tbuckley/cabot-search huggingface dataset:
The acme of efficiency
Authors: Alan Gibson
Journal: BMJ (2004)

In 1955 I was a registrar in a large mental hospital in the north of England. Most of the bedswere in the old buildings, which had remained largely unchanged for nearly 100 years. There was also a modern building in the grounds, to which new patients were admitted. If these patients needed electroconvulsive therapy, they were anaesthetised and given a muscle relaxant. Electroconvulsive therapy was also widely used in the chronic wards, where it was the consequence of disturbed behaviour. There, it was given “straight”—that is, without anaesthetic or relaxant. This policy was defended by the view …
Abstract OT1-1-03: PERSEPHONE: Duration of Trastuzumab with Chemotherapy in women with HER2 positive early breast cancer.
Authors: HM Earl, DA Cameron, D Miles, AM Wardley, ERM Ogburn, A-L Vallier, S Loi, HB Higgins, L Hiller, JA Dunn
Journal: Cancer Research (2012)

Abstract Background: Persephone is a phase III randomised controlled trial comparing six months of trastuzumab to the standard 12 month duration in patients with HER2 positive early breast cancer in respect of disease free survival, safety and cost-effectiveness. A Persephone sister study, the PHARE trial run by the National Institute for Cancer, successfully closed to recruitment in 2010. A prospective meta-analysis is planned once each trial has reported individually. Methods: A total of 4000 patients will be randomised into each of the two treatment groups. Eligible participants must be Her2 positive with a histological diagnosis of invasive breast cancer and no evidence of metastatic disease. Patients will receive neo-adjuvant or adjuvant chemotherapy and have no previous diagnosis of malignancy unless managed by surgical treatment only and disease-free for 10 years. Patients can be randomised at any time prior to receiving their 10th cycle of trastuzumab. The power calculations assume that the disease-free survival (DFS) of the standard treatment of 12 months trastuzumab will be 80% at 4 years. On this basis, with 5% 1-sided significance and 85% power, a trial randomising 2000 in each arm will have the ability to prove non-inferiority of the experimental arm defining non-inferiority as ‘no worse than 3%’ below the control arm 4 year DFS. Primary outcome is disease-free survival non-inferiority (equivalence) of 6 months trastuzumab compared with 12 months in women with early breast cancer. Secondary outcomes are overall survival non-inferiority (equivalence); expected incremental cost effectiveness; cardiology function and analysis of predictive factors for development of cardiac damage. Two mandatory sub-studies are: Tumour block collection to discover molecular predictors of survival with respect to duration of trastuzumab treatment and blood sample collection, used to discover single nucleotide polymorphisms (SNPs) as genetic/pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. A third optional sub-study is the quality of life questionnaires. Results: Persephone opened to recruitment in October 2007. To date, 2152 patients (54%) of its total have been randomised from 147 UK sites. Recruitment is due to complete by December 2013 and the first planned interim analysis of the primary outcome will be mid-2016. Conclusion: The IDSMC last reviewed the trial in December 2011 and congratulated the Trial Management Group on the conduct of the trial and the quality of the data. No safety concerns were identified, and the IDSMC proposed that the trial continue to planned recruitment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-03.
The Effects of Estradiol and Estriol on Plasma Levels of Cortisol and Thyroid Hormone-Binding Globulins and on Aldosterone and Cortisol Secretion Rates in Man*
Authors: Fred H. Katz, Attallah Kappas
Journal: Journal of Clinical Investigation (1967)

The effects of estriol and estradiol on the plasma levels of cortisol- and thyroxine-binding globulin activity, and on the secretion rates of aldosterone and cortisol were studied in man. The metabolite estriol had no consistent or significant influence on plasma levels of the hormone-binding globulin activities; the hormone estradiol increased these binding capacities significantly, as expected. Cortisol secretion rate rose slightly after estriol but was unchanged after estradiol. Both compounds induced substantial increases in the aldosterone secretion rate of most treated subjects. The mechanism of this apparently paradoxical effect of estrogens is not clear; it is suggested that the "salt-retaining" action of estrogens is mediated in part by the rapid enhancement of aldosterone output which follows their administration in man. Balance experiments in four subjects suggest that both estradiol and estriol may induce a transient early natriuresis in man; but other mechanisms for estrogen stimulation of aldosterone secretion may be operative as well.
P199The muscle recovery potential of vegf gene therapy in a mouse model of hindlimb ischemia
Authors: G Wirth, P Korpisalo, H Hakkarainen, T Liimatainen, S Yla-Herttuala
Journal: Cardiovascular Research (2014)

Aims: The purpose of therapeutic angiogenesis in ischemic disorders is to stimulate vessel growth in areas of insufficient vascularization in an attempt to increase blood supply, and thus to support the recovery of the affected tissue. Exploiting this concept, we aimed to investigate whether angiogenesis-induced by VEGF gene therapy helped skeletal muscle to recover from ischemia insult in a mouse model of hypercholesterolemia. Methods: Hindlimb ischemia in LDLR-/-ApoB100/100 female mice (age of 6-12 months) was generated by ligation of both femoral artery and vein proximal to the origin of the deep femoral branch, followed by intramuscular injection of adenovirus encoding human VEGF-A165 or control LacZ into posterior calf muscles. Results: Although experiencing significant necrosis on d4, AdhVEGF-A165 transduced muscles showed accelerated muscle recovery rate between d4-7 when compared to AdLacZ controls. Enhanced muscle recovery was associated with AdhVEGF-A165 induced capillary enlargement but may also have been related to satellite cell activation. However, the initial beneficial effect of VEGF gene transfer did not expedite morphological recovery of calf muscle on d30. Furthermore, a side effect of the treatment remained the induction of significant tissue edema on d4-7. Conclusions: A short term application of VEGF could be useful for initial tissue recovery but improving a chronic situation may require a longer VEGF expression.
Mutations in coenzyme Q10 biosynthetic genes
Authors: Salvatore DiMauro, Catarina M. Quinzii, Michio Hirano
Journal: Journal of Clinical Investigation (2007)

Although it was first described in 1989, our understanding of coenzyme Q10 (CoQ10) deficiency is only now coming of age with the recent first description of the underlying molecular defects. The diverse clinical presentations, classifiable into four major syndromes, raise the question as to whether the deficiencies are primary or secondary. Recent studies, including the one by Mollet, Rötig, and colleagues reported in this issue of the JCI, document molecular defects in three of the nine genes required for CoQ10 biosynthesis, all of which are associated with early and severe clinical presentations (see the related article beginning on page 765). It is anticipated that defects in the other six genes will cause similar early-onset encephalomyopathies. Awareness of CoQ10 deficiency is important because individuals with primary or secondary variants may benefit from oral CoQ10 supplementation.
Breast and Nipple Pain in Early Stages of Lactation
Authors: B. Gans
Journal: BMJ (1958)

Haemoglobin J was seen in two unrelated women of Gujerati-speaking Lohana stock.In one of them the haemoglobin J trait was present together with thal- assaemia minor.There was no evidence for a detri- mental interaction between the genes for thalassaemia and for haemoglobin J-that is, for a hypothetical haemoglobin J thalassaemia disease.We are grateful to Dr. G. D. Adhia for referring the two children to us, and to Dr. R. P. Vasani for his help in collecting samples of blood.We thank
Interposed abdominal compression--cardiopulmonary resuscitation.
Authors: I S Salgo
Journal: Circulation (1993)

important role in such activation because the effects of iron on platelets were abolished by blocking the prostaglandin G/Hsynthase enzyme by aspirin.Taken together, these data may suggest that high levels of iron stores could increase the risk of MI by favoring platelet activation in the setting of plaque fissuring in a major coronary artery.This hypothesis is currently being inves- tigated in vivo by studying platelet function in relation to the levels of serum ferritin.
THE PLACE OF PHARMACOLOGY IN MEDICINE.CHAIRMAN'S ADDRESS BEFORE THE SECTION ON PHARMACOLOGY AND THERAPEUTICS AT THE FIFTY-EIGHTH ANNUAL SESSION, ATLANTIC CITY, JUNE, 1907.
Authors: HORATIO C. WOOD
Journal: JAMA (1907)

The medical instinct, the impulse to relieve the distress of the sick, is as old as the human race; indeed, it is even older, for we find also among the lower animals positive evidences of attempts to alleviate the sufferings of themselves or their offspring. One of the most noteworthy features of these primordial medical efforts is the almost universal solitude of the remedial agents employed. Thus, the dog finds in grass his complete panacea; the precivilized man, with his strong religious instinct, essayed to cure all ills by incantations and exorcism. In other words, there was no separation of different kinds of suffering; diagnosis was undreamed of, pathology but a fancy, the whole of medicine was therapeutics. The powers of observing and of recording his experience, characteristic of the human animal, taught man to differentiate between various forms of disease, and thus gradually was developed diagnosis and pathology, but
The Relevance of Schistosomiasis
Authors: Howard L. Bleich, Mary Jean Moore, Kenneth S. Warren
Journal: New England Journal of Medicine (1980)

THE relevance of schistosomiasis to medicine in Boston as a paradigm for its relevance to medicine everywhere is the subject of this report.Schistosomiasis as a Major Global ProblemThe first question that arises is whether Boston has any concern for an infectious disease that affects 200 million persons, most of whom live in the rural tropics, and is spreading as the Agency for International Development and the World Bank support agricultural development through dams and irrigation. Today, we are constantly aware of (and often irritated by) difficult ethical questions concerning the individual patient: euthanasia, abortion, and medical experimentation are . . .
An approach to the evaluation and management of syncope in adults
Authors: S. W Parry, M. P. Tan
Journal: BMJ (2010)

#### Summary points

Cohort and population based studies suggest that around 40% of the adult population has experienced a syncopal episode (usually described as a “faint” or “blackout”),1 2 w1 w2 with women more likely than men to report such an episode.w1-3 The incidence is higher with advancing age,2 w3 and this trend coincides with the increase in prescription of vasoactive drugs and increasing incidence of cardiac arrhythmia in the elderly population. Although comprehensive reviews and guidelines are available for specialists who care for patients referred with syncope,3 4 w4 w5 guidance for the non-specialist is sparse. This review provides guidance for generalists who encounter patients who have had transient loss of consciousness that may be syncopal in nature. It is based on cohort studies, randomised controlled trial evidence, and expert consensus guidelines.

#### Sources and selection criteria

We searched Medline, PubMed, and Cochrane databases for English articles whose titles included the keywords “syncope”, “vasovagal syncope”, “orthostatic hypotension”, tilt table test”, “cardiac arrhythmia”, or “sudden cardiac death”, with and without the limits “meta-analysis”, “review”, and “randomised controlled trial”. We also consulted recent international guidelines on syncope (including the specialist societies the European Society of Cardiology and the American Heart Association/American College of Cardiology Foundation), and reviewed our personal archives and relevant current textbooks.

Patients with transient loss of consciousness often present non-specifically with an episode of …
Abstract 5416: Development of a nanoparticle platform for the targeted delivery of siRNA to HER2-positive breast cancers
Authors: Shaun M. Goodyear
Journal: Cancer Research (2014)

Abstract Successful siRNA based therapy has the potential to revolutionize cancer therapy by mediating the silencing of any gene deemed important for disease progression. However, unprotected siRNA has a short half-life in blood and lacks the ability to selectively identify target cells. Our group is developing an effective siRNA based nanoparticle platform that overcomes these shortcomings by utilizing a mesoporous silica nanoparticle electrostatically loaded with siRNA and conjugated with an antibody for target homing. The human epidermal growth receptor type 2 (HER2) is a highly validated therapeutic target in breast cancer due to its prognostic role in cancer aggressiveness and drug resistance when overexpressed in tumors. Suppression of HER2 with siRNA based therapy (siHER2) offers a new treatment modality and provides a testable system for the development of our nanoparticle platform. Incorporation of Herceptin, a monoclonal antibody which binds to HER2, serves to selectively target HER2-positive cancer cells. In vitro evaluation of the nanoconstruct loaded with a highly optimized siHER2 sequence against a panel of HER2-positive (HCC1954, JIMT-1, BT474) and HER2-negative (MCF-7, MCF-10A, HDFa) cell lines demonstrated efficient knockdown of HER2 gene expression (&amp;gt; 75% reduction of HER2 mRNA and protein). Concomitant cell viability assays showed increased cell death in HER2-positive and no HER2-negative cell lines further highlighting treatment specificity. Importantly, treatment of cells with the siHER2-nanoconstruct effectively inhibited growth in HER2-positive cell lines resistant to Herceptin and Lapatinib. Subsequent in vivo tumor modeling studies using orthotopic transplantation of HCC1954 in the mammary fat pad of SCID mice revealed that i.v. injection of the siHER2-nanocontruct reduced overall tumor burden. HER2 knockdown in the tumors was also significant. These findings provide the foundation for a novel translational platform for facilitating therapeutic siRNA. Citation Format: Shaun M. Goodyear. Development of a nanoparticle platform for the targeted delivery of siRNA to HER2-positive breast cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5416. doi:10.1158/1538-7445.AM2014-5416
Critical Care of Patients With AIDS
Authors: Robert M. Wachter
Journal: JAMA (1992)

We sought to review the clinical and ethical issues surrounding critical care for patients with the acquired immunodeficiency syndrome (AIDS).We reviewed published studies and abstracts dealing with the outcome of critical care for patients with AIDS, decision making about life-sustaining treatments in patients with AIDS, and infection control in the intensive care unit. We also consulted with a number of experts in the field.We selected outcome studies in which patients with documented AIDS or infection with the human immunodeficiency virus (HIV) were analyzed. We rejected data concerning patients with suspected or presumed AIDS and data concerning presumed cases of Pneumocystis carinii pneumonia (PCP).Most AIDS patients who require critical care do so because of respiratory failure caused by PCP. Although studies early in the epidemic reported survival rates to hospital discharge of 0% to 14%, recent studies demonstrate improved survival rates of 36% to 55%. Treatment for patients with PCP and respiratory failure should include either intravenous trimethoprim-sulfa-methoxazole or pentamidine isethionate, as well as adjuvant corticosteroids. Patients with AIDS may require critical care for many other indications, including seizures, sepsis, and hypotension, or reasons unrelated to their immunodeficiency. In general, such patients have a better prognosis than those with respiratory failure.The provision of critical care for PCP and respiratory failure specifically or AIDS generally cannot be considered futile. Therefore, decisions about the use of critical care should be guided by the particular clinical situation and the patient's preferences. More research is needed to elucidate the reasons for the improving survival for patients with PCP and respiratory failure and the predictors of such survival.
OBSERVATIONS ON ISOLATED CASES OF DIPHTHERIA.Read in the Section on Diseases of Children, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: W. A. DIXON
Journal: JAMA (1893)

Diphtheria is a frequent and most destructive disease, a large and familiar outlet of youthful life. Children of tender years are specially susceptible to it, and no condition of life seems to materially influenee the liability to the disease. The rich and the poor, alike, suffer severely from it. Sanitary conditions, as a matter of fact, seem to have little to do with its prevalence. Though most writers characterize it as a filth disease, a view of its history shows that it pays little regard to filthy or cleanly surroundings. Dr. Thursfield's observations as sanitary inspector of a district in England extending over twelve hundred square miles, show the number of fatal cases of diphtheria in the rural portion to be nearly three times that in the urban. Dr. Longstaff at another period, in his report on the "Geographical Distribution of Diphtheria in England and Wales," shows that the disease
Leading UK paediatrician reinstated
Authors: C. White
Journal: BMJ (2001)

North Staffordshire Hospital NHS Trust has reinstated consultant paediatrician Professor David Southall after a two year investigation into his work at the hospital in Stoke on Trent.

The investigation, which cost £750000 ($1.1m), involved five investigative panels, child health specialists, the Social Services Inspectorate, and the police.

The announcement, which the trust had intended to make at a press conference on 16 October, was rushed out on the preceding Friday afternoon, after it was leaked to a freelance journalist. Professor Southall, whose work is also being investigated by the General Medical Council, said, “I'm really pleased to be able to go back to looking after sick and injured children.”

Professor Southall, who was appointed in 1992, was suspended in November 1999 from his post on full pay along with another consultant, Dr Martin Samuels, after two independent external clinicians undertook a preliminary examination of his child protection and research work at the hospital (BMJ 2000;320:9). This was prompted by a series of serious complaints made about Professor Southall's professional conduct in January 1999, …
Quality improvement report Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study Commentary: presenting unbiased information to patients can be difficult
Authors: Jenny Donovan, Paul Little, Nicola Mills, Monica Smith, Lucy Brindle, Ann Jacoby, Tim Peters, Stephen Frankel, David Neal, Freddie Hamdy
Journal: BMJ (2002)

Recruitment to randomised trials is often difficult, and many important trials are not mounted because recruitment is thought to be "impossible."Controversial ProtecT (prostate testing for cancer and treatment) trial embedded within qualitative research.Screening for prostate cancer is hotly debated, and evidence from trials about the effectiveness of treatments (surgery, radiotherapy, and monitoring) is lacking. Mounting a treatment trial is controversial because of past failures and concerns that differences in complications of treatment but not survival make randomisation unacceptable to patients and clinicians, particularly for a trial including monitoring.In-depth interviews explored interpretation of study information. Audiotape recordings of recruitment appointments enabled scrutiny of content and presentation of study information by recruiters. Initial qualitative findings showed that recruiters had difficulty discussing equipoise and presenting treatments equally; they unknowingly used terminology that was misinterpreted by participants. Findings were used to determine changes to content and presentation of information.Changes to the order of presenting treatments encouraged emphasis on equivalence, misinterpreted terms were avoided, the non-radical arm was redefined, and randomisation and clinical equipoise were presented more convincingly. The randomisation rate increased from 40% to 70%, all treatments became acceptable, and the three arm trial became the preferred design.Changes to information and presentation resulted in efficient recruitment acceptable to patients and clinicians. Embedding this controversial trial within qualitative research improved recruitment. Such methods probably have wider applicability and may enable even the most difficult evaluative questions to be tackled.
Abstract 380: Optimization of novel therapeutic paradigms for ovarian cancer using molecular imaging
Authors: Hanxiao Wang, Stefanie Galban, Rong Wu, Brittany Bowman, Athena Fletcha, Amanda Witte, Komal Chughtai, Brian Ross, Kathleen Cho, Alnawaz Rehemtulla
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the fifth leading cause of cancer death among American woman. Platinum-based chemotherapy, such as cisplatin, represents the standard of care for ovarian cancer. However, toxicicity and acquired resistance to cisplatin have been proven challenging in the treatment of cancer patients. Here, we evaluate the efficacy of targeted inhibition of Akt in combination with cisplatin in an ovarian endometrioid adenocarcinoma (OEA) mouse model wherein Wnt and PI3K signaling pathways are disrupted thus recapitulating the human disease. In cell culture and mouse xenograft models, inhibition of Akt activity in combination with cisplatin is more potent at inducing apoptosis compared to either agent alone. To further explore this finding in living animals, we incorporate a bioluminescence apoptosis reporter into the existing OEA mouse model, to enable monitoring of apoptosis dynamically and non-invasively in real time. Our results demonstrate that Akt inhibitors augment the efficacy of cisplatin by inducing apoptosis more efficiently in our newly developed transgenic OEA model. Magnetic resonance (MR) imaging was also accomplished to determine tumor burden and normalize changes in bioluminescence. Our results show that inhibition of Akt sensitizes OEA to apoptosis in response to cisplatin thus resulting in reducing tumor burden. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 380. doi:1538-7445.AM2012-380
SCN5A MUTATIONS ASSOCIATED WITH DILATED CARDIOMYOPATHY COMMONLY LOCALIZE TO THE VOLTAGE-SENSING MECHANISM
Authors: Luisa Mestroni, William McNair, Gianfranco Sinagra, Andrea Di Lenarda, Debra Ferguson, Ernesto E. Salcedo, Dobromir Slavov, Dobromir Slavov, Xiao Zhu, John Caldwell, Matthew R.G. Taylor
Journal: Journal of the American College of Cardiology (2010)