tbuckley/cabot-search huggingface dataset:
Signal Transduction - a Practical Approach.
Authors: S. A Rees
Journal: Cardiovascular Research (1994)

Signal Transduction - a Practical Approach. Slan A Rees Slan A Rees Oxford, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 5, May 1994, Page 724, https://doi.org/10.1093/cvr/28.5.724 Published: 01 May 1994
A Comparison of the Effect of Desiccated Thyroid and Sodium Levothyroxine on the Serum Protein-Bound Iodine
Authors: Melvin I. Sturnick, Mark Falcon Lesses
Journal: New England Journal of Medicine (1961)

THE exact standardization of desiccated thyroid is A difficult as it is not a pure chemical substance. Within U.S.P. specifications, thyroid-gland preparations vary in physiologic activity. A number of more purified compounds have been introduced to make the administration and standardization of thyroid medication more exact and therefore more predictable.1 Through the work of Harington,2 Kendall, Pitt Rivers, Hems and Clayton, pure L-thyroxine became available for general use.3 There has been general agreement about the equivalent dosage of desiccated thyroid and sodium levothyroxine needed for a similar clinical effect. Starr and Liebhold-Schueck4 considered that 0.1 mg. of sodium levothyroxine . . .
An Abnormal Thyroid Finding Produced by a Phenothiazine
Authors: Edward H. Cransuick
Journal: JAMA (1962)

AS PART of an over-all thyroid investigation of ^schizophrenic subjects, the protein-bound iodine (PBI) was one of the indices studied. Deviations from the normal (4-8 meg 100 ml.) have seldom been encountered in our schizophrenic population. However, in an investigation of the effect of psychophannaceuticals on thyroid function, it was noticed that in a small group of patients receiving perphenazine the PBI tended to rise. Two patients, for example, had normal values for 3 base-line PBI's taken before going on medication (as part of a study in which their thyroid function was investigated every 3 months). At the end of 3 months of therapy with perphenazine at a dose of 24 mg. per day, all had PBI's above 8; the high values persisted during the 3-month placebo period which followed (table). A third patient who became disturbed and had to receive perphenazine had a normal PBI before receiving the drug,
BRIGHT'S DISEASE: ANURIA: INTESTINAL HAEMORRHAGE: DEATH
Authors: L. Cole-Baker
Journal: BMJ (1903)

can take long walks and cycle rides without getting blown," which speaks well for her cardiac condition.I have omitted the details of her treatment as the chief interest of the case, and its claim to be recorded lies in the unusual severity and persistence of the rheumatic invasion as shown by the sequelae.The associations between rheumatic fever, chorea, iritis, and endocarditis are well recognized, but it is rare for ,these complications to occur consecutively in one patient.I may add that the child had never previously suffered from rheumatism in any of its manifestations, and the only point of note in her family history was that a maternal aunt had *had chorea as a child.
"Constructive Conscious Control"
Authors: B. Bruce-Porter, J. R. Caldwell, J. H. Dick, M. Douglas, H. Duffett, C. A. Ensor, W. J. Graham, A. R. Gunn, P. Jakins, J. Kerr, D. Ligat, J. E. R. McDonagh, P. Macdonald, R. G. McGowan, A. Moss, A. Murdoch, F. J. Thorne, H. Webb, A. H. Winchester
Journal: BMJ (1937)
Abstract 18220: Aortic Valve Replacement is Associated with Increased Survival in Asymptomatic Patients with Severe Aortic Stenosis
Authors: S Chris Malaisrie, John Kubasiak, Robert O Bonow, Edwin C McGee, Richard Lee, Kameswari Maganti, Eric Tuday, Brittany Lapin, Patrick M McCarthy
Journal: Circulation (2010)

Objectives: Aortic valve replacement (AVR) in patients with asymptomatic, severe aortic stenosis (AS) remains controversial. Current guidelines recommend medical management for truly asymptomatic patients with severe AS and normal left ventricular function. This study sought to determine the natural history of patients with asymptomatic, severe AS, stratified to medical and surgical management. Methods: Patients with severe AS were identified by echocardiography performed in a single tertiary care institution from 2005 to 2009. Severe AS was defined as peak jet velocity >4.0 m/s, mean pressure gradient >40 mmHg, or an aortic valve area <1.0 cm2. Patients with dyspnea, chest pain, or syncope were excluded. Indications for AVR included ejection fraction < 50%, very severe AS, abnormal exercise stress test, concurrent cardiac surgery, and non-cardiac surgery preoperative optimization. Results: One hundred sixty-one patients were identified, of whom 118 were managed medically and 43 underwent AVR. The medical...
Robust antiviral activity of R1626, a novel nucleoside analog: A randomized, placebo-controlled study in patients with chronic hepatitis C
Authors: Stuart K. Roberts, Graham Cooksley, Gregory J. Dore, Richard Robson, David Shaw, Heather Berns, George Hill, Klaus Klumpp, Isabel Najera, Carla Washington
Journal: Hepatology (2008)

The nucleoside analog R1479 is a potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro. R1626, a tri-isobutyl ester prodrug of R1479, was developed to increase bioavailability and improve antiviral activity. A multicenter, observer-blinded, randomized, placebo-controlled, multiple ascending dose, phase 1b study was designed to evaluate the safety, pharmacokinetics, and antiviral activity and to potentially identify the maximum tolerated dose of R1626 in patients with chronic hepatitis C. Forty-seven treatment-naïve patients infected with HCV genotype 1 were treated with R1626 orally at doses of 500 mg, 1500 mg, 3000 mg, or 4500 mg or placebo twice daily for 14 days with 14 days of follow-up. Safety, tolerability, pharmacokinetics, and antiviral activity were assessed. Doses up to and including 3000 mg twice daily were well tolerated after 14 days of treatment. There was an increase in frequency of adverse events at the highest dose (4500 mg). Reversible mild to moderate hematological changes were observed with increasing doses. R1626 was efficiently converted to R1479, with dose-proportional pharmacokinetics observed over the entire dose range. The pharmacokinetics of R1479 were linear over the dose range evaluated. Dose-dependent and time-dependent reductions in HCV RNA were observed. Mean decreases (median; range) in viral load after 14 days of treatment with doses of 500, 1500, 3000, and 4500 mg were 0.32 (0.22; 0.01-0.71), 1.2 (0.8; 0.49-2.46), 2.6 (2.7; 1.27-3.93) and 3.7 (4.1; 2.15-4.39) log(10), respectively. No resistance to R1479 was observed after 14 days of treatment with R1626.These data support further studies of R1626 in combination with peginterferon alfa-2a and ribavirin for the treatment of patients with chronic HCV infection.
SYSTEMIC POISONING BY HAIR DYE
Authors: H. W. Nott
Journal: BMJ (1924)

MAC _,I)4 MDCLJWA 2 D-uring the course of acute infectiolns, especially influenza, meningeal symptoms may appear2 due to " meningismus "- that is to say, an increased formation of cerebro-spinal fluid without infection of the meninges.Professor Abram and others have showln that withdrawal of cerebro-spinal flulid
Intraglomerular microcirculation: Measurements of single glomerular loop flow in rats
Authors: Michael Steinhausen, Bernd Zimmerhackl, Heinz Thederan, Rudolf Dussel, Niranjan Parekh, Hans-Ulrich Eβlinger, Gunther von Hagens, Dymitr Komitowski, Frederick D. Dallenbach
Journal: Kidney International (1981)
Pneumonic Tularemia on Martha's Vineyard
Authors: Steven M. Teutsch, William J. Martone, Edward W. Brink, Morris E. Potter, Gail Eliot, Russell Hoxsie, Robert B. Craven, Arnold F. Kaufmann
Journal: New England Journal of Medicine (1979)

IN the United States tularemia occurs in both sporadic and epidemic forms.1 2 3 Although ulceroglandular tularemia is readily diagnosed, pneumonic tularemia is difficult to detect in the absence of a typical ulceroglandular lesion or a clear history of exposure. An outbreak of pneumonic tularemia on Martha's Vineyard, Massachusetts, has suggested that the island is an important focus of infection.The Case ClusterThe outbreak occurred at a vacation cottage in a largely rural area, where seven persons stayed together during the week of July 30 to August 6, 1978. The cottage shares its well with one other cottage, whose residents were . . .
Effect of Computed Tomography of the Appendix on Treatment of Patients and Use of Hospital Resources
Authors: Patrick M. Rao, James T. Rhea, Robert A. Novelline, Amy A. Mostafavi, Charles J. McCabe
Journal: New England Journal of Medicine (1998)

In patients with clinically suspected appendicitis, computed tomography (CT) is diagnostically accurate. However, the effect of routine CT of the appendix on the treatment of such patients and the use of hospital resources is unknown.
STUDIES ON MENINGOCOCCUS INFECTION
Authors: Geoffrey Rake
Journal: The Journal of Experimental Medicine (1933)

The production of monovalent sera for agglutinin or precipitin reactions with freshly isolated strains of meningococci is described. Agglutination reactions with such sera can be carried out more rapidly, at lower temperatures and in lower dilutions, than with the standard monovalent sera prepared from stock cultures, while the results so obtained are more satisfactory owing to the relative absence of cross-agglutination.
Peer review of statistics in medical research: the other problem
Authors: P. Bacchetti
Journal: BMJ (2002)

Peer review has long been criticised for failing to identify flaws in research. Here Peter Bacchetti argues that it is also guilty of the opposite: finding flaws that are not there

The process of peer review before publication has long been criticised for failing to prevent the publication of statistics that are wrong, unclear, or suboptimal. 1 2 My concern here, however, is not with failing to find flaws, but with the complementary problem of finding flaws that are not really there.

My impression as a collaborating and consulting statistician is that spurious criticism of sound statistics is increasingly common, mainly from subject matter reviewers with limited statistical knowledge. Of the subject matter manuscript reviews I see that raise statistical issues, perhaps half include a mistaken criticism. In grant reviews unhelpful statistical comments seem to be a near certainty, mainly due to unrealistic expectations concerning sample size planning. While funding or publication of bad research is clearly undesirable, so is preventing the funding or publication of good research. Responding to misguided comments requires considerable time and effort, and poor reviews are demoralising—a subtler but possibly more serious cost.

This paper discusses the problem, its causes, and what might improve the situation. Although the main focus is on statistics, many of the causes and potential improvements apply to peer review generally.

#### Summary points

Peer reviewers often make unfounded statistical criticisms, particularly in difficult areas such as sample size and multiple comparisons

These spurious statistical comments waste time and sap morale

Reasons include overvaluation of criticism for its own sake, inappropriate statistical dogmatism, time pressure, and lack of rewards for good peer reviewing

Changes in the culture of peer review could improve things, particularly honouring good performance

Mistaken criticism is a general problem, but may be especially acute for statistics. The examples below illustrate …
Tumor necrosis factor primes hepatocytes for DNA replication in the rat
Authors: Eric M. Webber, Jordi Bruix, Robert H. Pierce, Nelson Fausto
Journal: Hepatology (1998)

Signaling through tumor necrosis factor receptor type 1 (TNFR–1) using a pathway that involves nuclear factor κB (NF–κB), interleukin–6 (IL–6), and STAT3 is required for the initiation of liver regeneration. We have proposed that TNF primes hepatocytes to respond to the mitogenic effect of growth factors, but so far, there has been no experimental demonstration that TNF enhances growth factor responses of hepatocytes. To test this hypothesis, we infused hepatocyte growth factor (HGF) and transforming growth factor α (TGF–α) (40 μg/24 h) directly into the portal vein of rats for 24 hours using osmotic pumps and determined whether TNF injection (5 μg per rat) would significantly increase hepatocyte DNA labeling in these animals. All rats received 5–bromo–2′–deoxyuridine (BrdU) by intraperitoneal delivery during a 48–hour period (i.e., BrdU infusion continued for 24 hours after the end of growth factor administration). BrdU labeling in the liver was measured by both immunohistochemistry and flow cytometry, and the results obtained by these methods showed excellent concordance. The results demonstrate that TNF transiently activates NF–κB and STAT3 and increases the proliferative response of hepatocytes to HGF or TGF–α by fourfold. Priming effects on hepatocyte DNA replication were also obtained with injection of lipopolysaccharide (LPS) and gadolinium chloride (GdCl 3 ), agents that release TNF in the liver. Similarly to TNF, GdCl 3 injection caused the activation of NF–κB and STAT3, reaching a maximum 8 to 12 hours after the injection. The results show that TNF acts as a primer to sensitize hepatocytes to the proliferative effects of growth factors and offers a mechanism to explain the initiation and progression phases of liver regeneration after partial hepatectomy (PH).
Ischemic Heart Disease Prognosis
Authors: Donald R. Peterson
Journal: JAMA (1972)

Surveillance of hospitalizations for myocardial infarction from Jan 1, 1966 to Dec 31, 1969, yielded 6,987 reports from all 25 hospitals which admit such patients in King County, Washington. From these reports, we sought possible determinants of prognosis among the following factors: age, sex, race, marital status, hour, day of week, month of year and calendar year of admission, presence or absence of a coronary care unit; and size, location, and type of hospital. Only age had marked influence on hospital fatalities with patients less than 60 years of age averaging 12% fatalities and older patients showing a steadily increasing fatality percentage to 50% in the oldest age group. Patients hospitalized in facilities with coronary care units had slightly lower fatality rates than other patients. Monday admissions substantially exceeded those on other days of the week.
Nephrotic Syndrome Due to Primary Renal Disease in Adults: I. Survey of Incidence in South-east England
Authors: P. Sharpstone, C. S. Ogg, J. S. Cameron
Journal: BMJ (1969)

In a prospective survey of the nephritic syndrome due to primary renal disease in adult patients in the South-east Metropolitan Region of England 50 patients were seen in a two-year period-a minimum annual incidence of 9.0 new cases per million adult population. The frequency distribution of the three main histological groups was "minimal change" 30%, membranous nephropathy 12%, and proliferative glomerulonephritis 58%. The higher proportion of patients with minimal histological change compared with that found in most previously published series may be explained by the avoidance of selection of patients for inclusion. The much lower incidence of membranous nephropathy probably reflects the use of stricter histological criteria for this diagnosis.
SILICO-ANTHRACOSIS PRESENTING CURIOUS BODIES SIMILAR TO THOSE IN ASBESTOSIS
Authors: W. E. Cooke
Journal: BMJ (1932)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~IMIEDICAJ.JOURMALGothenburg, where epidemic catarrhal jaundice was extremely prevalent.3. The clinical history of the case here described is similar to that of many recorded from Sweden-an onset reseinbling in every way that of a benign case of epidemic catarrhal jaundice: improvement, then quite suddenly the appearance of symptoms pointing to an acute liver insufficiency.4. The pathological changes of epidemic catarrhal
Reduced Testing Frequency for Glycated Hemoglobin, HbA1c, Is Associated With Deteriorating Diabetes Control
Authors: Owen J. Driskell, David Holland, Jenna L. Waldron, Clare Ford, Jonathan J. Scargill, Adrian Heald, Martin Tran, Fahmy W. Hanna, Peter W. Jones, R. John Pemberton, Anthony A. Fryer
Journal: Diabetes Care (2014)

OBJECTIVE We previously showed that in patients with diabetes mellitus, glycated hemoglobin (HbA1c) monitoring outside international guidance on testing frequency is widespread. Here we examined the relationship between testing frequency and diabetes control to test the hypothesis that retest interval is linked to change in HbA1c level. RESEARCH DESIGN AND METHODS We examined repeat HbA1c tests (400,497 tests in 79,409 patients, 2008–2011) processed by three U.K. clinical laboratories. We examined the relationship between retest interval and 1) percentage change in HbA1c and 2) proportion of cases showing a significant HbA1c rise. The effect of demographics factors on these findings was also explored. RESULTS Our data showed that the optimal testing frequency required to maximize the downward trajectory in HbA1c was four times per year, particularly in those with an initial HbA1c of ≥7% (≥53 mmol/mol), supporting international guidance. Testing 3-monthly was associated with a 3.8% reduction in HbA1c compared with a 1.5% increase observed with annual testing; testing more frequently provided no additional benefit. Compared with annual monitoring, 3-monthly testing was associated with a halving of the proportion showing a significant rise in HbA1c (7–10 vs. 15–20%). CONCLUSIONS These findings provide, in a large, multicenter data set, objective evidence that testing outside guidance on HbA1c monitoring frequency is associated with a significant detrimental effect on diabetes control. To achieve the optimum downward trajectory in HbA1c, monitoring frequency should be quarterly, particularly in cases with suboptimal HbA1c. While this impact appears small, optimizing monitoring frequency across the diabetes population may have major implications for diabetes control and comorbidity risk.
"Endotoxicity" of the Legionnaires' Disease Bacterium
Authors: K. H. WONG
Journal: Annals of Internal Medicine (1979)

The Legionnaires' disease (LD) bacterium is a gram-negative organism whose "endotoxicity" appears to differ in several respects from the classic endotoxicity generally associated with gram-negative bacteria. Discrepancies were noted between the high activity of LD bacteria in gelating limulus lysate in vitro and their low pyrogenicity in rabbits. Further in-vivo biologic tests indicated that LD bacteria were relatively weak in "endotoxicity". Analysis of LD bacterial cells and in their cellular fractions by gas-liquid chromatography indicated that LD bacteria did not contain hydroxy fatty acids commonly associated with lipid A of endotoxin. The branched-chain fatty acids that were characteristic of LD bacteria were associated with the cell envelope, and were readily extracted into organic solvents without prior saponification. The presence of 2-keto-3-deoxyoctonate in LD bacteria and cell extracts was detected by a microassay method but remains to be confirmed with gas-liquid chromatography and mass spectrometry. The active principle "endotoxicity" in LD bacteria may be a new type of bacterial lipopolysaccharide.
Euthanasia Precise definitions are needed
Authors: A Rodway, K Collins, M L M Gilhooly, K Murray, R Twycross, T Helme, A Davis
Journal: BMJ (1994)

Precise definitions are needed EDrrOR,-The paper by B J Ward and P A Tate underlines some of the difficult issues that accompany many of the decisions concerning medical treatment at the end of life.'The paper addresses only doctors' difficulties, so is out of step with the modern management of the terminal phase of life: increasingly, this form of care is a team approach and such decisions are the result of discussions among the team.This approach clearly provides benefits and safeguards to both patients and the team.
Commentary: measures of early postoperative mortality
Authors: M McKee, C Sanderson
Journal: BMJ (1994)

The traditional image of the paternalistic surgeon failing to offer patients an informed choice about treatment based on knowledge of the risks and benefits is disappearing rapidly. Driven by growing consumerism and political pressure, there is an increasing volume of information to help patients make choices that are appropriate for them. Examples range from patient information leaflets, through provision of specialist advisers, to interactive video disks.1

If patients are to be enabled to make truly informed choices the information that they receive must be accurate. Unfortunately, much of what is published about the risk of postoperative death may be misleading. Textbooks frequently quote case series published by those working in centres of excellence and relating to patients who may be quite atypical.2 Furthermore, published papers may be subject to considerable bias, ranging from the decision to report a series to acceptance by a journal.3

There are two major problems facing those who wish to measure population based postoperative death rates in the United Kingdom. The first is the absence of data on …
Induction of a dose-related increase in sulfobromophthalein uptake velocity in freshly isolated rat hepatocytes by phenobarbital
Authors: Barry J. Potter, Jia-Zhang Ni, Kathleen Wolfe, Decherd Stump, Paul D. Berk
Journal: Hepatology (1994)

To determine whether phenobarbital affects hepatocellular bilirubin/sulfobromophthalein uptake mechanism, we administered it to male Sprague–Dawley rats, body weight 175 ± 25 gm, at doses of 1 to 75 mg/kg body wt/day for 7 days. Control rats were given an equivalent volume of physiological saline solution. On day 8, hepatocytes were isolated by means of collagenase perfusion, suspended in Hanks' solution without albumin and incubated with high specific activity (3 Ci/mmol) [35S]sulfobromophthalein, which was synthesized in our laboratory and purified by means of a new reverse–phase high–pressure liquid chromatography procedure. The initial uptake rate of sulfobromophthalein was determined at sulfobromophthalein concentrations of 1 to 50 μmol/L with a rapid filtration technique. The maximum uptake velocity and Michaelis constant for sulfobromophthalein uptake at each phenobarbital dose were determined by means of a computer analysis. In control studies, maximum uptake and Michaelis constant were 48.0 ± 16.7 (mean ± S.D.) pmol/50,000 cells/min and 22 ± 4 μmol/L, respectively. Maximum uptake velocity increased linearly with the log of the phenobarbital dose (r = 0.98, p &lt; 0.01), the increase achieving statistical significance at a dose of 3 mg/kg/day. Michaelis constant, however, was essentially unchanged at phenobarbital doses of 50 mg/kg/day or less. The maximal observed increase in maximum uptake velocity of sulfobromophthalein (to 619% of control values) was appreciably greater than the maximal increase in UDP–glucuronyltransferase activity (200% of control) or immunoreactive ligandin concentrations (260% of control) seen in earlier studies, suggesting a direct effect on the plasma membrane transport mechanism. (Hepatology 1994;20:1078-1085).
Vagus nerve contributes to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice
Authors: Xia Gao, Jelske N. van der Veen, Linfu Zhu, Todd Chaba, Marta Ordoñez, Susanne Lingrell, Debby P.Y. Koonen, Jason R.B. Dyck, Antonio Gomez-Muñoz, Dennis E. Vance, René L. Jacobs
Journal: Journal of Hepatology (2014)