tbuckley/cabot-search huggingface dataset:
Points from Letters: Extra Administrative Burdens
Authors: D. M. McClure
Journal: BMJ (1974)

1) That this commnittee agrees to ap- point an appropriate number of members to serve on its two District Medical Committees."(2) That if the General Medical Services Committee so advises, these members will not participate in-the work of the District Medical Committees until the ques- tion of remuneration or reimbursement for loss of earnings is agreed with the Depart- ment of Health and Social Security."-Weare, etc.,
COX-2 induction in mice with experimental nutritional steatohepatitis: Role as pro-inflammatory mediator
Authors: Jun Yu, Emilia Ip, Aileen dela Peña, Jing Yun Hou, Jayshree Sesha, Natasha Pera, Pauline Hall, Richard Kirsch, Isabelle Leclercq, Geoffrey C. Farrell
Journal: Hepatology (2006)

The underlying mechanisms that perpetuate liver inflammation in nonalcoholic steatohepatitis are poorly understood. We explored the hypothesis that cyclooxygenase-2 (COX-2) can exert pro-inflammatory effects in metabolic forms of fatty liver disease. Male wild-type (WT) C57BL6/N or peroxisome proliferator-activated receptor alpha knockout (PPAR-alpha-/-) mice were fed a lipogenic, methionine- and choline-deficient (MCD) diet or the same diet with supplementary methionine and choline (control). COX-2 was not expressed in livers of mice fed the control diet. In mice fed the MCD diet, hepatic expression of COX-2 messenger RNA and protein occurred from day 5, continued to rise, and was 10-fold higher than controls after 5 weeks, thereby paralleling the development of steatohepatitis. Upregulation of COX-2 was even more pronounced in PPAR-alpha-/- mice. Induction of COX-2 was completely prevented by dietary supplementation with the potent PPAR-alpha agonist Wy-14,643 in WT but not PPAR-alpha-/- mice. COX-2 upregulation was preceded by activation of nuclear factor kappaB (NF-kappaB) and coincided with increased levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and intercellular adhesion molecule 1 (ICAM-1). Selective COX-2 inhibitors (celecoxib and NS-398) protected against the development of steatohepatitis in WT but not PPAR-alpha-/- mice. In conclusion, induction of COX-2 occurs in association with NF-kappaB activation and upregulation of TNF-alpha, IL-6, and ICAM-1 in MCD diet-induced steatohepatitis. PPAR-alpha suppresses both COX-2 and development of steatohepatitis, while pharmacological inhibition of COX-2 activity ameliorates the severity of experimental steatohepatitis. COX-2 may therefore be a pro-inflammatory mediator in metabolic forms of steatohepatitis.
1003-94 Rheolytic thrombectomy for the treatment of acute myocardial infarction in patients with angiographic large thrombus burden: One-year results of the VeGAS 2 acute myocardial infarction registry
Authors: Jose A Silva, Stephen R Ramee, David Cohen, Joseph P Carrozza, Jeffrey J Popma, Kim Dandreo, Alexandra A Lansky, Donald S Baim, Barry S George, Daniel J McCormick, Cindy M Sefum, Richard E Kuntz
Journal: Journal of the American College of Cardiology (2004)
Biology of senescent liver peroxisomes: role in hepatocellular aging and disease.
Authors: J Youssef, M Badr
Journal: Environmental Health Perspectives (1999)

Despite rising interest in the health problems of the elderly, information on senescence-related alterations in essential metabolic pathways and their responses to various chemicals is scarce. Although peroxisomal pathways are involved in a multitude of cellular functions, little attention has been given to the potential relationship between senescence of these organelles and the process of aging and disease. Although the prevailing experimental evidence points to a decline in liver peroxisomal enzyme activities and a muted response to peroxisome-proliferating chemicals in aged animals, it is also evident that aged animals are more susceptible, in comparison to their young counterparts, to the hepatocarcinogenic effects of these chemicals. Furthermore, little is known about extraperoxisomal effects of peroxisome proliferators in aged animals. This review evaluates published studies on the impact of aging on basal hepatic peroxisomal metabolism, response to peroxisome proliferators, and changes in signal transduction pathways involved in these processes, with the aim of stimulating research efforts in this important area. The potential intricate relationship among senescent peroxisomes, aged hepatocytes, and health are also discussed.
THE INITIATION OF GROWTH OF CERTAIN FACULTATIVE ANAEROBES AS RELATED TO OXIDATION-REDUCTION PROCESSES IN THE MEDIUM
Authors: René Dubos
Journal: The Journal of Experimental Medicine (1929)

The growth of many pathogenic organisms in plain meat infusion broth is possible only when a large inoculum is used. This requirement is much less strict when the broth cultures are incubated (a) under anaerobic conditions, (b) in fresh media very recently boiled or autoclaved, (c) in fresh media reduced by means of hydrogen, or to which small amounts of cysteine or of blood have been added. It is suggested that these findings can be accounted for by assuming that the bacterial species under consideration can multiply only in media the oxidation potential of which is below a critical value. The favorable growth conditions obtained by the procedures enumerated above may be attributed to the establishment of a proper reduction potential in the medium; the same result is obtained by using a large inoculum, owing to the reducing properties of bacterial cells.
Gold exacerbates adjuvant arthritis in the rat.
Authors: D O Haskard, H L Currey
Journal: Annals of the Rheumatic Diseases (1984)

Gold exacerbates adjuvant arthritis in the rat SIR, The selection of drugs for clinical testing as 'slow acting' or 'disease modifying' agents in rheumatoid arthritis (RA) would be greatly facilitated if a suitable animal model was available as a screening test.Rat adjuvant arthritis has been tested in this regard and, despite some claims by others,' we have in this laboratory consistently failed to detect any inhibition of disease by drugs such as gold and penicillamine.23These experiments have, however, involved administration of the drugs for only relatively short periods compared with the 3-6 months necessary to achieve a response in RA patients.For this reason, we have now studied the influence on adjuvant disease of 12 weeks' pretreatment with gold injections.Sprague-Dawley rats, initially weighing approximately 140 g, received twice weekly intramuscular injections of sodium aurothiomalate (Myocrisin) 5 mg or 0 1 mg, or
The Ptolemy project: a scalable model for delivering health information in Africa
Authors: M. Beveridge
Journal: BMJ (2003)

How is Africa to build up the medical research it needs? Doctors in African research communities are starved of access to the journals and texts their colleagues in more developed countries regard as fundamental to good practice and research. Isolation, burden of practice, and resource limitations make education and research difficult, but the rapid spread of access to the internet reduces these obstacles and provides an increasingly attractive means to disseminate information and build partnerships in education and research.

The role of electronic health information in building local capacity to find, publish, and implement solutions has been emphasised recently in Science,1 Nature,2 the Lancet,3,4 and the BMJ.5 The Global Forum for Health Research gives priority to interventions designed to build research capacity in developing countries and correct the disparity in health research.6 The Coalition for Global Health Research (Canada) has recently reported how a major effort now can make a substantial difference.7 Access to reliable health information has been described as “the single most cost-effective and achievable strategy for sustainable improvement in health care.”8 We are interested in helping to build research, teaching, and clinical capacity for neglected yet substantial problems such as injury, which kills 5.1 million people annually.9-11
RELATIONS BETWEEN ENERGY TRANSFER SYSTEMS AND THE SYMPTOMS OF SCHIZOPHRENIA
Authors: PETER G. S. BECKETT, RITA SENF, CHARLES E. FROHMAN, GARFIELD TOURNEY, JACQUES S. GOTTLIEB
Journal: American Journal of Psychiatry (1962)

1. Intracellular energy producing metabolic systems were investigated in erythrocytes before and after insulin stress in 10 control, 10 acute schizophrenic, and 10 chronic schizophrenic male subjects. 2. Following complete clinical study 28 ratings of symptoms and course of illness were made for each subject. 3. Correlation coefficients (r's) were computed between the biochemical and clinical variables. 4. It was found that the primary symptoms were directly related to the failure of mobilization after stress of the compound fructose-1,6-diphosphate. 5. In contrast, the secondary symptoms were not significantly related to biochemical variables. 6. Scores indicating a chronic illness and a poor outcome at followup were found to be directly related to another very important substance in this metabolic scheme. This substance is adenosine triphosphate (ATP). 7. The possible significance of these findings is discussed in relation to a hypothetical serum factor in schizophrenia.
RADIODERMATITIS OF THE LIP AFTER EXPOSURE TO ARC WELDING
Authors: SIDNEY VERNON
Journal: JAMA (1949)

Control of the hazards of industry is the constant concern of the industrial surgeon. The early diagnosis of chronic lesions of the lip also commands attention, because cancer of the lip is frequently observed. In the 2 cases herein described there is a similar history of exposure to arc welding with the resultant formation of typical lesions of the lip. Since this condition has not been reported and has been an industrial hazard, it seems appropriate to record these cases.  REPORT OF CASES  Case 1.—  D. J. E., a sergeant aged 31, entered Fort Monmouth Station Hospital on May 18, 1948, because of a lesion of the lower lip on the left side. The condition had been noted by two medical officers, who advised biopsy.  The patient had noted a scab on the left side of his lower lip since November 1945. A crust about 3 mm. in diameter would
Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis.
Authors: K D Setchell, C M Rodrigues, M Podda, A Crosignani
Journal: Gut (1996)

The metabolism of tauroursodeoxycholic acid orally administered and its effects on the bile acid pool of patients with asymptomatic/mildly symptomatic primary biliary cirrhosis is described. Patients were randomly assigned 500, 1000, or 1500 mg/day of tauroursodeoxycholate for six months. Biliary and serum bile acids were measured before and during treatment by gas chromatography-mass spectrometry and by high performance liquid chromatography. During tauroursodeoxycholate administration, the proportion of total ursodeoxycholate in bile reached mean (SEM) 34.4 (4.5)%, 32.8 (2.8)%, and 41.6 (3.0)% with doses of 500, 1000, and 1500 mg/day, respectively. Significant decreases in the proportions of chenodeoxycholate and cholate resulted. The glycine/taurine ratio of the biliary bile acid pool decreased from 1.9 at baseline, to 1.1 with the highest dose. Ursodeoxycholate in bile was conjugated with glycine and taurine, indicating that tauroursodeoxycholate undergoes significant deconjugation and reconjugation during its enterohepatic recycling. The proportion of lithocholate in bile remained unchanged. Fasting serum conjugated ursodeoxycholate concentration positively correlated with the tauroursodeoxycholate dose, and the increased proportion of ursodeoxycholate was accompanied by substantial decreases in the endogenous bile acids. Compared with previously published data for ursodeoxycholic acid therapy, these findings indicate that the shift toward a more hydrophilic bile acid pool is greater and potentially more favourable with tauroursodeoxycholate, and this is because of the reduced intestinal biotransformation of tauroursodeoxycholate.
Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone
Authors: Michelle L. Hernandez, John C. Lay, Bradford Harris, Charles R. Esther, W. June Brickey, Philip A. Bromberg, David Diaz-Sanchez, Robert B. Devlin, Steven R. Kleeberger, Neil E. Alexis, David B. Peden
Journal: Journal of Allergy and Clinical Immunology (2010)
Misuse of dothiepin
Authors: A. Dorman, P. Byrne, D. Talbot, J. O'Connor
Journal: BMJ (1995)

These are not sufficient arguments for an editorial in the BMJ to recommend one class of ,3 blockade and should be accompanied by the proviso that measurements of blood pressure are only a sur- rogate: it is the prevention of cerebrovascular accidents and myocardial infarctions that matters.As a doctor treating patients with hypertension or ischaemic heart disease most days of the week, I tend to use low doses of the most j3I selective lipophilic agent, bisoprolol, for hypertension and the highest affinity non-selective agent, timolol, for ischaemic heart disease.These drugs have been selected on the basis of theoretical arguments and surrogate measures on which Cleophas and Kalmansohn and I agree.As a clinical pharmacologist unhappy at such evidence, I set up the East Anglian comparison of the two classes of drug in ischaemic heart disease that I mentioned in my editorial and included them in a long term randomised comparison of antihypertensive drugs that started in 1986.
Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV‐infected children
Authors: Ángeles Ruiz-Extremera, José Antonio Muñoz-Gámez, María Angustias Salmerón-Ruiz, Paloma Muñoz de Rueda, Rosa Quiles-Pérez, Ana Gila-Medina, Jorge Casado, Ana Belén Martín, Laura Sanjuan-Nuñez, Ángel Carazo, Esther José Pavón, Esther Ocete-Hita, Josefa León, Javier Salmerón
Journal: Hepatology (2011)

The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV-ve), with 128 children, and 33 were HCV-RNA-ve/HCV antibody+ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA+ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA-ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA+ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA+ve. In all, 26 of 128 (20%) infants born to the HCV-RNA+ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA-ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1.High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children.
Co-existence of heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura in a postoperative cardiac surgery patient
Authors: Stanley Benke, Catherine Moltzan
Journal: American Journal of Hematology (2005)

Up to 50% of patients undergoing coronary artery bypass surgery will develop antibodies against the heparin–platelet factor 4 complex, and a small percentage of those will go on to develop heparin-induced thrombocytopenia. Thrombotic thrombocytopenic purpura has also been reported post-coronary artery bypass surgery. In this case report, we describe a patient who developed both heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura post-coronary artery bypass surgery. This patient had clinical features consistent with both entities, and the clinical picture could not be explained by either heparin-induced thrombocytopenia or thrombotic thrombocytopenic purpura alone. It is hypothesized that these two entities may be related in this patient population, and this case report emphasizes the challenges in the diagnosis of thrombocytopenia in this patient population. Am. J. Hematol. 80:288–291, 2005. © 2005 Wiley-Liss, Inc.
Insulin Infusion During Normoglycemia Modulates Insulin Secretion According to Whole-Body Insulin Sensitivity
Authors: Christian Anderwald, Andrea Tura, Angela Grassi, Michael Krebs, Julia Szendroedi, Michael Roden, Martin G. Bischof, Anton Luger, Giovanni Pacini
Journal: Diabetes Care (2011)

OBJECTIVE Glucose is the major stimulus for insulin release. Time course and amount of insulin secreted after glycemic stimulus are different between type 2 diabetes mellitus (T2DM) patients and healthy subjects. In rodents, it was demonstrated that insulin can modulate its own release. Previous studies in humans yielded contrasting results: Insulin was shown to have an enhancing effect, no effect, or a suppressive effect on its own secretion. Thus, we aimed to evaluate short-term effects of human insulin infusion on insulin secretion during normoglycemia in healthy humans and T2DM subjects of both sex. RESEARCH DESIGN AND METHODS Hyperinsulinemic-isoglycemic clamps with whole-body insulin-sensitivity (M) and C-peptide measurements for insulin secretion modeling were performed in 65 insulin-sensitive (IS) subjects (45 ± 1 year, BMI: 24.8 ± 0.5 kg/m2), 17 insulin-resistant (IR) subjects (46 ± 2 years, 28.1 ± 1.3 kg/m2), and 20 T2DM patients (56 ± 2 years, 28.0 ± 0.8 kg/m2; HbA1c = 6.7 ± 0.1%). RESULTS IS subjects (M = 8.8 ± 0.3 mg · min−1 · kg−1) had higher (P &amp;lt; 0.00001) whole-body insulin sensitivity than IR subjects (M = 4.0 ± 0.2) and T2DM patients (M = 4.3 ± 0.5). Insulin secretion profiles during clamp were different (P &amp;lt; 0.00001) among the groups, increasing in IS subjects (slope: 0.56 ± 0.11 pmol/min2) but declining in IR (−0.41 ± 0.14) and T2DM (−0.87 ± 0.12, P &amp;lt; 0.00002 IR and T2DM vs. IS) subjects. Insulin secretion changes during clamp directly correlated with M (r = 0.6, P &amp;lt; 0.00001). CONCLUSIONS Insulin release during normoglycemia can be modulated by exogenous insulin infusion and directly depends on whole-body insulin sensitivity. Thus, in highly sensitive subjects, insulin increases its own secretion. On the other hand, a suppressive effect of insulin on its own secretion occurs in IR and T2DM subjects.
P231 Audit of pre-hospital oxygen therapy by North West Ambulance Service (NWAS) 1 year after publication of new JRCALC guidance for oxygen use
Authors: A. Matthews, C. Gavin, B. R. O'Driscoll
Journal: Thorax (2010)

We audited oxygen use amongst 443 cases brought to the “majors” A&amp;E area of a university hospital by NWAS ambulance teams in May–July 2010. We compared the findings with our 2007 audit conducted before publication of the BTS emergency oxygen guideline in 2008 and JRCALC guidance in 2009 (Hale K. <i>Emerg Med J</i> 2008;<b>25</b>:773). <h3>Results</h3> 90% of cases had oximetry recorded by ambulance teams in 2007, rising to 96% in 2010. 19% of cases were hypoxic in 2010 and 27% were given oxygen compared with 34% in 2007 (see Abstract P231 Table 1). The proportion given oxygen fell from 31% in the initial 4 weeks to 24% in the final 5 weeks of the audit when feedback was given to ambulance teams. The “ideal” figure for these cases was about 21% based on JRCALC guidance. 86% of cases were treated in accordance with JRCALC guidance in terms of receiving or not receiving oxygen and 73% were treated in full compliance (correct device and flow rate). The overall compliance rate was 4.4% higher (95% CI –2.3% to 11.0%) during the feedback period and full compliance rose by 9.9% (95% CI 1.6 to 18.2%) following feedback. Eight percent of cases received oxygen inappropriately and 3% were denied oxygen inappropriately. Our audit revealed that NWAS ambulance crews were unable to give controlled oxygen to COPD cases because Venturi masks were not carried. Several COPD cases received high dose oxygen from nebuliser masks throughout the journey because air driven nebulisers and nasal cannulae were not available. Only four of 14 cases with AECOPD had SpO<sub>2</sub> &lt;88% but 12 were given oxygen and 10 developed SpO<sub>2</sub> &gt;92%. <h3>Conclusions</h3> The proportion of NWAS cases receiving oxygen in pre-hospital care has fallen from 34% in 2007 to 27% in 2010 following publication of BTS and JRCALC oxygen guidelines. 86% of cases were treated in broad compliance with JRCALC guidance and 73% were in full compliance. There is potential for further slight reduction in oxygen use in ambulances, especially for COPD patients. This may be enhanced by feedback to ambulance crews and by providing a wider range of oxygen delivery equipment in ambulances.
Effect of Freezing on Oxytocin Ampules
Authors: Gemma C. Nassta, Richard J. Prankerd, Michelle P. McIntosh
Journal: New England Journal of Medicine (2013)

Researchers found that oxytocin concentrations in ampules remained stable after exposure to freezing temperatures. These results should reassure health care workers and skilled birth attendants that oxytocin ampules can be safely used even if temporarily frozen during transportation or storage.
Prodrug design, synthesis and pharmacokinetic evaluation of (3′R, 4′R)-3-hydroxymethyl-4-methyl-3′, 4′-di-O-(S)-camphanoyl-(+)-cis-khellactone
Authors: Huanfang Guo, Xiaomei Zhuang, Keduo Qian, Lianqi Sun, Xiaofeng Wang, Hua Li, Kuohsiung Lee, Lan Xie
Journal: Acta Pharmaceutica Sinica B (2012)

3-Hydroxymethyl-4-methyl-DCK (3, HMDCK) was discovered previously as a potent HIV non-nucleoside reverse transcriptase inhibitor (NNRTIs) (EC50: 0.004 μM, TI: 6225) with a novel mechanism of action. It exerts anti-HIV activity by inhibiting the production of HIV-1 double-stranded viral DNA from a single-stranded DNA intermediate, rather than blocking the generation of single-stranded DNA from a RNA template, which is the mechanism of action of current HIV-1 RT inhibitors. However, the insufficient metabolic stability of 3 limits its further clinical development. In the current study, a series of ester prodrugs of 3 was designed and synthesized to explore the new drug candidates as NNRTIs. The l-alanine ester prodrug 10 exhibited desirable pharmacokinetic properties in vitro and in vivo and showed improved oral bioavailability of 26% in rat, and would be a potential clinical candidate as a new anti-AIDS drug.
Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate
Authors: F Centorrino, R J Baldessarini, J Kando, F R Frankenburg, S A Volpicelli, P R Puopolo, J G Flood
Journal: American Journal of Psychiatry (1994)

Serum concentrations of clozapine, norclozapine, and clozapine-N-oxide were assayed in psychotic patients treated with clozapine alone (N = 17), clozapine with fluoxetine added (N = 6), or clozapine with valproic acid added (N = 11). Subjects were matched for age and other treatments, and concentrations were corrected for daily dose of clozapine (milligrams per kilogram of body weight). With valproic acid, there was a minor increase in total clozapine metabolites, which was even less with dose correction. Fluoxetine increased all clozapine analytes, in some cases to twice the levels in the subjects given only clozapine.