tbuckley/cabot-search huggingface dataset:
Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver
Authors: Markus Georg Donner, Dietrich Keppler
Journal: Hepatology (2001)

Cholestasis induces down–regulation of multidrug resistance protein 2 (Mrp2, symbol Abcc2), which is localized to the canalicular membrane. Given the overlapping substrate specificities of Mrp2 and multidrug resistance protein 3 (Mrp3, symbol Abcc3), we examined the hypothesis of a different subcellular and lobular localization of these members of the Mrp family in rat liver after bile duct ligation. We raised a polyclonal antibody against rat Mrp3 and detected this protein in the basolateral plasma membrane of hepatocytes surrounding the central veins and of cholangiocytes. The Mrp3 protein level was less than 2% of the expression observed after 72 hours of obstructive cholestasis. After 48 hours of bile duct ligation, the Mrp3 protein was increased and was further enhanced after 72 hours. In 72–hour–cholestatic rat liver Mrp3 was expressed, in addition, in periportal hepatocytes. However, there was a preponderance of Mrp3 in the pericentral area of the liver lobule. In Mrp2–deficient mutant rat liver, the Mrp3 protein expression was most enhanced and its zonation was lost. The Mrp3 immunostaining of cholangiocytes was preserved in cholestatic and in Mrp2–deficient mutant liver. Canalicular Mrp2 decreased and amounted to 34% of normal after bile duct ligation for 72 hours. We conclude that the hepatocellular up–regulation of Mrp3 in cholestasis together with cholangiocellular Mrp3 may compensate for the biliary obstruction and impaired canalicular Mrp2 function by clearing cholephilic anionic substances into the blood.
New tumour necrosis factor inhibitors for rheumatoid arthritis: are there benefits from extending choice?
Authors: D. L Scott, A. Cope
Journal: Annals of the Rheumatic Diseases (2009)

Certolizumab pegol (UCB, Brussels, Belgium) and golimumab (Centocor, Horsham, Pennsylvania, USA) are the latest tumour necrosis factor (TNF) inhibitors evaluated in double-blind, multicentre randomised controlled trials (RCT). Certolizimab is the pegylated (polyethylene glycolated) Fab′ fragment derived from a high affinity humanised anti-TNFα monocolonal antibody (mAb). Fab′ fragments lack the Fc portion of immunoglobulin, and so the repertoire of Fc-mediated effector responses, such as complement or antibody-dependent cell-mediated cytotoxicity, is distinct from those of other anti-TNF mAb. Nonetheless, it still neutralises membrane TNFα. Derivatisation of the Fab′ fragment prolongs the plasma half-life to 2 weeks. Certolizumab pegol is administered by subcutaneous injection (200 or 400 mg) every 2 weeks. Golimumab is a human anti-TNF mAb administered by subcutaneous injections (50 or 100 mg) every 4 weeks. Three RCT in this issue of Annals of the Rheumatic Diseases ,1–3 (see pages 789, 797 and 805) which report their use in active rheumatoid arthritis (RA), raise two questions. First, do we need more TNF inhibitors? Second, how effective and safe are these new TNF inhibitors?

Successful drugs are invariably replicated. “Breakthrough” treatments sound more impressive than subsequent “me too” replications, although the latter products might perform better. Lee4 has elegantly summarised the arguments for “me too” products, indicating that their presence “does not mean that imitation has replaced innovation”. Successful “me too” treatments improve efficacy, reduce toxicity and increase “cost effectiveness”. With biological agents such as TNF inhibitors their added benefits may include more favourable routes or frequencies of administration.

There are cogent reasons to anticipate that “me too” biological agents will be commonplace as experience with these agents solidifies and their use increases. There may be special factors with biologicals, particularly around their mechanism of action, which may complicate the comparison of different “me too” products. …
Tumor Scanning With Gallium 67
Authors: Gould A. Andrews
Journal: JAMA (1975)

IT IS OBVIOUS that for most, but not all, forms of cancer the effectiveness of treatment can be enhanced by early diagnosis and by accurate assessment of the extent of the disease after diagnosis. Methods for diagnosis and staging are improving progressively, and an important area of progress is in diagnostic nuclear medicine. Some radioisotopic procedures are applicable to only one organ, some are useful for only one specific type of tumor, and some disclose the tumor only as an area that fails to take up radioactively labeled material in an organ that normally shows relatively high concentration. Of particular interest is the availability of a few agents that localize selectively in a wide variety of tumors wherever they may be located. An example of the latter is gallium 67. Imaging with gallium citrate Ga 67 is proving to be distinctly useful, although it is not uniformly helpful and usually
Geoffrey David Phillips
Authors: M. Phillips
Journal: BMJ (2002)

Former general practitioner St Austell, Cornwall (b Redruth 1926; q St Bartholomew's Hospital, London, 1951), d 6 May 2002.

Geoffrey left school at the age of 15 and worked briefly as a mining surveyor before deciding to pursue a career in medicine. After several hospital posts, he found his vocation in general practice. Home visits and an understanding of the social context of illness were central to his philosophy. He served the people of St Austell for more than 30 years. For many years he was police surgeon and medical adviser to St John Ambulance. Outside medicine his main interests remained rugby football, Cornwall, and his family. He leaves a wife, Ute; and two sons.
Effect of Cuts in Medicare Reimbursement on Process and Outcome of Care for Acute Myocardial Infarction Patients
Authors: Kevin G. Volpp, R. Tamara Konetzka, Jingsan Zhu, Lori Parsons, Eric Peterson
Journal: Circulation (2005)

The Balanced Budget Act (BBA) of 1997 was designed to reduce Medicare reimbursements by $116.4 billion from 1998 to 2002. The objective of this study was to determine whether the process of care for acute myocardial infarction (AMI) worsened to a greater degree in hospitals under increased financial strain from the BBA and whether vulnerable populations such as the uninsured were disproportionately affected.We examined how process-of-care measures and in-hospital mortality for AMI patients changed in accordance with the degree of BBA-induced financial stress using data on 236,506 patients from the National Registry of Myocardial Infarction (NRMI) and Medicare Cost Reports from 1996 to 2001. BBA-induced reductions in hospital net revenues were estimated at 1.5% (2.9 million dollars) for hospitals with low BBA impact and 3.2% (3.7 million dollars) for hospitals with a high impact in 1998, worsening to 2.2% (4.4 million dollars) and 4.7% (6.0 million dollars), respectively, by 2001. For both insured and uninsured patients in high- versus low-impact hospitals, there was no systematic worsening of time to thrombolytic therapy, balloon inflation, medication use on admission, medication use on discharge, or mortality. There was no systematic pattern of different treatment among the insured and uninsured. Operating margins decreased to a degree commensurate with the degree of revenue reduction in high- versus low-impact hospitals.BBA created a moderate financial strain on hospitals. However, process-of-care measures for both insured and uninsured patients with AMI were not appreciably affected by these revenue reductions. It is important to note that these results apply only to AMI patients; we do not know the degree to which these findings generalize to other conditions.
Mental illness in deployed soldiers
Authors: R J Ursano, D M Benedek, C C Engel
Journal: BMJ (2007)

Is more likely as traumatic exposures increase, and this is often related to length of deployment

More than 29 armed conflicts involving 25 countries are now occurring around the globe.1 For people in the United Kingdom and United States the situation in Iraq and Afghanistan is a constant reminder of the cost of war. The price that soldiers, sailors, airmen, marines, and their families pay is always considerable.

In this week's BMJ , Rona and colleagues assess the effect of the frequency and duration of deployment on the mental health of 5547 randomly chosen military personnel with experience in deployment.2 They found that people who were deployed for more than 12 months in the past three years were more likely to have mental health problems (odds ratio for post-traumatic stress disorder 1.55, 95% confidence interval 1.07 to 2.32), although exposure to combat partly accounted for these associations. Post-traumatic stress disorder was more likely when a mismatch occurred between the expected and actual lengths of deployment.

The study could help identify those at high risk of long term disability and guide policy.3 Deployment is a strange term. Few people would suggest that deployment …
Waiting for the doctor.
Authors: E I Marshall
Journal: BMJ (1986)

The best time interval between appointments in general practice surgeries where patients were allocated specific times to see their doctor was studied. A mathematical model which simulates the pattern of the arrival of patients and consultations at the surgery, and which can be run rapidly on computer, was constructed. The model can be applied to any general practitioner9s surgery that operates an appointments system. The only inputs necessary are observations of the arrival times and consultation times of all patients at 10 of the doctor9s surgeries. The scope of the reduction in waiting times that was attained in one practice is discussed.
Effects of isometric strength training followed by no exercise and Humulus lupulus L–enriched diet on bone metabolism in old female rats
Authors: Hélène Figard, Fabienne Mougin, Maude Nappey, Marie-Jeanne Davicco, Patrice Lebecque, Véronique Coxam, Valérie Lamothe, Patrick Sauvant, Alain Berthelot
Journal: Metabolism (2007)
Endothelial NOS, estrogen receptor β, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer
Authors: Simona Nanni, Valentina Benvenuti, Annalisa Grasselli, Carmen Priolo, Aurora Aiello, Stefania Mattiussi, Claudia Colussi, Vittoria Lirangi, Barbara Illi, Manuela D’Eletto, Anna Maria Cianciulli, Michele Gallucci, Piero De Carli, Steno Sentinelli, Marcella Mottolese, Paolo Carlini, Lidia Strigari, Stephen Finn, Elke Mueller, Giorgio Arcangeli, Carlo Gaetano, Maurizio C. Capogrossi, Raffaele Perrone Donnorso, Silvia Bacchetti, Ada Sacchi, Alfredo Pontecorvi, Massimo Loda, Antonella Farsetti
Journal: Journal of Clinical Investigation (2009)

The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases.
RISK OF CARDIOVASCULAR AND ALL-CAUSE MORTALITY AS A FUNCTION OF RESTING HEART RATE IN ASYMPTOMATIC AORTIC STENOSIS: THE SEAS STUDY
Authors: Anders M. Greve, Casper Bang, Kenneth Egstrup, Anne Rossebø, Kurt Boman, Christoph Nienaber, Simon Ray, Christa Gohlke-Baerwolf, Peter Okin, Richard Devereux, Lars Kober, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2014)
Report of an Epidemiological Field Study about Neuroses and Psychosomatic Disorders
Authors: Heinz G.F. Schepank
Journal: Psychotherapy and Psychosomatics (1983)

Our field study deals with a cohort investigation and a follow-up study of the age groups 1935, 1945 and 1955. The sample consists of 600 randomly selected Germans living in an industrial city (Mannheim/FRG). 200 subjects of each of the age groups are to be examined personally with regard to ICD diagnoses 300-307 (WHO, 8th rev.); these are: psychoneuroses, personality disorders, sexual deviations, alcohol and drug addiction, functional and other psychosomatic diseases. Preliminary countings from the first research check-up of the sample revealed 26% of cases with a clear predominance of females and statistically significant connections between actual disease and impairing or disturbing influences during early childhood.
MECHANISTIC INSIGHTS, RESULTS OF CATHETER ABLATION, AND RISK FACTORS FOR ATRIAL TACHYCARDIA AFTER ABLATION OF ATRIAL FIBRILLATION: OSTIAL PULMONARY VEINS ABLATION, CIRCUMFERENTIAL PULMONARY VEINS ABLATION AND GANGLIONATED PLEXI ABLATION
Authors: Evgeny Pokushalov, Alexander Romanov, Sergey Artemenko, Pavel Shugaev, Nataliya Shirokova, Alex Turov
Journal: Journal of the American College of Cardiology (2010)
Gonococcal pili. Primary structure and receptor binding domain.
Authors: G K Schoolnik, R Fernandez, J Y Tai, J Rothbard, E C Gotschlich
Journal: The Journal of Experimental Medicine (1984)

The complete amino acid sequence of pilin from gonococcal strain MS11 and the sequence of constant and variable regions from strain R10 pilin have been determined in order to elucidate the structural basis for adherence function, antigenic diversity, and polymeric structure. The MS11 pilin sequence consists of 159 amino acids in a single polypeptide chain with two cysteines in disulfide linkage and serine-bonded phosphate residues. TC-2 (31-111), a soluble monomeric pilus peptide prepared by arginine-specific digestion, bound human endocervical, but not buccal or HeLa cells and therefore is postulated to encompass the receptor binding domain. Variable regions of CNBr-3 appear to confer antigenic diversity and comprise segments in which changes in the position of charged residues occur in hydrophilic, beta-turns. Residues 2-21 and 202-221 of gonococcal pilins and lower eucaryotic actins, respectively, exhibit 50% homology. When these residues are arranged at intervals of 100 degrees of arc on "helical wheels," the identical amino acids comprise a hydrophobic face on one side of the helix. This observation, the hydrophobic character of this region and the tendency for TC-1 (residues 1-30) to aggregate in water, suggest that this stretch interacts with other subunits to stabilize polymeric structure.
The role of microbiota in hepatic encephalopathy
Authors: Jasmohan S Bajaj
Journal: Gut Microbes (2014)

Hepatic encephalopathy (HE), which consists of minimal (MHE) and overt (OHE) stages, is a model for impaired gut-liver-brain axis in cirrhosis. Microbiota changes in both stages have been associated with impaired cognition, endotoxemia, and inflammation. There is dysbiosis (reduced autochthonous taxa [Lachnospiraceae, Ruminococcaceae, and Clostridiales XIV] and increased Enterobacteriaceae and Streptococcaceae) with disease progression. In MHE, there is an increased abundance of Streptococcus salivarius linked to cognition and ammonia. In OHE, stool Alcaligenaceae and Porphyromonadaceae are associated with poor cognition. Colonic mucosal microbiome in cirrhosis is significantly different compared with stool and independently related to cognition. HE treatment can affect microbial composition and function; cognitive improvement in MHE after rifaximin, a non-absorbable antibiotic, occurred without significant stool microbiota composition change but improved metabolic linkages. Similarly, there are only modest lactulose and rifaximin-associated changes on microbiota composition in OHE. HE represents an important model to study microbiome-brain interactions.
Bronchial reactivity in asthmatic children at high and low altitude. Effect of budesonide.
Authors: A L Boner, A Comis, M Schiassi, P Venge, G L Piacentini
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Inhaled steroids may control bronchial inflammation in asthmatics exposed to allergens. In this study we evaluated whether prophylactic budesonide would prevent relapse of asthma in children re-exposed to offending allergens at sea level, after a period of antigen avoidance at high altitude. Thirty children received either budesonide (200 micrograms b.i.d.) or placebo (double-blind). Following a 4-wk baseline period and 2 wk of treatment at high altitude, children were treated for 3 mo at sea level. Methacholine challenge and pulmonary function studies were performed before and after baseline period, after the 2 wk of treatment in the mountain environment, and at the end of treatment. ECP serum levels were evaluated after the baseline period and at the end of treatment. PEFR and symptoms were recorded in a diary card during the study. The increase in methacholine provocative dosage was greater, although not significant (p = 0.096), in the budesonide than in the placebo group after the treatment at high altitude and remained higher at the end of the treatment (p = 0.04). ECP levels increased in both the groups with no significant difference. Our results confirm that budesonide, in addition to its efficacy in treating pre-existent airway inflammation, is effective in preventing the increase of reactivity in asthmatic children re-exposed to allergens.
Economical Use of the Hospital Bed and of the Nurse
Authors: E. B. Brooke, J. P. Wetenhall
Journal: BMJ (1949)

Much of the content of this memorandum is not new matter. We have, however, deliberately attempted to incorporate a brief reference to the more important aspects which bear directly on the problem of the shortage of nurses. We have done this because we are strongly of the opinion that this problem is not resolvable by piecemeal approach, and that its solution depends upon a simultaneous attack on all its various angles as revealed in a survey which must of necessity be wide.
ABNORMAL CORONARY BLOOD FLOW BY 82RUBIDIUM POSITRON EMISSION TOMOGRAPHY MYOCARDIAL PERFUSION IMAGING CORRELATES WITH LEFT VENTRICULAR DYSSYNCHRONY IDENTIFIED BY SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Aasha S. Gopal, Andrew Van Tosh, Kenneth J. Nichols, Rena S. Toole, Eera Jain, Bradley Michalakis, Brie Cronin, Tanvir S. Gopal, Berthold Klas, Nathaniel Reichek
Journal: Journal of the American College of Cardiology (2012)
Ultrasonic Examination
Authors: ERIC MAURY, JEAN GUGLIELMINOTTI, MARC ALZIEU, BERTRAND GUIDET, GEORGES OFFENSTADT
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We evaluated ultrasonic examination as a diagnostic tool for catheter misplacement and pneumothorax after central venous catheter insertion. Physicians in the intensive care unit (ICU) performed the ultrasonic examinations, and the results were compared with those of chest radiography. Eighty-five central venous catheters (70 subclavian and 15 internal jugular) were inserted into 81 patients; 10 misplacements and one pneumothorax occurred. Ultrasonic examination feasibility was 99.6%. The only pneumothorax and all misplacements except one were diagnosed by ultrasound. Taking into consideration misplacements and pneumothorax research, ultrasonic examination did not give any false positive results. The mean time of the entire ultrasonic examination was 6.8 +/- 3.5 min, whereas 80.3 +/- 66.7 min were needed for the radiography (p < 0.0001). This study has suggested that ultrasonic diagnosis of catheter misplacement and pneumothorax related to central venous catheterization is a rapid and accurate method that can be easily performed by ICU physicians.
Interpretation of the ECG: Before or After Mounting? Admissibility as Evidence
Authors: William B. Smith
Journal: JAMA (1971)

To the Editor.—  As an attorney, I would certainly not attempt to criticize or to evaluate the scientific sufficiency or accuracy of the ECG. However, the question concerned the admissibility of an ECG in evidence . That is a legal and not a medical question. The most important point from a legal standpoint is the accuracy and completeness of the ECG. My answer presumed that the unmounted balance of the tracing would be discarded and would not be available for the cardiologist's examination. My answer pointed out that the cardiologist's judgment is only as good and as valid as the tracing which he sees. I do not think that any amount of semantics can avoid that conclusion. Dr. Littmann states that the unmounted portion of the tracing will be retained for the cardiologist's examination along with the mounted portion of the record. It therefore appears, that we are not really in
Maintenance treatment is not rocket science
Authors: A. Byrne
Journal: BMJ (2013)

Luty is unduly pessimistic about long term abstinence after opioid maintenance treatment.1 About 4% of addicted people become abstinent each year, regardless of treatment.2 By 10 years, over a third are abstinent. The remainder are mostly on maintenance treatment, a small, efficient part of any health system, which often needs little more than an …
Elasticity of the Pulmonary Alveolar Sheet
Authors: Y. C. FUNG, S. S. SOBIN
Journal: Circulation Research (1972)

An analysis of experimental data on the pulmonary alveolar sheet of the cat shows: (1) As far as elasticity in the plane of the sheet is concerned, the alveolar sheet may be regarded as uniform; the compliance of the posts is the same as that of the membranes. (2) Within a physiological range of positive transmural pressure, the mean thickness of the sheet varies linearly with the pressure. Also, the stress distribution in the alveolar-capillary membrane is nonuniform and nonisotropic. A theoretical sheet thickness-pressure relationship is derived in which the effect of stress resultants (sum of elastic stress and surface tension) is explicitly linked to the compliance of the sheet thickness. The sheet-flow theory then shows that average flow is very sensitive to the arteriole pressure. The flow per alveolar sheet is (1/ C ) ( h a 4 -- h v 4 ). Here h a and h v are equal to alveolar sheet thickness at the arteriole and venule, respectively. When art &gt; alv , h a = h 0 + α( art - alv ), where art is the blood pressure in the sheet at the arteriole, alv is the gas pressure in the alveolus, α is the compliance constant for the sheet thickness, and h 0 is the thickness at Δ = 0. The constant C = 4µf Lα/ (SA), where µ is the coefficient of viscosity of blood, f is a friction parameter (on the order of 4, depending on the post geometry), L is the average length of the streamlines in the sheet, S is the vascular space-tissue ratio (on the order of 0.9), and A is the sheet area. Comparison of this formula with the experimental results of Roos et al., using h 0 and α values from Glazier et al., shows reasonable agreement.