tbuckley/cabot-search huggingface dataset:
Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study
Authors: S. A Everson, J. W Lynch, M. A Chesney, G. A Kaplan, D. E Goldberg, S. B Shade, R. D Cohen, R. Salonen, J. T Salonen
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. <b>Design:</b> Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. <b>Setting:</b> Eastern Finland. <b>Subjects:</b> 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. <b>Main outcome measures:</b> Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. <b>Results:</b> Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P&lt;0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138<i>v</i> 0.123 mm) and maximum (0.320 <i>v</i> 0.261 mm) intima-media thickness and plaque height (0.347 <i>v</i> 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. <b>Conclusions:</b> Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis. <h3>Key messages</h3> Psychological stress plays an important part in the illness and premature death associated with cardiovascular disease, but individual susceptibility to disease varies according to biological predispositions, personality, behaviour, and environmental exposures This study found that a demanding work environment in combination with a predisposition to exaggerated blood pressure reactivity to stress was significantly related to progression of carotid atherosclerosis over four years among employed middle aged men and was independent of known atherosclerotic risk factors These findings support the role of stress induced reactivity in human atherogenesis Future research needs to confirm these findings in other populations and to examine the influence of other risk factors and environments on the progression of disease
Community-Based Health Care for the Homeless
Authors: Rebecca Voelker
Journal: JAMA (1994)

IN THE SPRAWLING, urban-and-rural landscape of Arizona's Maricopa County, homeless people wouldn't get far on the $15 000 in local funds allocated this year for a program of integrated services, including medical and psychiatric care. "We are one of the fastest-growing counties in the country, but we are one of the poorest in funds for indigent health care," says Julie Marshall, administrator of the Maricopa County Health Care for the Homeless program, which serves Phoenix and surrounding areas. The bulk of the program's $1.1-million annual budget comes from the federal Health Care for the Homeless (HCH) program sponsored by the Health Resources and Services Administration (HRSA), Rockville, Md. Through the Division of Programs for Special Populations within its Bureau of Primary Care, the HRSA doles out $58 million annually to 120 community-based organizations working to provide integrated primary medical care, mental health services, and substance abuse treatment while establishing an
THE USE OF HISTAMINE IN THE TREATMENT OF SPECIFIC TYPES OF HEADACHES
Authors: BAYARD T. HORTON
Journal: JAMA (1941)

Headache is undoubtedly among the most frequent ills to which the human flesh is heir. It is a complaint which has been known to mankind since the dawn of antiquity. Few contributions, however, have marked medical progress in this field. It is not my purpose to review or consider the differential diagnostic features of the various types of headaches and head pains which have been recorded in the literature but rather to describe a new syndrome of vascular headache and to report the results of treatment with histamine. Other less well defined types of headaches have also been treated with histamine and the results will be reported. This new syndrome of vascular headache, which MacLean, Craig and I<sup>1</sup>tentatively called "erythromelalgia of the head" and which I shall call "histaminic cephalgia" hereafter, was first encountered and recognized at the Mayo Clinic in September 1937. At that time the syndrome
Prolonged Extracellular Signal-Regulated Kinase 1/2 Activation during Fibroblast Growth Factor 1- or Heregulin β1-Induced Antiestrogen-Resistant Growth of Breast Cancer Cells Is Resistant to Mitogen-Activated Protein/Extracellular Regulated Kinase Kinase Inhibitors
Authors: Jaideep V. Thottassery, Yanjie Sun, Louise Westbrook, Sarah S. Rentz, Marina Manuvakhova, Zhican Qu, Shanti Samuel, Ramanda Upshaw, Amanda Cunningham, Francis G. Kern
Journal: Cancer Research (2004)

Abstract Increased growth factor receptor signaling is implicated in antiestrogen-resistant breast tumors suggesting that abrogation of such signaling could restore or prolong sensitivity to antihormonal agents. Activation of the mitogen-activated protein/extracellular regulated kinase kinase (MEK)-extracellular regulated kinase (ERK)1/2 cascade is a common component of such pathways. We investigated the ability of the MEK activation inhibitor U0126 to block the increased growth of estrogen receptor-positive MCF-7 breast cancer cells caused by fibroblast growth factor 1 (FGF-1), heregulin β1 (HRGβ1), and epidermal growth factor (EGF) in the presence of the pure antiestrogen ICI 182780 (Faslodex; fulvestrant). We found that either FGF-1 or HRGβ1 but not EGF substantially reduced the inhibitory effects of U0126 on growth and ERK1/2 activation, including the combined inhibitory effects of U0126 and ICI 182780. FGF-1 and HRGβ1 also reduced the inhibition of ERK1/2 phosphorylation by the MEK inhibitors PD98059 and PD184161. Interestingly, a transiently transfected dominant-negative MEK1 completely abrogated activation of a coexpressed green fluorescent protein-ERK2 reporter by all three of the factors. Despite a short-lived activation of Ras and Raf-1 by all three of the growth factors, both FGF-1 and HRGβ1, unlike EGF, induced a prolonged activation of MEK and ERK1/2 in these cells. Thus, activation of FGF-1- and HRGβ1-specific signaling causes MEK-dependent prolonged activation of ERK1/2, which is incompletely susceptible to known MEK inhibitors. We also demonstrate that the cytosolic phospholipase A2 inhibitor arachidonyl trifluoro methyl ketone and the pan PKC inhibitor bisindolymaleimide abrogated U0126-resistant phosphorylation of ERK1/2 induced by HRGβ1 but not by FGF-1. Phosphorylation of ERK5 by all three of the factors was also resistant to U0126 suggesting that its activation is not sufficient to overturn growth inhibition due to diminished ERK1/2 activation. Therefore, therapy combining antiestrogens and MEK inhibitors may be ineffective in some antiestrogen-resistant estrogen receptor-positive breast cancers.
Long-term Outcomes and Costs of Ventricular Assist Devices Among Medicare Beneficiaries
Authors: Adrian F. Hernandez, Alisa M. Shea, Carmelo A. Milano, Joseph G. Rogers, Bradley G. Hammill, Christopher M. O’Connor, Kevin A. Schulman, Eric D. Peterson, Lesley H. Curtis
Journal: JAMA (2008)

<h3>Context</h3>In 2003, Medicare expanded coverage of ventricular assist devices as destination, or permanent, therapy for end-stage heart failure. Little is known about the long-term outcomes and costs associated with these devices.<h3>Objective</h3>To examine the acute and long-term outcomes of Medicare beneficiaries receiving ventricular assist devices alone or after open-heart surgery.<h3>Design, Setting, and Patients</h3>Analysis of inpatient claims from the Centers for Medicare &amp; Medicaid Services for the period 2000 through 2006. Patients were Medicare fee-for-service beneficiaries who received a ventricular assist device between February 2000 and June 2006 alone as primary therapy (primary device group; n = 1476) or after cardiotomy in the previous 30 days (postcardiotomy group; n = 1467).<h3>Main Outcome Measures</h3>Cumulative incidence of device replacement, device removal, heart transplantation, readmission, and death, accounting for censoring and competing risks. Patients were followed up for at least 6 months and factors independently associated with long-term survival were identified. Medicare payments were used to calculate total inpatient costs and costs per day outside the hospital.<h3>Results</h3>Overall 1-year survival was 51.6% (n = 669) in the primary device group and 30.8% (n = 424) in the postcardiotomy group. Among primary device patients, 815 (55.2%) were discharged alive with a device. Of those, 450 (55.6%) were readmitted within 6 months and 504 (73.2%) were alive at 1 year. Of the 493 (33.6%) postcardiotomy patients discharged alive with a device, 237 (48.3%) were readmitted within 6 months and 355 (76.6%) were alive at 1 year. Mean 1-year Medicare payments for inpatient care for patients in the 2000-2005 cohorts were $178 714 (SD, $142 549) in the primary device group and $111 769 (SD, $95 413) in the postcardiotomy group.<h3>Conclusions</h3>Among Medicare beneficiaries receiving a ventricular assist device, early mortality, morbidity, and costs remain high. Improving patient selection and reducing perioperative mortality are critical for improving overall outcomes.
Chromosomal studies in patients taking phenylbutazone.
Authors: A C Stevenson, J Bedford, A G Hill, H F Hill
Journal: Annals of the Rheumatic Diseases (1971)

C A ring chromosome t', no acentric fragments.They may have been too small to see.'Cu' cell.B Dicentric chromosome probably derived from two C group chromosomes t .One paired fragment 4 'Cu' cell.Note that there are 46 centromeres.D The chromosome marked t' is presumptively a chromo- some No. 2 but a pericentric inversion has occurred, i.e. it is a 'marker' chromosome.Note the more terminal position ofthe centromere than in its normal homologue.'Cs' cell marked.The picture shows only 43 chromo- somes.The three remaining chromosomes were displaced to a portion off the field.copyright.
Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn’s disease
Authors: M F Neurath, R Wanitschke, M Peters, F Krummenauer, K-H Meyer zum Büschenfelde, J F Schlaak
Journal: Gut (1999)

BACKGROUND Crohn’s disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn’s disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients. AIMS To compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients with chronic active Crohn’s disease. METHODS Seventy patients with chronic active Crohn’s disease (Crohn’s disease activity index (CDAI) greater than 150) were randomised for treatment with azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered according to a standard protocol. Disease activity was monitored by clinical scores after one, two, three, and six months. RESULTS Treatment of patients with moderately active (CDAI 150–300) Crohn’s disease with MMF/cortisone led to a significant reduction in clinical activity scores comparable to treatment with azathioprine/cortisone. Treatment of patients with highly active Crohn’s disease (CDAI greater than 300) with MMF/cortisone caused significant suppression of clinical activity earlier than azathioprine/cortisone treatment. Treatment with MMF/cortisone was associated with few adverse effects. CONCLUSION Treatment of chronic active Crohn’s disease with MMF plus cortisone appears to be effective and well tolerated and should be considered in patients allergic to azathioprine or in whom azathioprine has failed.
German parliament considers three bills on preimplantation genetic diagnosis
Authors: N. Stafford
Journal: BMJ (2011)

Three proposals for a new law on preimplantation genetic diagnosis have been introduced in Germany’s Bundestag, with one of the proposals calling for a ban and two others allowing it in certain circumstances. At present the law in Germany is unclear.

No German political party has taken a stand on the issue, instead allowing party members in the lower house to vote according to their conscience. Before the first readings of the three proposed bills on 14 April, 192 of the 622 members of the Bundestag had signed a motion supporting a complete ban.

A total of 215 …
Abstract B20: Thyroid transcription factor 1 is embedded in a microRNA network
Authors: David Mu
Journal: Clinical Cancer Research (2012)

Abstract Thyroid transcription factor 1 (TTF-1 or NKX2-1) is an essential fetal lung developmental factor which can be recurrently activated by gene amplification in adult lung cancer. These findings imply that TTF-1 is a gain-of-function oncogene selected for gene amplification due to an undefined biological pressure in lung cancer cells. However, recent data in the literature showed that TTF-1 suppressed lung cancer progression in a mouse model system and that the chromosomal area harboring the TTF-1 amplicon also underwent allelic DNA loss in lung cancer. Despite the complexity surrounding TTF-1 in lung cancer, characterization of TTF-1 gene regulatory mechanisms is warranted as lung adenocarcinomas frequently amplified for TTF-1 are the most common histologic type of lung cancer. We have discovered the first microRNA that directly regulates TTF-1 by interacting with its 3′-untranslated region. By gene expression profiling, we identified other putative targets of the microRNA. In line with the microRNA/target relationship, the expression patterns of the microRNA and TTF-1 were in an inverse relationship in human lung cancer. Exploration of human lung cancer genomics data uncovered that TTF-1 gene amplification was significantly associated with DNA copy number loss at one of the two genomic loci encoding the precursor RNA of mature microRNA. This implies the existence of genetic selection pressure to lose the repressive microRNA that would otherwise suppress amplified TTF-1. We detected a signaling loop between transforming growth factor beta (TGFβ and the microRNA and this loop reinforced suppression of TTF-1, consistent with the concept that TTF-1 possesses anti-epithelial mesenchymal transition (EMT) activity. Paradoxically, the microRNA also targets an EMT-promoting gene HMGA2 which is known to be repressed by TTF-1. Our data suggest that there is a group of microRNAs that are directly regulated by TTF-1, reinforcing our hypothesis that TTF-1 in embedded in a microRNA network. In summary, these data connect the lung transcriptional program to the microRNA network.
Lepra Cells in Synovial Fluid of a Patient with Erythema Nodosum Leprosum
Authors: James S. Louie, Jack R. Koransky, Arthur H. Cohen
Journal: New England Journal of Medicine (1973)

ACUTE arthritis may occur in association with erythema nodosum leprosum, an exacerbation of lepromatous leprosy characterized by fever, nodular skin eruptions and occasionally iritis, orchitis, neuritis, nephritis and lymphadenopathy.1 , 2 The pathogenesis of this arthritis is not clear. Though direct infiltration from overlying skin has been reported, usually no organisms are described either in the synovial fluid or in synovial tissue,3 , 4 and immunologic phenomena are postulated.5 Lepra organisms, free and within foamy macrophages (lepra cells), were found within the synovial fluid of the patient with erythema nodosum leprosum described below.Case ReportA 47-year-old Mexican native was hospitalized with a one-week . . .
Invasive aspergillosis in haematological malignancies: Clinical findings and management for intensive chemotherapy completion
Authors: Annamaria Nosari, Pierluigi Oreste, Roberto Cairoli, Marco Montillo, Gianpaolo Carrafiello, Alberto Astolfi, Giuliana Muti, Laura Marbello, Alessandra Tedeschi, Enrico Magliano, Enrica Morra
Journal: American Journal of Hematology (2001)

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.
Eculizumab for the Treatment of Dense-Deposit Disease
Authors: Marina Vivarelli, Andrea Pasini, Francesco Emma
Journal: New England Journal of Medicine (2012)

the experimental data showing that either C5 gene deletion or anti-C5 antibodies ameliorate kidney disease in complement factor H-deficient mice with disease that is similar to dense-deposit disease. 5 We are aware of two other patients with dense-deposit disease who have received eculizumab (Smith RJH: personal communication).One patient, with high sC5b-9 levels, showed a good clinical response, whereas the other, who had normal sC5b-9 levels, did not benefit.We speculate that following sequential blood sC5b-9 levels might help in predicting the response to eculizumab in dense-deposit disease.
Blood carboxyhaemoglobin, plasma thiocyanate, and cigarette consumption: implications for epidemiological studies in smokers.
Authors: C J Vesey, Y Saloojee, P V Cole, M A Russell
Journal: BMJ (1982)

Carboxyhaemoglobin and plasma thiocyanate concentrations were found to be significantly correlated with self-reported daily cigarette consumption in 360 smokers (r = 0.416 and 0.412 respectively; p less than 0.001). The extent to which inhalation patterns affected the intake of cigarette smoke constituents was determined from the partial correlation between carboxyhaemoglobin and plasma thiocyanate concentrations after the number of cigarettes smoke per day had been allowed for (r = 0.48). Thus 23% of the variation in carboxyhaemoglobin and thiocyanate concentrations was accounted for by the was a cigarette was smoked and a further 21% by the number smoked a day. Furthermore, the relation between carboxyhaemoglobin or plasma thiocyanate and daily cigarette consumption was not linear but reached an asymptote at consumption rates above 25 cigarettes a day. These results suggest that by itself daily cigarette consumption will not identify those smokers most at risk and will also underestimate and dose-response relationship between smoking and selected diseases.
The Value of Neisser's Stain in the Diagnosis of Diphtheria
Authors: R. M. Beaton, F. F. Caiger, W. C. C. Pakes
Journal: BMJ (1901)

Nucleated Red Cells.-.Nucleus almost black, with sh4rp outline extranuclear portion, grey.Blood Plate8.-Deepruby-red with spiky margins, frequently showing a pale-blue peripheral zone surrounding the red centre.Bacilli and Mficrococci.-Speakinggenerally, these stain evenly blue, but, by prolonging the period of staining, and subsequently decolorising with absolute alcohol, many interesting differences may be noted with different organisms by which structural details are brought out, not generally observed by other staining methods.
An Arterial Prosthesis of Heterologous Vascular Origin
Authors: Norman Rosenberg, John Henderson, Geoffrey H. Lord, James W. Bothwell
Journal: JAMA (1964)

The PREPARATION of an acceptable biological arterial graft is based on an understanding of the physical properties of the various tissue components of the arterial wall,<sup>1</sup>and on an analysis of the reasons for failure of arterial heterografts and homografts as vascular substitutes.<sup>2</sup> Arterial heterografts either are nonviable at the time of insertion or die shortly thereafter, and their ability to withstand pulsatile arterial pressures without disruption depends on the duration of their structural integrity and the extent to which they are invaded or enveloped by supporting host collagenous tissue. Such invasion is rendered difficult and often delayed by an inflammatory reaction to necrotic cellular and smooth muscle elements and by the prior need of the host to debride the graft of such reactive dead tissue. If the rate of infiltration or encasement by host connective tissue is rapid and early, the supported mummified heterograft may avoid rupture,