tbuckley/cabot-search huggingface dataset:
Human Extracellular Proteins
Authors: M. J. Crumpton
Journal: BMJ (1967)

Interest in the subject of headache has greatly increased in the last decade as research acti- vities move rapidly into the sphere of chemical investigation rather than clinical description, but the literature is so scattered that the average physician finds difficulty in keeping up to date.This book is said to be the first of a series intended to bring together under one cover authoritative reviews on different facets of the problem, and edited by a dis- tinguished physician well known for his own work in this field the series has certainly made a good start.The contributors are drawn from widely separated parts of the world-Europe, Australia, and America- and are recognized authorities on the subjects they discuss.Though any book drawn up in this manner is bound to have a lot of repetition in it, this has been reduced to an acceptable minimum.The introduction by E. C. Kunkle forms a philosophical prelude, stressing the need to look at the "whole" patient, and often to temper one's therapeutic enthusiasm with sound common sense.It includes a number of classical quotations which will no doubt be a boon to speakers looking for an opening or dosing sentence to their discourse on headache.There then follows an extensive review by F. Sicuteri on vasoneuractive sub- stances and vascular pain.This is a valu- able article, with 163 references, tracing the development of thought and work on this aspect, and goes well beyond the action of
One nudge forward, two steps back
Authors: C. Bonell, M. McKee, A. Fletcher, P. Wilkinson, A. Haines
Journal: BMJ (2011)

Why nudging might make for muddled public health and wasted resources

In the linked article (doi:10.1136/bmj.d228), Marteau and colleagues offer a timely note of caution about “nudging”—an approach to behaviour change described in Nudge: Improving Decisions about Health, Wealth and Happiness , a book by the US academics Richard Thaler and Cass Sunstein—which is the coalition government’s preferred strategy for promoting public health.1

Based on an explicitly self contradictory concept termed “libertarian paternalism,”2 nudging recognises that our everyday decisions are often not conscious and rational. Much of our behaviour is automatic or follows perceived norms, and it relies on poor information about consequences or overinterpretation of misleading information. Consequently, nudging is based on the principle that it is legitimate to influence people’s behaviour to make their lives healthier (paternalism), but that such influence should be unobtrusive and not entail compulsion (libertarian). Nudges might involve subconscious cues (such as painting targets in urinals to improve accuracy) or correcting misapprehensions about social norms (like telling us that most people do not drink excessively). They can alter the profile of different choices (such as the prominence of healthy food in canteens) or change which options are the default (such as having to opt out of rather than into organ …
Abstract 2274: Metformin use and risk of lung cancer in patients with diabetes.
Authors: Lori C. Sakoda, Ninah S. Achacoso, Charles P. Quesenberry, Tiffany Peng, Samantha F. Ehrlich, Assiamira Ferrara, Laurel A. Habel
Journal: Cancer Research (2013)

Abstract Observational studies suggest that cancer incidence is lower in patients with type 2 diabetes treated with metformin, relative to patients treated with other diabetes medications. The few studies to examine metformin use in relation to lung cancer risk, however, have produced inconsistent results. To clarify this relationship, we conducted a retrospective cohort study of 50,722 adults aged 40 years or older included in the Kaiser Permanente Northern California Diabetes Registry, who completed a mailed survey administered in 1994 to 1996 on health-related traits and behaviors. All prescribed diabetes medications were identified for each patient from pharmacy records. Patients were followed for lung cancer from 1997 to 2009, with a median follow-up of 8.1 years. Using Cox regression, with age as the time scale, rate ratios (RR) and 95% confidence intervals (CI) were calculated to estimate risk of lung cancer associated with new use of metformin, adjusted for sex, race/ethnicity, smoking status, income, education level, diabetes duration, baseline measures of hemoglobin A1c and creatinine, and ever use of other types of diabetes medications. Measures of metformin use, along with ever use for each type of diabetes medication, were modeled as time-dependent variables. During 389,887 person-years of follow-up, 685 patients were diagnosed with lung cancer. The adjusted RR for ever use of metformin was 0.95 (95% CI, 0.79-1.14). For duration of metformin use, the adjusted RRs for &amp;lt;2.0, 2.0-4.9, and 5.0+ years were 1.01 (95% CI, 0.80-1.28), 0.94 (95% CI, 0.73-1.22), and 0.86 (95% CI, 0.63-1.18), respectively. In analyses stratified by smoking status, the adjusted RRs for ever use of metformin were 0.98 (95% CI, 0.79-1.21) in ever smokers and 0.59 (95% CI, 0.34-1.01) in never smokers. However, in never smokers, the number of users diagnosed with lung cancer was relatively small, and no dose-response decrease in risk with increasing duration of metformin use was found; the corresponding adjusted RRs for &amp;lt;2.0, 2.0-4.9, and 5.0+ years of metformin use were 0.52 (95% CI, 0.23-1.16), 0.58 (95% CI, 0.26-1.26), and 0.70 (95% CI, 0.31-1.58), respectively. Our results suggest that metformin use is not associated with lung cancer risk in former or current smokers with diabetes. Additional research is needed to determine whether metformin use might alter lung cancer risk in never smokers with diabetes. Citation Format: Lori C. Sakoda, Ninah S. Achacoso, Charles P. Quesenberry, Tiffany Peng, Samantha F. Ehrlich, Assiamira Ferrara, Laurel A. Habel. Metformin use and risk of lung cancer in patients with diabetes. [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 2274. doi:10.1158/1538-7445.AM2013-2274
Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion
Authors: Kevin T Bauerle, Rebecca E Schweppe, Bryan R Haugen
Journal: Molecular Cancer (2010)

Abstract Background Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines. Results Three pharmacologic inhibitors of NF-κB differentially inhibited growth in a panel of advanced thyroid cancer cell lines, suggesting that these NF-κB inhibitors may have off-target effects. We therefore used a selective genetic approach to inhibit NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα). These studies revealed decreased cell growth in only one of five thyroid cancer cell lines (8505C), which occurred through a block in the S-G2/M transition. Resistance to TNFα-induced apoptosis was observed in all cell lines, likely through an NF-κB-dependent mechanism. Inhibition of NF-κB by mIκBα sensitized a subset of cell lines to TNFα-induced apoptosis. Sensitive cell lines displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway, defining a potential mechanism of response. Finally, NF-κB inhibition by mIκBα expression differentially reduced thyroid cancer cell invasion in these thyroid cancer cell lines. Sensitive cell lines demonstrated approximately a two-fold decrease in invasion, which was associated with differential expression of MMP-13. MMP-9 was reduced by mIκBα expression in all cell lines tested. Conclusions These data indicate that selective inhibition of NF-κB represents an attractive therapeutic target for the treatment of advanced thyroid. However, it is apparent that global regulation of thyroid cancer cell growth and invasion is not achieved by NF-κB signaling alone. Instead, our findings suggest that other important molecular processes play a critical role in defining the extent of NF-κB function within cancer cells.
Tissue plasminogen activator and seizures: a clot-buster’s secret life
Authors: Robert Pawlak, Sidney Strickland
Journal: Journal of Clinical Investigation (2002)

Seizures, caused by hypersynchronized electrical activity, can occur when an area of the brain becomes injured as a result of various pathologies such as degenerative disorders, brain tumors, or head trauma. Seizures are an extremely widespread problem, with about 10% of the population experiencing them at least once in their lives. They are hazardous both because of the uncontrolled motor activity they generate and because they can cause neuronal death and in some cases permanent neurological deficits (1).

Phenytoin and related antiseizure agents act by prolonging the refractory period of the action potential. This extension prevents the neurons from entering into the rapid firing associated with seizures but allows normal conduction to occur. These drugs generally have a narrow therapeutic range and often have undesirable side effects even when the dosage is optimized. Therefore, a better understanding of seizure propagation might lead to insights about new therapies, and also perhaps a better understanding of normal neuronal activity.
Aneurism of the Abdominal Aorta
Authors: T. Smith
Journal: BMJ (1858)

Partly fed from mother's breast; Died of convulsions.also with boiled bread. 47.Girl; aged 2 months.Very little breast-milk; had baked Died of diarrhea.flour and biscuits boiled.48. Child; aged.5months.1These cases happened together Coroner's inquest: ver-in the same house.The child of a diet " overfeeding".wet nurse, and her nurseling, were 49.Child; aged 7 months.|fed on a hearty supper of bread Coroner's inquest: ver-food; and were found dead at diet " overfeeding.J 4 A.M. 50.C hild; aged 4 months.A similar case to the preceding Coroner's inquest : ver-two.dict " overfeeding'.These 5() cases may be thus classified:-Convulsions (in 7 coroner's inquests, verdicts
Prevalence of HIV infection among patients with leprosy and tuberculosis in rural Zambia.
Authors: K. Meeran
Journal: BMJ (1989)

shown higher anxiety scores among patients with no previous or unpleasant previous anaesthetic experience compared with those whose previous experience had been pleasant.This was also the case in this study, and the table shows the anxiety shown by these more nervous patients (n=50).These patients had a lower anxiety score after they took timolol 10 mg.This effect was often described as "a surprising absence of the 'butterflies'."Scores changed little after placebo.The change in mean anxiety score was compared for the timolol and placebo groups by the paired two sample t test, and the reduction in the multiple affect adjective checklist score was significant (t= 2 05, 48 df; p<005).
Carbohydrate Intolerance In Gastrectomy Patients
Authors: Samuel Alpert
Journal: JAMA (1966)

<h3>To the Editor:—</h3> I would like to comment on a recent editorial, "Carbohydrate Intolerance in Post-gastrectomy Patients" (<b>197</b>:918, 1966). We have observed results of oral glucose tolerance tests done on 34 gastrectomized patients.<sup>1</sup>Twenty-one of these exhibited the characteristic pattern of initial hyperglycemia followed by sharp descent to hypoglycemic levels. Six of these subjects underwent an intravenous glucose tolerance test. The subsequent one-, two-, and three-hour levels were within normal limits. No hypoglycemia was noted in reaction to the sharp rise in the systemic level of blood sugar, produced by the administration of glucose intravenously. None of these patients to date (and some have been observed for as long as 20 years), has exhibited clinical evidence of diabetes mellitus. To consider these patients as potential diabetics is, in my opinion, erroneous. Diabetes mellitus is a genetic disorder, exhibiting, in addition to the carbohydrate disturbance, accelerated atherosclerosis, microangiopathy (involving
A randomised controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis.
Authors: G M Hall, M Daniels, E C Huskisson, T D Spector
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To assess the effects of hormone replacement therapy (HRT) on disease activity in postmenopausal rheumatoid arthritis (RA). METHODS--Two hundred postmenopausal outpatients (aged 45-65 years) were admitted into a single blind randomised placebo controlled trial of transdermal oestradiol (50 micrograms daily) over six months. Patients continued with routine antirheumatic medications. Compliance with HRT was monitored using serum oestradiol (E2) levels. Disease activity was monitored at entry, three and six months using erythrocyte sedimentation rate (ESR), articular index (AI), visual analogue pain scale (VPS) and early morning stiffness (EMS). RESULTS--Ninety one and 77 patients completed six months treatment with placebo and HRT respectively. There were no significant differences in baseline characteristics between the groups and no overall effects of treatment. However, 35 patients (41.6%), who completed HRT, failed to achieve serum E2 levels &gt; 100 pmol/l at either three or six months and were considered 9poor-compliers9. In the remaining HRT 9compliers9 (58.4%) there were significant improvements after six months in articular index (28.9%; p &lt; 0.01) and pain score (21.7%; p &lt; 0.05) compared with placebo, as well as reductions in ESR (8.9%; NS) and morning stiffness (25.2%; NS). Comparisons between HRT 9compliers9 and 9poor-compliers9 confirmed significant improvements in articular index (p &lt; 0.001), pain score (p &lt; 0.05) and morning stiffness (p &lt; 0.001) in the 9compliers9. CONCLUSIONS--This study did not show an overall effect of HRT on disease activity when used as an adjunct therapy in postmenopausal patients. A subgroup of patients, who had greater increments in serum E2 whilst taking HRT, demonstrated improvements in some parameters of disease activity, suggesting a potential beneficial effect with good compliance and higher dose HRT. Most importantly, in the treatment of RA associated bone loss, HRT can be prescribed without fear of a disease flare up.
Comparative Genomics of Centrality and Essentiality in Three Eukaryotic Protein-Interaction Networks
Authors: Matthew W. Hahn, Andrew D. Kern
Journal: Molecular Biology and Evolution (2004)

Most proteins do not evolve in isolation, but as components of complex genetic networks. Therefore, a protein's position in a network may indicate how central it is to cellular function and, hence, how constrained it is evolutionarily. To look for an effect of position on evolutionary rate, we examined the protein-protein interaction networks in three eukaryotes: yeast, worm, and fly. We find that the three networks have remarkably similar structure, such that the number of interactors per protein and the centrality of proteins in the networks have similar distributions. Proteins that have a more central position in all three networks, regardless of the number of direct interactors, evolve more slowly and are more likely to be essential for survival. Our results are thus consistent with a classic proposal of Fisher's that pleiotropy constrains evolution.
RhoA Mediates Cyclooxygenase-2 Signaling to Disrupt the Formation of Adherens Junctions and Increase Cell Motility
Authors: Yu-Wen E. Chang, Jerry W. Marlin, Terry W. Chance, Rolf Jakobi
Journal: Cancer Research (2006)

Abstract Cyclooxygenase-2 (COX-2) represents an important target for treatment and prevention of colorectal cancer. Although COX-2 signaling is implicated in promoting tumor cell growth and invasion, the molecular mechanisms that mediate these processes are largely unknown. In this study, we show that the RhoA pathway mediates COX-2 signaling to disrupt the formation of adherens junctions and increase cell motility. Disruption of adherens junctions promotes tumor cell invasion and metastasis and is often associated with tumor progression. We detected high levels of RhoA activity in HCA-7 colon carcinoma cells that constitutively express COX-2. Inhibition of COX-2 significantly reduced the levels of RhoA activity in HCA-7 cells, suggesting that constitutive expression of COX-2 stimulates RhoA activity. Interestingly, inhibition of COX-2 or silencing of COX-2 expression with small interfering RNA (siRNA) stimulated the formation of adherens junctions, concomitant with increased protein levels of E-cadherin and α-catenin. Furthermore, inhibition of RhoA or silencing of RhoA expression with siRNA increased the levels of E-cadherin and α-catenin. Inhibition of Rho kinases (ROCK), the RhoA effector proteins, also increased levels of E-cadherin and α-catenin and stimulated formation of adherens junctions. The motility of HCA-7 cells was significantly decreased when COX-2 or RhoA was inhibited. Therefore, our data reveal a novel molecular mechanism that links COX-2 signaling to disrupt the formation of adherens junctions; COX-2 stimulates the RhoA/ROCK pathway, which reduces levels of E-cadherin and α-catenin leading to disruption of adherens junction formation and increased motility. Understanding of COX-2 downstream signaling pathways that promote tumor progression is crucial for the development of novel therapeutic strategies. (Cancer Res 2006; 66(24): 11700-8)
Incidence of Functional Splenic Tissue After Surgical Splenectomy
Authors: RICHARD P. SPENCER, ISAAC WASSERMAN, VIJAY DHAWAN, KOLLI SURESH
Journal: Clinical Nuclear Medicine (1977)

SPENCER, RICHARD P. M.D.; WASSERMAN, ISAAC M.D.; DHAWAN, VUAY M.D.; SURESH, KOLLI M.D. Author Information
SP0044 Learning and Using Behavior Change Techniques to Promote Physical Activity in Rheumatoid Arthritis
Authors: I. Demmelmaier
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> There are least two obvious purposes for studying health professionals (HPs) in behavior change interventions: 1) to assess treatment fidelity, i.e. to what extent was the intervention delivered as intended, and 2) to gain knowledge about how HP9s learn and use new clinical skills. This presentation focuses on the second purpose. To support health behaviors such as physical activity, HPs9 physiological and medical knowledge needs to be complemented with knowledge to support motivational and self-regulation in patients trying to change their habits. However, changing behavior in HP9s may be challenging and several barriers within and outside the individual HP have been identified. In 2010 we launched an out-sourced program over two years to implement health-enhancing physical activity in rheumatoid arthritis (RA). During the first year, 12 physical therapists (PT9s) guided 220 participants to increased physical activity using public gyms and support groups. The PT9s were to guide in several behavior change techniques: a) goal-setting, b) action planning, c) self-monitoring, d) relapse prevention, e) give feedback on physical activity and f) promote social support within the groups to prepare the participants for being in charge of the group sessions during the second year of the program. Qualitative and quantitative methods were used to assess how behavior change techniques were used by PT9s and adopted by participants. The results indicate that PT9s perceived initial challenges but gradually, assisted by education and feedback, adopted practices that facilitated their use of behavior change techniques. The participants reported the content of the program to be feasible, emphasizing the type of exercise and setting, as well as professional coaching. However, stringent use of goal-setting, action planning and follow-up of self-monitoring was not fully implemented and may need more tailoring to individual needs. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6216
Association of different HLA antigens with various toxic effects of gold salts in rheumatoid arthritis.
Authors: M Hakala, A.H van Assendelft, J Ilonen, S Jalava, A Tiilikainen
Journal: Annals of the Rheumatic Diseases (1986)

An association of gold induced proteinuria with HLA-D(R)3 has been reported. To investigate other possible relationships between gold toxicity and HLA antigens we studied 85 patients with rheumatoid arthritis (RA) divided into four subgroups: patients with gold induced interstitial pneumonitis, mucocutaneous lesions, proteinuria, and patients without gold toxicity. The HLA frequencies in patient groups and 283 healthy controls were compared in different pairwise combinations. Gold induced pneumonitis was associated with HLA-B40 and Dw1. An association between gold induced proteinuria and HLA-Dw3 was also seen. The increased prevalence of Dw4 in RA was observed only in the control patient group without gold induced side effects. The frequencies of HLA-B7 and Dw2 were decreased in all patient groups compared with the control population. These results further support the view of the heterogeneity of RA as manifested by the unique HLA associations with resistance and susceptibility to gold induced side effects characterising different subgroups.
Today's Health Guide: A Manual of Health Information and Guidance for the American Family
Authors: Edward A. Piszczek
Journal: JAMA (1965)

In this era when health is a major topic of interest to everyone, and sensational health stories are written in many of our periodicals,<i>Today's Health Guide</i>can become the standard of information for the American home. The 200 specialists in the professional health fields have given a basic knowledge of medicine, based on a philosophy of health which should appeal to a wide public of young people as well as adults. The underlying philosophy assumes that Mr. and Mrs. Homemaker want a wholesome, integrated life. The book therefore appeals to the desire for enjoyment of home and its comforts and gracious manners, with safety and prevention of disease, and at the same time with a feet-on-the-ground awareness of costs and values. This<i>Guide</i>assumes a moral, responsible attitude in the reader, and the chapters on sex education, aging, and grief are designed to give practical help along with concise
Cardiac auscultation skills of physicians in training
Authors: W. Nadoolman
Journal: JAMA (1997)

To the Editor.  —While I strongly believe that cardiac auscultation is a skill worth honing, I disagree with the conclusions of Drs Mangione and Nieman1that a deficiency in the skills they tested might be a serious problem and that board-certification examinations for primary care specialties should include evaluation of these skills.  Any physician practicing rural medicine or who has visited Third World physicians knows the value of keen physical examination skills—especially auscultation. However, where most physicians in the United States practice, the rules are different. While this study examined the ability of residents to identify specific cardiac sounds, it did not show what proportion of those residents tested either did not notice any abnormality or did not generally recognize a pathologic sound. This ability to identify the presence of an abnormality is much more important that the ability to identify what the abnormality is. Even presuming the auscultation