tbuckley/cabot-search huggingface dataset:
Dietary reduction of serum cholesterol concentration.
Authors: L E Ramsay, W W Yeo, P R Jackson
Journal: BMJ (1991)

ELISA would have failed to prevent transmission.Interestingly, these donors have given 15, 23, and 27 donations and have never been implicated in any other case of transmission of hepatitis.As far as we are aware, the seronegative status of the donors was known to the authors before their letter was published.Though we acknowledge that hepatitis C virus will have been transmitted to a number ofrecipients of transfusions before screening was introduced, we nevertheless firmly support the balanced arguments of Elizabeth Ann Fagan.The problems ofthe poor specificity of the first generation ELISA for antibody to hepatitis C virus and the resulting wastage of considerable quantities of blood were not the only arguments in favour of awaiting the availability of second generation assays.3Pereira and colleagues' arguments are fallacious and should not be left unchallenged.
Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis
Authors: S. Benoit, A. Toksoy, M. Ahlmann, M. Schmidt, C. Sunderkötter, D. Foell, M. Pasparakis, J. Roth, M. Goebeler
Journal: British Journal of Dermatology (2006)

Background The expression of calcium‐binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme‐linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705 ± 120 ng mL−1 (mean ± SEM, n = 18), those with a PASI of ≥15 showed levels of 1315 ± 150 ng mL−1 (n = 32) while controls presented with 365 ± 50 ng mL−1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. Conclusions Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium‐dependent signalling but also implying distinct extracellular functions.
Incidence of IDDM in the Marche Region, Italy
Authors: Valentino Cherubini, Maurizio Cantarini, Elsa Ravaglia, Edoardo Bartolotta
Journal: Diabetes Care (1994)

OBJECTIVE To provide reliable data concerning the incidence of insulindependent diabetes mellitus (IDDM) in children from the Marche Region in Italy and contribute to a better understanding of its geographical variability throughout Italy and Europe. RESEARCH DESIGN AND METHODS All newly diagnosed cases of IDDM in children 0–14 years of age in the Marche Region between 1 January 1990 and 31 December 1992 were recorded. The primary source of ascertainment was clinical records from the 59 hospitals of the region. Secondary and tertiary independent sources included local and national associations for diabetic children and local district centers of the National Health System. RESULTS Over the 3-year study period, the overall IDDM incidence rate was 8.1 per 100,000/year. No significant sex-related difference in incidence was noted, with a male:female ratio of 0.9. The completeness of ascertainment was estimated at 100%. CONCLUSIONS The Marche Region appears to have a slightly elevated incidence of IDDM among noninsular Italian regions.
Elevated pulmonary artery systolic pressure in patients with coronary artery disease and left ventricular dyssynchrony
Authors: Guo‐Hui Yan, Mei Wang, Wen‐Sheng Yue, Kai‐Hang Yiu, Chung‐Wah Siu, Stephen W.L. Lee, Chu‐Pak Lau, Hung‐Fat Tse
Journal: European Journal of Heart Failure (2010)
Postmortem examinations using magnetic resonance imaging: four year review of a working service
Authors: R A L Bisset
Journal: BMJ (2002)

An impressive downward trend in cases of occupational skin diseases in hairdressers has occurred in Northern Bavaria over the past decade.This seems to reflect improvements in working conditions due to new legislation and intensified preventive measures rather than a change in the natural history of occupational skin disease. 5 Because of the size of the region studied and the sampling scheme, the findings can be generalised and applied to Germany as a whole. 2 3 Although the prognosis for recovery from occupational skin disease has not changed significantly over the past five decades, 5 cooperation between dermatolo-gists, government physicians, employers, employees, the competent workers' compensation board, the hairdressers' guild, hair cosmetics manufacturers, and legislative authorities has led to a reduction in occupational skin diseases in hairdressing.However, to achieve a longlasting reduction, interdisciplinary cooperation must be continued and primary prevention should start as early as possible, preferably by legally binding supplementary medical pre-employment examination. 2 The Principle G24 "Skin diseases (other than skin cancer)" is under discussion in Germany.
Current system of buying medical supplies is unacceptably wasteful, say MPs
Authors: J. Wise
Journal: BMJ (2011)

MPs have criticised the current system of buying medical supplies as wasteful and inefficient, and called for specific measures to ensure that foundation trusts deliver improvements in procurement.

The Public Accounts Committee says the current fragmented system of procurement has produced a great deal of waste, with trusts being charged different prices for the same goods, ordering in inefficient ways, and failing to control the range of products which they buy.

The committee points out that a survey of 61 trusts by the National Audit Office found they had bought 652 different types of surgical gloves and 1751 different types of cannula ( BMJ 2011;342:d732 doi:10.1136/bmj.d732). One trust buys 177 different types of glove. In its report the National Audit Office estimated that …
Corneal Confocal Microscopy Detects Early Nerve Regeneration After Pancreas Transplantation in Patients With Type 1 Diabetes
Authors: Sanjay Mehra, Mitra Tavakoli, Panagiotis A. Kallinikos, Nathan Efron, Andrew J.M. Boulton, Titus Augustine, Rayaz A. Malik
Journal: Diabetes Care (2007)

Corneal confocal microscopy (CCM) is a rapid, noninvasive, clinical examination technique that quantifies small nerve fiber pathology. We have used it to assess the neurological benefits of pancreas transplantation in type 1 diabetic patients.In 20 patients with type 1 diabetes undergoing simultaneous pancreas and kidney transplantation (SPK) and 15 control subjects, corneal sensitivity was evaluated using noncontact corneal esthesiometry, and small nerve fiber morphology was assessed using CCM.Corneal sensitivity (1.54 +/- 0.28 vs. 0.77 +/- 0.02, P < 0.0001), nerve fiber density (NFD) (13.8 +/- 2.1 vs. 42 +/- 3.2, P < 0.0001), nerve branch density (NBD) (4.04 +/- 1.5 vs. 26.7 +/- 2.5, P < 0.0001), and nerve fiber length (NFL) (2.23 +/- 0.2 vs. 9.69 +/- 0.7, P < 0.0001) were significantly reduced, and nerve fiber tortuosity (NFT) (15.7 +/- 1.02 vs. 19.56 +/- 1.34, P = 0.04) was increased in diabetic patients before pancreas transplantation. Six months after SPK, 15 patients underwent a second assessment and showed a significant improvement in NFD (18.04 +/- 10.48 vs. 9.25 +/- 1.87, P = 0.001) and NFL (3.60 +/- 0.33 vs. 1.84 +/- 0.33, P = 0.002) with no change in NBD (1.38 +/- 0.74 vs. 1.38 +/- 1.00, P = 1.0), NFT (15.58 +/- 1.20 vs. 16.30 +/- 1.19, P = 0.67), or corneal sensitivity (1.23 +/- 0.39 vs. 1.54 +/- 00.42, P = 0.59).Despite marked nerve fiber damage in type 1 diabetic patients undergoing pancreas transplantation, small fiber repair can be detected within 6 months of pancreas transplantation using CCM. CCM is a novel noninvasive clinical technique to assess the benefits of therapeutic intervention in human diabetic neuropathy.
Synopsis of Clinical Tropical Medicine
Authors: A. R. D. Adams
Journal: BMJ (1965)

<h3>ABSTRACT</h3> Phosphatidylinositol-5-phosphate 4-kinase gamma (PI5P4Kγ), which phosphorylates phosphatidylinositol-5-monophosphate (PI(5)P), is a human lipid kinase with intriguing roles in inflammation, T cell activation, autophagy regulation, immunity, heart failure, and several cancers. To provide a high-quality chemical tool that would enable additional characterization of this protein, we designed and evaluated a potent, selective, and cell-active inhibitor of human PI5P4Kγ. We describe the use of the PI5P4Kγ NanoBRET assay to generate structure–activity relationships (SAR), support chemical probe (<b>2</b>) design, and identify a structurally related negative control (<b>4</b>). We have characterized the binding of our chemical probe to PI5P4Kγ using orthogonal assay formats reliant on competition with an ATP-competitive reagent. Based on our results in these assays, we hypothesize that <b>2</b> binds in the ATP active site of PI5P4Kγ. Kinome-wide profiling complemented by further off-target profiling confirmed the selectivity of both our chemical probe and negative control. When a breast cancer cell line (MCF-7) was treated with compound <b>2</b>, increased mTORC1 signaling was observed, demonstrating that efficacious binding of <b>2</b> to PI5P4Kγ in cells results in activation of a negative feedback loop also reported in PI5P4Kγ knockout mice.
Desert Island Reading
Authors: Jane A. McAdams
Journal: JAMA (1969)

<h3>To the Editor:—</h3> This year's book number is, as usual, great, but I disagree with Richard Armour's choice of books (<b>208</b>:139, 1969) If I were to be marooned on a desert island and could have only one book, I would choose neither the King James version of the Bible nor Richard Armour's suggested<i>New English Dictionary</i>, but rather Rowen's<i>Practical Art of Shipbuilding</i>.
Somatization and Medicalization-Reply
Authors: Arthur J. Barsky
Journal: JAMA (1996)

<h3>In Reply.</h3> —Somatization is a multidetermined phenomenon and represents the product of psychological, behavioral, interpersonal, and social factors. Therefore, effective treatment is often complex and multimodal. While the primary care physician is undoubtedly the cornerstone of therapy, he or she alone may not be sufficient. Primary care physicians can care more effectively for somatizing patients with the assistance of management guidelines, psychiatric consultation, and specific training and educational programs, as Smith et al<sup>1</sup>have shown using psychiatric consultation letters. However, more definitive symptom relief and improved functional status may require a more intensive targeted effort, which requires the time and expertise the primary care physician lacks. Contrary to Drs Fabian, Langsjoen, and Kent, we find impressive evidence of the efficacy and effectiveness of cognitive and behavioral techniques in a variety of conditions, including isolated functional somatic symptoms, somatization disorder, and hypochondriasis.<sup>2 6</sup>Although it is true that nonspecific
High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: Relationship to endotoxemia
Authors: D Ferro, C Quintarelli, A Lattuada, R Leo, M Alessandroni, P M Mannucci, F Violi
Journal: Hepatology (1996)

The aim of this study was to evaluate whether there is endothelial dysfunction in patients with cirrhosis and to detect the mechanism that may account for it. We measured plasma levels of von Willebrand factor (vWF), a marker of endothelial perturbation, and endotoxin, which releases vWF from endothelial cells in vitro, in 32 patients (18 men, 14 women, aged 39-70 years) with cirrhosis classified as mild (class A, n = 10), moderate (class B, n = 16), or severe (class C, n = 6) according to Child-Pugh's classification. vWF antigen (P < .0001) and endotoxemia (P < .0001) progressively increased from A to class C; but the increase of vWF antigen was not strictly related to liver failure, as shown by the lack of correlation between vWF and several indexes of liver protein synthesis. Analysis of the vWF subunit showed no sign of proteolytic fragmentation of the molecule. Multimeric analysis indicated intact vWF multimeric structure. In all patients, there was a strong correlation between vWF antigen and endotoxemia (rho = .92; P = .0001). In 20 selected patients, vWF antigen and endotoxemia were measured before and after 7 days of standard therapy (n = 10) or standard therapy plus nonabsorbable antibiotics. There was a significant decrease of vWF antigen (P < .02) concomitantly with the decrease of endotoxemia (P < .006) in patients taking nonabsorbable antibiotics. Human umbilical vein endothelial cells incubated in vitro with 125 to 500 pg/mL endotoxin released vWF antigen into the medium dose dependently. These results demonstrate that there is endothelial perturbation in cirrhosis and that endotoxemia may play a key role in its occurrence.
Optimising the value of interventions for populations
Authors: M. Gray, A. E. Turabi
Journal: BMJ (2012)

All clinician groups should estimate which interventions are most beneficial . 

Few big scientific ideas are so widely adopted and understood as the concept of the paradigm shift.1 Robert Brook, one of the founders of the quality improvement paradigm, in a recent article entitled, The End of the Quality Improvement Movement: Long Live Improving Value , described incisively the latest big paradigm shift that has arisen as a consequence of the economic imperatives challenging health systems globally.2

Quality, safety, and evidence of effectiveness in medical care—the previous paradigms—are still essential, but only in so far as they affect value. Consideration of value is what lies at the heart of a new report by IMPRESS (Improving and Integrating Respiratory Services)3—a collaboration between respiratory specialists and generalists with a special interest in lung health. The report calculated the relative value of different interventions within a particular system of healthcare: services for patients with chronic obstructive pulmonary disease (COPD).

Value relates the outcomes of healthcare interventions to their cost. Costs are considered not only in terms of money or carbon, but …
A monoclonal antibody to vascular endothelial–cadherin inhibits tumor angiogenesis without side effects on endothelial permeability
Authors: Monica Corada, Lucia Zanetta, Fabrizio Orsenigo, Ferruccio Breviario, Maria Grazia Lampugnani, Sergio Bernasconi, Fang Liao, Daniel J. Hicklin, Peter Bohlen, Elisabetta Dejana
Journal: Blood (2002)
Drug Delivery: Functional Silica Nanoparticles for Redox-Triggered Drug/ssDNA Co-delivery (Adv. Healthcare Mater. 6/2012)
Authors: Xing Ma, Kim Truc Nguyen, Parijat Borah, Chung Yen Ang, Yanli Zhao
Journal: Advanced Healthcare Materials (2012)

A mesoporous silica nanoparticle based co-delivery system for redox-triggered simultaneous release of drug and single strand DNA is reported by Y. L. Zhao and co-workers on page 690. High co-delivery efficiency of the biocompatible nanoparticles has been demonstrated in vitro, exhibiting the successful release of both anticancer drug doxorubicin and single strand DNA into Hela cancer cells for improved apoptosis.
Pulse methylprednisolone therapy in rheumatoid arthritis.
Authors: M D Smith
Journal: Annals of the Rheumatic Diseases (1989)

Adenosine deaminase activity in rheumatoid pleural effusion SIR, We read with interest the article by Ocania et al describing nine cases of rheumatoid pleural effusion, all with raised levels of adenosine deaminase activity in pleural fluid but none with specific changes in pleural biopsy.'We have recently seen a rheumatoid patient who developed a pleural effusion with raised levels of adenosine deaminase and showed a typical rheumatoid nodule in the pleural biopsy specimen.The patient, a 64 year old woman, had developed seropositive, nodular rheumatoid arthritis three years before admission.She had to stop gold salt injections because of a toxic skin reaction and she was receiving D-penicillamine at the time of admission to hospital, with good control of her arthritis.Two months before admission she started a cough with mucoid sputum, mild left thoracic discomfort, and disturbed sensation.She also had mild constitutional symptoms.There was no flare up of her arthritis.A chest radiograph showed left pleural effusion.Physical examination showed an afebrile patient with signs of left pleural effusion, ulnar deviation, synovial proliferation of her wrists, and mild arthritis in her knees.No subcutaneous nodules were found.The rest of the general examination was normal.Laboratory findings were: erythrocyte sedimentation rate 86 mm/h, haemoglobin 118 g/l, white blood cell count normal, platelets 540xiO0/l.Blood chemistry and urine analysis were normal.Rheumatoid factor was 1-090 IU.Antinuclear factor was positive at a dilution of 1/6400 with homogeneous pattem.Anti-dsDNA was negative.Thoracentesis gave a yellowish fluid with 1-15 x IO' cells/l,
Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses
Authors: Madeleine M. Hipp, Norbert Hilf, Steffen Walter, Daniela Werth, Katharina M. Brauer, Markus P. Radsak, Toni Weinschenk, Harpreet Singh-Jasuja, Peter Brossart
Journal: Blood (2008)
610 IMPACT OF ETHNICITY ON VIRAL KINETICS AND SUSTAINED VIROLOGICAL RESPONSE RATES OF GENOTYPE 4, CHRONIC HEPATITIS C PATIENTS TREATED WITH PEG-INTERFERON-A2A PLUS RIBAVIRIN
Authors: I. Elefsiniotis, C. Pavlidis, D. Dimitropoulos, C. Mihas, E. Vezali, S. Koutsounas, E. Paraskevas
Journal: Journal of Hepatology (2009)
The Effect of Intravenously Administered Digoxin on Water and Electrolyte Excretion and on Renal Functions
Authors: SAUL J. FARBER, J. D. ALEXANDER, E. D. PELLEGRINO, D. P. EARLE
Journal: Circulation (1951)

Digoxin causes a prompt and considerable water and salt diuresis in congestive heart failure. This may occur with little or no change in renal hemodynamics, but usually is associated with decreased venous pressure. At times, increased glomerular filtration rate may contribute to the diuresis. In patients with noncardiac edema and without edema, Digoxin may also initiate a slight but definite sodium diuresis. This effect is not as great as in patients with congestive heart failure and apparently is not associated with changes in renal hemodynamics, cardiac output or venous pressure.
Progress in Medical Virology. Vol. 3
Authors: Gilbert Dalldorf
Journal: JAMA (1961)

The essays in this third volume are devoted to serodiagnosis (Schmidt and Lennette); overwintering of arthropodborne virus (Reeves); fluorescent antibody methods (Poetschke); the search for antiviral drugs (Herrmann); Coxsackie and ECHO viruses (Gelfand); live virus vaccines for poliomyelitis, mumps, and measles ( Smorodintsev ); viruses and congenital malformations ( Blattner and Heys ); and viral leukemia ( Dmochowski). All are excellent and each includes long and well-chosen bibliographies. The chapter on serodiagnosis is a review of recent advances, and regrettably lacks a discussion of the usefulness of various methods in terms of particular diseases, something the authors might easily have provided from their own experience. Similarly, the chapter on chemotherapy is concerned with methodology and the difficulties in screening and judging the usefulness of drugs through laboratory tests, but is silent on the effectiveness of known preparations. Dr. Gelfand's chapter is unusually complete and scholarly. His discussion of the ecologic problems of enteric viruses is
Correlation between 18-fluorodeoxyglucose accumulation in large vessels and serological markers of inflammation in polymyalgia rheumatica: a quantitative PET study
Authors: F Moosig
Journal: Annals of the Rheumatic Diseases (2004)

To quantify 18-fluorodeoxyglucose (FDG) accumulation in large vessels in patients with polymyalgia rheumatica by positron emission tomography (PET), and to compare these data with serological markers of inflammation.13 untreated patients with active polymyalgia rheumatica underwent FDG positron emission tomography; eight were analysed in a second PET when in clinical remission. Six patients with other highly inflammatory conditions served as controls. For quantitative analysis, FDG uptake over nine defined vascular regions, divided by an individual background value, was expressed as a region of interest (ROI) index. These data were compared with the clinical status of the patient and with erythrocyte sedimentation rate (ESR), C reactive protein, haemoglobin, and platelet and leucocyte counts.By visual evaluation, 12 of the 13 patients showed an increased tracer uptake of the aorta or its major branches. By quantitative analysis, FDG uptake was significantly increased in polymyalgia rheumatica. In patients with active disease, the mean ROI index for all vascular regions exceeded that of controls by 70% (mean (SD): 1.58 (0.37) v 0.93 (0.12); p<0.001). In the eight patients who underwent follow up PET, the index declined substantially. In active polymyalgia rheumatica, FDG uptake was significantly correlated with C reactive protein (r = 0.8), ESR (r = 0.79), and platelet counts (r = 0.68).The observed FDG accumulation in the aorta and its branches and a strong correlation between tracer uptake and markers of inflammation is suggestive of large vessel arteritis. Quantitative ROI analysis appears to be a sensitive tool for detecting such inflammation.