tbuckley/cabot-search huggingface dataset:
Quebec introduces more private care into its health system
Authors: David Spurgeon
Journal: BMJ (2006)

The Canadian province of Quebec plans to reshape its public healthcare system to include more private medical care, in a move that has provoked strong support and virulent criticism across Canada. Quebec's premier, Jean Charest, has promised that hip and knee replacements and cataract surgery will be done within six months of diagnosis, even if it means that the provincial government has to pay for them to be done at private clinics. And if government funded hospitals extend waiting times to nine months, Quebec will pay to send patients outside the province, including to the United States.

Quebec's initiative is likely to be followed elsewhere. Already the provinces of Alberta and British Columbia are planning to increase private intervention in the public healthcare system. Also, the …
Gammopathy and Spherocytosis
Authors: KENNETH D. LEMPERT
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 July 1978Gammopathy and SpherocytosisKENNETH D. LEMPERT, M.D.KENNETH D. LEMPERT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-1-145_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the report of a possible pathogenic relation between monoclonal gammopathy and hereditary spherocytosis (Ann Intern Med 88:45-46, 1978). The proposal by Schafer and associates that chronic stimulation of the reticuloendothelial system might foster the neoplastic transformation of immunocytes is intriguing. I too have seen a patient with both disorders.An 80-year-old woman was referred to the University of Wisconsin Hospitals for the evaluation of anemia of 4 years' duration. Iron supplementation had not improved her condition. She had not had a splenectomy. Her hematocrit was 20% and reticulocyte count 6.1%. Peripheral smear showed... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: KENNETH D. LEMPERT, M.D.Affiliations: University of Wisconsin Madison, WI 53706 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1978Volume 89, Issue 1Page: 145-146KeywordsAnemiaHematocritPathogensReticulocytesSplenectomy ePublished: 1 December 2008 Issue Published: 1 July 1978 PDF downloadLoading ...
STUDIES ON THE CHEMOTHERAPY OF THE HUMAN MALARIAS. X. THE SUPPRESSIVE ANTIMALARIAL EFFECT OF PALUDRINE 12
Authors: David P. Earle, Robert W. Berliner, John V. Taggart, Charles G. Zubrod, William J. Welch, Frederick S. Bigelow, Thomas J. Kennedy, James A. Shannon
Journal: Journal of Clinical Investigation (1948)
Effect of Radiofrequency Catheter Ablation on Health-Related Quality of Life and Activities of Daily Living in Patients With Recurrent Arrhythmias
Authors: Rosemary S. Bubien, Susan M. Knotts-Dolson, Vance J. Plumb, G. Neal Kay
Journal: Circulation (1996)

Although radiofrequency catheter ablation can be used to effectively treat a variety of arrhythmias, the effects of this procedure on health-related quality of life have not been systematically studied.The SF-36 (a measure of general health status), the Symptom Checklist-Frequency and Severity Scale (an instrument specific for cardiac arrhythmias), and an Activities of Daily Living questionnaire were used to assess quality of life in 161 patients before radiofrequency catheter ablation. These same instruments were used to measure quality of life 1 and 6 months after ablation with complete data in 159 of the original 161 patients. Before ablation, SF-36 scores of the study population were low compared with the US normative data base reflecting significant impairment in physical functioning and well-being. The lowest scores were reported by patients with atrial fibrillation and atrial flutter. Catheter ablation was associated with significant improvement in quality of life that was sustained over the 6 months after ablation. Improvements were measured in both the generic SF-36 health status questionnaire and the disease-specific Symptom Checklist-Frequency and Severity Scale. Catheter ablation was followed by improved performance of activities of daily living and a marked decrease in the number of visits to physicians and emergency rooms in the 6 months after ablation compared with the 6 months before ablation.Radiofrequency catheter ablation improves the health-related quality of life for patients with a variety of cardiac arrhythmias.
Sibutramine — Another Flawed Diet Pill
Authors: Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2010)

On September 15, 2010, an advisory committee of the Food and Drug Administration (FDA) will meet to determine the fate of sibutramine, an appetite-suppressant drug that carries the brand name Meridia. This reassessment of sibutramine by the FDA is based on new information derived from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, the results of which are published in this issue of the Journal.1 The FDA advisory committee will be asked to recommend whether the drug should be subject to new regulatory action.Sibutramine, an agent that blocks the reuptake of serotonin and norepinephrine by presynaptic nerve terminals and thereby . . .
Sagopilone crosses the blood–brain barrier in vivo to inhibit brain tumor growth and metastases
Authors: Jens Hoffmann, Iduna Fichtner, Margit Lemm, Philip Lienau, Holger Hess-Stumpp, Andrea Rotgeri, Birte Hofmann, Ulrich Klar
Journal: Neuro-Oncology (2008)

The aim of this study was to determine the efficacy of sagopilone (ZK-EPO), a novel epothilone, compared with other anticancer agents in orthotopic models of human primary and secondary brain tumors. Autoradiography and pharmacokinetic analyses were performed on rats and mice to determine passage across the blood-brain barrier and organ distribution of sagopilone. Mice bearing intracerebral human tumors (U373 or U87 glioblastoma, MDA-MB-435 melanoma, or patient-derived non-small-cell lung cancer [NSCLC]) were treated with sagopilone 5-10 mg/kg, paclitaxel 8-12.5 mg/kg (or temozolomide, 100 mg/kg) or control (vehicle only). Tumor volume was measured to assess antitumor activity. Sagopilone crossed the blood-brain barrier in both rat and mouse models, leading to therapeutically relevant concentrations in the brain with a long half-life. Sagopilone exhibited significant antitumor activity in both the U373 and U87 models of human glioblastoma, while paclitaxel showed a limited effect in the U373 model. Sagopilone significantly inhibited the growth of tumors from CNS metastasis models (MDA-MB-435 melanoma and patient-derived Lu7187 and Lu7466 NSCLC) implanted in the brains of nude mice, in contrast to paclitaxel or temozolomide. Sagopilone has free access to the brain. Sagopilone demonstrated significant antitumor activity in orthotopic models of both glioblastoma and CNS metastases compared with paclitaxel or temozolomide, underlining the value of further research evaluating sagopilone in the treatment of brain tumors. Sagopilone is currently being investigated in a broad phase II clinical trial program, including patients with glioblastoma, NSCLC, breast cancer, and melanoma.
Pathway analysis of primary central nervous system lymphoma
Authors: Han W. Tun, David Personett, Karen A. Baskerville, David M. Menke, Kurt A. Jaeckle, Pamela Kreinest, Brandy Edenfield, Abba C. Zubair, Brian P. O'Neill, Weil R. Lai, Peter J. Park, Michael McKinney
Journal: Blood (2008)
Reduced transplant arteriosclerosis in plasminogen-deficient mice.
Authors: L Moons, C Shi, V Ploplis, E Plow, E Haber, D Collen, P Carmeliet
Journal: Journal of Clinical Investigation (1998)

Recent gene targeting studies indicate that the plasminogen system is implicated in cell migration and matrix degradation during arterial neointima formation and atherosclerotic aneurysm formation. This study examined whether plasmin proteolysis is involved in accelerated posttransplant arteriosclerosis (graft arterial disease). Donor carotid arteries from wild-type B10.A2R mice were transplanted into either plasminogen wild-type (Plg+/+) or homozygous plasminogen-deficient (Plg-/-) recipient mice with a genetic background of 75% C57BL/6 and 25% 129. Within 15 d after allograft transplantation, leukocytes and macrophages infiltrated the graft intima in Plg+/+ and Plg-/- recipient mice to a similar extent. In Plg+/+ recipients, the elastic laminae in the transplant media exhibited breaks through which macrophages infiltrated before smooth muscle cell proliferation, whereas in Plg-/- recipients, macrophages failed to infiltrate the transplant media which remained structurally more intact. After 45 d of transplantation, a multilayered smooth muscle cell-rich transplant neointima developed in Plg+/+ hosts, in contrast to Plg-/- recipients, in which the transplants contained a smaller intima, predominantly consisting of leukocytes, macrophages, and thrombus. Media necrosis, fragmentation of the elastic laminae, and adventitial remodeling were more pronounced in Plg+/+ than in Plg-/- recipient mice. Expression of the plasminogen activators (PA), urokinase-type PA (u-PA) and tissue-type PA (t-PA), and expression of the matrix metalloproteinases (MMPs), MMP-3, MMP-9, MMP-12, and MMP-13, were significantly increased within 15 d of transplantation when cells actively migrate. These data indicate that plasmin proteolysis plays a major role in allograft arteriosclerosis by mediating elastin degradation, macrophage infiltration, media remodeling, medial smooth muscle cell migration, and formation of a neointima.
The B-cell tumor–associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor
Authors: Michael Hudecek, Thomas M. Schmitt, Sivasubramanian Baskar, Maria Teresa Lupo-Stanghellini, Tetsuya Nishida, Tori N. Yamamoto, Marie Bleakley, Cameron J. Turtle, Wen-Chung Chang, Harvey A. Greisman, Brent Wood, David G. Maloney, Michael C. Jensen, Christoph Rader, Stanley R. Riddell
Journal: Blood (2010)
HIV infection in older people
Authors: K. A Gebo
Journal: BMJ (2009)

Increased longevity as a result of HAART raises new questions about the best treatment

The median age of people living with HIV in the developed world is increasing because of improved longevity from highly active antiretroviral therapy (HAART) and an increase in new HIV infections in older people.1 The prevalence of HIV in older people will continue to increase over the next decade, and around 50% of people living with HIV will be older than 50 by 2015.2 Although 50 years is not a common threshold for advanced age, early in the HIV epidemic the Centres for Disease Control and Infection identified HIV infected patients aged 50 or more as a separate group because the mean age of infected people was then much lower than 50.

In the early days of the HIV epidemic older patients had higher morbidity, higher mortality, and a shorter AIDS free survival than younger people with HIV. …
Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone.
Authors: A J Mixson, P Hauser, G Tennyson, J C Renault, D L Bodenner, B D Weintraub
Journal: Journal of Clinical Investigation (1993)

Thyroid hormone resistance (THR) is primarily an autosomal dominant inherited disease characterized by resistance of pituitary and peripheral tissues to the action of thyroid hormone. We investigated whether the heterogeneous phenotypic features that occur not only among kindreds but also within the same kindred might be due to the expression of differing ratios of mutant and normal receptors in tissues. Using an allele-specific primer extension method, we determined the relative expression of normal and mutant mRNAs from the fibroblasts of affected and unaffected members of two kindreds with TRH: A-H and N-N. While two affected members of A-H, as expected, had nearly equal amounts of normal and mutant hTR beta mRNA, two other members had mutant mRNA levels that accounted for at least 70% of the hTR beta mRNA. Phenotypic variability within and between kindreds with generalized resistance to thyroid hormone GRTH may be due to this differential expression of the mutant and wild type mRNA. Furthermore, when several clinical parameters of THR were compared in several affected members from two kindreds with GRTH, we found that two cases in one kindred exhibited a high mutant-to-normal hTR beta ratio and had considerably more bone resistance during their development. In certain kindreds with THR, differing ratios of normal and mutant hTR receptors may be age and growth related and may account for the reported attenuation of phenotypic symptoms with age.
Abstract B19: Fetal lung adenocarcinoma: Characterization of primary cell culture and in vitro drug response
Authors: Cecilia Menna, Mohsen Ibrahim, Daniela Peruzzi, Luca Pacini, Michela Ciancamerla, Antonella Calogero, Erino Angelo Rendina
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Fetal lung adenocarcinoma (FLAC) is an extremely rare subtype of pulmonary adenocarcinoma estimated to be the 0.5% of all lung cancers. Therefore a standardized model of FLAC primary cell culture and evidence-based treatment guidelines are not available. The aim of this study is to characterize FLAC primary cell culture, to evaluate the biological features of this uncommon tumor and the in vitro drug response. Methods: FLAC specimen was obtained from a 59-years-old female patient, cultured in vitro with DMEM-F12 medium supplemented with 5% FBS and maintained in culture for more than 6 passages. Primary cells from a lung adenocarcinoma specimen were as well cultured and used as control for all the in vitro experiments. Immunohistochemistry for β-catenin, TTF-1, Ki67, cKit, MDM2, p53, S-100, EGFR, E-cadherin, cytokeratin 7 and 8/18 was performed on paraffin-fixed specimen. Immunofluorescence on cells in culture was assessed for MDM2, p53, CD133. Specimen and cells in culture were analyzed by real time PCR for oncogenic mutations (KRAS, EGFR) and for a stem cells gene panel. In vitro tumorigenicity was tested by plating efficency and soft agar colony formation assays. Cell proliferation was determined and a cell viability test was performed after treatment of FLAC cells with tyrosine kinase inhibitors (erlotinib and gefitinib), temozolomide (TMZ), cisplatin, gemcitabine and cysplatin+gemcitabine by MTS assay. Results: A primary cell culture of human FLAC was characterized and standardized. FLAC histotype was confirmed by immunohistochemistry. Immunofluorescence showed a positivity for MDM2, but not for p53 and CD133. By molecular analysis, DNA from both specimen and cells in culture was found to harbor epidermal growth factor receptor (EGFR) kinase domain non-sense mutation in exon 20 and no mutations in the K-ras gene. Primary FLAC cells showed a colony formation activity and the soft agar assay revealed an anchorage-indipendent growth. At 48 hours FLAC cells proliferation was inhibited of 56% and 41% by erlotinib and gefitinib respectively, with an IC50 value of 10 μM, compared with the control proliferation (lung adenocarcinoma cells) inhibited of 25% and 60% by erlotinib and gefitinib respectively (p=0,17; p=0,005). However, FLAC cell viability at 48 hours after being treated with cisplatin 10 μM was 3%, compared with the control viability that was 16% (p=0,007). Conclusion: This well-characterized FLAC primary cell culture provide a unique model for future studies in lung cancer biology and drug response. Although chemosensitivity to cisplatin was determined, erlotinib and gefitinib were effective against FLAC cells and appear to represent a novel targeting approach for the treatment of this rare tumor.
508 Insulin resistance, fibrosis and genotype are predictors of sustained response rate to pegylated interferon plus ribavirin in patients with chronic hepatitis C
Authors: M. Romero-Gomez, M.M. Viloria, R. Corpas, M. Cruz, D. Sanchez-Munoz, L. Grande, J. Castillo, E. Suarez, I. Camacho, M.C. Nogales
Journal: Journal of Hepatology (2004)
IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma
Authors: Zhi-Zhang Yang, Deanna M. Grote, Steven C. Ziesmer, Toshiro Niki, Mitsuomi Hirashima, Anne J. Novak, Thomas E. Witzig, Stephen M. Ansell
Journal: Journal of Clinical Investigation (2012)

The cytokine IL-12 induces IFN-γ production by T and NK cells. In preclinical models, it contributes to antitumor immunity. However, in clinical testing, it has shown limited benefit in patients with any one of a variety of malignancies. Moreover, in a clinical trial testing a combination of IL-12 and rituximab in patients with follicular B cell non-Hodgkin lymphoma (FL), those treated with IL-12 showed a lower response rate, suggesting that IL-12 actually plays a detrimental role. Here, we investigated whether the failure of IL-12 treatment for FL was due to T cell exhaustion, a condition characterized by reduced T cell differentiation, proliferation, and function, which has been observed in chronic viral infection. We found that extended exposure to IL-12 induced T cell exhaustion and contributed to the poor prognosis in FL patients. Long-term exposure of freshly isolated human CD4+ T cells to IL-12 in vitro caused T cell dysfunction and induced expression of TIM-3, a T cell immunoglobulin and mucin domain protein with a known role in T cell exhaustion, via an IFN-γ–independent mechanism. TIM-3 was required for the negative effect of IL-12 on T cell function. Importantly, TIM-3 also was highly expressed on intratumoral T cells that displayed marked functional impairment. Our findings identify IL-12– and TIM-3–mediated exhaustion of T cells as a mechanism for poor clinical outcome when IL-12 is administered to FL patients.
Developmental Exposure to Low-Dose PBDE-99: Effects on Male Fertility and Neurobehavior in Rat Offspring
Authors: Sergio N. Kuriyama, Chris E. Talsness, Konstanze Grote, Ibrahim Chahoud
Journal: Environmental Health Perspectives (2004)

In utero exposure to a single low dose of 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) disrupts neurobehavioral development and causes permanent effects on the rat male reproductive system apparent in adulthood. PBDEs, a class of flame retardants, are widely used in every sector of modern life to prevent fire. They are persistent in the environment, and increasing levels of PBDEs have been found in biota and human breast milk. In the present study we assessed the effects of developmental exposure to one of the most persistent PBDE congeners (PBDE-99) on juvenile basal motor activity levels and adult male reproductive health. Wistar rat dams were treated by gavage on gestation day 6 with a single low dose of 60 or 300 μg PBDE-99/kg body weight (bw). In offspring, basal locomotor activity was evaluated on postnatal days 36 and 71, and reproductive performance was assessed in males at adulthood. The exposure to low-dose PBDE-99 during development caused hyperactivity in the offspring at both time points and permanently impaired spermatogenesis by the means of reduced sperm and spermatid counts. The doses used in this study (60 and 300 μg/kg bw) are relevant to human exposure levels, being approximately 6 and 29 times, respectively, higher than the highest level reported in human breast adipose tissue. This is the lowest dose of PBDE reported to date to have an in vivo toxic effect in rodents and supports the premise that low-dose studies should be encouraged for hazard identification of persistent environmental pollutants.
Serious eye injuries due to war games
Authors: G M B Dawidek
Journal: BMJ (1989)

turbance of higher cerebral function, which together suggest extensive ischaemia in the distri- bution of the carotid artery.This pattern was present in case 2 reported by Koudstaal et al; their case 1 may have lacked the hemianopia.Patho- logical evidence suggests that occlusion of the internal carotid or middle cerebral artery, or both, is usually necessary to cause such extensive ischaemia.The case fatality rate at 30 days for patients with this syndrome was 37% (27 of 73) compared with only 10% for all types of cerebral infarction combined.The direct neurological sequelae of the stroke, transtentorial herniation, caused seven deaths.Thus from the calculation used by Koudstaal et al the risk of two consecutive patients dying in this way would be one in 109.A further 16 (59%) deaths, however, occurred from complications of immobility, such as pneumonia, pulmonary embolism, and sepsis.When the sur- vivors were assessed one year after their stroke fewer than 10% were capable of independent existence.These data suggest that a group of patients who are at high risk of death or serious disability can be identified rapidly using simple clinical criteria; this will be necessary if thrombolytic treatment is to be given to patients so early that their computed tomograms will show no evidence of infarction.The data also show that when larger numbers of patients are studied, preferably in randomised controlled trials, functional assessment of the survivors will be as important an outcome measure as simple survival.