tbuckley/cabot-search huggingface dataset:
Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection
Authors: Florian van Bömmel, Thomas Wünsche, Stefan Mauss, Petra Reinke, Alexandra Bergk, Dirk Schürmann, Bertram Wiedenmann, Thomas Berg
Journal: Hepatology (2004)

Adefovir dipivoxil was recently approved for the treatment of wild–type and lamivudine–resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine–resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (&gt;6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty–five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir–treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 105 copies/mL in contrast to 100% of the tenofovir–treated patients ( P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir–treated patients in the long term (up to 130 weeks). In conclusion , tenofovir may become an effective alternative for the treatment of patients with lamivudine–resistant HBV infection. (Hepatology 2004;40:1421-1425.)
The Biology and Pathology of Oxygen Radicals
Authors: JOE M. McCORD
Journal: Annals of Internal Medicine (1978)

Superoxide radicals (O2-) are commonplace products of the biological reduction of oxygen. Their intrinsic reactivity and ability to generate other more reactive entities constitute a threat to cellular integrity. Superoxide dismutases, enzymes that catalytically scavenge these radicals, have evolved to meet this threat. These metalloenzymes are essential for respiring organisms to survive. Several compounds, such as the antibiotic streptonigrin and the herbicide paraquat, augment the production rate of O2- inside cells. This accounts for the oxygen-enhancement of their lethality. Some bacteria respond to this artificially increased rate of O2- production by synthesizing additional superoxide dismutase. Ionizing radiation generates O2- in its passage through oxygenated aqueous media, and superoxide dismutase, added to the suspending medium, decreases the oxygen-enhancement of the lethality of such irradiation of the bacterium Escherichia coli. Production of O2- by activated neutrophils is clinically significant, since it is an important component of the bactericidal actions of these cells and the inflammatory process. Superoxide dismutases exert an anti-inflammatory action that may be useful in managing inflammations.
Timothy Clive Northfield
Authors: M. Mendall
Journal: BMJ (2009)

Timothy Clive Northfield (“Tim”) was born in London in 1935. He was the son of a distinguished neurosurgeon in the London Hospital. He decided not to follow his father into medicine, and after national service he took up a place at Peterhouse, Cambridge, intending to read history. However, almost straight away he switched to natural sciences with a view to training to become a doctor.

As a medical student at Guy’s, he began to win prizes and his great achievements began soon after qualifying. He was awarded a Medical Research Council fellowship to undertake research at the Mayo Clinic in America. Here he developed an interest in bile salt metabolism. The other lasting interest which he developed early on in his career …
Lymphomas of African Children
Authors: Gregory T. O'Conor
Journal: JAMA (1963)

<h3>To the Editor:</h3> —In the article "Lymphomas of African Children" in the Sept 22 issue ofThe Journal(<b>181</b>:1026), Dalldorf suggests that this syndrome is the African manifestation of malignant lymphomatous disease, which parellels and has its counterpart in lymphatic leukemia in this country and elsewhere. This is indeed an attractive concept, and one which was first introduced in our original paper on the subject in 1960.<sup>1</sup>It is important to keep in mind that clinical impressions and ratios, particularly in Africa, are dangerous bases for conclusions and have led to considerable misinformation in the literature of African disease. Until incidence rates of cancer based on accurate census figures are available, and the medical coverage warrants reasonable interpretation, this idea of "lymphoma instead of leukemia" in Africa must remain speculative. There are many features which give greater support to a rebuttal of this notion, such as the occurrence
Preservation of the glomerular capillary ultrafiltration coefficient during rat nephrotoxic serum nephritis by a specific leukotriene D4 receptor antagonist.
Authors: K F Badr, G F Schreiner, M Wasserman, I Ichikawa
Journal: Journal of Clinical Investigation (1988)

Leukotriene D4, a potent biologically active lipoxygenase derivative of arachidonic acid in activated leukocytes, depresses the glomerular capillary ultrafiltration coefficient (Kf) and contracts mesangial cells in culture. We therefore investigated its potential role in mediating the reduction in nephron filtration rate seen after induction of experimental nephrotoxic serum (NTS)-induced glomerulonephritis in the rat. Micropuncture measurements were performed in euvolemic Munich-Wistar rats 2 h after i.v. administration of 0.8 ml of rabbit serum (group 1, n = 6), 0.8 ml of rabbit anti-rat glomerular basement membrane antibody in the absence (group 2, n = 8), or presence (group 3, n = 7) of the new highly specific LTD4 receptor antagonist SK&F 104353. Quantitation of antibody binding and neutrophil infiltration revealed no differences between groups 2 and 3. Antagonism of endogenous LTD4 actions, however, was associated with prevention of the NTS-induced fall in SNGFR because of the abrogation of the fall in Kf which characterizes this form of experimental glomerulonephritis. Antagonism of endogenous LTD4 had no effect on the NTS-induced increases in pre- and postglomerular arteriolar resistances, and did not affect nephron plasma flow rate or net transcapillary hydraulic pressure difference. The observed highly localized protective action of the LTD4 antagonist on the glomerular capillary points to a possibly major functional role for intraglomerularly released LTD4, likely originating from infiltrating leukocytes, in the pathophysiology of this form of glomerulonephritis.
Evaluating the provision of service for percutaneous endoscopic gastrostomy (PEG) within the United Kingdom (UK): results of a national survey
Authors: M. Kurien, C. Romaya, D. S. Sanders
Journal: Gut (2011)

<h3>Introduction</h3> Controversies exist about PEG feeding because of the significant morbidity and mortality associated with the procedure and the lack of evidence regarding its use in certain indications. We aimed to establish the provision of service for PEG that currently exists within the UK. <h3>Methods</h3> All UK NHS hospitals providing an endoscopy service (n = 260) were invited to participate in this study. A custom designed web based questionnaire was sent to all providers enquiring about service arrangements for PEG. Questions were asked regarding the number of PEG insertions undertaken, referral practice, specialists performing the procedure, the time interval between referral and PEG insertion, triage systems, PEG aftercare, local guidelines and prophylactic antibiotic usage. <h3>Results</h3> Questionnaires were returned by 215 of 260 hospitals (82.7%), of which 57.2% (123/215) were Joint Advisory Group (JAG) accredited units. Specialists inserting PEGs within these hospitals included Gastroenterologists (100%), Surgeons (33%), Nurse Endoscopists (36%), Specialist Registrars (51%) and Geriatricians (3%). More than 50 PEGs per year were inserted by 32.5% (70/215) of hospitals, with 4 hospitals inserting more than 150. 18% (38/215) of units were low-volume service providers, undertaking fewer than 25 procedures a year. Stroke and neurodegenerative conditions were the main indications for PEG insertion, with 36% (77/215) of hospitals inserting PEGs for dementia. There were variations in the timing of PEG insertion, with 33% (72/215) having a strict policy of waiting more than 2 weeks from referral to insertion, 14% (30/215) performing immediately and 34% (74/215) determining the time delay dependent upon the underlying condition. Local guidelines for PEG insertion existed in 87% (186/215) of hospitals and 78% (168/215) had access to radiologically inserted gastrostomies. Prophylactic antibiotics were used in 93% (201/215) of hospitals9. Only 64% (137/215) had a dedicated PEG aftercare service. There were no differences when comparing; JAG (34%) and non-JAG centres (38%) for PEG insertion in dementia p = 0.55 and JAG (96%) and non-JAG centres (90%) for antibiotic use (p = 0.09). When comparing low volume centres (&lt;25) to high volume centres (&gt;150) no differences in practice could be observed (example, dementia, p = 0.38). <h3>Conclusion</h3> This is the most comprehensive study evaluating provision of service for PEG within the UK. We have described variations in practice (particularly with regards to the policy for dementia and number of procedures undertaken). This may account for the significant morbidity and mortality associated with this procedure. The high participation in this survey suggests that a prospective national audit of PEG outcomes is feasible.
DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma
Authors: Adriana L. da Silva, Sabrina V. Martini, Soraia C. Abreu, Cynthia dos S. Samary, Bruno L. Diaz, Sandra Fernezlian, Vanessa Karen de Sá, Vera Luiza Capelozzi, Nicholas J. Boylan, Rodolfo Gustavo Goya, Jung Soo Suk, Patricia R.M. Rocco, Justin Hanes, Marcelo M. Morales
Journal: Journal of Controlled Release (2014)
Insulin Action and the Insulin Signaling Network*
Authors: BENTLEY CHEATHAM, C. RONALD KAHN
Journal: Endocrine Reviews (1995)

IN THE fasted state, glucose homeostasis depends upon the balance between hepatic glucose production and glucose utilization by the major insulin-dependent tissues, such as liver, adipose, and muscle, and by insulin-independent tissues, such as brain and kidney. This balance is tightly regulated by pancreatic hormones. Thus, in normal individuals, the response to increased plasma glucose levels is an increase in secretion of insulin from β-cells of the pancreatic islets. This increase in circulating insulin levels stimulates glucose transport into peripheral tissues and inhibits hepatic gluconeogenesis. In type II diabetes there are at least two fundamental defects: one is a decrease in the ability of peripheral tissues to respond to insulin (insulin resistance), and the second is impaired β-cell function, which results from long-term hyperglycemia. It appears that both genetic and environmental factors are responsible for the progression from normal glucose tolerance to type II diabetes (1–4). In addition to its primary effects on glucose homeostasis, insulin also promotes a number of other cellular events including regulation of ion and amino acid transport, lipid metabolism, glycogen synthesis, gene transcription and mRNA turnover, protein synthesis and degradation, and DNA synthesis (Fig. 1). Thus the actions of insulin play key roles in the normal storage of ingested fuels and in normal cellular growth and differentiation. The biological importance of these effects of insulin are most obvious in the uncontrolled type I diabetic in ketoacidosis (1, 3–5). To fully understand the events leading to insulin-resistant states and the pathophysiology of insulin deficiency, it is necessary to identify, at the molecular level, the key components in the insulin-signaling pathway.
Number of cases operated on is important in volume-outcome debate for colorectal cancer
Authors: F. Kee
Journal: BMJ (1999)

EDITOR—Comber draws a distinction between hospital based registration systems and a population based registry and raises the possibility that we missed cases of colorectal cancer.1 2

The leaders of both the Northern Ireland cancer register and the colorectal cancer register have shared their data for several years. Those at the colorectal cancer register are aware that their ascertainment focuses on patients having surgical intervention. As our paper indicated,2 we focused our analysis on patients who had surgical intervention …
The Oregon Experience With Impaired Physicians on Probation
Authors: James H. Shore
Journal: JAMA (1987)

Sixty-three addicted or impaired physicians who had been on probation with the Oregon Board of Medical Examiners were followed up in a new rehabilitation program for eight years. A majority (59%) were still on probation at follow-up, and 75% were rated as stable and improved. Problems of addiction affected 78%. The most successful treatment outcomes were for addicted physicians whose improvement was significantly associated with random urine monitoring to detect repetitive drug abuse. This research confirms an effective treatment approach for addicted or impaired physicians and is compared with other outcome studies.
High Complication Rate of Bile Duct Stents in Patients With Chronic Alcoholic Pancreatitis Due to Noncompliance
Authors: K. Kiehne, U. R. Fölsch, R. Nitsche
Journal: Endoscopy (2000)

Background and Study Aims: Biliary obstruction in chronic pancreatitis is frequently treated by endoscopic insertion of a plastic stent into the common bile duct, a therapy regarded as having a low complication rate. The aim of this study is to analyze the frequency and severity of complications caused by biliary stents in patients with chronic alcoholic pancreatitis.
Indoor Allergens—Assessing and Controlling Adverse Health Effects
Authors: Andrew M. Pope
Journal: JAMA (1993)

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Venlafaxine and cardiovascular toxicity
Authors: D. Taylor
Journal: BMJ (2010)

Risk seems no greater than for selective serotonin reuptake inhibitors

People with depression have a higher incidence of cardiovascular disease and mortality from cardiovascular disease than people without depression.1 Ideally, the use of antidepressants should not add to this risk. Depression may also provoke suicide, so toxicity in overdose is a crucial consideration when choosing an antidepressant.

Older tricyclic antidepressants may increase mortality from cardiovascular disease when used therapeutically and are often fatally toxic in overdose, whereas selective serotonin reuptake inhibitors (SSRIs) show little if any cardiotoxicity at any dose, although, their antiplatelet effect has potential for harm.2 The serotonin-noradrenaline reuptake inhibitor venlafaxine has been thought to show cardiovascular toxicity somewhere between that of tricyclics and SSRIs, so its use has been restricted in some countries. In the linked case-control study (doi:10.1136/bmj.c249), however, Martinez and colleagues challenge the notion that venlafaxine is more cardiotoxic than SSRIs.3

In their study using data from the general practice research database in the United Kingdom, which looked at 207 384 first …
Preparation by Reverse Osmosis of Pyrogen-free Sterile Water for Operative Endoscopy in Urology
Authors: P. Brühl, F. Dahm
Journal: Endoscopy (1976)

A new combination of equipment for processing pyrogen-free sterile water by reverse osmosis for operative endoscopy in urology is presented. This apparatus provides purest bubble-free water which meets the requirements of DAB 7 and which may be used directly without the need for interim storage, so that danger to the patient is excluded. Thus conditions for asepsis in transurethral operations in all regions are guaranteed for the first time.
Long-term outcome after repair of coarctation in infancy: Subclavian angioplasty does not reduce the need for reoperation
Authors: Robert H. Beekman, Albert P. Rocchini, Douglas M. Behrendt, Edward L. Bove, Macdonald Dick, Dennis C. Crowley, A. Rebecca Snider, Amnon Rosenthal
Journal: Journal of the American College of Cardiology (1986)
Differences in Metabolism of Sulfonamides Predisposing to Idiosyncratic Toxicity
Authors: NEIL H. SHEAR
Journal: Annals of Internal Medicine (1986)

Individual differences in metabolism of the sulfonamides may predispose patients to idiosyncratic reactions. Sulfonamides are metabolized by N-acetylation (mediated by a genetically polymorphic enzyme) and oxidation to potentially toxic metabolites. We examined 6 patients who had severe reactions to sulfonamides and compared them with 20 controls. Acetylator phenotype was determined with caffeine, a safe in-vivo probe of enzyme activity. All 6 patients were slow acetylators (expected, 55%; p < 0.05). Detoxification of oxidative metabolites was studied in vitro with a lymphocyte assay evaluating cell death from metabolites generated by a murine hepatic microsomal system. Cells from each patient showed increased toxicity from sulfonamide metabolites but not from the drugs themselves. Cells from parents of 3 patients had intermediate toxicity from sulfonamide metabolites, whereas cells from a sibling of 1 patient had a normal response. Susceptibility to sulfonamide reactions may be due to interaction of metabolic pathways, possibly under genetic control, regulating N-acetylation and specific detoxification of toxic metabolites of the drugs.
INCREMENTAL PROGNOSTIC VALUE OF MYOCARDIAL PERFUSION STRESS-ECHOCARDIOGRAPHY IN PATIENTS WITH KNOWN CORONARY ARTERY DISEASE
Authors: Thomas Porter, Juefei Wu, Feng Xie, Stacey Therrien, Valentina Lorenzoni, Sabrina Molinaro, Claudio Reverberi, Nicola Gaibazzi
Journal: Journal of the American College of Cardiology (2013)
Autoantibodies in twins discordant for rheumatoid arthritis
Authors: A J Svendsen, J V Hjelmborg, A Wiik, G Houen, K O Kyvik, P Junker
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is characterised by frequent occurrence of autoantibodies. The anti-cyclic citrullinated peptide antibodies (anti-CCP) are now used routinely as they may antedate the development of seropositive RA, because their diagnostic sensitivity and specificity is better than rheumatoid factors (RFs), and because they may predict a more severe outcome.1,–,3 Previous studies have observed an increased prevalence of RF and anti-CCP in first-degree relatives of patients with RA.4 One study on RA discordant twin pairs provided evidence for genetic effects on IgM-RF and IgG-RF independent of HLA-DR.5 Anti-CCPs have been reported to be independently associated with the HLA-DRB1 shared epitope, PTPN22 and smoking, …
Lack of association between the –260 C→T promoter polymorphism of the endotoxin receptor CD14 gene and the CD14 density of unstimulated human monocytes and soluble CD14 plasma levels
Authors: Michael Heesen, Brunhilde Blömeke, Bernhard Schlüter, Nicole Heussen, Rolf Rossaint, Dagmar Kunz
Journal: Intensive Care Medicine (2001)
Two Populations of Rh Groups together with Chromosomally Abnormal Cell Lines in the Bone Marrow
Authors: S. T. Callender, H. E. M. Kay, S. D. Lawler, R. E. Millard, R. Sanger, P. A. Tippett
Journal: BMJ (1971)

At the onset of his disease a man with polycythaemia vera had chromosomally normal cells in the bone marrow and Rh blood group CDe/cDE. Five years later he developed pancytopenia with erythroid hyperplasia of the bone marrow. This was associated with the presence of a major abnormal clone, 45,XY,B-,C-,16+, a minor clone, 45,XY,2+,3-,C-, and a few apparently normal cells. At the same time Rh blood grouping showed two populations of red cells, one CDe/cDE and one giving the reactions of CDe/CDe which can be interpreted as CDe. If monosomic CDe be the correct interpretation the case provides a strong hint that the Rh complex locus is sited either on the long arm of a B-group chromosome or, less probably, on an autosome of the C group.
Low-tar medium-nicotine cigarettes: a new approach to safer smoking.
Authors: M A Russell
Journal: BMJ (1976)

The logic of expecting people who cannot stop smoking to switch to cigarettes that have hardly any nicotine is questionable. Tar and nicotine yields of cigarettes available in Britain today correlate 0-93, and further reduction of tar intake is limited by the reluctance of smokers to tolerate similar reductions in nicotine. A new approach would be to aim at lowering tar yields of cigarettes from the present average of 18 mg to around 6 mg but maintaining nicotine yields at around 1-0 to 1-2 mg, which would be acceptable to most smokers. This approach requires that emphasis be placed on tar: nicotine ratios as well as on the absolute yields. These ratios for brands on sale in Britain today average 14-2 and range from 9-6 to 20-8. They provide an additional guide for comparing the relative harmfulness of different brands. For example, 35% of cigarette smokers in Britain smoke either Embassy Filter or Players No 6 Filter; by changing to John Player Carlton King Size they could reduce their tar intake by more than 20% without having to suffer any nicotine deprivation.
Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock
Authors: Mathias W. Pletz, Frank Bloos, Olaf Burkhardt, Frank M. Brunkhorst, Stefanie M. Bode-Böger, Jens Martens-Lobenhoffer, Mark W. Greer, Heino Stass, Tobias Welte
Journal: Intensive Care Medicine (2010)
Spontaneous Hemorrhage with Anticoagulants
Authors: LOUIS B. JAQUES
Journal: Circulation (1962)

When dicumarolized animals are subjected to various types of stress, a high mortality from spontaneous internal hemorrhage occurs. This phenomenon is observed with various combinations of the treatments—Dicumarol, phenylindanedione, heparin, frostbite, insulin convulsions, hypertonic saline intraperitoneally, adrenalectomy, adrenocorticotropic hormone, corticosteroids, histamine, adrenalin, salicylates, P 32 , reserpine. Hemostasis depends on blood coagulation, platelets, and vascular integrity. Experimental results demonstrate that spontaneous hemorrhage results when any two of these mechanisms are deranged simultaneously. Hormonal and neural factors affect the blood vessels and in this way determine spontaneous hemorrhage with anticoagulants. Spontaneous hemorrhage has a multiple causation.