tbuckley/cabot-search huggingface dataset:
Abstract A32: Combined inhibition of phosphoinositide-3-kinase and mitogen-activated protein kinase pathways prevents activation of feedback loops in cancer
Authors: Martin L. Sos, Stefanie Fischer, Roland Ulrich, Martin Peifer, Roman K. Thomas
Journal: Cancer Research (2009)

Abstract In tumor cells, genetically activated oncogenes often induce dependency on the constitutive activity of the mutant oncoprotein. Therapeutic inhibitors exploit this dependency by abrogating the oncogenic signaling, inducing massive apoptosis and thus leading to tumor regressions in patients. The phosphoinositide-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways are key regulators of tumor maintenance and oncogenic transformation. A major hurdle in the transition from preclinical drug discovery to clinical trials lies in the genomic diversity of human tumors and the lack of preclinical models that capture this diversity. Given the impact of genomic aberrations on therapeutic response, such models are necessary in order to identify genetic lesions linked with individual drug response. In order to overcome these limitations we have recently established a panel of 84 NSCLC cell lines that we have characterized in depth in gene copy number, gene expression and mutation space (Sos et al.; J Clin Invest 2009). In this study, we interrogated whether upstream dependency encodes for a certain “downstream” dependency either in the PI3K- or the MAPK- pathway and analyzed whether such a downstream pathway dependency can be linked to certain genetic lesions. We demonstrate by systematically linking compound activity to genetic lesions in vitro and in vivo, that tumors with genetically activated receptor tyrosine kinases predominantly depend on PI3K signaling while tumors with mutations in the Ras/Raf pathway depend on MAPK signaling. However, release of negative feedback loops limited the efficacy of downstream pathway inhibition. By contrast, combined blockade of both PI3K- and MAPK-pathways was able to block the reciprocal pathway activation induced by inhibitor-mediated release of negative feedback loops and resulted in a significant increase in apoptosis. Using a systematic chemo-genomics approach, we provide a framework for PI3K and MAPK pathway activation in connection with particular genetic aberrations and provide a rationale for combined inhibition of both pathways. Our findings may impact patient stratification in clinical trials involving PI3K and MAPK inhibitors either as single agents or in combination. Citation Information: Cancer Res 2009;69(23 Suppl):A32.
Pain as a Manifestation of Acute Anterior-Spinal-Artery Thrombosis
Authors: John J. Deller, Raymond Scalettar, Arthur J. Levens
Journal: New England Journal of Medicine (1960)

THE syndrome of acute anterior-spinal-artery thrombosis has been well described.1 , 2 Although earlier reports1 considered pain a major symptom of this syndrome, more recent publications2 have not emphasized this manifestation. We have recently observed 2 patients with this syndrome. In both cases not only was pain the initial manifestation, but its severity obscured the immediate neurologic diagnosis. Therefore, this report re-emphasizes pain as an important presenting manifestation of this syndrome and one that might initially becloud the correct diagnosis.Case ReportsCase 1. A 52-year-old woman had been well until approximately 5 hours before entering Walter Reed General Hospital, when a . . .
ETHER AS A DISINFECTANT
Authors: J. Livingston
Journal: BMJ (1915)

<h3>Abstract</h3> A single incidence of whole-genome doubling (WGD) is common early in tumorigenesis. In addition to increasing ploidy, WGD doubles centrosome number. In the ensuing mitoses, excess centrosomes form a multipolar spindle, resulting in a lethal multipolar cell division. To survive, cells must cluster centrosomes into two poles to allow a bipolar cell division. Cancer cells are typically more proficient at centrosome clustering than untransformed cells, but the mechanism behind increased clustering ability is not well understood. Heterozygous missense mutations in <i>PPP2R1A</i>, which encodes the alpha isoform of the A-subunit of protein phosphatase 2A (PP2A-Aα), positively correlate with WGD. To understand this correlation, we introduced a heterozygous hotspot mutation, P179R, in endogenous PP2A-Aα in human tissue culture cells. We find that PP2A-Aα<sup>P179R</sup> decreases PP2A assembly and targeting. Strikingly, when centrosome number is increased, either through cytokinesis failure or centrosome amplification, PP2A-Aα mutant cells are more proficient than WT cells at centrosome clustering, likely due to PP2A-Aα loss-of-function. PP2A-Aα<sup>P179R</sup> appears to enhance centrosome clustering by altering the interactions between centrosomes and the cell cortex. Thus, cancer-associated mutations in PP2A-Aα may increase cellular fitness after WGD by enhancing centrosome clustering.
Macular degeneration and early menopause: a case-control study
Authors: J. R Vingerling, I. Dielemans, J. C M Witteman, A. Hofman, D. E Grobbee, P. T V M de Jong
Journal: BMJ (1995)

lenses, seem to be particularly ineffective against Acanthamoeba.Although contact lens disinfection systems in Britain have to comply with stringent tests of efficacy against a panel of microbes, these are directed against planktonic organisms in vitro, rather than the more resistant sessile organisms that are found in vivo and do not include Acanthamoeba."Increased emphasis on the importance of maintaining good hygiene with soft conventional and reused disposable lenses, using hydrogen peroxide or other disinfection systems that are effective against Acanthamoeba, could almost eliminate this severe cause of keratitis.Contact lens practitioners, the contact lens industry, and the Department of Health all have roles to play in achieving this aim-not least by holding back licences from disinfection systems that are ineffective against Acanthamoeba.
Screening for asymptomatic bowel cancer in general practice.
Authors: R C Lallemand, P A Vakil, P Pearson, V Box
Journal: BMJ (1984)

General practitioners screened 4284 asymptomatic people aged over 40 to compare the incidence of large bowel cancer and polyps with a control general practice (4288 patients). Compliance was best in young women (60%), and overall it was 42%. Twenty six patients who had a positive Haemoccult test result (1.5% of those screened) were examined by colonoscopy and 10 had polyps. The incidence of cancers in the two groups was similar but in the control (unscreened patients) practice no polyps were found.
Prognostic Value of MIB-1 Score, p53, EGFr, Mitotic Index and Papillary Status in Primary Superficial (Stage pTa/T1) Bladder Cancer: A Prospective Comparative Study
Authors: Tapani Liukkonen, Pertti Rajala, Mika Raitanen, Erkki Rintala, Eero Kaasinen, Pertti Lipponen
Journal: European Urology (1999)
World Bank helps fund growth of health services in central Europe
Authors: C. Kovac
Journal: BMJ (2001)

A healthcare provider based in Budapest, Euromedic International NV, will receive $13m (£9.2m) from the International Finance Corporation, the World Bank's private sector arm, to help fund a $33 million expansion programme in central and eastern Europe.

The rest of the money will come from the company's own resources, medical equipment manufacturers, and banks.

“This is the World Bank's first investment in health care in Hungary, and the largest in the region,” said Elena Bourganskaya, senior health …
A136: Assessing the Efficacy of Pediatric Rheumatology Video-based Curriculum
Authors: Renee Modica
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Musculoskeletal complaints are common in pediatrics. Practitioners are often under-skilled in performing the musculoskeletal exam and deficient in basic knowledge regarding rheumatologic diseases. We sought to determine if learning the pediatric musculoskeletal exam and rheumatic conditions in a video-enriched case-based lecture series will improve their knowledge of rheumatic diseases.



Methods:

This prospective pre/post test single group design study was conducted at a pediatric tertiary care center with a pediatric residency. A convenience sample of students attending a monthly lecture series was included in this study. We designed a video case-based curriculum; Pediatric Rheumatology Video-based Curriculum (PRVC), using a disease specific video/image timeline to demonstrate abnormal physical findings. Novel features included: “voice over” explanation of findings while the patient is being examined, split screen display of abnormal vs. normal findings, graphics to highlight subtle findings seen in rheumatic diseases and evolution of physical exam with treatment. A single experimental group was administered a pretest prior to being exposed to the PRVC. After each intervention, effectiveness was assessed with a posttest. The primary outcome measure was measured by improvement on pre-/post- intervention questionnaires using a paired t-test. Secondary outcome measure was learner satisfaction assessed by a 5-point Likert questionnaire.



Results:

Over a 10-month period, 8 (1 hour) lectures were given to audiences consisting of medical students and pediatric residents. Eleven to 28 listeners performed an assessment pre and post-test for each lecture. Based on pre-test and post-test results from each lecture, each lecture demonstrated statistically significant improvement for the learner (Table 1). Similarly, respondents expressed overall satisfaction with an average score of 4.8 on a 5-point Likert scale. 


Table 1. Results for pre/post-test improvement for each lecture	Lecture Topic	n	Pre-test (%)	Post-test (%)	p valuea


a

p value calculated using paired t-test




	
MSK (Musculoskeletal Exam)	15	66.7	80	0.01	
JIA (Juvenile Idiopathic Arthritis)	24	44.2	78.6	<0.0001	
ERA (Enthesitis Related Arthritis)	20	61.5	85.8	<0.0001	
JDMS (Juvenile Dermatomyositis)	11	50	78.8	0.0005	
SCL (Juvenile Scleroderma)	14	52.5	80.4	<0.0001	
SARC (Juvenile Sarcoidosis)	28	53	96.4	<0.0001	
SLE (Systemic Lupus)	18	51.4	78.2	0.0002	
PFS (Periodic Fever Syndromes)	11	50	92.2	<0.0001	
Overall	141	53.6	83.5	<0.00001	



Conclusion:

The PRVC is a unique curriculum that demonstrated effectiveness and satisfaction as assessed by the learners.
REPORT OF CASES OF ABDOMINAL SECTION AT ROBINWOOD HOSPITAL FOR WOMEN, FROM MAY 1, 1893, TO JAN. 1, 1894.Read before the Detroit Gynecological Society, April 4, 1894.
Authors: C. A. KIRKLEY
Journal: JAMA (1894)

It is to be regretted that the entire profession has not yet realized the importance of timely operation in destructive disease of the abdomen and pelvis. By<i>timely</i>is meant as soon as operation is clearly indicated. To delay, until the surrounding parts have become involved, or until perforation of some of the viscera has occurred may be mainly attributed the fatal and sometimes imperfect results after operation. The question of palliation and delay in cases of ovarian cyst has long since been settled, not only in the minds of specialists, but also in the minds of the general surgeon and practitioner. Why should any better results be expected from palliation in cases of ovarian abscess, destructive inflammation of the tubes and ectopie pregnancy? Dr. Chas. P. Noble in his interesting report on "Abdominal Surgery at the Kensington Hospital for Women," very truly says that, "without operation it is only
Calcium and postmenopausal bone loss: Authors' reply
Authors: J. C Stevenson, M. I Whitehead
Journal: BMJ (1988)

4% greater forearm trabecular bone density, and 9% greater forearm cortical bone density.The fact that all four methods of measurement were in favour of a high calcium intake makes the odds 16 to 1. (I would accept 8 to 1 on.)There were 15 women in each group.The differences were not statistically significant, but that is not the same as concluding that "the bone density of women in the early menopause is not influenced by current dietary intake of calcium."
SPECT Detection of Pulmonary Artery Branch Obstruction from a Migrated Gianturco Coil
Authors: PAUL C. M. S. VERHAGEN, PETER P. VAN RIJK, TYCHO M.T.W. LOCK, JAN H.M. BLOM, BERTHE L.F. VAN ECK-SMIT
Journal: Clinical Nuclear Medicine (1992)

In an 18-year-old patient with a left-sided varicocele, Gianturco coils were used for percutaneous embolization of the left spermatic vein. One coil dislodged and migrated to the inferior lobe of the right lung. This complication happened without any clinical symptom. The planar ventilation-perfusion scintigram was normal. However, perfusion SPECT imaging demonstrated a sub-segmental defect in the inferior lobe of the right lung.
Extreme bodies: art to stimulate the mind, or a modern day freak show?
Authors: N. Puri
Journal: BMJ (2010)

Rating: **

Mark Quinn is a British artist who is preoccupied with extremes of human form. His 2005 sculpture Alison Lapper Pregnant on the fourth plinth of Trafalgar Square attracted huge media attention ( BMJ 2005;331:849, doi:10.1136/bmj.331.7520.849). A confident, poised, and pregnant Lapper, born with shortened legs and no arms because of phocomelia, was presented as the embodiment of dignity. 

Quinn’s current exhibition, at the White Cube gallery, in North East London, is named after a series of individuals who have undergone extreme physical transformation through hormone therapy, cosmetic surgery, and gender reassignment. Unfortunately, the apparent intention to shock almost gives the exhibition the feel of a modern day freak show, and has the effect of marginalising the extremes Quinn has previously sought to champion through his work.

As you walk through the oversized doors of the White Cube gallery, your attention …
Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study
Authors: Stefan Flasche, Albert Jan Van Hoek, Elizabeth Sheasby, Pauline Waight, Nick Andrews, Carmen Sheppard, Robert George, Elizabeth Miller
Journal: PLoS Medicine (2011)

Background We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. Methods and Findings Nasopharyngeal swabs were taken from children <5 y old and family members (n = 400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case∶carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76–1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. Conclusion Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary
&lt;emph type="ital"&gt;Portrait of Marthe Marie Tronchin&lt;/emph&gt;
Authors: M. Therese Southgate
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Distinct roles of erythropoietin, insulin-like growth factor I, and stem cell factor in the development of erythroid progenitor cells.
Authors: K Muta, S B Krantz, M C Bondurant, A Wickrema
Journal: Journal of Clinical Investigation (1994)

Erythropoietin (EP), insulin-like growth factor I (IGF-I) and stem cell factor (SCF) each reduce apoptosis of human erythroid progenitor cells. To determine if these growth factors have additional roles in stimulating erythropoiesis, the proliferation, maturation, and survival of highly purified human erythroid colony-forming cells (ECFCs) were studied during the application of different combinations of these growth factors in a serum-free liquid culture. EP maintained cell viability and supported heme synthesis during erythroid maturation, with little increase in viable cell number or stimulation of DNA synthesis. The addition of SCF with EP resulted in a substantial increase in DNA synthesis, which was greater than that seen with the addition of EP and was associated with a large expansion in the number of ECFCs. Thus EP, by itself, produces little increase in cell proliferation, and expansion of the number of erythroid cells depends upon the presence of SCF with EP. The addition of IGF-I with EP led to enhanced heme synthesis and moderate cellular proliferation, but also greatly enhanced nuclear condensation and enucleation in the late erythroblasts. Thus EP, by itself, is not sufficient for complete end-terminal nuclear condensation/enucleation and the presence of IGF-I is necessary for this complete process. While EP greatly reduced apoptosis during 16 h of incubation at 37 degrees C, the addition of SCF and IGF-I with EP had little additional effect, but these additions enhanced DNA synthesis > 3.4-fold. Thus SCF may have an additional role in directly stimulating proliferation through a process that is distinct from apoptosis. Our observations indicate that EP prevents apoptosis and maintains erythroid cell viability and development. IGF-I enhances erythroid maturation and proliferation, but the proliferation of erythroid progenitors is mainly controlled by the addition of SCF with EP, independent of an effect on apoptosis.
Prospective study of body mass index in patients with coeliac disease
Authors: W. Dickey, S. Bodkin
Journal: BMJ (1998)

Population screening suggests that coeliac disease is much commoner than previously supposed. The prevalence of biopsy proved classic coeliac disease, with subtotal or total villous atrophy of the small bowel, ranges from 1:150 to 1:300 in adults in western Europe 1 2 and many patients have mild symptoms. We noticed that few of our new patients with coeliac disease were obviously malnourished and conducted a prospective study of body mass index to investigate further.

Over a period of 26 months 50 adult patients (age 16-64 years) were diagnosed as having uncomplicated coeliac disease by WD in this district general hospital (catchment population around 160 000). Seven patients aged ≥65 years who received a diagnosis during this period were excluded from the study. Patients had …
Do women who develop an iatrogenic chronic hepatitis C virus (HCV) infection in a health care service differ in their psychological well-being, quality of life and health beliefs/feelings from women with a genetic liver disorder known as haemochromatosis?
Authors: Barbara Coughlan, John Sheehan, AnneMarie Flanagan, Eleanor Ryan, Alan Carr, John Crowe
Journal: Journal of Hepatology (2001)
Comparative Effectiveness of Robot-Assisted and Open Radical Prostatectomy in the Postdissemination Era
Authors: Giorgio Gandaglia, Jesse D. Sammon, Steven L. Chang, Toni K. Choueiri, Jim C. Hu, Pierre I. Karakiewicz, Adam S. Kibel, Simon P. Kim, Ramdev Konijeti, Francesco Montorsi, Paul L. Nguyen, Shyam Sukumar, Mani Menon, Maxine Sun, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2014)

Given the lack of randomized trials comparing robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we sought to re-examine the outcomes of these techniques using a cohort of patients treated in the postdissemination era.Overall, data from 5,915 patients with prostate cancer treated with RARP or ORP within the SEER-Medicare linked database diagnosed between October 2008 and December 2009 were abstracted. Postoperative complications, blood transfusions, prolonged length of stay (pLOS), readmission, additional cancer therapies, and costs of care within the first year after surgery were compared between the two surgical approaches. To decrease the effect of unmeasured confounders, instrumental variable analysis was performed. Multivariable logistic regression analyses were then performed.Overall, 2,439 patients (41.2%) and 3,476 patients (58.8%) underwent ORP and RARP, respectively. In multivariable analyses, patients undergoing RARP had similar odds of overall complications, readmission, and additional cancer therapies compared with patients undergoing ORP. However, RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications (all P ≤ .02). Additionally, RARP led to a lower risk of experiencing blood transfusion and of having a pLOS (all P < .001). Finally, first-year reimbursements were greater for patients undergoing RARP compared with ORP (P < .001).RARP and ORP have comparable rates of complications and additional cancer therapies, even in the postdissemination era. Although RARP was associated with lower risk of blood transfusions and a slightly shorter length of stay, these benefits do not translate to a decrease in expenditures.