tbuckley/cabot-search huggingface dataset:
Molecular Pathogenesis of the Antiphospholipid Syndrome
Authors: Jacob H. Rand
Journal: Circulation Research (2002)

The antiphospholipid (aPL) syndrome is an acquired autoimmune disorder of unknown etiology in which patients present with thrombosis together with laboratory evidence for antibodies in blood that recognize anionic phospholipid-protein complexes. The main antigenic target for the aPL antibodies has been identified to be β 2 glycoprotein I (β 2 GPI), a phospholipid-binding protein. The high affinity of aPL antibody-β 2 GPI complex for phospholipid membranes seems to be a critical step in the mechanism of this disease. This review focuses on some of the major mechanisms that have been proposed to explain this disorder.
Pharmacological Stress Thallium Scintigraphy With 2-Cyclohexylmethylidenehydrazinoadenosine (WRC-0470)
Authors: David K. Glover, Mirta Ruiz, Joo Y. Yang, Bruce A. Koplan, Terry R. Allen, William H. Smith, Denny D. Watson, Richard J. Barrett, George A. Beller
Journal: Circulation (1996)

Background Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A 2A receptors, these side effects result from stimulation of the A 1 , A 2B , or A 3 adenosine receptors. We hypothesized that a selective adenosine A 2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor–mediated side effects. Methods and Results Infusions of a potent and selective A 2A adenosine receptor agonist, WRC-0470 (0.1 to 3 μg · kg −1 ·min −1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In the same dogs, adenosine (300 μg · kg −1 · min −1 for 4 minutes) produced coronary vasodilatation that was limited by significant hypotension. To determine the utility of WRC-0470 for pharmacological stress imaging, the hemodynamic responses to WRC-0470 (0.6 μg · kg −1 · min −1 for 10 minutes) and adenosine (250 μg · kg −1 · min −1 for 4 minutes) were compared in dogs with critical LAD stenoses. 201 Tl was injected at the peak WRC-0470 stress response. WRC-0470 increased LCx flow nearly fivefold but did not significantly lower mean arterial pressure. Anteroseptal defects were readily apparent in slice images from all dogs. The mean defect ratio (LAD/LCx) was 0.59±0.06. Conclusions The potent A 2A -selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.
Model for detection of membrane-associated antigens on epithelial cells (HLA-A, -B, -C alloantigens and pemphigus antigens)
Authors: B. J. VERMEER, S. H. KARDAUN, H. K. KOERTEN, F. H. J. CLAAS, J. S. PLOEM
Journal: British Journal of Dermatology (1985)

Incubation of skin explant culture with HLA-A, -B and -C alloantibodies results in detachment of cells at the periphery of the outgrowth. This detachment can be observed within 1 1/2 h, using the reflection contrast microscope. During the detachment of the epithelial cell, characteristic changes occur, such as disorganization of the filopodia and lifting up of the cell borders from the surface of the Petri dish. The same changes were seen using antibodies against pemphigus antigens.
IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.
Authors: S Gupta, A M Pablo, X c Jiang, N Wang, A R Tall, C Schindler
Journal: Journal of Clinical Investigation (1997)

The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional IFN-gamma, was documented in apoE 0 atheromata. Then, the apoE 0 mice were crossed with IFN-gamma receptor (IFNgammaR) 0 mice to generate apoE 0/IFNgammaR 0 mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts. These observations suggest that IFN-gamma promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata.
Behavioral and psychophysiological markers of disordered attention.
Authors: A F Mirsky
Journal: Environmental Health Perspectives (1987)

Behavioral and psychophysiological assays provide the most sensitive indication of whether a presumed neurotoxin has a deleterious effect on the nervous system. The effects of lead on the nervous system are strongly suggestive that this agent can produce disturbances in attention; moreover, there are clinical reports of such effects. The action of lead is also manifest in behaviors described as
Medical reports for compensation claims
Authors: R C Shepherd
Journal: BMJ (1983)

<h3>Background</h3> Pregnancy-related morbidity and mortality is much more prevalent among adolescents than adults. Adolescent pregnancy is therefore a significant public health problem. Most births to adolescents (95%) occur in resource-constrained countries. <h3>Objective</h3> The aim was to review the available evidence about the factors associated with adolescent pregnancy in low-income and lower middle-income countries. <h3>Methods</h3> The review used the PRISMA procedure of identification, screening and eligibility of publications. PubMed, OVID MEDLINE, SCOPUS and CINAHL plus were searched systematically for peer-reviewed English language papers published before December 2013. <h3>Findings</h3> In total, 2005 articles were identified and 12 met the inclusion criteria and were reviewed. Despite varied methods, there was substantial consistency in the findings. Limited education, low socioeconomic position, insufficient access to and non-use of contraception were consistently found to be risks for pregnancy among adolescents. There was some evidence that early marriage, living in a rural area, early sexual initiation, belonging to an ethnic and religious minority group also increased the risk of adolescent pregnancy. Higher education, access to income-generating work and family support were found to protect against adolescent pregnancy. <h3>Conclusions</h3> In resource-constrained countries, as in well-resourced countries, low socioeconomic position appears to increase the risk of pregnancy among adolescents. Additional risks specific to these contexts include cultural traditions such as early marriage and inaccurate beliefs about contraception. It is unlikely that strategies to reduce pregnancy among women aged less than 20 years will be effective unless these are addressed directly.
Serum eosinophil cationic protein in relation to bronchial asthma in a young Swedish population
Authors: E. Björnsson, C. Janson, L. Håkansson, I. Enander, P. Venge, G. Boman
Journal: Allergy (1994)

How are the serum concentration of eosinophil cationic protein (S‐ECP) and the blood eosinophil count (B‐Eos) related to symptoms of asthma, allergy, and bronchial hyperresponsiveness (BHR)? We measured S‐ECP, B‐Eos, and total and specific IgE in serum in blood samples from 699 randomly selected persons 20–44 years old. They also underwent a structured interview, spirometry, a methacholine provocation test, and skin prick tests as part of the European Community Respiratory Health Survey. B‐Eos and S‐ECP were found to be closely related to asthma symptom score ( P &lt; 0.001), total IgE ( P &lt; 0.001), and BHR ( P &lt; 0.001). On the basis of the results, the subjects were divided into four groups: healthy controls, patients with allergic rhinitis, patients with nonallergic asthma, and patients with allergic asthma. There were significant differences in both B‐Eos and S‐ECP among the groups ( P &lt; 0.001), the highest values being found in the allergic asthma group. B‐Eos and S‐ECP each had an additive value in predicting the occurrence of asthma. Among persons with high concentrations of both variables, asthma was eight times more common than in those with low concentrations. Allergy and BHR were also found to be independently related to B‐Eos and S‐ECP levels. Furthermore, both B‐Eos and S‐ECP showed good correlation to subjective and objective measures of asthma activity. We conclude that both B‐Eos and S‐ECP and their interrelationship may be of value in assessing the activity of asthma. However, their role in disease management was not established in this cross‐sectional study.
A memorable patient: Sometimes life isn't fair
Authors: W. Murdoch
Journal: BMJ (2000)

I was working as a locum house officer during my vocational training in a local teaching hospital. The senior house officer and I had split the work between us, he to the accident and emergency department and I had gone to the general practitioner admission unit. As always the flow of patients was relentless, but as the day wore on I became familiar with some of the friendly faces of the patients on the unit. Some were my patients, others were awaiting transfer.

After several hours of work, a charming elderly woman caught my gaze. “I've been watching you all day, rushing about. Have you had your lunch? I'm worried about you.” I was quite taken aback; after all she was the one who had been in hospital for a few days. She was the one who needed looking after. The day plodded on and each time I walked past her she would ask how I was feeling, making sure that I'd taken a break and had something to drink.

About 15 hours had passed without any break and I was writing up notes when there was a little commotion among the nurses, something about a patient fainting. The second-on house officer was called and he asked me for my advice about the patient.

The patient hadn't fainted; she'd had a stroke—and this was the woman who had been so kind to me. I spoke to her: “Do you remember who I am?” She stared at me blankly and asymmetrically, her dense rightsided weakness obvious to all.

After I gave my advice I returned to my notes and did something I hadn't done for a long time. I cried. Sometimes life just isn't fair.
Prazosin, Diuretics, and Glucose Intolerance
Authors: Herbert Ross
Journal: Annals of Internal Medicine (1993)

Letters15 October 1993Prazosin, Diuretics, and Glucose IntoleranceHerbert Ross, MD and Marvin Moser, MDHerbert Ross, MDSearch for more papers by this author and Marvin Moser, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-8-199310150-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Pandit and colleagues [1] are to be commended for a concise, comprehensive overview of drug-induced disorders of glucose metabolism. Certain assertions on the effects of diuretics deserve comment, however, because of their wide use in the treatment of patients with hypertension.The failure to dramatically reduce the risk for coronary artery disease in diuretic-based clinical trials may be more illusory than real. A recent meta-analysis of 17 treatment trials in middle-aged and elderly patients with hypertension [2] shows a 16% reduction in the risk for fatal and total coronary events (95% CI, 5% to 26% and 8% ...References1. Pandit MK, Barke J, Gustafson AB, Minocha A, Peiris AN. Drug-induced disorders of glucose tolerance. Ann Intern Med. 1993; 118: 529-39. Google Scholar2. Hebert P, Moser M, Mayer J, Glynn RJ, Hennekins CH. Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heart disease. Arch Intern Med. 1993; 153:578-81. Google Scholar3. Moser M, Ross H. The treatment of hypertension in diabetic patients. Diabetes Care. 1993; 16:542-7. Google Scholar4. Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, et al. Insulin resistance in essential hypertension. N Engl J Med. 1987; 317:350-7. Google Scholar5. Gurwitz JH, Bohn RL, Glynn RJ, Monane M, Mogun H, Avorn J. Antihypertensive drug therapy and the initiation of treatment for diabetes mellitus. Ann Intern Med. 1993; 118:273-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNeural dysregulation of peripheral insulin action and blood pressure by brain endoplasmic reticulum stress 15 October 1993Volume 119, Issue 8Page: 859-860KeywordsDiureticsDrugsElderlyGlucose intoleranceGlucose metabolismHyperglycemiaHypertensionInsulin resistanceMortalityStable coronary artery disease Issue Published: 15 October 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Comparison between Allergists and Non-allergists on Issues Related to Food-induced Anaphylaxis
Authors: M. Desjardins, A. Clarke, R. Alizadehfar, D. Grenier, H. Eisman, S. Carr, T. Vander Leek, L. Teperman, N. Higgins, L. Joseph, G. Shand, M. Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2012)
Clinical experience with a new specimen capturing bone marrow biopsy needle
Authors: Alec S. Goldenberg, James J. Tiesinga
Journal: American Journal of Hematology (2001)

Abstract The SNARECOIL ™ needle is a specimen capturing bone marrow biopsy needle that incorporates a tiny internal capturing coil. It was developed to minimize postinsertion needle manipulation and to facilitate specimen recovery. Forty‐four patients underwent 50 bone marrow biopsy procedures with the SNARECOIL needle for a variety of hematologic indications. Second and third procedures were done for follow‐up or staging. Each procedure retrieved a specimen with an average length of 2.1 cm. Fifty‐two percent of the specimens were ⩾2.0 cm in length. The majority of specimens demonstrated intact marrow architecture enabling a pathologic diagnosis in every case. Delicate cores of nontrabeculated marrow were recovered in three cases. The SNARECOIL bone marrow biopsy needle reliably retrieves intact bone marrow core specimens for pathologic interpretation. Am. J. Hematol. 68:189–193, 2001 © 2001 Wiley‐Liss, Inc.
Delivering interventions for depression by using the internet: randomised controlled trial
Authors: H. Christensen
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the efficacy of two internet interventions for community-dwelling individuals with symptoms of depression—a psychoeducation website offering information about depression and an interactive website offering cognitive behaviour therapy. <b>Design</b> Randomised controlled trial. <b>Setting</b> Internet users in the community, in Canberra, Australia. <b>Participants</b> 525 individuals with increased depressive symptoms recruited by survey and randomly allocated to a website offering information about depression (n = 166) or a cognitive behaviour therapy website (n = 182), or a control intervention using an attention placebo (n = 178). <b>Main outcome measures</b> Change in depression, dysfunctional thoughts; knowledge of medical, psychological, and lifestyle treatments; and knowledge of cognitive behaviour therapy. <b>Results</b> Intention to treat analyses indicated that information about depression and interventions that used cognitive behaviour therapy and were delivered via the internet were more effective than a credible control intervention in reducing symptoms of depression in a community sample. For the intervention that delivered cognitive behaviour therapy the reduction in score on the depression scale of the Center for Epidemiologic Studies was 3.2 (95% confidence interval 0.9 to 5.4). For the “depression literacy” site (BluePages), the reduction was 3.0 (95% confidence interval 0.6 to 5.2). Cognitive behaviour therapy (MoodGYM) reduced dysfunctional thinking and increased knowledge of cognitive behaviour therapy. Depression literacy (BluePages) significantly improved participants9 understanding of effective evidence based treatments for depression (P &lt; 0.05). <b>Conclusions</b> Both cognitive behaviour therapy and psychoeducation delivered via the internet are effective in reducing symptoms of depression.
Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection
Authors: Paula Licona-Limón, Jorge Henao-Mejia, Angela U. Temann, Nicola Gagliani, Ileana Licona-Limón, Harumichi Ishigame, Liming Hao, De’Broski R. Herbert, Richard A. Flavell
Journal: Immunity (2013)

Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4+ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection.
Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans
Authors: Liesbeth Van Wesenbeeck, Paul R. Odgren, Fraser P. Coxon, Annalisa Frattini, Pierre Moens, Bram Perdu, Carole A. MacKay, Els Van Hul, Jean-Pierre Timmermans, Filip Vanhoenacker, Ruben Jacobs, Barbara Peruzzi, Anna Teti, Miep H. Helfrich, Michael J. Rogers, Anna Villa, Wim Van Hul
Journal: Journal of Clinical Investigation (2007)

This study illustrates that Plekhm1 is an essential protein for bone resorption, as loss-of-function mutations were found to underlie the osteopetrotic phenotype of the incisors absent rat as well as an intermediate type of human osteopetrosis. Electron and confocal microscopic analysis demonstrated that monocytes from a patient homozygous for the mutation differentiated into osteoclasts normally, but when cultured on dentine discs, the osteoclasts failed to form ruffled borders and showed little evidence of bone resorption. The presence of both RUN and pleckstrin homology domains suggests that Plekhm1 may be linked to small GTPase signaling. We found that Plekhm1 colocalized with Rab7 to late endosomal/lysosomal vesicles in HEK293 and osteoclast-like cells, an effect that was dependent on the prenylation of Rab7. In conclusion, we believe PLEKHM1 to be a novel gene implicated in the development of osteopetrosis, with a putative critical function in vesicular transport in the osteoclast.
Makers of anticancer drugs are "profiteering," say 100 specialists from around the world
Authors: J. Laurance
Journal: BMJ (2013)

More than 100 specialists in chronic myeloid leukaemia from around the world, including nine from the United Kingdom, have warned that the high prices that drug companies charge for anticancer drugs are leaving patients without access to treatments that could save their lives.

The group said that the drug industry was guilty of “profiteering” and compared its actions to those of unethical speculators who raise the price of grain after a natural disaster.

“What determines a morally justifiable ‘just price’ for a cancer drug?” they asked in a paper published in Blood .1 “A reasonable drug …
P5-19-13: A Randomized Phase II Trial of First-Line Metastatic Breast Cancer (MBC) Patients: Sub-Set Analysis of Albumin-Bound Paclitaxel (ab-pac) Given Weekly at 150 mg/m2.
Authors: WJ Gradishar, D Krasnojon, S Cheporov, AN Makhson, GM Manikhas, A Clawson, P Bhar
Journal: Cancer Research (2011)

Abstract Background We previously reported the results of a phase II study evaluating the efficacy and safety of 3 different dosing regimens of ab-pac and docetaxel for the first-line treatment of MBC (Gradishar et al. J ClinOncol. 2009;27:3611). Here we report outcomes for a subset of patients (pts) during treatment with ab-pac at 150 mg/m2 weekly for the first 3 weeks of a 4-week schedule (qw 3/4). Methods: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms: arm A, ab-pac at 300 mg/m2 q3w; arm B, ab-pac at 100 mg/m2 qw 3/4; arm C, ab-pac at 150 mg/m2 qw 3/4; arm D, docetaxel at 100 mg/m2 q3w. A step-down statistical approach was used for pairwise comparisons of treatment groups. The trial was powered for antitumor activity and safety. Results: Treatment arm C produced the longest overall survival (OS) (33.8 months) with an 11.6-month longer median OS vs arm B (22.2 months, HR 0.575; P = .008) and a 7.2-month longer median OS vs arm D (26.6 months, HR 0.688; P not statistically significant). Median OS in arm A was 27.7 months. These OS data were consistent with previously published overall response rates (ORR) and progression-free survival (PFS). Forty-seven percent of pts in arm C required dose reduction due to toxicity, including 27% due to neutropenia (np), 15% due to sensory neuropathy (SN), 3% due to allergy/immunology, 1% due to febrile np, and 1% due to ulceration of the skin. The median OS for the subset of pts requiring DRs in arm C was comparable to pts not dose reduced: 35.2 and 31.8, respectively. Pts who were dose reduced in arm C received a median of 2 additional cycles of treatment compared with those without DRs: 10 (range 2 — 27) vs 8 (range 1 — 27). Investigator assessed ORR and PFS were numerically higher in pts dose reduced vs those not reduced. Baseline characteristics were similar between pts requiring DRs vs not. qw 3/4, first 3 out of 4 weeks; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status. aInvestigator assessed. bAll grade 3, no grade 4. Conclusion: Pts in the ab-pac 150 mg/m2qw 3/4 arm who were dose reduced achieved a similar OS compared to patients who were not dose reduced. No clear trends in baseline characteristics emerged to predict the requirement for dose reduction in the 150 mg/m2 ab-pac arm. The ab-pac 150 mg/m2 qw 3/4 dosing regimen provided a survival advantage in this phase II trial in first-line MBC and dose reductions could be used to manage toxicities and prolong treatment duration without compromising efficacy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-13.