tbuckley/cabot-search huggingface dataset:
NIDDM and Blood Pressure as Risk Factors for Poor Cognitive Performance: The Framingham Study
Authors: Penelope K Elias, Merrill F Elias, Ralph B D'Agostino, L Adrienne Cupples, Peter W Wilson, Halit Silbershatz, Philip A Wolf
Journal: Diabetes Care (1997)

To determine if NIDDM and blood pressure are risk factors for poor cognitive performance and if history and duration of NIDDM and blood pressure interact such that the risk of poor performance is greater for subjects with both NIDDM and hypertension.We used a large prospective cohort sample with 187 NIDDM subjects and 1,624 nondiabetic subjects who were followed for 28-30 years. Cognitive function was assessed using eight tests of learning, memory, visual organization, verbal fluency attention, concept formation, and abstract reasoning. A composite score was also calculated. Odds ratios were used to estimate the relative risk of performing below the lower 25th percentile of z scores on these tests.NIDDM and blood pressure interacted such that diagnosis and duration of NIDDM were associated with greater risk of poor performance on tests of visual memory and on the composite score for hypertensive subjects. Duration of NIDDM was associated with increased risk for poor performance on tests of verbal memory and concept formation. Insulin-treated NIDDM subjects were at higher risk for poor cognitive performance than those NIDDM subjects treated with oral agents or diet. Blood pressure level was associated independently with a measure of verbal fluency.History and duration of NIDDM and high blood pressure are significant risk factors for poor cognitive performance. Hypertensive people with NIDDM are at greatest risk for poor performance on tests measuring visual organization and memory.
Abstract 2510: Efficacy of the Chk1 inhibitor SCH900776 at abrogating cell cycle arrest and enhancing DNA damage-induced cytotoxicity: Comparison with UCN-01
Authors: Alan Eastman, Ryan E. Montano, Kristen M. Garner, Injae Chung, David A. Parry
Journal: Cancer Research (2010)

Abstract Many anticancer agents damage DNA and arrest cell cycle progression primarily in S or G2 phase of the cell cycle depending on drug concentration. Previous studies with the topoisomerase I inhibitor SN38 have demonstrated the efficacy of the Chk1 inhibitor UCN-01 to overcome arrest forcing cells through S, G2 and lethal mitosis. UCN-01 was limited in clinical trials by high plasma protein binding; as a consequence many alternate Chk1 inhibitors have now been developed. SCH900776 is a novel Chk1 inhibitor entering Phase II clinical trials. SCH900776 inhibits Chk1 and overcomes SN38-mediated S and G2 arrest at 300 nM in several carcinoma cell lines which is comparable to UCN-01 at 50 nM. While both Chk1 inhibitors accelerated the rate of cell killing induced by SN38, neither enhanced the overall cell killing. Similarly, no overall sensitization to cisplatin was observed. In contrast, both Chk1 inhibitors induced dramatic sensitization of cells to antimetabolite-induced damage. For example, inhibition of Chk1 sensitized MDA-MB-231 cells to hydroxyurea with the 50% growth inhibitory concentration decreasing from 3 mM to 30 µM, a 100 fold sensitization. Importantly, concentrations of hydroxyurea that exhibited no activation of a checkpoint and no growth inhibition alone were sensitized by inhibition of Chk1. SCH900776 also induced a 50-fold sensitization to cytarabine, 10 fold sensitization to gemcitabine, but no sensitization to 5-fluorouracil. Hence, this sensitization does not extend to all antimetabolites. The 100-fold sensitization to hydroxyurea appeared to require complete inhibition of Chk1 (2 µM 776), although 10-fold sensitization to hydroxyurea was still observed at 200 nM SCH900776. In an MDA-MB-231 derivative expressing shRNA that resulted in almost undetectable levels of Chk1, the full level of sensitization to hydroxyurea could be achieved at 200 nM SCH900776 demonstrating that the response of tumors may vary with the endogenous level of Chk1. We are currently comparing the differential response of a panel of carcinoma cell lines and find some that are sensitized to hydroxyurea up to 100-fold at 200 nM SCH900776, although there appear to be determinants other than the Chk1 levels. These results can be extrapolated to suggest that marked differences in efficacy of SCH900776 can be expected in patients. It will be important to define the parameters of response as these may facilitate selection of patients most likely to respond to combination therapy with Chk1 inhibitors. 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 2510.
Impact of a new national screening policy for Down's syndrome in Denmark: population based cohort study
Authors: C. K Ekelund, F. S. Jorgensen, O. B. Petersen, K. Sundberg, A. Tabor
Journal: BMJ (2008)

Objectives To evaluate the impact of a screening strategy in the first trimester, introduced in Denmark during 2004-6, on the number of infants born with Down's syndrome and the number of chorionic villus samplings and amniocenteses, and to determine detection and false positive rates in the screened population in 2005 and 2006. Design Population based cohort study. Setting 19 Danish departments of gynaecology and obstetrics and a central cytogenetic registry 2000-7. Participants 65 000 pregnancies per year. Main outcome measures The primary outcomes measured were number of fetuses and newborn infants with Down's syndrome diagnosed prenatally and postnatally and number of chorionic villus samplings and amniocenteses carried out. Secondary outcomes measured were number of women screened in 2005 and 2006, screen positive rate, and information on screening in 2005 and 2006 for infants with a postnatal diagnosis of Down's syndrome. Results The number of infants born with Down's syndrome decreased from 55-65 per year during 2000-4 to 31 in 2005 and 32 in 2006. The total number of chorionic villus samplings and amniocenteses carried out decreased from 7524 in 2000 to 3510 in 2006. The detection rate in the screened population in 2005 was 86% (95% confidence interval 79% to 92%) and in 2006 was 93% (87% to 97%). The corresponding false positive rates were 3.9% (3.7% to 4.1%) and 3.3% (3.1% to 3.4%). Conclusion The introduction of a combined risk assessment during the first trimester at a national level in Denmark halved the number of infants born with Down's syndrome. The strategy also resulted in a sharp decline in the number of chorionic villus samplings and amniocenteses carried out, even before full implementation of the policy.
Website of the week: Death, sex, and gardening
Authors: C. Martyn
Journal: BMJ (2002)

It's well known that what the person on the Clapham omnibus believes about health, death, and disease often conflicts with the professional understanding of these matters. But it's a bit odd that patients are much more aware of the nature of the health professionals' biomedical explanatory model than most doctors are of lay accounts of illness, diagnosis, and treatment. Doctors tend to regard medical sociology …
Cyclosporin A does not affect epidermal proliferation following standardized injury
Authors: W.P. Arnold, M.-J.P. Gerritsen, P.C.M. Kerkhof
Journal: British Journal of Dermatology (1993)

Journal Article Cyclosporin A does not affect epidermal proliferation following standardized injury Get access W.P. Arnold, W.P. Arnold Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.‐J.P. Gerritsen, M.‐J.P. Gerritsen Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.C.M. van de Kerkhof P.C.M. van de Kerkhof Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 6, 1 December 1993, Pages 751–753, https://doi.org/10.1111/j.1365-2133.1993.tb03351.x Published: 01 December 1993
Mechanistic profiling of the siRNA delivery dynamics of lipid–polymer hybrid nanoparticles
Authors: Stefano Colombo, Dongmei Cun, Katrien Remaut, Matt Bunker, Jianxin Zhang, Birte Martin-Bertelsen, Anan Yaghmur, Kevin Braeckmans, Hanne M. Nielsen, Camilla Foged
Journal: Journal of Controlled Release (2014)
Tongue Necrosis in a Patient with Essential Thrombocytosis
Authors: Alejandro Fernandez-Casado, Blanca Sanchez-Gonzalez
Journal: New England Journal of Medicine (2009)

A 69-year-old woman had been taking acenocoumarol for 10 years for the treatment of deep vein thrombosis. The drug was withdrawn before implantation of a pacemaker. Twenty-four hours later, intense lingual pain developed.
Essential thrombocythemia: A retrospective analysis of 39 cases
Authors: Y. L. Kwong, R. H. S. Liang, E. K. W. Chiu, A. K. W. Lie, L. C. Chan, D. Todd, T. K. Chan
Journal: American Journal of Hematology (1995)

Abstract Thirty‐nine Chinese patients presenting as essential thrombocythemia (ET) were analyzed retrospectively. The median age at presentation was 69 years and the M:F ratio was 1.35:1. At diagnosis, 33 cases (84%) were asymptomatic and the diagnosis was made incidentally, while 3 cases (8%) presented with small vessel, and 2 cases (5%) with large vessel, thrombosis. One patient (3%) presented with minor bleeding. The platelet count ranged from 0.9‐34 × 10 12 /1. Of 12 karyotypes done, 2 cases were abnormal, both showing the Philadelphia (Ph) chromosome. First‐line therapy was radiophosphorus ( 32 P) in 3 cases, melphaian in 20 cases, and hydroxyurea in 12 cases; 4 cases did not receive specific therapy. During the follow‐up (mean = 4 years), no thrombotic or bleeding episodes were observed. One patient with the Ph chromosome underwent blastic transformation. These results indicate that bleeding and thrombosis occur significantly less in Chinese patients than in Western patients. The Ph chromosome appears to be a bad prognostic indicator. Because of the very low incidence of complications and good prognosis, the authors believe that cytoreductive therapy is best achieved by the use of hydroxyurea instead of alkylating agents or radiophorphours, as the latter agents are potentially leukemogenic. © 1995 Wiley‐Liss, Inc.
Increased Macrophage Inflammatory Protein-1 α and Macrophage Inflammatory Protein-1 β Levels in Bronchoalveolar Lavage Fluid of Patients Affected by Different Stages of Pulmonary Sarcoidosis
Authors: ARMANDO CAPELLI, ANTONINO DI STEFANO, MIRCO LUSUARDI, ISABELLA GNEMMI, CLAUDIO F. DONNER
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Macrophage inflammatory protein (MIP)-1 α and MIP-1 β are two CC chemokines that induce lymphocyte migration. MIP-1 α preferentially mediates chemotaxis of CD8 rather than CD4 lymphocytes, whereas the reverse is true for MIP-1 β . Both these chemokines recognize CCR5 as a cellular receptor in T lymphocytes and alveolar macrophages. We measured the concentrations of MIP-1 α and MIP-1 β in bronchoalveolar lavage fluid (BALF) of 30 subjects affected by different stages of pulmonary sarcoidosis and 18 healthy normal subjects. We also evaluated the expression of CCR5 in alveolar macrophages and lymphocytes. The BALF concentrations of MIP-1 α were significantly increased only in Stage II and III sarcoidosis. On the contrary, the concentrations of MIP-1 β were significantly increased at all stages. A striking increase of CCR5 expression was observed in both lymphocytes and macrophages of all patients, along with a trend to decreased positivity from Stage I to III of the disease. The MIP-1 β concentrations correlated with the number of total (r = 0.65, p = 0.0001) and both CD4 (r = 0.64, p = 0.0001) and CD8 (r = 0.62, p = 0.0001) lymphocytes; on the contrary, the MIP-1 α concentrations correlated only with CD8 lymphocytes (r = 0.45, p = 0.002). Finally, significant negative correlations were observed between the neutrophil percentage and CCR5 expression in alveolar macrophages (r = − 0.53, p = 0.005) and lymphocytes (r = − 0.43, p = 0.01). Our results help to explain the mechanism of CD4 and CD8 recruitment and the possible involvement of CC chemokines in the fibrotic progression of sarcoidosis.
Geoffrey W C Hanks
Authors: D. Doyle
Journal: BMJ (2013)

The death of Geoffrey W C Hanks (“Geoff”), aged 67, will have brought sadness to thousands of clinicians worldwide. He was a truly international figure, a polymath, described by a fellow pioneer as the “gentle giant” in the world of palliative medicine. He will be remembered for his research, his passion for teaching, his gently persuasive manner, and, above all else, his modesty and concern for others. Asked for one word that totally described him, arguably his closest colleague said “perfectionist.”

He came into this specialty, as did so many, with the surge of interest in, and commitment to, best possible “terminal care” in the late 1970s and the 1980s. Care of dying patients had always been a priority in medical practice, but evidence was accumulating that such care, and particularly its scientific base, could be improved in home and hospital. Some—often expressing their ideas with missionary fervour—saw freestanding “charitable” hospices as the answer, challenging as it was to conduct research in them. Geoff, ever the rigorous researcher, was not one of them.

Others thought palliative care services or teams in hospitals …
Abstract 2611: Role of circadian genes in breast cancer: Analysis of the CECILE study, a population-based case-control study conducted in France
Authors: Therese Truong, Florence Menegaux, Sylvia Richardson, Pascal Guénel
Journal: Cancer Research (2012)

Abstract Breast cancer risk has been associated with shift work and light exposure at night. It has been suggested that disruption of circadian rhythms induced by these exposure may play a role in tumorigenesis. Circadian rhythms regulate diverse physiologic processes, including regulation of sex hormone levels, and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle regulation and apoptosis. However, only few studies have investigated the role of these genes in breast cancer. The purpose of this study was to analyze the association between polymorphisms in circadian genes and breast cancer risk. The CECILE study is a population-based case-control study on environmental and genetic factors. A total of 1135 incident cases and 1167 controls provided DNA samples. We genotyped 570 tagging and functional SNPs from the 22 genes in the circadian rhythm pathway defined by KEGG. Preliminary results based on a SNP by SNP analysis using unconditional logistic regression highlighted 36 SNPs with p-value&amp;lt;0.05 in RORA, CUL1, NPAS2, CRY1, CRY2 and CLOCK genes. Of these, 3 SNPs in RORA were significantly associated with breast cancer after Bonferroni correction for multiple testing (p&amp;lt;0.0001). In ongoing analyses, we use the Multilevel Inference for SNP Association (MISA) method, which is a more powerful method that allows estimating associations at the SNP, gene and pathway level. These analyses will be presented. Our results suggest a role of the circadian gene in breast cancer risk. Further analysis on possible interaction between shift work and genetic variants highlighted in this study in relation to breast cancer risk will be conducted in the CECILE study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2611. doi:1538-7445.AM2012-2611
Perinatal practice and compensation for handicap
Authors: P. Diggory
Journal: BMJ (1980)

preservation of antimicrobial factors (other than milk cells) approaching 100%.There is no simple correct way of running a human milk bank.However, great caution should be exercised in recommending the wholesale adoption of a policy of using raw bacteriologically unmonitored human milk for sick low-birthweight infants, especially in hospitals which have had little or no previous experience of human milk banking.I believe that, apart from the use of fresh milk from an individual mother for her own baby, it is safer to opt for a simple system based on precise pasteurisation,2 which can be relied on to provide bacteriologically clean milk with the majority of its bacteriostatic properties intact.
Nanovesicle‐Based Bioelectronic Nose for the Diagnosis of Lung Cancer from Human Blood
Authors: Jong Hyun Lim, Juhun Park, Eun Hae Oh, Hwi Jin Ko, Seunghun Hong, Tai Hyun Park
Journal: Advanced Healthcare Materials (2013)

A human nose‐mimetic diagnosis system that can distinguish the odor of a lung cancer biomarker, heptanal, from human blood is presented. Selective recognition of the biomarker is mimicked in the human olfactory system. A specific olfactory receptor recognizing the chemical biomarker is first selected through screening a library of human olfactory receptors (hORs). The selected hOR is expressed on the membrane of human embryonic kidney (HEK)‐293 cells. Nanovesicles containing the hOR on the membrane are produced from these cells, and are then used for the functionalization of single‐walled carbon nanotubes. This strategy allows the development of a sensitive and selective nanovesicle‐based bioelectronic nose (NvBN). The NvBN is able to selectively detect heptanal at a concentration as low as 1 × 10 −14 m , a sufficient level to distinguish the blood of a lung cancer patient from the blood of a healthy person. In actual experiments, NvBN could detect an extremely small increase in the amount of heptanal from human blood plasma without any pretreatment processes. This result offers a rapid and easy method to analyze chemical biomarkers from human blood in real‐time and to diagnose lung cancer.
Revenue sources for community health services.
Authors: A P Tait, G I Benson
Journal: BMJ (1977)

<h3>Summary</h3> Northern lakes are ice-covered for a large part of the year, yet our understanding of microbial diversity and activity during winter lags behind that of the ice-free period. In this study, we investigated under-ice diversity and metabolism of Verrucomicrobia in seasonally ice-covered lakes in temperate and boreal regions of Quebec, Canada using 16S rRNA sequencing, metagenomics and metatranscriptomics. Verrucomicrobia, particularly the V1, V3 and V4 subdivisions, were abundant during ice-covered periods. A diversity of Verrucomicrobia genomes were reconstructed from Quebec lake metagenomes. Several genomes were associated with the ice-covered period and were represented in winter metatranscriptomes, supporting the notion that Verrucomicrobia are metabolically active under ice. Verrucomicrobia transcriptome analysis revealed a range of metabolisms potentially occurring under ice, including carbohydrate degradation, glycolate utilization, scavenging of chlorophyll degradation products, and urea use. Genes for aerobic sulfur and hydrogen oxidation were expressed, suggesting chemolithotrophy may be an adaptation to conditions where labile carbon may be limited. The expression of genes for flagella biosynthesis and chemotaxis was detected, suggesting Verrucomicrobia may be actively sensing and responding to winter nutrient pulses, such as phytoplankton blooms. These results increase our understanding on the diversity and metabolic processes occurring under ice in northern lakes ecosystems.
Treatment of the Carpal-tunnel Syndrome
Authors: R. S. Crow
Journal: BMJ (1960)

MEDICAL JOURNALremain unsuspected in such a case is thus perfectly understandable and reflects no discredit on the clinical acumen of any physician.But we do feel that it was a pity that, in the absence of any attempt at bacteriological confirmation, Case 12 was written off as " streptococcal tonsillitis."This diagnosis made-as, in our experience, it not infrequently is-with the unaided senses is not merely a delusion of muddled minds, it is a dangerous snare which by the mesmeric influence of a jargonistic label closes the mind to the possibility of reappraisal." Tonsillitis " is a perfectly valid clinical diagnosis; only the laboratory can ascribe to it a specific aetiology.We do not wish to embark here on the perennial controversy concerning the indications for antibiotics or chemotherapeutic agents in the treatment of acute sore throats, but it is pertinent to plead that if the physician in charge has made up his mind to administer one of these drugs he should at least take a throat swab-he need not await the result of the culture-before starting his course of treatment. SummaryA localized epidemic of diphtheria involving 12 cases (one fatal), the brunt of which fell on one infants' school class, is described.Virulent C. diphtheriae gravis was isolated from nine of these cases and 14 other carriers.The relatively low immunity status of the school community (less than 50% of the children having been immunized) was thought to be an important factor in the development of the epidemic.The treatment of carriers is considered, the obstacles (notably the widespread use of antibiotics) to bacteriological diagnosis are recounted, and the difficulties in tracing the original source of infection is discussed.Our thanks are due to Dr. A. J. H. Tomlinson and the staff of the Public Health Laboratory, London County Hall, for accepting our strains for confirmation and virulence tests, and for accepting direct the enormous number of swabs taken when the mass swabbing had to be extended.It is a pleasure to acknowledge our debt to the medical, nursing, and administrative staffs of the Barking Public Health Department and to local family doctors for their ready help and full co-operation throughout the epidemic.
False-Positive Uptake of 1–131 MIBG
Authors: SEHER N. ÜNAL, ISIK ADALET, AYSE MUDUN, TARIK TERZIOGLU, FARUK ALAGÖL, MEHMET AGAN, SEMA CANTEZ
Journal: Clinical Nuclear Medicine (1995)

A patient with a clinical suspicion of pheochromocytoma was studied with MIBG labeled I-131. The patient had marked uptake of the radiopharmaceutical in the mediastinum, which was found to be the thymus gland at excisional biopsy. While interpreting I-131 MIBG imaging, possible MIBG uptake of normal thymic tissue must be considered to avoid a false-positive diagnosis of primary metastatic tumors.
Problem of Hypothyroidism after I<sup>131</sup>Therapy of Hyperthyroidism
Authors: John B. Stanbury, Leslie J. DeGroot
Journal: New England Journal of Medicine (1964)

THE introduction of radioactive iodine into clinical therapeutics in 1941 revolutionized the treatment of Graves's disease. It is now employed as the primary form of treatment for most of these patients, but in the early exploratory years, it was used cautiously because of fear that the radiation might cause thyroid cancer, leukemia or genetic damage. Hypothyroidism was recognized as an occasional complication and was accepted as a minor risk of treatment.The initial concern for the dangers of I131 have not in general been supported by experience, and arbitrary age barriers to its use have gradually fallen until now most . . .