tbuckley/cabot-search huggingface dataset:
P1-07-05: HER2 Status Resolution in FISH and IHC “Double Equivocal” Breast Carcinomas by Quantitative Real-Time PCR.
Authors: BP Portier, Z Wang, E Downs-Kelly, GT Budd, C Lanigan, RR Tubbs
Journal: Cancer Research (2011)

Abstract Background: Clinical testing for HER2 amplification/over-expression is performed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) as outlined by the ASCO/CAP guidelines. Although these guidelines standardize testing and reporting, in a subset of patients, HER2 is equivocal by both IHC and FISH (“Double Equivocal”). These double equivocal patients represent a clinically problematic sub-group that currently lack standardized management guidelines. In this study, we utilize Quantitative Real-Time PCR (Q-RT-PCR) to resolve HER2 status in invasive breast cancer cases that could not be resolved via IHC and FISH testing. Material and Methods: FISH for HER2 was performed on 2259 invasive breast carcinomas from 1/2008 to 12/2010. In accordance with ASCO/CAP, all equivocal HER2 FISH cases were reflex tested by IHC. In double equivocal cases, RNA extraction was performed following macro-dissection using High Pure RNA Paraffin Kit (Roche Applied Biosciences, Indianapolis, IN). Q-RT-PCR was carried out using TaqMan® RNA-to-CT™ 1-Step Kit with primers and probes for HER2, B2M, and GAPDH (Applied Biosystems, Foster City, CA). Q-RT-PCR results were expressed as the relative quantification of HER2 vs. two control genes, all normalized against calibrator RNA from the MCF7 cell line. Cut off for Q-RT-PCR HER2 overexpression was set using ROC curve analysis (MedCalc, Belgium). Results: In our cohort of 2259 patients, 124 (5.5%) had an equivocal HER2 result by primary FISH testing. Reflex HER2 testing by IHC was unable to resolve the HER2 status in 35 (1.5%) patients. Detection of HER2 overexpression by Q-RT-PCR was validated using 50 FISH confirmed amplified and 50 non-amplified cases. Q-RT-PCR performed on these 2 control populations generated two non-overlapping populations and ROC curve analysis using a cut off value of 7.0 showed 100% sensitivity and specificity in detection of HER2 overexpression. Application of Q-RT-PCR in the double equivocal sub-group resulted in resolution of HER2 status in all cases, 8 HER2 positive (test value ranging from 7.12 - 15.37) and 14 HER2 negative (test value ranging from 1.05 - 6.92). Conclusion: Application of Q-RT-PCR for HER2 represents a viable approach to resolve HER2 status in cases that fail classification by both FISH and IHC. Q-RT-PCR combines the precision and high sensitivity of real-time PCR with the morphological specificity of histological evaluation and ultimately allows definitive HER2 classification at the time of initial diagnosis. This knowledge of HER2 status at the time of diagnosis allows for comprehensive neoadjuvant treatment although, additional studies correlating response to anti-HER2 therapy and HER2 status by Q-RT-PCR are warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-05.
Accurate Diagnosis of Renal Transplant Rejection by lndium-111 Platelet Imaging Despite Postoperative Cyclosporin Therapy
Authors: B DAVID COLLIER, MARK B. ADAMS, H MYRON KAUFFMAN, LISAANN TREMBATH, RAYMOND G. HOFFMANN, PATRICIA L. TISDALE, SHYAM A. RAO, ROBERT S. HELLMAN, ALI T. ISITMAN
Journal: Clinical Nuclear Medicine (1988)

Previous reports indicate that in-111 platelet scintigraphy (IPS) is a reliable test for the early diagnosis of acute post-operative renal transplant rejection (TR). However, the recent introduction of cyclosporin for post-transplantation immunosuppression requires that the diagnostic efficacy of IPS once again be established. Therefore, a prospective IPS study of 73 post-operative renal transplant recipients was conducted. Fourty-nine patients received cyclosporin and 24 patients did not receive this drug. Between these two patient groups, there were no significant differences in the diagnostic sensitivities (0.86 vs 0.80) and specificities (0.93 vs 0.84) with which TR was identified. We conclude that during the first two weeks following renal transplantation the cyclosporin treatment regimen used at our institution does not limit the reliability of IPS as a test for TR.
Activation of gene expression by metal-responsive signal transduction pathways.
Authors: Timothy K Adams, Nurten Saydam, Florian Steiner, Walter Schaffner, Jonathan H Freedman
Journal: Environmental Health Perspectives (2002)

Metallothioneins are small, cysteine-rich, metal-binding proteins that play important roles in maintaining intracellular metal homeostasis and in transition metal detoxification. MTF-1 (metal transcription factor-1) plays a central role in regulating the metal-inducible, transcriptional activation of metallothionein. Here we report that the phosphorylation of MTF-1 plays a critical role in the activation of MTF-1/metal-responsive element-mediated transcription. Inhibitor studies indicate that signal transduction cascades, including those mediated by protein kinase C, tyrosine kinase, and casein kinase II, are essential for zinc- and cadmium-inducible transcription. In addition, calcium signaling is also involved in regulating transcription. In contrast, cAMP-dependent protein kinase may not be directly involved in the metal response. Contrary to what has been reported for other transcription factors, the inhibition of transcriptional activation does not impair the binding of MTF-1 to DNA, suggesting that phosphorylation is not regulating DNA binding. Elevated phosphorylation of MTF-1 is observed under conditions of protein kinase C inhibition, suggesting that dephosphorylation of this transcription factor mediates its activation.
Private patients are more likely to have a caesarean section, finds study
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Pregnant women who opt for private medical care are more than twice as likely as those who use public health services to have a planned caesarean section, a study has found.

For the study researchers analysed deliveries among 30 000 women with singleton pregnancies who gave birth in a large urban maternity hospital in Ireland between January 2008 and July 2011. Of these women 24 574 were publicly funded and 5479 were private patients.

Irish hospitals have offered both private (20% …
Orificial tuberculosis: detection by polymerase chain reaction
Authors: F. NCHBAR, V. CASSEN, T. NCHBAR, M. MURER, C.G. SCHIRREN, K. DGITZ
Journal: British Journal of Dermatology (1996)

Orificial tuberculosis (OT) is a rare manifestation of cutaneous tuberculosis in immunocompromised individuals. Due to its variable clinical features, the diagnosis may be missed at the onset of the disease. We report a 53‐year‐old patient who had OT and miliary spread of Mycobacterium tuberculosis to the lungs, liver, bones and skin. The diagnosis was established by polymerase chain reaction (PCR) amplification of a Mycobacterium‐specific gene segment, and confirmed by culture. PCR allows the detection of mycobacterial DNA within a few days, whereas culture takes many weeks. PCR may improve the accurate diagnosis of skin tuberculosis and allow early treatment.
Orthoxine in Bronchial Asthma
Authors: Irving W. Schiller, Francis C. Lowell, William Franklin, Clarence Denton
Journal: New England Journal of Medicine (1949)

SINCE the elucidation by Chen and Schmidt1 (1923) of the chemical structure and the pharmacologic effects of ephedrine, this drug has ranked with epinephrine as one of the most valuable medications for the treatment of bronchial asthma. Although less active as a bronchodilator than epinephrine, ephedrine is effective, and its action is prolonged. However, undesirable effects such as nervousness, tremulousness, sleeplessness, vertigo, sweating, anorexia, nausea and palpitation often interfere with the use of the drug or require the additional administration of sedatives. In the last few years, therefore, attempts have been made to produce sympathomimetic compounds with less effect on . . .
Urinary Tract Infection
Authors: P. C. C. Brown, M. C. Donaghy, P. H. Dootson, D. M. MacLaren, D. H. M. Titcombe
Journal: BMJ (1968)

n UTI is an extremely common medical problem. n Many infections resolve spontaneously, but may progress to renal impairment/sepsis. n UTI implies causation by gram negative gut flora of the group Enterobacteraciae. Rarely, UTI can result from virus, fungus, TB, staph etc. n Diagnosis of UTI is the exclusion of infections which only involve the urethra, such as gonococcal urethritis or the acute urethral syndrome
A SCARLATINOID INFECTION DUE TO STREPTOCOCCUS VIRIDANS
Authors: Edward Steinfield
Journal: JAMA (1926)

During the winter of 1925-1926 there was noted with considerable frequency an acute infection due presumably to a<i>Streptococcus viridans</i>which was uniformly recovered from the throat and inflammatory exudates. The occurrence of a cutaneous eruption and a predilection to produce hemorrhagic nephritis were the causes of some confusion in differentiating this syndrome from true scarlet fever due to the hemolytic streptococcus. All ages were affected and in many instances most of the members of the same household. The onset was sudden and resembled grip or influenza, with fever of from 101 to 103 F., intense headache, nausea and vomiting. Herpes was absent. The throat was markedly injected, the pulse was rapid out of proportion to the temperature; there were no pulmonary signs throughout the course. A moderate leukocytosis was the rule. In from twenty-four to forty-eight hours an indefinite exanthem appeared over the trunk and to a
Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition
Authors: Petra S. Bachmann, Rocco G. Piazza, Mary E. Janes, Nicholas C. Wong, Carwyn Davies, Angela Mogavero, Vivek A. Bhadri, Barbara Szymanska, Greta Geninson, Vera Magistroni, Giovanni Cazzaniga, Andrea Biondi, Diego Miranda-Saavedra, Berthold Göttgens, Richard Saffery, Jeffrey M. Craig, Glenn M. Marshall, Carlo Gambacorti-Passerini, John E. Pimanda, Richard B. Lock
Journal: Blood (2010)
PROGNOSTIC VALUE OF MICROVASCULAR OBSTRUCTION AND INFARCT SIZE MEASURED BY CARDIAC MAGNETIC RESONANCE IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: A META-ANALYSIS OF INDIVIDUAL PATIENT DATA
Authors: Matthijs van Kranenburg, Michael Magro, Suzanne de Waha, Holger Thiele, Vicente Bodi Peris, Alexandre Cochet, Gert Klug, Edwin Wu, Dan Atar, Peter Bernhardt, Ronak Delewi, Eric Boersma, Felix Zijlstra, Robert-Jan van Geuns
Journal: Journal of the American College of Cardiology (2013)
Breast Cancer Metastasis: Challenges and Opportunities
Authors: Jing Lu, Patricia S. Steeg, Janet E. Price, Savitri Krishnamurthy, Sendurai A. Mani, James Reuben, Massimo Cristofanilli, Gabriela Dontu, Luc Bidaut, Vicente Valero, Gabriel N. Hortobagyi, Dihua Yu
Journal: Cancer Research (2009)

Despite exciting progress in the understanding of breast cancer development and progression, and in the development of novel therapeutic strategies, breast cancer remains the second leading cause of cancer-related death in women, with a yearly toll of more than 40,000 deaths in the United States
DEVELOPMENT OF TRUE SARCOMA IN A CASE OF MULTIPLE IDIOPATHIC PIGMENT SO-CALLED SARCOMA (KAPOSI)
Authors: J. H. SEQUEIRA, R. T. BRAIN
Journal: British Journal of Dermatology (1926)

Journal Article DEVELOPMENT OF TRUE SARCOMA IN A CASE OF MULTIPLE IDIOPATHIC PIGMENT SO‐CALLED SARCOMA (KAPOSI) Get access J. H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S., J. H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. Search for other works by this author on: Oxford Academic Google Scholar R. T. BRAIN, M.B., B.S., M.R.C.P. R. T. BRAIN, M.B., B.S., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 38, Issue 12, 1 December 1926, Pages 501–504, https://doi.org/10.1111/j.1365-2133.1926.tb10010.x Published: 01 December 1926
Family trends in psychotropic and antibiotic prescribing in general practice.
Authors: J G Howie, A R Bigg
Journal: BMJ (1980)

A ten-year retrospective study of the consultations of 50 families with a city general practice was used to test the hypothesis that mothers who receive an excess of psychotropic drugs have children who receive an excess of antibiotics for episodes of acute respiratory illness. The children of the 10 mothers classed as high psychotropic users were seen twice as often with acute respiratory illness and received twice as many antibiotics as the children of the mothers who had received no psychotropic medication. The association between high psychotropic and high antibiotic use was not linked in time, and indeed the time of highest antibiotic use coincided with the time when the mother received fewest psychotropic prescriptions. It is suggested that at many of these consultations the mother rather than the child should have been treated as the patient.
Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis
Authors: Pedro M. Rodríguez Cruz, Michal Al-Hajjar, Saif Huda, Leslie Jacobson, Mark Woodhall, Sandeep Jayawant, Camilla Buckley, David Hilton-Jones, David Beeson, Angela Vincent, Maria Isabel Leite, Jacqueline Palace
Journal: JAMA Neurology (2015)

Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice.To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG).All patients with clinical suspicion of MG who were seen within the Division of Clinical Neurology at the John Radcliffe Hospital in Oxford, England, between November 1, 2009, and November 30, 2013. Their serum antibodies and clinical features were studied.Radioimmunoprecipitation assay (RIPA) and CBA were used to test for standard AChR antibodies and antibodies to clustered AChRs in 138 patients. All available samples from patients with SNMG were retrospectively tested for lipoprotein receptor-related protein 4 (LRP4) antibodies.Demographic, clinical, neurophysiological, and laboratory data.In total, 138 patients were tested for antibodies to clustered AChRs, and 42 had a final diagnosis of MG. The clustered AChR CBA detected antibodies in 38.1% (16 of 42) of RIPA-negative patients with MG with 100% specificity. All patients with SNMG who were tested for LRP4 antibodies (21 of 26) were negative by CBA. Compared with patients with SNMG, patients with antibodies only to clustered AChRs had frequent prepubertal onset (62.5% [median age, 6 years; age range, 1-52 years] vs 11.5% [median age, 38 years; age range, 2-72 years], P ≤ .05), high prevalence of ocular MG (62.5% vs 42.3%), milder disease severity with less bulbar involvement (25.0% vs 46.2%), and absence of respiratory symptoms (0% vs 23.1%). Response to treatment and prognosis was good, with a reduced need for thymectomy (6.3% vs 19.2%) and a high proportion of patients going into remission (50.0% vs 8.3%, P ≤ .05). These observations also apply to the classic AChR MG phenotype seen in large series.Cell-based assay is a useful procedure in the routine diagnosis of RIPA-negative MG, particularly in children. Patients with antibodies only to clustered AChRs appear to be younger and have milder disease than other patients with MG. These observations will have implications in planning treatment.
Oesophageal foreign bodies.
Authors: A Baraka, G Bikhazi
Journal: BMJ (1975)

Impaction of foreign bodies in the oesophagus was analysed in 54 patients, 45 of whom were children. Of the 45 children 28 were aged 2-4 years. Coins were the most common foreign body in children (27 cases) while in adults a bolus of meat was most common (nine cases). In 41 children there was no predisposing factor, but an underlying mechanism was detected in 88% of the adults. The mechanisms were of three types: oesophageal (stricture), neuromuscular (myasthenia gravis), and extrinsic and mechanical (ankylosing spondylitis). In children most of the foreign bodies were impacted in the upper oesophagus at the cricopharyngeal junction, which is the narrowest part of the oesophagus, while in adults the foreign body was usually impacted at the site of the predisposing lesion or in the lower oesophagus. In all patients oesophagoscopy was performed under general anaesthesia to remove the impacted foreign body. Complications were more frequent in adults, mainly owing to the underlying condition.
Esthesioneuroblastoma Imaged with Bone Scintigraphy
Authors: ROBIN ACKER, JOE C. LEONARD
Journal: Clinical Nuclear Medicine (1986)

An esthesioneuroblastoma, a rare malignancy of the olfactory nerve, was identified with bone imaging in a four year old male who presented with a history of headaches and proptosis of the right eye. Correlation with CT is provided
Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells.
Authors: R P Schleimer, E S Schulman, D W MacGlashan, S P Peters, E C Hayes, G K Adams, L M Lichtenstein, N F Adkinson
Journal: Journal of Clinical Investigation (1983)

Purified human lung mast cells released histamine, leukotrienes, prostaglandin (PG) D2, thromboxane B2 (TxB2), and PGF2 alpha in response to anti-IgE stimulation. Incubation of the cells for 24 h with 10(-6) M dexamethasone, a treatment that inhibits mediator release from human basophils, had no effect on the release of these mediators from mast cells. Dexamethasone treatment of human lung fragments led to little or no inhibition of anti-IgE-induced release of the mast cell-derived mediator, histamine, but produced a significant inhibition of the release of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. As was the case with purified mast cells, the steroid did not inhibit the release of PGD2 or TxB2 from human lung fragments. Comparison of the quantities of PGD2 and TxB2 produced by purified cells and human lung fragments reveals that the mast cells produce quantities of these metabolites sufficient to account for the entire amount produced by challenged lung fragments. Dexamethasone inhibited spontaneous release from lung fragments of all cyclooxygenase products measured. These results suggest that the human lung parenchymal mast cell phospholipase is not inhibited by dexamethasone, whereas other phospholipase(s) in the lung are inhibited by the steroid. These results may be useful in explaining the resistance of acute allergic reactions, including anaphylaxis, to steroids, despite the potent antiinflammatory activity of steroids on subacute and chronic inflammation, such as in bronchial asthma, which may be initiated by IgE-dependent mechanisms.
Metastasis to Psoas Muscle Detected by F-18 FDG PET-CT Imaging
Authors: Peeyush Bhargava, Gordana Verstovsek, Matthew Stair, Joseph Vollink
Journal: Clinical Nuclear Medicine (2008)

We present the PET-CT images of a 67-year-old man who initially presented with seizures and was found to have a brain metastasis from lung adenocarcinoma. F-18 FDG PET-CT was performed for whole body staging, which showed focal hypermetabolism in the psoas muscle without any definite morphologic changes seen on the coregistered CT. Fused PET-CT images were used for assisting CT-guided needle biopsy, which showed metastatic adenocarcinoma of lung origin. The images show an extremely rare but possible site of metastasis to the psoas muscle detected by F-18 FDG PET before any definite morphologic changes, and CT may help in anatomic localization and biopsy.
THE PATHOGENESIS OF THE RENAL INJURY PRODUCED IN THE DOG BY HEMOGLOBIN OR METHEMOGLOBIN
Authors: H. E. Harrison, H. Bunting, N. K. Ordway, W. S. Albrink
Journal: The Journal of Experimental Medicine (1947)

Severe and persistent impairment of kidney function has been produced in dogs by intravascular hemolysis due to arsine, or by the intravenous injection of solutions of dog hemoglobin and methemoglobin. The kidneys of these animals have been examined by the usual histological methods and also by means of the ferrocyanide histochemical method to determine the pathogenesis of the renal injury. These observations indicate that obstruction to flow of urine through the renal tubules is an important factor in the early reduction of kidney function. The material filling the lumina of the renal tubules was found to be chiefly methemoglobin in concentrated solution of gel-like consistency. No evidence of formation of a pigment insoluble at the pH of the urine such as hemochromogen or hematin was found. The cessation of urine flow is most readily explained by the increased viscosity of the tubule contents. The intravenous administration of methemoglobin was found to produce more severe renal injury than the injection of equal amounts of oxyhemoglobin. Necrosis of the proximal convoluted tubule cells was present as a late lesion in animals injected with methemoglobin, large amounts of hemoglobin, or following extensive intravascular hemolysis. Such injury is probably a contributing factor in the persistent severe depression of renal function seen in these animals. Following disappearance of most of the intratubular pigment, a large number of collapsed tubules lined by hemosiderin-filled cells were found. The ferrocyanide histochemical studies indicated that these represented non-functioning nephrons although no obstructing intratubular material was present. Direct measurements in two animals failed to reveal any reduction of renal blood flow following the injection of methemoglobin in amounts sufficient to produce renal injury.