tbuckley/cabot-search huggingface dataset:
MEPs shun cancer advocacy group because of industry funding
Authors: Ned Stafford
Journal: BMJ (2008)

A group of members of the European parliament with a special interest in breast cancer has cut its ties with a breast cancer advocacy group, Europa Donna, because of the group’s acceptance of financial support from drug companies.

Karin Jons, chairman of the European parliamentary group on breast cancer (EPGBC), issued a press release last week announcing the decision, saying that 86% of Europa Donna’s income of about €424 000 (£330 000; $660 000) in 2007 came from the industry.

“We at EPGBC reject further cooperation with Europa …
Clinical course of primary HIV infection: consequences for subsequent course of infection.
Authors: C. Pedersen, B. O. Lindhardt, B. L. Jensen, E. Lauritzen, J. Gerstoft, E. Dickmeiss, J. Gaub, E. Scheibel, T. Karlsmark
Journal: BMJ (1989)

To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection.Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables.86 Men in whom seroconversion occurred within 12 months.Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV.Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively).The course of primary infection may determine the subsequent course of the infection.
Loss of Phosphatase and Tensin Homolog Protein Expression Is an Independent Poor Prognostic Marker in Lung Adenocarcinoma
Authors: Naoki Yanagawa, Charles Leduc, Derek Kohler, Mauro A. Saieg, Thomas John, Jenna Sykes, Maisa Yoshimoto, Melania Pintilie, Jeremy Squire, Frances A. Shepherd, Ming-Sound Tsao
Journal: Journal of Thoracic Oncology (2012)
Abstract 4927: <i>MGMT</i> promoter methylation is enriched in glioblastoma derived spheres as compared to respective original tumor tissue and is associated with loss of expression
Authors: Davide Sciuscio, Annie-Claire Diserens, Danielle Martinet, Ilse Vlassenbroeck, Marie-France Hamou, Robert-Charles Janzer, Claudio Pollo, Roger Stupp, Marc Levivier, Monika E. Hegi
Journal: Cancer Research (2010)

Abstract Epigenetic silencing of the O6-methylaguanine DNA methyl transferase (MGMT) gene by promoter hypermethylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Quantitative methylation specific PCR (Q-MSP) suggests that not all cells in a glioblastoma exhibiting MGMT methylation carry a methylated MGMT allele, even after adjustment for tumor cell content. This raises the question of the clinically relevant methylation threshold for predicting response to therapy for treatment stratification. There are several potential reasons: heterogeneity of glioblastoma; contaminating normal tissue; a heterogenous methylation pattern not correctly detectable by the assay, or presence of MGMT methylation in distinct subpopulations of cells, namely tumor initiating cells. In order to address the question we investigated the degree and pattern of MGMT promoter methylation in 10 paired samples of glioblastoma and spheres derived thereof using Q-MSP and methylation specific clone sequencing. We observed that in MGMT methylated glioblastoma, the percentage of methylated alleles ranged from 10 to 90%. In contrast, in most of the respective glioblastoma derived spheres, cultured under stem cell conditions, methylated alleles were highly enriched (10/10 clones), even if both MGMT-alleles were retained. The methylation pattern was conserved in the spheres, even when passing them in nude mice. Most importantly, this hypermethylation was associated with complete loss of MGMT expression. For one case we observed only 50% methylated clones in the sphere fraction, associated with low expression of MGMT. Taken together, our data suggest that in MGMT methylated glioblastoma, cells with MGMT promoter hypermethylation are enriched in the sphere fraction which supposedly comprises cancer initiating cells. Thus, even a low percentage of MGMT methylation in a glioblastoma could be predictive marker for a benefit from alkylating agent therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4927.
Partial protection of 1α-hydroxyvitamin D3 against the development of diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice
Authors: Masaaki Inaba, Yoshiki Nishizawa, Keifu Song, Hitoshi Tanishita, Senji Okuno, Takami Miki, Hirotoshi Morii
Journal: Metabolism (1992)
Atenolol Compared with Nifedipine: Effect on Cognitive Function and Mood in Elderly Hypertensive Patients
Authors: Michael H. Skinner, Andrew Futterman, Diane Morrissette, Larry W. Thompson, Brian B. Hoffman, Terrence F. Blaschke
Journal: Annals of Internal Medicine (1992)

Objective: To compare the effects of atenolol and nifedipine on mood and cognitive function in elderly hypertensive patients. Design: Randomized, double-blind, crossover trial. Patients: Thirty-one elderly volunteers (7 women and 24 men) 60 to 81 years of age with mild to moderate hypertension were recruited from the general community and a Veterans Affairs hospital hypertension clinic. Six volunteers withdrew at early phases of the study for reasons unrelated to adverse drug effects. Interventions: Participants had 2 weeks of placebo, 2 to 6 weeks of titration with atenolol or nifedipine, and 4 weeks of treatment followed by similar periods with the other drug. Measurements: Psychometric tests designed to assess mood and cognitive function. Results: In the group first treated with nifedipine, the summed recall score on the Buschke selective reminding test (a test of verbal learning and memory) decreased by 9.3 words (95% Cl, 2.8 to 15.6 words), or 9%, during nifedipine treatment compared with placebo (P = 0.031). The group first treated with atenolol showed no improvement in summed recall scores when results seen during atenolol therapy and placebo administration were compared (P = 0.10); however, this group had an improvement of 16.1 words (Cl, 5.6 to 26.5 words), or of 16%, when the atenolol score was compared with the nifedipine score (P = 0.026). In the group first treated with nifedipine, 6 of 11 patients (55%) showed a decrease of 5 words or more during nifedipine therapy compared with placebo, whereas only 1 of the 14 patients (7%) in the group first treated with atenolol showed a similar decrease (P < 0.01). On the digit symbol test (a psychomotor test), patients treated first with atenolol tended to improve, whereas patients treated first with nifedipine tended to decline. The difference between nifedipine and atenolol, in terms of the change from the score seen during placebo, was 4.3 codings (Cl, 0.7 to 7.9 codings) or 10% (P = 0.043). No statistically significant differences were seen between nifedipine and atenolol therapy regarding the other measures of psychomotor ability, sustained attention, motor performance, verbal fluency, or abstract reasoning, and no effects of either drug on mood or PsychopathologicPsychopathologic symptoms were noted. Conclusions: Although atenolol and nifedipine are generally free of gross effects on cognition or mood, nifedipine may subtly impair learning and memory in some elderly hypertensive patients.
RADIAL ARTERY PATENCY AFTER TRANSRADIAL ACCESS: EFFECTIVE AND EASY WAY TO REDUCE THE RADIAL ARTERY OCCLUSION RATE, RESULTS OF THE CRASOC (COMPRESSION OF RADIAL ARTERIES WITHOUT OCCLUSION) STUDY
Authors: Vincent Dangoisse, Antoine Guedes, Patrick Chenu, Jacques Jamart, Laurence Gabriel, Baudouin Marchandise, Clara Albert, Christine Dury, Erwin Schroeder
Journal: Journal of the American College of Cardiology (2012)
Bad medicine: cardiology
Authors: Des Spence
Journal: BMJ (2011)

We are scientists. But the Big Book of Medical Facts is in fact just a pamphlet printed at home, with two paragraphs in a very large font. The only certainty of science is uncertainty. Medicine is often little more than an opinion, a faith system: we believe that what we do is right. This is despite history telling us that what we do now is almost certainly wrong. Our faith has invented words, rituals, elaborate costumes, and a culture of reverence and deference. And, with clinical signs so subtle that you might question their existence, …
In vivo delineation of myocardial hypoxia during coronary occlusion using fluorine-18 fluoromisonidazole and positron emission tomography: A potential approach for identification of jeopardized myocardium
Authors: Marc E. Shelton, Carmen S. Dence, Dah-Ren Hwang, Pilar Herrero, Michael J. Welch, Steven R. Bergmann
Journal: Journal of the American College of Cardiology (1990)
Surrogate Decision Makers' Interpretation of Prognostic Information
Authors: Lucas S. Zier
Journal: Annals of Internal Medicine (2012)

Background: Little is known about why surrogate decision makers for patients with advanced illness often have overly optimistic expectations about prognosis. Objective: To determine how surrogates interpret prognostic statements and to explore factors influencing surrogates' interpretations of grim prognostic information. Design: Multicenter, mixed-methods study. Setting: Intensive care units of 3 hospitals in San Francisco, California. Participants: 80 surrogates of critically ill patients. Measurements: Participants recorded their interpretation of 16 prognostic statements using a standard probability scale. Generalized estimating equations were used to determine whether participants interpreted statements more optimistically as the expressed probability of survival decreased. Fifteen surrogates whose responses exhibited this trend participated in a semistructured interview. Results: Participants' interpretations of prognostic statements expressing a low risk for death were relatively accurate, but interpretations of statements conveying a high risk for death were more optimistic than the actual meaning (P < 0.001; generalized estimating equation model). Interpretations of the statement "90% chance of surviving" did not differ from the actual meaning, but interpretations of "5% chance of surviving" were more optimistic and showed substantial variability (median, 90% [interquartile range, 90% to 95%; P = 0.11] vs. 15% [interquartile range, 5% to 40%; P < 0.001], respectively). Two main themes from the interviews explained this trend: surrogates' need to register optimism in the face of a poor prognosis and surrogates' belief that patient attributes unknown to the physician would lead to better-than-predicted outcomes. Limitation: Surrogates' interpretations were elicited in an experimental setting rather than during actual clinician–surrogate conversations. Conclusion: Inaccurate interpretations of physicians' prognostications by surrogates arise partly from optimistic biases rather than simply from misunderstandings. Primary Funding Source: National Heart, Lung, and Blood Institute.
Phase I and Pharmacokinetic Trial of Carboplatin in Refractory Adult Leukemia
Authors: E. J. Lee, M. J. Egorin, D. A. Van Echo, A. E. Cohen, N. Tait, C. Schiffer
Journal: JNCI Journal of the National Cancer Institute (1988)

Sixteen patients [13 acute nonlymphocytic leukemia (ANLL), 2 acute lymphocytic leukemia, 1 chronic myelogenous leukemia in a blast crisis; median age, 40 yr; range, 25-78 yr; 9 male, 7 female] received 23 courses of carboplatin given as a bolus on a daily X 5 schedule. Six patients were given 7 courses of carboplatin at 200 mg/m2/day; 3 patients received 5 courses at 250 mg/m2; 9 patients received 11 courses at 300 mg/m2; 2 patients initially treated at 200 mg/m2 were given their 2nd course at 300 mg/m2. Significant hearing loss documented by audiometry occurred in five patients, including three of nine treated at 300 mg/m2. All five had prior or recent exposure to aminoglycoside antibiotics. Three patients developed cancer and acute leukemia group B grade 3 or 4 mucositis, and 18 of 23 courses were complicated by nausea and vomiting. Marrows were hypocellular or aplastic in all patients treated at the highest dose. No complete responses occurred, although two patients with ANLL treated at 300 mg/m2 achieved partial responses lasting 71 and 138 days. The t1/2 alpha [half-life (t1/2)], t1/2 beta, and total body clearance of ultrafilterable platinum were comparable to those previously described by us in patients receiving bolus doses of carboplatin of 22-77 mg/m2/day X 5. Carboplatin has activity in ANLL.
What is intermediate care?: More than a health service term
Authors: Jill Manthorpe, Michelle Cornes
Journal: BMJ (2004)

EDITOR—Any search for clarity or consensus on the meaning of intermediate care, as discussed by Melis et al,1 is doomed to end in disagreement and disappointment. Much of the confusion stems from misunderstanding it as a medical intervention.

Intermediate care is a function or form of …
Alpha-1-antitrypsin deficiency: A new paradigm for hepatocellular carcinoma in genetic liver disease
Authors: David A. Rudnick, David H. Perlmutter
Journal: Hepatology (2005)

Abstract Liver disease in alpha-1-antitrypsin (α1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated. Recent investigations suggest that a specific repertoire of signaling pathways are involved, including the autophagic response, mitochondrial- and ER-caspase activation, and nuclear factor kappaB (NFκB) activation. Whether activation of these signaling pathways, presumably to protect the cell, inadvertently contributes to liver injury or perhaps protects the cell from one injury and, in so doing, predisposes it to another type of injury, such as hepatocarcinogenesis, is not yet known. Recent studies also suggest that hepatocytes with marked accumulation of α1ATZ, globule-containing hepatocytes, engender a cancer-prone state by surviving with intrinsic damage and by chronically stimulating in ‘trans’ adjacent relatively undamaged hepatocytes that have a selective proliferative advantage. Further, this paradigm may apply to other genetic and infectious liver diseases that are predisposed to hepatocellular carcinoma. (Hepatology 2005.)
Mumps and Presternal Edema
Authors: Lewis E. Braverman, Isadore Gershman
Journal: New England Journal of Medicine (1956)

SINCE the first description of a nontender presternal swelling associated with epidemic parotitis in 19181 few references to this phenomenon have appeared in the medical literature.2 3 4 Its occurrence in large epidemics in the armed forces has been variously placed between 1 and 6 per cent.5 6 7 8 It is a benign complication of mumps, and should be recognized as such. The following case report is illustrative of the clinical course of this entity.Case ReportR.L. (C.V.C.H., 95182), a 4 1/2-year-old boy, first entered the hospital because of a nonpainful swelling over the upper sternum of 12 hours' duration. Seven days previously . . .
Subversion in the provinces
Authors: J. Smith
Journal: BMJ (1994)

<h3>Background and Objectives</h3> The diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed because of the lack of objective clinical tools, which increases the diagnostic uncertainty and hampers the therapeutic development in progressive multiple sclerosis (MS). Optical coherence tomography (OCT) has been proposed as a promising biomarker of progressive neurodegeneration. To explore longitudinal changes in the thicknesses of retinal layers on OCT in individuals with relapsing-remitting MS (RRMS) who converted to SPMS vs matched patients with RRMS who did not convert to SPMS. Our hypothesis is that the 2 cohorts exhibit different rates of retinal thinning. <h3>Methods</h3> From our prospective observational cohort of patients with MS at the American University of Beirut, we selected patients with RRMS who converted to SPMS during the observation period and patients with RRMS, matched by age, disease duration, and Expanded Disability Status Scale (EDSS) at the first visit. Baseline retinal measurements were obtained using spectral domain OCT, and all patients underwent clinical and OCT evaluation every 6–12 months on average throughout the study period (mean = 4 years). Mixed-effect regression models were used to assess the annualized rates of retinal changes and the differences between the 2 groups and between converters to SPMS before and after their conversion. <h3>Results</h3> A total of 61 participants were selected (21 SPMS and 40 RRMS). There were no differences in baseline characteristics and retinal measurements between the 2 groups. The annualized rates of thinning of all retinal layers, except for macular volume, were greater in converters before conversion compared with nonconverters by 112% for peripapillary retinal nerve fiber layer (<i>p</i> = 0.008), 344% for tRNFL (<i>p</i> &lt; 0.0001), and 82% for cell-inner plexiform layer (GCIPL) (<i>p</i> = 0.002). When comparing the annualized rate of thinning for the same patients with SPMS before and after conversion, no significant differences were found except for tRNFL and GCIPL with slower thinning rates postconversion (46% and 68%, respectively). <h3>Discussion</h3> Patients who converted to SPMS exhibited faster retinal thinning as reflected on OCT. Longitudinal assessment of retinal thinning could confirm the transition to SPMS and help with the therapeutic decision making for patients with MS with clinical suspicion of disease progression.
Hepatitis C virus in autoimmune liver disease in the UK: aetiological agent or artefact?
Authors: B P Rowan, A Smith, D Gleeson, L P Hunt, T W Warnes
Journal: Gut (1994)

Hepatitis C virus antibody titres (anti-HCV) were measured in serum from 122 patients with autoimmune liver disease (96 with primary biliary cirrhosis and 26 with autoimmune chronic active hepatitis using three generations of enzyme immunoassay (EIA): first generation--Ortho, EIA1; second generation--Abbott, EIA2; and third generation--Murex, EIA3. Anti-HCV was below the positive cut-off level in all 26 autoimmune chronic active hepatitis patients for all tests, while seropositivity values in primary biliary cirrhosis were 31% (EIA1), 14% (EIA2), and 0% (EIA3). In primary biliary cirrhosis, anti-HCV values as measured by all three tests correlated positively with serum IgG concentrations, serum storage time, and a number of other indices of hepatic dysfunction. Multiple regression analysis showed that anti-HCV values were independently affected by both serum IgG and the length of storage time, although the magnitude of the effects varied between tests. When all three multiple regression models were applied to an extreme clinical example, however, EIA3 was least likely to give a false-positive result. The difference in test performance was emphasised further by examination of anti-HCV values in nine primary biliary cirrhosis patients (confirmed negative by recombinant immunoblot assay 2) in whom serial samples were tested (seven to 14 per patient, stored for one to 138 months). Apparent anti-HCV values (EIA1 and EIA2) increased with increasing serum storage time, but were unchanged when measured by EIA3. A similar pattern was evident in a limited study of five autoimmune chronic active hepatitis patients. As the second generation EIA is in widespread use and confirmatory testing is not always available, the effect of serum storage in addition to hyperglobulinaemia should be considered in the interpretation of positive results in auto immune and in other types of chronic liver disease.
Treatment of Disseminated Gonococcal Infection
Authors: Robert M. Blankenship, Randall K. Holmes, Jay P. Sanford
Journal: New England Journal of Medicine (1974)

DISSEMINATED gonococcal infection is being recognized increasingly often and may occur with characteristic skin lesions, tenosynovitis or acute septic arthritis.1 Currently accepted therapy includes hospitalization and treatment for 10 to 14 days with parenterally administered antibiotics. However, the minimal duration for effective therapy has not been well defined. The present study was carried out to evaluate the efficacy of short-term high-dose antibiotic therapy in disseminated gonococcal infection.MethodsClinical EvaluationAll adult patients admitted to Parkland Memorial Hospital from October, 1972, to August, 1973, with a suspected diagnosis of disseminated gonococcal infection were seen shortly after hospitalization by one of . . .
Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.
Authors: Brenda Eskenazi, Paolo Mocarelli, Marcella Warner, Steven Samuels, Paolo Vercellini, David Olive, Larry L Needham, Donald G Patterson, Paolo Brambilla, Nicoletta Gavoni, Stefania Casalini, Stefania Panazza, Wayman Turner, Pier Mario Gerthoux
Journal: Environmental Health Perspectives (2002)

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis.