tbuckley/cabot-search huggingface dataset:
Prevalence and Mechanisms of Gastro-Oesophageal Reflux in Adult Cystic Fibrosis Patients
Authors: M J Ledson, J Tran, M J Walshaw
Journal: Journal of the Royal Society of Medicine (1998)

Gastro-oesophageal reflux (GOR) occurs frequently in children with cystic fibrosis (CF) but has not been studied in adult CF. We surveyed such symptoms by structured questionnaire in 50 adult CF patients (mean age 26 years, range 16-50; 24 male) and performed oesophageal manometry and 24-hour pH recording in 10 who had reflux symptoms (mean age 28 years, range 21-35; 8 men). 47 patients (94%) had upper gastrointestinal symptoms: 40 (80%) heartburn (27 worse when supine); 26 (52%) regurgitation; and 28 (56%) dyspepsia. At oesophageal manometry, lower oesophageal sphincter barrier pressure (LOSBP) was subnormal in 6 of the 10 patients and 3 had uncoordinated peristalsis in the mid oesophagus. 8 patients had raised DeMeester scores, indicating significant GOR. Those patients with a LOSBP < 5mm Hg had a higher DeMeester score (mean 81.0, range 47.9-128.8) than the patients with a normal LOSBP (26.9, 8.7-56.5; p < 0.002). These results show that adult CF patients have high rates of GOR symptoms, diminished LOSBP, and acid reflux.
Letter to the editor. Spotlight on measles 2010: Measles in healthcare workers – vaccination should be revisited
Authors: E Botelho-Nevers, L Chevereau, P Brouqui
Journal: Eurosurveillance (2010)

Preview this article: Letter to the editor. Spotlight on measles 2010: Measles in healthcare workers – vaccination should be revisited, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/15/41/art19687-en-1.gif
Antiangiogenic therapy for squamous cell carcinoma using combinatorial agents
Authors: V. W. Li, R. A. Ball, N. Vasan, W. W. Li
Journal: Journal of Clinical Oncology (2005)

3032 Background: Squamous cell carcinoma (SCC) is an invasive neoplasm affecting epithelial tissues including mucocutaneous surfaces. Conventional therapies involve surgery or destructive modalities. Because angiogenesis is a critical event in tumor progression, antiangiogenic therapy may be a molecular strategy for SCC. We developed protocol OLCAT-005 (imiquimod, tretinoin, calcipotriene, diclofenac, hydrocortisone valerate) as a topical treatment for cutaneous SCC. Each drug targets specific antiangiogenic mechanisms, including upregulating interferons, IL-12, RAR-alpha, endothelial survival, COX-2 mediated VEGF production, and basement membrane integrity. Methods: OLCAT-005 was used to treat in situ and invasive squamous cell carcinoma (SCC) in 20 patients unable to undergo or refusing conventional treatment modalities. Punch biopsies confirmed the SCC diagnosis. OLCAT-005 was initiated 2x/week (M, F) and increased to at least 3x/week (M, W, F). Dose schedule per lesion was optimized by the Individualized Maximally Tolerated Dose (IMTD) algorithm. Monthly clinical assessment was performed. At 18 weeks, sites were re-biopsied and evaluated for tumor presence, and immunostained for CD31 and αSMA. Quality of life (QoL), cosmesis, and SCC recurrence were evaluated at follow-up visits. Results: A total of 61 SCC lesions (35 invasive, 26 in situ) received OLCAT-005 from 1998–2004. Complete response with pathological clearance occurred after 12 treatment weeks in 33/35 (94%) of invasive SCC and 23/26 (88%) of SCC in situ. In the SCC in situ partial responders (3/26), all residual tumors cleared with 6 more weeks of treatment. No recurrence was observed in follow-up to 5 years. OLCAT-005 was well tolerated and erythema was the most frequent tissue reaction. In treated lesions, vascular density was inhibited and microvessels appeared normalized. QoL and cosmesis were excellent. Conclusions: OLCAT-005 is well tolerated and highly effective in regressing cutaneous SCC in situ and invasive SCC in patients unable to undergo or refusing conventional treatment modalities. An antiangiogenic mechanism is evident. This approach merits evaluation in other forms of SCC. No significant financial relationships to disclose.
Are our Babies Becoming Bigger?
Authors: E Alberman
Journal: Journal of the Royal Society of Medicine (1991)

I have tried to show, using a contemporary international data set, the overall consistency in shape of curves of national birthweight distributions which reflect the biological and social characteristics of the population from which they are derived, and the effects of changes in these characteristics. For several countries, including the United States and England and Wales, the trends in recent years have been such as to shift the main distribution upwards, so that the median weight has increased. Also shown has been the close and specific relationship within each population group between infant mortality and birthweight, with sharp falls of mortality with increasing birthweight. It has been shown elsewhere that similar patterns are seen with short- and long-term morbidity, thus underlining the importance to be attached to increasing birthweight particularly in underprivileged groups. In the short term this can be done by reducing the frequency of parental smoking, where this is a problem, and in the longer term by improving maternal health and nutrition. The shift towards higher birthweights if it persists, should make an important contribution towards the improvement of the public health of the next generation.
Abstract 230: Protein Kinase C is Requisite for Interstitial Membrane Type-1 Matrix Metalloproteinase Activity during Ischemia and Reperfusion
Authors: Anne M Deschamps, Juozas A Zavadzkas, Rebecca L Murphy, Julie E McLean, Laura B Jeffords, Stuart M Saunders, Francis G Spinale
Journal: Circulation (2006)

Background: Matrix metalloproteinases (MMPs), in particular membrane type-1 MMP (MT1-MMP), have been implicated to contribute to transient left ventricular (LV) dysfunction with ischemia and reperf...
Book: Stuart: A Life Backwards
Authors: Angela Jones
Journal: BMJ (2006)

Stuart Shorter spent his late teens and adult life alternating between the streets and prison with occasional, mostly short lived, forays into accommodation. He exemplifies the so called “chaotic” homeless people, who are on the streets because, curiously, it is the only place where they can manage. Because their lives are so confused and devastated by addiction, mental health problems, and broken relationships, they cannot cope with the complications presented by having their own place.​place.



Figure 1

Perennial, £7.99, pp 304 ISBN 0 00 720037 4



Telling the story backwards was Stuart's idea—he envisaged a sort of thriller, a page turner that explains who, or what, “murdered” the loving, kind, helpful little boy that he was, replacing him with a “polydrug-addicted-alcoholic Jekyll and Hyde personality with a fondness for... knives.” What emerges is a complex and touching tale of a boy from semirural Cambridgeshire, who battles bravely and successfully with the stigmatisation of a physical disability but who suddenly finds his life shattered by events in his early teens from which he never truly recovers.

Stuart's rages against “the system” are unsettlingly cogent, his insights into his own plight and those of others are disarmingly frank and at times uproariously funny. Masters' own insights into the torturous process of writing his book and into the results of his own research into the issue of homelessness are similarly to the point and informative.

The average doctor rarely comes into professional contact with a homeless person. Emergency departments have been the commonest venue, and these contacts are often challenging, frightening, or unsatisfactory (or all three). Does it matter that we, as a profession, are not well versed in the realities of homelessness? I believe that it does—if we were all to have a notion of what it is to be a person who is homeless, and of how this can happen to someone, we might all acknowledge the special potential of our professional contact with all patients, but particularly with patients who hold “the system” in such low esteem.

People like Stuart have been serially failed by society, and we, as doctors, will fail them too, if we do not ensure that we have the ability, skills, insight and compassion to manage our contacts with them appropriately.

There are many manifestations of housing need, of which the chaotic rough sleeper is arguably the most extreme example. Stuart's story is not the worst I have come across nor can it alone represent all the individual narratives of rough sleepers on our streets. However, if every medical professional read Stuart: A Life Backwards, it may prevent the health service from contributing to further marginalisation of the already marginalised.
Abstract 1: Implementing a “Resuscitation Bundle” Decreases Incidence and Improves Outcomes in Inpatient Cardiopulmonary Arrest
Authors: Rebecca E Sell, Brenna Lawrence, Daniel P Davis
Journal: Circulation (2009)

Background: Despite recent advances in the understanding of cardiopulmonary arrest (CPA), survival to hospital discharge remains poor. Traditional training models appear inadequate in achieving and...
Magnetic resonance imaging measurement of posterior fossa structures in schizophrenia
Authors: E H Aylward, A Reiss, P E Barta, A Tien, W Han, J Lee, G D Pearlson
Journal: American Journal of Psychiatry (1994)

Previous research has yielded conflicting results regarding the hypothesis that structural abnormalities of the cerebellar vermis and other posterior fossa structures are associated with schizophrenia. The purpose of this study was to apply techniques of measuring posterior fossa structures from magnetic resonance imaging scans that have proven reliable in identifying structural abnormalities in other patient populations.Midsagittal areas of cerebellar vermis and its subsections (anterior vermis, lobules VI-VII, and lobules VIII-X), brainstem (pons, medulla, and midbrain), and fourth ventricle, as well as intracranial area and cortical area, were measured. Subjects included 36 schizophrenic patients and 51 normal comparison subjects. Groups were matched on age, sex, race, and family socioeconomic status.No significant group differences were detected for any posterior fossa structure. When corrected for intracranial area, fourth ventricle area was significantly larger in patients than in the comparison group. Fourth ventricle area was not, however, correlated with any measures of symptom severity.The size of posterior fossa structures is not abnormal in schizophrenia.
Abstract 14646: Quantity and Complexity of PVCs, Heart Rate and QRS duration Predict Abnormal Left Ventricular Function in Patients with Frequent PVCs Undergoing 24-Hour Ambulatory ECG Monitoring
Authors: Seth R Bender, Joseph J Marmora, Peter M Okin, Jim W Cheung
Journal: Circulation (2012)

Background: Frequent premature ventricular complexes (PVCs) have been associated with development of cardiomyopathy. Recent studies examining predictors of cardiomyopathy in pts with frequent PVCs ...
Abstract 3678: Protein Kinase C-zeta (PKCζ) Is A Novel Mediator Of Endothelial Dysfunction By Inhibiting The ERK5/ Kruppel-like Factor 2 (KLF2) Pathway
Authors: Patrizia Nigro, Chang Hoon Woo, Maria Antonietta Belisario, Carolyn McClain, Jun-ichi Abe, Bradford C Berk
Journal: Circulation (2008)

Background: Shear stress-induced activation of ERK5 and KLF2 leads to eNOS expression maintaining normal endothelial cell (EC) function. PKCζ has emerged as a pathologic mediator of EC dysfunction based on 1) a positive correlation between PKCζ activity and disturbed flow pattern; and 2) PKCζ activation is essential for TNFα stimulation of JNK, caspase-3 and EC apoptosis. Therefore we hypothesized that TNFα and its pathologic mediator ONOO − would inhibit ERK5 transcriptional activity and eNOS expression induced by flow. Results: TNFα and ONOO − significantly inhibited ERK5 transcriptional activity, KLF2 promoter activity, and eNOS expression induced by flow (shear stress = 12 dyn/cm2, 24 hrs). Both TNFαand ONOO − increased PKCζ activity. Transfection of wild type PKCζ (WT-PKCζ) and catalytic domain of PKCζ (CATζ) significantly inhibited ERK5 transcriptional activity (38±1.4% and 57±2.8% respectively; p&lt;0.01, p&lt;0.005). Also, transfection of PKCζ siRNA reversed TNFα-mediated inhibition of ERK5 transcriptional activity (control vs PKCz siRNA, 28±2.5% vs 9±0.3%, p&lt;0.05), suggesting a critical role for PKCζ in ERK5 transcriptional repression. Surprisingly, TNFα and ONOO − did not significantly decrease ERK5 phosphorylation, suggesting that inhibition occurred downstream of ERK5 phosphorylation. Previously we reported that ERK5-SUMOylation inhibited flow-mediated eNOS expression, but we could not detect increased ERK5-SUMOylation in WT-PKCζ or CATζ transfected cells. Importantly, we found that ONOO − significantly increased PKCζ-ERK5 interaction. PKCζ is known to contain a PB1 domain, a well studied protein-protein interaction domain. However, mutational analysis demonstrated that the ERK5 binding site in PKCζ was within the catalytic domain of PKCζ, not the PB1 domain. These data suggest that the PKCζ-ERK5 interaction likely inhibits ERK5 transcriptional activity by direct phosphorylation of ERK5 by PKCζ kinase. Conclusion: PKCζ is a novel mediator of TNFα and ONOO − induced endothelial dysfunction by inhibiting ERK5 transcriptional activity independent of kinase activity and ERK5-SUMOylation.
Abstract 17143: RASSF5, a New Mediator of Angiogenesis, Mediates Integrin Endocytosis in Endothelial Cells and Vessel Stability in vivo
Authors: Yosif Manavski, Guillaume Carmona, Sabrina Del Galdo, Thomas Wieland, Stefanie Dimmeler, Jens Kroll, Emmanouil Chavakis
Journal: Circulation (2011)

Integrins are critical mediators of angiogenesis. In our previous work, we identified the GTPase Rap1 as a mediator of integrin activation in endothelial cells (EC) and angiogenesis. RASSF5/RAPL is an effector protein of Rap1 promoting integrin activation and adhesion in lymphocytes. However, the role of RASSF5 for integrin regulation in EC and angiogenesis is unclear. Silencing of RASSF5 with siRNA significantly decreased angiogenic sprouting of HUVEC in a 3-dimensional spheroidal system (83 % inhibition) and blocked VEGF-induced invasion (68 % inhibition), while not inhibiting EC proliferation. Surprisingly, while silencing of Rap1 reduced HUVEC adhesion, silencing of RASSF5 unexpectedly significantly increased integrin-dependent adhesion suggesting distinct roles for RASSF5 and Rap1 in integrin regulation in EC. In line with these results, silencing of RASSF5 significantly increased surface expression of beta1-integrin as assessed by FACS, while not affecting total beta1-integrin protein levels in HUVEC. It is conceivable, that the enhanced surface expression of beta1-integrins upon silencing of RASSF5 is caused by a redistribution of the integrin from an intracellular pool to the cell surface. Therefore, we studied the role of RASSF5 for the endocytosis of beta1-integrins in HUVEC. Strikingly, silencing of RASSF5 blocked beta1-integrin endocytosis by 43 ± 6 %. Interestingly, silencing of RASSF5 preferentially reduced the internalization of activated (matrix-bound) alpha5beta1-integrins. Endogenous alpha5-integrin co-immunoprecipitated with overexpressed RASSF5. In addition, silencing of RASSF5 enhanced actin polymerization and Rac1 activity in EC. Strikingly, in vivo silencing of the RASSF5 homologue in the zebrafish embryo with morpholino led to hemorrhages in the newly formed vessels. In conclusion, our results demonstrate that RASSF5 is binding to the alpha5beta1-integrin and mediating integrin internalization and actin cytoskeleton reorganization in EC, thereby promoting angiogenic sprouting and migration. Our data identify a new angiogenic signaling pathway and shed light on the relevance of alpha5beta1-integrin endocytosis for angiogenic functions such as sprouting, migration and vessel stability.
Abstract 250: Over-expression of Human Arginase (ARG1) in Macrophages Reduces Atherosclerosis in LDL-receptor Deficient Mice
Authors: Daniel Teupser, Ivonne Haffner, Johannes Wilde, Ralph Burkhardt, Joachim Thiery
Journal: Circulation (2007)

Background: In previous work we have identified arginase I (ARG1) as a novel candidate gene of atherosclerosis resistance in macrophages (Teupser et al ATVB 2006). In macrophages, L-arginine can be metabolized by NO synthase and arginase to form NO and urea, respectively. Thus, high expression of ARG1 in macrophages (as observed in atherosclerosis resistant our rabbits) may be an effective mechanism of reducing macrophage NO-production and thus vascular inflammation. Methods and Results: To test the hypothesis that ARG1 exerts anti-atherogenic properties, we generated ARG1-transgenic mice, expressing human ARG1 under the control of a CMV promoter. In these animals, ARG1 was over-expressed in various tissues including bone-marrow-derived macrophages. Under basal conditions, expression of human ARG1 in macrophages of transgenic mice was significantly higher compared to endogenous murine ARG1 (27062±13652 vs. 176±81 copies ARG1/10 6 copies cyclophilin, respectively). To test the functionality of the human transgene, macrophages were incubated with lipopolysaccharide (1 μg/mL). After 6 hours of incubation, NO-release was significantly diminished in macrophages of transgenic mice, compared to non-transgenic controls (94±9 vs. 140±16 μmol/ng cell protein, respectively p = 0.03), indicating that hARG1 transgene expression influences NO synthesis by competing with iNOS for the common substrate L-arginine. To test the effect of the transgene on atherosclerosis susceptibility, bone marrow from ARG1-transgenic and non-transgenic animals were transplanted onto LDL-receptor deficient C57BL/6 recipients at 8 weeks of age. Animals were sacrified at 20 weeks of age and no significant differences in lipid and lipoprotein levels were noted. However, atherosclerosis of animals transplanted with transgenic bone marrow (n=16) was significantly reduced compared to controls (n=15) (75160±9914 vs. 121500±18410 μm 2 , p=0.03). Conclusion: Our data show for the first time that over-expression of human ARG1 in macrophages has direct anti-atherogenic properties by reducing NO-release in macrophages. We conclude that ARG1 might constitute an interesting novel target for the prevention of atherosclerosis.
Calreticulin Biosynthesis and Processing in Human Myeloid Cells: Demonstration of Signal Peptide Cleavage and N-Glycosylation
Authors: Gerene M. Denning, Kevin G. Leidal, Valerie A. Holst, Shankar S. Iyer, Doran W. Pearson, Joshua R. Clark, William M. Nauseef, Robert A. Clark
Journal: Blood (1997)
Abstract 15580: Use of Anti-Coagulant/Anti-Platelet Therapy for Atrial Fibrillation in the US Outpatient Settings: is it Guided by Appropriate Risk Stratification?
Authors: Sunil K Agarwal, Jawad Kiani, Ross Simipson, Samir Saba
Journal: Circulation (2011)

Background New oral anticoagulant agents are becoming increasingly available now. However, there is limited information on the recent use of anticoagulation and anti-platelet therapy for atrial fib...
Abstract 11018: Left Atrial Volume Index (LAVI) over Late Diastolic Mitral Annular Velocity (a') is a Powerful Predictor of Cardiac Death and Heart Failure in Patients with a First ST Elevation Acute Myocardial Infarction
Authors: Noriaki Iwahashi, Masami Kosuge, Mitsuaki Endo, Nobuhiko Maejima, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Toshiaki Ebina, Shinichi Sumita, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2010)

Background: Increased left atrial volume index (LAVI) is a powerful predictor of mortality after acute myocardial infarction (AMI). Recently, the late diastolic mitral annular velocity (a'), which ...
Abstract P157: Mechanical Cardiopulmonary Resuscitation (M-CPR) versus manual CPR according to pressure of end tidal Carbon Dioxide (PETCO2) during CPR in Out-of Hospital Cardiac Arrest (OHCA)
Authors: Christer Axelsson, Thomas Karlsson, Asa Axelsson, Johan Herlitz
Journal: Circulation (2009)

Background: Measuring pressure of end tidal Carbon dioxide (PETCO2) has in animal and human studies showed to be a practical non invasive method that correlates well with the pulmonary blood flow a...
Assault on the therapist
Authors: Roy M. Whitman, Beatrice B. Armao, Oran B. Dent
Journal: American Journal of Psychiatry (1976)

The authors conducted a questionnaire survey among psychotherapists in psychiatry, psychology and social work to determine how many patients posed a threat to others or to the therapist and how many actually assaulted the therapist. They found that 9.2% of all patients seen by 101 therapists in one year presented a threat to others, 1.9% posed a physical threat to the therapist, and .63% actually assaulted the therapist. The authors conclude that attacks on a therapist are infrequent but almost inevitable and suggest the development of techniques for coping with assaultive patients that therapists can use in crisis situations.
R-ICE Versus R-DHAP in Relapsed Patients with CD20 Diffuse Large B-Cell Lymphoma (DLBCL) Followed by Stem Cell Transplantation and Maintenance Treatment with Rituximab or Not: First Interim Analysis on 200 Patients. CORAL Study.
Authors: Christian Gisselbrecht, Norbert Schmitz, Nicolas Mounier, David Ma, Marek Trneny, Hans Hagberg, David C. Linch, Ofer Shpilberg, Nicolas Ketterer, Bertram Glass, Andre Bosly, Devinder Gill, Philippe Gaulard, Craig Moskowitz
Journal: Blood (2007)
Abstract 1612: L-4F Inhibits Platelet Aggregation and Prolongs Bleeding Time by Inhibiting the Formation of Arachidonic Acid Metabolites in Apo-E Null Mice
Authors: Georgette M Buga, Mohamad Navab, Satoshi Imaizumi, Srinivasa T Reddy, Babak Yetka, Greg Hough, GM Anantharamaiah, Alan M Fogelman
Journal: Circulation (2009)

Hyperlipidemia is associated with both increased plasma levels of oxidized lipids and platelet hyper-reactivity. Since L-4F, an apoA-I mimetic peptide, reduces plasma levels of oxidized lipids, we ...
Abstract 18345: Accumulation of Islet Amyloid Polypeptide Oligomers in the Heart in Type-2 Diabetes Alters Ca Cycling in Myocytes
Authors: Sanda Despa, Donald M Bers, Florin Despa
Journal: Circulation (2010)

Islet amyloid polypeptide (IAPP) toxic oligomers form within the secretory pathway of pancreatic β-cells and represent the primary toxic species of amyloids in type-2 diabetes mellitus. These toxic...