tbuckley/cabot-search huggingface dataset:
Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma.
Authors: S H Lock, A B Kay, N C Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Patients with severe asthma who require long-term oral corticosteroid therapy are at risk of unwanted effects. Several immunosuppressive drugs have been assessed as corticosteroid-sparing agents in chronic asthma. We previously showed that cyclosporin A (CsA) administered for 12 wk improved lung function in corticosteroid-dependent patients. We have now investigated the corticosteroid-sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39 corticosteroid-dependent asthmatic patients were randomized to receive CsA (19 patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk. Attempts were then made by a physician ignorant of the trial therapy to reduce their prednisolone dosages at 14-d intervals, provided that a patient's asthma remained stable or improved. Three patients receiving CsA had to be withdrawn from the study before they completed 12 wk of therapy. The remaining 16 patients achieved a statistically significant reduction in median daily prednisolone dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in the patients taking placebo (p = 0.043). This reduction was most pronounced during the last 12 wk of active therapy. In addition, morning peak expiratory flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active-treatment group but not in the placebo group (p = 0.026 between groups). Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia, were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as compared with placebo, allowed a significant reduction in oral corticosteroid dosages in patients with severe asthma, and also improved lung function.
STROPHANTHUS; A CLINICAL STUDY.
Authors: REYNOLD W. WILCOX
Journal: JAMA (1897)

For many years I have been convinced that the very discordant reports made by competent observers were due to the fact that the source of strophanthus preparations was varied, for otherwise it would be impossible to believe that excellent effects could be obtained from one preparation while another would give rise to alarming or even dangerous symtoms. And further it is impossible to believe that the very large doses so frequently mentioned in literature could be safely administered, if the preparation had been made from an active crude drug. Last January, I read a paper before the Medical Society of the State of New York which was published in the May number of the<i>American Journal of the Medical Sciences</i>giving the results of a careful study of strophanthus kombé. In this paper I stated that I believed that kombé was not a variety of strophanthus hispidus, but a distinct
Precise plaster wedging: fracture-angle/cast-diameter ratio.
Authors: F. B. Thomas
Journal: BMJ (1965)

Retinoic acid–inducible gene-I (RIG-I)–like receptors (RLRs), including RIG-I (encoded by <i>Ddx58</i>) and melanoma differentiation–associated gene 5 (MDA5) (encoded by <i>Ifih1</i>), are crucial for initiating antiviral responses. Endogenous retroviral elements (ERVs) are transposable elements derived from exogenous retroviruses that are integrated into the genome. KRAB-associated protein 1 (KAP1) is a key epigenetic suppressor of ERVs that protects cells from detrimental genome instability. Increased ERV transcripts are sensed by RLRs and trigger innate immune signaling. However, whether KAP1 directly controls RLRs activity remains unclear. In this study, we show that KAP1 attenuates RNA viral infection–induced type I IFNs and facilitates viral replication by inhibiting RIG-I/MDA5 expression in primary peritoneal macrophages (PMs) of C57BL/6J mice. <i>Kap1</i> deficiency increases IFN-β expression and inhibits vesicular stomatitis virus replication in C57BL/6J mice in vivo. Mechanistically, KAP1 binds to the promoter regions of <i>Ddx58</i> and <i>Ifih1</i> and promotes the establishment of repressive histone marks in primary PMs of C57BL/6J mice. Concordantly, KAP1 suppresses the expression of RIG-I and MDA5 at the transcriptional level in primary PMs of C57BL/6J mice. Our results establish that KAP1 epigenetically suppresses host antiviral responses by directly targeting RIG-1 and MDA5, thus facilitating the immune escape of RNA viruses.
Computer Programme to Estimate Recurrence Risks for Multifactorial Familial Disease
Authors: C. Smith
Journal: BMJ (1972)

A computer programme to estimate recurrence risks for multifactorial genetic disease in affected families uses parameters on population prevalence and on heritability of liability of the condition and details of the family history. Information on affected and unaffected relatives (first-degree, second-degree, and third-degree) and on sex or age effects on prevalence and on heritability can all be accommodated by the programme.
Studies in Mental Deviations.
Authors: Kimball Young, S. D. Porteus
Journal: JAMA (1923)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Left Abdominal Uptake of Tc-99m MAG3 on Renal Imaging
Authors: RECIP BEKIS, HATICE DURAK, BANU ÖNER
Journal: Clinical Nuclear Medicine (1998)

A 57-year-old man who underwent cystectomy and ureterosigmoidostomy because of bladder cancer 5 years earlier showed increased uptake in the left side of the abdomen on Tc-99m MAG3 renal imaging, which simulated left ureteral reflux. An intravenous pyelogram showed passage of urine to the descending and sigmoid colon and reflux of the contrast material. The cause of the activity in the left side of the abdomen was radiopharmaceutical reflux to the descending colon.
Transforming growth factor beta: is it a downregulator of stem cell inhibition by macrophage inflammatory protein 1 alpha?
Authors: J Maltman, I B Pragnell, G J Graham
Journal: The Journal of Experimental Medicine (1993)

Transforming growth factor beta 1 (TGF-beta 1) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) have recently been identified as potent inhibitors of hemopoietic stem cell proliferation. From previous studies, these molecules appear to have similar functions in the control of stem cell proliferation. This study was designed to investigate the relationship, if any, between these two negative regulators in an attempt to elucidate possible distinctive roles for each within the hemopoietic system. We report here that both MIP-1 alpha and TGF-beta are capable of inhibiting the same stem cell population (colony-forming unit [CFU]-A/CFU-S) with similar potencies. We further show that TGF-beta potently inhibits MIP-1 alpha gene expression in bone marrow-derived macrophages, the presumed source of MIP-1 alpha in the bone marrow. This inhibition is not specific to MIP-1 alpha in that expression of MIP-1 beta, a related molecule that does not exhibit potent stem cell inhibitory properties, is inhibited in a similar manner. The inhibition of MIP-1 alpha gene expression is also seen as a reduction in MIP-1 alpha protein production, which markedly decreases 24 h after treating RAW 264.7 cells, a murine macrophage cell line, with TGF-beta. These in vitro results suggest that in the presence of active TGF-beta in vivo, and in the absence of upregulators of MIP-1 alpha transcription, very little MIP-1 alpha will be produced. To address how MIP-1 alpha's target cells, the stem cells, would respond to TGF-beta, and the consequently low levels of MIP-1 alpha produced, we analyzed the effect of TGF-beta on MIP-1 alpha receptor levels on FDCP-MIX cells, a murine stem cell line. We show that TGF-beta (100 pM) reversibly downregulates MIP-1 alpha receptor levels on these cells to a maximum of 50-70% after 24 h. This level of downregulation does not change upon increasing the concentration of TGF-beta or the length of exposure of the cells to TGF-beta. Scatchard analysis shows that TGF-beta downregulates MIP-1 alpha receptor numbers with no change in affinity of the remaining receptors. These results suggest that TGF-beta may be capable of interfering with MIP-1 alpha's role as a stem cell inhibitor. Indeed, they suggest that in the presence of active TGF-beta in vivo, MIP-1 alpha is at best a weak contributor to the overall physiological inhibition of stem cells.
Organisations not individual people are to blame, says Francis
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The widespread system failure at Mid Staffordshire NHS Trust makes the identification of individual people responsible a “futile exercise” because so many are accountable, said Robert Francis QC in his report into the public inquiry.1 Naming names would “risk perpetuating the illusion that removal of particular individuals is all that is necessary” and focusing on “blame will perpetuate the cycle of defensiveness, concealment, lessons not being identified, and further harm.” 

Instead, he said, “it is far more effective to learn rather than to punish.” His criticisms target the organisations involved and only at the level of trust are individual people singled out for personal inadequacies.

Mid Staffordshire NHS Trust comes in for the most criticism. Leaders there “failed to appreciate the enormity of what was happening, reacted too slowly, if at all, to some matters of concern of which they were aware, and downplayed the significance of others.” 

Martin Yeates , chief executive of the trust from September 2005 to March 2009, was described by Francis as “the most dangerous of leaders; one who was persuasive but ineffective.” Staff saw him as intimidating and unapproachable. He was intent on gaining foundation status for the trust and “was much better at giving an appearance of intent to address issues raised with him than he was at ensuring that the appropriate action was actually taken.” 

David Newsham , the trust’s finance director, was blind to …
Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation
Authors: Jeffrey K. Davies, Lee M. Nadler, Eva C. Guinan
Journal: Science Translational Medicine (2009)

Transplantation of donor bone marrow cells treated to be tolerant to patient antigens results in expansion of regulatory T cells that suppress immune responses that mediate graft-versus-host disease.
AN EVALUATION OF PROMAZINE HYDROCHLORIDE IN PSYCHIATRIC PRACTICE
Authors: STANLEY LESSE
Journal: American Journal of Psychiatry (1957)

1. Fifty psychiatric patients treated with promazine hydrochloride, a new phenothiazine derivative, are reviewed. 2. The drug was effective in one-third of the patients treated, but only in those who demonstrated marked anxiety. 3. Dosages and methods of administration are considered. 4. Adverse side-effects are mild and relatively uncommon as compared with those produced by chlorpromazine. 5. Promazine appears to be as effective as chlorpromazine as a tranquillizer in psychiatric practice and deserves further study.
The Vulnerable Atherosclerotic Plaque: Scope of the Literature
Authors: Alawi A Alsheikh-Ali, Georgios D Kitsios, Ethan M Balk, Joseph Lau, Stanley Ip
Journal: Annals of Internal Medicine (2010)

The scope of recent literature on the concept of “vulnerable plaque” was reviewed by examining 463 abstracts of primary and review articles identified through MEDLINE (2003 to April 2010). Proposed definition criteria of vulnerable plaque included active inflammation, a thin cap with a large lipid core, endothelial denudation, fissured cap, severe stenosis, or combinations of these findings. In 242 primary studies, histopathology, biomarkers, and imaging of carotid and coronary artery plaques were evaluated for features suggestive of vulnerability. Notably, 89% of these studies were cross-sectional in design and were exclusively conducted in patients with known cardiovascular disease. None of the imaging studies documented whether the identified lesions were responsible for cardiovascular events. Cross-sectional design precludes evaluation of the predictive utility of biomarkers. Because vulnerable plaque is not an established medical diagnosis, no studies have been done that explicitly evaluate the treatment of vulnerable plaques. Few studies examined potential systemic treatments (for example, statins) to modify vulnerability features. Large prospective studies in patients with and without previous cardiovascular events during long follow-up are required to validate this concept.
THE PSYCHOLOGY OF PROGRESSIVE DEAFNESS
Authors: GORDON BERRY
Journal: JAMA (1933)

Sir Joshua Reynolds, the painter, was hard of hearing. He made several portraits of himself with his ear trumpet. Of his deafness, Goldsmith wrote in his poem Retaliation:  To coxcombs averse, yet most skillfully steering:  When they judged without skill, he was still hard of hearing;  When they talked of their Raphaels, Corregios and stuff,  He shifted his trumpet, and only took snuff.  Here was a man who used his deafness as an escape. Fortunately, his life was so filled with purpose and accomplishment that he resorted to this escape more as a convenience than as a necessity. George Meredith accepted his infirmity in a more chastened fashion, for in 1908 he wrote to Mrs. Saleeby: And worse—the Sexton has filled one of my ears, and seems to be at work on the other; so that conversation is not smooth or pleasant for me, and can hardly be agreeable for
Tc-99m DMSA Renal Scan in Polyarteritis Nodosa With Bilateral Intraparenchymal Renal Artery Aneurysms
Authors: TARIK BASOGLU, TEKIN AKPOLAT, FEVZIYE CANBAZ, IREM BERNAY, SELAHATTIN ALBAYRAK, MURAT KILIC, MURAT DANACI
Journal: Clinical Nuclear Medicine (1999)

Polyarteritis nodosa is a multisystemic disorder that results in various signs and symptoms depending on the specific site of the blood vessel involved. The disease affects the kidneys in 70% of cases, sometimes with aneurysm formation, which can result in perirenal and intrarenal bleeding. The authors describe a patient with polyarteritis nodosa with multiple bilateral aneurysmal dilatations confirmed by angiography. The Tc-99m DMSA renal scan revealed bilateral intraparenchymal photopenic areas mimicking polycystic renal disease.
Retracted: Sustained Exposure to the Widely Used Herbicide Atrazine: Altered Function and Loss of Neurons in Brain Monoamine Systems
Authors: Veronica M. Rodriguez, Mona Thiruchelvam, Deborah A. Cory-Slechta
Journal: Environmental Health Perspectives (2005)

The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH+) and -negative (TH-) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks.
Wall Street and Clinical Trials
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2005)

Should physicians sell their expertise and knowledge about clinical research to Wall Street? In recent months, financial relationships between some physicians and the investment industry have come under scrutiny.13 Physicians have been paid to provide investors with general information about therapeutic problems, the mechanism of action of drugs, and the regulatory process. Some of these activities may ultimately have benefit to society. However, some physicians have also allegedly been paid to reveal specific confidential data.In August 2005, the Seattle Times reported that it had found “at least 26 cases in which doctors have leaked confidential and critical details . . .
Preload reserve: A determinant of clinical status in patients with left ventricular systolic dysfunction
Authors: Marvin A. Konstam, Marvin W. Kronenberg, James E. Udelson, Debra Kinan, Jeanne Metherall, Noreen Dolan, Tonya Edens, Donna Howe, Salim Yusuf, Marston Youngblood, Joan F. Barrtt
Journal: Journal of the American College of Cardiology (1991)
Calcification of the Vas Deferens
Authors: James L. Wilson, Joseph H. Marks
Journal: New England Journal of Medicine (1951)

IN 1942 Marks and Ham1 reported 9 cases of calcification of the vas deferens demonstrated by roentgenography in patients seen at the New England Deaconess Hospital. Since then an increasing number of patients in the practice of Dr. Elliott P. Joslin and his associates have been found with this rather unusual condition. It is, however, not a newly discovered condition, for calcium deposits within structures of the male genital tract have been recognized and reported at intervals for more than a century. All previously reported cases involving calcification in either the seminal vesicles or the vas deferens have been summarized . . .
TCT-831 Biodegradable-Polymer Drug-Eluting Stents versus Bare Metal Stents versus Durable-Polymer Drug-Eluting Stents : A Systematic Review and Bayesian Approach Network Meta-Analysis
Authors: Si-Hyuck Kang, Kyung Woo Park, Do-Yoon Kang, Woo-Hyun Lim, Kyung Taek Park, Jung-Kyu Han, Hyun-Jae Kang, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, David Kandzari, David Cohen, Seung-Sik Hwang, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2013)
Abstract 226: Chemopreventive potential of curcumin in prostate cancer
Authors: Hisamitsu Ide, Yan Lu, Raizo Yamaguchi, Satoru Muto, Shigeo Horie
Journal: Cancer Research (2014)

Abstract Curcumin contains multiple active compounds that have potent anti-inflammatory and anti-cancer properties. The present study investigates the molecular mechanisms of curcumin in the prostate cancer models. Treatment of LNCaP and 22Rv-1 prostate cancer cells with curcumin inhibited the cell proliferation. Genome-wide expression profiling, using oligonucleotide microarrays, revealed genes differentially expressed with curcumin treatment in prostate cancer cells. We identified one of the up-regulated genes, Aldo-Keto reductase 1C-2(AKR1C-2) which is involved in testosterone metabolism. Quantitative PCR confirmed significant up-regulation of AKR-1C2. The suppression of tumor growth is associated with the inhibition of expression of androgen receptor and androgen metabolism through AKR1C2 leading the induction of cell death by apoptosis. These results suggest that curcumin natural bioactive compounds could have potent anti-cancer property and the regulation of both androgen and androgen receptor. These pathways could exert pleiotrophic effects in prevention and treatment of prostate cancer. Citation Format: Hisamitsu Ide, Yan Lu, Raizo Yamaguchi, Satoru Muto, Shigeo Horie. Chemopreventive potential of curcumin in prostate 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 226. doi:10.1158/1538-7445.AM2014-226
Therapeutic nanomedicine based on dual-intelligent functionalized gold nanoparticles for cancer imaging and therapy in vivo
Authors: Wei-Hai Chen, Xiao-Ding Xu, Hui-Zhen Jia, Qi Lei, Guo-Feng Luo, Si-Xue Cheng, Ren-Xi Zhuo, Xian-Zheng Zhang
Journal: Biomaterials (2013)
Communicating risks through analogies
Authors: A. Edwards
Journal: BMJ (2003)

EDITOR–Articles in this theme issue have described approaches that try to enhance the communication of risk by developing communication skills, using decision aids, and simplifying the representation of information. But when clinicians talk about actual risks with individual patients they often use analogies. We asked visitors to bmj.com to tell us some of their analogies.1 Many of their responses addressed screening and chronic disease–perhaps because they are both particularly fraught with difficulty.

   ![][1] 

The value of illustrations was reinforced by Barth, a surgeon: he described how he gives patients a digital picture of their scan that includes a risk calculation. This, of course, also indicates the extent of disease.

Many of the examples from readers try to convey the size of a risk. People know, for example, that smoking is a risk but find it difficult to comprehend its magnitude. Mackay relates how Richard Peto (responsible for many of the big studies on the effects of smoking) tosses a coin and slaps it on the back of his hand to illustrate to his audience the (true) 50% risk of being killed from long term tobacco smoking. “It always produces a gasp of surprise.”

Clinicians may be faced with conveying very small risks. Markowicz relates how he sometimes engages in the following dialogue:

“Do you know …

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Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus
Authors: P Dreger, P Corradini, E Kimby, M Michallet, D Milligan, J Schetelig, W Wiktor-Jedrzejczak, D Niederwieser, M Hallek, E Montserrat
Journal: Leukemia (2006)
579 FAILURE OF LAMIVUDINE TO REVERSE HBV ASSOCIATED CHANGES IN ERK, AKT AND CELL CYCLE REGULATORY PROTEINS
Authors: R. Chin, L. Earnest-Silveira, B. Koeberlein, S. Franz, H. Zentgraf, S. Bowden, C.-T. Bock, J. Torresi
Journal: Journal of Hepatology (2008)