tbuckley/cabot-search huggingface dataset:
Immunology and allergy
Authors: G. Spickett, A. Frew
Journal: BMJ (1997)

Specialists in clinical immunology and clinical allergy work with a wide range of illnesses, from very common and relatively mild conditions such as hay fever, to rarer and serious conditions such as anaphylaxis, vasculitis, and primary immunodeficiency. In Britain the specialties are small, and these conditions have often been managed by general practitioners or organ based specialists such as chest physicians, dermatologists, or ear, nose, and throat specialists largely for historical reasons.

Many of these doctors are knowledgeable about allergic diseases, but others are not; the way patientso problems are handled may depend greatly on where they live and the interests of the doctor who is consulted. This variation, the rising prevalence of allergic conditions, and the advent of the Calman report all gave impetus to a fundamental re-examination of future training in immunology and allergy Until recently, immunology has really meant “immunopathology”, with posts being based in clinical immunology laboratories, the incumbent consultants predominantly laboratory oriented and trained under the auspices of the Royal College of Pathologists. Clinical work was limited. Allergy fared even less well, and most current practising “clinical allergists” in Britain were trained as organ based specialists (mainly in respiratory medicine) and developed their allergy interest in post. Academic posts have provided niches for clinical scientists with specific immunology or allergy interests who have often developed clinical services from their academic positions.

After much consultation, a joint committee of the Royal Colleges of Physicians and Pathologists has drawn up two training programmes, one in immunology, and one in allergy, both of which will lead to the certificate of completion of specialist training (CCST). Flexibility of the programme to meet the needs of trainees with differing skills and interests will be a key feature of these programmes. Training posts have been allocated to major regional centres where …
Concordant F-18 FDG PET and Y-90 Bremsstrahlung Scans Depict Selective Delivery of Y-90-Microspheres to Liver Tumors: Confirmation With Histopathology
Authors: Neda Tehranipour, Adil AL-Nahhas, Ruben Canelo, Gordon Stamp, Karen Woo, Paul Tait, Philip Gishen
Journal: Clinical Nuclear Medicine (2007)

Selective Internal Radiation Therapy using yttrium-90 (Y-90) microspheres is a novel method for the treatment of advanced liver cancer. The procedure involves intrahepatic arterial delivery of the Y-90 microspheres. Since hepatic tumors derive their blood supply mainly from the hepatic arteries, it is assumed that the microspheres will be preferentially delivered to tumor cells. However, this has not been confirmed at histology. We report a case of hepatic metastasis from an unknown primary, where treatment with Y-90 microspheres was the only available option due to inoperability and low tolerance to chemotherapy. Pretherapy F-18 FDG-PET scan defined the distribution of the active tumor within the liver. Following the injection of Y-90 microspheres, Bremsstrahlung imaging showed uptake only in the F-18 FDG-PET-defined tumor area. Post therapy debulking surgery was performed and histopathology of tumor samples confirmed the preferential distribution of the injected microspheres in the hepatic tumor circulation with very little in the healthy liver tissue. The case confirms the preferential blood flow to hepatic tumors as depicted by the distribution of Y-90 microspheres injected directly in the hepatic arteries. It also demonstrates that concordance between F-18 FDG-PET and Y-90 Bremsstrahlung scans can be a useful clue to the in vivo distribution of microspheres.
Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10)
Authors: Y SHEN, L ZHANG, B UTAMA, J WANG, Y GAN, X WANG, J WANG, L CHEN, G VERCELLOTTI, J COSELLI
Journal: Cardiovascular Research (2005)

Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV) infection may play a role in the development of this disease. Diminished expression and/or activity of endothelial nitric oxide synthase (eNOS) are an early event in atherogenesis. In the current study, we investigated the effects of HCMV infection on eNOS activation in human aortic endothelial cells (HAECs).We found that HCMV inhibited eNOS phosphorylation/activation in HAECs. The signaling upstream of eNOS involving Akt and PDK1 were also suppressed by the HCMV infection. Moreover, HCMV infection increased the expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10). Silencing PTEN expression with specific siRNA reversed the inhibitory effects on eNOS activation in HCMV-infected cells indicating the involvement of PTEN in mediating HCMV's inhibitory effects. Next we observed that the activation of p38 MAPK stress signaling pathway mediates HCMV's effects on PTEN up-regulation and eNOS inactivation.In summary, our findings suggest that inhibition of eNOS leading to endothelial dysfunction may be a basis of the pro-atherogenic effects of HCMV. Importantly, upregulation of PTEN and activation of stress signal p38 MAPK are involved in HCMV's inhibitory effects on eNOS activation.
IMPACT OF PHYSICAL FITNESS ON ECHOCARDIOGRAPHIC LEFT VENTRICULAR MASS IN HEALTHY YOUNG BLACK AND WHITE ADULT MEN AND WOMEN: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY
Authors: Eveline Oestreicher, Elyse Foster, Celina M. Yong, Stephen Sidney, Kofo O. Ogunyankin, Kirsten Bibbins-Domingo
Journal: Journal of the American College of Cardiology (2010)
A Survey On Drug Reactions in Latin America
Authors: Edgardo J. Jares, Mario Sánchez Borges, Luis Felipe C. Ensina, Maximiliano Gómez, Galie Mimessi, Alfredo Arias Cruz, Carlos Serrano, Susana Diez-Zuloaga, Mabel Noemi Cuello, Sandra González Díaz, Alejandra Macias Weinmann, Dirceu Sole, Alicia De Falco, Inês Camelo Nunes, Susana Barayazarra, Ivan Cherrez, Andrea Zanacchi, Juan F. Schuhl, Adolfo Salvatierra, Ricardo Cardona-Villa
Journal: Journal of Allergy and Clinical Immunology (2013)
Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis
Authors: Norbert Krug, Abhya Gupta, Philipp Badorrek, Ruediger Koenen, Meike Mueller, Anna Pivovarova, James Hilbert, Kristiane Wetzel, Jens M. Hohlfeld, Chester Wood
Journal: Journal of Allergy and Clinical Immunology (2013)
Chronic Atrial Flutter in Brothers with the Marfan Syndrome
Authors: P. BENNY CIPOLLONI, STANLEY R. SHANE, ROBERT J. MARSHALL
Journal: Circulation (1965)

Chronic atrial flutter was found in two teenage brothers with classical features of the Marfan syndrome. Since neither patient has a gross cardiovascular defect, it is postulated that the arrhythmias may be secondary to an alteration in the fine structure of the atrial myocardium.
An Address on Our Hospitals and the Interests of Patients and Pupils
Authors: E. D. Mapother
Journal: BMJ (1888)

R~SLMDCLJUNLtrute of miany other subjects, especially the purely scientific ones, A N AD DR E SS wherefro:m the stipend cannot execeed £100 a year, so that earnest ON a n ( I ~~~1 ~ori minal work cannot be-hoped for, is it not time that indi- 'idual intre'n-ts andl sentimtents shouild be merged.towards an OUR HOSPITALS AND THE INTERESTS amalgamiation (if schools.? Amiongst, other 1great.things then attain- Ithe volidbethe establishmen4"lt of a residential hail.Ilowe'ver, OF PATIENTS AND PUPILS.these topies itre to 1)4 di-scussedl in a prac'tical way elsewhere.Delivred a theAnnua.Jfeth~q f theDubln Rrarhl'ost-graduate cotirses have Iruag beven p~opuilar in America and Deliere attheAnnal eetin~q9f he ubln Iran'h I' n the Continent; for instance, thrut' hundred often attend the the BritisRh Medical Association., January, 1888.P~olyclinic in New York.lnI the great hospitals -of thmat, city the By EDWARD DILLON MAPOTIII~R .Dordinary clinics are very thinly atne-e mitoninstead of of te Drnchx-Prsl~lnt o tim i~o'alollee ofSurgons, eduction being in view-and thie be-tter class,;, after pa.,ssing, either President to St. V~~~~nccn~w ork in their own hospitals or come to Europe to adapt them-Irelad; Cosultig Sureon Iospitl, I~lliu.selves for imimediate ,scientific practice; but tsome may trespass on the, publici field without fitnes.164DURING the past year our Branch has been moved towards the Our licens-ingixbodies could encouragle clinical and pathological provision in Dublin of ptroper opportunities for ptathological study, work by setting those stuili('s alone for the final year's examina- and a Blue Book of extreme value, touching the curative and edlu-tions ; but, do our hospitals grive opl)Ortuniliies ?if ain officer of a cational facilities of our hospitals, has beemi presented.On these feI'as t~igi h ary, nav, or dis~pensary services
Medical Conditions — What Role in Crashes?
Authors: Julian A. Waller
Journal: New England Journal of Medicine (1970)

There is now little doubt that alcoholism is the medical condition contributing most frequently to the occurrence of highway crashes. About half of all fatally injured drivers and pedestrians, and a smaller but substantial proportion of persons in less severe crashes, have alcohol in their systems at the time of the crash, and studies show that most of them are problem drinkers.1 It is estimated that about a third of the 55,000 people fatally injured on the highway each year are problem drinkers impaired by alcohol at the time of their crashes. Clearly, crashes involving problem drinking deserve highest priority. . . .
Epstein-Barr virus associated with a post-transplant lymphoproliferative disorder presenting as isolated gastrointestinal tract bleeding
Authors: K. Badham, A. Mirchandani, N. Arumainayagam, D. West
Journal: Endoscopy (2007)

A 46-year-old woman underwent a cadaveric renal transplant. Three months later, she developed diarrhoea, fresh rectal bleeding, and cervical lymphadenopathy. Renal biopsy showed no evidence of rejection. Flexible sigmoidoscopy revealed multiple colonic ulcers, with no active bleeding (Figure [1]). Biopsies showed post-transplant lymphoproliferative disorder (PTLD). The cells were positive for Epstein-Barr virus (EBV) latent membrane protein, and positive for CD20, CD23, Pax 5, and EBV DNA. Tacrolimus (Astellaf Pharma, Ireland) was discontinued and anti-CD20 antibody treatment (rituximab; Roche, Basle, Switzerland) was started.
The Use of Local Anesthesia with N-DO Injector (Physion) for Transurethral Resection (TUR) of Bladder Tumors and Bladder Mapping: Preliminary Results and Cost-Effectiveness Analysis
Authors: Maurizio A. Brausi, Giorgio Verrini, Giuseppe De Luca, Massimo Viola, Gian Luca Simonini, Giancarlo Peracchia, Mirko Gavioli
Journal: European Urology (2007)
Human Subjects Research: A Handbook for Institutional Review Boards
Authors: George J. Annas
Journal: JAMA (1983)

According to the editors, this book "is designed to fill the perceived need for an operational guide to IRB function... for the IRB member [and] the IRB staff person." There is a need for such a book, and this volume makes a reasonable, if flawed, attempt to meet it. Institutional Review Boards (IRBs) have existed in most teaching hospitals for more than 15 years. Their primary purpose is the protection of human subjects, but they also protect the institution and the research enterprise itself. Institutional Review Boards review research proposals to ensure that risks are outweighed by benefits, subjects are protected, and informed consent is obtained. Few dispute these goals, but IRBs have been criticized for getting involved in minutia and creating red tape. In response, both the Department of Health and Human Services and the Food and Drug Administration issued new regulations in 1981 that streamline review for most
Is your mum on drugs?
Authors: R. Moynihan
Journal: BMJ (2011)

When “de-prescribing” may be the best medicine

Soon after she went into a small hospital a few years back, Johanna Trimble’s mother in law seemed to enter a rapid physical and cognitive decline.

Fervid Trimble was at the time a woman in her late 80s, living independently in a senior citizens’ home near Seattle in the United States. After a bout of diarrhoea and dizziness she was admitted to the healthcare centre close to the home, but her family was soon shocked by the quick deterioration in her health and the emergence of some strange new symptoms, including delusions. “She wasn’t able to wake up, and we couldn’t wake her,” says Johanna. “It didn’t seem like normal sleep.”

After discussions with the centre’s staff the family discovered that Fervid was taking several new drugs, including a painkiller and an antidepressant. “They said she was depressed,” says Johanna, “but we believed that she was rightly grieving for the loss of her former life, because she was now stuck inside a hospital room. It made sense …
In-situ self-assembling protein polymer gel systems for administration, delivery, and release of drugs
Authors: J Cappello, J.W Crissman, M Crissman, F.A Ferrari, G Textor, O Wallis, J.R Whitledge, Xia Zhou, D Burman, L Aukerman, E.R Stedronsky
Journal: Journal of Controlled Release (1998)
The Costs of Making Practice More Cost-effective—Reply
Authors: James Mason
Journal: JAMA (2002)

Drug Therapy for Patients With Type 2 DiabetesTo the Editor: In his Scientific Review article about treatment of type 2 diabetes, Dr Inzucchi 1 advocates achieving glycemic control by using any available antihyperglycemic therapy.He bases this recommendation on decreased rates of microvascular complications observed in the Diabetes Control and Complications Trial (DCCT) 2 and the United Kingdom Prospective Diabetes Study (UKPDS). 3 An ancillary study of the DCCT, however, showed that intensive drug treatment of patients with type 1 diabetes resulted in greater weight gain than conventional treatment. 4 With intensive treatment, subjects in the highest quartile of weight gain had the highest body mass index, blood pressure, and levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol.In addition, this group had a higher waist-tohip ratio, a higher percentage of their cholesterol as very lowdensity lipoprotein and dense low-density lipoprotein fractions, and lower high-density lipoprotein cholesterol compared with those in the first quartile.These findings suggest that changes in lipid levels and blood pressure that occur with excessive weight gain during intensive therapy may increase the risk of coronary artery disease in patients who have type 1 diabetes, who are not usually considered at risk for macrovascular complications.The majority of deaths in type 2 diabetes are due to macrovascular complications. 5 Although there was significant weight gain in the intensive therapy group in the UKPDS, 3 a follow-up study to assess the cardiac risk profile of individuals who gained weight was not done.It is imperative to know whether weight gain associated with antihyperglycemic therapy contributes to increased macrovascular complications and death before advocating glycemic control as the primary objective of therapy in patients with type 2 diabetes.
MHC-derived allopeptide activates TCR-biased CD8+ Tregs and suppresses organ rejection
Authors: Elodie Picarda, Séverine Bézie, Vanessa Venturi, Klara Echasserieau, Emmanuel Mérieau, Aurélie Delhumeau, Karine Renaudin, Sophie Brouard, Karine Bernardeau, Ignacio Anegon, Carole Guillonneau
Journal: Journal of Clinical Investigation (2014)

In a rat heart allograft model, preventing T cell costimulation with CD40Ig leads to indefinite allograft survival, which is mediated by the induction of CD8+CD45RClo regulatory T cells (CD8+CD40Ig Tregs) interacting with plasmacytoid dendritic cells (pDCs). The role of TCR-MHC-peptide interaction in regulating Treg activity remains a topic of debate. Here, we identified a donor MHC class II–derived peptide (Du51) that is recognized by TCR-biased CD8+CD40Ig Tregs and activating CD8+CD40Ig Tregs in both its phenotype and suppression of antidonor alloreactive T cell responses. We generated a labeled tetramer (MHC-I RT1.Aa/Du51) to localize and quantify Du51-specific T cells within rat cardiac allografts and spleen. RT1.Aa/Du51-specific CD8+CD40Ig Tregs were the most suppressive subset of the total Treg population, were essential for in vivo tolerance induction, and expressed a biased, restricted Vβ11-TCR repertoire in the spleen and the graft. Finally, we demonstrated that treatment of transplant recipients with the Du51 peptide resulted in indefinite prolongation of allograft survival. These results show that CD8+CD40Ig Tregs recognize a dominant donor antigen, resulting in TCR repertoire alterations in the graft and periphery. Furthermore, this allopeptide has strong therapeutic activity and highlights the importance of TCR-peptide-MHC interaction for Treg generation and function.
Treatment Regimen and Side Effects of Treatment Measures
Authors: William W. Busse, Richard Maisiak, K. Randall Young
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The severity of asthma can be judged by many features, including the need for medication and associated side effects. Since asthma has both acute and chronic characteristics, therapeutic regimens should be valuable as an instrument to define disease severity and the consequence of intervention. However, because of the variability of asthma severity within each patient, medication quantitation as an index of asthma severity is not without difficulty and limitation. Furthermore, the philosophy of asthma therapy has undergone changes over the past decade. Previously, anti-inflammatory therapy was reserved for only the most severely ill patients. Now, inflammation is recognized as a critical component of asthma, and all patients with active asthma (other than mild symptoms) are recommended to use anti-inflammatory therapy. Although there is little published experience with treatment regimens as an index of disease severity, those that have been used have found validity and reproducibility with this approach. In this paper, a scoring approach to medication use is recommended. Medication is classified into bronchodilator (beta-agonists, theophylline, and anticholinergic) or anti-inflammatory (corticosteroid and cromolyn sodium). Medication scores are given on either a per-use or a new-dosage basis. Furthermore, the eight medications are stratified according to potency (i.e., inhaled corticosteroid < oral corticosteroid < parenteral corticosteroid). From this approach, the severity of an individual patient's asthma can be quantitated, and this value can serve as one instrument to assess disease severity.
Differential Expression of S6K2 Dictates Tissue-Specific Requirement for S6K1 in Mediating Aberrant mTORC1 Signaling and Tumorigenesis
Authors: Caterina Nardella, Andrea Lunardi, Giuseppe Fedele, John G. Clohessy, Andrea Alimonti, Sara C. Kozma, George Thomas, Massimo Loda, Pier Paolo Pandolfi
Journal: Cancer Research (2011)

The S6K1 and S6K2 kinases are considered important mTOR signaling effectors, yet their contribution to tumorigenesis remains unclear. Aberrant mTOR activation is a frequent event in cancer that commonly results from heterozygous loss of PTEN. Here, we show for the first time a differential protein expression between S6K1 and S6K2 in both mouse and human tissues. Additionally, the inactivation of S6k1 in the context of Pten heterozygosity (Pten(+/-)) suggests a differential requirement for this protein across multiple tissues. This tissue specificity appears to be governed by the relative protein expression of S6k2. Accordingly, we find that deletion of S6k1 markedly impairs Pten(+/-) mediated adrenal tumorigenesis, specifically due to low expression of S6k2. Concomitant observation of low S6K2 levels in the human adrenal gland supports the development of S6K1 inhibitors for treatment of PTEN loss-driven pheochromocytoma.
Investigation of suspected breast cancer
Authors: Peter Britton, Ruchi Sinnatamby
Journal: BMJ (2007)

Practice the patientAn 81 year old woman was referred to a multidisciplinary breast clinic with a lump in her right breast.Such patients undergo "triple" assessment-clinical examination, imaging, and, if necessary, needle biopsy.On clinical examination she had a mass in the upper outer quadrant, which was suspected to be an underlying carcinoma. What tests do i order?It is usual practice for patients over 35 years with discrete breast lumps to undergo mammography and ultrasound.In patients under 35 years, ultrasound is the first line investigation. MammographyMammography has been evaluated more extensively than any other imaging technique and remains a mainstay of the diagnosis of breast cancer.Reported sensitivity in detecting palpable breast cancer is 80-90%, 1 but it is lower in patients with dense breast parenchyma.A normal mammogram can be seen in the presence of a palpable breast cancer, so national guidance recommends that all breast units should provide triple assessment clinics for symptomatic women rather than an open access imaging service for general practitioners.
Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein.
Authors: J Hombach, H Pircher, S Tonegawa, R M Zinkernagel
Journal: The Journal of Experimental Medicine (1995)

Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.
Sarcoidois and Radiation-Induced Astrogliosis Causes Pitfalls in Neuro-Oncologic Positron Emission Tomography Imaging by <i>O</i>-(2-[<sup>18</sup>F]Fluoroethyl)-<scp>l</scp>-Tyrosine
Authors: Robert Pichler, Gabriele Wurm, Karin Nußbaumer, Ognian Kalev, René Silyé, Serge Weis
Journal: Journal of Clinical Oncology (2010)