tbuckley/cabot-search huggingface dataset:
Coagulation studies in cases of intrauterine death: overkill?
Authors: G Constantine, V Menon
Journal: BMJ (1987)

Schering Company (personal communication) has information from 16 pregnancies, all normal, in which there was low dose exposure.The company is also aware of four pregnancies exposed to the Hammerstein regimen.Two normal girls were born after treatment with 50 mg cyproterone acetate daily during the first 10 and 18 weeks of pregnancy, respectively.Two boys were born after exposure to 100 mg cyproterone acetate daily but little is known about these pregnancies.One of them occurred in Britain (treatment for 20 weeks, child probably normal) and the other in the'United States (data inadequate but possible exposure for six weeks, outcome unknown) (Schering Company, personal communication).In our patient we considered that the male fetus was at particular risk of genital malformation because ofthe high dose and prolonged exposure to the antiandrogenic drug during a sensitive period of fetal life.Postabortal examination of the fetus, however, showed no sign of anatomical malforma- tion, so the abortion may have been unnecessary.Nevertheless, normal genital anatomy does not exclude the risk of disturbed sexual function in adult life.4 The question what to advise should another patient be exposed to cyproterone acetate during early pregnancy remains open.Our case and the few available data from other patients suggest that apparently normal development may occur in a male fetus and that induced abortion may therefore not be absolutely necessary.
LEVELS OF SOLUBLE WNT-INHIBITORS ARE RELATED TO SYSTOLIC FUNCTION AND PREDICT OUTCOME IN PATIENTS WITH CHRONIC HEART FAILURE
Authors: Erik T. Askevold, Christen P. Dahl, Kaspar Broch, Svend Aakhus, Arne Yndestad, Lars Gullestad, Pål Aukrust, Thor Ueland
Journal: Journal of the American College of Cardiology (2010)
Salicylic Acid Treatment Contrasted with Other Remedies in the Treatment of Acute Rheumatism
Authors: J. Russell
Journal: BMJ (1882)

sive pus.The liver weighed five pounds and five ounces.From its cut surface a greyish-white infiltration could be squeezed out.This whitish fluid, as pointed out by Virchow and Bottcher in leucocyth:emic cases, consisted of closely packed free nuclei and small cells.The naked eye appearance was remarkably purulent.Section of the kidney gave a somewhat similar material, which, however, more resembled thickened greenish pus.The lymphatic glands were not appreciably enlarged.I did not then examine the blood ; but when I sent for some after a little time, the cadaver was removed to its final resting-place.No reliable history of the case was obtainable.It was said that her circumstances was somewhat straightened; that she suffered hunger and privations at times; severe and prolonged trials for years.Her appearance was always cachectic.The pain in her side dated from a fall (uncertair.)or some sudden exertion (?) months previously.It is probable that a fall was the starting-point in the displacement of this leukaemic spleen; and then that its own increasing weight, with that of the superincumbent enlarged liver, caused it to be jammed deeper and deeper into the pelvis, till gradual pressure on the sigmoid flexure ended in obstruction and death.
Abstract 2628: Antitumor activity of MPC-3100, a synthetic Hsp90 inhibitor, in combination with erlotinib and sorafenib
Authors: Vijay R. Baichwal, Brita Brown, Daniel Wettstein, Damon I. Papac, Gary G. Mather, Robert O. Carlson
Journal: Cancer Research (2011)

Abstract Introduction: MPC-3100 is a fully synthetic, orally bioavailable, Hsp90 inhibitor in clinical development. It is active as a single agent in xenograft models with many cancer types including colon, gastric, ovary, prostate, breast, lung and myeloid leukemia. We evaluate here the activity of MPC-3100 in combination with erlotinib or sorafenib in xenograft models. Methods: Three to five million cells, depending on cell-type, were implanted subcutaneously into athymic mice (nu/nu) for tumor studies. Dosing was initiated when median tumor volume was &amp;gt;100 mm3. All compounds were dosed orally, once daily. MPC-3100 (100 mg/kg) and erlotinib (100 mg/kg) were dosed on Days 1-21 and sorafenib (60 mg/kg) was dosed on Days 1-9. Results: Anti-tumor activity for the combination of MPC-3100 and erlotinib was compared to that of the single agents in a lung cancer (A549) xenograft model sensitive to EGFR inhibition. Administration of MPC-3100 or erlotinib resulted in 52% and 64% tumor growth inhibition (TGI), respectively relative to vehicle by the end of dosing on Day 19. By contrast, the combination of MPC-3100 and erlotinib resulted in 30% tumor regression over the same period. Thus the combination of MPC-3100 and erlotinib was more effective at inhibiting tumor growth than either agent alone (p&amp;lt;0.05). The combined anti-tumor activity of MPC-3100 and sorafenib was compared to administration of the single agents in a xenograft model with the melanoma cell line A375 that harbors the activating B-raf mutation, V600E. The median tumor volume (MTV) of the cohorts dosed with vehicle, MPC-3100 or sorafenib as single agents was comparable and increased by 4.8-, 6.4- and 8.2-fold, respectively by the end of dosing on study Day 20, whereas MTV of the cohort dosed with a combination of MPC-3100 and sorafenib increased by only 1.6-fold. The combination of MPC-3100 and sorafenib resulted in 66% tumor growth inhibition relative to vehicle on Day 20 and was more effective at inhibiting tumor growth than single agent (p&amp;lt;0.05). Conclusions: The combination of MPC-3100 with erlotinib or sorafenib shows greater anti-tumor activity than either agent alone. Thus, in addition to its broad activity in xenograft models as a single agent, MPC-3100 has the potential to be combined with other targeted therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2628. doi:10.1158/1538-7445.AM2011-2628
Health is a human right
Authors: F. Godlee
Journal: BMJ (2009)

Alex Jadad and Laura O’Grady’s call for a debate on the definition of health has stimulated fascinating responses to both their editorial (doi:10.1136/bmj.a2900) and their blog (http://blogs.bmj.com/bmj/2008/12/10/alex-jadad-on-defining-health). I particularly like Richard Smith’s response to the blog, in which he suggests that health is “the capacity to do what matters most to you” (http://blogs.bmj.com/bmj/2009/01/05/richard-smith-can-poetry-define-health).

Two other responses appear in this week’s Letters. Peter Mansfield recalls the Peckham experiment in London in the 1930s and 1940s, which aimed to investigate the nature of health (doi:10.1136/bmj.b83). An expanded vision of health is unlikely to come from within medicine, he says. “Economic and …
Life threatening liver disease during treatment with monoclonal antibodies
Authors: T. Kaiser, J. Moessner, K. Patel, J. G McHutchison, H. L Tillmann
Journal: BMJ (2009)

A 66 year old man with an exacerbation of erythrodermic psoriasis despite several weeks of treatment with efalizumab, a recombinant humanised monoclonal antibody that binds to CD11a and acts as an immunosuppressant, was treated with adalimumab, a fully humanised monoclonal antibody that binds and deactivates tumour necrosis factor α (TNFα). Before starting treatment tuberculosis was excluded. The patient had no risk factors for infectious diseases and had never received blood products. Ten days after starting adalimumab, the patient developed jaundice. Blood tests showed the presence of the surface antigen of the hepatitis B virus (HBV) and higher than normal values of alanine aminotransferase (9.14 µkat/l; normal value <0.85 µkat/l), γ glutamyl transferase (2.92 µkat/l; <1.1 µkat/l), alkaline phosphatase (2.19 µkat/l; <2.15 µkat/l), and bilirubin (155 µmol/l; <20.5 µmol/l). Despite appropriate treatment, he developed progressive coagulopathy (international normalised ratio 2.5), and his serum bilirubin increased to more than 40 times the upper limit of normal (809 µmol/l; <20.5 µmol/l). The coagulopathy normalised over four weeks, whereas bilirubin normalised only after months of effective treatment. Fortunately, the patient did not clinically decompensate during this period of severe liver injury. ### Short answers
RATE OF BLOOD FLOW THROUGH STANDARD GAGE NEEDLES UNDER PRESSURE
Authors: JAMES D. BREW
Journal: JAMA (1949)

The recent war coupled the great need for the rapid transfusion of blood with the need for readily available supplies of blood and plasma. The use of large needles and methods of pumping these fluids intravenously under positive pressure resulted in the transfusion of previously unheard of quantities at almost unbelievable rates of flow. Most civilian hospitals are well aware of these methods, and several articles have been published with standard technics. Reports of the use of large amounts of blood are now a daily occurrence.  Except in emergency rooms where treatment for traumatic accidents is frequent, the main need for the rapid transfusion of large quantities of blood exists almost solely on the delivery floor and in the operating room. It is still difficult, even in many well equipped institutions, to obtain the apparatus for supplying blood under pressure and needles of sufficient size for the rapid transfusion of
Chloroquine Naphthoate for Malaria
Authors: L. J. Bruce-Chwatt, L. J. Charles
Journal: BMJ (1957)

Because of heavy pressure on our space, correspondents are ,asked to keep their letters short.Chloroquine Naphthoate for Malaria SIR,-The intensely bitter taste of many antimalarial com- pounds is an obvious disadvantage in their use as therapeutic or protective drugs, particularly in children.The two chlor- oquine salts (diphosphate and sulphate) used at the present time are almost as bitter as quinine, and medical practi- tioners in the tropics have often expressed the need for a more palatable though equally effective drug.Chloro- quine naphthoates, of low solubility, have little if any taste.
THE ADVANCEMENT OPERATION IN SQUINT
Authors: VARD H. HULEN
Journal: JAMA (1910)

Teachers of ophthalmic surgery have long advocated the more frequent performance of advancing and shortening operations, and some do them exclusively in preference to tenotomy for strabismus, but I believe that most of us are still very largely doing tenotomies. It must be that none of the various methods of advancement are considered entirely satisfactory, the simpler operation of tenotomy being more frequently chosen, hoping thereby to obtain an acceptable result. Most ophthalmologists will agree that the advancement operation is more certainly corrective, physiologically more scientific, and functionally safer than tenotomy, and it is my conviction that a tenotomy alone should rarely be done in any case of squint. A rather extensive observation of the work of various operators, including repeated visits to many of the large European eye clinics, convinces me that the ideal advancement operation has not yet been presented. There are certain requisites for this ideal
Failure to Thrive and Metabolic Alkalosis
Authors: Joseph I. Wolfsdorf
Journal: JAMA (1980)

This report concerns two infants with failure to thrive and hypochloremic metabolic alkalosis. Both infants were fed exclusively with a soybean-based formula, which, as a result of a manufacturing error, was severely deficient in chloride. When an alternative formula containing an adequate amount of chloride was prescribed, the electrolyte abnormality was corrected, and the infants resumed their normal weight gain.
Gonococcal Antibodies in Acute Arthritis
Authors: Evelyn V. Hess
Journal: JAMA (1965)

Diagnosis of acute gonococcal arthritis has been hampered by the lack of a reliable and specific procedure for the detection of gonococcal antibodies. The indirect immunofluorescent method, using formalin-fixed smears of Neisseria gonorrhoeae organisms, has provided a sensitive and specific method for measurement of this antibody. Gonococcal antibody was present in 19 of 22 patients (86%) with definite and 17 of 35 patients (49%) with presumptive gonococcal arthritis. Only seven of 42 patients (17%) with active Reiter's syndrome gave positive reactions. Patients with acute infectious arthritis caused by other organisms gave negative results. Cross reactivity of gonococcal arthritis sera with Mimea polymorpha was not observed. The results indicate that the method described provides a means for specific recognition of gonococcal antibodies, and permits epidemiologic study of gonococcal infection and its complications.
Galactose tolerance in patients with atopic cataracts
Authors: M.F. MUHLEMANN, J.N. MOUNT, J.J. CREAM
Journal: British Journal of Dermatology (1987)

Galactosaemia has been suggested as a contributory factor in the pathogenesis of some presenile and senile cataracts. To assess whether galactosaemia plays any part in the development of atopic cataracts a galactose tolerance test was carried out in eight atopic dermatitis patients whose cataracts had appeared between the ages of 12 and 39 years. In seven patients a normal result was obtained and in one the result was just above normal. Impaired galactose tolerance appears to have no role in the pathogenesis of atopic cataract.
Accuracy of Spleen Stiffness Measurement in Detection of Esophageal Varices in Patients With Chronic Liver Disease: Systematic Review and Meta-analysis
Authors: Siddharth Singh, John E Eaton, Mohammad H Murad, Hironori Tanaka, Hiroko Iijima, Jayant A Talwalkar
Journal: Clinical Gastroenterology and Hepatology (2013)
Megaloblastic Anaemia and Vitamin-B12 Deficiency After Anticonvulsant Therapy
Authors: P. Kidd, D. L. Mollin
Journal: BMJ (1957)

HUMAN LIVER METABOLISM BRITISN infiltration of the organ by carcinoma or leukaemia.Such functional disturbances quite likely initiate the gross structural changes in the liver.Anaesthesia used during biopsy does not modify liver cell metabolism.
Functional state of the endothelium determines the response to endothelin in the coronary circulation
Authors: D. J Stewart, R. Baffour
Journal: Cardiovascular Research (1990)

Study objective – The aim was to study the effects of endothelin on the heart with special attention to an interaction with endothelium derived relaxing factor (EDRF). Design – Bolus injections of various amounts of endothelin (1-300 ng) were given into the coronary circulation of isolated perfused rabbit hearts while coronary flow was held constant at 35 ml·min−1 and coronary perfusion pressure and other physiological variables were measured. The effects of indomethacin and haemoglobin on the responses were examined. Experimental material – 15 New Zealand white rabbits, 1.0-1.5 kg, were used for the studies. The animals were anaesthetised and the hearts rapidly excised and perfused in the Langendorff manner. Measurements and results – With coronary flow held constant, bolus injections of endothelin up to 300 ng caused no consistent increase in perfusion pressure, but resulted in a slight increase in left ventricular developed pressure. Indomethacin (10 μM) did not alter the response to endothelin; however, when endothelium dependent dilatation was inhibited by haemoglobm (10 μM), a dose dependent endothelin induced constriction was unmasked, with EC50 of 41 (SEM 15) ng, maximum +46(8) mm Hg. This constrictor response was further augmented by air infusion (0.5 ml), EC50 26(10) ng, maximum +102(12) mm Hg, and endothelin now caused a substantial dose dependent reduction in left ventricular contractile function. Endothelium dependent dilatation was not significantly reduced after air embolisation. Conclusions – The remarkable ability of the endothelium to protect against vasoconstrictor action of circulating endothelin in the coronary bed may not be due only to EDRF release, but perhaps also to an additional mechanism related to endothelial barrier of metabolic function.
Selective Suppression of Antibody Production with the Aid of Radiolabelled Birch Pollen Allergen
Authors: G. Filipp, G. Biró, W. D. Hartung, G. Lehmann
Journal: Allergy (1981)

In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of the radiolabelled pollen allergen (75-1000 microCi125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, is accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of subsequent intravenously administered radiolabelled birch pollen allergen (750-100 microCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected.
Hepatic O2 exchange and liver energy metabolism in hyperdynamic porcine endotoxemia: effects of iloprost
Authors: Karl Träger, Martin Matejovic, Carl Zülke, Arnim Vlatten, Josef Vogt, Ulrich Wachter, Jürgen Altherr, Alexander Brinkmann, Karl W. Jauch, Michael Georgieff, Peter Radermacher
Journal: Intensive Care Medicine (2000)
Neutrophil extracellular traps as a new paradigm in innate immunity: friend or foe?
Authors: Paul R. Cooper, Lisa J. Palmer, Iain L. C. Chapple
Journal: Periodontology 2000 (2013)

Abstract The discovery of neutrophil extracellular traps in 2004 opened a fascinating new chapter in immune‐mediated microbial killing. Brinkman et al. demonstrated that neutrophils, when catastrophically stimulated, undergo a novel form of programmed cell death (neutrophil extracellular trap formation) whereby they decondense their entire nuclear chromatin/ DNA and release the resulting structure into the cytoplasm to mix with granule‐derived antimicrobial peptides before extruding these web‐like structures into the extracellular environment. The process requires the activation of the granule enzyme peptidyl arginine deiminase‐4, the formation of reactive oxygen species (in particular hypochlorous acid), the neutrophil microtubular system and the actin cytoskeleton. Recent work by Yousefi et al. demonstrated that exposure to different agents for shorter stimulation periods resulted in neutrophil extracellular trap release from viable granulocytes, and that such neutrophil extracellular traps comprised mitochondrial DNA rather than nuclear DNA and were also capable of microbial entrapment and destruction. Deficiency in NADPH ‐oxidase production (as found in patients with chronic granulomatous disease) results in an inability to produce neutrophil extracellular traps and, along with their failure to produce antimicrobial reactive oxygen species, these patients suffer from severe, and sometimes life‐threatening, infections. However, conversely the release of nuclear chromatin into tissues is also potentially autoimmunogenic and is now associated with the generation of anti‐citrullinated protein antibodies in seropositive rheumatoid arthritis. Other neutrophil‐derived nuclear and cytoplasmic contents are also pathogenic, either through direct effects on tissues or via autoimmune processes (e.g. autoimmune vasculitis). In this review, we discuss the plant origins of a highly conserved innate immune method of microbial killing, the history and biology of neutrophil extracellular traps and their role in defence and in human diseases. We attempt to resolve areas of controversy and propose roles for excess neutrophil extracellular trap release from hyperactive/reactive neutrophils and for the unique peptidyl arginine deiminase enzyme of Porphyromonas gingivalis in the pathogenesis of periodontitis, and subsequently a role for periodontitis/the peptidyl arginine deiminase enzyme of P. gingivalis in the causal pathway of autoimmune diseases such as rheumatoid arthritis. We propose that neutrophil extracellular trap and peptidyl arginine deiminase release may propagate tissue‐destructive mechanisms rather than provide protection in susceptible individuals and that release of host‐derived DNase may play an important role in the digestion and removal of neutrophil extracellular traps within tissues.
Abstract 3301: Inhibition of the secretory pathway calcium ATPase 1 (SPCA1) in MDA-MB-231 breast cancer cells and the effect on protein expression
Authors: Jane M. Lee, Diana G. Ross, Gregory R. Monteith, Sarah J. Roberts-Thomson
Journal: Cancer Research (2014)

Abstract SPCA1 is a Ca2+ pump located on the membrane of the Golgi apparatus and is involved in controlling calcium levels within the Golgi. We have previously shown that SPCA1 is upregulated in some basal-like breast cancers. Given the role of the Golgi in protein trafficking and processing, we hypothesised that SPCA1 may be involved in regulating the expression of proteins important in cancer. To address this hypothesis we used 2D-DIGE to identify proteins that are altered when SPCA1 is silenced in MDA-MB-231 basal cancer cells. MDA-MB-231 cells were seeded into 6-well plates (75,000 cells/well) and treated with SPCA1 or non-targeting siRNA. Protein was isolated 72 h post siRNA treatment, and SPCA1 silencing was confirmed by immunoblotting. 2D-DIGE and MS/MS were used to identify proteins with differential expression with SPCA1 silencing. Heat shock protein 60 (HSP60) was identified as a protein potentially sensitive to SPCA1 silencing using 2D-DIGE. Immunoblotting and real time RT-PCR showed that SPCA1 silencing reduced HSP60 protein and mRNA expression by 81±2% and 60±7% (n=3, P&amp;lt;0.05), respectively. Given the role of HSP60 in cell death pathways, we also assessed the consequences of SPCA1 silencing on heat shock and staurosporine-induced cell death. SPCA1 silencing had no effect on heat shock-induced cell death but reduced the sensitivity of MDA-MB-231 breast cancer cells to staurosporine. Although further studies are required to fully characterize the functional consequences of HSP60 downregulation upon SPCA1 silencing, this work suggests that SPCA1 is a complex regulator of proteins important in cancer pathways. Citation Format: Jane M. Lee, Diana G. Ross, Gregory R. Monteith, Sarah J. Roberts-Thomson. Inhibition of the secretory pathway calcium ATPase 1 (SPCA1) in MDA-MB-231 breast cancer cells and the effect on protein expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3301. doi:10.1158/1538-7445.AM2014-3301