tbuckley/cabot-search huggingface dataset:
Periprosthetic Anesthetic for Postoperative Pain After Laparoscopic Ventral Hernia Repair
Authors: Aimee E. Gough, Steven Chang, Subhash Reddy, Lisa Ferrigno, Marc Zerey, Jonathan Grotts, Samantha Yim, David S. Thoman
Journal: JAMA Surgery (2015)

Laparoscopic ventral hernia repair (LVHR) using mesh is a well-established intervention for ventral hernia, but pain control can be challenging.To determine whether instillation of a long-acting local anesthetic between the mesh and the peritoneum after LVHR reduces pain or narcotic requirements.A prospective, double-blind, randomized clinical trial with data collection during a brief hospital stay in a tertiary care, community teaching hospital over 3 years between December 15, 2011, and March 28, 2014. Of 120 screened patients undergoing LVHR in this intention-to-treat analysis, 99 eligible patients were randomized. Forty-two patients received the study drug, and 38 patients received placebo. Patients with a history of chronic narcotic use were excluded.After mesh placement, a long-acting local anesthetic (bupivacaine hydrochloride, 0.50%) or placebo (0.9% normal saline) was injected between the mesh and the peritoneum.Postoperative pain (on a standard scale ranging from 0 to 10), and narcotic medication use (intravenous morphine equivalents). There were no adverse events.Baseline and operative characteristics were similar except that the treatment group was older (61.8 vs 52.3 years, P = .001). After surgery, pain scores in the recovery room (3.2 vs 4.7, P = .003), interval total narcotic use (6.7 vs 12.5 mg, P = .003 at <4 hours and 0 vs 2.7 mg, P = .01 at 8-12 hours), and total intravenous narcotic use (9.2 vs 17.2 mg of morphine sulfate equivalents, P = .03) were significantly less in the treatment group.Administration of a long-acting local anesthetic between the mesh and the peritoneum significantly reduces postoperative pain and narcotic use after LVHR.clinicaltrials.gov Identifier: NCT01530815.
Abstract 595: Functional, Histologic, and Radiographic Characteristics of Global Ischemia-reperfusion Brain Injury in a Mouse Model Of Cardiac Arrest
Authors: Akshay Pendyal, Cameron Dezfulian, Luhua Zhang, Jeeva Munasinghe, Mark T Gladwin
Journal: Circulation (2008)

Cardiac arrest (CA) and subsequent CPR constitute a clinically relevant form of global ischemia-reperfusion injury (IR). Global IR often results in widespread ischemic brain damage and severe neurologic sequelae. In the present study, we sought to describe the functional, histologic, and radiographic brain changes that occur following CA/CPR. 8–10 week old C57BL/6 mice were subjected to 12 minutes of normothermic cardioplegic CA and resuscitated with chest compressions, mechanical ventilation, and epinephrine. Sham mice underwent surgery, but not CA. At 3 and 24 hours, 10-point functional neurological score and rectal temperature were assessed prior to trans-cardiac perfusion with PBS and 10% buffered formalin. Sectioned brains were stained using hematoxylin and eosin (H/E) and the terminal deoxyuridine triphosphate nick end-labeling (TUNEL) technique. An additional cohort of mice underwent quantitative diffusion MRI at 24 and 72 hours, gadolinium (Gd)-enhanced MRI at 24 hours, and quantitative T2 imaging at 72 hours. Compared to shams, mice undergoing CA/CPR displayed significantly lower functional neurological score at 3 hours (3±2 vs. 10±0; P&lt;.001) and 24 hours (8±1 vs. 10±0, P&lt;.05), and significantly higher rectal temperature at 3 hours (35.8±1.5 vs. 34.1±0.8, P&lt;.001) and lower rectal temperature at 24 hours (33.8±2.5 vs. 37.1±0.8, P=.08). TUNEL and H/E staining revealed injury in the cortex, thalamus, hippocampus, and cerebellum, but neither a consistent pattern nor clear temporal progression was observed. Gd-enhanced MRI revealed increased signal intensity, particularly in the cortex, after CA (3.7×105±0.96×105 vs. 0.66×105±0.017×105, P&lt;.05), consistent with breakdown of the blood-brain barrier. Diffusion MRI revealed a strong trend towards globally decreasing diffusion coefficients at 24 and 72 hours (P=0.14), consistent with widespread cell death. In our model of CA, global IR results in poor neurological function and global injury by MRI that is not reflected by early histology. MRI thus appears to be a more sensitive measure of visualizing neurological injury in the early stages after CA and may predict the delayed neuronal death remarked upon by other authors.
Abstract 10968: Optical Coherence Tomography as a Novel Diagnostic Tool for Distal-type Chronic Thromboembolic Pulmonary Hypertension
Authors: Shunsuke Tatebe, Yoshihiro Fukumoto, Koichiro Sugimura, Kimio Satoh, Makoto Nakano, Yutaka Miura, Saori Miyamichi, Hiroaki Shimokawa
Journal: Circulation (2010)
Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context- dependent manner
Authors: Richard Festenstein, Soheila Sharghi-Namini, Margaret Fox, Kathleen Roderick, Mauro Tolaini, Trisha Norton, Alexander Saveliev, Dimitris Kioussis, Prim Singh
Journal: Nature Genetics (1999)
Soundings: Choosing socks
Authors: Colin Douglas
Journal: BMJ (2000)

We are fortunate that here in Auchendreich our senior house officer posts continue to attract numerous applicants from all over the world. Such is our luxury of choice that a selection process, perhaps unique but undoubtedly deserving of wider notice, has gradually evolved to help us make important decisions that are both swift and fair.

To save everyone's time the 110 applications for this year's dozen posts were short listed by our appointment committee chairman's secretary—a woman of great experience and sound judgment—and only the 25 most promising candidates invited to interview yesterday afternoon. And, although the prospect of 25 consecutive 10 minute interviews is at first daunting, our little committee settled quickly to its task, finishing by half past six.

Our chairman believes that the special nature of the posts on offer requires to be explained in some detail to candidates, which relieves the rest of us from much of the burdensome duty of thinking up questions to ask. And, although it is sometimes disappointing for keen young applicants—particularly those whose attendance involves long haul flights—not to have more than a couple of minutes to explain their enthusiasm for the post in question, at least it helps to keep things running on time.

I admit to experiencing a certain listlessness towards a quarter past four, but just then the chairman's secretary came in to announce that a candidate had failed to make his way from Omdurman to Auchendreich in time for his interview, and coffee would now be served.

At that point our consultant haematologist, still fairly new to the Auchendreich scene, expressed concerns about the selection process. Our chairman simply confirmed that senior house officer posts in Auchendreich were not for the fainthearted. But really, she insisted, was 10 minutes adequate?

Perfectly adequate, he explained. Appointing a fellow consultant was in his view a bit like buying a suit. The result had to last, so it was worth spending maybe 20 minutes on it. Appointing registrars was more like buying a shirt. No sensible man would give it more than 15. And senior house officers? He patted our haematologist's hand gently. “Nobody wastes a lot of their time buying socks.”
Negligence claims to rise by 50% in Wales
Authors: Roger Dobson
Journal: BMJ (2000)

The Welsh Assembly has been warned that clinical negligence claims against the NHS in Wales could spiral out of control unless remedial action is taken. A report on the annual accounts of the NHS in Wales says that the forecast cost of claims is £214m ($321m), a £69m increase in 12 months.

“A potential £214m bill for clinical negligence claims …
Satisfaction after rehabilitation for stroke: Patient versus family ratings
Authors: Kenneth Ottenbacher, Leigh Tooth
Journal: Circulation (2003)

Context. Overall satisfaction has important social and economic implications for patients who have received inpatient medical rehabilitation for stroke. Objective. Examine satisfaction at three to six month follow-up for patients with stroke discharged from medical rehabilitation.Design. The study was retrospective using information from a national database representative of medical rehabilitation patients across the United States.Setting. Information submitted from 1999 - 2001 to the Uniform Data System for Medical Rehabilitation by 744 hospital and rehabilitation facilities from 50 states was examined.Participants. Admission and dischargedata were available for 19,670 patients and follow-up data for 18,375, with missing data (n=1,295) due to patient deaths. Complete admission, discharge and follow-up data were available for 17,593 patients with stroke.Main Outcome Measures. Level of satisfaction withmedical rehabilitation at 80 to 180 days post-discharge follow-up. Results. A higher proportion of dissatisfied ratings were found when proxies reported the data (57%), compared to when patients reported the information (43%). Separate logistic regression models were computed for patient (n=9,707) and proxy (n=7,886) sub-samples. The significant (x213 = 67.8, p <.001) influences on satisfaction for patients were Functional Independence Measure scores (motor and cognitive), rehospitalization, who patients were living with, ethnicity, age, andfollow-up therapy. The significant (x213 = 146.9, p < .001) influences on satisfaction for the proxy reported sub-sample were rehospitalization, type of stroke, ethnicity, cognitive FunctionalIndependence Measure scores, length of rehabilitation stay, and follow-up therapy services received.Conclusion. Satisfaction with rehabilitation services was perceived differently by patients and proxies (family members) suggesting important implications for patient satisfaction as a quality outcome indicator.Copyright © 2003 American Heart Association, Inc. All rights reserved
1011. Tumor Specific Oncolytic Adenovirus Vector VRX-011 Which Overproduces ADP and Has the E4 Promoter Replaced by the hTERT Promoter
Authors: Mohan Kuppuswamy, Ann E. Tollefson, Karoly Toth, Jacqueline F. Spencer, Konstantin Doronin, Drew L. Lichtenstein, Lou Zumstein, William S. M. Wold
Journal: Molecular Therapy (2004)

We have previously evaluated the conditionally replicating adenovirus (Ad) vector named KD3 for possible use in anti-cancer therapy. KD3 markedly overexpresses ADP, an Ad nuclear membrane glycoprotein required at late stages of infection for efficient cell lysis and release of Ad from cells. KD3 also has two E1A mutations that reduce its replication in primary cells but allow efficient replication in cancer cells. We have also reported on a replication-competent vector named VRX-007 which overexpresses ADP and has wild type E1A. VRX-007 showed remarkable early cytopathic effects, early cell lysis, large plaques, increased cell to cell dissemination in cultured cells, enhanced cytolysis of cultured cancer cells, and efficient suppression of tumor growth in animal models. In this report we describe the vector VRX-011, which is similar to VRX-007 except that the Ad E4 promoter has been replaced by the promoter for human telomerase (hTERT). Telomerase is an enzyme involved in the maintenance of chromosomal termini known as telomeres. About 90% of cancer cells have elevated levels of telomerase activity, whereas telomerase activity is not detected in normal somatic cells. Since E4 proteins are required for Ad replication, VRX-011 is expected to replicate in most cancer cell types but not (well) in non-cancerous cells. VRX-011 replicated as well as Ad5 in the majority of cancer cell lines tested and was growth restricted in primary cells. Ad late protein expression was at normal levels in A549 human lung cancer cells but was markedly reduced in primary cells. Intratumor administration of VRX-011 effectively suppressed Hep3B liver carcinoma xenograft growth in nude mice. Systemic administration of VRX-011 by tail vein injection also efficiently suppressed Hep3B xenograft growth in nude mice. Also, intravenous administration of VRX-011 significantly reduced the number and size of A549 cancer cell metastases in nude mice lungs. Single tail vein administration of different PFU doses of VRX-011 in C57B/6 mice showed no toxicity as indicated by liver enzyme levels and animal weights. These in vitro and in vivo data show that VRX-011 has enhanced specific oncolytic efficacy and restriction in primary cells. VRX-011 may be useful in treating different types of human cancer.
Abstract P196: Unhealthful Dietary Intake Pattern Identified by Reduced Rank Regression is Associated with Increased Arterial Stiffness among Youth with Type 1 Diabetes
Authors: Archana P Lamichhane, Angela D Liese, Elaine M Urbina, Jamie L Crandell, Lindsay M Jaacks, Dana Dabelea, Mary Helen Black, Anwar T Merchant, Elizabeth J Mayer-Davis
Journal: Circulation (2014)

Introduction: Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile and outcomes. Objective: We applied reduced rank regression (RRR) to identify a specific dietary pattern that explained the maximum amount of variation in CVD risk factors, and was strongly associated with markers of arterial stiffness (AS) in a cohort of youth with T1DM. Methods: Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, LDL-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1,153 youth aged ≥10 years with T1DM from the SEARCH for Diabetes in Youth Study. Dietary intake patterns were identified using 33 food-groups as predictors and six CVD risk factors as responses in an RRR analysis. AS outcomes were measured on average 18.9±7.1 months after the baseline diet assessment and were available only in a subset of participants from the SEARCH CVD pilot study. Associations between the RRR-derived dietary pattern explaining the maximum variation in CVD risk factors and AS measures [augmentation index(AIx75),n=229; pulse wave velocity(PWV),n=237; and brachial distensibility(BrachD),n=228] were then assessed using linear regression. Results: The RRR-derived pattern of interest was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats, and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in the adverse CVD risk profile and was subsequently positively associated with AIx75 in the final model (β=0.47; p&lt;0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. Associations of the dietary pattern with the other measures of AS, PWV and BrachD, were attenuated and became non-significant after adjustment for potential confounders. Conclusions: Intervention strategies to reduce consumption of unhealthful foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS. Future studies with larger samples are needed to explore the associations between the derived dietary pattern and other measures of AS (PWV and BrachD), which can provide further insights into possible pathways linking diet to AS in this high risk population.
Abstract #4409: Changes of cellular phosphoproteome in pancreas cancer cells in response to transketolase inhibitor oxythiamine
Authors: Rui Cao
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

In our newly developed method, we have demonstrated that metabolic labeling of protein with amino acids of low isotope enrichment (mSILAC) can be used to determine protein synthesis or turnover rate. In this communication, using this new method we demonstrated that transketolase inhibitor oxythiamine (OT) can interfere cellular proteomic profile at both translational and post-translational levels in MIA PaCa cancer cells. MIA PaCa cell as a model was cultured in media containing an algal 15N amino acid mixture at 50% enrichment. The cellular proteome expressed differentially in MIA cells in response to OT treatment has been analyzed by using two dimensional gel electrophoresis (2-DE) coupled with MALDI-TOF/TOF MS. Analysis of cell lysates was then subjected to the identification of 15 phosphoproteins and 5 non-phosphoproteins differentially expressed in OT treated MIA cancer cells as compared to that in control group. The identified proteins include antioxidant enzymes, chaperones, calcium-binding proteins, proteases, and signal transduction proteins. Among these proteins, the expression of Hsps 90/27, 60S acidic ribosomal protein P0, nucleophosmin, \#945;-enolase, peroxiredoxin 4, and nuclear autoantigenic sperm protein were significantly suppressed by OT treatment. Comparing the calculated turnover rates of the phophosproteins to that of non-phosphoproteins, we found thatthe average turnover rates for phosphoproteins (70%) are much higher than that for non-phospho proteins (50%) among 20 differentially expressed proteins. Among the phosphoproteins, the turnover rate for hsp27 with the highest turnover rate is 75%. Therefore, this protein was further validated using immunohistochemical stain, showing that the sensitivity and specificity for this protein is 90% (n=15). We also observed that OT treatment deactivated p38 and JNK cascades and caused cancer cell cycle arrest. The phosphoproteins differentially expressed in OT treated cells may be related to the changes of the cellular activity. Our findings from this study may provide a valuable surrogate biomarker or novel drug target that could be used for early diagnosis of the disease and evaluation of therapeutic effectiveness.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4409.
ABC of psychological medicine: Depression in medical patients
Authors: R. Peveler
Journal: BMJ (2002)

Depressive illness is usually treatable. It is common and results in marked disability, diminished survival, and increased healthcare costs. As a result, it is essential that all doctors have a basic understanding of its diagnosis and management. In patients with physical illness depression may

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Aretaeus of Cappadocia (circa 81–138 AD) is credited with the first clinical description of depression

The term depression describes a spectrum of mood disturbance ranging from mild to severe and from transient to persistent. Depressive symptoms are continuously distributed in any population but are judged to be of clinical significance when they interfere with normal activities and persist for at least two weeks, in which case a diagnosis of a depressive illness or disorder may be made. The diagnosis depends on the presence of two cardinal symptoms of persistent and pervasive low mood and loss of interest or pleasure in usual activities.

#### Criteria for major depression*

Five or more of the following symptoms during the same two week period representing a change from normal

View this table:

Adjustment disorders are milder or more short lived episodes of depression and are thought to result from stressful experiences.

Major depressive disorder refers to a syndrome that requires the presence of five or more symptoms of depression in the same two week period.



“Neurotic” symptoms, including depression, are continuously distributed in the UK population





The association between depression and mortality after myocardial infarction



Dysthymia covers persistent symptoms of depression that may not be severe enough to meet the criteria for major depression, in which depressed mood is present for two or more years. Such chronic forms of depression are associated with an increased risk of subsequent major depression, considerable social disability, and unhealthy lifestyle choices …

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A memorable period: A small United Nations
Authors: O. P Sharma
Journal: BMJ (1999)

The SCOFF questionnaire seems highly effective as a screening instrument for detecting eating disorders; it is simple, memorable, and easy to apply and score, and it is designed to raise suspicion of a likely case rather than to diagnose.We consider that the SCOFF questionnaire performed well against the 10 questions suggested by Greenhalgh to assess screening tests. 5The false positive rate of 12.5% is an acceptable trade off for very high sensitivity.Further work is needed to establish validity and reliability in a wider population, and particularly in those at risk of eating disorders in the general population.None the less, there is sufficient evidence of validity for it to be used routinely in all patients considered at risk of eating disorders.We thank Professor Martin Bland, professor in medical statistics, for guidance in planning the research methodology.
IRBs Search for Answers and Support During a Time of Institutional Change
Authors: D F Phillips
Journal: JAMA (2000)

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Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
Authors: Koenraad Devriendt, Annette S. Kim, Gert Mathijs, Suzanna G.M. Frints, Marianne Schwartz, Joost J. Van den Oord, Gregor E.G. Verhoef, Marc A. Boogaerts, Jean-Pierre Fryns, Daoqi You, Michael K. Rosen, Peter Vandenberghe
Journal: Nature Genetics (2001)
Milburn's vision of a new NHS
Authors: R. Klein
Journal: BMJ (2001)

Adopting the missionary position 

News p 1083 

Having established a reputation as the most centralising secretary of state for health in the history of the British National Health Service, Alan Milburn now seems determined to recast himself as the man who shifted the “centre of gravity within the health service from Whitehall to the NHS frontline.” This, he emphasised in a much advertised speech last week,1 is to be the theme of Labour's second term in office.

Power and resources are increasingly to be transferred to primary care trusts, which are expected to control 75% of the NHS's budget by 2004. Clinicians are to be more involved in the design of services at all levels, starting with the Department of Health itself, as well as being given more control over budgets. NHS trusts, including primary care trusts, “will have greater operational freedom.” And to promote this “new decentralised approach,” the structure of bureaucratic control is to be simplified: responsibility for “performance managing the local health care system” …