tbuckley/cabot-search huggingface dataset:
Abstract 2474: Synthesis and antiproliferative activity of novel 17β-acetyl-testosterone-7α-platinum(II) hybrids designed for the treatment of human prostate cancer.
Authors: Sébastien Fortin, Kevin Brasseur, Nathalie Morin, Éric Asselin, Gervais Bérubé
Journal: Cancer Research (2013)

Abstract Prostate cancer is a major public health problem worldwide. In the United-States, prostate cancer is ranked first of all new cancer cases diagnosed in men and it is the second most lethal cancer. Antiandrogens are normally used in clinic to slow down the progression of androgen-sensitive (AR+) prostate cancer inducing prolonged remission without definite cure. In general, 10 years after the initial treatment of early prostate cancers, 19% of patients will experience local tumor progression, 15% distant metastases and 10% will die. Furthermore, advanced prostate cancers quickly (18 to 24 months) become androgen-insensitive (AR-) and antihormone therapy becomes ineffective. At this point, the median survival of approved drug combination treatments is then under 20 months. Consequently, the search for new, more selective and efficient treatments is still a subject of intense research. To that end, we used the natural tropism of testosterone for prostate tissues to target platinum(II) complexes to prostate cancer cells. The platinum complexes were linked to the 7α position on testosterone as it is located between the 3-carbonyl and 17-hydroxyl groups involved in key hydrogen bonds essential for androgen receptor interactions. L- and D-2-pyridylalanine, L-histidine and L-4-thiazolylalanine derivatives were linked to 17β-acetyl-testosterone selected to chelate platinum(II). Four new amino acid platinum(II) complexes were prepared (compounds 1a-1d), characterized and evaluated for their antiproliferative activity on LNCaP (AR+), PC3 (AR-) and DU145 (AR-) human prostate adenocarcinoma cancer cell lines. The new testosterone-platinum(II) complexes exhibited antiproliferative activities at the micromolar level on all prostate cancer cell lines tested. Structure-activity relationships show that the stereochemistry of amino acids (compounds 1a, b) does not affect the antiproliferative activity. Moreover, the replacement of a pyridinyl moiety by an imidazolyl group (compound 1c) decreased the activity by up to 10 fold whereas the replacement by a thiazolyl group (compound 1d) showed an antiproliferative activity between 2.5 to 8.0 times higher than that of cisplatin. The innovative design and the significant activity of our testosterone-platinum(II) complexes toward AR+ and AR- prostate cancer cells suggest that they might be useful for treatment of advanced prostate cancers. Citation Format: Sébastien Fortin, Kevin Brasseur, Nathalie Morin, Éric Asselin, Gervais Bérubé. Synthesis and antiproliferative activity of novel 17β-acetyl-testosterone-7α-platinum(II) hybrids designed for the treatment of human prostate cancer. [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 2474. doi:10.1158/1538-7445.AM2013-2474
Gene Diversity Patterns at 10 X-Chromosomal Loci in Humans and Chimpanzees
Authors: T. Kitano
Journal: Molecular Biology and Evolution (2003)

We have investigated the pattern and extent of nucleotide diversity in 10 X-chromosomal genes where mutations are known to cause mental retardation in humans. For each gene, we sequenced the entire coding region from cDNA in humans, chimpanzees, and orangutans, as well as about 3 kb of genomic DNA in 20 humans sampled worldwide and in 10 chimpanzees representing two “subspecies.” Overall nucleotide diversity in these genes is about twofold lower in humans than in chimpanzees, and nucleotide diversity within and between species is low, suggesting that a high level of functional constraint acts on these genes. Strikingly, we find that a summary of the allele frequency spectrum is significantly correlated in humans and chimpanzees, perhaps reflecting very similar levels of constraint at these genes in the two species. A possible exception is FMR2, which shows a higher number of nonsynonymous than synonymous substitutions on the human lineage, suggesting the action of positive selection.
The effect of high lung conductivity on electrocardiographic potentials. Results from human subjects undergoing bronchopulmonary lavage.
Authors: Y Rudy, R Wood, R Plonsey, J Liebman
Journal: Circulation (1982)

The effect of increased lung conductivity on ECG potentials was studied in human subjects undergoing pulmonary lavage of a whole lung. In this procedure, the air in the lung is replaced by physiologic saline solution, which is a highly conductive fluid. The same situation was simulated theoretically with an eccentric spherical model of the heart and torso. Both the experimental results and theoretical simulations show a decrease in body-surface potentials as the lung conductivity increases. In particular, a large decrease was observed in the posterior vector and the scalar Z lead both experimentally and theoretically. The model simulation shows that the scalar Z lead is maximal at a conductivity value that is very close to the typical normal lung conductivity, so that low voltages are predicted for low lung conductivities as well.
Perceptual Dysfunction in Schizophrenia : Clinical and Auditory Evoked Response Findings
Authors: REESE T. JONES, K. H. BLACKER, ENOCH CALLAWAY
Journal: American Journal of Psychiatry (1966)

Impaired attention, particularly the inability to attend selectively, is a prominent feature of schizophrenia. Schizophrenic and nonschizophrenic mental patients can be distinguished by differences in the wave forms of pairs of averaged auditory evoked responses recorded from scalp electrodes with a computer. In this study evoked response was used as a measure of attention. In a group of newly admitted schizophrenics, the authors found a relationship between individual clinical symptoms and the two-tone evoked response measure. These findings are consistent with the presence of a disturbance in the selective and inhibitory aspects of attention in certain schizophrenics.
Clinical data on high risk medical devices should be made publicly available
Authors: M. Billingsley
Journal: BMJ (2011)

Doctors and patients should have access to information on clinical trial data used to approve high risk medical devices so that they can make informed decisions about the devices they use, a WHO agency says. 

In a report the Belgian Health Care Knowledge Centre recommends that the EU Medical Devices Directive should be adapted to require all manufactures of high risk medical devices to carry out “high quality randomised trials . . . with clinically relevant endpoints.” 

The Belgian Health Care Knowledge Centre is part of WHO’s Health Evidence Network, which promotes the use of research evidence in health policy and health technology assessment. Its report places more emphasis on testing devices for their clinical effectiveness rather than the current focus on assessing …
Magnesium hydrogen breath test using end expiratory sampling to assess achlorhydria in pernicious anaemia patients.
Authors: P Humbert, P Lopez de Soria, F Fernandez-Banares, J Junca, J Boix, R Planas, J C Quer, E Domenech, M A Gassull
Journal: Gut (1994)

A modified magnesium hydrogen breath test, using end expiratory breath sampling, is described to investigate achlorhydria. The efficacy of this test in the diagnostic investigation of pernicious anaemia was compared with that of serum pepsinogen I. Twenty one patients with pernicious anaemia--that is, patients with achlorhydria--and 22 with healed duodenal ulcer and normal chlorhydria were studied. Magnesium hydrogen breath test, serum pepsinogen I, serum gastrin, and standard gastric acid secretory tests were performed in all subjects. The mean (SEM) hydrogen peak value was lower in patients with pernicious anaemia than in the duodenal ulcer group (21.7 (1.9) v 71.3 (5.2) ppm; p = 0.00005). The hydrogen peak value had a 95.2% sensitivity and a 100% specificity to detect pentagastrin resistant achlorhydria. Mean serum pepsinogen I concentrations were also significantly lower in patients with pernicious anaemia than in the duodenal ulcer group (10.7 (2.7) v 123.6 (11.8) micrograms/l p = 0.00005). Sensitivity and specificity to detect pernicious anaemia were both 100% for pepsinogen I. It is concluded that this modified magnesium hydrogen breath test is a simple, noninvasive, cost effective, and accurate method to assess achlorhydria and may be useful in the diagnostic investigation of patients with suspected pernicious anaemia.
Compulsory registration of clinical trials: Under-reporting is not an option
Authors: Peter Jay, Mike Wallace
Journal: BMJ (2004)

General practitioners say that evidence based information is changing practiceEditor-As the publishers of the BMJ's Clinical Evidence we have more than a passing interest in the extent to which the provision of evidenced based information changes clinical practice.In this context, the results of an evaluation of Clinical Evidence commissioned by us assumed some importance.A total of 5960 general practitioners in England were contacted by Stingray Research, an independent market research company, and asked to provide some broad perceptions about the role of evidence in their day to day practice and to pass judgment on Clinical Evidence.The response rate was 838/5960 (14.1%).Some findings were not surprising.Seventy five per cent of general practitioner respondents reported that their patients were likely to show interest in the latest research findings.Ninety seven per cent of the general practitioners had used an information resource to find the latest evidence, and 45% expected to do so at least once every fortnight.Subject matter ranged across the broad spectrum of disease.Clinical Evidence was used mainly around clinical consultations-before, during, and after.However, other uses, such as education and teaching, and assisting the development of practice guidelines, were also reported by 77% and 52% of respondents, respectively.The most crucial findings related to the proportion of doctors, 75%, who reported that they had changed their practice as a result of using Clinical Evidence.Two thirds of these had done so in the previous six months.Change of practice in response to Clinical Evidence was most likely in younger doctors, but was also reported by 56% of respondents aged over 55.Quotes from respondents underlined the message; that provision of evidence from an independent, trusted source supported them in developing their practice and improved the quality of their consultations.There are limitations to this evaluation.We don't know what the non-respondents thought, for example.However, the evidence seems to imply that there is a substantial body of clinicians of all ages-in this case English general practitioners, but we know that similar results have been found among Italian 1 and US doctors-who are motivated to use evidence based sources to improve their care for patients.
Isolated Left Ventricular Noncompaction: A Diagnosis to Consider With Left Ventricular Wall Akinesis
Authors: Kimberly Fagen, Michael Lane, Eugene D. Silverman
Journal: Clinical Nuclear Medicine (2005)

A 12-year-old boy presented with isolated noncompaction of the ventricular myocardium (INVM), a rare cardiomyopathy of childhood. Echocardiography revealed spongy myocardium with deep intratrabecular recesses at the left ventricular apex. Gated blood-pool scintigraphy revealed an akinetic lateral wall and apex with a normal ejection fraction.
Cbl-b Is a Negative Regulator of Receptor Clustering and Raft Aggregation in T Cells
Authors: Connie Krawczyk, Kurt Bachmaier, Takehiko Sasaki, Russell G Jones, Scott B Snapper, Dennis Bouchard, Ivona Kozieradzki, Pamela S Ohashi, Frederick W Alt, Josef M Penninger
Journal: Immunity (2000)
Dances of death, occupational mortality statistics, and social critique
Authors: J. P Mackenbach
Journal: BMJ (1996)

In the late middle ages and early renaissance dances of death were a popular art form. Despite important differences in outlook, the moral messages of these art forms and of modern analyses of socioeconomic inequalities in mortality overlap considerably. This theme has survived in modern dances of death, which are popular in certain parts of Europe, especially in Germany and other German speaking countries in central Europe, and are clearly inspired by the late medieval and early renaissance examples. In the modern dances of death, however, unlike their historical counterparts, social critique (criticism of social inequality) is almost absent, although they include representations of differences between people in social position. Remarkably, references to socioeconomic inequalities in mortality, which have been documented extensively, are also uncommon in the modern examples. This raises important questions about public perception of social inequality in general and socioeconomic inequalities in mortality in particular, and it suggests that modern Western society has not developed the cultural means of conveying the moral message that follows from research into socioeconomic inequalities in health.
The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans
Authors: Ming Zheng, Haili Zhang, David L. Dill, J. David Clark, Susan Tu, Arielle L. Yablonovitch, Meng How Tan, Rui Zhang, Dan Rujescu, Manhong Wu, Lino Tessarollo, Wilfred Vieira, Michael M. Gottesman, Suhua Deng, Livia S. Eberlin, Richard N. Zare, Jean-Martin Billard, Jean-Pierre Gillet, Jin Billy Li, Gary Peltz
Journal: PLoS Medicine (2015)

We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.
Abstract LB-156: A diet-derived sialic acid promotes inflammation and hepatocellular cancer
Authors: Annie N. Samraj, Heinz Laubli, Oliver Pearce, Patrick Secrest, Andrea E. Garcia-Bingman, Nissi Varki, Ajit Varki
Journal: Cancer Research (2014)

Abstract N-glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid derived from the diet (primarily red meat) that can be metabolically incorporated into human tissues despite being an antigen. Since this incorporation occurs in the face of circulating anti-Neu5Gc antibodies, we hypothesized that this generates an antibody-antigen reaction and leads to inflammation termed “xenosialitis”. Although red meat consumption is prominently associated with cancer development, pathological mechanisms behind this link are yet to be conclusively proven. The purpose of our research is to investigate the relationship between “xenosialitis”, inflammation and cancer. We used a Cmah null mouse model (mimicking the human lack of Neu5Gc) to provide evidence for such inflammation and cancer promotion. Anti-Neu5Gc antibodies were generated by immunizing Cmah null mice, with chimpanzee red blood cell membranes, or with human red blood cell membranes as controls. Pooled immune or control sera were repeatedly adsorbed with human red blood cells, and the resulting polyclonal antisera passively transferred into additional Cmah null mice that were on a diet with or without Neu5Gc. Mice fed with Neu5Gc and injected with anti-Neu5Gc antibodies showed dose-dependent elevation in acute phase proteins (Serum Amyloid A and Haptoglobin) in the serum as compared to controls. Such C57BL/6 mice are prone to developing hepatic adenomas and occasional carcinomas. Cmah null but not wild-type C57BL/6 mice immunized with chimpanzee red blood cell membranes and fed with Neu5Gc developed a higher frequency of hepatocellular cancer and liver histology showed Neu5Gc accumulation and foci of inflammation. In conclusion, Neu5Gc that has metabolically incorporated into tissues from the diet interacts with anti-Neu5Gc antibodies, generating xenosialitis. Potential correlations of human anti-Neu5Gc antibody levels with red meat consumption and cancer risk are being investigated. Methods to flush out the xenogenic Neu5Gc are being pursued. Similar mechanisms may be operative in other chronic inflammatory processes in diseases epidemiologically associated with red meat consumption, such as atherosclerosis. Citation Format: Annie N. Samraj, Heinz Laubli, Oliver Pearce, Patrick Secrest, Andrea E. Garcia-Bingman, Nissi Varki, Ajit Varki. A diet-derived sialic acid promotes inflammation and hepatocellular cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2014-LB-156
Recommendations on Use of Prostate-Specific Antigen for Prostate Cancer Screening—Reply
Authors: Jeri Kim, John W. Davis
Journal: JAMA (2012)

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Long-term follow-up on the morbidity and mortality of patients hospitalized for heart failure with a normal ejection fraction
Authors: Marc Klapholz, Nikita Varshneya, Eliezer Hernandez, Radha Voleti, Sanjay Bhargava, Vijayasree Kudithipudi, Zaheed Tai, Rakesh Gupta, Gunawardena Ratnasiri, Khashayar Sehhat, Morcos Hanah, John A. Ambrose, Joyce Burcham, Thierry LeJemtel
Journal: Journal of the American College of Cardiology (2003)
Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding
Authors: H-J Lin, G-Y Tseng, C-L Perng, F-Y Lee, F-Y Chang, S-D Lee
Journal: Gut (1999)

BACKGROUND Peptic ulcers with active bleeding or a non-bleeding visible vessel require aggressive endoscopic treatment. AIMS To determine whether endoscopic adrenaline injection alone or contact probe therapy following injection is a suitable treatment for peptic ulcer bleeding. METHODS A total of 96 patients with active bleeding or non-bleeding visible vessels received adrenaline alone, bipolar electrocoagulation alone, or combined treatment (n=32 in each group). RESULTS Initial haemostasis was not achieved in one patient in the adrenaline group, two in the gold probe group, and two in the injection gold probe group (p&gt;0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30, 6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the study was less in the injection gold probe group (mean 491 ml) than in the adrenaline group (1548 ml, p&lt;0.0001) and the gold probe group (1105 ml, p&lt;0.01). Duration of hospital stay, numbers of patients requiring urgent surgery, and death rate were not statistically different among the three groups. CONCLUSIONS For patients with peptic ulcer bleeding, combined adrenaline injection and gold probe treatment offers an advantage in preventing rebleeding and decreasing the need for blood transfusion.
The Impact of the Quality of Laboratory Staff on the Accuracy of Laboratory Results
Authors: Mary E. Lunz
Journal: JAMA (1987)

This study tests the premise that laboratories employing medical technologists certified by the Board of Registry of the American Society of Clinical Pathologists (MT[ASCP]) produce more accurate laboratory test results, as measured by the College of American Pathologists proficiency tests. Licensed laboratories in Illinois provided the sample. An accuracy score on the College of American Pathologists proficiency tests was calculated for each laboratory. The accuracy score of a subgroup of laboratories employing all (100%) certified medical technologists was compared with the accuracy score of a subgroup of laboratories employing only noncertified medical technologists. Those laboratories employing only certified medical technologists had a mean accuracy score of 95% (SD = 4%), while laboratories employing only noncertified medical technologists had a mean accuracy score of 75% (SD = 30%). The Mann-Whitney U test was used to identify differences between the two groups of laboratories. A difference in the accuracy scores between the two groups of laboratories was statistically discernible. Since most laboratories employ some certified medical technologists, a second analysis considered the relationship of the proportion of certified medical technologists employed in the laboratory and accuracy on College of American Pathologists proficiency tests. A significant positive Spearman rs correlation confirmed a relationship between employing a higher proportion of certified medical technologists and accuracy of test results.