authorities to cope with mass lead poisoning in the northern Nigerian state of Zamfara, described by the World Health Organization as an “unprecedented environmental emergency.”

The charity Medecins Sans Frontieres (MSF), whose staff first discovered the problem, says that gold mining activity in the area has led to a substantial rise in numbers of deaths of children and that hundreds of people are needing treatment for dangerously high levels of lead poisoning.

A total of 161 deaths have been attributed to the incident so far, with hundreds and potentially thousands more people becoming seriously ill.

MSF’s …
Management of the Fetus With a Urinary Tract Malformation
Authors: Michael R. Harrison
Journal: JAMA (1981)

Obstetric sonography revealed urinary tract malformations in 13 fetuses. Six had severe dysplastic lesions incompatible with postnatal life; in all six, oligohydramnios and inability to detect normal kidney or bladder allowed appropriate counseling and management. Four fetuses had unilateral lesions (three hydronephrotic, one multicystic); all had evidence of adequate contralateral function and were successfully treated after delivery near term. Three fetuses had bilateral hydronephrosis secondary to urethral obstruction. The two who were born near term died of hypoplastic lungs, end-stage hydronephrosis, and facial and skeletal deformities. The other, electively delivered at 32 weeks, had none of the stigmata of Potter's syndrome, and early decompression salvaged sufficient renal function for survival. Prenatal sonographic assessment of urinary tract anatomy and function can improve perinatal management. The fetus with hydronephrosis may benefit from early decompression. (<i>JAMA</i>1981;246:635-639)
Depression and Survival Following Myocardial Infarction
Authors: Jonathan B. Tocks
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The most obvious implication from the study by Frasure-Smith et al<sup>1</sup>was that to treat depression in the post-MI patient the clinician needs to know how to recognize depression. If further studies show that intervening and treating the depression help to lessen the increased mortality associated with it, then clearly recognition and diagnosis become very important. Screening for depression could have the same mortality implications as some of the present tests such as checking laboratory parameters, low-level stress testing, and other measures that are routinely performed. The literature is full of articles showing how depression is underdiagnosed, even by family physicians who have been trained in the recognition of this common problem. How are subspecialists whose training devoted little or no time to the recognition and treatment of depression going to diagnose this problem? Should they routinely administer some type of a rating scale such as
Ceramide Reduction and Transcriptional Up-Regulation of Glucosylceramide Synthase through Doxorubicin-Activated Sp1 in Drug-Resistant HL-60/ADR Cells
Authors: Yoshikazu Uchida, Mitsuru Itoh, Yoshimitsu Taguchi, Syohei Yamaoka, Hisanori Umehara, Shin-ichi Ichikawa, Yoshio Hirabayashi, Walter M. Holleran, Toshiro Okazaki
Journal: Cancer Research (2004)

Abstract Treatment with doxorubicin (DOX) induced apoptosis with an increase of ceramide content in drug-sensitive HL-60 cells, but not in drug-resistant HL-60/ADR cells. In HL-60/ADR cells (but not in HL-60 cells), the levels of mRNA, protein, and activity in glucosylceramide synthase (GCS), which converts ceramide to glucosylceramide, were up-regulated in response to DOX. Thus, abrogation of apoptosis in HL-60/ADR cells might be involved in ceramide reduction through DOX-induced up-regulation of GCS function. Because we reported that a GC-rich/Sp1 promoter binding region was of importance in the regulation of GCS expression, the role of Sp1 in DOX-induced up-regulation of GCS and apoptosis was investigated. DOX induced Sp1 activation in HL-60/ADR cells, as assessed by Sp1 gel shift and promoter-luciferase reporter assays, whereas transfection of double-stranded oligodeoxynucleotides (ODNs) containing a GC-rich/Sp1 region (Sp1 decoy ODNs) inhibited DOX-induced Sp1 activation. In addition, DOX-increased mRNA and enzyme activity in GCS were inhibited by Sp1 decoy, in conjunction with corresponding elevations of ceramide content. Moreover, DOX-induced apoptotic cell death was significantly increased in Sp1 decoy ODN-transfected HL-60/ADR cells over mock-transfected HL-60/ADR cells. Together, the results suggest that transcriptional up-regulation of GCS through DOX-induced activation of Sp1 is one potential mechanism to regulate ceramide increase and apoptosis in HL-60/ADR cells.
Health Decisions for the American People Subject of New National Bioethical Policy Group
Authors: Marsha F. Goldsmith
Journal: JAMA (1988)

REACHING DECISIONS about medical care has taken on a new dimension in the United States in the 1980s, with traditional physician input frequently joined and sometimes superseded by patient participation. Grass roots groups have sprung up around the country to provide forums for education and dialogue between providers and consumers on a wide range of bioethical issues. The Community Health Decisions movement, as this effort is called, entered a new phase recently when representatives of state projects met in Denver to lay the groundwork for the first national umbrella organization. The group's goals grew from the original project designed to give ordinary people a voice along with experts in determining health policy: Oregon Health Decisions Inc, a private, nonprofit organization, began in 1982 to develop awareness throughout the state of ethical issues in health care. Ralph Crawshaw, MD, a Portland psychiatrist, is the dedicated project director, often cited as the
A New Technique of Endoscopic Full-Thickness Resection Using a Flexible Stapler
Authors: G. Kaehler, R. Grobholz, C. Langner, K. Suchan, S. Post
Journal: Endoscopy (2006)

There is a significant need for a safe and easy technique for endoluminal endoscopic resection of gastrointestinal lesions, but such procedures are usually restricted to resection of the mucosal layer in order to preserve the integrity of the wall of the gastrointestinal tract. We present two patients, one with early cancer and one with a carcinoid tumor, who were treated by endoscopic full-thickness resection. We used a stapling device, consisting of a flexible shaft, which was positioned intraluminally, and a remote control. After pilot investigations in pigs and in human anatomical preparations, we performed a full-thickness resection of the gastric wall in these patients, using the flexible stapling device under gastroscopic control. Gastric wall specimens up to 4 cm x 4 cm in size were resected with the use of two to three stapler magazines. Both procedures followed an uneventful course and the patients made an uncomplicated recovery. Further studies are necessary to test the applicability of the technique in the management of other gastric neoplastic lesions.
Glial Dysfunction Causes Age-Related Memory Impairment in Drosophila
Authors: Daisuke Yamazaki, Junjiro Horiuchi, Kohei Ueno, Taro Ueno, Shinjiro Saeki, Motomi Matsuno, Shintaro Naganos, Tomoyuki Miyashita, Yukinori Hirano, Hiroyuki Nishikawa, Masato Taoka, Yoshio Yamauchi, Toshiaki Isobe, Yoshiko Honda, Tohru Kodama, Tomoko Masuda, Minoru Saitoe
Journal: Neuron (2014)
Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase
Authors: F J Giles, H M Kantarjian, P D le Coutre, M Baccarani, F-X Mahon, R E Blakesley, N J Gallagher, K Gillis, S L Goldberg, R A Larson, A Hochhaus, O G Ottmann
Journal: Leukemia (2011)