tbuckley/cabot-search huggingface dataset:
Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.
Authors: C C McDonald, H J Stewart
Journal: BMJ (1991)

OBJECTIVE--To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN--Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING--Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS--1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES--Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS--Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION--Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.
Toward the Conquest of Cancer
Authors: James P. Cooney
Journal: JAMA (1961)

This book is a straightforward, realistic discussion of the present status of cancer —the disease and the cure. The book's theme is cancer drugs—chemistry's weapon of hope against cancer. Actually, the basic plea is recorded in the introduction, "Of all Americans who die of cancer today, the deaths of one-fourth might have been avoided had proper treatment been started in time." New drugs that let the patient live with his disease are cited as evidence that chemicals are vital to the welfare of the 265,000 Americans slated to die of cancer this year. Of these, it is claimed that 85,000 could yet be cured, if earlier and better treatment could be started. Chemist Battista delves superficially into the basic nature and chemistry of normal and cancerous cells, deftly inciting the reader's interest in the role of nucleic acid, "the closest chemical to the mysterious spark of life." He offers a
Is the Cortical Blindness Due to Diaschisis?
Authors: ORHAN DENIZ, ERHAN VAROĞLU, SALIM DEĞIRMENCI, MUSTAFA YILMAZ, HATICE USLU
Journal: Clinical Nuclear Medicine (1997)

Cortical blindness is defined as a loss of vision that is caused by bilateral occipital lobe lesions. Many reports of patients with cortical blindness describe bilateral occipital lesions visualized on morphologic and functional imaging studies. The authors present the case of a patient who became cortically blind after a hemorrhagic lesion of the right occipital lobe. CT failed to reveal bilateral occipital involvement, but the brain SPECT showed decreased perfusion of both parieto-occipital areas. The brain SPECT findings correlated better with the clinical status. SPECT may be more useful than CT for detecting functional brain abnormalities, and the clinical and imaging findings of the present patient could be attributed to the transhemispheric diaschisis.
Radiology and Lumbar Disks
Authors: J. R. Armstrong
Journal: BMJ (1954)

<h3>Background</h3> Advances in neonatal healthcare have resulted in decreased mortality after preterm birth but have not led to parallel decreases in morbidity. Academic performance provides insight in the outcomes and specific difficulties and needs of preterm children. <h3>Objective</h3> To study academic performance in preterm children born in the antenatal steroids and surfactant era and possible moderating effects of perinatal and demographic factors. <h3>Design</h3> PubMed, Web of Science and PsycINFO were searched for peer-reviewed articles. Cohort studies with a full-term control group reporting standardised academic performance scores of preterm children (&lt;37 weeks of gestation) at age 5 years or older and born in the antenatal steroids and surfactant era were included. Academic test scores and special educational needs of preterm and full-term children were analysed using random effects meta-analysis. Random effects meta-regressions were performed to explore the predictive role of perinatal and demographic factors for between-study variance in effect sizes. <h3>Results</h3> The 17 eligible studies included 2390 preterm children and 1549 controls. Preterm children scored 0.71 SD below full-term peers on arithmetic (p&lt;0.001), 0.44 and 0.52 SD lower on reading and spelling (p&lt;0.001) and were 2.85 times more likely to receive special educational assistance (95% CI 2.12 to 3.84, p&lt;0.001). Bronchopulmonarydysplasia explained 44% of the variance in academic performance (p=0.006). <h3>Conclusion</h3> Preterm children born in the antenatal steroids and surfactant era show considerable academic difficulties. Preterm children with bronchopulmonarydysplasia are at particular risk for poor academic outcome.
Results According to Age in Avex, a Randomized Phase 3 Trial of Bevacizumab with Capecitabine for Elderly Patients with Mcrc
Authors: Mark Saunders, Istvan Lang, Eugenio Marcuello, Vito Lorusso, Janja Ocvirk, Derek Jonker, Stuart Osborne, Markus Loeffler, Daniel Waterkamp, David Cunningham
Journal: Annals of Oncology (2013)
American Association of Clinical Endocrinologists Meeting, May 2002
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2002)

This is the first of two articles covering the American Association of Clinical Endocrinologists Meeting in Chicago, 1–5 May 2002. Topics include the sequencing of the human genome, obesity and diabetes, PPAR agonists, and erectile dysfunction.

J. Craig Venter (Rockville, Maryland) gave the keynote address, discussing his work in the sequencing of the human genome using high through-put technologies with biocomputational analysis. He reviewed his initial work in the field during the 1980s sequencing the epinephrine receptor, a task which took a decade. He subsequently developed an approach using a “shotgun sequencing strategy” using mechanical shearing to cut a whole genome into different sized expressed sequence tags (ESTs), developing a computational algorithm to piece the EST into a full genome. With the development of more powerful algorithms and computers, his group progressed from sequencing the Haemophilus influenzae genome, 1.8 Mbp, in 1995, to analyzing the Drosophila genome, 120 Mbp, and to sequencing the 3,000-Mbp human genome, reported in June 2000. “The biggest surprise,” Venter stated, “was the small number of genes.” Approximately 26,000 different genes were present, with some sections of chromosomes highly dense in genes, but many sections with very few genes. Overall, only 1.1% of the genome actually encodes genes, and 42% of those discovered are of unknown function. Comparison of the genomes of Drosophila with man reveals that new genes appear in the immune and hemostatic systems as well as many aspects of cell signaling, particularly those transcription factors that regulate the expression of other genes.

Venter noted the phenomenon of repeat gene sequences in the human genome. Chromosome 19 has the highest density of genes, many of which are repeated in other chromosomes. Analysis of these repeats, he suggested, may allow assessment of our “genetic history.” The mouse genome is 90% the size of that of …
Distribution of cholesterol between vesicles and micelles in human gallbladder bile: Influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid
Authors: Staffan Sahlin, Per Thyberg, Jon Ahlberg, Bo Angelin, Kurt Einarsson
Journal: Hepatology (1991)

The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 Å. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% ± 4%) compared with the gallstone-free (28% ± 3%), ursodeoxycholic acid (28% ± 3%) and chenodeoxycholic acid (18%± 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% ± 12%, 51% ± 9% and 65% ± 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenode-oxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The cholesterol/phospholipid ratio was about 0.15 in all micellar fractions. The nucleation time of bile from the gallstone group was short (2 ± 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 ± 3, 24 ± 6 and 14 ± 3 days, respectively). These observations give further support to the concept that the mechanism for gallstone dissolution is complex and different for chenodeoxycholic acid and ursodeoxycholic acid. (Hepatology 1991;13:104-110).
Clinical outcomes after the arterial switch operation for transposition. Patient, support, procedural, and institutional risk factors. Congenital Heart Surgeons Society.
Authors: J W Kirklin, E H Blackstone, C I Tchervenkov, A R Castaneda
Journal: Circulation (1992)

BACKGROUND As the probability increases that the arterial switch operation is optimal treatment for transposition, detailed information about outcomes and the circumstances in which they are suboptimal becomes important. METHODS AND RESULTS A multi-institutional prospective study with annual detailed follow-up included 513 neonates with simple transposition or transposition and ventricular septal defect entering for diagnosis and treatment at &lt; 15 days of age and undergoing an arterial switch repair. The 1-month and 1- and 5-year survivals were 84%, 82%, and 82%, respectively. The hazard function for death had a rapidly declining single phase that approached zero by 12 months after surgery. Among the eight patients who died &gt; or = 3 months after the operation, four had severe ventricular dysfunction, probably related to imperfect coronary arterial transfer. Coexisting single ventricular septal defect was not a risk factor for death. Origin of the left main coronary artery or only the left anterior descending or the circumflex artery from the right posterior sinus (sinus 2) was a risk factor that was even stronger when an intramural course was present; multiplicity of ventricular septal defects was a risk factor. Longer global myocardial ischemic time and total circulatory arrest time were risk factors. Certain institutions were shown to be risk factors for death; the results in some improved with increasing experience, in some they did not, and in some they worsened. CONCLUSIONS Good early and intermediate-term clinical outcomes can be obtained in neonates with simple transposition and transposition and ventricular septal defect by use of the arterial switch operation. Certain coronary artery patterns and certain institutions lessen the goodness of outcome.
Brief Report: Natural History of Individuals With Clinically Recognized Monoclonal B-Cell Lymphocytosis Compared With Patients With Rai 0 Chronic Lymphocytic Leukemia
Authors: Tait D. Shanafelt, Neil E. Kay, Kari G. Rabe, Timothy G. Call, Clive S. Zent, Kami Maddocks, Greg Jenkins, Diane F. Jelinek, William G. Morice, Justin Boysen, Susan Schwager, Deborah Bowen, Susan L. Slager, Curtis A. Hanson
Journal: Journal of Clinical Oncology (2009)

The diagnosis of monoclonal B-cell lymphocytosis (MBL) is used to characterize patients with a circulating population of clonal B cells, a total B-cell count of less than 5 x 10(9)/L, and no other features of a B-cell lymphoproliferative disorder including lymphadenopathy/organomegaly. The natural history of clinically identified MBL is unclear. The goal of this study was to explore the outcome of patients with MBL relative to that of individuals with Rai stage 0 chronic lymphocytic leukemia (CLL).We used hematopathology records to identify a cohort of 631 patients with newly diagnosed MBL or Rai stage 0 CLL. Within this cohort, 302 patients had MBL (B-cell counts of 0.02 to 4.99 x 10(9)/L); 94 patients had Rai stage 0 CLL with an absolute lymphocyte count (ALC) < or = 10 x 10(9)/L; and 219 patients had Rai stage 0 CLL with an ALC more than 10 x 10(9)/L. Data on clinical outcome were abstracted from medical records.The percentage of MBL patients free of treatment at 1, 2, and 5 years was 99%, 98%, and 93%, respectively. B-cell count as a continuous variable (hazard ratio [HR] = 2.9, P = .04) and CD38 status (HR = 10.8, P = .006) predicted time to treatment (TTT) among MBL patients. The likelihood of treatment for MBL patients was lower (HR = 0.32, P = .04) than that of both Rai stage 0 CLL patients with an ALC less than 10 x 10(9)/L (n = 94) and Rai stage 0 CLL patients with an ALC more than 10 x 10(9)/L (n = 219; P = .0003).Individuals with MBL identified in clinical practice have a low risk for progression at 5 years. Because B-cell count seems to relate to TTT as a continuous variable, additional studies are needed to determine what B-cell count should be used to distinguish between MBL and CLL.
Changes Over Time in Indications, Diagnostic Yield, and Clinical Effects of Double-Balloon Enteroscopy
Authors: Seong Ran Jeon, Jin–Oh Kim, Hyun Gun Kim, Tae Hee Lee, Wan Jung Kim, Bong Min Ko, Joo Young Cho, Joon Seong Lee, Moon Sung Lee
Journal: Clinical Gastroenterology and Hepatology (2012)
Surgery of Rheumatoid Arthritis
Authors: Reginald R. Cooper
Journal: JAMA (1972)

In light of the unpredictable and unexplained vacillations in the clinical course of patients with rheumatoid arthritis, selection of appropriate surgical procedures at a given stage of the disease becomes a formidable, albeit critical, task. The authors of this treatise outline possible operations for each joint at multiple stages of the disease, give the indications, advantages, and disadvantages, describe the surgical technique, and, in most sections, document a series of patients wherein each operation was employed. This they do with clarity and with as much precision as the nature of the disease permits. The book, written by several distinguished physicians and surgeons and often expressing their individual opinions, originated from a conference on rheumatoid arthritis. The chapters by Drs. Cruess and Mitchell summarizing the guidelines for selection of knee and hip operations provide extremely valuable information. Some sections direct attention to procedures too often forgotten in the management of the
Bacterially produced human insulin given therapeutically
Authors: William A. Check
Journal: JAMA (1981)

In mid-December, five Wichita, Kan, patients with newly diagnosed diabetes became the first humans to be treated with a substance produced by recombinant DNA technology. The five began therapy with insulin produced by bacteria into which the human insulin gene had been introduced. The recombinant insulin (also known as biosynthetic insulin), which is being produced by Eli Lilly and Co, had previously been administered to healthy human volunteers in the United States, Great Britain, Greece, and West Germany and found to be free of toxic effects. Phase II testing of the substance is now being carried out under the supervision of Richard Guthrie, MD, professor and chairman of the Department of Pediatrics at the University of Kansas School of Medicine in Wichita; Arthur Krosnick, MD, of the Mercer Medical Center in Trenton, NJ; and Frederick Whitehouse, MD, a former president of the American Diabetes Association who is with the Henry
Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles
Authors: Hae Yun Nam, Seok Min Kwon, Hyunjin Chung, Seung-Young Lee, Seung-Hae Kwon, Hyesung Jeon, Yoonkyung Kim, Jae Hyung Park, Joon Kim, Songwook Her, Yu-Kyoung Oh, Ick Chan Kwon, Kwangmeyung Kim, Seo Young Jeong
Journal: Journal of Controlled Release (2009)
Abstract B15: The pan-BCR-ABL inhibitor ponatinib inhibits viability of gatekeeper mutant BCR-ABLT315I cells with greater potency than a nilotinib/MEK inhibitor combination
Authors: Alexa B. Schrock, Joseph M. Gozgit, Victor Rivera
Journal: Clinical Cancer Research (2012)

Abstract Introduction: The second generation BCR-ABL inhibitor nilotinib has recently been shown to have weak off-target activity against RAF and drive the paradoxical activation of BRAF and CRAF in cells with activated RAS. Importantly, this effect has been seen in cells expressing T315I mutant BCR-ABL, against which nilotinib is ineffective (Packer, Cancer Cell 20:715). Interestingly, nilotinib was shown to synergize with an inhibitor of MEK, a downstream effector of RAF, to inhibit the viability of cells expressing BCR-ABLT315I. Ponatinib is a pan-BCR-ABL inhibitor that potently kills cells expressing BCR-ABLT315I and is in a pivotal phase 2 trial in patients with CML. Here we examined the activity of ponatinib against RAF and compared the cellular potency of ponatinib against BCR-ABLT315I to that of a nilotinib/MEK inhibitor combination. Results: Ponatinib potently inhibited the in vitro kinase activity of ARAF, BRAF, and CRAF with IC50s of 71, 33, and 17 nM, respectively, compared to IC50s of 4390, 235, and 188 for nilotinib. In 2 RAS mutant cell lines tested, nilotinib (1 to 10 μM) induced feedback activation of RAF/MEK/ERK signaling as reported previously; however ponatinib (0.01 to 10 μM) did not. Both ponatinib and nilotinib potently inhibited viability of Ba/F3 cells expressing native BCR-ABL, with IC50s of 1.5 and 10 nM, respectively. While nilotinib has no activity against cells expressing BCR-ABLT315I, when combined with a concentration of the MEK inhibitor AZD6244 that inhibits MEK signaling (2 μM), nilotinib inhibited viability with an IC50 of 550 nM. In contrast, ponatinib potently inhibited viability of cells expressing BCR-ABLT315I with an IC50 of 6 nM. Similarly, single agent ponatinib induced apoptosis in BCR-ABLT315I cells with 100-fold greater potency than the combination of nilotinib and AZD6244. Conclusion: In contrast to nilotinib, ponatinib does not appear to induce the paradoxical activation of RAF/MEK/ERK signaling in RAS mutant cells, possibly due to its inhibition of all 3 RAF family members. Although nilotinib synergizes with a MEK inhibitor to kill BCR-ABLT315I mutant cells, this effect requires a concentration of nilotinib approximately 50-fold higher than that required to kill native BCR-ABL cells. Substantially greater potency, at clinically achievable drug concentrations, is achieved via the direct inhibition of BCR-ABLT315I by ponatinib.
Abstract 2595: Vesicular stomatitis virus as a treatment for colorectal cancer
Authors: John H. Stewart, Maryam Ahmed, Scott A. Northrup, Douglas S. Lyles
Journal: Cancer Research (2010)

Abstract Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Despite progress in many aspects of combating colorectal cancer, the cause of death in nearly a third of all patients is metastatic disease. Vesicular stomatitis virus (VSV) is an attractive candidate as an oncolytic virus for the treatment of CRC due to its potent ability to induce apoptosis. Our group has generated a genetically engineered recombinant VSV containing an M protein mutation (rM51R) to enhance its tumor selectivity while preserving its oncolytic effects. As an extension of these findings, we hypothesized that oncolytic VSV can effectively treat CRC cells and therefore serve as an oncolytic therapy for the treatment of metastatic CRC. Methods: We compared the cytolytic effects of wild type (rwt) and M51R VSV in RKO, HCT116 and Lovo CRC cell lines via MTS assays. We initially sought to determine if CRC cells were susceptible to the oncolytic effects of VSV in single-cycle and multiple-cycle infection conditions. Viral protein synthesis and the production of viral progeny by CRC cell lines was quantified by S35 methionine labeling and viral plaque assays respectively. RKO tumor xenografts were established in athymic nude mice and injected with 108 pfu of M51R VSV. Results: We found that CRC cells display differential sensitivity to oncolytic VSV. RKO and HCT116 CRC cells were very sensitive to the oncolytic effects of both rwt and M51R viruses at 48 hours after both single and multiple-cycle infections. On the other hand, Lovo cells were somewhat resistant to VSV-induced cell killing under identical treatment conditions. All CRC cell lines supported the production of viral progeny with the peak viral production occurring at 36 hours after single and multiple-cycle infections with rwt and M51R VSV. Treatment of RKO xenografts with M51R VSV resulted in stabilization of tumor size relative to untreated controls after 21 days. Conclusions: These findings suggest that M51R VSV is a good candidate oncolytic virus for the treatment of metastatic colorectal cancer. Our future work will focus on defining the proportion of colorectal cancers that are susceptible to the oncolytic effects of VSV. In addition, we will identify molecular targets that may enhance the therapeutic efficacy of M51R VSV. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2595.
The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective
Authors: J. D. Campbell, D. E. Spackman, S. D. Sullivan
Journal: Allergy (2010)

Omalizumab, an anti-immunoglobulin E antibody, reduces exacerbations and symptoms in uncontrolled allergic asthma. The study objective was to estimate the costs and consequences of omalizumab compared to usual care from a US payer perspective.We estimated payer costs, quality-adjusted survival (QALYs), and the incremental cost-effectiveness ratio (ICER) of omalizumab compared to usual care using a state-transition simulation model that included sensitivity analyses. Every 2 weeks, patients could transition between chronic asthma and exacerbation health states. The best available evidence informed the clinical and cost input estimates. Five years of omalizumab treatment followed by usual care was assumed to estimate a lifetime horizon. Omalizumab responders (60.5% of treated) were modeled as a separate scenario where nonresponders reverted back to usual care after 16 weeks of active treatment.The mean lifetime discounted costs and QALYs were $83,400 and 13.87 for usual care and $174,500 and 14.19 for omalizumab plus usual care resulting in $287 200/QALY (95% interval: $219,300, $557, 900). The ICER was $172 300/QALY when comparing omalizumab to usual care in the responder scenario. One-way sensitivity analyses indicated that the results were sensitive to the difference in treatment-specific utilities for the chronic state, exacerbation-associated mortality, omalizumab price, exacerbation rates, and response definition.The results suggest that adding omalizumab to usual care improves QALYs at an increase in direct medical costs. The cost-effectiveness of omalizumab is similar to other chronic disease biologics. The value increases when omalizumab response is used to guide long-term treatment.