tbuckley/cabot-search huggingface dataset:
Restructuring as gratification
Authors: Jeffrey Braithwaite, Johanna Westbrook, Rick Iedema
Journal: Journal of the Royal Society of Medicine (2005)

Almost everyone does it. It is pleasurable for some, apparently, and stressful for others—you only have to watch people at it. Others find it painful. A relatively small number is opposed to it, and will fight hard to stop it happening. But they are few, and most people simply grin and bear it.

Restructuring is so pervasive, in fact, that observers could be forgiven for thinking it is the only change tool available. In the health sectors of Britain, New Zealand, Canada, the USA and Australia the activity seems virtually continuous. Primarily it consists of regular mergers, altering the responsibilities between central and peripheral bodies, setting up new agencies that trigger domino-like changes to the official responsibilities of other agencies, constantly tweaking organizational charts and re-orienting who reports to whom.
Medicine, the Vanishing Sacred Elephant
Authors: Phillip Cozzi
Journal: Annals of Internal Medicine (1991)

Ad Libitum15 September 1991Medicine, the Vanishing Sacred ElephantPhillip Cozzi, MDPhillip Cozzi, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-6-495 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGirlie girl, come step right up,pardon if I seem abrupt.Watch the purple power tiewhile I fill my coffee cup.Tell me where your troubles lieand faster than the human eye,quickly as your wish commands,watch the lightning scribbles fly:healing with a sleight of hand,healing with a song and dance,penned elixirs, take your pick,here among the office plants.Step right up, my welcome sick,for my latest, greatest trickI will make the thing with ears,jewelled trunk, so grey and thick,vanish into thinnest air.What it stood for all these... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 9219 Shields Brookfield, IL 60513 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1991Volume 115, Issue 6Page: 495-495KeywordsCoffee ePublished: 1 December 2008 Issue Published: 15 September 1991 PDF downloadLoading ...
Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Mendenhall's syndrome.
Authors: Y Takahashi, H Kadowaki, A Ando, J D Quin, A C MacCuish, Y Yazaki, Y Akanuma, T Kadowaki
Journal: Journal of Clinical Investigation (1998)

Rabson-Mendenhall's syndrome is one of the most severe forms of insulin resistance syndrome. We analyzed an English patient described elsewhere and found novel mutations in both alleles of the insulin receptor gene. One is a substitution of G for A at the 3' splice acceptor site of intron 4, and the other is an eight-base pair deletion in exon 12. Both decrease mRNA expression in a cis-dominant manner, and are predicted to produce severely truncated proteins. Surprisingly, nearly normal insulin receptor levels were expressed in the patient's lymphocytes, although the level of expression assessed by immunoblot was approximately 10% of the control cells. Insulin binding affinity was markedly reduced, but insulin-dependent tyrosine kinase activity was present. Analyzing the insulin receptor mRNA of the patient's lymphocytes by reverse transcription PCR, we discovered aberrant splicing caused by activation of a cryptic splice site in exon 5, resulting in a four-amino acid deletion and one amino acid substitution, but restoring an open reading frame. Skipped exon 5, another aberrant splicing, was found in both the patient and the mother who had the heterozygotic mutation, whereas activation of the cryptic splice site occurred almost exclusively in the patient. Transfectional analysis in COS cells revealed that the mutant receptor produced by cryptic site activation has the same characteristics as those expressed in patient's lymphocytes. We speculate that this mutant receptor may be involved in the relatively long survival of the patient by rescuing otherwise more severe phenotypes resulting from the complete lack of functional insulin receptors.
Contribution of endogenous nitric oxide to basal vasomotor tone of peripheral vessels and plasma B-Type natriuretic peptide levels in patients with congestive heart failure
Authors: Yutaka Ishibashi, Toshio Shimada, Takeshi Sakane, Nobuyuki Takahashi, Takashi Sugamori, Syuzo Ohhata, Shin-ichi Inoue, Harumi Katoh, Kazuya Sano, Yo Murakami, Michio Hashimoto
Journal: Journal of the American College of Cardiology (2000)
Importance of internal controls, statistical methods, and side effects in short-term trials of vasodilators: a study of hydralazine kinetics in patients with aortic regurgitation.
Authors: C R McKay, M Nana, D T Kawanishi, U Elkayam, P A Chandraratna, J N Weiss, S H Rahimtoola
Journal: Circulation (1985)

We determined that the spontaneous changes in cardiac output (CO) over 12 hr in 21 patients with chronic severe aortic regurgitation averaged +/- 8.9% (p = .03). We then measured changes in CO over time after administering incremental doses of oral hydralazine (50, 100, 150, and 200 mg) every 12 hr and analyzed these changes by several methods. Changes over time of only + 14% were highly significant (p less than .001) when analyzed by t test, but were not significant by repeated-measures analysis of variance (ANOVA). When changes in CO were compared with internal control values (spontaneous changes over 12 hr), only changes of 20% or more were significant (p less than .05). Transient "peak effects" markedly overestimated the maximum effects after all doses. We then compared the incremental doses of hydralazine, given either every 8 or every 12 hr, with respect to (1) the hemodynamic changes induced, and (2) the relative incidence of acute side effects. Maximal increases in CO were similar when hydralazine was given every 8 hr (16 patients) and every 12 hr (21 patients), and ranged from + 14% after 50 mg to + 61% after 200 mg. After the 150 and 200 mg doses, marked sustained increases in CO were present at 8 hr and mild increases in CO were still present at 12 hr. Hydralazine every 8 hr was associated with side effects in 25% to 86% of patients, but when the drug was given every 12 hr it was associated with side effects in only 5% to 19% of patients (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Bile Duct Injury During Cholecystectomy and Survival in Medicare Beneficiaries
Authors: David R. Flum, Allen Cheadle, Cecilia Prela, E. Patchen Dellinger, Leighton Chan
Journal: JAMA (2003)

ContextCommon bile duct (CBD) injury during cholecystectomy is a significant source of patient morbidity, but its impact on survival is unclear.ObjectiveTo demonstrate the relation between CBD injury and survival and to identify the factors associated with improved survival among Medicare beneficiaries.Design, Setting, and PatientsRetrospective study using Medicare National Claims History Part B data (January 1, 1992, through December 31, 1999) linked to death records and to the American Medical Association's (AMA's) Physician Masterfile. Records with a procedure code for cholecystectomy were reviewed and those with an additional procedure code for repair of the CBD within 365 days were defined as having a CBD injury.Main Outcome MeasureSurvival after cholecystectomy, controlling for patient (sex, age, comorbidity index, disease severity) and surgeon (procedure year, case order, surgeon specialty) characteristics.ResultsOf the 1 570 361 patients identified as having had a cholecystectomy (62.9% women), 7911 patients (0.5%) had CBD injuries. The entire population had a mean (SD) age of 71.4 (10.2) years. Thirty-three percent of all patients died within the 9.2-year follow-up period (median survival, 5.6 years; interquartile range, 3.2-7.4 years), with 55.2% of patients without and 19.5% with a CBD injury remained alive. The adjusted hazard ratio (HR) for death during the follow-up period was significantly higher (2.79; 95% confidence interval [CI]; 2.71-2.88) for patients with a CBD injury than those without CBD injury. The hazard significantly increased with advancing age and comorbidities and decreased with the experience of the repairing surgeon. The adjusted hazard of death during the follow-up period was 11% greater (HR, 1.11; 95% CI, 1.02-1.20) if the repairing surgeon was the same as the injuring surgeon.ConclusionsThe association between CBD injury during cholecystectomy and survival among Medicare beneficiaries is stronger than suggested by previous reports. Referring patients with CBD injuries to surgeons or institutions with greater experience in CBD repair may represent a system-level opportunity to improve outcome.
Practical Method to Regulate PEEP
Authors: Claude Lenfant
Journal: New England Journal of Medicine (1975)

As we all know, scientific research is often criticized because its results are not widely known or are so esoteric that their applicability is ignored.Four years ago, I prepared an editorial1 on a very interesting paper2 reviving an old area of research — namely, the effects of continuous vs. intermittent positive-pressure breathing. Since then, numerous related studies have been performed and the benefits of positive end-expiratory pressure (PEEP) have been carefully analyzed and clearly demonstrated. In their paper in this issue, Suter and his associates review the various indexes that have been used to assess the efficiency of PEEP; . . .
Lack of JunD Promotes Pressure Overload–Induced Apoptosis, Hypertrophic Growth, and Angiogenesis in the Heart
Authors: Denise Hilfiker-Kleiner, Andres Hilfiker, Karol Kaminski, Arnd Schaefer, Joon-Keun Park, Kim Michel, Anja Quint, Moshe Yaniv, Jonathan B. Weitzman, Helmut Drexler
Journal: Circulation (2005)

The Jun family of activator protein 1 (AP-1) transcription factors (c-Jun, JunB, and JunD) is involved in fundamental biological processes such as proliferation, apoptosis, tumor angiogenesis, and hypertrophy. The role of individual AP-1 transcription factors in the stressed heart is not clear. In the present study we analyzed the role of JunD in survival, hypertrophy, and angiogenesis in the pressure-overloaded mouse heart after thoracic aortic constriction.Mice lacking JunD (knockout [KO]) showed increased mortality and enhanced cardiomyocyte apoptosis and fibrosis associated with increased levels of hypoxia-induced factor-1alpha, vascular endothelial growth factor (VEGF), p53, and Bax protein and reduced levels of Bcl-2 protein after 7 days of severe pressure overload compared with wild-type (WT) siblings. Cardiomyocyte hypertrophy in surviving KO mice was enhanced compared with that in WT mice. Chronic moderate pressure overload for 12 weeks caused enhanced left ventricular hypertrophy in KO mice, and survival and interstitial fibrosis were comparable with WT mice. Cardiac function, 12 weeks after operation, was comparable among shams and pressure-overloaded mice of both genotypes. In addition, KO mice exposed to chronic pressure overload showed higher cardiac capillary density associated with increased protein levels of VEGF.Thus, JunD limits cardiomyocyte hypertrophy and protects the pressure-overloaded heart from cardiac apoptosis. These beneficial effects of JunD, however, are associated with antiangiogenic properties.
The effects of long-term aerobic exercise and energy restriction on protein synthesis
Authors: Harvey L. Katzeff, Kaie M. Ojamaa, Irwin Klein
Journal: Metabolism (1995)

Long-term aerobic exercise and energy intake regulate body composition in a complex manner. To study the combined effects of exercise and energy restriction on muscle mass, we measured skeletal and cardiac muscle protein synthesis after 28 days of two levels of energy restriction with or without daily running-wheel exercise in female rats. Protein synthesis was measured as 3H-Phe incorporation 10 minutes' postbolus of a flooding pulse injection. The two exercise plus energy-restriction groups had greater skeletal muscle and cardiac muscle mass compared with their food-matched groups. Cardiac, gastrocnemius, and soleus muscle protein synthetic rates were proportional to their muscle masses. Exercise-induced energy deficits preserved cardiac and soleus mass to a greater extent than gastrocnemius mass, whereas the effects of energy restriction were similar in all three muscles. These findings suggest that energy intake and exercise have independent effects on the regulation of muscle mass and protein synthesis.
Abstract 2385: Activated Kras and INK4a/Arf deficiency cooperate to produce pancreatic cancer involved with Notch and NF-κB pathways
Authors: Zhiwei Wang, Sanjeev Banerjee, Aamir Ahmad, Asfar S. Azmi, Bin Bao, Shadan Ali, Ramzi M. Mohammad, Lucio Miele, Murray Korc, Fazlul H. Sarkar
Journal: Cancer Research (2011)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Kras mutations are observed in 80%-90% of pancreatic cancer. Oncogenic Kras is involved with the initiation or early phase of PDAC. To understand the molecular mechanisms, several mouse models of PDAC have been generated by targeting a conditionally mutated KrasG12D to recapitulate the progression of PDAC. It was previously shown that one mouse model which activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic PDAC. However, the molecular mechanism(s) by which Kras and Ink4a/Arf deficiency contribute to PDAC has not been fully elucidated. Here, we assessed the molecular alterations in mice which are activated Kras and Ink4a/Arf deficiency. For the first time, we demonstrated that deletion of Ink4a/Arf in Kras expressing mice leads to PDAC partly through Notch and NF-κB signaling pathways. Moreover, we show that several miRNAs, such as miR-200 family and miR-34 could partially play roles in tumorigenesis in activated Kras and Ink4a/Arf deficiency mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2385. doi:10.1158/1538-7445.AM2011-2385
A Century of Black Surgeons: The USA Experience
Authors: William Lynn Weaver
Journal: JAMA (1989)

The medical community's preoccupation with medical history is based on our continued amazement at the accomplishments of our predecessors, without the diagnostic and therapeutic tools that we believe are indispensable in today's practice of medicine, such as computed tomographic scans, lasers, and third-generation antibiotics. If you are intrigued by medical history, then<i>A Century of Black Surgeons: The USA Experience</i>is required reading. This two-volume set documents a facet of medical history that has not been previously compiled in one text. Of equal importance is the social history of this country, which is chronicled as a necessary part of this unique story. Dr Claude Organ, Jr, and Margaret M. Kosiba, RN, have done an impressive amount of research and documentation in compiling this work. As is well known, much of the history of blacks in the United States has been lost because of destruction of records and lack of documentation.
IDSA Creates MRSA Treatment Guideline
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

that it planned to consolidate from 10 groups to5.Oneof thegroupswillbe the existing pediatric group, which was createdbycombining4groupsseveralyears ago. There will also be 4 groups focused onadultcancers.TheNCIwillrevieweach group’sperformanceindividuallyandalso createmoreincentivesforgroupstowork cooperativelywithoneanother.Doroshow said having fewer groups should make it easier to implement the changes already under way. To determine the compositionofthenewgroups,theagencywillsolicit proposals from the existing groups. Doroshow noted that 3 groups have alreadycreatedanagreementtomanageall dataatasinglesiteandthat theyare likely to also join their scientific efforts. While the changes have been well received so far, much work remains to be done. Allen S. Lichter, MD, chief executive officer of the American Society of Clinical Oncology (ASCO), noted that ASCO supports the recommendations of the IOM and the work done so far by the NCI. However, he cited other existing roadblocks to swift completion of trials. For example, he said, it will be important toboost interagencycooperationand to better coordinate oversight of trials by multiple federal agencies to prevent trials from being caught up in prolonged backand-forth between agencies. Additionally, Lichter said, it will be important to implement the IOM’s recommendations in their entirety. ASCO and the National Cancer Policy Forum are holding a workshop March 21 to discuss with a range of stakeholders how to best implement the IOM’s recommendations. Of particular concern is the need to increase reimbursements for investigators and centers participating in trials. He noted that reimbursements for investigators haven’t increased in a decade, despite increased regulatory burdens, more stringent reporting requirements, and a corresponding need for more investigator time to meet such demands. ASCO calls for doubling the current reimbursement rates, although Lichter acknowledged this may be difficult in the current economicandpolitical environment. “We understand the complexities of this,” he said. “Yet if funding stays flat, inflation and other requirements mean that the reimbursement is being cut every year.” Doroshow said that as a former investigator in the program, he is well aware of the need for increased reimbursement rates, and that the NCI is working to determine “how we can change the way we operate to provide additional resources to investigators, even in the face of difficult economic times.” Lichter emphasized the increasing importance of the trials conducted by the cooperative groups, noting that studies comparing drugs or assessing combinations of compounds or treatment modes will simply not be conducted by industry. “With all the emphasis on value and comparative effectiveness, these studies are the bedrock on which we base cancer treatment,” he said.
Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model☆
Authors: Lei Ye, Husnain Kh. Haider, Shujia Jiang, Lieng H. Ling, Ruowen Ge, Peter K. Law, Eugene K.W. Sim
Journal: European Journal of Heart Failure (2005)
CXCR4 alters ID family and ITF2B/E2-2/TCF-4 dynamics to confer invasive phenotype to breast cancer cells.
Authors: HN Appaiah, P Bhat-Nakshatri, H Nakshatri, S Badve
Journal: Cancer Research (2009)

Abstract Abstract #2045 Introduction: Breast cancer is characterized by a distinct metastatic pattern involving lymph nodes, bone marrow, lung, liver and brain. The chemokine CXCL12 and its receptor CXCR4 are suggested to play a role in invasion and organ-specific metastasis. Signaling pathways downstream of CXCL12:CXCR4 involved in invasion and/or metastasis are not known.&amp;#x2028; Methods: MDA-MB-231 breast cancer cells were sorted for CXCR4-positive and CXCR4-negative subpopulation by FACS and subjected to microarray gene expression analysis. Differentially expressed genes were further verified by RT-PCR or qRT-PCR. siRNA or shRNA expression studies were used to evaluate the role of genes overexpressed in CXCR4-positive cells in invasion through Matrigel. Orthotopic xenograft model is being used to evaluate primary tumor growth and metastasis pattern of CXCR4-positive and CXCR4-negative subpopulation with various manipulations.&amp;#x2028; Results: ITF2B, a class I bHLH transcription factor, is expressed at ∼4-fold higher level in CXCR4-positive cells. ITF2B mRNA level was lower in CXCR4 siRNA treated or CXCR4shRNA expressing CXCR4-positive cells suggesting that ITF2B is the direct target of CXCL12:CXCR4. ITF2B siRNA reduced invasion of CXCR4-positive cells whereas ITF2B overexpression increased invasive capacity of CXCR4-negative cells. ITF2B is a Wnt β-catenin regulated gene with transforming ability and controls the function of Inhibitor of DNA binding family of transcription factors (ID1 to ID4). ID1 is essential for lung metastasis whereas ID2 induces differentiation of breast cancer cells and higher levels of ID2 correlates with favorable prognosis in breast cancer. ID2 expression was higher in CXCR4-negative cells and its overexpression in CXCR4-positive cells reduced invasion. Both CXCR4 and ITF2B are involved in reducing ID2 expression as siRNA against both of these genes increased ID2 mRNA in CXCR4-positive cells. Interestingly, CXCR4-negative cells appear to have adapted to alternative mode of invasion/metastasis as these cells express higher levels of metastasis-associated genes such as TWIST and MT1-MMP. Xenograft studies with cells overexpressing ITF2B and ID2 are currently underway.&amp;#x2028; Conclusions: CXCL12:CXCR4 activated signaling pathways target ID family/bHLH transcription factor network to promote invasion of breast cancer cells. Inducers of ID2 may help to overcome CXCR4- mediated invasion and/or metastasis of cancer cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2045.
Premature discontinuation of patients: a potential bias in COPD clinical trials
Authors: S. Kesten, M. Plautz, C. A. Piquette, M. P. Habib, D. E. Niewoehner
Journal: European Respiratory Journal (2007)

Premature discontinuation from clinical trials may bias results against effective therapies. In the present study mortality rates were retrospectively reviewed in a 6-month, randomised, placebo-controlled trial in which tiotropium 18 μg daily was shown to decrease chronic obstructive pulmonary disease exacerbations. Patients participated for 6 months even if trial medication was prematurely discontinued. Exposure-adjusted incidence rates (IRs) were calculated for randomisation–end trial, randomisation–end trial drug (0–ED) and end trial drug–end trial (ED–ET). Of 1,829 patients (forced expiratory volume in one second 1.04 L (36% predicted), mean age 68 yrs, 99% male), 16% tiotropium and 27% placebo patients prematurely stopped trial medication. The number of fatal events for the entire cohort was: 62 all cause, including 16 cardiac and 16 lower respiratory. IRs for fatal events per 100 patient-yrs were higher in the discontinued period: 1.9 (0–ED) versus 23.0 (ED–ET) in the tiotropium group and 1.8 versus 19.0 in the placebo group. Respective IRs for fatal cardiac events were 0.7 versus 2.8 (tiotropium) and 0.5 versus 6.2 (placebo); for fatal lower respiratory events were 0.7 versus 2.8 (tiotropium) and 0.8 versus 5.4 (placebo). Rate ratios (tiotropium/placebo) for fatal events were lower in the discontinued period: 1.4 versus 0.5 for cardiac and 0.9 versus 0.5 for lower respiratory. Higher incidence rates of fatal events occurred following premature discontinuation of study medication. Incomplete information from rate ratios occurs as a result of failure to consider outcomes of patients who discontinue early from clinical trials.