tbuckley/cabot-search huggingface dataset:
Abstract 2770: Antitumor activity of heat shock protein 90 (HSP90) inhibitor AT13387 in head and neck squamous cell carcinoma
Authors: Kristy Truong, Christopher Gouveia, Jamie Coupar, Tomoko Smyth, John Lyons, Zhong Chen, Carter Van Waes
Journal: Cancer Research (2012)

Abstract Heat shock protein 90 (HSP90) has been shown to be overexpressed in a wide range of cancers, and plays a critical role in tumor cell growth and survival by stabilizing aberrant signaling proteins and by interfering with apoptosis. Several natural and synthetic inhibitors of HSP90 have been shown to have antitumor effects, but single agent development has been limited by poor solubility, poor availability and off-target toxicities (hepatotoxicity, retinal toxicity). The aim of this study is to investigate the biological activity of the small-molecule HSP90 inhibitor, AT13387 (Astex Pharmaceuticals) for antitumor activity in head and neck squamous cell carcinoma (HNSCC). Human HNSCC cell lines, UMSCC −1 (wild-type p53) and −46 (mutant p53) were treated with AT13387. The inhibitory concentrations (IC[[Unsupported Character - Codename &amp;shy;]]50) of AT13387 on HNSCC cell lines were determined using MTT proliferation assay. AT13387 (55 mg/kg two consecutive days every week) antitumor activity, toxicity and survival were evaluated in the UMSCC −1 and −46 xenograft model in BALB/c SCID mice. AT13387 inhibited the proliferation of both UMSCC cell lines in vitro with IC50 levels of 0.05-.10 µM by MTT assay. In vivo, AT13387, at 55 mg/kg showed significant antitumor effect and improved survival in both wtTP53 UMSCC-1 and mtTP53 UMSCC-46 xenograft models. The treatment was well-tolerated and no significant body weight loss observed. These data suggest that AT13387 may possess potent antitumor activity in human HNSCC, regardless of the p53 mutation status. The potential of AT13387 as a chemosensitizer for radiotherapy is being investigated. These preclinical data suggest that AT13387 holds promise as a potential chemotherapeutic agent for HNSCC clinical trials. (Supported by NIDCD project ZIA-DC-000073 and AT13387 provided to NCI by Astex Pharmaceuticals) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2770. doi:1538-7445.AM2012-2770
Two Phase I Studies of Carboplatin Dose Escalation in Chemotherapy-Naive Ovarian Cancer Patients Supported With Patients Supported With Granulocyte-Macrophage Colony-Stimulating Factor
Authors: J. Rusthoven, L. Levin, E. Eisenhauer, J. Mazurka, J. Carmichael, G. O'Connell, P. Bryson, H. Hirte, B. Koski
Journal: JNCI Journal of the National Cancer Institute (1991)

Recombinant human granulocyte-mac-rophage colony-stimulating factor (rHuGM-CSF) may reduce myelosup-pression and, thus, allow dose escalation of certain chemotherapeutic agents. We conducted two sequential phase I trials of escalating doses of carboplatin and a Fixed dose and schedule of rHuGM-CSF in ovarian cancer patients who had not previously had chemotherapy, i.e., chemotherapy-naive patients. In the First trial, patients were assigned to regimens of increasing dose levels of carboplatin (starting at 400 mg/m 2 ) and fixed doses and schedules of cyclophosphamide (600 mg/m 2 ) and rHuGM-CSF (10 μg/kg given sub-cutaneously once daily on days 2–11). Chemotherapy was given every 3 weeks (regimen A). In the subsequent trial, the design was the same except that cyclophosphamide was omitted (regimen B). Fifteen patients received regimen A, and seven patients received regimen B. In regimen A, all three patients treated at the First dose level tolerated Five cycles at full doses. Hematologic toxicity was dose limiting at the 600-mg/m 2 dose level. When 500 mg/m 2 carboplatin was given, six of eight patients tolerated three or four cycles at full doses before requiring dose reductions or treatment delays. In regimen B, doses could not be escalated above the First dose level (600 mg/m 2 ) because of severe hematological toxicity. Nonhematological toxicity was tolerable and managed with acetaminophen, antihistamines, and/or non-steroidal, anti-inflammatory medication. Compliance was excellent. We conclude that (a) rHuGM-CSF can be given safely and reliably to chemotherapy-naive ovarian cancer patients receiving these treatment regimens, (b) early and severe thrombocytopenia was a major problem with or without cyclophosphamide with doses of carboplatin at or above 600 mg/m 2 , and (c) 500 mg/m 2 carboplatin administered every 3 weeks is the highest dose in regimen A that can be given safely in the outpatient setting. [J Natl Cancer Inst 83:1748–1753,1991]
Diabetes in Midlife and Cognitive Change Over 20 Years
Authors: Andreea M. Rawlings, A. Richey Sharrett, Andrea L.C. Schneider, Josef Coresh, Marilyn Albert, David Couper, Michael Griswold, Rebecca F. Gottesman, Lynne E. Wagenknecht, B. Gwen Windham, Elizabeth Selvin
Journal: Annals of Internal Medicine (2014)

Type 2 diabetes is associated with dementia risk, but evidence is limited for possible associations of diabetes and prediabetes with cognitive decline.To determine whether diabetes in midlife is associated with 20-year cognitive decline and to characterize long-term cognitive decline across clinical categories of hemoglobin A1c (HbA1c) levels.Prospective cohort study.The community-based ARIC (Atherosclerosis Risk in Communities) study.13,351 black and white adults aged 48 to 67 years at baseline (1990 to 1992).Diabetes was defined by self-reported physician diagnosis or medication use or HbA1c level of 6.5% or greater. Undiagnosed diabetes, prediabetes, and glucose control in persons with diagnosed diabetes were defined by clinical categories of HbA1c level. Delayed word recall, digit symbol substitution, and word fluency tests were used to assess cognitive performance and were summarized with a global Z score.Diabetes in midlife was associated with a 19% greater cognitive decline over 20 years (adjusted global Z-score difference, -0.15 [;95% CI, -0.22 to -0.08];) compared with no diabetes. Cognitive decline was significantly greater among persons with prediabetes (HbA1c level of 5.7% to 6.4%) than among those with an HbA1c level less than 5.7%. Participants with poorly controlled diabetes (HbA1c level ≥ 7.0%) had greater decline than those whose diabetes was controlled (adjusted global Z-score difference, -0.16; P = 0.071). Longer-duration diabetes was also associated with greater late-life cognitive decline (P for trend < 0.001). Rates of decline did not differ significantly between white and black persons (P for interaction = 0.44).Single HbA1c measurement at baseline, 1 test per cognitive domain, and potential geographic confounding of race comparisons.Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline.National Institutes of Health.
The healing touch
Authors: V. Edwards
Journal: BMJ (2001)

I read with fascination the BMJ article about the “patient friendly alarm system” in the last Christmas issue (2000;321:1565-6). For me it raised a memory; one that will remain evergreen.

Some years ago, on a wet sombre September afternoon, I responded to a persistent ringing on my front door bell. Aroused from a deep sleep, Kim, my Belgian shepherd dog, rushed to the door, his ears quivering alertly. I welcomed in a woman, whom I will call Christina. Thin, haggardly underweight, she sank speechlessly into …
A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell–dependent murine model of allergic asthma
Authors: Megan M. Price, Carole A. Oskeritzian, Yves T. Falanga, Kuzhuvelil B. Harikumar, Jeremy C. Allegood, Sergio E. Alvarez, Daniel Conrad, John J. Ryan, Sheldon Milstien, Sarah Spiegel
Journal: Journal of Allergy and Clinical Immunology (2012)
Infection with Yersinia enterocolitica in patients with iron overload.
Authors: H Y Chiu, D M Flynn, A V Hoffbrand, D Politis
Journal: BMJ (1986)

Infection with Yersinia enterocolitica in patients with iron overload Yersinia enterocolitica commonly causes fever and mild gastroenteritis' but occasionally causes severe illness, particularly in patients with iron overload in whom its virulence is enhanced.2Desferrioxamine used therapeutically may potentiate the growth of yersinia, which uses desferrioxamine as a siderophore to chelate iron.3We describe three patients with transfusional haemosiderosis and infection with Y enterocolitica. Case reports CASE 1A 25 year old white man with congenital sideroblastic anaemia, which had been diagnosed in 1965 and who had subsequently received regular blood transfusions (450 units) and subcutaneous desferrioxamine (serum ferritin 2460 pg/I), was admitted with symptoms of anaemia, three days of fever (395°C), slight diarrhoea, which he initially denied, but no abdominal pain.He had hepatomegaly (10 cm) and slight abdominal tenderness.His haemo- globin concentration was 53 g/l with normal white cells.The day after admission he started to receive a blood transfusion ofthree units with 6 g ofdesferrioxamine.Within eight hours he had severe diarrhoea, after 12 hours severe dyspnoea due to a persistent metabolic acidosis (bicarbonate 13 mmol (mEq)/l), and by 40 hours he had died.Intravenous penicillin, gentamicin, metronidazole, and rehydration were given to no avail.Necropsy showed an ulcer in the terminal ileum, multiple tiny colonic ulcers, and grossly enlarged purulent mesenteric lymph nodes.Stools and blood culture
Diagnosis of the Lesch-Nyhan Syndrome
Authors: Phillip Frost
Journal: JAMA (1970)

<h3>To the Editor.—</h3> The purpose of the paper we wrote was primarily to indicate that the hypoxanthine-guanine phosphoribosyl transferase deficiency is also present in skin epithelial tissue, and to point out that mosaicism is not discernible in female heterozygotes for this disorder. As a practical matter, skin biopsy specimens may be useful for diagnosis in situations in which it is not possible to assay blood samples quickly. One can inject labelled precursor into the skin 30 minutes before taking the biopsy specimen, or incubate skin specimens with labelled precursor in vitro. Such specimens may be stored in formaldehyde solution indefinitely, until autoradiographs are prepared for study at one's convenience.
Watching cement dry: a necessary but costly irritation in lower limb orthopaedics
Authors: A. B. Scrimshire, E. M. Holt
Journal: BMJ (2013)

Polymethyl-methacrylate (PMMA), synthesised in 1902, has many uses, including in aircraft windows and dentures.But it was not until 1959 that PMMA cement (bone cement) was used in hip replacements, to secure femoral and acetabular implants, by a UK pioneer of the hip replacement operation, John Charnley.Antibiotics were added to the cement to reduce infection rates, and today over a million implants have been fixed with bone cement worldwide.
Fundamental aspects of solid dispersion technology for poorly soluble drugs
Authors: Yanbin Huang, Wei-Guo Dai
Journal: Acta Pharmaceutica Sinica B (2013)

The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.
Barium Enema Complications
Authors: Eric Larsen
Journal: JAMA (1974)

To the Editor.—  The report of a case of barium enema septicemia as reported by Day and Cho (227:1258, 1974) calls to mind another case that occurred in an otherwise healthy individual.  Report of a Case.—  A healthy 64-year-old white man was admitted to the hospital because of a history of rectal bleeding. During the work-up, a barium enema was performed. Approximately 16 hours later, the temperature spiked to 40 C (104 F), with a tachycardia of 140 beats per minute and systolic blood pressure fall to 80 mm Hg. After 24 hours, the temperature was 39.6 C (103.4 F), the white blood cell count was 28,000/cu mm, and the systolic blood pressure was 90 mm Hg. He was given broadspectrum antibiotics and large quantities of fluid, to which he responded well. There was only ill-defined tenderness low in the pelvis, and his rectal examination findings were repeatedly within normal
Proving Planck Wrong
Authors: Henry I. Miller
Journal: JAMA (1987)

An important scientific innovation rarely makes its way by gradually winning over and converting its opponents.... What does happen is that its opponents gradually die out and that the growing generation is familiarized with the idea from the beginning. Max Planck, 1936 ALTHOUGH Nobel laureate Planck made this observation in another context, it may be applicable to "new" biotechnology. This would be unfortunate, because new biotechnology has just begun to fulfill its promise. The trickle of products undergoing testing has become a flood, and the numbers of governmental approvals of products are increasing exponentially. However, some recent government approvals and industry's proposals to test a variety of products, especially those that involve live organisms outside a manufacturing facility, have received mixed responses from an uncertain popular press and public. A very few vocal, well-organized opponents of biotechnology have confused the issue by mixing facts with myths. One myth is that
Changes in human colonic mucosal-submucosal blood flow after body surface cooling.
Authors: D W Forrester, J S Davison, V A Spence, W F Walker
Journal: Gut (1981)

Mucosal-submucosal blood flow in the human colostomy was measured by a radioisotopic washout technique. Changes in blood flow were recorded in 10 subjects after peripheral vasoconstriction evoked by surface cooling of the body. Accompanying the vasoconstriction was a rise in mucosal-submucosal blood flow of approximately 40%. An interpretation of the blood flow changes and the associated alterations in mean arterial blood pressure provide evidence for vasomotor and local regulatory control in the colostomy microcirculation. We believe, therefore that the colostomy is a suitable preparation for studying the human colonic microcirculation.
FDG Positron Emission Tomography in Diffuse Lewy Body Disease
Authors: ROZET TATLIDIL, PAMELA NEW, HELEN MAYBERG
Journal: Clinical Nuclear Medicine (2000)

Lewy body disease is a clinicopathologic condition that includes Parkinson’s disease at one end and diffuse Lewy body disease at the other hand. The latter is often associated with progressive cognitive deterioration, levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, and visual and auditory hallucinations. In addition, it can be a familial disease. Clinical and positron emission tomographic findings are described in a patient with atypical dementia and movement disorder and a pathologically proved diagnosis of diffuse Lewy body disease.
Diagnosis of Cholecystoses
Authors: R. Dick
Journal: Gut (1978)

<h3>Abstract</h3> Non-enzymatic, high-gain signal amplification methods with single-cell, single-molecule resolution are in great need. We present a new method (click-amplifying FISH; clampFISH) for the fluorescent detection of RNA that combines the specificity of oligonucleotides with bioorthogonal click chemistry in order to achieve high specificity and high-gain (&gt;400x) signal amplification. We show that clampFISH signal enables detection with low magnification microscopy and separation of cells by RNA levels via flow cytometry. Additionally, we show that clampFISH is multiplexable, compatible with expansion microscopy, and works in tissue samples.
P3-069: IFCT0401 trial: Phase II study of gefitinib administered as first-line treatment in non-resectable adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC) - Does disease control on gefitinib affect progression free survival and overall survival in ADC-BAC?
Authors: Jacques Cadranel, Elisabeth Quoix, Pascal Debove, Denis Morot-Sibilot, Jeanne-Marie Brechot, Pierre-Jean Souquet, Jean-Charles Soria, Franck Morin, Bernard Milleron
Journal: Journal of Thoracic Oncology (2007)
Diet and Congenital Defects
Authors: D. Baird
Journal: BMJ (1973)

Sixty-two patients with classical or definite rheumatoid arthritis were subjected to lung function analysis. The various parameters--spirography, plethysmography, blood gas analysis, measurement of lung compliance, and diffusion capacity--were correlated with duration and stage of disease, and with rheumatoid factor titres. A statistically significant correlation was found to exist between Rose-Waaler titre and specific diffusion capacity. Similar results between Rose-Waaler titre and lung compliance, however, were not statistically significant.
Listening and talking to patients. V: Communicating with children.
Authors: J Apley
Journal: BMJ (1980)

Ours is a period when the spread of communication has become almost explosive?pulling the communication cord is not what it was. I find it surprising that paediatricians have not been in the forefront medically. We might have been expected to be, if only because we explore tentatively the learning difficulties of children and witness the near miraculous speed with which normal and most abnormal children overcome them. The difficulties have been daunting but there is plenty of evidence that the communication problems of children are being pene trated both in theory and in daily practice. Communication should not be thought of only in terms of the child who can obviously hear and speak. The unborn baby is certainly sharing communication of a sort when he moves or kicks violently in response to an external stimulus. The newborn infant can hardly wait to communicate if given a chance; we have only to observe mother-child eye fixation, the child's response to the mother's cuddling and cooing, the mother's reactions to her baby's smile to recognise that a two-way form of communication is in action. Handicapped children pose further problems. At the other extreme of childhood we can detect an opposite trend, a decrease in communication. This is not uncommon even in the normal adolescent. The adolescent iron curtain comes down. Communication with adults slows down and may stop altogether. These troubled adolescents for a time become isolated from adults and dominated by their peers.
Medicine as a Science: Neurology
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1951)

AS IS the case with the other special disciplines of medicine, neurology has been profoundly affected by changes in medicine during the last fifty years, from both within and without its own special field.The sulfonamides and antibiotics almost wiped out the infections, and even the two major enemies of 1901, tuberculosis and syphilis, were greatly weakened. Little headway was made against poliomyelitis, multiple sclerosis and the intrinsic degenerative processes, but their attendant problems were better defined and plans for combating them were fully organized and co-ordinated.Pharmacology, physiology and anatomy have brought about many changes in the daily tasks . . .
Evolution of the Phosphoglycerate mutase Processed Gene in Human and Chimpanzee Revealing the Origin of a New Primate Gene
Authors: Esther Betrán, Wen Wang, Li Jin, Manyuan Long
Journal: Molecular Biology and Evolution (2002)

Processed genes are created by retroposition from messenger RNA of expressed genes. The estimated amount of processed copies of genes in the human genome is 10,000–14,000. Some of these might be pseudogenes with the expected pattern for nonfunctional sequences, but some others might be an important source of new genes. We have studied the evolution of a Phosphoglycerate mutase processed gene (PGAM3) described in humans and believed to be a pseudogene. We sequenced PGAM3 in chimpanzee and macaque and obtained polymorphism data for human coding region. We found evidence that PGAM3 likely produces a functional protein, as an example of addressing functionality for human processed pseudogenes. First, the open reading frame was intact despite many deletions that occurred in the 3′ untranslated region. Second, it appears that the gene is expressed. Finally, interspecies and intraspecies variation for PGAM3 was not consistent with the neutral model proposed for pseudogenes, suggesting that a new functional primate gene has originated. Amino acid divergence was significantly higher than synonymous divergence in PGAM3 lineage, supporting positive selection acting in this gene. This role of selection was further supported by the excess of rare alleles in a population genetic analysis. PGAM3 is located in a region of very low recombination; therefore, it is conceivable that the rapid fixation events in this newly arising gene may have contributed to a selective sweep of variation in the region.
Withholding or Withdrawing Life-Prolonging Medical Treatment
Authors: Thomas E. Corbett
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I have read with considerable interest the letters in your July 25 issue on the statement of the Council on Ethical and Judicial Affairs entitled "Withholding or Withdrawing Life-Prolonging Medical Treatment."<sup>1</sup>I am the Corbett who initiated the Corbett case in Florida, which resulted in an appellate court decision legalizing the Council's statement in Florida. I, too, attended the New Orleans meeting where the statement was presented. For some years, I have been a member of the Hastings Center and the American Society of Law and Medicine. My wife of 48 years was in a permanent vegetative state for nearly three years. I am appalled at the misconceptions I find rampant on this issue involving law, medicine, and ethics. I am not an expert in any of these fields, but I am a former librarian and superintendent of schools, so I know how to read and
Preventive Medicine Organizer: Patient-Specific Preventive Medicine Flow Sheet
Authors: Charles B. Arnold
Journal: JAMA (1991)

If implementing the recommendations of the US Preventive Services Task Force interests you, this software package warrants your consideration.  Today, accessible preventive care information is needed by primary care physicians. Whenever an issue arises, the route to a reliable answer will involve either personal study or outside help. These days, personal study in preventive care must begin with the Guide to Clinical Preventive Services (Baltimore, Md: Williams & Wilkins; 1989), the report from the US Task Force, a mid-1980s creation of the Secretary of the Department of Health and Human Services. The document is, however, lengthy and scholarly in style, better suited for background reading than for practice management.  For use in practice, the Guide 's conversion into a suitable clinical format has become necessary. This alternative exists in the form of a program by Dr Gary Tabas, a straightforward conversion of the Guide into personal computer software. Preventive Medicine
Whipple's Disease
Authors: Chester M. Jones, John A. Benson, Agustin L. Roque
Journal: New England Journal of Medicine (1953)

IN 1907 Whipple1 first described intestinal lipodystrophy, an entity that has since been recorded but 37 times. Theories of the pathogenesis of the lipogranulomatosis of the small intestine and mesenteric lymph nodes have failed to suggest an effective form of therapy. The majority of reported cases have occurred in males, and most of the patients have died after a debilitating course of abdominal pain, steatorrhea, malnutrition with striking pigmentation and arthritis, despite various forms of treatment, including bile salts, pancreatic extract, choline, lecithin, folic acid, liver extract, aqueous adrenocortical extract, desoxycorticosterone, duodenal fluid, the fat-soluble vitamins and supportive measures.Whipple . . .