tbuckley/cabot-search huggingface dataset:
Medical Care for Mountain Climbers
Authors: C. Clarke
Journal: BMJ (1976)

This is a book to dip into, not a book for the individual to buy.Medical libraries will perhaps wish to add it to a well-established collection on psychiatry, but it could not stand as the only representative of books on therapeutics in the specialty.It has many useful things to say about the broad principles of treatment, but, inevitably, it cannot provide the detailed account of each procedure that would make it a true therapist's handbook.
Handling of injectable antineoplastic agents.
Authors: R S Knowles, J E Virden
Journal: BMJ (1980)

Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents.
Case 30-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, E.P. Richardson, E.T. Hedley-Whyte
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 52-year-old woman was admitted to the hospital because of progressive neurologic deterioration.She was well until several years earlier, when she became increasingly irritable. Five years before admission psychotherapy was initiated for a manic—depressive illness. During the next few years she used barbiturates, tranquilizers, and amphetamines regularly and was admitted to a hospital on one occasion because of drug overdose. One year before entry her behavior at work began to decline; she avoided complex decisions, made errors in judgment, and often berated her co-workers.Six months before admission she became lost en route to an appointment . . .
Abstract 3508: A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II
Authors: Gaik-Lean Chee, Jack Yalowich, Brian B. Hasinoff
Journal: Cancer Research (2010)

Abstract Etoposide is a widely used anticancer drug that targets topoisomerase II, an essential nuclear enzyme. However, despite the fact that it has been in use and studied for more than 30 years the specific site on the enzyme to which it binds is unknown. In order to identify the etoposide binding site(s) on topoisomerase II, a diazirine-based photoaffinity etoposide analog probe has been synthesized and its photoreactivity and biological activities have been characterized. Upon UV irradiation, the diazirine probe rapidly produced a highly reactive carbene species that formed covalent adducts containing stable carbon-based bonds indicating that it should also be able to form stable covalent adducts with amino acid residues on topoisomerase II. The human leukemia K562 cell growth and topoisomerase II inhibitory properties of the diazirine probe suggest that it targets topoisomerase II in a manner similar to etoposide. The diazirine probe was also shown to act as a topoisomerase II poison through its ability to cause topoisomerase IIα-mediated double-strand cleavage of DNA. Additionally, the diazirine probe significantly increased protein-DNA covalent complex formation upon photoirradiation of diazirine probe-treated K562 cells, as compared to etoposide-treated cells. This result suggests that the photoactivated probe forms a covalent adduct with topoisomerase IIα. In conclusion, the present characterization of the chemical, biochemical, and biological properties of the newly synthesized diazirine-based photoaffinity etoposide analog indicates that use of a proteomics mass spectrometry approach will be a tractable strategy for future identification of the etoposide binding site(s) on topoisomerase II through covalent labeling of amino acid residues. This work was supported by institutional grants from the University of Manitoba, Canadian Institutes of Health Research, National Institutes of Health grant CA090787 to J.C.Y. and a Canada Research Chair for Drug Development for B.B.H Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3508.
Near patient testing for influenza in children in primary care: comparison with laboratory test
Authors: A. Harnden
Journal: BMJ (2003)

Influenza is an important cause of acute respiratory illness in young children. Common complications include febrile convulsions, otitis media, bronchiolitis, and croup. In epidemic years attack rates among preschool children often exceed 40%. During these years children with influenza may account for up to 30% of the increase in antibiotic prescribing.1 Symptoms and signs of influenza in children are not specific and can mimic a range of other common respiratory viral pathogens. One quick way of reaching a precise diagnosis in primary care is to use a near patient test. Near patient testing for many conditions has expanded widely in primary care, though many tests have not been rigorously evaluated.2

Previous studies in children have compared near patient influenza tests with viral culture analysis using throat or nasal swabs.3 However, a nasopharyngeal aspirate is the best specimen for detecting influenza viruses, and …
Abstract B2: Delineating the metabolic pathway to DHT in castration-resistant prostate cancer
Authors: Kai-Hsiung Chang, Amy Li, Nima Sharifi
Journal: Cancer Research (2012)

Abstract After an initial response to androgen deprivation therapy (ADT) by depletion of gonadal testosterone, re-fueling androgen receptor in metastatic tumors is a critical mechanism required to drive castration resistant prostate cancer (CRPC) progression. Testosterone (T) is generally regarded as an obligate precursor for dihydrotestosterone (DHT) synthesis from adrenal precursors in CRPC and the up-regulation of steroid-5α-reductase isoenzyme-1 (SRD5A1) over SRD5A2 in CRPC is thought to convert T to DHT. Our recent findings demonstrated that an alternative pathway, namely androstenedione (AD) → 5α-androstanedione (5α-dione) → DHT, is dominant in CRPC. In this alternative pathway, AD prevails over T as a preferred substrate for 5α-reduction in CPRC. In particular, SRD5A1-mediated conversion of AD to 5α-dione is a prerequisite for converting adrenal steroids to DHT and for CRPC growth in mouse xenograft models. How 5α-dione is processed in CRPC is unknown. There are two possible routes from 5α-dione to DHT in the alternative pathway. The first route is direct 17-ketoreduction of 5α-dione by 17β-hydroxysteroid dehydrogenase-3 (17βHSD3) or 17βHSD5 (also known as aldo-keto reductase family 1, member C3, AKR1C3), both of which are up-regulated in CRPC progression. The second route is through a circuitous pathway, which requires 3-keto-reduction to 3α-hydroxyl, prior to 17-keto-reduction, namely 5α-dione → androsterone (AST) → 5α-androstane- 3α,17β-diol (Adiol) → DHT. Here, we show that ectopic expression of HSD17B5 in 293T cells efficiently converts 5α-dione to DHT, whereas AKR1C2 robustly catalyzes 5α-dione to AST and ultimately to DHT. This suggests that metabolism of 5α-dione may be determined by the relative expression and enzymatic activities of AKR1C3 and AKR1C2. These findings offer insights into the synthesis of DHT in CRPC and for the development of new therapeutic strategies. Citation Format: Kai-Hsiung Chang, Amy Li, Nima Sharifi. Delineating the metabolic pathway to DHT in castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B2.
Disturbance of plasma and platelet thrombospondin levels in sickle cell disease
Authors: Paul V. Browne, Deane F. Mosher, Martin H. Steinberg, Robert P. Hebbel
Journal: American Journal of Hematology (1996)

Thrombospondin (TSP), a large protein found in platelet α-granules (as TSP-1), mediates adhesion of sickle reticulocytes to cultured vascular endothelium. To further explore the physiologic relevance of this observation, we have measured plasma TSP levels and platelet TSP-1 content in subjects with sickle cell disease. Plasma TSP levels were similar for normal controls (mean 491 ng/ml, range 331–723) and steady-state HbSS patients (mean 536, range 333–1107) and were significantly (P = 0.012) but variably elevated for HbSS patients presenting with acute painful crisis (mean 868, range 442–2780). Some of these elevated plasma TSP levels reached those previously observed to support maximal red cell adhesion to endothelium in vitro. Compared to normals, both steady-state and in-crisis HbSS patients had significantly (P < 0.001) depressed platelet TSP-1 content (82.6 ± 11.9, 47.1 ± 16.0 and 45.9 ± 20.7 ng/109 platelets, respectively, mean ± SD). HbSC disease patients, all examined during steady state, had low-normal plasma levels of TSP and either normal or depressed platelet TSP-1 content. Serial observations on three sickle cell anemia subjects indicated a probable relationship between platelet TSP-1 release, elevated plasma TSP levels, and acute vasoocclusive episodes. These results suggest a state of ongoing release and depletion of TSP-1 from activated platelets in patients with sickle cell disease. © 1996 Wiley-Liss, Inc.
Case 26-1966
Authors: William E. Strole, Wallace A. Jones
Journal: New England Journal of Medicine (1966)

Presentation of CaseA twenty-one-year-old female typist entered the hospital because of jaundice.Three weeks previously her friends noticed that the whites of her eyes had become yellow. At that time she began to pass dark urine, and during the week before admission the stools were light in color.Twelve years earlier her father had been confined to another hospital because of pulmonary tuberculosis; two years later the patient's tuberculin skin test was found to be positive. X-ray films of the chest with fluoroscopic examination were normal, although slight enlargement of the spleen was found on physical examination. One year . . .
Rat lung Cu,Zn superoxide dismutase. Isolation and sequence of a full-length cDNA and studies of enzyme induction.
Authors: M A Hass, J Iqbal, L B Clerch, L Frank, D Massaro
Journal: Journal of Clinical Investigation (1989)

The synthesis of Cu,Zn SOD by rat lung increases spontaneously in the fetus in late gestation and during exposure of neonatal and adult rats to greater than 95% O2. To explore the regulation of these increases, we measured rat lung Cu,Zn SOD synthesis and activity. We also cloned and sequenced a rat lung Cu,Zn SOD cDNA that was used to measure Cu,Zn SOD mRNA concentration. We found that (a) under normal gestational and postgestational conditions the synthesis of this enzyme was regulated pretranslationally; (b) the increased synthesis that occurs under hyperoxia (greater than 95% O2), was pretranslationally mediated in otherwise unmanipulated neonatal rats but translationally controlled in hyperoxic adult rats; and (c) in lungs of rats made tolerant to greater than 95% O2 by allowing 24 h rest in air after an initial 48 h in greater than 95% O2, the increased Cu,Zn SOD synthesis that occurred during the second period of hyperoxia was regulated pretranslationally. We conclude Cu,Zn SOD gene expression in the lung is developmentally regulated under normal conditions and in response to an oxidant challenge. Tolerance, whether endogenous or induced, appears to require the accumulation of increased amounts of Cu,Zn SOD mRNA.
THE PROGNOSIS IN CONGENITAL DISLOCATIONS OF THE HIP
Authors: EDWARD H. OCHSNER
Journal: JAMA (1910)

The subject of congenital dislocations of the hip has in recent years been so thoroughly covered in orthopedic text-books and monographs that most of its phases can be looked on as definitely settled. There are, however, a few problems that still remain open and require further observation and discussion. There is still considerable difference of opinion as to the ultimate prognosis in congenital dislocations of the hip, and, as is usual in such cases, only carefully compiled statistics can definitely settle the question. It is with the hope of aiding a little in the solution of this phase of the problem that I have decided to consider it and to add a report of the cases which I have myself treated, and to discuss briefly some of the factors which seem to me to have been most potent in producing the large percentage of complete or partial failures reported in
Normal Insulin Sensitivity During the Late Preclinical Stage of Type 1 Diabetes
Authors: Etienne Larger, Benjamin Rakotoaminina, Mohammed Eddouks, José Timsit, Christian Boitard, Roger Assan, Rémy Burcelin, Jean-Jacques Robert
Journal: Diabetes Care (2004)

In most cases, type 1 diabetes is the late consequence of a β-cell autoimmune destruction leading to absolute insulin deficiency (1). At onset of clinical diabetes, β-cell mass is thought to be reduced by 80–90% (2), and 73% of adult patients have ketosis or ketoacidosis at diagnosis (3). Patients with type 1 diabetes have major defects in insulin sensitivity at diagnosis of overt diabetes (4–8). However, the fact that pre-diabetic patients can maintain normal blood glucose levels in spite of dramatically low insulin secretory capacities suggests that their insulin sensitivity is normal.

Here we report that insulin sensitivity, measured by the glucose clamp method in nine patients, remains normal even during the very late preclinical stage of type 1 diabetes. None of these patients …
Review of Cynthia R. Daniels, <i>At Women's Expense: State Power and the Politics of Fetal Rights</i>
Authors: Virginia Ashby Sharpe
Journal: The American Journal of Bioethics (2002)

"Review of Cynthia R. Daniels, At Women's Expense: State Power and the Politics of Fetal Rights." The American Journal of Bioethics, 2(1), pp. 65–66
Helium Ion Charged Particle Therapy for Choroidal Melanoma
Authors: Devron H. Char, Joseph R. Castro, Jeanne M. Quivey, George T.Y. Chen, John T. Lyman, Robert D. Stone, Alexander R. Irvine, Michael Barricks, J. Brooks Crawford, George F. Hilton, Lawrence I. Lonn, Ariah Schwartz
Journal: Ophthalmology (1980)
Skin replacement after burn injury.
Authors: J E Laing, P G Shakespeare
Journal: BMJ (1983)

enveloping impermeable exhaust-ventilated suits in addition to working in an ultraclean environment the rate of deep sepsis fell even further, to only 0 9%.With the wisdom of hindsight (and the example of the gases) it is a pity that we do not know how effective exhaust-ventilated suits would have been if used in conventionally ventilated operating rooms.The rates noted so far were achieved without prophylactic perioperative antibiotics.The use of prophylactic antibiotics was not controlled during the experiment, but a retrospective examination of the data showed that when they were used during operations done in conventional operating rooms the deep sepsis rate was 0-8%.In ultraclean conditions there was further but insignificant improvement to 0.70,/ and when exhaust-ventilated suits were worn as well deep sepsis was reduced to a near-perfect 0 0600" (one in 1584 operations).This dramatic effect has been confirmed by an independent study in which use of antibiotics was fully controlled.3If ultraclean air more than halves the rate of sepsis in prosthetic orthopaedic surgery, why not perform all such operations in these conditions ?The implications of an affirma- tive answer need careful consideration.The available data suggest that prophylactic antibiotics are at least as effective as ultraclean air and exhaust-ventilated suits in reducing deep sepsis.Close attention to the choice of prophylactic agentsand the timing of their administration-might possibly improve their effectiveness still further.When all three measures are used simultaneously the final improvement is less than 1 0. So the cost of equipping large numbers of orthopaedic operating rooms with ultraclean air delivery and exhaust-ventilated suits could be justified only if deep sepsis rates after prosthetic surgery in conventionally ventilated operating rooms had already been reduced to the minimum possible; the further improvement of a fraction of 1 % might then be thought worth while.In the mean time attention directed to general measures and more efficient use of anti- biotics seem likely to produce greater benefit at a fraction of the cost of providing ultraclean air delivery and exhaust- ventilated suits.Should these results be extended to the rest of surgery?
Hemispheric dominance has its origins in the control of the midline organs of speech
Authors: Norman D. Cook
Journal: Behavioral and Brain Sciences (2003)

Unlike all other lateral specializations, the necessity for unilateral dominance is clear only for the case of the motor control of the speech organs lying on the midline of the body and innervated from both hemispheres. All functional asymmetries are likely to be a consequence of this asymmetry of executive control.
Omentin Prevents Myocardial Ischemic Injury Through AMP-Activated Protein Kinase- and Akt-Dependent Mechanisms
Authors: Yoshiyuki Kataoka, Rei Shibata, Koji Ohashi, Takahiro Kambara, Takashi Enomoto, Yusuke Uemura, Yasuhiro Ogura, Daisuke Yuasa, Kazuhiro Matsuo, Takanobu Nagata, Toyoharu Oba, Hideo Yasukawa, Yasushi Numaguchi, Takahito Sone, Toyoaki Murohara, Noriyuki Ouchi
Journal: Journal of the American College of Cardiology (2014)
Natural history of "early" gastric cancer: results of a 10-year regional survey.
Authors: J W Fielding, D J Ellis, B G Jones, J Paterson, D J Powell, J A Waterhouse, V S Brookes
Journal: BMJ (1980)

In "early" gastric cancer the depth of invasion by the primary tumour is confined to the submucosa of the stomach. Out of 13228 cases of gastric cancer notified to the Birmingham Cancer Registry during 1960-9, 90 (0 . 7%) were identifed as early gastric cancer. The crude five-year survival rate of these 90 patients was 57 . 8% (age-adjusted rate 70 . 4%) compared with 3 . 7% (age-adjusted rate 4 . 7%) for all cases and 14 . 6% (age-adjusted rate 17 . 4%) for the cases treated radically. Prognostic factors established for gastric cancer pertained equally to early gastric cancer. Most of the 90 patients had had symptoms related to the gastrointestinal tract, but in contrast to patients with advanced gastric cancer only 19% had lost weight on admission. These findings suggest that early investigation of dyspeptic symptoms would increase the detection of early gastric cancer, the most important prognostic group identified in gastric cancer.
Transcatheter Closure of Patent Foramen Ovale Without an Implant
Authors: Horst Sievert, Evelyn Fischer, Corinna Heinisch, Nico Majunke, Albrecht Roemer, Nina Wunderlich
Journal: Circulation (2007)

Background— Currently available catheter techniques for closure of a patent foramen ovale (PFO) rely on the placement of an implantable closure device. The objective of the Paradigm I study was to evaluate the safety and feasibility of transcatheter closure of PFO using radiofrequency energy without an implanted device in patients with cryptogenic stroke or transient ischemic attack. Methods and Results— Thirty patients were enrolled (15 females; mean age 48 years). Mean PFO size was 8.5±2.7 mm. Technical success (ie, successful application of radiofrequency energy) was achieved in 27 patients. The remaining 3 patients received an implantable closure device. All 30 patients were free from serious procedure-related adverse events. No recurrent strokes, deaths, or perforations occurred as a result of the procedure. The mean follow-up was 6 months, and 13 (43%) of the 30 patients experienced PFO closure after the first procedure. Nine of the patients whose PFOs remained patent after the first procedure elected to receive a second procedure using radiofrequency. The PFO was closed for 6 of those patients after the second procedure, which resulted in a secondary closure rate of 63%. Conclusions— This study demonstrates that transcatheter closure of an intracardiac defect without a permanent implant is technically feasible. Achievement of improved primary closure rates through technique and device modifications will warrant randomized clinical comparison to permanently implanted devices.
Does prior angina predict outcomes following acute myocardial infarction? Testing the relevance of ischemic pre-conditioning in the era of primary angioplasty
Authors: Kishore J. Harjai, Cindy L. Grines, H.Mehrdad Sadeghi, Calvin Ledford, Dominic Marsalese, Judith Boura, Robert D. Safian, James A. Goldstein, Joel Kahn, William W. O'Neill
Journal: Journal of the American College of Cardiology (2002)
Influence of Pregnancy on the Risk for Cardiac Events in Patients With Hereditary Long QT Syndrome
Authors: Eric J. Rashba, Wojciech Zareba, Arthur J. Moss, W. Jackson Hall, Jennifer Robinson, Emanuela H. Locati, Peter J. Schwartz, Mark Andrews
Journal: Circulation (1998)

The effects of pregnancy on women with the hereditary long QT syndrome are currently unknown. The appropriate medical management of pregnant patients with the long QT syndrome has not been established.The study was a retrospective analysis of the 422 women (111 probands affected with the long QT syndrome and 311 first-degree relatives) enrolled in the long QT syndrome registry who had one or more pregnancies. The first-degree relatives were classified as affected (QTc >0.47), borderline (QTc=0.45 to 0.47), and unaffected (QTc <0.45). Cardiac events were defined as the combined incidence of long QT syndrome-related death, aborted cardiac arrest, and syncope. The incidence of cardiac events was compared during equal prepregnancy, pregnancy, and postpartum intervals (40 weeks each). Multivariate logistic regression analysis was performed by use of a mixed-effects model to identify independent predictors of cardiac events among probands. The pregnancy and postpartum intervals were not associated with cardiac events among first-degree relatives. The postpartum interval was independently associated with cardiac events among probands (odds ratio [OR], 40.8; 95% confidence interval [CI], 3.1 to 540; P=.01); the pregnancy interval was not associated with cardiac events. Treatment with beta-adrenergic blockers was independently associated with a decrease in the risk for cardiac events among probands (OR, 0.023; 95% CI, 0.001 to 0.44; P=.01).The postpartum interval is associated with a significant increase in risk for cardiac events among probands with the long QT syndrome but not among first-degree relatives. Prophylactic treatment with beta-adrenergic blockers should be continued during the pregnancy and postpartum intervals in probands with the long QT syndrome.
Paying for the view
Authors: Ike Iheanacho
Journal: BMJ (2008)

It’s a wonder they can talk at all, given their mouths are so stuffed with industry gold. Somehow, though, they manage it, and often to great effect.

Opinion leaders are megastars of the medical world. Groomed, pampered, and promoted by drug companies, they are the role models whose views are to be taken seriously.

Such individuals are part of an elaborate game that supposedly ensures “transparency” about the relationships between doctors and their industry paymasters. The declarations of competing interests so …