tbuckley/cabot-search huggingface dataset:
IMMUNOLOGICAL RELEASE OF HISTAMINE AND SLOW REACTING SUBSTANCE OF ANAPHYLAXIS FROM HUMAN LUNG
Authors: Michael Kaliner, Robert P. Orange, K. Frank Austen
Journal: The Journal of Experimental Medicine (1972)

The immunologic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung tissue can be enhanced by stimulation with either alpha adrenergic agents (phenylephrine or norepinephrine in the presence of propranolol) or cholinergic agents (acetylcholine or Carbachol). The finding that atropine prevents cholinergic but not comparable alpha adrenergic enhancement is consistent with the view that cholinergic and alpha adrenergic agonists interact with separate receptor sites on the target cells involved in the immunologic release of chemical mediators. The consistent qualitative relationship between the antigen-induced release of mediators and the level of cyclic adenosine monophosphate (cyclic AMP) as measured by the isolation of 14C-labeled cyclic AMP after incorporation of adenine-14C into the tissues or by the cyclic AMP binding protein assay suggests that changes in the level of this cyclic nucleotide mediate adrenergic modulation of the release of histamine and SRS-A. The addition of 8-bromo-cyclic guanosine monophosphate (cyclic GMP) produces an enhancement of the immunologic release of mediators while dibutyryl cyclic AMP is inhibitory. As cholinergic-induced enhancement was not associated with a measurable change in the levels of cyclic AMP, the possibility is suggested that cyclic GMP may be the intracellular mediator of cholinergic-induced enhancement of the immunologic release of histamine and SRS-A.
Severe spinal injuries in alpine skiing and snowboarding: a 6-year review of a tertiary trauma centre for the Bernese Alps ski resorts, Switzerland
Authors: T Franz, R M Hasler, L Benneker, H Zimmermann, K A Siebenrock, A K Exadaktylos
Journal: British Journal of Sports Medicine (2007)

Objective: To analyse the epidemiological data, injury pattern, clinical features and mechanisms of severe spinal injuries related to alpine skiing and snowboarding. Study design: A six-year review of all adult patients with severe spinal injuries sustained from alpine skiing or snowboarding. Setting: Tertiary trauma centre in Bern, Switzerland. Patients and methods: All adult patients (over 16 years of age) admitted to a tertiary trauma centre from 1 July 2000, through 30 June 2006, were reviewed using a computerised database. From these records, a total of 728 patients injured from snow sports were identified. Severe spinal injuries (defined as spinal fractures, subluxations, dislocations or concomitant spinal cord injuries) were found in 73 patients (17 female, 56 male). The clinical features of these patients were reviewed with respect to epidemiological factors, mechanism of injury, fracture pattern, and neurological status. Results: The majority of severe spinal injuries (n = 63) were related to skiing. Fatal central-nervous injuries and transient or persistent neurological symptoms occurred in 28 patients (23 skiers, 5 snowboarders). None of the snowboarders suffered from persistent neurological sequelae. Snowboarders with severe spinal injuries (n = 10) were all male (p&lt;0.05), and were significantly younger than skiers (p&lt;0.001). The most commonly affected site was the lumbar spine. However, 39 patients (53.4%) suffered from injury pattern at two or more levels. Conclusions: With advances in technology and slope maintenance, skiers and snowboarders progress to higher skill levels and faster speeds more rapidly than ever before. Great efforts have been focused on reducing extremity injuries in snow sports, but until recently very little attention has been given to spinal injury prevention on the slopes. Suggestions for injury prevention include the use of spine protectors, participation on appropriate runs for ability level, proper fit and adjustment of equipment, and taking lessons with the goal of increasing ability and learning hill etiquette.
When Your Favorite Patient Relapses: Physician Grief and Well-Being in the Practice of Oncology
Authors: Tait Shanafelt, Alex Adjei, Frank L. Meyskens
Journal: Journal of Clinical Oncology (2003)

Article Tools ART OF ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.06.075 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12829683 When Your Favorite Patient Relapses: Physician Grief and Well-Being in the Practice of Oncology Tait ShanafeltxTait ShanafeltSearch for articles by this author , Alex AdjeixAlex AdjeiSearch for articles by this author , Frank L. MeyskensxFrank L. MeyskensSearch for articles by this author Show More From the Department of Oncology, Mayo Clinic, Rochester, MN; and Department of Medicine and Biological Chemistry, University of California at Irvine, Irvine, CA. https://doi.org/10.1200/JCO.2003.06.075 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Reactivity of Vascular Smooth Muscle in Hypertensive Rats
Authors: EDWIN T. HOLLOWAY, DAVID F. BOHR
Journal: Circulation Research (1973)

The reactivity of vascular smooth muscle in helical strips from femoral arteries of normotensive, spontaneously hypertensive, renal hypertensive, and deoxycorticosterone acetate-- (DCA-) hypertensive rats was studied. Spontaneous rhythmic contractions occurred in 25 of the 30 strips from the three groups of hypertensive rats and in only 2 of the 10 strips from normotensive rats. Strips from renal and DCA hypertensive rats had lower thresholds to epinephrine and potassium chloride (KCl) than did strips from spontaneously hypertensive and normotensive rats. Lanthanum (2.5 mM) caused contraction of all 10 strips from spontaneously hypertensive rats but failed to cause contraction of any strip from the other three groups of rats. Strontium (5 mM) caused contraction in 8 of 10 strips from spontaneously hypertensive rats but caused contraction in only 7 of the 30 strips from the other three groups. The optimal calcium concentration for tension development in response to a KCl stimulus was approximately twice as high for strips from hypertensive rats as it was for strips from normotensive rats. Strips from DCA-hypertensive rats showed less tachyphylaxis to angiotensin II than did strips from the other three groups of rats. These results quantify our earlier observation that the reactivity of vascular smooth muscle from hypertensive rats is importantly different from that of normotensive rats. In addition, the study delineates individuality in vascular smooth muscle reactivity in different types of experimental hypertension. The results suggest that the cell membrane of the vascular smooth muscle in the hypertensive rat is more labile than that in the normal rat.
VEGF targeting by active immunisation improves joint inflammation and destruction in a murine model of rheumatoid arthritis
Authors: E. Assier, L. Semerano, L. Delavallee, D. Damotte, G. Grouard-Vogel, E. Bernier, D. Zagury, N. Bessis, M. C. Boissier
Journal: Annals of the Rheumatic Diseases (2010)

Cytokines play a key role in the development of rheumatoid arthritis (RA), allowing hypertrophy of the pannus by neovascularisation, articular inflammation and destruction. We recently demonstrated in experimental models the efficacy of vaccination against cytokines, using a heterocomplex of keyhole limpet hemocyanin (KLH) and human tumour necrosis factor (TNF), called TNF kinoid (K). Vascular endothelial growth factor (VEGF) is a …
Functional abdominal pain, psychiatric illness, and life events.
Authors: F Creed, T Craig, R Farmer
Journal: Gut (1988)

Patients undergoing appendicectomy, attending a gastroenterology clinic or admitted to hospital after self-poisoning have been examined using the same reliable measures to establish whether life events and psychiatric illness preceded abdominal pain. Life events involving threat were experienced more commonly by those with organic and functional abdominal illness, compared with community comparison subjects. The greatest difference was with severe events, especially those involving the break-up of close relationships, which preceded the development of functional abdominal pain as often as they occurred before self-poisoning, and significantly more frequently than before the onset of organic gastrointestinal illness. Abdominal pain of recent onset, for which no organic cause is found, is often preceded by environmental stress, whether it presents to the surgeon or the physician. Those presenting in the clinic were older than those undergoing appendicectomy and had experienced more long lasting interpersonal difficulties. Many had psychiatric illness, but for the remainder the stress might either have caused colonic pain directly or led to consultation for abdominal pains that had not previously presented to a gastroenterologist.
Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death.
Authors: N Zamzami, P Marchetti, M Castedo, D Decaudin, A Macho, T Hirsch, S A Susin, P X Petit, B Mignotte, G Kroemer
Journal: The Journal of Experimental Medicine (1995)

Programmed cell death (PCD) is a physiological process commonly defined by alterations in nuclear morphology (apoptosis) and/or characteristic stepwise degradation of chromosomal DNA occurring before cytolysis. However, determined characteristics of PCD such as loss in mitochondrial reductase activity or cytolysis can be induced in enucleated cells, indicating cytoplasmic PCD control. Here we report a sequential disregulation of mitochondrial function that precedes cell shrinkage and nuclear fragmentation. A first cyclosporin A-inhibitable step of ongoing PCD is characterized by a reduction of mitochondrial transmembrane potential, as determined by specific fluorochromes (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine++ + iodide; 3,3'dihexyloxacarbocyanine iodide). Cytofluorometrically purified cells with reduced mitochondrial transmembrane potential are initially incapable of oxidizing hydroethidine (HE) into ethidium. Upon short-term in vitro culture, such cells acquire the capacity of HE oxidation, thus revealing a second step of PCD marked by mitochondrial generation of reactive oxygen species (ROS). This step can be selectively inhibited by rotenone and ruthenium red yet is not affected by cyclosporin A. Finally, cells reduce their volume, a step that is delayed by radical scavengers, indicating the implication of ROS in the apoptotic process. This sequence of alterations accompanying early PCD is found in very different models of apoptosis induction: glucocorticoid-induced death of lymphocytes, activation-induced PCD of T cell hybridomas, and tumor necrosis factor-induced death of U937 cells. Transfection with the antiapoptotic protooncogene Bcl-2 simultaneously inhibits mitochondrial alterations and apoptotic cell death triggered by steroids or ceramide. In vivo injection of fluorochromes such as 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide; 3,3'dihexyloxacarbocyanine iodide; or HE allows for the detection of cells that are programmed for death but still lack nuclear DNA fragmentation. In particular, assessment of mitochondrial ROS generation provides an accurate picture of PCD-mediated lymphocyte depletion. In conclusion, alterations of mitochondrial function constitute an important feature of early PCD.
Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial
Authors: Cyrille Hulin, Thierry Facon, Philippe Rodon, Brigitte Pegourie, Lotfi Benboubker, Chantal Doyen, Mamoun Dib, Gaelle Guillerm, Bruno Salles, Jean-Paul Eschard, Pascal Lenain, Philippe Casassus, Isabelle Azaïs, Olivier Decaux, Laurent Garderet, Claire Mathiot, Jean Fontan, Ingrid Lafon, Jean Marc Virion, Philippe Moreau
Journal: Journal of Clinical Oncology (2009)

Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma.Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival.After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003).This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.
Dawn Phenomenon and Somogyi Effect in IDDM
Authors: Judith M Stephenson, Guntram Schernthaner
Journal: Diabetes Care (1989)

We examined the clinical relevance of a rise in fasting blood glucose (BG) between 0300 and 0600 in 97 patients with insulin-dependent diabetes mellitus (IDDM) receiving sequentially conventional (CT) and basal-bolus (BBIT) insulin therapies and assessed the impact of one potential causal factor, i.e., posthypoglycemic hyperglycemia, with 231 BG profiles (97 during CT, 134 during BBIT) in which BG was measured every 3 h over a 24-h period. A rise in BG between 0300 and 0600 occurred in 157 of 231 (68%) profiles. The mean magnitude of this rise was 56 ±39 mg/dl and was lower (P &amp;lt; .05) during BBIT (48 ± 35 mg/dl, n = 97) than CT (62±43 mg/dl, n = 97). A dawn rise (between 0300 and 0600) &amp;gt;50 mg/dl occurred in 40 of 97 (41%) profiles during CT and 26 of 97 (27%) during BBIT (P &amp;lt; .05). When all profiles were grouped according to the magnitude of this rise in BG, the mean daytime BG (from 0900 to 1800) was higher (P &amp;lt; .05) after an 0300–0600 BG rise &amp;gt;50 mg/dl compared with groups of profiles showing either a fall in BG or a rise &amp;lt;50 mg/dl; a rise in BG between 0300 and 0600 correlated (r = .38, P &amp;lt; .0001) with the subsequent mean daytime BG. Nocturnal hypoglycemia (BG &amp;lt;60 mg/dl) recorded at 2400 and/or 0300 occurred in 57 of 231 (25%) profiles. After nocturnal hypoglycemia, the highest BG recorded before breakfast was only 215 mg/dl, and the mean BG at 0600 was considerably lower (P &amp;lt; .0001) in profiles showing at least one episode of nocturnal hypoglycemia (116 ± 45 mg/dl, n = 57) compared with all profiles in which no nocturnal hypoglycemia was detected (174 ± 85 mg/dl, n = 174). In addition, postbreakfast BG levels at 0900 were lower (P &amp;lt; .0001) after nocturnal hypoglycemia (171 ± 87 mg/dl, n = 57) than when no nocturnal hypoglycemia was detected (211 ± 91 mg/dl, n = 174). We conclude that a dawn rise in BG commonly occurs in IDDM patients receiving either CT or BBIT. A dawn BG rise &amp;gt;50 mg/dl may lead to significant exacerbation of daytime hyperglycemia. Nocturnal hypoglycemia does not contribute to morning hyperglycemia, but conversion from CT to BBIT can achieve a modest reduction in the frequency and magnitude of an early-morning rise in BG.
Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers.
Authors: S Sjögren, M Inganäs, A Lindgren, L Holmberg, J Bergh
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the prognostic and predictive value of c-erbB-2 overexpression in breast cancer in relation to other prognostic markers. PATIENTS AND METHODS Paraffin-embedded tumors from 315 consecutive primary breast cancer patients were screened for c-erbB-2 protein (p185) overexpression by immunohistochemistry using the monoclonal antibody CB11. RESULTS c-erbB-2 protein overexpression was detected in 19% of tumors and was associated with shorter 5-year overall survival (OAS) rate compared with c-erbB-2-negative cases in the total patient material (58% and 77%, respectively; P = .004) and in the 96 node-positive patients (31% and 61%, respectively; P = .02), but not in node-negative patients. For 47 node-positive patients treated with adjuvant tamoxifen and radiotherapy, the 5-year OAS was 13% for c-erbB-2 overexpression and 75% for c-erbB-2-negative patients (P = .00004). The frequency of c-erbB-2 overexpression decreased with age at diagnosis. The prognostic value of c-erbB-2 on OAS was independent of age, node status, tumor size, histopathologic grade, hormone receptor status, S phase, p53 status, and adjuvant treatment. c-erbB-2 status added prognostic information to p53-negative and low S-phase cases, but not to p53-positive and high S-phase cases. Correspondingly, these only added information to c-erbB-2-negative cases. CONCLUSION c-erbB-2 protein overexpression may have a predictive value with regard to adjuvant therapy in node-positive patients, for whom adjuvant tamoxifen with radiotherapy appears insufficient in the presence of c-erbB-2 overexpression. Combination of conventional and newer tumor markers may identify patients with a worse prognosis within groups with a generally favorable prognosis.
QTc: how long is too long?
Authors: J N Johnson, M J Ackerman
Journal: British Journal of Sports Medicine (2009)

Congenital long QT syndrome (LQTS) affects an estimated 1 in 2500 people and typically presents with syncope, seizures or sudden death. Whereas someone exhibiting marked prolongation of the QT interval with QTc exceeding 500 ms who was just externally defibrillated from torsades de pointes while swimming poses negligible diagnostic challenge as to the unequivocal probability of LQTS, the certainty is considerably less for the otherwise asymptomatic person who happens to host a QTc value coined “borderline” (QTc ⩾440 ms). Although a normal QT interval imparts a much lower risk of life-threatening events, it does not preclude a patient from nevertheless harbouring a potentially lethal LQTS-causing genetic mutation. Indeed, genetic testing exerts significant diagnostic, prognostic and therapeutic implications. However, the 12-lead ECG remains the universal initial diagnostic test in the evaluation of LQTS and is subject to miscalculation, misinterpretation and mishandling. This review discusses the components of accurate QTc measurement and diagnosis, re-examines what is known about factors affecting QT interval measurement, and clarifies current recommendations regarding diagnosis of so-called “borderline” QT interval prolongation. The current guideline recommendations for the athlete with LQTS are also summarised.
Postprandial serum bile acids in healthy man. Evidence for differences in absorptive pattern between individual bile acids.
Authors: B Angelin, I Bjorkhem
Journal: Gut (1977)

The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) before and after a standardised meal were determined in five healthy female subjects using a highly specific and accurate gas chromatographic-mass spectrometric technique. The C level rose significantly 60 minutes after the meal, reached a peak after 90 minutes, and had returned to the original level after 150 minutes. In contrast, the serum concentrations of CD and D displayed a significant rise by 30 minutes, reached a peak after 90 minutes, but had not returned to fasting levels after 150 minutes. The serum bile acid responses after a meal suggest that there is considerable absorption of dihydroxy bile acids in the proximal small intestine in man.
Alterations in collagen production in mixed mononuclear leukocyte-fibroblast cultures.
Authors: M S Hibbs, A E Postlethwaite, C L Mainardi, J M Seyer, A H Kang
Journal: The Journal of Experimental Medicine (1983)

The cell-cell interactions between fibroblasts and mononuclear leukocytes (MNL) which promote alterations in collagen accumulation were examined using a system of co-culture of human fibroblasts and peripheral blood MNL. The stimulation of collagen production was optimal after 48 h of co-culture and the increase in collagen correlated directly with the number of MNL added. The enhancement of collagen production was seen in both autologous and allogeneic co-cultures. Stimulation of non-collagenous protein was also noted. Co-culture supernatants contained soluble substances that were capable of stimulating collagen production, although they stimulated collagen production to a lesser degree than direct co-culture. Fractionation of these supernatants on Sephadex G-200 revealed a predominant area of stimulatory activity at 160,000 mol wt. Lesser areas of activity were noted at molecular weights of 80,000 and 25,000. Determination of the types of collagen produced by fibroblasts during co-culture with MNL showed that the ratio of type I:III collagen was decreased. These alterations in both the quantitative and qualitative accumulation of collagen mimic the changes often seen in wound healing and early inflammation suggesting that cellular interactions between fibroblasts and MNL may be important in the modulation of collagen production in normal and pathologic states.
The ‘Quality and Outcomes Framework’: improving care, but are all patients benefiting?
Authors: Elizabeth Koshy, Christopher Millett
Journal: Journal of the Royal Society of Medicine (2008)

The Quality and Outcomes Framework (QOF), introduced as part of the General Practitioner contract in 2004, has been described as the boldest shift towards pay for performance in any health care system.1 Around one quarter of general practice income is now derived through the achievement of quality targets in managing chronic diseases – such as diabetes and coronary heart disease – and risk factors – such as hypertension – through QOF. Early evidence suggests that this policy has resulted in a step-change in quality for some conditions such as asthma and diabetes but not for coronary heart disease.2
Advances in the diagnosis and management of chronic pulmonary aspiration in children
Authors: R. P. Boesch, C. Daines, J. P. Willging, A. Kaul, A. P. Cohen, R. E. Wood, R. S. Amin
Journal: European Respiratory Journal (2006)

Chronic pulmonary aspiration (CPA) in children is an important cause of recurrent pneumonia, progressive lung injury, respiratory disability and death. It is sporadic, intermittent and variable, and often occurs in children with complicated underlying medical conditions and syndromes that produce symptoms indistinguishable from CPA. For most types of aspiration there is no gold-standard diagnostic test. The diagnosis of CPA is currently made clinically with some supporting diagnostic evaluations, but often not until significant lung injury has been sustained. Despite multiple diagnostic techniques, the diagnosis or exclusion of CPA in children is challenging. This is of particular concern given the outcome of unrecognised progressive lung injury and the invasiveness of definitive therapies. Although new techniques have been introduced since the 1990s and significant advances in the understanding of dysphagia and gastro-oesophageal reflux have been made, characterisation of the aspirating child remains elusive.