tbuckley/cabot-search huggingface dataset:
Ultrasonographic Evidence of a Consistent Orbital Involvement in Graves's Disease
Authors: Sidney C. Werner, D. Jackson Coleman, Louise A. Franzen
Journal: New England Journal of Medicine (1974)

B-mode ultrasonography of one or both orbits was performed in 47 patients with Graves's disease to determine whether a single mechanism is responsible for the different degrees of eye changes. According to clinical criteria, 30 patients had no or nonthreatening eye changes (Class 0 to 1), and 17 had more severe changes (Class 2 to 4). Ultrasonic changes, primarily in extraocular muscles, were minimal to moderate in 44 patients, equivocal in two and absent in only one patient. This uniform orbital involvement, even in the absence of clinical signs, favors the theory of a single and common pathologic mechanism in the thyroidal and ocular derangement in Graves's disease. Ultrasonic patterns resembling those in pseudotumor or tumor of the eye were found in eight patients with Graves's disease. In such cases misinterpretation was avoided by ultrasonography of the other eye. (N Engl J Med 290:1447–1450, 1974)
A Comparison of Single-Dose Cefixime with Ceftriaxone as Treatment for Uncomplicated Gonorrhea
Authors: H H Handsfield, W M McCormack, E W Hook, J M Douglas, J M Covino, M S Verdon, C A Reichart, J M Ehret
Journal: New England Journal of Medicine (1991)

Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration.
Effects of Measles, Gamma-Globulin-Modified Measles and Vaccine Measles on the Tuberculin Test
Authors: Saul Starr, Sumner Berkovigh
Journal: New England Journal of Medicine (1964)

THAT the tuberculin test can become negative with measles has been known since the report of Pirquet1 in 1908. At that time he gave credit to Preisich, in Budapest, who had found in November, 1907, that measles caused a negative tuberculin reaction. Pirquet,2 in 1911, stated that in the first days of the eruption, the tuberculin reaction always "disappears" and reappeared only after a week. Textbooks3 note "anergy" to tuberculin in measles, but an absolute negative reaction to tuberculin in measles has not been reported. In fact Grüner,4 in 1909, using subcutaneous tuberculin tests, showed that larger doses of Old . . .
Arteriosclerotic Aneurysm of the Abdominal Aorta
Authors: Chilton Crane
Journal: New England Journal of Medicine (1955)

THE arteriosclerotic aneurysm of the abdominal aorta has recently become an important lesion. A few years ago this diagnosis held little practical significance. Therapy was relatively ineffective, prognosis regarding time was utterly uncertain, and the ultimate prognosis for life was hopeless. With the present possibility of resection and graft replacement,1 2 3 the outlook for the patient, although serious, is at least hopeful. As infectious deaths have greatly diminished, these aneurysms have definitely become more common.4 In the management of these cases perplexing problems arise. The patients concerned have widespread and often severe arteriosclerotic vascular disease involving the coronary arteries, brain, kidneys . . .
bmjlearning.com: Childhood asthma
Authors: Kieran Walsh
Journal: BMJ (2004)

Over the past 25 years the prevalence of childhood asthma has risen from 4% to 10%. The main symptoms are chronic or recurrent cough and wheeze. You can confirm the diagnosis by checking peak expiratory flow in children old enough to do this. To find out more, take our learning module on the diagnosis and treatment of childhood asthma on bmjlearning.com. After reading the module, you can test your knowledge with our “Best of many questions” quiz.
Human Infection from an Unidentified Erythrocyte-Associated Bacterium
Authors: Gordon L. Archer, Philip H. Coleman, Roger M. Cole, Richard J. Duma, Charles L. Johnston
Journal: New England Journal of Medicine (1979)

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rod-shaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extra-erythrocytic and was 0.2 micrometer wide by 1.0 to 1.7 micrometer long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. This bacterium may be the cause of other chronic, fever-producing, multisystem diseases of unknown origin.
<i>Bartonella (Rochalimaea) quintana</i>Endocarditis in Three Homeless Men
Authors: Michel Drancourt, Jean Luc Mainardi, Philippe Brouqui, François Vandenesch, Anne Carta, Franck Lehnert, Jerome Etienne, Fred Goldstein, Jacques Acar, Didier Raoult
Journal: New England Journal of Medicine (1995)

Bartonella (Rochalimaea) quintana is the agent of trench fever and is transmitted by the body louse. We searched for this organism in three alcoholic homeless men with endocarditis.Blood samples were cultured on a human endothelial cell line and on blood agar. Bacteria were identified by sequencing the amplified 16S ribosomal RNA gene. The presence of bartonella in tissue was assessed by Gram's staining, immunostaining, and polymerase-chain-reaction amplification. Serologic studies for antibodies to bartonella species were performed by indirect immunofluorescence and Western immunoblotting.B. quintana was isolated from one patient in the blood-agar culture and from the other two patients in the endothelial-cell culture. The organism was also identified by both immunostaining and molecular techniques in the valvular vegetations from the three patients and in a cervical lymph node from one patient. The 16S ribosomal RNA gene sequences of the three isolates were almost identical to that of the prototype strain of B. quintana. High titers of antibodies to B. quintana were detected in all three patients, but so were cross-reacting antibodies to chlamydia species. In all three patients studies were repeatedly negative for antibodies to the human immunodeficiency virus.B. quintana is a cause of endocarditis in homeless patients and may be serologically misdiagnosed as a chlamydial infection.
PTH-053 Inflammatory bowel disease and liver function disturbance: literature review and retrospective study of 574 patients
Authors: S Bouri, K Wallis, M Shariff
Journal: Gut (2015)

<h3>Introduction</h3> Abnormal liver function tests (LFTs) are present in up to 40% of patients with Inflammatory Bowel Disease (IBD). These abnormalities are often transient. A few studies in the current literature suggest that transient disturbances may be related to disease activity,<sup>1,2</sup>whilst others have failed to find a causal association.<sup>3</sup>The aim of this study is to identify the link between abnormal LFTs and IBD activity. <h3>Method</h3> Literature review was performed using Pubmed. For the retrospective study, patients with Ulcerative Colitis (UC) and Crohn’s disease (CD) who were admitted to our institution in 2013 were identified. Patient’s electronic records were used. Exclusion criteria: less than 16 years old, LFTs documented for less than 12 months or on less than 3 occasions. Abnormalites were defined as ’transient’ if at least one of: alanine transaminase, alkaline phosphatase or bilirubin was disturbed for less than 4 weeks or ‘persistent’ if disturbed for more than 4 weeks. <h3>Results</h3> 8 studies were included in the literature review. There was significant heterogeneity in the frequency of abnormal LFT (3%<sup>4</sup>to 40%<sup>2</sup>) due to variations in the definitions used. Our study included 264 CD patients and 310 UC patients who were followed for a median of 34 months. Abnormal LFTs were found in 242/574 (42%) patients. 66% of abnormalities were transient and 34% were persistent. The causes identified for 192 patients with transient abnormalities were: 70 IBD flare, 52 antibiotics/infection, 3 thiopurine drugs, 59 unknown, 3 fatty liver, 5 other. The causes identified for 99 patients with persistent abnormalities were: 22 IBD flare, 14 infections, 12 PSC, 18 unknown cause, 5 fatty liver, 4 Gilberts, 5 thiopurine drugs, 3 pregnant, 16 other. <h3>Conclusion</h3> This study lends support to the notion that an IBD flare can cause deranged LFTs independently of thiopurine drugs. Mild abnormalities during a flare can be monitored. Further investigations are warranted if the bilirubin is raised or if the LFTs are markedly deranged or persist more than 4 weeks after resolution of the flare. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Broome U, Glaumann H, Hellers G, Nilsson B, Sorstad J, Hultcrantz R. Liver disease in ulcerative colitis: an epidemiological and follow up study in the country of Stockholm. Gut. 1994;35(1):84–89 Yamamoto-Furusho JK, Sanchez-Osorio M, Uribe M. Prevalence and factors associated with the presence of abnormal liver function tests in patients with ulcerative colitis. Ann Hepatol. 2010;9(4):397–401 Mendes FD, Levy C, Enders FB, Loftus EV, Angulo P, Lindor KD. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. <i>Am J Gastroenterol. </i>2007;102:344–350 Shepherd HA, Selby WS, Chapman RW, Nolan D, Barbatis C, McGee JO, Jewell DP. Ulcerative colitis and persistent liver dysfunction. Q J Med.1983;52(208):503–13
Prognosis in Acute Liver Disease of the Alcoholic Patient
Authors: William G. Hardison, Frank I. Lee
Journal: New England Journal of Medicine (1966)

ACUTE liver disease of the alcoholic patient has been well described in recent years.1 2 3 4 Most studies have correlated the clinical course with histologce findings on liver biopsy or autopsy. In clinical practice, however, liver biopsy of patients who are ill is often unsafe, and other guides to prognosis must be sought. We have reviewed the hospital records of all alcoholic patients with acute liver disease admitted to the Second and Fourth (Harvard) Medical Services, Boston City Hospital, from January 1, 1960, through December 31, 1963. Particular attention has been paid to the symptoms and physical signs on admission and the . . .
Induction of growth arrest and apoptosis by MNNG is associated with up-regulation of Cdk inhibitor p21 and down-regulation of cyclooxygenase-2 expression
Authors: Christina C. Niemeyer, Brandi Bailey, Jack Reifert, Heather Bendall, Jacques Corbeil, Lorenzo M. Leoni
Journal: Cancer Research (2004)

1129  SDX-105 (bendamustine) is an anti-tumor agent with demonstrated clinical activity in the treatment of hematological malignancies, including those refractory to conventional DNA-damaging agents. SDX-105 has three sub-structural elements: a 2-chloroethylamine alkylating group (in common with the nitrogen mustard family), a benzimidazole ring, and a butyric acid side-chain. The multi-faceted structure of SDX-105 may contribute to its unique anti-neoplastic activity profile and distinguish it from conventional alkylators. Experimental evidence supporting a unique mechanism of action for SDX-105 include: (1) Identification by gene expression profile analysis (Affymetrix GeneChip) signature genes that are regulated by SDX-105, but not by chlorambucil and the cyclophosphamide active metabolite (phosphoramide mustard); (2) Demonstration that SDX-105, unlike cyclophosphamide, produces DNA damage repaired via base-excision repair (BER) rather than alkylguanine transferase mechanisms. Specifically, the cytotoxic activity of cyclophosphamide, but not SDX-105, was increased when the drug was used in combination with O6-Benzylguanine, an inhibitor of O6-Alkylguanine-DNA alkyltransferase (O6-AGT), in NHL cell lines expressing high levels of 06-AGT; (3) Demosntration that cellular drug penetration and cytotoxicity of SDX-105, as opposed to melphalan, was not affected by inhibition of aminoacid transport system using 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) and, additionally, was not influenced by exposing the cells at low temperature (4°C). These results suggest that cell entry of SDX-105 is mediated via passive diffusion; (4) Lack of activity profile correlation between SDX-105 and other drugs present in the NCI-DTP database. Using the NCI human tumor 60 cell lines panel by COMPARE algorithm identified no other drugs that displayed a significant (>0.7) match in activity profile with SDX-105. This lack of correlation with SDX-105 is compelling considering that most nitrogen mustard compounds tested by COMPARE analysis display very high correlation coefficients (>0.8) with each other. In summary, these results suggest that SDX-105 has a unique profile of activity divergent from that of other common nitrogen mustard drugs.
Metronomic capecitabine in advanced patients with hepatocellular carcinoma (HCC): Preliminary results
Authors: G. Brandi, S. Fanello, F. Piscaglia, A. Falanga, L. Bolondi, S. Flori, E. Derenzini, E. Palassini, M. Fedele, G. Biasco
Journal: Journal of Clinical Oncology (2007)

15163 Background: No standard therapies are available for HCC patients (pts) ineligible for curative treatments. HCC has a rich neovasculature and neoangiogenesis is a negative prognostic factor: a high density of microvessels and hyperexpression of VEGF correlates with an increased propensity for invasion and metastatization and with a decreased DFS after resection. High level of circulating endothelial progenitors cells (CEPc) are related with insurgence and progression of HCC. Phase II trials with antiangiogenic agents in monotherapy had a response rate lower than 10% but stable disease (SD) is encouraging ranging between 30 and 60%. Retrospective analysis of standard capecitibine showed a response of 11% and similar SD rate. Experimental data on solid tumors suggest that metronomic CT prolongs inibihition of tumor growth, avoiding CEPc mobilization. Methods: Starting in september 2006, twenty-two patients were started on treatment (19 male; median age 63.7, range 47–82 ). BCLC (Barcelona Consensus Liver Cancer): 5 pts = B; 17 pts = C; Child: 12 pts =A, 8=B, 2=C. 14 pts had portal thrombosis. 15 pts were treated in front line, 7 in second line (4 pts previously treated with Sorafenib and 3 with experimental protocol of CPT-11 HAI; ASCO 2006 Abs 14061 ). The first cycle was carried out with standard capecitabine (2000 mg/sq.mt; 14 over 21 days), followed by metronomic capecitabine (1300 mg) without interruption. To compare the angiogenic role of metronomic capecitabine versus standard administration, VEGF and trombospondine have been dosed at baseline and after the first cycle of standard capecitabine and after one month of metronomic capecitabine. The response has been assessed by CT scan every three months. Results: Five out of 22 patients have been dismissed for toxicity (liver failure) during the standard capecitabine treatment. Among the 17 remaining patients, two have discontinued the treatment due to toxicity (liver failure) during the metronomic treatment and 10 have accomplished at least the first month of metronomic schedule. 6 patients have been evaluated for response: 2 PR (one second line), 3 SD (all in second line), 1 PD (second line). Conclusions: Metronomic capecitabine seems to have a better tolerability than standard schedule and promises good efficacy. No significant financial relationships to disclose.
Masatinib mesylate in imatinib-naive locally advanced or metastatic gastrointestinal stromal tumor (GIST): Results of the French Sarcoma Group phase II trial
Authors: A. Le Cesne, J. Blay, N. B. Bui, O. Bouché, A. Adenis, J. Domont, A. Cioffi, A. Moussy, O. Hermine
Journal: Journal of Clinical Oncology (2009)

10507 Background: Masitinib mesylate (AB1010, AB Science, Paris, France) is a novel protein tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib mesylate against bith wild-type c-Kit receptor and its mutated form in the juxtamembrane region. Masatinib also inhibits PDGFR and FGFR3. This multicenter phase II study evaluated the efficacy and safety of masatinib as a first-line treatment of advanced GIST. Methods: Imatinib-naïve patients with inoperable, locally advanced or metastatic GIST received oral masatinib (7.5 mg/kg/day) until progression, refusal or toxicity. A Simon “minimax two stage” design was used. Efficacy variables included response rate at two months, best response according to RECIST, disease control rate (DCR), metabolic response rate and progression free survival (PFS). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. The most frequent relevant grade 3 toxicities were rash (10%), neutropenia (7%) and abdominal pain (7%). One patient presented a grade 4 skin exfoliation. Three patients discontinued treatment due to suspected toxicity. At two months, the response rate was 20% (6/30 patients) according to RECIST (DCR of 98.7%, 29/30 patients) and 84.6% (11/13 evaluable patients) according to FDG-PET response criteria. After a median follow-up of 23.7 months, there were 6.7% of CR, 43.3% of PR, 46.7% of SD and 3.3% of PD as best response (DCR of 96.7%). Mean time to response was 5.7 months (0.8 to 23.3 months). The median PFS was 27.2 months with PFS rates of 68.8% at 1 year and 60.2% at 2 years. Up to date, all but one patient are alive (one patient died of post-surgical complications, unrelated to treatment). Mutational analyses of the patients’tumors are ongoing. Conclusions: The results observed with masatinib compare favorably with those reported with imatinib in front-line treatment of advanced GIST both in term of safety and efficacy and support the initiation of a phase III randomized clinical trial. [Table: see text]
62P Novel therapeutic strategies in NSCLC: Lung-tumorspheres as an effective in vitro screening platform
Authors: E. Munera Maravilla, A. Herreros Pomares, S. Calabuig-Fariñas, E. Jantus Lewintre, R. Lucas, R. Guijarro, A.I. Martinez Madriaga, A. Blasco Cordellat, C. Camps
Journal: Journal of Thoracic Oncology (2016)
Case 24-2006
Authors: N Stuart Harris
Journal: New England Journal of Medicine (2006)

A 40-year-old woman was transferred to the emergency department of this hospital because of hypotension. Seven hours earlier she had ingested 100 sample tablets of amlodipine (10 mg) in a suicide attempt. She was taken to an emergency department, where her blood pressure fell from 100/60 mm Hg to 58/38 mm Hg despite the use of pressors.
The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism
Authors: Mary Ann Anderson, Jing Deng, John F. Seymour, Constantine Tam, Su Young Kim, Joshua Fein, Lijian Yu, Jennifer R. Brown, David Westerman, Eric G. Si, Ian J. Majewski, David Segal, Sari L. Heitner Enschede, David C. S. Huang, Matthew S. Davids, Anthony Letai, Andrew W. Roberts
Journal: Blood (2016)
Authors’ reply to Males
Authors: Lucy Bowes, Carol Joinson, Dieter Wolke, Glyn Lewis
Journal: BMJ (2015)

Our population attributable fraction (PAF) suggested that 29.2% (95% confidence interval 10.9% to 43.7%) of depression at age 18 years could be explained by peer victimisation if this were a causal association.1 Males suggests that, owing to serious limitations in our dataset—particularly “the confounding variable of previous adult bullying in childhood”—this is an overestimate.2

Firstly, it is important to …
Case 59-1962
Authors: Thomas C. Hall, Robert E. Scully
Journal: New England Journal of Medicine (1962)

Presentation of Case*A sixty-six-year-old man entered the hospital because of pain in the chest and abdomen.Six weeks previously the patient experienced the onset of difficulty in breathing and a cough productive of a cup of white sputum daily. Severe parasternal and costal pain developed; at first the pain was aggravated by rotation of the trunk and by sitting upright, but eventually it was precipitated by any body movement. Episodes of abdominal pain that he characterized as "painful tightening" in the lower quadrants often accompanied the chest pain. Paroxysmal nocturnal dyspnea, painful exertional dyspnea and orthopnea requiring two pillows . . .
P187 The difficulty in implementing a safety checklist for pleural procedures
Authors: HJG Meredith, C-L Tey, S Sivanantham, G Boehmer
Journal: Thorax (2015)

<h3>Introduction</h3> There are significant risks associated with pleural procedures.<sup>1</sup> NHS England have been cataloguing never events since 2012 and pleural procedure related events are one of the most common procedures causing harm that we as physicians perform.<sup>2</sup> The WHO Surgical Checklist was developed to minimise morbidity and mortality associated with high-risk procedures.<sup>3 </sup>We introduced a modified WHO safety checklist for all pleural procedures following 2 never events in our trust. <h3>Aim</h3> We wished to establish the use of the modified WHO safety checklist for all pleural procedures throughout the trust, excepting those done in emergency situations. <h3>Methods</h3> We completed audits to review the implementation of the checklist. This was following writing trust guidelines, extensive teaching and presentations throughout the trust and to multiple departments on its use over a three-year period. We completed retrospective, spot check audits for one month of all pleural procedures in November 2013 and then re-audit in November 2014. <h3>Results</h3> In 2013 the checklist was used in 14/40 of cases (35% overall, 47% of medical patients) and re-audit showed similar results with its use in 20/47 (38%). <h3>Discussion</h3> Following Route Cause Analysis of 2 never events, a modified WHO safety checklist was identified as a potential way of preventing future similar adverse events in our trust. Despite numerous teaching sessions and discussion in other fora we have seen that it is still not being used in the majority of cases. We feel that the use of safety checklists should be considered for all procedures that have the potential for serious harm and will continue to strive towards implementing this within our trust. It is possible that if it were to be nationally mandated or included in national guidelines that this would bring further weight towards its use. <h3>References</h3> 1 National Patient Safety Agency. <i>Rapid Response Report: Risks of Chest Drain Insertion</i>. 2008, reference NPSA/2008/RRR003. http://www.nrls.npsa.nhs.uk/resources/?entryid45=59887 (accessed 1 Oct 2015) 2 NHS England. <i>Never Events Summary</i> 2014 http://www.england.nhs.uk/wp-content/uploads/2014/12/2013-14-NE-data-FINAL.pdf (accessed 1 Oct 2015) 3 Haynes AB, Weiser TG, Berry WR, <i>et al.</i> A surgical safety checklist to reduce morbidity and mortality in a global population. <i>N Engl J Med</i> 2009;<b>360</b>:491–9