tbuckley/cabot-search huggingface dataset:
Evidence produced in evidence based medicine needs to be relevant
Authors: J. Barker
Journal: BMJ (2000)

EDITOR—It was encouraging to see all the research papers on patient involvement in healthcare decision making in the issue of the BMJ on 18 September devoted to patient partnership. Research findings in this area go some way to filling the enormous gap in evidence that has existed for too long. There are publications that offer guidance on how to involve patients and the public, but these give practical advice and do …
The role of the LDL receptor in apolipoprotein B secretion
Authors: Jaap Twisk, Donald L. Gillian-Daniel, Angie Tebon, Lin Wang, P. Hugh R. Barrett, Alan D. Attie
Journal: Journal of Clinical Investigation (2000)

Familial hypercholesterolemia is caused by mutations in the LDL receptor gene (Ldlr). Elevated plasma LDL levels result from slower LDL catabolism and a paradoxical lipoprotein overproduction. We explored the relationship between the presence of the LDL receptor and lipoprotein secretion in hepatocytes from both wild-type and LDL receptor–deficient mice. Ldlr–/– hepatocytes secreted apoB100 at a 3.5-fold higher rate than did wild-type hepatocytes. ApoB mRNA abundance, initial apoB synthetic rate, and abundance of the microsomal triglyceride transfer protein 97-kDa subunit did not differ between wild-type and Ldlr–/– cells. Pulse-chase analysis and multicompartmental modeling revealed that in wild-type hepatocytes, approximately 55% of newly synthesized apoB100 was degraded. However, in Ldlr–/– cells, less than 20% of apoB was degraded. In wild-type hepatocytes, approximately equal amounts of LDL receptor–dependent apoB100 degradation occured via reuptake and presecretory mechanisms. Adenovirus-mediated overexpression of the LDL receptor in Ldlr–/– cells resulted in degradation of approximately 90% of newly synthesized apoB100. These studies show that the LDL receptor alters the proportion of apoB that escapes co- or post-translational presecretory degradation and mediates the reuptake of newly secreted apoB-containing lipoprotein particles.
AIDS in the Nervous System
Authors: Lyn R. Frumkin
Journal: JAMA (1989)

The stated objective of the authors is to help physicians diagnose and manage the neurological complications of the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. The reader will find that this book achieves the authors' goal and more. The nervous system is one of the most frequently involved organ systems affected by HIV infection. Disorders of the brain, meninges, spinal cord, peripheral nerve, and muscle have all been associated with primary HIV infection or HIV-related secondary opportunistic infections and tumors. Such nervous system disorders have appeared in diverse clinical settings, ranging from the initial manifestations of HIV infection to a myriad of opportunistic infections in persons with AIDS. In addressing the frequency and diversity of neurological disease associated with HIV infection, the authors, one a clinical neurologist and the other a neuropathologist, have skillfully combined their expertise. The book's seven chapters are "The Character of AIDS," "Epidemiology,"
PORCINE CONTAGIOUS PLEUROPNEUMONIA
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1964)

An acute frequently rapidly fatal respiratory illness occurring as an epidemic disease in Argentine swine has been shown to have a bacterium of the genus Hemophilus as its causative agent. This organism, for which the name Hemophilus pleuropneumoniae is suggested, causes a singular, fulminating pleuropneumonia in experimental swine. The very marked effectiveness of H. pleuropneumoniae as a respiratory pathogen contrasts strikingly with the relatively mild pathogenicity of the well known swine Hemophilus, H. influenzae suis, which, in concert with a virus, causes a less highly fatal respiratory ailment, swine influenza. Porcine contagious pleuropneumonia (PCP) is contagious under experimental conditions. In the pathogenesis of the disease, histopathological studies of early cases suggest that the lymphatics of the lung and pleura may be primarily involved and that the pneumonia and pleuritis then proceed from these initial sites of reaction.
S137 The natural history of IPF in patients eligible for clinical trials vs patients not eligible
Authors: P. Macfarlane, Z. H. Hoo, R. L. S. Hammersley, C. M. McErlean, S. Anpalakhan, G. A. Stewart, W. A. Wallace, J. T. Murchison, A. J. Simpson, N. Hirani
Journal: Thorax (2011)

Recruitment to clinical trials is a key objective in the management of IPF. For phase 3 trials, the inclusion and exclusion criteria are stringent. It is not known if the natural history of IPF in patients eligible for clinical trials differs from that in non-eligible patients. <h3>Aims</h3> To determine the natural history of IPF in patients eligible for phase 3 trials vs those not eligible <h3>Methods</h3> Since 1/1/2002, all patients with IPF presenting to the Edinburgh Royal Infirmary lung fibrosis clinic have been recruited prospectively to a database. The diagnosis of IPF was made by multi-disciplinary consensus after integration of clinical, HRCT and pathological data, based on ATS/ERS criteria. Management and follow-up was by standardised protocol. IPF-directed therapy, including corticosteroids, azathioprine and anti-oxidants, was considered only in advanced disease, acute exacerbation or in those who exhibited pre-specified fall in lung function. Patients were grouped into those eligible for phase 3 clinical trials and those ineligible, based on the major inclusion/exclusion criteria used in a recently published study (CAPACITY, Lancet 2011 377;1760–1769). <h3>Results</h3> Of 199 consecutively presenting patients with IPF, 61 (31%) were eligible for a phase 3 trial. The proportion of males in the eligible and ineligible groups was similar, but eligible patients were younger (68 vs 74 yrs, p&lt;0.0001), comprised fewer individuals with &gt;20 pack/year smoking history (50% vs 65%, p=0.057), had lower % predicted VC (82.6 vs 95.8 p=0.0003) and higher % predicted TLCO (56.6 vs 51.9, p=0.07). Eligible patients had less % emphysema on HRCT scoring compared to non-eligible patients (0.74% vs 6% p&lt;0.0001). The 3yr-survival of eligible and ineligible patients were not significantly different (Abstract S137 figure 1 74% vs 63%, p=0.3). Event-free survival, defined as time to death <i>or</i> =10% fall in VC <i>or</i> =15% fall in TLCO <i>or</i> acute exacerbation of IPF <i>or</i> hospital admission with respiratory illness, was not significantly different between eligible and ineligible groups, such that in both groups 40% and 60% experienced a progression-defining event by 12 -and 24-months respectively. <h3>Conclusions</h3> Trial ineligible patients are demographically and phenotypically different from eligible patients, but have identical mortality and progression-free survival. These data have important implications for translation of trial data to clinical practice and for IPF trial design.
Cross-species bone marrow transplantation: evidence for tolerance induction, stem cell engraftment, and maturation of T lymphocytes in a xenogeneic stromal environment (rat----mouse).
Authors: S T Ildstad, S M Wren, S S Boggs, M L Hronakes, F Vecchini, M R Van den Brink
Journal: The Journal of Experimental Medicine (1991)

Transplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344----B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat. Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific; MHC disparate third party mouse and rat skin grafts were promptly rejected while donor-specific F344 grafts were significantly prolonged (MST greater than 130 days). Multi-lineage rat stem cell-derived progeny including lymphoid cells (T- and B-lymphocytes), myeloid cells, erythrocytes, platelets, and natural killer (NK) cells were present in the fully xenogenic chimeras up to 7 months after bone marrow transplantation. Immature rat T-lymphocytes matured and acquired the alpha/beta T-cell receptor in the thymus of chimeras in a pattern similar to normal rat controls, suggesting that immature T-lymphocytes of rat origin could interact with the murine xenogeneic thymic stroma to undergo normal maturation and differentiation. This model may be useful to study the mechanisms responsible for the induction and maintenance of donor-specific transplantation tolerance across a species barrier.
Surgical Management of Synchronous Colorectal Liver Metastases: Simultaneous Versus Staged Resections I.B. Shchepotin, O.O. Kolesnik, A.V. Lukashenko, A.A. Burlaka, V.V. Primak Department of Abdominal Surgery, National Cancer Institute, Kyiv, Ukrain
Authors: Shchepotin Ighor, Kolesnik Olena, Lukashenko Andrii, Burlaka Anton, Primak Viktor
Journal: Annals of Oncology (2014)
Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy
Authors: Michael Vouche, Ali Habib, Thomas J. Ward, Edward Kim, Laura Kulik, Daniel Ganger, Mary Mulcahy, Talia Baker, Michael Abecassis, Kent T. Sato, Juan-Carlos Caicedo, Jonathan Fryer, Ryan Hickey, Elias Hohlastos, Robert J. Lewandowski, Riad Salem
Journal: Hepatology (2014)

Resection and radiofrequency ablation (RFA) are treatment options for hepatocellular carcinoma (HCC) <3 cm; there is interest in expanding the role of ablation to 3-5 cm. RFA is considered high-risk when the lesion is in close proximity to critical structures. Combining microcatheter technology and the localized emission properties of Y90, highly selective radioembolization is a possible alternative to RFA in such cases. We assessed the efficacy (response, radiology-pathology correlation, survival) of radiation segmentectomy in solitary HCC not amenable to RFA or resection. Patients with treatment-naïve, unresectable, solitary HCC ≤ 5 cm not amenable to RFA were included in this multicenter study. Administered dose, response rate, time-to-progression (modified Response Evaluation Criteria in Solid Tumors [mRECIST]), radiology-pathology correlation and long-term survival were assessed. In all, 102 patients were included in this study. mRECIST complete response (CR), partial response (PR), and stable disease (SD) were 47/99 (47%), 39/99 (39%), and 12/99 (12%), respectively. Median time-to-disease-progression was 33.1 months. In all, 33/102 (32%) patients were transplanted with a median (interquartile range [IQR]) time-to-transplantation of 6.3 months (3.6-9.7). Pathology revealed 100% and 50-99% necrosis in 17/33 (52%) and 16/33 (48%), respectively. Median overall survival was 53.4 months. Univariate analysis demonstrated a survival benefit for Eastern Cooperative Oncology Group (ECOG) 0 patients. In the multivariate model, age <65, ECOG 0, and Child-Pugh A were characteristics associated with longer survival.Radiation segmentectomy is an effective technique with a favorable risk profile and radiology-pathology outcomes for solitary HCC ≤ 5 cm. This approach may allow for treatment of HCC in difficult locations. Since RFA and resection are not options given tumor location, there appears to be a strong rationale for this technique as second choice.
Abdominal Obesity and Breast Cancer Risk
Authors: David V. Schapira
Journal: Annals of Internal Medicine (1990)

To determine if body fat distribution affects breast cancer risk.Prospective case-control study.The anthropometric measurements of 216 consecutively and newly diagnosed women with invasive carcinoma of the breast were compared with those of 432 age-matched controls. The anthropometric measurements taken were abdomen, thigh, suprailiac, biceps, triceps, subscapular, and midaxillary skinfolds; waist and hip circumference; and weight and height. Women between 25 and 83 years of age were included in the study.Patients with breast cancer had a significantly greater waist:hip circumference ratio than controls (P less than 0.001) and a significantly greater suprailiac:thigh skinfold ratio (P less than 0.001). The relative risk for breast cancer increased with increasing waist:hip circumference ratio (less than 0.73 = 1.00; 0.73 to 76 = 1.90; 0.77 to 0.80 = 2.83; greater than 0.80 = 6.46) and with suprailiac:thigh skinfold ratio (less than 0.42 = 1.00; 0.42 to 0.56 = 1.85; 0.57 to 0.71 = 2.25; greater than 0.71 = 5.85). At other sites of upper body obesity, such as the biceps and triceps, skinfolds were significantly greater in patients with breast cancer.Although obese women are at slightly higher risk for developing breast cancer, women with android obesity are a segment of obese women who appear to be at a significantly higher risk for developing breast cancer.
Malignant tumors of the liver and lungs in an area with a PVC industry.
Authors: M Saric, Z Kulcar, M Zorica, I Gelić
Journal: Environmental Health Perspectives (1976)

The incidence of malignant tumors of the lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-yr period in a city with several factories, including a PVC industry. Prior to the study two cases of angio-sarcoma of the liver were diagnosed in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the period of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the same as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angiosarcoma is associated with exposure to vinyl chloride.
Lichen Sclerosus With Vaginal Involvement
Authors: Kate Zendell, Libby Edwards
Journal: JAMA Dermatology (2013)

Lichen sclerosus (LS) is an uncommon chronic inflammatory disease that most commonly affects anogenital skin of postmenopausal women. It typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring. Rarely, LS has been observed to affect mucosal tissues in the mouth and the penile urethra. It is generally taught that LS does not affect the vagina, unlike lichen planus. To our knowledge, only one case report of LS with vaginal involvement exists in the literature.Two cases of severe vulvar LS with vaginal involvement are reported. Both cases exhibited characteristic features of LS on vaginal biopsy, and both patients were followed up clinically without further treatment of the vagina.Vaginal LS may be more common than previously thought and may be underdiagnosed. Patients with more severe disease or with significant vaginal atrophy may be more likely to have involvement of the vagina. In addition, patients with pelvic organ laxity may be at increased risk if their vaginal walls are chronically exposed because of prolapse. Physicians managing patients with vulvar LS should be aware of the possibility of vaginal involvement so that vaginal lesions may be diagnosed and followed up appropriately.
Cushing's syndrome without excess cortisol
Authors: D R Woods, C S Arun, P A Corris, P Perros
Journal: BMJ (2006)

In patients taking inhaled corticosteroids the biochemical detection of a suppressed hypothalamicpituitary-adrenal axis is well documented.1 2 Fluticasone propionate is the most potent inhaled glucocorticoid,3 4 and adrenocortical insufficiency has been reported in 12% of patients on a high dose of inhaled fluticasone.1 5 The incidence of addisonian crises is lower, but crises may occur during intercurrent illness or after dose reduction or withdrawal.5

Itraconazole is an orally active antifungal triazole that inhibits cytochrome P450 dependent CYP3A4 and consequently decreases the clearance of synthetic glucocorticoids.6 The combination of long term inhaled steroid with oral itraconazole may exacerbate suppression of the hypothalamic-pituitary-adrenal axis. In a cohort of 25 patients with cystic fibrosis, six were reported to have adrenal insufficiency.7 However, overt Cushing's syndrome as a result of this drug combination is less well understood. We report the rapid development and the resolution of iatrogenic Cushing's syndrome in a patient taking itraconazole for six weeks in addition to inhaled fluticasone.

A 55 year old man with bronchiectasis and asthma developed an exacerbation of allergic bronchopulmonary aspergillosis. His regular medication included long acting and short acting inhaled β2 agonists (formoterol and terbutaline respectively), the leucotriene receptor antagonist montelukast (10 mg once daily), alendronate (75 mg weekly), amitriptyline (50 mg daily at night), and codeine phosphate (60 mg as required). In addition, he had been taking inhaled fluticasone (1-1.5 mg twice daily) for over two years with …
Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cells
Authors: Lori Rink, Artur Slupianek, Tomasz Stoklosa, Margaret Nieborowska-Skorska, Katarzyna Urbanska, Ilona Seferynska, Krzysztof Reiss, Tomasz Skorski
Journal: Blood (2007)
RIGHT TO LEFT SHUNTING THROUGH PATENT FORAMEN OVALE DURING SIMULATED EPISODES OF OBSTRUCTIVE SLEEP APNEA
Authors: Tomas Konecny, Amber D. Khann, Jan Novak, Abdi A. Jama, Jan Bukartyk, Marek Orban, Tomas Kara, Barry A. Borlaug, Virend K. Somers, Guy Reeder
Journal: Journal of the American College of Cardiology (2012)
Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction
Authors: Emanuela Marcenaro, Claudia Cantoni, Silvia Pesce, Carola Prato, Daniela Pende, Sophie Agaugué, Lorenzo Moretta, Alessandro Moretta
Journal: Blood (2009)
Enzyme‐Linked Immunosorbent Assay for Determination of Major Excrement Allergens of House Dust Mite Species <i>D. pteronyssinus, D. farinae</i> and <i>D. microceras</i>
Authors: P. Lind
Journal: Allergy (1986)

Species‐specific enzyme‐linked immunosorbent assays (ELISA) for major excrement allergens (Dp42, Df6 and Dm6) of D. pteronyssinus, D. farinae and D. microceras in house dust were established, using immunoabsorbed, monospecific rabbit antibodies, coupled to horse radish peroxidase. The limit of detection was 13, 4 and 38 ng/ml, respectively. The coefficient of variation for the entire procedure, including dust sieving (212 μm) and extraction was 5–16% for allergen levels above 1000 ng/g dust. Allergen concentration by ELISA correlated well with the number of mite bodies identified and counted by microscopy in 31 dusts (r = 0.88, 0.86 and 0.82 for combined Dermatophagoides sp., D pteronyssinus and D farinae group, resp.) Dermatophagoides allergen was recorded in 21/22 mattress dusts (median: 26000 ng/g; maximum: 290,000 ng/g). D. pteronyssinus allergen occurred in largest amounts (median 7500 ng/g) followed by D. microceras (median 650 ng/g) and D. farinae (median 240 ng/g).
The co‐seasonal application of anti‐IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children
Authors: C. Rolinck‐Werninghaus, E. Hamelmann, T. Keil, M. Kulig, K. Koetz, B. Gerstner, J. Kuehr, S. Zielen, U. Schauer, W. Kamin, A. Von Berg, J. Hammermann, B. Weinkauf, G. Weidinger, S. Stenglein, U. Wahn
Journal: Allergy (2004)

Background: Specific immunotherapy (SIT) and treatment with anti‐immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. Objective: A randomized, double‐blind, placebo‐controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti‐IgE (Omalizumab) in reducing symptom severity and rescue medication use. Methods: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6–17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti‐IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. Results: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti‐IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti‐IgE showed superior efficacy on symptom severity compared with anti‐IgE alone. Conclusions: Co‐seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.
Management of "Bad Trips" in an Evolving Drug Scene
Authors: Robert L. Taylor
Journal: JAMA (1970)

"Bad trips" arise out of an increasingly complex drug scene. Rational therapy must consider completely, social, psychological and physiological factors. Complexity results from the development of new drugs, indiscriminate ingestion, contamination, and adulteration. Drug-induced psychological changes occasionally lead to fatal behavior. Bad trips from anticholinergic compounds may be seriously worsened by phenothiazine treatment. Protection of the patient from dangerous behavior is fundamental to treatment. A clear history is invaluable but should be augmented by physical and mental examinations. Treatment begins with establishment of verbal contact without the use of tranquilizers, if possible. Reassurance and reality defining are often sufficient. With severe ego disruption, medication in combination with verbal interaction may be required. Administration of phenothiazines or sedatives helps to reestablish the observing ego with rapid dissolution of perceptual distortion and reestablishment of the premorbid ego functioning in most cases. Optimal treatment includes a follow-up visit.
Survival factors, intracellular signal transduction, and the activation of endonucleases in apoptosis
Authors: Alan Eastman
Journal: Seminars in Cancer Biology (1995)

Cell survival is normally mediated by factors in the extracellular environment, whereas genetic changes that constitutively activate intracellular survival pathways often occur in cancer. It is suggested that a Ras/Raf/MAP kinase-dependent pathway is critical for cell survival. Apoptosis results from loss of these survival factors or deregulation of survival pathways. If protein kinase cascades mediate survival, then it is likely that phosphatases mediate apoptosis. Potential targets for dephosphorylation include regulators of ion homeostasis as these have been implicated in the regulation of endonucleases associated with apoptosis. Survival factors also modulate anticancer drug response and understanding these pathways may improve therapy.