tbuckley/cabot-search huggingface dataset:
A PHASE III RANDOMIZED CONTROLLED TRIAL OF SHORT-COURSE RADIOTHERAPY WITH OR WITHOUT CONCOMITANT AND ADJUVANT TEMOZOLOMIDE IN ELDERLY PATIENTS WITH GLIOBLASTOMA (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677)
Authors: J. R. P. MD, C. J. O'Callaghan, K. Ding, W. Roa, W. P. Mason, J. G. Cairncross, A. A. Brandes, J. Menten, C. Phillips, M. F. Fay, R. Nishikawa, C. Winch, N. Laperriere
Journal: Neuro-Oncology (2014)

BACKGROUND: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed GBM showed increased survival with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71 (median 56) years; however a sub-group analysis noted a trend of decreasing benefit from the addition of TMZ with increasing age, such that for age 65-71, the hazard ratio of 0.8 did not reach statistical significance (p = 0.340). This may reflect a lack of efficacy in elderly patients, or simply be due to a lack of statistical power in this subgroup. Recent RCTs in elderly GBM found improved survival with RT compared to supportive care alone and detected non-inferiority of 40 Gy/15 vs. a 60 Gy/30 RT regimen and superior survival was noted for MGMT-methylated patients treated with TMZ alone vs RT alone. Based upon these results short-course hypofractionated RT is often recommended for elderly pts. However, whether the addition of TMZ to RT confers a survival advantage in elderly pts, particularly for those with methylated MGMT, remains unanswered. METHODS: We conducted a global randomized phase III clinical trial for patients ≥65 yrs of age with histologically confirmed newly diagnosed glioblastoma, ECOG 0-2, randomized 1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant temozolomide plus monthly adjuvant TMZ until progression or 12 cycles. Stratification is by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. RESULTS: Accrual of n = 562 patients was completed Sept 19, 2013. Accrual by participating group was NCIC CTG 199, EORTC 249, TROG 97, and Japan 17 patients. Median age of randomized patients was 73 (65-90) years with 70% of patients over the age of 71. The study was powered to detect a HR of 0.75 in median OS, requiring 520 events for analysis. At the time of writing the required number of deaths had not been reached. A comprehensive analysis, including MGMT promoter methylation and QOL, is planned. CONCLUSIONS: A global cooperative group trial was completed randomizing 562 elderly patients with glioblastoma. The final results will add to our knowledge on the optimal treatment of these patients. SECONDARY CATEGORY: n/a.
Potential Health Hazards of Materials Used by Artists and Sculptors
Authors: Jerome T. Siedlecki
Journal: JAMA (1968)

A painter or sculptor usually is unaware of the potential health hazards of exposure to materials he selects to enhance his creative efforts. Although most of the substances and processes to which he is exposed have no effect on health, some may have an adverse effect on his well-being under certain conditions of exposure. <h3>Painting</h3><h3>Traditional Media.—</h3> As early as 1713, Bernardino Ramazzini, the "patron saint" of occupational medicine, described in his classic book,<i>De Morbis Artificum</i>(<i>Diseases of Workers</i>),<sup>1</sup>the hazards of materials to which painters are exposed. He wrote: I have observed that nearly all the painters whom I know, both in this and other cities, are sickly; and if one reads the lives of painters it will be seen that they are by no means long-lived, especially those who were the most distinguished.... Their sedentary life and melancholic temperament may be partly to blame, for they
Only half of Dutch doctors report euthanasia, report says
Authors: T. Sheldon
Journal: BMJ (2003)

A study shows that in 2001 just over half of doctors in the Netherlands fulfilled their legal responsibility to report their actions concerning euthanasia.

Researchers for the study, which was commissioned by the Dutch government, admit dissatisfaction with the levels of reporting but deny that there is cause for serious concern. Instead they say that reporting levels have increased steadily since the last report commissioned by the government six years ago and that the overall number of cases of euthanasia has stabilised.

The researchers were able to extrapolate the number of cases of euthanasia each year in the Netherlands from written questionnaires …
Long Survival in Hodgkin's Disease
Authors: MORTIMER J. LACHER
Journal: Annals of Internal Medicine (1969)

Of 402 patients with Hodgkin's disease seen at the Memorial Center from 1949 to 1955, 90 survived more than 10 years. Lymphangiograms were not done during this period of time. Overall survival improved considerably compared with two previous reviews at the Memoral Center. Five-year survival improved from 17.7% to 38.3%. Ten-year survival improved from 7.7% to 22.4%. Stage IA and IIA patients had the best survival rate (28/74, IA; 26/73, IIA). Patients with extensive symptomatic disease (IIB and IIIB) also could achieve long survival and should not be considered hopeless. These results were achieved (with a few exceptions) with initial orthovoltage radiation therapy using moderate doses without "prophylactic" therapy. Factors of survival that could be demonstrated included stage of disease at time of biopsy diagnosis, natural individual defense against the tumor, and follow-up radiation and chemotherapy.
Polio vaccination worker is shot and killed in Pakistan
Authors: A. Gulland
Journal: BMJ (2012)

The World Health Organization has described as a “hero” a polio vaccination worker who was shot and killed in Pakistan.

Muhammad Ishaq was shot at a dispensary in Karachi on Friday evening, just three days after two WHO workers were shot at in the same area of the city.1

A statement released by WHO said that Ishaq, who was not a member of WHO staff but a local community worker, had worked with the polio eradication campaign for several months, helping to plan and implement vaccination campaigns. It said, “Because of the dedication of heroes like Mr Ishaq Pakistan is this year closer than ever to the eradication of polio. He was known for his dedication and diligence to immunise all children against polio.”

The shooting took place …
A new survival trick of hepatitis C virus: Blocking the activation of interferon regulatory factor-3
Authors: Markus H. Heim
Journal: Hepatology (2003)

Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks the phosphorylation and effector action of interferon regulatory factor–3 (IRF–3), a key cellular antiviral signaling molecule. Disruption of NS3/4A protease function by mutation or a ketoamide peptidomimetic inhibitor relieved this blockade and restored IRF–3 phosphorylation after cellular challenge with an unrelated virus. Furthermore, dominant–negative or constitutively active IRF–3 mutants, respectively, enhanced or suppressed HCV RNA replication in hepatoma cells. Thus, the NS3/4A protease represents a dual therapeutic target, the inhibition of which may both block viral replication and restore IRF–3 control of HCV infection.
The Neurologist's Experience With Pheochromocytoma
Authors: Juergen E. Thomas
Journal: JAMA (1966)

This communication is based on a review of the clinical histories of 100 patients with proved pheochromocytoma seen at the Mayo Clinic between 1945 and 1965. The tumor was identified at operation in 97 patients and at autopsy in three. In 85% of cases only one adrenal gland was involved. Symptoms occurred almost always paroxysmally, the commonest symptom combination being headache, perspiration, palpitation, and pallor. The attacks were sudden in onset, generally less than one hour in duration, and of variable frequency. Basal metabolic rate and sugar concentration in the blood were increased in more than half of the patients. The neurological conditions most likely to be confused with pheochromocytoma include vasodilating headache, intracranial tumor, diencephalic-autonomic epilepsy, hypertensive encephalopathy, focal arterial brain disease, and anxiety state.
Kaposi's Sarcoma–Associated Herpesvirus Confers a Survival Advantage to Endothelial Cells
Authors: Ling Wang, Blossom Damania
Journal: Cancer Research (2008)

Abstract Kaposi's sarcoma–associated herpesvirus (KSHV) is associated with three different human malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease. The KS lesion is of endothelial cell in origin and is highly dependent on autocrine and paracrine factors for survival and growth. In this study, we show that KSHV infection of endothelial cells induces the activation of the prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway. KSHV infection of endothelial cells augmented cell survival in the presence of apoptotic inducers, including etoposide and staurosporine, and under conditions of serum deprivation. We found that KSHV infection of endothelial cells also increased the ability of these cells to form an in vitro tubular network under conditions of stress and growth factor deprivation. Finally, we show that the nuclear factor-κB and PI3K pathways are also required for endothelial tubular network formation. Collectively, these results suggest that KSHV infection of endothelial cells modulates cell signaling pathways and induces cell survival and angiogenesis, thereby contributing to the pathogenesis induced by KSHV. [Cancer Res 2008;68(12):4640–8]
CARBOHYDRATE HISTOCHEMISTRY STUDIED BY ACETYLATION TECHNIQUES
Authors: J. F. A. McManus, Jane E. Cason
Journal: The Journal of Experimental Medicine (1950)

An acetic anhydride pyridine mixture acetylates hydroxyl groups in tissue sections. The acetyl groups can be removed from tissue sections by weak alkali. Sections acetylated by acetic anhydride pyridine no longer produce aldehydes after oxidation by periodic acid. Acetylated sections subjected to weak alkali regain the ability to produce aldehydes after oxidation by periodic acid. Acetylation of tissue sections and the removal of acetyl groups by weak alkali can be used as histochemical confirmation of the carbohydrate nature of materials coloring with Schiff's reagent after periodic acid.
Neuroleptic Malignant Syndrome-Reply
Authors: Robert G. Feldman
Journal: JAMA (1986)

<h3>In Reply.—</h3> We thank Drs Sandyk and Iacono for their interest in our article and for their intriguing hypothesis. Testing any hypothesis concerning NMS is difficult given the rarity of the condition, the absence of an animal model, and the critical nature of the illness, necessitating immediate intervention. Our criticisms of their hypothesis include the following: (1) The arguments advanced are logical but tenuous in that the cited animal work deals with rodents that were not parkinsonian models. Also they were given intracisternal<sup>1</sup>or intraventricular<sup>2</sup>injections of β-endorphin and were, therefore, clearly not physiological models. (2) We think it more reasonable to state that β-endorphin may modulate catecholamine systems rather than that they "control" them. (3) The use of nalaxone in septic shock is not universally accepted, as implied in the letter.<sup>3</sup>(4) Nalaxone has been tried in the treatment of Parkinson's disease but was without benefit.
Single Perfusion Defect Secondary to Intrathoracic Kidney
Authors: MICHAEL J. HALLISEY, VICENTE J. CARIDE
Journal: Clinical Nuclear Medicine (1990)

In ventilation-perfusion imaging, the mismatched perfusion defect is the hallmark of acute pulmonary thromboembolism. There are, however, numerous causes for perfusion defects that must also be considered to evaluate ventilation-perfusion mismatches on pulmonary imaging studies adequately. A case of a right intrathoracic kidney traversing a pleuroperitoneal defect, creating a single perfusion defect on ventilation-perfusion imaging, is Dresented.
Thomas Anderson McAllister
Authors: Morag C Timbury
Journal: BMJ (2008)

Thomas Anderson McAllister (“Tom”) had a distinguished undergraduate career and, after qualification, trained in bacteriology in Professor (later Sir) James Howie’s department in the Western Infirmary in Glasgow. A research fellowship with Professor Ed Kass in Boston kindled his early interest in urinary tract infection, and this was followed by research on the use of hyperbaric oxygen in anaerobic infection.

In …
HEMOPHILIA WITH VOLKMANN SYNDROME: REPORT OF CASE
Authors: John Prentiss Lord
Journal: JAMA (1926)

In January, 1926, a lad aged 16, consulted me about his hands and wrists, which were disabled. His history was that of a "bleeder," and he had had the usual experiences of such subjects. Slight cuts were serious and the bleeding hard to control. He had on a few occasions hemorrhage into his knees, which resulted in the usual symptoms of inflammation and disability. At the age of 3 years, the right knee was diagnosed as tuberculous and a cast applied. There had been numerous subcutaneous hemorrhages in and about the right wrist six years previously. This had been untreated because all the local surgeons were away on military duty. The wrist was contracted to a right angle, although it could be extended to 45 degrees. Otherwise, there was fair function. The extreme disability of the left wrist and forearm had caused him to seek relief. This member had been
EFFECTS OF INTER-STENT COMPRESSED INTIMAL VOLUME AFTER DRUG-ELUTING STENT TREATMENTS FOR BARE METAL IN-STENT RESTENOSIS: A VOLUMETRIC INTRAVASCULAR ULTRASOUND ANALYSIS
Authors: Kenji Sakamoto, Katsuhisa Waseda, Paul Yock, David Holmes, Gregg Stone, Peter Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2012)
Treatment of Neurosyphilis
Authors: Robert T. Rolfs
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 April 1989Treatment of NeurosyphilisRobert T. Rolfs, MD, Jonathan M. Zenilman, MD, Harold W. Jaffe, MDRobert T. Rolfs, MDSearch for more papers by this author, Jonathan M. Zenilman, MDSearch for more papers by this author, Harold W. Jaffe, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-7-574_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Lukehart and associates (1) have confirmed previous reports that the central nervous system is commonly involved in patients with primary and secondary syphilis. Also, they have shown that in some patients, Treponema pallidum may persist in the central nervous system after the recommended benzathine penicillin therapy has been given. Although the number of patients coinfected with human immunodeficiency virus (HIV) who had cerebrospinal fluid evaluation after treatment was small, these data, along with those from reports of neurosyphilis in HIV-infected patients (2), suggest that patients coinfected with HIV may be at increased risk for neurosyphilis.Although these...References1. LukehartHookBaker-ZanderCollierCritchlowHandsfield SESACH. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and therapy. Ann Intern Med. 1988;109:855-62. LinkGoogle Scholar2. BerryHootonCollierLukehart CTAS. Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med. 1987;316:1587-9. CrossrefMedlineGoogle Scholar3. Musher D. How much penicillin cures early syphilis? Ann Intern Med. 1988;109:849-51. LinkGoogle Scholar4. QuinnGlasserCannon TDR. Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases. N Engl J Med. 1988;318:197-203. CrossrefMedlineGoogle Scholar5. SchroeterTurnerLucasBrown ARJW. Therapy for incubating syphilis: effectiveness of gonorrhea treatment. JAMA. 1971;218:711-3. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Robert T. Rolfs, MD; Jonathan M. Zenilman, MD; Harold W. Jaffe, MDAffiliations: Centers for Disease Control Atlanta, GA 30333 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNeurosyphilisNeuro-ophthalmic Manifestations of Human Immunodeficiency Virus Infection 1 April 1989Volume 110, Issue 7Page: 574-575KeywordsCentral nervous systemCerebrospinal fluidHIVPenicillinRisk managementSyphilisTreponema pallidum ePublished: 1 December 2008 Issue Published: 1 April 1989 PDF downloadLoading ...
Immunological Visibility: Posttranscriptional Regulation of Human NKG2D Ligands by the EGF Receptor Pathway
Authors: Pierre Vantourout, Carrie Willcox, Andrea Turner, Chad M. Swanson, Yasmin Haque, Olga Sobolev, Anita Grigoriadis, Andrew Tutt, Adrian Hayday
Journal: Science Translational Medicine (2014)

Environmental changes induce human NKG2D ligand expression—immunological visibility—through the EGFR stress response.
Subcutaneous Panniculitis-Like T Cell Lymphoma Demonstrated on Gallium-67 Scintigraphy
Authors: Lily Shen, Sharon Alam-Fotias, Robert Mansberg, Diep Nguyen, Chuong Bui
Journal: Clinical Nuclear Medicine (2005)

A 52-year-old obese, diabetic man presented with fever, night sweats, a 20-kg weight loss, and subcutaneous masses on the legs, arms, and abdominal wall. Whole-body gallium-67 scintigraphy was performed to investigate pyrexia of unknown origin and demonstrated gallium avidity in the subcutaneous masses. Subsequent core biopsy of a skin lesion demonstrated subcutaneous panniculitis-like T cell lymphoma (SPTCL). The patient underwent combination chemotherapy and responded clinically with resolution of his systemic symptoms, healing of the subcutaneous masses, and complete resolution of the previously demonstrated gallium-avid skin lesions. Gallium scintigraphy should be considered in cases of possible lymphomatous infiltration of the skin.
Doxorubicin induces slow ceramide accumulation and late apoptosis in cultured adult rat ventricular myocytes
Authors: E Delpy, S N Hatem, N Andrieu, C de Vaumas, M Henaff, C Rücker-Martin, J P Jaffrézou, G Laurent, T Levade, J J Mercadier
Journal: Cardiovascular Research (1999)

Anthracyclines cause apoptotic death in many cell types through activation of the ceramide pathway. We tested the hypothesis that doxorubicin induces cardiac myocyte apoptosis through ceramide generation.Adult rat ventricular myocytes were grown in the presence of 10% fetal calf serum, and exposed to 0.5 microM doxorubicin (Dox) for 1 h on the day of cell isolation (day 0). We used the membrane-permeant ceramide analog C2-ceramide (C2-cer) to mimic the effects of endogenous ceramide and PDMP to induce endogenous ceramide accumulation. Apoptosis was assessed upon morphological criteria and DNA fragmentation by the TUNEL method and agarose gel electrophoresis. Ceramide concentration was assessed using the DAG kinase assay.Myocyte exposure to Dox was associated with cellular and nuclear alterations typical of apoptosis on day 7 but not on day 3. At day 7, the percentage of TUNEL-positive myocytes was markedly increased in Dox-treated cultures compared to control (Cl) cultures (82 +/- 3 vs. 12 +/- 1%, n = 7; p < 0.001); internucleosomal DNA fragmentation was confirmed by the observation of DNA ladders. These alterations were associated with an increase in the intracellular ceramide concentration (1715 +/- 243 vs. 785 +/- 99 pmol/mg prot, n = 5; p < 0.01), a phenomenon also detected on day 3 (731 +/- 59 vs. 259 +/- 37 pmol/mg prot, n = 5; p < 0.001). Incubation of myocytes at day 0 with 50 microM C2-cer induced rapid cell shrinkage and DNA fragmentation (45 +/- 3 vs. 10 +/- 1% TUNEL-positive myocytes on day 1 in C2-cer-treated and Cl cultures, respectively; n = 6, p < 0.001). Myocyte exposure to 10 microM PDMP for 7 days (n = 5), caused ceramide accumulation (1.7-fold increase vs. Cl, p < 0.01), and a marked increase in the percentage of TUNEL-positive myocytes (62 +/- 6 vs. 11 +/- 3% in Cl cultures, p < 0.001). Ventricles of rats injected intraperitoneally with a cumulative dose of 14 mg/kg Dox over a period of 2 weeks also showed an increased ceramide concentration 2 weeks later (11.01 +/- 0.64 vs. 5.24 +/- 0.88 pmol/mg prot, n = 6; p < 0.001).Our study confirms the existence of a functional ceramide pathway related to apoptosis in cardiac myocytes, and points to its possible involvement in doxorubicin-induced cardiomyopathy.
Recommendations for Mammography in the Presence of Advanced Age and Coexisting Disease
Authors: Daniel Temianka
Journal: JAMA (1989)

To the Editor.—  The recent Council Report on mammography screening 1 makes a blanket recommendation to perform an annual screening mammogram... in asymptomatic women 50 years of age or older. This recommendation ignores the presence of coexisting disease and extremely advanced age. Should octogenarians with atrophic and readily palpable breasts really continue to have such screening annually ad infinitum? Should patients with congestive heart failure be referred for mammography every year, despite their limited prognosis?  I believe these are real questions that have not been addressed adequately by the various policy-setting organizations. These considerations may be obvious to clinicians, but they are not obvious to patients, who frequently insist that their primary physicians carry out these recommendations to the letter, notwithstanding other important clinical circumstances. Such pressure is further amplified by the legal community.  Those who formulate recommendations concerning repetitive screening procedures should make more effort to address the effects of
Cost-Effectiveness of Catheter Ablation in Patients With Ventricular Tachycardia
Authors: Hugh Calkins, J. Thomas Bigger, Stacey J. Ackerman, Steven B. Duff, David Wilber, Robert A. Kerr, Miriam Bar-Din, Kathleen M. Beusterien, Michael J. Strauss
Journal: Circulation (2000)

Background —This study evaluated the cost-effectiveness of catheter ablation therapy versus amiodarone for treating ventricular tachycardia (VT) in patients with structural heart disease. The analysis used a societal perspective for a hypothetical cohort of VT patients with implantable cardioverter-defibrillators, who were experiencing frequent shocks. Methods and Results —We calculated incremental cost-effectiveness of ablation relative to amiodarone over 5 years after treatment initiation. Event probabilities were from the Chilli randomized clinical trial (Chilli Cooled Ablation System, Cardiac Pathways Corporation, Sunnyvale, Calif), the literature, and a consensus panel. Costs were from 1998 national Medicare reimbursement schedules. Quality-of-life weights (utilities) were estimated using an established preference measurement technique. In a hypothetical cohort of 10 000 patients, 5-year costs were higher for patients undergoing ablation compared with amiodarone therapy ($21 795 versus $19 075). Ablation also produced a greater increase in quality of life (2.78 versus 2.65 quality-adjusted life-years [QALYs]). This yielded a cost-effectiveness ratio of $20 923 per QALY gained for ablation compared with amiodarone. Results were relatively insensitive to assumptions about ablation success and durability. In less severe patients with good ejection fractions who suffer their first VT episode, the incremental cost-effectiveness ratio was $6028 per QALY gained. These cost-effectiveness ratios are within the range generally thought to warrant technology adoption. Conclusions —This study demonstrates that, from a societal perspective, catheter ablation appears to be a cost-effective alternative to amiodarone for treating VT patients.
“Copyright and Terms of Use”
Authors: F. Graepler
Journal: Endoscopy (2006)

It was with great interest that I read the contribution of Korman and co-workers proposing a standardized and structured terminology for reporting capsule endoscopy procedures [1]. The authors address an important topic concerning a young field of endoscopy. The accompanying paper, in which the results of a retrospective testing and validation study are reported, further underlines their commendable intentions [2].