tbuckley/cabot-search huggingface dataset:
Quantitative assessment of lives lost due to delay in the regulation of occupational exposure to benzene.
Authors: W J Nicholson, P J Landrigan
Journal: Environmental Health Perspectives (1989)

Benzene exposure can cause leukemia, aplastic anemia, and possibly lymphoma. In 1978, on the basis of strong but incomplete data then available on the risk of benzene-induced leukemia, the U.S. Occupational Safety and Health Administration (OSHA) reduced the permissible occupational exposure standard for benzene from 10 ppm to 1 ppm. Shortly thereafter, the Fifth Circuit Court of Appeals stayed this ruling, and in 1980, the Supreme Court overturned the regulation, citing insufficient evidence of benefit. Thus, from 1978 until the standard was again lowered to 1 ppm in 1987, American workers were exposed to benzene at levels in excess of 1 ppm. An estimated 9600 were exposed to levels between 1 and 10 ppm, and an additional 370 were exposed at levels above 10 ppm. To assess the risk resulting from this delay in regulation, we have conducted an epidemiologic risk analysis. We merged data on numbers of persons (238,000) exposed to benzene in seven occupational categories with dose-response data from three epidemiologic studies. The range of risk in these studies indicates that 44 to 152 excess leukemia deaths will ultimately result from exposure to benzene at 10 ppm over a working lifetime (45 years) and that lower or briefer exposures will result in proportionately fewer deaths. On this basis, we calculated that between 30 and 490 excess leukemia deaths will ultimately result from occupational exposures to benzene greater than 1 ppm that occurred between 1978 and 1987. Deaths from aplastic anemia and lymphoma will likely add to this toll. These data confirm the risk of regulatory delay. They suggest that the courts, in reviewing public health regulations, must beware of facile cost-benefit arguments and be willing to accept strong evidence of health risk even when such evidence is incomplete.
The Apolipoprotein E E4 Allele and Sex-Specific Risk of Alzheimer's Disease
Authors: Elizabeth H. Corder, Ann M. Saunders, Warren J. Strittmatter, Don E. Schmechel, P. C. Gaskell, A. D. Roses, M. A. Pericak-Vance, G. W. Small, J. L. Haines
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Recently, Dr Payami and colleagues proposed a difference in Alzheimer's disease (AD) risk between men and women who have one copy of the apolipoprotein E (apo E) E4 allele.<sup>1</sup>Specifically, they suggested that men with no or one copy of<i>E4</i>(the<i>E2/E2, E2/E3, E3/E3, E2/E4</i>, and<i>E3/E4</i>genotypes) have a decreased risk of AD compared with men with two copies (the<i>E4/E4</i>genotype), while women with no copy of<i>E4</i>have a decreased risk of AD compared with those with one or two copies. Our studies do not suggest this sex-specific pattern of risk.<sup>2,3</sup>We find instead that risk of AD, both familial and sporadic (ie, no family history), increases with the number of<i>E4</i>alleles in men and women. The<i>E4</i>gene dose effect was initially found in 234 members of 42 AD families older than 60 years and can be seen when
An Auchendreich farewell
Authors: Colin Douglas
Journal: BMJ (2006)

Our newest consultant orthopod, a Mr Palchaudri, toys nervously with his haggis pakora. “I really wasn't sure about this evening. Lovely to be invited, though perhaps one should have declined. Dr MacEachern was exceptionally kind at my interview, but as a very new boy in school, so to speak . . .” A senior general practitioner pats his arm. “Not at all, laddie. It's a great way o' meeting folk, a farewell dinner.” 

It certainly …
Learning from Jacintha Saldanha's death
Authors: R. Madhok
Journal: BMJ (2013)

Royal nurse Jacintha Saldanha’s suicide highlights the immense pressure felt by healthcare workers (HCWs) when involved in serious incidents. Wu previously raised awareness of the “second victim phenomenon,” whereby HCWs experience serious functional impairment, with some leaving their profession and a few committing suicide.1

During its annual conference in November, the British Association of Physicians …
A former health minister looks back--and forward
Authors: J. Warden
Journal: BMJ (1987)

Eight years ago at this time, in 1979, the Labour government was on its last legs and the country was emerging from a winter of strikes that had brought picket lines outside hospitals.In a few weeks Mrs Thatcher would be Prime Minister, elected on a Conservative manifesto which said this of the NHS: "In our National Health Service standards are falling; there is a crisis of morale; too often patients' needs do not come first.It is not our intention to reduce spending on the health service; indeed we intend to make better use of what resources are available.So we will simplify and decentralise the service and cut back bureaucracy."The man she put in day to day charge of carrying through that task was Dr Gerard Vaughan, an MP since 1970, who became the first Minister for Health in a Thatcher administration, spanning its initial three years.Now Sir
Adjuvant Oophorectomy in the Treatment of Early-Stage<i>BRCA</i>Mutation–Positive Breast Cancer
Authors: Mary L. Disis
Journal: JAMA Oncology (2015)

TheUSPreventiveServicesTaskForce recently releasedasystematic review focused on the risk of breast and ovarian cancer in BRCA1 and BRCA2mutation carriers and the impact of genetic testing and counseling on the patient.1 A metaanalysis of 70 studiesdemonstrated that breast cancer prevalencewas46%to71%by 70 years of age for thosewith BRCA1orBRCA2mutationsandovariancancerprevalencewas 41%to46%forBRCA1and 17%to23%forBRCA2mutationcarriers. Patientswith germlinemutations in theBRCAgene family often choose prophylactic surgery, mastectomy and/or oophorectomy, to reducetheir riskofdevelopingbreastorovariancancer. In this issueofJAMAOncology,Metcalfeetal2 evaluated the impact of oophorectomy on overall survival of patientswhohave already received a diagnosis of breast cancer. Theparticipantswere676patientswith stage I or II breast cancer andBRCA1orBRCA2mutations. Smaller studies have suggested that oophorectomy after a breast cancer diagnosis results in reduced mortality in these individuals at extreme genetic risk. The cohort reported byMetcalfe et al2 did or did nothave their ovaries removedandwereobserved for 20years tomonitor for recurrence. The results provide a validation of the roleof oophorectomy inconveyingbothadisease-free and overall survival benefit for BRCA1mutation carriers. Oophorectomy after the primary diagnosis of breast cancer significantly reducedbreast cancer–specificmortality inwomenwith BRCA1mutations (HR, 0.38 [95% CI, 0.19-0.77]; P = .007) but not in BRCA2mutation carriers (HR, 0.57 [95% CI, 0.23-1.43]; P = .23). In the entire group, oophorectomy was particularly effective for survivalbenefit inwomenwithestrogenreceptor– negativebreast cancer (HR,0.07 [95%CI, 0.01-0.51];P = .009). Ofnote, themean timeelapsedbeforeoophorectomyafter the diagnosis of breast cancerwas 6.1 years. The hazard ratiowas further reduced,however, if the surgerywasperformedwithin 2 years of the breast cancer diagnosis. The data reported here are compelling and suggest that the potential of oophorectomy should become part of the treatment discussion at the time of diagnosis forBRCAmutation carrierswith early-stage breast cancers.
Study: Exercise May Match Medication in Reducing Mortality Associated With Cardiovascular Disease, Diabetes
Authors: Mike Mitka
Journal: JAMA (2013)

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
Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine
Authors: David E. L. Wilcken, Bridget Wilcken, Nicholas P. B. Dudman, Pauline A. Tyrrell
Journal: New England Journal of Medicine (1983)

The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine beta-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P less than 0.001) and an increase in total cysteine levels (P less than 0.001). Changes in plasma methionine concentrations were variable. Fasting levels of plasma amino acids became normal in two patients, and in six there was immediate clinical improvement. There were no unwanted effects. We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels.
How is maternal survival related to reproductive success?
Authors: X. T. Wang, Ralph Hertwig
Journal: Behavioral and Brain Sciences (1999)

Campbell's target article is a stimulating attempt to extend our understanding of sex differences in risk-taking behaviors. However, Campbell does not succeed in demonstrating that her account adds explanatory power to those (e.g., Daly &amp; Wilson 1994) previously proposed. In particular, little effort was made to explore the causal links between survival (staying alive) and reproduction.
The Journal and Publication in Other Languages and Countries
Authors: James H. Sammons
Journal: JAMA (1983)

DURING the years when the major scientific discoveries and advances originated in Europe, the flow of new medical knowledge ran clearly westward, casting the United States in the role—scientifically speaking—of a net importer. By the time of World War I, however, the current had begun to shift. Benefiting from the reforms in medical education, the availability of funds for new facilities, and a surge in biomedical research, American medicine embarked on a course that took it to worldwide preeminence after World War II. In that process,<i>The Journal of the American Medical Association</i>acquired a growing stature as a scientific publication, and, as the United States transformed itself into a prolific exporter of new medical knowledge,The Journalgrew into an increasingly important international vehicle, communicating Americans' advances in clinical medicine to physicians in other countries. To broaden its editorial reach,The Journalmade early excursions into publication in other
Can House Calls Survive?
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1997)

The number of house calls has been steadily declining for decades. The house call is now barely perceptible as a part of what American physicians do. Despite the aging of the population, Medicare's expenditures for house calls are now only about 0.2 percent of all reimbursements to physicians. A report in this issue of the Journal documents that although the house call has not yet vanished, it has become a rarity and is in danger of becoming extinct.1 From their analysis of a 5 percent sample of Medicare claims data, Meyer and Gibbons1 conclude that physicians made about 727,000 house . . .
Headpin: A Serpin with Endogenous and Exogenous Suppression of Angiogenesis
Authors: Thomas D. Shellenberger, Abhijit Mazumdar, Ying Henderson, Katrina Briggs, Mary Wang, Chandrani Chattopadhyay, Arumugam Jayakumar, Mitchell Frederick, Gary L. Clayman
Journal: Cancer Research (2005)

Abstract Headpin is a novel serine proteinase inhibitor (serpin) with constitutive mRNA expression in histologically normal oral mucosa but with lost or down-regulated expression in head and neck squamous cell carcinoma. Several serpin family members are similarly lost in multiple cancer types and hold tumor suppressor functions including the inhibition of angiogenesis. However, the functional significance for the loss of headpin expression in cancer is not known. Using immunohistochemical analysis of invasive squamous cell carcinoma and matched normal squamous mucosa of patient specimens, headpin expression was lost or down-regulated in the vast majority of tumor specimens. We investigated the functions of exogenous recombinant headpin and endogenously expressed headpin related to angiogenesis. In a rat corneal assay of neovascularization, recombinant headpin protein blocked in vivo angiogenesis mediated by interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF). In assays of cellular events in angiogenesis, headpin blocked the invasion, migration, and tube formation of endothelial cells. In light of our findings of nuclear subcellular localization of headpin, we investigated the expression and secretion of angiogenic factors and found reduced mRNA, protein, and promoter activities of IL-8 and VEGF. Finally, using a murine flank tumor model, headpin expression reduced growth and microvessel density in tumors derived from headpin-expressing UMSCC1 cells relative to those from vector control cells. These findings of nuclear regulatory functions of a serpin in the inhibition of angiogenesis bring new understanding to the cellular and molecular mechanisms of serpins. Therefore, this novel serpin targets diverse mechanisms against tumor angiogenesis on which to base therapeutic strategies. (Cancer Res 2005; 65(24): 11501-9)
Abstract 5463: ICG-001 induces cell cycle arrest to inhibit <i>in vitro</i> and <i>in vivo</i> pancreatic cancer growth
Authors: Michael D. Arensman, Anna R. Lay, David W. Dawson
Journal: Cancer Research (2014)

Abstract Wnt/β-catenin signaling is an important mediator of pancreatic ductal adenocarcinoma (PDAC) initiation and progression, warranting its exploration as a target of therapeutic intervention. Wnt modulators with acceptable in vivo bioavailability and efficacy as Wnt/β-catenin transcriptional inhibitors have only recently become available and include the small molecule compound ICG-001. Discovered in a library screen for inhibitors of Wnt/β-catenin reporter activity, ICG-001 interacts with cyclic AMP-response element-binding protein (CBP) to block its function as a co-transcriptional activator of β-catenin/TCF-mediated transcription. ICG-001 inhibits both in vitro and in vivo colon cancer growth and has demonstrated efficacy in a variety of other in vivo Wnt-driven disease models. Having recently shown subsets of PDAC tumors are dependent on increased levels of Wnt ligand-dependent autocrine signaling, we addressed the efficacy and function of ICG-001 on in vitro and in vivo PDAC growth. As a single agent, ICG-001 significantly inhibited anchorage-dependent and -independent growth of PDAC cell lines in vitro and increased survival in an orthotopic xenograft model of PDAC (HR=0.207, 95%CI: 0.079-0.543, P=0.001). ICG-001 also synergized with gemcitabine to inhibit anchorage-dependent growth in vitro and improve survival in the orthotopic xenograft model (HR= 0.074, 95%CI: 0.026, 0.212, P&amp;lt;0.001). Mechanistically, ICG-001 treatment did not significantly increase apoptosis in PDAC cell lines, but instead dramatically inhibited cell cycle progression via G1 arrest. Although ICG-001 inhibited β-catenin/TCF-mediated transcription as measured by luciferase-based reporter assays and endogenous target gene expression, these changes occurred at concentrations above those seen to induce G1 cell cycle arrest, suggesting ICG-001 growth inhibitory effects may be unrelated to its specific effects as a Wnt pathway inhibitor. Gene expression microarray analysis revealed ICG-001 treatment alters the expression of known Wnt target genes, as well as a much larger number of genes involved in DNA replication and cell cycle control. In conclusion, this study indicates ICG-001 is a promising small-molecule therapeutic for pancreatic adenocarcinoma and identifies numerous target genes whose altered expression provide insights into mechanism of action and candidate biomarkers for following therapeutic response. . Citation Format: Michael D. Arensman, Anna R. Lay, David W. Dawson. ICG-001 induces cell cycle arrest to inhibit in vitro and in vivo pancreatic cancer growth. [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 5463. doi:10.1158/1538-7445.AM2014-5463
Does Thinking Precede Feeling?-Reply
Authors: Aaron T. Beck
Journal: JAMA (1964)

I was interested in the letter from Dr. Harvey in response to the editorial, "Thinking Disorder in Neuroses." I agree that a multiplicity of<i>equally acceptable</i>alternatives reduces one's confidence in a given hypothesis. In the present instance, however, the conventional hypothesis of the primacy of affective over cognitive processes simply did not provide an adequate explanation for the data obtained in the clinical study. In fact, this concept appeared to be contradictory to the clinical findings. The complete formulation presented in my paper gradually evolved as the most parsimonious explanation of the findings in the course of testing a variety of alternatives to the standard concept of depression.<sup>1</sup> Two of the clinical phenomena may be cited here to illustrate this point. First, the patients frequently observed that they experienced a depressive-type thought prior to the emergence of the depressed feeling. Secondly, when they were able to correct a
When I Use A Word . . .: Got an ology?
Authors: J. Aronson
Journal: BMJ (1997)

There are about 400 different -ologies listed in Chambers Dictionary , from acar- to zym-, from o- to psychoneuroimmun-. The Greek word logos, from legein meaning to say or read, meant a word, either a word used to express a thought or, by extension, the thought itself. An apologos, literally something that comes from speaking, was a tale, and an apologia was a defence, which is what Plato's Apology was: an …
FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway
Authors: Erich Gulbins, Reid Bissonnette, Artin Mahboubi, Seamus Martin, Walter Nishloka, Thomas Brunner, Gottfried Baier, Gabriele Baler-Bltterlich, Cynthia Byrd, Florian Lang, Richard Kolesnick, Amnon Altman, Douglas Green
Journal: Immunity (1995)
Suicide gap among young adults in Scotland: population study
Authors: Paul Boyle, Daniel Exeter, Zhiqiang Feng, Robin Flowerdew
Journal: BMJ (2004)

The number of deaths from suicide increased among young adults between 1981-3 and 1991-3 but fell among older adults.1 2 The gap between such deaths in the most and least deprived areas of Scotland widened during this period, particularly for young adults. We examine changes in suicide rates between 1980-2 and 1999-2001 by area according to deprivation for young men and women to test whether the gap has widened further.

The general register office for Scotland provided data on deaths from suicide and undetermined causes for 1980-2 and 1999-2001 (international classification of diseases, ninth revision (ICD-9), codes E950-E959 E980-E989; ICD-10 X60-X84, Y10-Y34, Y87.0). These were aggregated from the postcodes of those who died to about 10 000 small areas (CATTs) which are consistent through time.3 The suicide rate declined significantly among older adults aged 3 45 years, from 22.99 per 100 000 (95% confidence interval 21.69 to 24.29) in 1980-2 to 16.73 (15.73 to 17.73) in 1999-2001, but increased significantly from 15.38 (14.38 to …
Demonstration of nitric oxide on asbestos and silicon carbide fibers with a new ultraviolet spectrophotometric assay.
Authors: P Leanderson, V Lagesson, C Tagesson
Journal: Environmental Health Perspectives (1997)

Nitric oxide (NO) has a number of important functions in biological systems and may play a role in the toxicity of mineral fibers. We investigated whether NO might be present on the surface of mineral fibers and if crocidolite could adsorb NO from NO gas or cigarette smoke. NO was determined with a new gas chromatography-ultraviolet spectrophotometric technique after thermal desorption from the fiber surface and injection in a gas flow cell. NO was found in different amounts on chrysotile B, crocidolite, amosite, and silicon carbide whiskers. There was a strong correlation between the amount of NO and the specific surface area of these fibers (r = 0.98). NO could not be demonstrated on rockwool fibers [man-made vitreous fiber(s) (MMVF)21 and MMVF22] or silicon nitride whiskers. NO on crocidolite, amosite, and silicon carbide whiskers was readily desorbed from the fibers at increased temperature, while NO on chrysotile B seemed to be more firmly adsorbed to the fiber and required a longer period of time to be desorbed. The amount of NO bound to crocidolite increased from 34 micrograms/g fiber to 85 and 474 micrograms/g after exposing the fibers to cigarette smoke and NO gas, respectively. These findings indicate that a) NO adsorbs to fiber surfaces, b) some fibers adsorb more NO than others, c) some fibers adsorb NO more strongly than others, and d) the amounts of NO on fibers may be increased after exposure of the fiber to cigarette smoke or other sources of NO. The biological significance of NO on mineral fibers remains to be investigated.