tbuckley/cabot-search huggingface dataset:
Abstract 4900: Bortezomib induces G2-M arrest through ROS-inducible phosphorylation of ATM independent on genotypes of KRAS in human colon cancer cells
Authors: Seung-Mi Kim, Yong Sang Hong, Seung-Woo Hong, Dong-Hoon Jin, Tae Won Kim
Journal: Cancer Research (2012)

Abstract The use of cetuximab (CET) as an inhibitor of EGFR for treatment of colorectal cancer (CRC) has revolutionized. However, a number of CRC patients exhibits resistance to CET. In this report, we suggest the possibility of using bortezomib as a proteasome inhibitor in human colon cancer cells. Although bortezomib has been known to induce apoptosis and cell cycle arrest in various human cancer cells, the inhibitory mechanism of it was not clear. First, bortezomib induced G2-M arrest independent on genotype of KRAS in all of tested human colon cancer cells. Its treatment causes an increase of intracellular ROS levels and activation of ATM-CHK1 pathway, but not ATR. Also, activation of that pathway led to inactivation of cdc2. Moreover, treatment with NAC, Reactive Oxygen Species (ROS)scavenger, inhibited phosphorylation of ATM and subsequent to decrease of cell number at G2-M phase in response to bortezomib indicating that the increased level of ROS after exposure to bortezomib is a result of ATM phosphorylation. In addition, knockdown of endogenous ATM by RNA interference induced the decreased sensitivity to bortezomib. Therefore, these results suggest that bortezomib induces G2-M arrest through ROS-inducible ATM phosphorylation and responses to colon cancer cells independent on genotype of KRAS, implying a potential possibility of it in the treatment of CRC patients. 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 4900. doi:1538-7445.AM2012-4900
Symptoms and problems in the end-of-life phase of high-grade glioma patients
Authors: E. M. Sizoo, L. Braam, T. J. Postma, H. R. W. Pasman, J. J. Heimans, M. Klein, J. C. Reijneveld, M. J. B. Taphoorn
Journal: Neuro-Oncology (2010)

Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor treatment seems realistic, patients in the Netherlands are often referred to a primary care physician for end-of-life care. This end-of-life phase has not been studied adequately yet. The purpose of this study was to explore specific problems and needs experienced in the end-of-life phase of patients with HGG. We retrospectively examined the files of 55 patients who received treatment in our outpatient clinic and died between January 2005 and August 2008. The clinical nurse specialist in neuro-oncology maintained contact on a regular basis with (relatives of) HGG patients once tumor treatment for recurrence was no longer given. She systematically asked for signs and symptoms. The majority of the patients experienced loss of consciousness and difficulty with swallowing, often arising in the week before death. Seizures occurred in nearly half of the patients in the end-of-life phase and more specifically in one-third of the patients in the week before dying. Other common symptoms reported in the end-of-life phase are progressive neurological deficits, incontinence, progressive cognitive deficits, and headache. Our study demonstrates that HGG patients, unlike the general cancer population, have specific symptoms in the end-of-life phase. Further research is needed in order to develop specific palliative care guidelines for these patients.
Diabetes, Major Depression, and Functional Disability Among U.S. Adults
Authors: Leonard E. Egede
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to determine prevalence and odds of functional disability in individuals with diabetes and comorbid major depression compared with individuals with either diabetes or major depression alone. RESEARCH DESIGN AND METHODS—Data on 30,022 adults aged ≥18 years from the 1999 National Health Interview Survey (NHIS) were analyzed. Four disease categories were created: no diabetes and no major depression, major depression alone, diabetes alone, and diabetes and comorbid major depression. Prevalence of functional disability was calculated for each disease category. Multiple logistic regression was used to determine the odds and correlates of functional disability by disease category controlling for age, sex, race/ethnicity, education, income, census region, and disability-associated comorbidity. STATA was used for all analyses to account for the complex survey design of NHIS. RESULTS—Prevalence of functional disability by disease category was as follows: no diabetes and no major depression (24.5%); major depression (51.3%); diabetes (58.1%); and diabetes and comorbid major depression (77.8%). With no diabetes and no major depression as reference and after adjusting for relevant covariates, the odds of functional disability was 3.00 (95% CI 2.62–3.42) for major depression, 2.42 (2.10–2.79) for diabetes, and 7.15 (4.53–11.28) for diabetes and comorbid major depression. CONCLUSIONS—Individuals with diabetes and comorbid major depression have higher odds of functional disability compared with individuals with either diabetes or major depression alone. Additional studies are needed to establish a causal relationship.
Cord-Blood Transplantation in Patients with Leukemia — A Real Alternative for Adults
Authors: Miguel A. Sanz
Journal: New England Journal of Medicine (2004)

A steady stream of advances in allogeneic hematopoietic stem-cell transplantation has not only improved the clinical outcome in a variety of malignant and nonmalignant diseases but also widened the indications for such transplants. One important advance is the use of sources of hematopoietic stem cells other than bone marrow from HLA-identical siblings, which is a resource available to only about 30 percent of potential recipients.By searching international databases, which contain more than 9 million potential volunteer stem-cell donors,1 a matched unrelated donor can be found for an additional 50 to 80 percent of patients, depending on ethnic group. In . . .
1236 MECHANISMS OF ISOLATED UNCONJUGATED HYPERBILIRUBINEMIA INDUCED BY THE HCV NS3/4A PROTEASE INHIBITOR BI201335
Authors: R. Sane, L. Podila, A. Mathur, K. Mease, M. Taub, Q. Huang, M. Elgadi, G. Nehmiz, G. Steinmann
Journal: Journal of Hepatology (2011)
Problems of Orthopaedic Appointment
Authors: K. S. Mackenzie
Journal: BMJ (1965)

When the diathermy is applied to the thorax or neck of an insulated patient the shortest electrical path is through the anaes- thetic tubing and machine or the anaesthetist, who usually has bare hands and conducting boots.When patients are intubated, the endotracheal tube is non-conducting when dry, and electrical contact is first made with the metal connector, which can easily make contact with the skin of the face but is often
Retroviral integration and human gene therapy
Authors: Frederic D. Bushman
Journal: Journal of Clinical Investigation (2007)

Long-term correction of genetic diseases requires permanent integration of therapeutic genes into chromosomes of affected cells. Retroviral vectors are the most widely used delivery vehicles because of their efficiency and precision of integration. However, retroviral integration can take place at a variety of chromosomal sites, and examples have been reported of integration of therapeutic vectors activating oncogenes and causing cancer in patients. This issue of the JCI presents three articles that update successful human gene therapy trials and furthermore evaluate the sites of integration in cells from treated patients, including samples from individuals experiencing serious adverse events following therapy (see the related articles beginning on pages 2225, 2233, and 2241).
A woman with tuberous sclerosis and acute onset right sided abdominal pain
Authors: A. Balan, D. Kessel
Journal: BMJ (2009)

A 40 year old woman with a history of tuberous sclerosis presented to the accident and emergency department with severe, acute onset right sided abdominal pain. On clinical examination she looked pale, had poor capillary refill, and was tachycardic and hypotensive. Her abdomen was distended, with bilaterally tender, palpable flank masses. Her haemoglobin measured 8 g/dl. After aggressive resuscitation with intravenous fluids, she was deemed stable enough to undergo computed tomography, as an intra-abdominal source of acute haemorrhage was suspected. Figures 1 ⇓ and 2⇓ are computed tomography images of the mid-abdomen and lower abdomen. Fig 1 Computed tomogram of the mid-abdomen Fig 2 Computed tomogram of the lower abdomen ### Short answers
Mothers who kill their children can show intense grief
Authors: Z. Kmietowicz
Journal: BMJ (2001)

<h3>Objective:</h3> To validate near-infrared reflectance analysis (NIRA) as a fast, reliable and suitable method for routine evaluation of human milk’s nitrogen and fat content. <h3>Setting:</h3> One neonatal intensive care unit. <h3>Patients:</h3> 124 samples of expressed human milk (55 from preterm mothers and 69 from term mothers). <h3>Intervention:</h3> Measurement of nitrogen and fat content by NIRA and traditional methods (Gerber method for fat and Kjeldahl method for nitrogen). <h3>Main outcome measures:</h3> Agreement between NIRA and traditional methods. Variability in fat and nitrogen content of human milk. <h3>Results:</h3> A strong agreement was found between the results of traditional methods and NIRA for both fat and nitrogen content (expressed as g/100 g of milk) in term (mean fat content: NIRA = 2.76; Gerber = 2.76; mean nitrogen content: NIRA = 1.88; Kjeldahl = 1.92) and preterm (mean fat content: NIRA = 3.56; Gerber = 3.52; mean nitrogen content: NIRA = 1.91; Kjeldahl = 1.89) mothers’ milk. Nitrogen content of the milk samples, measured by NIRA, ranged from 1.18 g/100 g to 2.71 g/100 g of milk in preterm milk and from 1.48 g/100 g to 2.47 g/100 g in term milk; fat content ranged from 1.27 g/100 g to 6.23 g/100 g of milk in preterm milk and from 1.01 g/100 g to 6.01 g/100 g of milk in term milk. <h3>Conclusion:</h3> NIRA can be used as a quick and reliable tool for routine monitoring of macronutrient content of human milk and for devising individualised human milk fortification regimens in the feeding of very premature infants.
Apathetic Thyrotoxicosis: A Distinctive Clinical and Laboratory Entity
Authors: Fred B. Thomas, Ernest L. Mazzaferri, Thomas G. Skillman
Journal: Annals of Internal Medicine (1970)

Nine patients with apathetic thyrotoxicosis were studied over a 1-year period and compared with 29 typical hyperthyroid subjects. These apathetic patients were significantly older and had a longer duration of symptoms and greater weight loss. The study group had a rather typical apathetic, placid, or depressed appearance often thought to represent "old age depression." Cardiovascular symptoms, atrial fibrillation, and congestive heart failure were common. They typically had evidence of a moderately severe proximal myopathy. Thyromegaly, although usually present, was not prominent and was usually multinodular. There was a striking absence of eye signs generally associated with thyrotoxicosis, and blepharoptosis was frequently observed. Although the protein-bound iodine and 131I thyroidal uptake were not markedly elevated, the diagnosis was easily established by utilizing the usual tests of thyroid function and integrating the results with the rather typical clinical features.
The Resource-Based Relative Value Scale
Authors: M. L. Janower
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The Resource-Based Relative Value Scale is well described by Hsiao et al<sup>1</sup>in their article in the Aug 14,1987, issue of<i>JAMA</i>. The purpose of this letter is to alert readers ofTHE JOURNALto the shortcomings of the study by Hsiao et al. A similar study has been carried out twice in Massachusetts and at no time did the participants—the physician-advisers—consider the study to be adequate. No consensus was reached by the physician-consultants and no attempt was made by Hsiao et al to reach agreement between the physician-specialty participants. The authors suggest that theirs is an objective study. One has only to look at their formula for establishing relative values by using five factors and a computer to appreciate the sense of objectivity and validity that is implied. However, it must be realized that there is also much subjectivity. For example, the "intensity" factor cannot
Longitudinal Monitoring of Lung Injury in Children after Acute Chlorine Exposure in a Swimming Pool
Authors: Gea Bonetto, Massimo Corradi, Silvia Carraro, Stefania Zanconato, Rossella Alinovi, Giuseppina Folesani, Liviana Da Dalt, Antonio Mutti, Eugenio Baraldi
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Acute exposure to chlorine gas results in respiratory impairment, but few data are available on the pathobiology of the underlying lung damage.To assess lung function and potential lung damage pathways in the acute phase and longitudinally over a 15-mo follow-up after acute chlorine exposure.Ten previously healthy children were accidentally exposed to chlorine gas at a swimming pool because of an erroneous servicing procedure. The fraction of nitric oxide in exhaled air (Fe(NO)), exhaled breath condensate compounds, and serum Clara cell-specific protein CC16 were repeatedly measured.In the acute phase, all patients had respiratory distress (one child required mechanical ventilation) and reduced lung function (median and interquartile range: FVC, 51 [43-60]% predicted; FEV(1), 51 [46-60]% predicted). This was accompanied by low Fe(NO) (4.7 [3.9-7.9] ppb), high exhaled breath condensate leukotriene B(4) (LTB(4)) levels (24.4 [22.5-24.9] pg/ml), and increased serum CC16 levels (mean +/- SEM, 23.4 +/- 2.5 microg/L). Lung function returned to normal in 15 d (FVC, 97% predicted [82-108], and FEV(1), 92% predicted [77-102]). Fe(NO) reached normal values after 2 mo (12.6 [11.4-15] ppb), whereas LTB(4) levels were still increased (12 [9.3-17.1] pg/ml).Children acutely exposed to chlorine in a swimming pool presented a substantial lung function impairment associated with biochemical exhaled breath alterations, represented mainly by an increase in LTB(4) and a reduction in Fe(NO). Although lung function and Fe(NO) improved within a few weeks, the increased levels of exhaled LTB(4) persisted for several months.
Medical Aspects of Civilian Defense
Authors: Charles H. Bradford
Journal: New England Journal of Medicine (1950)

DOCTORS have never played a tactical part in war. Even in the recent conflict, in which casualties were heavy, the medical profession did vastly more to lighten the load of human suffering than to strengthen the nation's fighting arm. As one studies the outlook of the future, it may well be shown that doctors will carry on one of the most vital parts in the defense of the nation under circumstances that will be extraordinarily different from the past. Yet they tend to be so absorbed in the scientific interests of their profession that few give serious thought to the . . .
Understanding AIDS: A Comprehensive Guide
Authors: David G. Ostrow
Journal: JAMA (1986)

It has been at least a year since a comprehensive review of the acquired immunodeficiency syndrome (AIDS) written for the general public has appeared. Therefore, the appearance of a book written by medical scientists for the general public that claims to be an up-to-date and comprehensive review of the subject would be quite useful given the major scientific advances made during the last several years. In addition, the institution of screening for the human T-cell lymphotropic virus type III has created many important issues relevant to the general population. Unfortunately,<i>Understanding AIDS: A Comprehensive Guide</i>does not provide such an up-to-date review of AIDS. It was obviously written in early 1984 and reflects few of the recent advances in our understanding of AIDS. That is not to say that there aren't some important contributions to the general public's understanding of the disease to be found in this multiauthored text. The
Endoscopic Ultrasound-Guided Fine-Needle Aspiration in the Evaluation of Gallbladder Masses
Authors: S. Varadarajulu, M. A. Eloubeidi
Journal: Endoscopy (2005)

There are very few data on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of gallbladder masses. The aim of this study was to assess the utility and safety of EUS-FNA in the evaluation of patients with gallbladder masses.Six patients who underwent EUS-FNA of gallbladder masses over a 2-year period between 2002 and 2004 were studied retrospectively. Reports of endoscopic ultrasound (EUS) procedures, EUS images, cytology results, and clinical records were reviewed. Abdominal computed tomography (CT) prior to EUS had revealed a definitive gallbladder mass in only one of the six patients and no gallbladder masses were identified in any of the patients who had undergone prior transabdominal ultrasound.At EUS, all the patients were found to have an echo-poor mass arising from the gallbladder wall or within the lumen of the gallbladder. EUS-FNA of the gallbladder masses revealed adenocarcinoma in five patients and benign disease in one patient. After a mean follow-up period of 127 days (range 90 - 187 days), three patients had died, two were undergoing palliative chemoradiotherapy, and one had been confirmed as having chronic cholecystitis at surgery. No complications occurred.In patients with obstructive jaundice and equivocal ultrasound or CT findings, evaluation of the gallbladder for the presence of a primary malignancy by EUS is useful. In patients with gallbladder masses, EUS-FNA can be performed safely and can help to make a definitive diagnosis.
James Morton Muir
Authors: A. M Muir
Journal: BMJ (2008)

James Morton Muir (“Jimmy”) spent most of the second world war serving overseas with the Royal Army Medical Corps in the Middle East, Libya, Italy, and ultimately Berlin; this final posting made a deep and lasting impression on him. He was wounded and awarded the DSO after the battle of Sidi Barrani in the Western Desert in December 1940 when serving as a medical officer with the 1st Battalion The Argyll and Sutherland …
Book: Wine: A Scientific Exploration
Authors: F. Kavalier
Journal: BMJ (2003)

Eds Merton Sandler, Roger Pinder Taylor and Francis, £65, pp 336 www.tandf.co.uk/ Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> ISBN 0 415 24734 9 There's something about the fermented juice of grapes that attracts doctors. Hippocrates recommended wine as a treatment for almost all illnesses, although he drew the line at giving it to patients with meningitis. Christopher Rawson Penfold, the founder of one of Australia's leading wineries, was a young English doctor who emigrated to Australia in 1844 and soon realised that there was more to life than setting broken bones in the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
In patients at high CV risk, a Mediterranean diet plus olive oil reduced diabetes more than advising a low-fat diet
Authors: Ashley Jensen, Scott Sherman
Journal: Annals of Internal Medicine (2014)

ACP Journal Club17 June 2014In patients at high CV risk, a Mediterranean diet plus olive oil reduced diabetes more than advising a low-fat dietAshley Jensen, MPA, Scott Sherman, MD, MPHAshley Jensen, MPAVA New York Harbor Healthcare System and NYU School of Medicine, New York, New York, USA (A.J., S.S.)Search for more papers by this author, Scott Sherman, MD, MPHVA New York Harbor Healthcare System and NYU School of Medicine, New York, New York, USA (A.J., S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-160-12-201406170-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSalas-Salvadó J, Bulló M, Estruch R, et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann Intern Med. 2014;160:1-10. https://pubmed.ncbi.nlm.nih.gov/24573661Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: References1 Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25:2165-71. [PMID: 12453955] Google Scholar2 Esposito K, Maiorino MI, Ceriello A, Giugliano D. Prevention and control of type 2 diabetes by Mediterranean diet: a systematic review. Diabetes Res Clin Pract. 2010;89:97-102. [PMID: 20546959] Google Scholar Author, Article, and Disclosure InformationAuthors: Ashley Jensen, MPA; Scott Sherman, MD, MPHAffiliations: VA New York Harbor Healthcare System and NYU School of Medicine, New York, New York, USA (A.J., S.S.)This article was published at Annals.org on 3 June 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis 17 June 2014Volume 160, Issue 12Page: JC2KeywordsBlood plasmaCardiovascular diseasesDiabetes preventionDietExerciseGlucoseHazard ratioHypertensionOilsWeight loss ePublished: 17 June 2014 Issue Published: 17 June 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit
Authors: Hitoshi Ishimoto, Robert B. Jaffe
Journal: Endocrine Reviews (2010)

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex.