tbuckley/cabot-search huggingface dataset:
Treating acute gouty arthritis with selective COX 2 inhibitors
Authors: A. G Fam
Journal: BMJ (2002)

Few arthritides are as painful, incapacitating, and stressful as a severe attack of acute gout, pseudogout, or calcific periarthritis. Successful treatment of these acute microcrystalline events depends on early use of an effective and safe anti-inflammatory drug in full dosage. The sooner such treatment is started the more rapid and complete the response. Treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids including adrenocorticotrophic hormone.1 Although colchicine is traditionally rooted in the treatment of acute gout, in recent years its use has declined steadily.1 Its drawbacks include slow onset of action, narrow ratio of benefit to toxicity, and reduced efficacy when used more than 24 hours after the an attack begins. Colchicine (0.6 mg orally every 2 hours, up to 4-6 mg/day) is now reserved for patients without renal, hepatic, or bone marrow disease, in whom the more effective NSAIDs are contraindicated or poorly tolerated. Intravenous colchicine is best avoided given its potential for serious toxicity, which potentially can result in myelosuppression, hepatic necrosis, renal failure, hypotension, seizures, and death.

Intra-articular corticosteroids (for example, methylprednisolone acetate 5-25 mg per joint), systemic corticosteroids (oral prednisone 20 mg/day tapered off over 4-10 days, or intramuscular triamcinolone hexacetonide 60 mg/day, repeated …
Depletion of intestinal resident macrophages prevents ischaemia reperfusion injury in gut
Authors: Y Chen
Journal: Gut (2004)

The cellular and molecular events involved in ischaemia reperfusion (IR) injury are complex and not fully understood. Previous studies have implicated polymorphonuclear neutrophils (PMN) as major inflammatory cells in IR injury. However, anti-PMN antiserum treatment offers only limited protection, indicating that other inflammatory cells are involved. We have therefore investigated the contribution of resident macrophages in IR injury using an IR gut injury model.DA rats were divided into sham operation and IR groups. The superior mesenteric artery was clamped for 30, 45, or 60 minutes (ischaemia) followed by 60 minutes of reperfusion. IR injuries were evaluated by histological staining. Expression of early growth response factor 1 (Egr-1), myeloperoxidase (MPO), and proinflammatory cytokines was analysed by immunohistochemistry, reverse transcription-polymerase chain reaction, and western blotting analysis. The specific role of macrophages in IR gut injury was also evaluated in resident macrophage depleted rats.Mucosal sloughing and villi destruction were seen in 45/60 minute and 60/60 minute IR guts. PMN infiltration at the damaged mucosal area was undetectable in 45/60 minute and 60/60 minute IR guts. PMN were localised around the capillaries at the base of the crypts in 60/60 minute IR gut. Obvious PMN infiltration was only observed in damaged villi after three hours of reperfusion. Elevated nuclear Egr-1 immunostaining was localised in resident macrophages at the damaged villi before histological appearance of mucosal damage. Furthermore, resident macrophages at the damaged site expressed MPO. Protein levels of the proinflammatory cytokines RANTES and MCP-1 were increased in IR gut. Depletion of resident macrophages by dichloromethylene bisphosphonate significantly reduced mucosal damage in rat guts after IR.Our findings indicate that resident macrophages play a role in early mucosal damage in IR gut injury. Therefore, macrophages should be treated as a prime target for therapeutic intervention for IR damage.
Asthma associated with N-acetylcysteine infusion and paracetamol poisoning: report of two cases.
Authors: S W Ho, L J Beilin
Journal: BMJ (1983)

Une administration intraveineuse de N-acetylcysteine s'est averee efficace contre l'intoxication au paracetamol. Les complications severes sont rares. Description de 2 personnes ayant en un asthme chez qui une reaction asthmatique s'est produite apres le traitement
Bias in observational study designs: prospective cohort studies
Authors: P. Sedgwick
Journal: BMJ (2014)

The Women’s Health Initiative Observational Study, a prospective cohort study, was designed to investigate causes of morbidity and mortality in postmenopausal women. In total, 93 676 women aged 50-79 years were recruited at 40 clinical centres throughout the United States between 1993 and 1998. Women were not recruited if they had conditions that were predictive of survival less than three years or had complicating conditions such as alcoholism, drug dependency, or dementia.

Researchers used the data collected for this study to investigate the association between smoking and the risk of invasive breast cancer. For this analysis, 13 686 women from the original cohort were excluded, including 12  075 with a history of cancer (except non-melanoma skin cancer) at baseline and 1168 whose smoking status was missing. In addition, 443 women were lost to follow-up. The size of the remaining cohort for analysis was 79 990.1

The primary outcome was pathologically diagnosed invasive breast cancer. Smoking behaviour had been assessed at baseline using self reported measures of lifetime passive and active smoking exposure. Information on other risk factors as potential confounders had also been collected at baseline, including age, ethnicity, body mass index, physical activity, and alcohol intake. The women were followed prospectively until 14 August 2009, or until they were diagnosed with invasive breast cancer, whichever came first. The average length of follow-up was 10.3 years. In total, 3520 incident cases of invasive breast cancer were identified. Compared with women who had never smoked, the risk of breast cancer was significantly higher in former smokers (adjusted hazard ratio 1.09, 95% CI 1.02 to 1.17) and in current smokers (1.16, 1.00 to 1.34). Among women who had never smoked, those with the most extensive exposure to passive smoking had a significantly increased risk of breast cancer compared with those who had never been exposed …
MAXIMAL HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION UNDER THE STIMULUS OF DEPLETION
Authors: F. S. Robscheit-Robbins, L. L. Miller, G. H. Whipple
Journal: The Journal of Experimental Medicine (1945)

The maximal output ceiling for hemoglobin in anemia due to blood loss is about 60 gm. per week-the dog receiving a rich protein diet plus high iron intake. Ferrous and ferric salts are equally effective. Iron intravenously plus a rich protein diet may push this level up to 90 to 100 gm. per week. Evidently iron absorption is a limiting factor. Maximal output for hemoglobin plus plasma protein in doubly depleted dogs may reach 120 to 130 gm. per week and using intravenous iron may reach 140 to 160 gm. per week. Maximal output for plasma protein alone in hypoproteinemia due to plasmapheresis reaches 60 to 70 gm. per week but this is not the true ceiling. Technically we cannot remove the new plasma protein as fast as it is formed and the hypoproteinemia is not maintained in the face of a rich protein diet intake. Furthermore the evidence points to the protein circulating pool contributing to the accretion of tissue protein in such dogs with a strong positive nitrogen balance and weight gain. Maximal figures for hemoglobin production in anemia run close to 1 gm. hemoglobin per kilo per day. Maximal figures for new hemoglobin plus plasma protein production in anemia and hypoproteinemia using iron given intravenously, may reach 1.5 gm. blood protein per kilo per day. The actual maximal plasma protein production equals about 1 gm. per kilo per day but the true production ceiling cannot be reached by this technique, for reasons given above.
Cases of Craniotomy, with Remarks
Authors: J. G. Swayne
Journal: BMJ (1850)

have yet tried for the subcutaneous nuevi, where the ligature is objectionable, is that suggested by Sir B. Brodie, of breaking down the structure with a probe, previously steeped in fused nitrate of silver, and introduced through a small incision made in the skin covering the naevus.The bulb should be removed, and the end of the probe rounded; the instrument must be pushed freely about in the morbid structure, for the cure probably depends rather upon the laceration of the tissue than upon the action of the nitrate of silver.Once I cured a large subcutaneous venous neevus situated on the left side of the occiput by tying the left occipital artery, which was a good deal enlarged.A nevus of the same kind on the ear, was a short time before treated successfully in this hospital by a ligature to the posterior auricular artery.This kind of operation, however, has failed in the greater number of instances in which it has been tried.It is likely to answer only when the nevus is supplied by one chief vessel, that vessel being enlarged.Mr. Wardrop relates in the twelfth volume of the Lancet, a case of extensive subcutaneous non-pulsating naevus affecting the nose, eyebrow, and orbit, in a child aged five months, which was quite cured by tying the common carotid artery in the same side; and another case of the same kind of nevus affecting the parts about the angle of the jaw in an infant where sloughing of the mass, -which had commenced before the operation, terminated fatally on the thirteenth day after the carotid was tied.The last form of nuevus, the arterial subcutane- ous, or the aneurism by anastomosis, is much more rare than the others, and is very seldom congenital; indeed it generally makes its first appearance in the adult.It grows quickly and throbs or pulsates so forcibly as distinctly to raise the finger placed upon it, and to cause much pain and annoyance to the patient.When it shines through the skin it is seen to have a bright red colour.Like the other nwevi, it yields under pressure.In almost every instance it has been situated upon the face or head, and in the orbit more frequently than in any other part.The ligature of the common carotid artery is the treatment that has been adopted in most of the recorded cases of this affection, and in three out of four it has proved successful.
Deaths from Poliomyelitis Among British Doctors
Authors: R. Doll, A. B. Hill
Journal: BMJ (1957)

POLIOMYELITIS STUDIESBRSrelatively late in life, but that antibody levels, where present, showed little variation over a three-year period.Serological evidence of widespread recent infections in children and adults with Coxsackie B3 virus corroborated reports of Bornholm disease in the area.
Rheumatic Fever: A Guide to its Recognition, Prevention and Cure
Authors: E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1982)

Society and no mean intellect and an observant clinician, even he in his Bowman lecture on gout and conditions of the eye confesses, 'I must admit little or no evidence as to deposits of urate of soda in any ocular structures....I doubt if it has been shown even in a single case though several observers have suggested its presence....I trust, however, that we are long past the stage of belief which regards such deposit as essential to a gouty inflammation'.It would seem at this point in time that William Heberden's and A. B. Garrod's observations had fallen on relatively stony ground.Even Sherlock Holmes would have had dif- ficulties in this misty diagnostic jungle, and his creator was merely following up current ideas.
Disorders of Speech, Perception, and Symbolic Behavior
Authors: James F. Toole
Journal: JAMA (1970)

Here is what the clinical neurologist has been waiting for in the<i>Handbook</i>series, an up-to-date series of definitive, tersely written, readable and at times, exciting, chapters which contain a wealth of information which is poorly understood by most clinical neurologists. Volume 4 is a companion of other volumes previously reviewed. As the editors correctly point out, it is no longer possible to consider neuropsychology separate from neurophysiology and experimental psychology. As a consequence, great attention is given to interrelating these three fields in Volume 4. For helping them to accomplish this, the editors give particular thanks to Drs. Arthur L. Benton and Lamar Roberts. The list of contributors is a Who's Who in the field and includes J. De Ajuriaguerra and R. Tissot on "The apraxias"; F. Lhermitte and J. C. Gautier, "Aphasia"; O. L. Zangwill, "Intellectual status in aphasia"; D. F. Benson and N. Geschwind, "The Alexias"; E.
416. Glucose-Dependent Insulin Production by Liver-Specific, Glucose-Regulatable Synthetic Promoters Results in the Cure of Diabetes
Authors: Jaeseok Han, Brienne McLane, Hee-Sook Jun, Ji-Won Yoon
Journal: Molecular Therapy (2005)

Top of pageAbstract
Type 1 diabetes is caused by insulin deficiency. Insulin gene therapy has been attempted to cure diabetes; however, there is no satisfactory system that results in the tight regulation of insulin production in response to physiological changes in glucose levels. To develop a liver-specific, glucose-responsive synthetic promoter that can tightly regulate insulin production in response to blood glucose levels, we employed 3 kinds of transcription factor-binding cis-elements: hepatocyte nuclear factor-1, CAAT/enhancer binding protein response element, and glucose-response element. We generated a library of synthetic promoters that contained 9 of these cis-elements in random combinations and screened each promoter for transcriptional activity. Among 821 promoters tested, we selected 3 with the highest transcriptional activity for further testing. To determine the glucose responsiveness of these promoters in vivo, we generated recombinant adenoviruses expressing furin-cleavable rat insulin under the control of selected synthetic promoters (rAd-SP-rINSfur) and the cytomegalovirus promoter (rAd-CMV-rINSfur) as a control for ubiquitous strong activity. rAd-SP-rINSfur (1010 viral particles) or rAd-CMV-rINSfur (109 viral particles) was administered into streptozotocin-induced diabetic NOD.scid mice (n=6/group) via the tail vein, and blood glucose levels were examined. We found that diabetic mice treated with rAd-SP-rINSfur became normoglycemic a few days after treatment, and normoglycemia was maintained for more than 1 month, whereas mice treated with rAd-CMV-rINSfur were dead within 10 days due to uncontrolled constitutive expression of the insulin gene. Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice produced insulin in response to glucose and cleared exogenous glucose from the blood in a manner similar to non-diabetic control mice. Insulin expression in rAd-SP-rINSfur-treated mice was observed only in the liver, not in other tissues or organs, whereas insulin expression in rAd-CMV-rINSfur-treated mice was present in all tissues tested, indicating that the synthetic promoters were liver-specific. On the basis of these observations, we conclude that our newly constructed, liver-specific synthetic promoters can tightly regulate insulin production in response to glucose and may have therapeutic potential for the cure of diabetes in humans by liver-directed insulin gene therapy.
Lasker Awards Suspended Indefinitely
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Lasker Awards Suspended Indefinitely Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 6, 21 March 1990, Pages 451–452, https://doi.org/10.1093/jnci/82.6.451 Published: 21 March 1990
Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response
Authors: J.E. Signorovitch, K.A. Betts, Y.S. Yan, C. LeReun, M. Sundaram, E.Q. Wu, P. Mulani
Journal: British Journal of Dermatology (2014)

Journal Article Comparative efficacy of biological treatments for moderate‐to‐severe psoriasis: a network meta‐analysis adjusting for cross‐trial differences in reference arm response Get access J.E. Signorovitch, J.E. Signorovitch Analysis Group, Inc. 111 Huntington Avenue 10th floor Boston MA 02199 U.S.A Correspondence James E. Signorovitch. E‐mail: jsignorovitch@analysisgroup.com Search for other works by this author on: Oxford Academic Google Scholar K.A. Betts, K.A. Betts Analysis Group, Inc. 111 Huntington Avenue 10th floor Boston MA 02199 U.S.A Search for other works by this author on: Oxford Academic Google Scholar Y.S. Yan, Y.S. Yan University of California Santa Cruz CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar C. LeReun, C. LeReun Independent Biostatistician Carrigaline Ireland Search for other works by this author on: Oxford Academic Google Scholar M. Sundaram, M. Sundaram AbbVie Inc. North Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar E.Q. Wu, E.Q. Wu Analysis Group, Inc. 111 Huntington Avenue 10th floor Boston MA 02199 U.S.A Search for other works by this author on: Oxford Academic Google Scholar P. Mulani P. Mulani AbbVie Inc. North Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 2, 1 February 2015, Pages 504–512, https://doi.org/10.1111/bjd.13437 Published: 01 February 2015
Chromosomal Aberrations in Lymphocytes of Healthy Subjects and Risk of Cancer
Authors: Pavel Rossner, Paolo Boffetta, Marcello Ceppi, Stefano Bonassi, Zdenek Smerhovsky, Karel Landa, Dagmar Juzova, Radim J. Šrám
Journal: Environmental Health Perspectives (2005)

There is evidence that increased frequency of chromosomal aberration (CA) in peripheral blood lymphocytes is a predictor of cancer, but further data are needed to better characterize CA as marker of cancer risk. From the archives of 15 laboratories we gathered cytogenetic records of 11,834 subjects who were free of cancer at the moment of blood drawing and who underwent cytogenetic examination for preventive purposes in the Czech Republic during 1975–2000. We linked these records to the national cancer registry, revealing a total of 485 cancer cases. Subjects were classified according to the percentiles of CA distribution within each laboratory as low (0–33rd percentile), medium (34–66th percentile), and high (66–100th percentile). Subjects were further classified by occupational exposure and by subclass of CA. We found a significant association between the overall cancer incidence and the presence of chromosome-type aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence interval (CI), 1.03–1.50] but not chromatid-type aberrations. Stomach cancer showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01–60.0). The predictivity of CA observed in subjects exposed to various classes of carcinogens did not significantly differ from the group of nonexposed subjects. This study contributes to validation of CA as a predictive marker of cancer risk, in particular, of stomach cancer; the association between CA frequency and cancer risk might be limited to chromosome-type aberrations.
Abstract 846: ROS-mediated activation of AKT induces apoptosis via pVHL in prostate cancer cells .
Authors: Mahandranauth A. Chetram, Kia J. Jones, Christopher Coke, Ayesha Don-Salu-Hewage, Danaya A. Bethea, Cimona V. Hinton
Journal: Cancer Research (2013)

Abstract Reactive oxygen species (ROS) play a central role in oxidative stress, which leads to the onset of diseases, such as cancer. Furthermore, ROS contributes to the delicate balance between tumor cell survival and death. However, the mechanisms by which tumor cells decide to elicit survival or death signals during oxidative stress are not completely understood. We have previously reported that ROS enhanced tumorigenic functions in prostate cancer cells, such as cell migration and invasion, which depended on CXCR4 and AKT signaling. Here, we report a novel mechanism by which ROS facilitated cell death through activation of AKT. We initially observed that ROS increased expression of phosphorylated AKT (p-AKT) in 22Rv1 human prostate cancer cells. The tumor suppressor PTEN, a negative regulator of AKT signaling, was rendered catalytically inactive through oxidation by ROS, although the expression levels remained consistent. Despite these events, cells still underwent apoptosis. Further investigation into apoptosis revealed that expression of the tumor suppressor pVHL increased, with concomitant decreased expression of HIF1α. Further investigation into pVHL during apoptosis revealed that the tumor suppressor becomes phosphorylated at S111 prior to activity; S111 is within a target motif (RXXS) forphosphorylation by AKT kinase. We then determined that pVHL and p-AKT associated in vitro via co-immunoprecipitation assay. Moreover, knockdown of pVHL by siRNA rescued HIF1α protein expression and rescued cells from apoptosis, which was determined by Annexin-V and cleaved-PARP. Collectively, our study suggests that in the context of oxidative stress, activatedAKT facilitated apoptosis by inducing pVHL function. Moreover, our studies suggest a novel paradigm for AKT-that it may participate in tumor suppressor rather than oncogenesis. Citation Format: Mahandranauth A. Chetram, Kia J. Jones, Christopher Coke, Ayesha Don-Salu-Hewage, Danaya A. Bethea, Cimona V. Hinton. ROS-mediated activation of AKT induces apoptosis via pVHL in prostate cancer cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 846. doi:10.1158/1538-7445.AM2013-846
Analysis of the Causes of Failed Antireflux Surgery and the Principles of Treatment
Authors: Marco G. Patti, Marco E. Allaix, P. Marco Fisichella
Journal: JAMA Surgery (2015)

Although the diagnostic evaluation and technical elements for a successful laparoscopic fundoplication have been clearly identified, 10% to 20% of patients will eventually experience recurrence of their symptoms. The management of patients who fail antireflux surgery is complex and not well codified.To provide an evidence- and experience-based analysis of the causes of failed antireflux surgery and to underscore the principles of treatment.PubMed was searched for articles published between 1980 and 2014. The search terms included were the following: heartburn, regurgitation, dysphagia, gastroesophageal reflux disease, cough, aspiration, laryngitis, GERD, GORD, endoscopy, manometry, pH monitoring, proton pump inhibitors, and Nissen fundoplication.Before planning therapy, a careful workup is necessary to determine whether the symptoms are due to recurrent reflux and to understand what caused the recurrence. Subsequently, therapy needs to be individualized based on the symptoms and on the findings of the workup. In some patients, a nonesophageal cause will be identified. Among patients with recurrent reflux, some will do well with acid-reducing medications and others will need another operation.Laparoscopic antireflux surgery is a very effective and long-lasting treatment for gastroesophageal reflux disease. Its success is based on a careful preoperative evaluation and on the performance of a fundoplication that respects the key technical elements. Patients who are still symptomatic postoperatively must be thoroughly evaluated to identify the cause of failure, and treatment must be individualized.