tbuckley/cabot-search huggingface dataset:
Laboratory tests for protein C deficiency
Authors: Bernard Khor, Elizabeth M. Van Cott
Journal: American Journal of Hematology (2010)

Hereditary protein C deficiency is a hypercoagulable state associated with an increased risk for venous thrombosis. The recommended initial test for protein C is an activity (functional) assay, which may be clotting time based or chromogenic. The advantages and disadvantages of the various testing options are presented. The causes of acquired protein C deficiency are much more common than hereditary deficiency. Therefore, this article describes the appropriate steps to take when protein C activity is low, to confirm or exclude a hereditary deficiency. The causes of falsely normal results are also described, including lupus anticoagulants and direct thrombin inhibitors.
Energy expenditure, sex, and endogenous fuel availability in humans
Authors: Søren Nielsen, ZengKui Guo, Jeanine B. Albu, Samuel Klein, Peter C. O’Brien, Michael D. Jensen
Journal: Journal of Clinical Investigation (2003)

Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because "normal" FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean and obese adults (25 women). Resting energy expenditure (REE), but not body composition, predicted most of the interindividual variation in FFA release. There was a significant, positive linear relationship between palmitate release and REE; however, women released approximately 40% more FFA than men relative to REE. Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women. Glucose release rates were not different in men and women whether related to REE or fat free mass. These findings indicate that nonoxidative FFA clearance is greater in women than in men. This could be an advantage at times of increased fuel needs. We conclude that "normal" adipose tissue lipolysis is different in men and women and that the fuel export role of adipose tissue in obesity will need to be reassessed.
UK introduces far reaching law to protect whistleblowers
Authors: C. Dyer
Journal: BMJ (1999)

A new law to protect UK employees who blow the whistle on wrongdoing or malpractice at work came into force this week. The Public Interest Disclosure Act 1998, described by US campaigners as “the most far reaching whistleblower law in the world,” comes in the wake of the Bristol heart surgery case and other medical tragedies.

Introduced as a private member's bill by the Conservative MP Richard Shepherd, the legislation owes much to the work of the Freedom of Information Campaign and the charity Public Concern at Work, which offers free legal advice to employees concerned about serious malpractice.

The Labour government has enthusiastically …
The relationship between RAST and skin test results in patients with asthma or rhinitis: A quantitative study with purified major allergens
Authors: Agnes M. Witteman, Steven O. Stapel, Gerrard J. Perdok, Deman H.S. Sjamsoedin, Henk M. Jansen, Rob C. Aalberse, Jaring S. van der Zee
Journal: Journal of Allergy and Clinical Immunology (1996)
Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.
Authors: John S Vogel, Garrett A Keating, Bruce A Buchholz
Journal: Environmental Health Perspectives (2002)

Full toxicologic profiles of chemical mixtures, including dose-response extrapolations to realistic exposures, is a prohibitive analytical problem, even for a restricted class of chemicals. We present an approach to probing in vivo interactions of pesticide mixtures at relevant low doses using a monitor compound to report the response of biochemical pathways shared by mixture components. We use accelerator mass spectrometry (AMS) to quantify [14C]-diisopropylfluorophosphate as a tracer at attomole levels with 1-5% precision after coexposures to parathion (PTN), permethrin (PER), and pyridostigmine bromide separately and in conjunction. Pyridostigmine shows an overall protective effect against tracer binding in plasma, red blood cells, muscle, and brain that is not explained as competitive protein binding. PTN and PER induce a significant 25-30% increase in the amount of tracer reaching the brain with or without pyridostigmine. The sensitivity of AMS for isotope-labeled tracer compounds can be used to probe the physiologic responses of specific biochemical pathways to multiple compound exposures.
Disruption of Nitric Oxide Synthase 3 Protects Against the Cardiac Injury, Dysfunction, and Mortality Induced by Doxorubicin
Authors: Tomas G. Neilan, Sarah L. Blake, Fumito Ichinose, Michael J. Raher, Emmanuel S. Buys, Davinder S. Jassal, Elissa Furutani, Teresa Miriam Perez-Sanz, Amanda Graveline, Stefan P. Janssens, Michael H. Picard, Marielle Scherrer-Crosbie, Kenneth D. Bloch
Journal: Circulation (2007)

Flavoprotein reductases are involved in the generation of reactive oxygen species by doxorubicin. The objective of the present study was to determine whether or not one flavoprotein reductase, endothelial nitric oxide synthase (nitric oxide synthase 3 [NOS3]), contributes to the cardiac dysfunction and injury seen after the administration of doxorubicin.A single dose of doxorubicin (20 mg/kg) was administered to wild-type (WT) mice, NOS3-deficient mice (NOS3-/-), and mice with cardiomyocyte-specific overexpression of NOS3 (NOS3-TG). Cardiac function was assessed after 5 days with the use of echocardiography. Doxorubicin decreased left ventricular fractional shortening from 57+/-2% to 47+/-1% (P<0.001) in WT mice. Compared with WT mice, fractional shortening was greater in NOS3-/- and less in NOS3-TG after doxorubicin (55+/-1% and 35+/-2%; P<0.001 for both). Cardiac tissue was harvested from additional mice at 24 hours after doxorubicin administration for measurement of cell death and reactive oxygen species production. Doxorubicin induced cardiac cell death and reactive oxygen species production in WT mice, effects that were attenuated in NOS3-/- and were more marked in NOS3-TG mice. Finally, WT and NOS3-/- mice were treated with a lower dose of doxorubicin (4 mg/kg) administered weekly over 5 weeks. Sixteen weeks after beginning doxorubicin treatment, fractional shortening was greater in NOS3-/- than in WT mice (45+/-2% versus 28+/-1%; P<0.001), and mortality was reduced (7% versus 60%; P<0.001).These findings implicate NOS3 as a key mediator in the development of left ventricular dysfunction after administration of doxorubicin.
PMO-157 HBSAG plasma levels decline helps to predict HBEAG loss but is similar in different NUCLEOS(T)IDE analogues regimens
Authors: M Horner, M J Bruce, S Knighton, M Al-Freah, D Joshi, S Hughes, A Suddle, P M Harrison, K Agarwal, I Carey
Journal: Gut (2012)

<h3>Introduction</h3> The kinetics of serum HBsAg (qHBsAg) decline predict response to treatment with pegylated interferon (Peg-IFN) in chronic hepatitis B (CH-B). Whereas nucleos(t)ide analogue (NA) therapy is associated with a sharp decrease in serum HBV DNA level due to inhibition of the viral polymerase, only limited data are available comparing the effect of different treatment regimens on qHBsAg kinetics. This study compared serum qHBsAg and HBV DNA kinetics in patients with CH-B receiving de-novo therapy with either tenofovir (TDF) 245 mg/day, entecavir (ETV) 0.5 mg/day or lamivudine 100 mg/day plus adefovir 10 mg/day (LAM+ADV). <h3>Methods</h3> 205 CH-B therapy naïve monoinfected patients (75% males, 21% HBeAg positive, 21% cirrhotic, median age 36 years) were treated with TDF (n=50), ETV (n=62) or LAM+ADV (n=93) for at least 12 months. We quantified qHBsAg (Abbott ARCHITECT® assay) and HBV DNA (real-time TaqMan PCR) in serial serum samples at baseline, months 3 (M3), 6 (M6) and 12 (M12). <h3>Results</h3> Median qHBsAg levels were similar at each time-point and were not influenced by treatment regimen. No patient achieved HBsAg loss. More patients receiving TDF achieved optimal virological response (VR), defined as HBV DNA &lt;20 IU/ml), at M3 compared to ETV and LAM+ADV (60% vs 43% vs 40%, respectively; p=0.05) but not at M6 (76% vs 74% vs 79%) and M12 (80% vs 82% vs 82%). The proportion of patients achieving HBsAg decline &gt;0.5 log<sub>10</sub> IU/ml was higher in ETV cohort at M3 than in TDF and LAM+ADV (10% vs 2% and 2% respectively; p=0.05), but not at M6 (10% vs 6% vs 5%) and M12 (12% vs 10% vs 8%). HBeAg loss was more frequent in LAM+ADV and TDF groups than ETV (47% vs 33% vs 6%, respectively; p=0.03) and correlated with greater qHBsAg decline at all treatment time-points (M3: r=0.47, p=0.04; M6: r=0.55, p=0.03 &amp; M12: r=0.58, p=0.03). Patients achieving VR had higher qHBsAg levels (M3: 3.71 vs 3.29 log<sub>10</sub>IU/ml; M6: 3.67 vs 3.24; and M12: 3.66 vs 3.24; all p&lt;0.01), slower qHBsAg decline and fewer patients with qHBsAg &gt;0.5 log<sub>10</sub>IU/ml from baseline compared to those with detectable HBV DNA. <h3>Conclusion</h3> Serum qHBsAg kinetics during therapy were a good predictor of HBeAg loss. However, antiviral therapy in CH-B with nucleos(t)ide analogues in the first 12 months was similar between variable therapeutic approaches and there was no significant qHBsAg decline in contrast to HBV DNA suppression. <h3>Competing interests</h3> M Horner: None declared, M Bruce: None declared, S Knighton: None declared, M Al-Freah: None declared, D Joshi: None declared, S Hughes: None declared, A Suddle: None declared, P Harrison: None declared, K Agarwal: None declared, I Carey grant/research support from: BMS, Gilead.
Carving corneas for aphakic patients
Authors: Phil Gunby
Journal: JAMA (1979)

New York researchers are encouraged by results of an experimental microsurgical procedure for altering corneal curvature after cataract removal. Richard C. Troutman, MD, Downstate Medical Center, State University of New York, Brooklyn, told a Research to Prevent Blindness seminar in Los Angeles that he and colleagues have used the refractive keratoplasty procedure with 38 patients since October 1977. The keratophakia approach (combined with intracapsular cataract extraction) was used in most cases. A slice of donor cornea is removed with a special microkeratome, frozen, and carved on a modified contact lens lathe into a lens 0.2 mm thick. The homograft is inserted between layers of the patient's cornea to change its curvature. In a related keratomileusis approach, a slice of the patient's own cornea is frozen, carved on the lathe, and sutured back onto the remaining cornea to provide a curvature that has been preprogrammed by computer to correct the optical
The Role of Mycoplasma (Pleuropneumonia-like Organisms) in Human Disease
Authors: Maurice C. Shepard, George L. Calvy
Journal: New England Journal of Medicine (1965)

CAMP LE JEUNE, NORTH CAROLINAIN early 1960, at a meeting of the Armed Forces Epidemiological Board, one of us (G.L.C.) asked a member, "What are your thoughts on the etiologic significance of the pleuropneumonia-like organisms in relation to human disease?" The following reply came without hesitation:This group of organisms may very well be the next area of important breakthrough in infectious disease. There is a great need for more basic research confined to this area, for the biology of the pleuropneumonia-like organisms is still not well understood. Much conscientious and careful work has already been done, and it . . .
Assessment of Inspiratory Flow Limitation Invasively and Noninvasively during Sleep
Authors: SUSANNE A. CLARK, CHRISTINE R. WILSON, MAKOTO SATOH, DAVID PEGELOW, JEROME A. DEMPSEY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To define the standard of airway flow limitation, pharyngeal pressure and flow rate were measured during wakefulness and sleep in seven habitual snorers with widely varying degrees of sleep-induced increases in upper airway resistance. Inspiratory pressure:flow relationships were used to group breaths into four categories of flow limitation, including linear (Level 1), mildly alinear (Level 2), constant flow rate with no pressure dependence (Level 3), and decreasing flow rate throughout significant portions of inspiration, i.e., negative pressure dependence (Level 4). These pressure:flow rate gold standards of flow limitation were used to evaluate a flow limitation index derived from the time profile (or "shape") of three noninvasive estimates of flow rate: (1) pneumotach flow rate, (2) differentiated sum respiratory inductance plethysmography (RIP), and (3) nasal pressure. A nonflow limited template for each of these noninvasive measurements was taken from awake breaths and the difference in area determined between the template breath and each of the noninvasive signals measured during nonrapid eye movement (NREM) sleep. The noninvasive flow limitation indices were found to be effective in differentiating severe types of inspiratory flow limitation, i.e., Level 1 versus Level 3 or Level 4 (sensitivity/specificity > 80%). On the other hand, these indirect indices were not able to consistently detect mild levels of flow limitation (Level 1 versus Level 2; sensitivity/specificity = 62 to 72%); nor were these noninvasive estimates of flow rate "shape" sensitive to breaths with a high but fixed resistance throughout inspiration. The area index derived from measurements of pressure at the nares (Pn) was the most sensitive, nonperturbing, noninvasive measure of flow rate and flow limitation, and we recommend its use for recognizing most of the common types of moderate to severe levels of airway flow limitation in sleeping subjects.
Medical Education: Past, Present and Future
Authors: John A.D. Cooper
Journal: New England Journal of Medicine (1977)

Before 1930, medical schools in the United States were relatively simple institutions with small basic-science departments and largely volunteer clinical faculty members who donated time taken from their private practice of medicine. Education for the medical degree was almost the only mission of the institution. Little effort was devoted to biomedical research and patient care. It was easy for the institutions to march to the clear beat of a single drummer.Changes that began during World War II and accelerated over the next three decades transformed medical schools into large, complex academic medical centers with a vast array of inter-related . . .
Book Review Effects of A-Bomb Radiation on the Human Body Edited by the Hiroshima International Council for Medical Care of the Radiation-Exposed, with Itsuzo Shigematsu, Chikako Ito, nanao Kamada, Mitoshi Akiyama, and Hideo Sasaki. 419 pp. Langhorne, Pa., Harwood Academic, 1995. $50. 3-7186-5418-0
Authors: John W. Fowler
Journal: New England Journal of Medicine (1995)
Abstract P4-03-09: Time points to diagnosis and treatment of invasive breast cancer in southwestern Ontario
Authors: TA Vandenberg, B Ballantyne, LA Diaz Rodriguez, FJ Whiston, LW Stitt
Journal: Cancer Research (2013)

Abstract Background Delays in breast cancer diagnosis and treatment are associated with increased tumour size at presentation, higher incidence of lymph node metastasis, higher relapse rates and lower 5-year survival rates in some studies. Diagnosis and treatment of breast cancer is complex, involving many health care practitioners at multiple locations. New advances in diagnostic and prognostic indicators make the process ever more complex. We reviewed the timing of crucial events in breast cancer diagnosis and treatment in Southwestern Ontario. Methods: Two time periods (2001, 2011) were assessed. Patients with new early invasive breast cancer with specific TNM criteria (T1c or greater plus any N, or any T plus N1-3; M0) were included. Data collection and analysis explored significant time points from first suspicion of malignancy, to diagnosis and definitive treatment, as well as patient demographic information. Results: 300 and 451 eligible patients were identified in 2001 and 2011 cohorts. Distribution of T and N status by cohort was compared by Chi-square test and time from first suspicion to diagnosis by Wilcoxon testing. The proportion of patients in which the time from first suspicion (clinical by lay person or health professional or by imaging) to pathological diagnosis exceeded two months increased from 20.4% in 2001 to 42.1% in 2011. There were no differences in time from first suspicion to diagnosis when analyzed by age (p = 0.54) or location (p = 0.50). Pathological T2-4 status at diagnosis increased from 48.4% in 2001 to 56.8% in 2011, and N2-3 status increased from 7.3% to 12.6%. Patients who had mammograms increased from 52.7% to 59.4%. A positive or suspicious mammogram was the first sign in 36% and 39.1% of cases. There was a trend towards more pathological diagnoses and definitive surgeries at tertiary centers compared to community hospitals. Conclusions: There is a longer time interval from first suspicion of malignancy to pathological diagnosis in 2011 compared to 2001 for both urban and rural populations. The number of non-low risk, non-metastatic cancers at diagnosis increased by 50% over the time interval studied (300 v 451), but number of T2-T4 non-metastatic cancers increased by 77% (145 v 256) and N2,3 cancers by 136% (22 v 52). This is despite more patients receiving mammograms (52.7% v 59.4%). Delays in breast cancer treatment are multifactorial, including both system-, and patient-related factors. This is an under-researched area and more investigation is needed to understand the reasons for the diagnostic delays and more serious cancers at presentation in order to improve outcomes. Reasons for higher proportions of advanced cancers will be discussed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-03-09.
Computers in Medicine: Applications and Possibilities
Authors: Vincent Scott
Journal: JAMA (1987)

In the preface of<i>Computers in Medicine</i>the author laments that his search for a basic book introducing physicians to computers proved fruitless. After reading his contribution, one finds the search must still continue. Although timely and informative,<i>Computers in Medicine</i>offers little to the physician who has minimal or no computer literacy. One cannot hope to gain a good education about computers solely from reading this book. Physicians finding computers intimidating and mysterious will not find them less so after reading<i>Computers in Medicine</i>. The book is divided into two parts. Part 1 describes what computers are, how personal productivity can be maximized, and how computers may be integrated into medical practice and education. It succeeds in informing the reader why computers are important and how a computerized medical practice can be efficient. Part 2 is about applications of computers to patient care. Chapters 7 and 8 are especially
Impotence in Progressive Systemic Sclerosis
Authors: EDWARD V. LALLY
Journal: Annals of Internal Medicine (1981)

Five men with progressive systemic sclerosis presented with impotence as a significant initial feature of their disease. Endocrine, urologic, and psychiatric evaluations failed to reveal another cause for impotence. We suggest that male erectile dysfunction represents another manifestation of systemic sclerosis. Possible mechanisms for this phenomenon are discussed.
A Guide to Drugs in Current Use
Authors: John D. Archer
Journal: JAMA (1971)

This multiauthored book, organized by therapeutic categories, provides synopses of the major properties of most prominent, single-entity drugs currently prescribed. Monographs on these typically include summaries of selected features of pharmacology, usual therapeutic indications, common or important adverse reactions, and contraindications. The nomenclature for drugs is primarily British, but nonproprietary US synonyms are usually given; trademark names are not used. Most of the book succeeds quite well in presenting essential and valid information of the limited scope intended. Unfortunately, however, the quality is not even throughout. Certain surprising omissions of important drugs and needed information, a few unrealistic comparisons between drugs, and occasional statements subject to challenge tend to compromise the overall usefulness of a generally worthwhile effort. Less important, but mildly distracting, are occasional lapses in style. In summary, this little book can provide a fair general knowledge of drugs and would be a worthwhile addition to a medical
Significance of Programmed Cell Death-Ligand 1 Expression and its Association with Survival in Patients with Small Cell Lung Cancer
Authors: Hidenobu Ishii, Koichi Azuma, Akihiko Kawahara, Kazuhiko Yamada, Yohei Imamura, Takaaki Tokito, Takashi Kinoshita, Masayoshi Kage, Tomoaki Hoshino
Journal: Journal of Thoracic Oncology (2014)
Optimal Parameters of Electrical Impulses for Defibrillation by Condenser Discharges
Authors: Bohumil Peleška, Z. Blažek, M. Rábl, E. Sládkovaá, Z. Roth
Journal: Circulation Research (1966)

The defibrillation threshold for various wave forms of condenser discharge, using capacitors from 4 to 200 µF, has been measured. Condenser discharge alone was used, or condenser discharge 0.25 henry (20 ohms) with an iron core series inductance, or condenser discharge, 0.29 henry (27 ohms) inductance, but without the iron core. Statistical analysis of the results showed that the last of these three circuits gave the lowest threshold voltage values. Optimal parameters of inductance-altered discharges are obtained with values of 24, 32, and 50 µF. Detailed analysis of the separate physical parameters of the discharge show that optimal pulse duration is 8.5 to 16.6 msec. Further increase of duration does not decrease the voltage or current for threshold shocks, but merely increases the energy delivered. Pulse duration appears to be one of the more important parameters for successful defibrillation, and for this reason, a series inductance is also important.
Diagnostic accuracy studies: how to report and analyse inconclusive test results
Authors: B. Shinkins, M. Thompson, S. Mallett, R. Perera
Journal: BMJ (2013)

Failure to report inconclusive test results can lead to misleading conclusions regarding the accuracy and clinical usefulness of a diagnostic tool. We show that these results are often overlooked in research on test accuracy and provide guidance on suitable approaches to reporting and analysing these problematic results.
Concurrent Antiplatelet and Fibrinolytic Therapy
Authors: Richard A. Lange, L. David Hillis
Journal: New England Journal of Medicine (2005)

In patients who have myocardial infarction with ST-segment elevation, rupture of an atherosclerotic plaque leads to platelet adhesion, activation, and aggregation, with subsequent vessel occlusion due to thrombus formation. In these circumstances, the most effective pharmacologic reperfusion regimen is concurrent fibrinolytic therapy and platelet inhibition. The marked benefit of such a combination was first established in the Second International Study of Infarct Survival, in which 35-day mortality among patients with suspected myocardial infarction was 13.2 percent for those receiving neither streptokinase nor aspirin, approximately 10.5 percent for those given one or the other, and 8.0 percent for those receiving both . . .
Lower Intestinal Hemorrhage Due to a Dislodged Metallic Stent
Authors: S. Y. Wong, F.-H. Ng
Journal: Endoscopy (1997)

A case of a 72 year old man is reported who developed a choledochoduodenal fistula due to distal biliary obstruction by a tumor of the papilla. A metal stent, introduced through this fistula into the common bile duct, dislodged and passed spontaneously with the feces. Plastic stents were then successfully inserted.