tbuckley/cabot-search huggingface dataset:
P2-12-18: A Prognostic Model Based on Node Status, Cathpesin-D and Ki-67 Predict the Outcome of Patients Failing To Achieve Pathological Complete Response after Anthracycline-Based Neoadjuvant Chemotherapy for Breast Cancer.
Authors: S Chen, C Chen, K Yu, Z Shao
Journal: Cancer Research (2011)

Abstract Background Aim of this study was to evaluate factors which could possibly affect the outcome of patients failing to achieve pathological complete response (pCR) after anthracycline-based neoadjuvant chemotherapy (NCT) for breast cancer, and built a prognostic model to predict disease free survival (DFS) and overall survival (OS). Material and Methods: We retrospectively collected data of 199 stage II-III breast cancer patients who had failed to achieve pathological complete response after neoadjuvant chemotherapy in Shanghai Cancer Hospital. The NCT regimens were NE (navelbine 25mg/m2, day 1, 8 and epirubicin 60mg/m2, day 1; every three weeks) or CEF (cyclophosphamide 600 mg/m2, day 1; epirubicin 60 mg/m2, day 1 and 5-fluorouracil 600 mg/m2, day 1; every three weeks) for a median treatment course of 3 cycles. To develop the prognostic model, variables at baseline(age, menopausal status, tumor size, node status, ER, PR, and HER-2) and at surgery(tumor size, grade, histotype, node status, vascular invasion, ER, PR, HER-2, Cathpesin-D, P53, Topo-IIα, Nm-23, Bcl-2, BAX, MDR, GSTn, PS2, P27, Cyclin D1 and Ki-67) were investigated. Multivariate Cox regression model and Kaplan-Meier method was used to build the model, and show the discrimination of DFS and OS in different risk groups. Results: By multivariate analysis, ≥4 lymph node metastasis (HR=1.9, P=0.009), Cath-D positive (HR=2.5, P=0.006), and Ki-67 index≥20% (HR=1.9, P=0.001) at surgery were independent predictors for lower DFS and OS rate among non-pCR responders. We built a prognostic scoring model on the basis of these variables, in which ≥4+ nodes, Cath-D + or Ki-67 index≥20% would contribute 1 point separately to the risk score. The 5-year DFS rates in low(0 point), intermediate-low(1 point), intermediate-high(2 points) and high risk groups(3 points) were 94%, 65%, 43%, and 28%, respectively (Log-rank teat p&amp;lt;0.001). The 5-year OS rates in these four groups were 94%, 84%, 66% and 34%, respectively (Log-rank test p&amp;lt;0.001). Conclusion: Post-NCT node status, Cathpesin-D and Ki-67 were used to develop a prognostic model which could simply discriminate patients with poor prognosis among non-pCR responders after anthracycline-based neoadjuvant chemotherapy, and might help to tailor further individualized treatment strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-18.
TCTAP A-065 To Evaluate Clinical Results of Repeat Drug-eluting Stent (DES) Implantation for DES Restenosis at Coronary Artery Lesions with High Degree Hinge Motion
Authors: Masatsugu Nakano, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Itou, Hiroshi Ishimori, Keisuke Hirano
Journal: Journal of the American College of Cardiology (2014)
Immunoreactivity of a 70 kD protein purified from Mycobacterium bovis Bacillus Calmette-Guerin by monoclonal antibody affinity chromatography.
Authors: W J Britton, L Hellqvist, A Basten, A S Inglis
Journal: The Journal of Experimental Medicine (1986)

The protein antigens from Mycobacterium bovis (BCG), M. tuberculosis, and M. leprae share a number of common determinants. We have used a murine mAb (L7) recognizing such a determinant on a protein of Mr 70,000 to purify this antigen from M. bovis sonicate by affinity chromatography. Enrichment of the protein in column eluates was confirmed by immunoblotting and in antigen inhibition assays. After radiolabelling with 125I, the protein could be immunoprecipitated with human lepromatous leprosy sera. Stimulation of peripheral blood mononuclear cells from BCG-vaccinated and naturally mantoux-positive individuals induced proliferation and IFN-gamma secretion, while intradermal injection of purified antigen into the same subjects resulted in a delayed-type hypersensitivity reaction. Thus, the 70,000 molecule carried epitopes capable of reacting with B cells, and eliciting a potentially protective T cell response. The first 15 N-terminal residues were sequenced using a gas-phase sequenator.
REPORT OF THE SURGICAL CLINICS,Held at the Western Pennsylvania Hospital, before the Students of the Western Pennsylvania Medical College,
Authors: J. B. MURDOCH
Journal: JAMA (1892)

[Reported by E. E. Wible, M.D., a member of the Graduating Class.]  ( Concluded from page 420. )  TREPHINING FOR INJURY TO THE HEAD.  Here is another very interesting case. This young man was found along the Alleghany Valley railroad track last night, in an unconscious condition, due to some injury of the head. When he arrived here in the hospital, he was not paralyzed in any of his muscles but vomiting, pupils were equal. This morning he is paralyzed on one side and convulsive on the other. The left side is paralyzed and the leg and arm of the right side he is constantly throwing and tossing about. The question is whether it is due to concussion or compression. When paralysis is present immediately, from the time of an accident to the head, it is due to depressed bone, when it comes on gradually sometime after an accident, it is due
Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus
Authors: Sujin Lee, Mei Zheng, Bumseok Kim, Barry T. Rouse
Journal: Journal of Clinical Investigation (2002)

In this report, we demonstrate that herpes simplex virus (HSV) infection of the cornea results in the upregulation of the matrix-degrading metalloproteinase enzyme MMP-9. This enzyme was shown to contribute to the neovascularization process that occurs in the corneal stroma in response to HSV infection. The likely source of MMP-9, at least initially after infection, was neutrophils that were signaled to invade the cornea soon after infection. Corneal infiltrating neutrophils were shown to express MMP-9, and preventing the neutrophil response with specific mAb diminished MMP-9 expression as well as the extent of angiogenesis. Further supporting a role for MMP-9 in HSV-induced corneal angiogenesis was the observation that inhibition of MMP-9 with the specific inhibitor TIMP-1 resulted in reduced angiogenesis. In addition, angiogenesis was diminished in ocularly infected MMP-9 knockout mice. Our results demonstrate that MMP-9 is involved in angiogenesis caused by HSV. Since angiogenesis appears to represent a vital step in the pathogenesis of herpetic stromal keratitis, these results indicate that targeting MMP-9 for inhibition should prove useful for the therapy of herpetic stromal keratitis.
Ian Macdonald Hill
Authors: Gareth Rees, Alison Hill
Journal: BMJ (2008)

After service in the Royal Air Force, Ian Macdonald Hill worked with Russell Brock at Guy’s at an exciting period in the development of surgical techniques. He was then appointed to Barts and Lewisham Hospitals. An excellent technical surgeon and fine clinician in both pulmonary and cardiac surgery, he performed a large number of closed mitral valvotomies. Always a popular teacher of medical …
Endothelial basement membrane laminin α5 selectively inhibits T lymphocyte extravasation into the brain
Authors: Chuan Wu, Fredrik Ivars, Per Anderson, Rupert Hallmann, Dietmar Vestweber, Per Nilsson, Horst Robenek, Karl Tryggvason, Jian Song, Eva Korpos, Karin Loser, Stefan Beissert, Elisabeth Georges-Labouesse, Lydia M Sorokin
Journal: Nature Medicine (2009)
Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial
Authors: J. W L Cals, C. C Butler, R. M Hopstaken, K. Hood, G.-J. Dinant
Journal: BMJ (2009)

<b>Objective</b> To assess the effect of general practitioner testing for C reactive protein (disease approach) and receiving training in enhanced communication skills (illness approach) on antibiotic prescribing for lower respiratory tract infection. <b>Design</b> Pragmatic, 2×2 factorial, cluster randomised controlled trial. <b>Setting</b> 20 general practices in the Netherlands. <b>Participants</b> 40 general practitioners from 20 practices recruited 431 patients with lower respiratory tract infection. <b>Main outcome measures</b> The primary outcome was antibiotic prescribing at the index consultation. Secondary outcomes were antibiotic prescribing during 28 days' follow-up, reconsultation, clinical recovery, and patients' satisfaction and enablement. <b>Interventions</b> General practitioners' use of C reactive protein point of care testing and training in enhanced communication skills separately and combined, and usual care. <b>Results</b> General practitioners in the C reactive protein test group prescribed antibiotics to 31% of patients compared with 53% in the no test group (P=0.02). General practitioners trained in enhanced communication skills prescribed antibiotics to 27% of patients compared with 54% in the no training group (P&lt;0.01). Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days' follow-up. Clinicians in the combined intervention group prescribed antibiotics to 23% of patients (interaction term was non-significant). Patients' recovery and satisfaction were similar in all study groups. <b>Conclusion</b> Both general practitioners' use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients' recovery and satisfaction with care. A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care. <b>Trial registration</b> Current Controlled Trials ISRCTN85154857.
Scleromyxoedema-like changes in four renal dialysis patients
Authors: V. Hubbard, A. Davenport, M. Jarmulowicz, M. Rustin
Journal: British Journal of Dermatology (2003)

We describe four renal dialysis patients from our hospital who, over a 6-month period, developed erythematous, thickened, indurated dermal plaques. The plaques were limited to the limbs and in three patients there were associated flexion contractures. The clinical features most resembled scleromyxoedema. All patients had previously received at least one renal transplant. Histopathology of the plaques showed features of scleromyxoedema in two patients, whereas the other two showed a different picture, more suggestive of a morphoea-like process. There are important differences between our patients and classical scleromyxoedema. All four patients had normal immunoglobulins and no paraprotein was detected. Almost all cases of classical scleromyxoedema are associated with an IgGlambda paraproteinaemia. We have not yet identified an underlying cause for this cluster of cases in our hospital. It is possible that the skin changes seen may have been precipitated by an environmental agent, such as in 'toxic oil syndrome' and vinyl chloride-induced scleroderma. We discuss the differences between our patients and those with scleromyxoedema, localized or generalized morphoea and environmentally induced scleroderma. We feel that our patients show a constellation of features similar, but not identical, to scleromyxoedema. There has been only one previous report of similar patients. We believe this to be a new and distinct phenomenon.
Ideology in the ascendant
Authors: F. Godlee
Journal: BMJ (2010)

Urbanization presents unique environmental challenges to human commensal species. The Afrotropical Anopheles gambiae complex contains a number of synanthropic mosquito species that are major vectors of malaria. To examine ongoing cryptic diversification within the complex, we performed reduced representation sequencing on 941 mosquitoes collected across four ecogeographic zones in Cameroon. We find evidence for clear subdivision within An. coluzzii and An. gambiae s.s. - the two most significant malaria vectors in the region. Importantly, in both species rural and urban populations of mosquitoes were genetically differentiated. Genome scans of cryptic subgroups reveal pervasive signatures of selection centered on genes involved in xenobiotic resistance. Notably, a selective sweep containing eight detoxification enzymes is unique to urban mosquitoes that exploit polluted breeding sites. Overall, our study reveals that anthropogenic environmental modification is driving population differentiation and local adaptation in African malaria mosquitoes with potentially significant consequences for malaria epidemiology.
Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats.
Authors: B P Sawaya, H Weihprecht, W R Campbell, J N Lorenz, R C Webb, J P Briggs, J Schnermann
Journal: Journal of Clinical Investigation (1991)

In anesthetized rats we tested the hypothesis that amphotericin B (AmB) reduces glomerular filtration rate (GFR) by activating the tubuloglomerular feedback (TGF) mechanism. Infusion of 1 mg/kg AmB over 50 min was followed by a reduction in kidney GFR (from 0.47 +/- 0.03 to 0.39 +/- 0.02 ml/min per 100 g body wt during the second hour after infusion; P less than 0.05) and by an increase in urine flow and urinary chloride excretion. Single-nephron GFR (SNGFR) measured in proximal (TGF interrupted) or distal tubules (TGF intact) decreased to a similar degree from 33.4 +/- 1.8 and 30.6 +/- 1.2 nl/min in the control period to 19.7 +/- 1.9 and 21.2 +/- 1.6 nl/min during the second hour after AmB infusion (P less than 0.05). Distal chloride concentrations and TGF responses to changes in loop of Henle flow rate were not significantly altered by AmB. AmB at 10(-5) M reduced the diameter of isolated perfused afferent arterioles from rabbit kidneys. In isometrically contracting rings of rabbit aorta and renal artery in vitro AmB produced endothelium-independent constriction, with half-maximal contraction (EC50) being achieved by 1.8 x 10(-6) and 2.6 x 10(-6) M in intact vessels and 1.3 x 10(-6) and 1.7 x 10(-6) M in endothelium-denuded vessels respectively. Tension development did not occur in Ca-free media or in the presence of Ca channel blockers. Pretreatment with ouabain or Bay K 8644 potentiated the effect of AmB. The vasoconstrictive effect of AmB was counteracted by aminophylline and atrial natriuretic peptide. We conclude that the AmB-induced reduction in GFR is not caused by TGF activation and that AmB has a direct vasoconstrictor effect that is probably initiated by depolarization-induced opening of Ca channels. This effect may be an important component of the nephrotoxic actions of AmB.
An Unpublished Case in the Practice of the great Piorry.
Authors: Henry Raymond Rogers
Journal: JAMA (1889)

<h3>To the Editor:</h3> —Piorry was in the full tide of his reputation in 1853. His demonstration of the value of percussion as a means of physical exploration had then placed his name high on the roll of honor in his profession. His skill in detecting pathological conditions and changes through this process was almost magical. It was my good fortune to be present on one occasion when he demonstrated his masterly powers in this field. At the Hospital La Charité, Paris, I found him one morning surrounded by physicians and students and engaged in examining a young girl of 15 or 18 years. The patient was lying in the prone position while her back, over the region of the kidneys, was covered with a surface of adhesive plaster. He was examining the right kidney. After percussion over a small area above the kidney he made a pencil mark upon the
In vivo efficacy of intravenous gammaglobulins in patients with lupus anticoagulant is not mediated by an anti‐idiotypic mechanism
Authors: Monica Galli, Sergio Cortelazzo, Tiziano Barbui
Journal: American Journal of Hematology (1991)

Abstract The authors have investigated the presence in commercially available intravenous gammaglobulins (IVlg) of anti‐idiotypic antibodies directed to Lupus Anticoagulant (LA). In vitro incubation of 4 LA plasmas with increasing concentrations of IVlg (from 0 to 39 mg/ml) resulted in a dose‐dependent inhibition of LA activity (the highest inhibitions ranged from 14.0 to 53.4%). Similar results were obtained when patients' plasma was substituted with total IgG (the highest inhibitions ranged from 43.0 to 55.0% and were obtained at IgG:IVIg molar ratios ranging from 1:15 to 1:50). Also the incubation of patients' F(ab's)2 with F(ab')2 from IVIg produced a similar dose‐dependent inhibition of LA activity. These data are suggestive of an in vitro idiotypic‐anti‐idiotypic interaction between LA and IVIg. However, when injected in patients with LA, IVIG do not seem to operate by this mechanism of action. In fact, reduction or disappearance of LA was only observed in 2 out of 4 patients; also the quick reappearance of LA activity was not consistent with the time course of anti‐idiotypic response. Finally, this effect was reached by half the IVIg concentrations necessary to produce an appreciable inhibitory effect on LA activity in vitro. Thus, it is concluded that, even if IVIg contain anti‐idiotypic antibodies reacting with LA, the clinical efficacy of IVIg treatment in patients with these autoantibodies should be attributed to other mechanisms.
Endoscopic Ultrasound-Guided Drainage of a Biloma: A Novel Approach
Authors: R. Ponnudurai, A. George, S. Sachithanandan, A. Abdullah, K. Ganesaligam, L. Sanker, I. Merican, S. Seewald, N. Soehendra
Journal: Endoscopy (2006)

A 42-year-old man with symptoms of cholecystitis underwent open cholecystectomy. The gallbladder was found to be distended with pus and the dilated cystic duct contained a stone. The common bile duct was not explored. He was referred to our hospital 30 days later with a 1-week history of fever and progressive jaundice, associated with pain and tenderness over the right upper quadrant of his abdomen. Computed tomography of his abdomen confirmed that there was a fluid collection in the gallbladder fossa (Figure [1]), with a mildly dilated common bile duct.
RNAi-mediated TCR Knockdown Prevents Autoimmunity in Mice Caused by Mixed TCR Dimers Following TCR Gene Transfer
Authors: Mario Bunse, Gavin M Bendle, Carsten Linnemann, Laura Bies, Stephan Schulz, Ton N Schumacher, Wolfgang Uckert
Journal: Molecular Therapy (2014)

Genetically modified T cells that express a transduced T cell receptor (TCR) α/β heterodimer in addition to their endogenous TCR are used in clinical studies to treat cancer. These cells express two TCR-α and two TCR-β chains that do not only compete for CD3 proteins but also form potentially self-reactive mixed TCR dimers, composed of endogenous and transferred chains. To overcome these deficits, we developed an RNAi-TCR replacement vector that simultaneously silences the endogenous TCR and expresses an RNAi-resistant TCR. Transduction of the virus-specific P14 TCR without RNAi resulted in unequal P14 TCR-α and -β chain surface levels, indicating heterodimerization with endogenous TCR chains. Such unequal expression was also observed following TCR gene optimization. Equal surface levels of the introduced TCR chains were however achieved by silencing the endogenous TCR. Importantly, all mice that received cells transduced with the native or optimized P14 TCR developed lethal TCR gene transfer-induced graft-versus-host-disease (TI-GVHD) due to formation of mixed TCR dimers. In contrast, TI-GVHD was almost completely prevented when using the RNAi-TCR replacement vector. Our data demonstrate that RNAi-assisted TCR replacement reduces the formation of mixed TCR dimers, and thereby significantly reduces the risk of TI-GVHD in TCR gene therapy.
Abstract IA08: Ataxia-telangiectasia: Broad implications from the study of a rare disease
Authors: Michael B. Kastan
Journal: Cancer Research (2014)

Abstract DNA damage signaling pathways are critical mediators of both tumor development and tumor responses to chemotherapy and radiation therapy. Significant progress has been made in recent years in elucidating the molecular controls of cellular responses to DNA damage in mammalian cells. Much of what we have learned about damage signaling pathways has come from the study of human diseases, particularly cancer predisposition syndromes. Ataxia-Telangiectasia (A-T) is a pleiotropic disorder with multiple phenotypic abnormalities, including progressive neurodegeneration, immunodeficiencies, cancer predisposition, insulin resistance, telangiectasia development, infertility, and extreme radiosensitivity. ATM, the gene mutated in A-T, is a central mediator of responses to DNA double strand breaks in cells. Once activated, ATM phosphorylates numerous substrates in the cell that modulate the cell's response to the DNA damage. Though ATM clearly plays a central role in mediating cellular responses to DNA breakage, some of the clinical abnormalities in A-T are difficult to attribute directly to alterations in DNA damage signaling. The broad-based symptoms in A-T and recently acquired data suggest that ATM may have roles that extend beyond its regulation of DNA damage responses. In particular, ATM appears to affect insulin signaling pathways and evidence has been generated supporting a direct role for ATM in mitochondrial function. These new insights suggest that Ataxia-Telangiectasia should be considered, at least in part, as a mitochondrial dysfunction disease and provide links between cancer-related DNA damage signaling and more general metabolic signaling pathways. Some of these new insights are also providing opportunities for considerations of novel ways to modulate ATM function for clinical benefit. Citation Format: Michael B. Kastan. Ataxia-telangiectasia: Broad implications from the study of a rare disease. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA08.
Acquired sideroblastic anaemia associated with penicillamine therapy for rheumatoid arthritis.
Authors: L Kandola, A J Swannell, A Hunter
Journal: Annals of the Rheumatic Diseases (1995)

Exposure to chemicals and systemic sclerosisOccupational exposure to various chemicals, including vinyl chloride, silica dust, epoxy resin, benzene, trichloroethylene, perchloro- ethylene, and other solvents, has been described as a potential provoking factor of systemic sclerosis (SSc) and scleroderma like disorders.'However, the precise contribution made by occupational environmental factors to the occurrence of scleroderma remains unknown.
Case 38-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case A fifty-nine-year-old man entered the hospital because of fever and weakness. During the six weeks before admission the patient experienced drenching night sweats, with daily elevations of the temperature to between 100 and 102°F. Increasing weakness and fatigue were present, and he lost 6 pounds in weight. Three weeks before admission he experienced two episodes of sudden, severe, sharp pain in the left upper quadrant of the abdomen and in the left shoulder that was accentuated by inspiration. An x-ray film of the chest taken at another hospital revealed an ill defined density in the lower lobe . . .
Impaired Antibody Response to<i>Haemophilus influenzae</i>Type b Polysaccharide and Low IgG2 and IgG4 Concentrations in Apache Children
Authors: George R. Siber, Mathuram Santosham, G. Raymond Reid, Claudette Thompson, Janné Almeido-Hill, Andreas Morell, Gerda deLange, Jeffrey K. Ketcham, Elaine H. Callahan
Journal: New England Journal of Medicine (1990)

Because Native American children are at much higher risk for invasive Haemophilus influenzae type b infection than white children, we compared the antibody responses to H. influenzae type b polysaccharide vaccine in healthy Apache and white children.