tbuckley/cabot-search huggingface dataset:
Interferon Alfa Therapy for Malignant Melanoma: A Systematic Review of Randomized Controlled Trials
Authors: Marko B. Lens, Martin Dawes
Journal: Journal of Clinical Oncology (2002)

No standard systemic adjuvant therapy has been proven to increase overall survival in melanoma patients. The effect of interferon alfa (IFNalpha) as a single agent or in combination has been widely explored in clinical trials. The purpose of this study was to assess the benefit of IFNalpha therapy in malignant melanoma.We performed a systematic review of randomized controlled trials comparing regimens with or without IFNalpha adjuvant therapy in melanoma patients. We assessed the effect of IFNalpha therapy on overall survival (OS), disease-free survival (DFS), melanoma recurrences, and toxicity. The quality of each trial was systematically evaluated.Nine randomized controlled trials (RCTs) of IFNalpha therapy in melanoma patients were identified. Eight were published and one was unpublished. Eight trials comprising 3,178 patients fulfilled our inclusion criteria and were analyzed. Quality assessment scores ranged from 22 to 71, with a mean score of 55.4 (95% confidence interval, 53.8 to 57.0). For OS, only one trial reported a statistically significant benefit for IFNalpha, but our analysis did not confirm it. Two trials reported statistically significant benefit in DFS for the patients treated with IFNalpha, but our analysis confirmed it in only one trial. There was a wide clinical heterogeneity between included trials, making meta-analysis inappropriate.In our review, results from included RCTs demonstrated no clear benefit of IFNalpha therapy on OS in melanoma patients. A large RCT is required to answer whether a full regimen of IFNalpha therapy is effective and to identify the subgroups of patients who might benefit from IFNalpha treatment.
A historical whopper
Authors: Theodore Dalrymple
Journal: BMJ (2007)

Does it matter—in so far as anything literary matters these days—if historical fiction is inaccurate? Does anyone mind if Richard III is a tendentious, even a sycophantic and opportunist, justification of the Tudor dynasty, and that the real Richard III of history was a jolly Good Thing (in the Sellar and Yeatman sense), or at least a very much less Bad Thing? 

Not long ago, I read Sebastian Faulks's novel Human Traces (reviewed in BMJ 2005;331:1029 doi: 10.1136/bmj.331.7523.1029). It brought out the inner pedant in me: there was more rejoicing in my mind over one historical mistake than over 99 true facts. 

As it happens, there is …
Society's failure to protect a precious resource: antibiotics
Authors: Jean Carlet, Peter Collignon, Don Goldmann, Herman Goossens, Inge C Gyssens, Stephan Harbarth, Vincent Jarlier, Stuart B Levy, Babacar N'Doye, Didier Pittet, Rosana Richtmann, Wing H Seto, Jos WM van der Meer, Andreas Voss
Journal: The Lancet (2011)
Selection of saphenous vein bypass graft diameter to support patency of the stenosed coronary artery
Authors: S. E. MOSKOWITZ, B. S. LEWIS, S. MILO, R. AMAR
Journal: Cardiovascular Research (1979)

Injudicious selection of a saphenous vein graft can adversely affect the late postoperative patency of the proximal coronary artery which it bypasses. The purpose of this investigation was to deduce an upper bound for graft diameter, at small angle of distal anastomosis, below which the stenosed artery will remain patent, from a mathematical model of aortocoronary bypass haemodynamics.
Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes.
Authors: M B Oldstone, J L Whitton, H Lewicki, A Tishon
Journal: The Journal of Experimental Medicine (1988)

We define a nine-amino acid (aa) sequence of VAL-GLU-ASN-PRO-GLY-GLY-TYR-CYS-LEU as a major epitope for immunologic recognition of lymphocytic choriomeningitis virus (LCMV) by H-2b-restricted CTL. The epitope was characterized using molecular genetics to bracket broadly and chemistry to precisely identify aa residues 278-286 of the viral glycoprotein. The epitope's composition is characteristic of a reverse (beta turn) but not an amphipathic alpha helix. A series of peptides with a single aa substitution in position 278 of VAL with other nonpolar (hydrophobic) amino acids (LEU, ILE, ALA, or GLY) coat targets that are recognized and lysed by CTL clones recognizing this epitope. In contrast, substitution of VAL with either large aromatic amino acids (that add bulk: PHE, TYR) or polar side chains (SER, THR) segregates CTL clones normally recognizing aa 278-286 into two groups, one that remains lytic (permissive) despite these changes and another that fails to lyse, indicating CTL can discriminate at a single aa. A change in charge at this position (VAL----ASP or GLU), in general, reduces CTL lysis while a change of VAL to LYS or ASN has minimal affect for four of the five CTL clones analyzed. CTL reactivity with the viral epitope is restricted by the Db but not the Kb of the murine MHC haplotype. A 16-aa peptide of Db that spans alpha 1 residues 37-52 blocks CTL lysis, whereas the corresponding Kb peptide that differs from Db in a single aa in position 50 does not.
Arrhythmogenesis in experimental models of heart failure: the role of increased load
Authors: M Pye
Journal: Cardiovascular Research (1996)

Objectives: To assess the effects of cardiac failure due to doxorubicin cardiotoxicity or chronic myocardial infarction on arrhythmia induction, ventricular repolarization and refractoriness in isolated perfused rabbit hearts under different loading conditions. Methods: Cardiac failure was induced by doxorubicin injection (1–1.25 mg · kg−1 twice weekly for 8 weeks, n = 16) or coronary ligation (n = 12), with 12 controls. Cardiac failure was defined by an echocardiographic ejection fraction ≤ 0.40. Arrhythmia susceptibility was assessed by programmed ventricular stimulation and fibrillation threshold measurement during Langendorff and during working heart perfusion under baseline conditions and at maximum tolerated preload and afterload. Monophasic action potential duration, dispersion of refractoriness, conduction time and effective refractory period were measured at each level of load. Results: During unloaded (Langendorff) perfusion, there was a low incidence of arrhythmia induction in all hearts. Increasing load did not alter arrhythmogenesis significantly in normal hearts, but led to increases in arrhythmia inducibility and falls in fibrillation threshold which were significantly greater in failing than in non-failing hearts. Monophasic action potential duration was significantly (P < 0.05) shorter in failing than in non-failing hearts in the doxorubicin-treated [mean (s.e.m.) 140(2) vs. 147(2) ms] and post-infarction groups [146(2) vs. 154 (3) ms] during working heart perfusion. The shortening in action potential duration and effective refractory period during increased preload tended to be greater in failing than in non-failing hearts. There were no changes in conduction times in response to changes in loading. Conclusions: The inducibility of ventricular arrhythmias is greater in failing than in non-failing hearts and is further enhanced by increases in preload. Shortening of repolarization and refractoriness due to increased preload may contribute to the increased risk of ventricular tachyarrhythmias and sudden death in cardiac failure.
Biodegradation kinetics of aromatic hydrocarbon mixtures by pure and mixed bacterial cultures.
Authors: Kenneth F Reardon, Douglas C Mosteller, Julia Bull Rogers, Nancy M DuTeau, Kee-Hong Kim
Journal: Environmental Health Perspectives (2002)

Microbial growth on pollutant mixtures is an important aspect of bioremediation and wastewater treatment. However, efforts to develop mathematical models for mixed substrate kinetics have been limited. Nearly all models group either the microbial population (as "biomass") or the chemical species (e.g., as biological oxygen demand). When individual chemical species are considered, most models assume either no interaction or that the nature of the interaction is competition for the same rate-limiting enzyme. And when individual microbial species are considered, simple competition for the growth substrate is the only interaction included. Here, we present results using Pseudomonas putida F1 and Burkholderia sp. strain JS150 growing individually and together on benzene, toluene, phenol, and their mixtures and compare mathematical models to describe these results. We demonstrate that the simple models do not accurately predict the outcome of these biodegradation experiments, and we describe the development of a new model for substrate mixtures, the sum kinetics with interaction parameters (SKIP) model. In mixed-culture experiments, the interactions between species were substrate dependent and could not be predicted by simple competition models. Together, this set of experimental and modeling results presents our current state of work in this area and identifies challenges for future modeling efforts.
Mast cells and basophils in cutaneous immune responses
Authors: A. Otsuka, K. Kabashima
Journal: Allergy (2014)

Mast cells and basophils share some functions in common and are generally associated with T helper 2 (Th2) immune responses, but taking basophils as surrogate cells for mast cell research or vice versa for several decades is problematic. Thus far, their in vitro functions have been well studied, but their in vivo functions remained poorly understood. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for mast cells and basophils in several skin disorders. Newly developed mast cell-deficient mice provided evidence that mast cells initiate contact hypersensitivity via activating dendritic cells. In addition, studies using basophil-deficient mice have revealed that basophils were responsible for cutaneous Th2 skewing to haptens and peptide antigens but not to protein antigens. Moreover, human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of skin diseases ranging from atopic dermatitis to autoimmune diseases. In this review, we will discuss the recent advances related to mast cells and basophils in human and murine cutaneous immune responses.
Detection of patients with high alcohol intake by general practitioners.
Authors: A L Reid, G R Webb, D Hennrikus, P P Fahey, R W Sanson-Fisher
Journal: BMJ (1986)

General practitioners have the potential to treat patients with alcohol problems effectively. Despite the medical implications of excessive alcohol intake, it appears that general practitioners are not sufficiently aware of the drinking habits of their patients. The aim of the study was to investigate the accuracy of 56 randomly chosen general practitioners in detecting which of their patients had a high alcohol intake. Altogether, 2081 patients were recruited in general practitioners9 waiting rooms, where they answered questions about their drinking habits. After the consultations general practitioners were asked to indicate the patients9 levels of alcohol intake. The results showed that general practitioners correctly identified only 27.5% of patients who were classified as "high risk" drinkers, using Australian Medical Association criteria. They correctly identified only 45.2% of patients who were classified as "moderate to heavy" drinkers, defined by them as drinkers who consume four or more standard drinks a day. These findings have important implications for clinical practice since they indicate that general practitioners are failing to perform adequately in an important area of preventive medicine. This issue needs to be addressed in undergraduate and postgraduate medical education.
1012-126 Contemporary dosing of angiotensin converting enzyme inhibitors and beta blockers in chronic heart failure: Report from the STAMINA:HFP (study of anemia in a heart failure population) registry
Authors: Javed Butler, Alan Miller, Ron M Oren, Jalal K Ghali, Biljana Pavlovic-Surjancev, Carla A Sueta, Christopher M O'Connor, Kathy Hebert, Mihai Gheorghiade, Douglas Schocken, William Cotts, Todd A Schwartz, Kirkwood F Adams
Journal: Journal of the American College of Cardiology (2004)
Bacteriologic Relapse in<i>Haemophilus influenzae</i>Meningitis
Authors: James D. Cherry, Charles P. Sheenan
Journal: New England Journal of Medicine (1968)

THE effectiveness of ampicillin as the sole antibiotic in the treatment of meningitis due to Haemophilus influenzae, Diplococcus pneumoniae and Neisseria meningitidis has been reported.1 2 3 Although comparative studies have demonstrated little difference between the results of ampicillin therapy in meningitis and prior conventional therapy there are apparent advantages to ampicillin administration: one drug is used rather than two or three; and the risk of chloramphenicol and sulfonamide toxicity is eliminated.1 2 3 With chloramphenicol therapy for H. influenzae meningitis it is perhaps ill advised, but not an uncommon practice, to change the route of antibiotic administration from parenteral to oral when the . . .
Vitamin D from sun exposure may protect against solid cancers, researchers find
Authors: Roger Dobson
Journal: BMJ (2007)

Sun exposure may protect against a number of cancers, according to research based on a study of more than four million people in 11 countries.

Vitamin D produced in the skin as a result of exposure seems to reduce the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers, say the authors ( European Journal of Cancer 2007 May 30 doi: 10.1016/j.ejca.2007.04.018).

The researchers, who used registered cases of skin cancer as markers of sun exposure, found that the greatest protective effect was after non-melanoma skin cancer, which …
Does age influence normal gastro-oesophageal reflux?
Authors: R A Spence, B J Collins, T G Parks, A H Love
Journal: Gut (1985)

Prolonged oesophageal pH monitoring is being used increasingly to detect abnormal gastro-oesophageal reflux. To assess the influence of age on normal reflux patterns, a group of 13 young asymptomatic subjects (mean age 22 years) was compared with a group of 14 middle aged asymptomatic subjects (mean age 49 years). An ambulatory system using a radiotelemetry capsule and a portable receiving system was used, oesophageal pH being recorded for at least 16 hours during an overnight hospital stay under standardised conditions. There was no significant difference in the duration or frequency of reflux episodes as defined by pH less than 5, less than 4, less than 3, or as a fall in pH of more than two units. It is concluded that it is an acceptable practice to use young volunteers to establish normal values in reflux studies of young and middle aged patients.
Family of woman who had DNR order put in her notes without her knowledge is refused right to challenge its legality
Authors: C. Dyer
Journal: BMJ (2012)

The family of a woman who had a “do not resuscitate” notice placed in her medical notes without her knowledge has been refused permission to challenge the lawfulness of the decision in the High Court.

Mrs Justice Nicola Davies held that the DNR notice in 63 year old Janet Tracey’s notes had had “minimal causative effect” because it was cancelled five days later without being put into effect, after her family discovered it.

A new notice placed in her records three days later and two days before she died followed consultation with the family members, although they had been unwilling to discuss it with her, the judge decided …
P53 The cost-effectiveness of HCV antiviral treatment for injecting drug user populations
Authors: N. K. Martin, P. Vickerman, G. R. Foster, A. Miners, S. J. Hutchinson, D. J. Goldberg, M. Hickman
Journal: Gut (2011)

<h3>Introduction</h3> Injecting drug use is the main risk of HCV transmission in most developed countries. Hepatitis C virus antiviral treatment (peginterferon + ribavirin) is cost-effective for patients with no reinfection risk. Concerns about reinfection and non-compliance may discourage clinicians from treating injecting drug users (IDUs), despite the potential use of treatment as prevention in this population. <h3>Aim</h3> Using a cost-utility analysis, we examined the cost-effectiveness of providing antiviral treatment for IDUs as compared to treating ex/non-IDUs or no treatment. <h3>Method</h3> A dynamic model of hepatitis C transmission and disease progression among IDUs and ex-/non-IDUs was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after initial treatment failure, and potential re-infection for cured IDUs. We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes (measured in QALYs) and calculating the incremental cost-effectiveness ratio (ICER) to determine the cost-effectiveness of treating IDUs as compared to treating ex/non-IDUs or no treatment for three baseline IDU HCV prevalence scenarios (20%, 40%, and 60%). <h3>Results</h3> Antiviral treatment of IDUs is the most cost-effective option in both the 20% and 40% baseline chronic prevalence settings, with ICERs as compared to no treatment (best supportive care) of £521 and £2539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treatment of ex/non-IDUs or IDUs is roughly equally cost-effective; treating ex/non-IDUs is more likely to be the most cost-effective option (with an ICER as compared to no treatment of £6803), and treating IDUs is dominated due to the high re-infection at this prevalence. A sensitivity analysis indicates that these rankings hold even when IDU SVR rates as compared to ex/non-IDUs are halved. <h3>Conclusion</h3> Despite the possibility of re-infection, the model projections suggest that providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios &lt;60%. Further research on how HCV treatment for injectors can be scaled up, and its impact on prevalence is warranted.
Roads to Good Intentions Are Paved with Hell: The Shape of Academic Health Centers
Authors: Sherman M. Melinkoff
Journal: New England Journal of Medicine (1977)

In one legend a university president dies. To his surprise, he finds himself in an office identical with the one he occupied in life. Confusion about the president's fate is cleared by the sudden appearance of Mephistopheles."I do not understand," the president protests. "Presidency of the university was no bed of roses, but seldom did I think of it as Hell.""Quite so," Mephistopheles replies, "but down here you have two medical schools."Even apocryphal tales bear a grain of truth. No doubt the administration of a large modern "academic health center" is a complex and onerous task. A . . .
Acute myeloid leukemia bearing t(7;11)(p15;p15) is a distinct cytogenetic entity with poor outcome and a distinct mutation profile: comparative analysis of 493 adult patients
Authors: W-C Chou, C-Y Chen, H-A Hou, L-I Lin, J-L Tang, M Yao, W Tsay, B-S Ko, S-J Wu, S-Y Huang, S-C Hsu, Y-C Chen, Y-N Huang, M-H Tseng, C-F Huang, H-F Tien
Journal: Leukemia (2009)
Mechanism of Spontaneous Termination of Functional Reentry in Isolated Canine Right Atrium
Authors: Takanori Ikeda, Takumi Uchida, Dustan Hough, John J. Lee, Michael C. Fishbein, William J. Mandel, Peng-Sheng Chen, Hrayr S. Karagueuzian
Journal: Circulation (1996)

According to the spiral wave hypothesis of reentry, the core of functional reentry remains excitable but not excited. We sought to determine whether the core remains excitable and whether excitation of the core by an outside wave front leads to termination of the reentry in the atrium.In nine isolated canine right endocardial atrial tissues (3.8 by 3.2 cm wide), reentry was induced by a premature point stimulus (S2). The isochronal activation maps and dynamics of the activation patterns were visualized with the use of 509 bipolar electrodes (1.6-mm resolution). The S2 applied after 8 regular beats induced reentry with a mean cycle length of 162 +/- 20 ms (15 episodes). Reentry had a large excitable gap (93 +/- 26 ms) as determined by early capture with twice the level of threshold stimuli. The central area (core) around which the wave fronts rotated had a mean surface area of 12 +/- 3 mm2. The electrograms located in the core of the reentry registered no or very low amplitude potentials. In 13 of 15 episodes, reentry terminated when an outside new wave front merged with the original wave front and excited the core. Core excitation caused disruption of the original wave front, and the newly formed wave front(s) vanished at the tissue border within 77 +/- 18 ms. In 2 episodes, reentry terminated abruptly when an outside new wave front propagating in a direction opposite to the reentrant wave front collided with the leading edge of the reentrant wave front.Functional reentry in the atrium is compatible with a spiral wave of excitation with an excitable but nonexcited core and a large excitable gap. Reentry may be terminated either by direct excitation of the core that displaces the wave front to the tissue border or by collision with an outside new wave front.
Risk Factors in Pregnancy and Diseases of the Fetus and Newborn
Authors: Jay D. Iams
Journal: JAMA (1985)

Drs Naeye and Tafari bring a pathological and a pediatric point of view, respectively, to this review of obstetric epidemiology drawn from three sources. The first is the Collaborative Perinatal Project (CPP), a prospectively collected data base drawn from 53,518 women and their children at 12 university-affilitated medical centers in the United States from 1959 to 1966. The second is a study from Addis Ababa, Ethiopia, in progress since 1974, and the third is a study of pregnancy outcome among the Zulus of South Africa. The union of these three sources of data is awkward and adds little to the text. This is primarily a review of CPP data and a compendium of Dr Naeye's previously published articles based on the CPP data, with a little African data thrown in. That the authors are not obstetricians is at once the best and worst thing about this book. The CPP data
Treatment options for benign prostatic hyperplasia
Authors: T. J Wilt
Journal: BMJ (2002)

Papers p 1059 

Lower urinary tract symptoms consistent with benign prostatic hyperplasia become increasingly prevalent with age. While rarely life threatening, bothersome irritative urinary symptoms like urgency, frequency, and nocturia, and obstructive ones like a weak stream, hesitancy, intermittency, and incomplete emptying occur in up to 70% of men aged 70 years and older. Community and practice based studies suggest that men can expect slow progression of the symptoms. However, these symptoms can wax and wane without treatment, and rates of acute urinary retention range from 1-2% per year.1 By the age of 80 years, an estimated one in four men will have undergone treatment to relieve symptoms due to benign prostatic hyperplasia that reduce quality of life.2

Treatment options depend, in part, on the severity of symptoms and how bothersome they are. Options include watchful waiting (conservative or lifestyle management), phytotherapies, prescription medications, surgical procedures, and minimally invasive techniques. To help choose between treatments patients and providers rely on evidence from randomised controlled trials and systematic reviews to provide reliable information about efficacy and safety of various treatments.

For many years, transurethral resection of the prostate has been the gold standard treatment for benign prostatic hyperplasia. In 1994, almost 400 000 procedures were performed in the United States at a total cost of $5 billion.3 In the United Kingdom approximately 40 000 resections are carried out annually.4 …
Prednisone inhibits late asthmatic reactions and airway inflammation induced by toluene diisocyanate in sensitized subjects
Authors: Piera Boschetto, Leonardo M. Fabbri, Elena Zocca, Gianfranco Milani, Fausto Pivirotto, Aldo Dal Vecchio, M. Plebani, Cristina E. Mapp
Journal: Journal of Allergy and Clinical Immunology (1987)