tbuckley/cabot-search huggingface dataset:
Bayer is forced to release documents over withdrawal of cerivastatin
Authors: C. Marwick
Journal: BMJ (2003)

Pharmaceutical giant Bayer has, for the first time, been forced to release confidential company documents to the US courts in a damages case over the lipid lowering drug cerivastatin. The case, held in a Texan court, reveals just how much the company knew about the problems with the drug before withdrawing it in 2001.

Bayer withdrew cerivastatin (marketed as Baycol in the United States and Lipobay in Europe) from the US market and Europe in August 2001 and subsequently in Japan because of an increasing number of reports to the US Food and Drug Administration of rhabdomyolysis—a rare disorder in which muscle tissue breaks down and that can lead to organ failure and death—in …
Rehabilitation of Heart Patients
Authors: B. Parsons-Smith
Journal: BMJ (1943)

JOURNALHb 50%; erythroblasts and normoblasts present in moderate numbers.The child was treated by blood transfusion and re- covered.Father abroad; mother, Group A Rh-negative; child, Group A Rh-positive.The mother's serum, taken 3 weeks after her delivery, reacted against 3 Rh-positive Group A bloods and gave no reaction against 3 Rh-negative Group 0 bloods.The titre of the antibodies was not determined.Case 3.-Child aged 2 days; jaundiced since birth; moderately severe hyperchromic anaemia.R.B.C. 2.15 millions per c.mm.; Hb 48%; moderate numbers of erythroblasts and normoblasts.Blood transfusion was given, but the child died.Father, Group 0 Rh-positive; mother, Group A Rh-negative; child, Group A Rh- positive.The mother's serum, tested 4 weeks after her delivery, reacted against 11 Rh-positive bloods (2 Group A, 9 Group 0), but gave no reaction with 9 Rh-negative bloods (2 Group A, 7 Group 0).When titrated against 3 Rh-positive Group 0 bloods the serum reacted in dilutions up to 1:32.Case 4.-Child aged 3 weeks; jaundiced since birth; moderately severe anaemia.Small numbers of erythroblasts and normoblasts were present in the blood film.The child died before any treat- ment could be given.Father, Group A Rh-positive; mother, Group A Rh-negative; child, Group A Rh-positive.The mother's serum, 2 weeks after her delivery, reacted against 14 Rh-positive Group 0 bloods-to a titre of 1: 32 with two of them and 1: 8 with one.There was no reaction with 2 Rh-negative Group 0 bloods.Case S.-Child aged 10 days; jaundiced since birth; very severe hyperchromic anaemia.R.B.C. 830,000 per c.mm.; Hb 27%; large numbers of erythroblasts and normoblasts seen.The child received blood transfusion, but died.Father, Group 0 Rh-positive; mother, Group A Rh-negative ; child, Group 0 Rh-positive.The mother's serum, 21 weeks after delivery, reacted against 6 Rh-positive bloods (2 Group A, 4 Group 0).There was no reaction with 3 Rh-negative bloods (1 Group A, 2 Group 0).The titre was 1:16 when tested against 3 Rh-positive Group 0 bloods.
Effects of Increased Myocardial Oxygen Consumption on Coronary Reactive Hyperemia in the Awake Dog
Authors: ROBERT J. BACHE, FREDERICK R. COBB, JOSEPH C. GREENFIELD
Journal: Circulation Research (1973)

This study was undertaken to determine whether coronary reactive hyperemia is coupled to myocardial metabolic activity and thus proportional to myocardial oxygen consumption or whether it is mechanically determined, resulting from direct myogenic relaxation of coronary vascular smooth muscle in response to loss of the stretch stimulus provided by arterial blood pressure. In ten unanesthetized dogs, coronary artery occlusions 1-7 seconds in duration produced reactive hyperemia resulting in 260-420% repayment of the blood flow debt incurred during occlusion. When myocardial oxygen consumption and coronary blood flow were increased by paired ventricular stimulation, reactive hyperemia increased to a commensurate degree so that debt repayments remained unchanged at 270-420%. That this augmentation of reactive hyperemia was actually related to increased myocardial metabolic activity during the occlusion was demonstrated by a similar increase in the hyperemic response when paired ventricular stimulation was applied during the occlusion only. To demonstrate that augmented reactive hyperemia during paired ventricular stimulation did not merely represent direct myogenic relaxation imposed on a vascular bed more dilated from the onset, coronary blood flow was increased by infusion of adenosine with no increase in myocardial oxygen consumption. During adenosine infusion, the total volume of reactive hyperemic blood flow was similar to that observed during the control situation. Thus, in the coronary system reactive hyperemia is related to myocardial metabolic activity during the interval of arterial occlusion and not influenced by alterations in resting coronary blood flow which occur independently of myocardial oxygen consumption.
The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold
Authors: Brian M. Sicari, Scott A. Johnson, Bernard F. Siu, Peter M. Crapo, Kerry A. Daly, Hongbin Jiang, Christopher J. Medberry, Stephen Tottey, Neill J. Turner, Stephen F. Badylak
Journal: Biomaterials (2012)
Comparison of two assays for measuring plasma concentrations of paracetamol
Authors: C V Egleston, C Browning, I Hamdi, G Campbell-Hewson, S M Robinson
Journal: BMJ (1997)

An overdose of paracetamol can cause fatal hepatic necrosis, but acetylcysteine is an effective antidote if given early.1 An estimation of plasma concentrations of paracetamol is required if a patient is suspected of having taken a toxic dose. We compared the AcetaSite test card and Stat-Site reflectance meter (GDS Diagnostics, Elkhart, IN), a bedside method of determining paracetamol concentrations that takes 2 minutes, with the Quantase assay (Porton Products, Maidenhead), an established laboratory method.

Altogether 192 patients were recruited into the study; of these, 92 had taken paracetamol. Patients who had not ingested paracetamol but required venepuncture for other reasons made up the control group. A blood sample was obtained 4 hours after suspected overdose or on arrival if 4 hours had already passed. A drop of this blood was used to measure paracetamol concentration with the AcetaSite card and …
The Most Critical Aspects Of Snake Envenomization
Authors: W. Peter Horen
Journal: JAMA (1967)

<h3>To the Editor:—</h3> A letter to the editor on snakebite treatment<sup>1</sup>noted the tragedy of Dr. F. A. Shannon's death. Two of the most critical aspects of snake envenomization are the species of snake involved and the route of venom inoculation. Dr. Shannon was bitten by<i>Crotalus scutulatus scutulatus</i>, and one of its fangs entered a blood vessel, greatly accelerating absorption of the venom. He was in shock within a few minutes, was unable to perform effective first aid treatment, and died that evening. The median lethal dose of the venom from the snake that bit him was 0.2 mg/kg, 20 times that of<i>C atrox</i>.<sup>2</sup><i>C s scutulatus</i>venom is strongly neurotoxic. It shares one antigen with the highly lethal neurotoxic South American rattler<i>C durissus terrificus</i>. This antigen is absent in cytotoxic crotalid venoms.<sup>3</sup> From my research experience I can testify that venom of<i>C</i>
St. Mary's Hospital, Manchester. CASES ILLUSTRATIVE OF OVARITIS AND CONGESTION OF THE OVARY, AS A CAUSE OF HYSTERIA
Authors: G. B. Masfen
Journal: BMJ (1855)

She had generally had good health, but in the pre- vious June she had had a severe attack of fever, from which she did not entirely recover for two months, and which left her totally without voice: in other respects, she was apparently in perfect health.On examination, I found that she was not only without voice, but that she had lost the power of speech, so that she could not even whisper.If she endeavoured to say " yes", her lips slightly opened,
Diagnostic Yield and Optimal Duration of Continuous-Loop Event Monitoring for the Diagnosis of Palpitations: A Cost-Effectiveness Analysis
Authors: Peter J. Zimetbaum
Journal: Annals of Internal Medicine (1998)

Background: Continuous-loop event recorders are widely used for the evaluation of palpitations, but the optimal duration of monitoring is unknown. Objective: To determine the yield, timing, and incremental cost-effectiveness of each week of event monitoring for palpitations. Design: Prospective cohort study. Patients: 105 consecutive outpatients referred for the placement of a continuous-loop event recorder for the evaluation of palpitations. Measurements: Diagnostic yield, incremental cost, and cost-effectiveness for each week of monitoring. Results: The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and $5832 per new diagnosis in week 3. Conclusions: In patients referred for evaluation of palpitations, the diagnostic yield of continuous-loop event recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring period is reasonably cost-effective for most patients and should be the standard period for continuous-loop event recording for the evaluation of palpitations.
TSLP: a novel potent proinflammatory mediator that activates myeloid dendritic cells to stimulate Th1 and Th17 activity in rheumatoid arthritis
Authors: F. M. Moret, C. E. Hack, K. M. van der Wurff-Jacobs, F. P. Lafeber, J. A. van Roon
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Thymic stromal lymphopoietin (TSLP) is well known for its potent activation of myeloid dendritic cells (mDCs) resulting in Th2-mediated immune responses. TSLP signals cells via the interleukin (IL)-7 receptor-α chain (IL-7Rα), shared with IL-7, together with the TSLP receptor (TSLPR) subunit. Recently, the authors have demonstrated that prevention of TSLPR signalling strongly reduces Th17-driven experimental arthritis and immunopathology. Furthermore, the authors have shown that administration of TSLP enhances severity of inflammation and joint destruction in collagen induced arthritis. <h3>Objective</h3> To determine the levels of TSLP and TSLPR in joints of rheumatoid arthritis (RA) patients and the capacity of TSLP to induce mDC-dependent T cell activation. <h3>Methods</h3> TSLP was measured in synovial fluid (SF) of RA (n=44) and osteoarthritis (OA) patients (n=20). CD1c<sup>+</sup> mDC numbers and TSLPR expression on these cells were assessed by FACS analysis in paired samples of SF and peripheral blood (PB) from RA patients (n=7). mDCs, isolated from PB of RA patients (n=10) were stimulated with TSLP for 24 h and cytokine production was measured. Washed TSLP-activated mDCs were added to autologous CD4 T cells from PB in the absence of additional stimuli, cultured for 6 days and subsequently proliferation was measured. T cell cytokine production was measured upon restimulation with ionomycin/PMA. <h3>Results</h3> TSLP levels in SF of RA patients were increased compared to OA patients (460 vs 75 pg/ml, respectively, p&lt;0.01). CD1c<sup>+</sup> mDC numbers from SF were increased compared to PB (3.8% vs 0.7%, respectively, p&lt;0.02). mDCs from SF and PB expressed substantial levels of TSLPR (SF: 76% positive cells, MFI 19; PB: 70% positive cells, MFI 15). TSLP significantly stimulated production of chemokines TARC and MIP1α by mDCs (TARC; from 4 to 89, MIP1α; from 1545 to 6293 pg/ml, p&lt;0,02). Upon incubation with TSLP, TSLPR-expressing mDCs potently stimulated proliferation of autologous CD4 T cells compared to unstimulated mDCs (ratio T cell: DC 5:1; from 1537 to 18903 cpm). Upon restimulation, TSLP-mDC-activated CD4 T cells produced increased levels of tumour necrosis factor (TNF)-α (4737 vs 12125 pg/ml, p&lt;0.02), IFN-γ (163 vs 818 pg/ml, p&lt;0.02) and IL-17 (50 vs 592 pg/ml, p&lt;0.05) in addition to IL-4 (24 vs 300 pg/ml, p&lt;0.03). Induction of TNF-α and IL-17 was significantly higher in RA patients compared to healthy controls (p&lt;0.05). <h3>Conclusion</h3> The authors9 data indicate that increased intra-articular TSLP concentrations in RA potently activate TSLPR-expressing mDCs from RA patients to cause chemotaxis and activation of arthritogenic T cells. This suggests that TSLP and its receptor are novel therapeutic targets for RA.
Allergy and Human Emotions
Authors: William B. Sherman
Journal: JAMA (1967)

For many years a large group of physicians has attempted to treat the allergic diseases by purely immunologic methods, while others have employed a psychosomatic approach. Too often the devotees of one method have ignored the other or even expressed hostility toward it. The avowed purpose of this book is to blend the two methods into a "holistic" approach to the patient whose disease is considered an outcry of the whole individual. Like many other appeals for cooperation and equal recognition, it is devoted almost entirely to one view of the problem. In its attempt at a broad and thorough approach and "caution about identifying any one factor as the cause of an illness," interpersonal relationships are discussed in great detail. Poison ivy and ragweed pollen are not once mentioned. The result is not a balanced guide for the inexperienced, but rather a plea for those who already use the
The mobilization of arachidonic acid in platelets exposed to thrombin or ionophore A23187. Effects of adenosine triphosphate deprivation.
Authors: S Rittenhouse-Simmons, D Deykin
Journal: Journal of Clinical Investigation (1977)

In studies conducted with human gel-filtered platelets, we have found: (a) that the release of serotonin and transfer of [3H]arachidonic acid from phosphatidylcholine and phosphatidylinositol to plasmalogen phosphatidylethanolamine which are associated with the activation of platelets by thrombin are both strongly dependent upon the presence of metabolic ATP; (b) that serotonin release and arachidonic acid mobilization in labeled phosphatides are promoted by the calcium ionophore A-23187 in media free of calcium ions; (c) that inhibitors of ATP synthesis, while leading to impairment of the release reaction induced by ionophore, do not inhibit ionophore-stimulated mobilization of arachidonic acid. We conclude that the activation of phospholipase A2 responsible for freeing arachidonic acid from platelet phosphatides is solely dependent upon the increased cytoplasmic levels of calcium ions promoted by either ionophore or, in an energy-dependent fashion by thrombin. Phospholipase activation is not a function of latent hydrolytic activity made available by the release reaction.
Lordotic right posterior oblique projection of the left coronary artery: a speical view for special anatomy.
Authors: D T Arani, I L Bunnell, D G Greene
Journal: Circulation (1975)

The lordotic right posterior oblique projection of the left coronary artery is obtained by combining cranial angulation of the X-ray beam with rotation of the patient into the right posterior oblique position. This projection is helpful for separation of the main left coronary artery and the proximal portions of the left anterior descending and circumflex divisions, especially in patients in whom the left anterior descending artery is directed cephalad early in its course. The obtaining of an image from the lordotic right posterior oblique projection adds less than two minutes to the procedure and improves arteriographic assessment of the left coronary artery.
Public Health in New York City In the Revolutionary Period
Authors: John Duffy
Journal: JAMA (1976)

Prior to the American Revolution, New York City was a pleasant town, still reflecting its Dutch origin in the architecture and the cleanliness of its people. By 1760, the town consisted of approximately 3,000 houses and a population of about 17,000. Homes were usually built with brick, and the streets, although irregular, were paved with "round pebles [sic]." According to visitors, the houses were well kept and neatly painted, and the streets were clean. The one criticism all agreed on was the lack of good water. The main source was the city's shallow wells from which the water was disagreeable in taste and virtually undrinkable—a fortunate circumstance since it was also contaminated—and most inhabitants bought their supply from water carriers who obtained it from the Tea Water Pump, a well located outside town. The most devastating comment on the local water was made by Peter Kalm,<sup>1</sup>a Swedish traveler,
Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent
Authors: C A Camargo, J F Madden, W Gao, R S Selvan, P Clavien
Journal: Hepatology (1997)

Interleukin-6 (IL-6) is an acute reactant cytokine with anti-inflammatory properties, which has been found to prevent injury in a model of acute hepatitis in mice through downregulation of tumor necrosis factor alpha (TNF-alpha); to correlate inversely with markers of hepatocellular injury in patients with liver ischemia; and to initiate liver regeneration in mice. In this study, we investigated the role of IL-6 in rodent models of hepatic warm ischemia/reperfusion (WI/Rp) injury. IL-6-deficient mice (-/-) were subjected to hepatic WI and compared with C57BL/6 mice, as well as IL-6 -/- mice pretreated with recombinant IL-6 (rIL-6). The effects of rIL-6 following various periods of ischemia were further studied in models of hepatic ischemia in rats. IL-6 -/- mice had increased reperfusion injury as assessed by transaminase levels and a tissue necrosis scoring system when compared with controls, an effect prevented by pretreatment with rIL-6. Similarly, rats pretreated with rIL-6 had reduced reperfusion injury and better survival than controls in each respective WI group. Tissue TNF-alpha expression measured by Northern blot analysis and serum C-reactive protein (CRP) levels, a marker of inflammation, were significantly reduced in animals pretreated with rIL-6. Administration of antibodies to TNF-alpha reproduced the beneficial effect of rIL-6. Hepatocyte proliferation, as assessed by a scoring method for mitotic index and proliferating nuclear cell antigen staining, was markedly increased in rIL-6-treated rats when compared with controls. In conclusion, this study suggests that IL-6 could play an important role in limiting hepatic warm ischemia/reperfusion (WI/Rp) injury, probably through its anti-inflammatory properties, modulation of TNF-alpha, and/or promotion of liver regeneration. rIL-6 might become an important cytokine in clinical situations associated with WI/Rp injury.
AIDS-Related Malignancies: State of the Art and Therapeutic Challenges
Authors: Jean-Philippe Spano, Dominique Costagliola, Christine Katlama, Nicolas Mounier, Eric Oksenhendler, David Khayat
Journal: Journal of Clinical Oncology (2008)

Despite the impact of combination antiretroviral therapy (cART) on HIV-related mortality, malignancy remains an important cause of death in the current era. Although the advent of cART has resulted in reductions in the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma, non–AIDS-defining malignancies present an increased risk for HIV-infected patients, characterized by some common clinical features, generally with a more aggressive behavior and a more advanced disease at diagnosis, which is responsible for poorer patient outcomes. Specific therapeutic recommendations are lacking for these new nonopportunistic malignancies, such as Hodgkin's lymphoma, anal cancer, lung cancer, hepatocarcinoma, and many others. Antiretroviral agents have a propensity for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Because many antineoplastic drugs are also metabolized by the CYP system, coadministration with cART could result in either drug accumulation with increased toxicity, or decreased efficacy of one or both classes of drugs. Further research delineating the combined safety and pharmacokinetics of antiretrovirals and antineoplastic therapy is necessary. Special considerations of these AIDS-related and non–AIDS-related malignancies and their clinical and therapeutic aspects constitute the subject of this review.
BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability
Authors: A Slupianek, R Falinski, P Znojek, T Stoklosa, S Flis, V Doneddu, D Pytel, E Synowiec, J Blasiak, A Bellacosa, T Skorski
Journal: Leukemia (2012)
Reaction of alveolar macrophages to inhaled metal aerosols.
Authors: P Camner, A Johansson
Journal: Environmental Health Perspectives (1992)

For more than a decade we have exposed rabbits to different metals, usually in soluble form, and investigated the effects on the lungs. The metal concentrations have been around 1 mg/m3,i.e., not more than a factor of 10 above occupational threshold limit values. The exposure periods have been 1-8 months (6 hr/day, 5 days/week). We have studied especially the morphology and function of alveolar macrophages (AM), the morphology of alveolar type I and type II epithelial cells, and analyzed lung phospholipids. Several metals produce specific, complex effects. For example, metallic and soluble nickel (NiCl2) increase both number and size of the type II cells, increase the production of surfactant, and affect morphology and function of AM. Cobalt (CoCl2) induces a different effect on type II cells from nickel, causing the formation of nodules in these cells. Trivalent chromium [Cr(NO3)3] does not affect either type II cells or the amount of surfactant significantly, but markedly affects AM. The administered metals affect AM both directly and indirectly. For example, nickel induces an increased production of surfactant, resulting in overfed AM with an increased metabolic activity. However, nickel also induces a direct decrease in the release of lysozyme activity by AM. Our results emphasize the complexity of the effects on the lungs of inhaled agents, which can act both directly and indirectly on AM.