tbuckley/cabot-search huggingface dataset:
Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study.
Authors: A J Thompson, A G Kermode, D G MacManus, B E Kendall, D P Kingsley, I F Moseley, W I McDonald
Journal: BMJ (1990)

OBJECTIVE--To compare the abnormalities shown by magnetic resonance imaging of the brain in three clinically distinct groups of patients with multiple sclerosis, and to correlate the extent of abnormality with the degree of clinical disability in the three groups. DESIGN--All patients underwent magnetic resonance imaging and full neurological examination, and their disability was scored according to the expanded Kurtzke disability state scale. SETTING--National Hospital for Nervous Diseases (Multiple Sclerosis NMR Research Group). PATIENTS--Three groups of patients with confirmed multiple sclerosis were studied: 12 patients with minimal disability despite a long (greater than 10 years) duration of illness (benign multiple sclerosis), 16 who had developed progressive disability after a relapsing and remitting course (secondary progressive multiple sclerosis), and 13 who had had progressive disability from the onset of the disease (primary progressive multiple sclerosis). MAIN OUTCOME MEASURES--Number and size of lesions in 17 anatomically defined sites; total lesion load, estimated with an arbitrary scoring system weighted for the size of lesions; and disability score. RESULTS--Magnetic resonance imaging showed that all 41 patients had abnormalities. These were extensive in the groups with secondary progressive and benign disease compared with the group with primary progressive disease. The lesions in the patients with secondary progressive disease were larger and more confluent than those in the two other groups (p = 0.007). Most lesions (85%) in the patients with primary progressive disease were under 5 mm in diameter; this percentage was higher than that in the two other groups (p = 0.032). Consequently the patients with primary progressive disease had the lowest mean lesion load (36.7); that in the patients with benign disease was 52.7 and that in the patients with secondary progressive disease 64.6 (p = 0.05). No correlation existed between disability and total lesion load. The distribution of brain lesions and of detectable lesions of the spinal cord, and the frequency of cortical atrophy, were similar in all groups. CONCLUSIONS--No relation was found between the degree of clinical disability and the extent of abnormality shown by magnetic resonance imaging: patients with clinically benign disease often had extensive abnormalities and those with primary progressive disease had surprisingly few lesions. Though magnetic resonance imaging increases knowledge of the disease process in multiple sclerosis and is invaluable in diagnosis, it is not helpful in predicting disability in individual patients.
Subclavian Vein Cannulation
Authors: Leon G. Robb
Journal: JAMA (1967)

To the Editor:—  This route is the least bothersome to the patient post-operatively and gives less artifacts in recording by the nurses. The neck need not be immobilized as often is the case in jugular vein catheterization, and the arm need not be restricted as in basilic or cephalic vein catheterization.  In our institution all of the catheterizations are done by or under the careful scrutiny of those well
Private firms enlisted to cut waiting lists for tests and surgery in 780m contract
Authors: M. Limb
Journal: BMJ (2015)

To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, we examined the effects of MTH on hippocampal CA1 and neocortical neurons<i>via</i> extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 μM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region, but enhanced γ-aminobutyric acid (GABA)<sub>A</sub>-mediated inhibitory postsynaptic currents and induced spontaneous inhibitory postsynaptic currents in neocortical and hippocampal CA1 neurons. In addition, MTH induced a tonic, bicuculline-sensitive hyperpolarization in association with increases in membrane conductance, suggesting a direct stimulation of GABA<sub>A</sub> receptors by MTH. Spontaneous epileptiform activity was not observed in the neocortex and hippocampus after exposure of slices to MTH, neither in the standard <i>in vitro</i>condition nor in the presence of 4-aminopyridine, which promotes rhythmic synaptic activities. We suggest that the activation of epileptiform activity <i>in vivo</i> by MTH may result from increased neuronal synchrony <i>via</i> the potentiation of GABA<sub>A</sub>-mediated synaptic inhibition.
Prenatal Screening for Down's Syndrome in Maine, 1980 to 1993
Authors: Glenn E. Palomaki, James E. Haddow, Laurent J. Beauregard
Journal: New England Journal of Medicine (1996)

To the Editor: Prenatal screening and diagnostic services for fetal Down's syndrome have been offered to women since the early 1970s, when reliable techniques of chromosome analysis became availabl...
Sunitinib in Urothelial Cancer: Clinical, Pharmacokinetic, and Immunohistochemical Study of Predictors of Response
Authors: David J. Gallagher, Hikmat Al-Ahmadie, Irina Ostrovnaya, Scott R. Gerst, Ashley Regazzi, Ilana Garcia-Grossman, Jamie Riches, Sivaraman K. Gounder, Anne-Marie Flaherty, Alisa Trout, Matthew I. Milowsky, Dean F. Bajorin
Journal: European Urology (2011)
Failure to demonstrate a humoral mechanism in the antinatriuresis of acute caval constriction
Authors: George J. Kaloyanides, Maher Azer
Journal: Journal of Clinical Investigation (1972)

Previous studies reported from this laboratory provided support for the hypothesis that the natriuresis of volume expansion is mediated in part by a humoral mechanism. In the present study we examined whether suppression of this factor participates in the antinatriuresis of acute constriction of the thoracic inferior vena cava. An isolated kidney was perfused by a second dog pretreated with deoxycorticosterone acetate. Expansion of the perfusion dog with equilibrated blood from a reservoir resulted in an increase in sodium excretion from 102+/-30 to 259+/-65 muEq/min, P < 0.001. Fractional sodium excretion increased from 2.3+/-0.6 to 6.2+/-1.2%, P < 0.01. Inulin clearance, plasma protein concentration, and packed cell volume remained constant; renal perfusion pressure and renal blood flow decreased. After the natriuresis was established, the thoracic inferior vena cava was constricted to decrease systemic arterial pressure in the perfusion dog 50 mm Hg. This maneuver suppressed urine output in the dog but did not significantly alter sodium excretion in the isolated kidney. During the period of caval constriction absolute sodium excretion in the isolated kidney measured 198+/-42 muEq/min and fractional sodium excretion measured 5.7+/-1.1%. Neither value is significantly different from that measured during volume expansion alone. The data suggest that the antinatriuresis of acute caval constriction probably does not require suppression of a humoral natriuretic factor and that other more rapidly acting mechanisms, presumably hemodynamic and neural, may be involved.
Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies
Authors: Naveed Sattar, Alex McConnachie, A Gerald Shaper, Gerard J Blauw, Brendan M Buckley, Anton J de Craen, Ian Ford, Nita G Forouhi, Dilys J Freeman, J Wouter Jukema, Lucy Lennon, Peter W Macfarlane, Michael B Murphy, Chris J Packard, David J Stott, Rudi G Westendorp, Peter H Whincup, James Shepherd, S Goya Wannamethee
Journal: The Lancet (2008)
A relation between HLA antigens and clinical features in patients with acquired valvular heart disease.
Authors: C Ward, K Gelsthorpe, R W Doughty
Journal: BMJ (1976)

Analysis of the HLA antigen patterns in patients with acquired valvular heart disease showed that antigens A29 and AW30/31 occurred more often in those patients whose valvular disease was not preceeded by a history of rheumatic fever or chorea. Patients with no rheumatic history but with antigen A29 or AW30/31 had clinical features that distinguished them from others with valvular disease--namely, (a) isolated mitral valve disease and (b) the need for surgery, often at an early age, after a relatively short duration of symptoms.
FDA looks afresh at adulteration of products
Authors: B. Roehr
Journal: BMJ (2009)

The US Food and Drug Administration is hoping to develop new strategies to predict, screen for, and identify economically motivated adulteration of food, supplements, and drugs. The first public meeting in what is likely to become a series of ongoing collaborations took place near Washington, DC, on 1 May.

Such adulteration was one of the main reasons for the agency’s creation more than a century ago. Concern was revived recently by incidents of melamine in pet food and infant formula and of substitutions in heparin, all of which led to illness and death within the past two years ( BMJ 2008;337:a1890, doi:10.1136/bmj.a1890; 2008;336:412-3, doi:10.1136/bmj.39496.419248.DB).

“The reason this problem has resurged is largely because of globalisation. That is the …
Mini- and microsatellites.
Authors: C Ramel
Journal: Environmental Health Perspectives (1997)

While the faithful transmission of genetic information requires a fidelity and stability of DNA that is involved in translation into proteins, it has become evident that a large part of noncoding DNA is organized in repeated sequences, which often exhibit a pronounced instability and dynamics. This applies both to longer repeated sequences, minisatellites (about 10-100 base pairs), and microsatellites (mostly 2-4 base pairs). Although these satellite DNAs are abundantly distributed in all kinds of organisms, no clear function has been discerned for them. However, extension of trinucleotide microsatellite sequences has been associated with several severe human disorders, such as Fragile X syndrome and Huntington's disease. Rare alleles of a minisatellite sequence have been reported to be associated with the ras oncogene leading to an increased risk for several human cancers. A dynamic behavior of repeated DNA sequences also applies to telomeres, constituting the ends of the chromosomes. Repeated DNA sequences protect the chromosome ends from losing coding sequences at cell divisions. The telomeres are maintained by the enzyme telomerase. Somatic cells, however, lose telomerase function and gradually die. Cancer cells have activated telomerase and therefore they acquire immortality.
AB0695 Anti-prothrombin/phosphatidyl-serine complex autoantibodies in antiphospholipid syndrome: Preliminary data using a new ELISA method
Authors: M. Fabris, E. Mansutti, L. Quartuccio, J. Peresan, F. Curcio, S. De Vita, E. Tonutti
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> New emerging anti-phospholipid (aPL) assays could improve our ability in diagnosing anti-phospholipid syndrome (APS). However, the availability of aPL assays in routine laboratory practice is limited and present available assays frequently not so efficient. <h3>Objectives</h3> To test the performance of a new immunometric assay for prothrombin/phosphatidylserine IgG and IgM complex autoantibodies (aPT/PS) in routinely attending patients (Autoimmunology Unit, University Hospital of Udine, Italy). <h3>Methods</h3> The study included 138 consecutive patients (78% female, age 53±15 years; range 18-88) amongst which 83 with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) or APS. 52 healthy donors (29F/23M, age 37±13 yrs, range 18-65) were enrolled as controls. From the laboratory point of view, there were 108 lupus anticoagulant (LAC) positive patients (70.4% of which anti-cardiolipin/anti-beta2 glycoprotein I-negative) and 25 LAC/aCL/anti-b2GPI-negative. All the serum samples were analysed for the anti-PT/PS IgG and IgM antibodies using the new ELISA method under development by Inova (San Diego, CA). Fifty-two samples were analysed also for IgG/IgM anti-prothrombin autoantibodies by the routinely used method (Orgentec, Mainz, Germany). <h3>Results</h3> Overall, the Inova ELISA test revealed a high prevalence of the anti-PT/PS antibodies amongst LAC positive patients (anti-PT/PS IgG and/or IgM positive in 64/108, 59.3% of LAC-positive patients versus 4/52, 7.7% of controls; p&lt;0.001). This prevalence was in line with that awaited (1). Globally, patients with SLE, UCTD or APS, were 47/83 (56.6%) anti-PT/PS positive. The percentage increased when considering only the LAC-positive cases (39/53, 73.6%). Compared to the routinely used IgG/IgM anti-prothrombin assay, the new anti-PT/PS complex assay confirmed 5/8, 62.5% of the positive samples, but was able to identify another 24 (46.1% of the 52 cases analysed with both assays) new positive cases, who were all SLE/UCTD/APS patients. <h3>Conclusions</h3> As reviewed by Amengual et al (1), the antibodies more closely associated with APS and LAC are directed to the complex between PT and anionic phospholipid (such as PT/PS) rather than PT alone. The new anti-PT/PS complex antibodies assay by Inova improves the capability to identify such reactivity and may help to better characterize patients with APS. <h3>References</h3> Amengual O. et al, Arthritis &amp; Rheum 2003. <h3>Disclosure of Interest</h3> None Declared
Seven die in polio outbreak in Namibia
Authors: Pat Sidley
Journal: BMJ (2006)

The Namibian government has launched a mass immunisation programme against polio after at least 34 people developed the disease and seven died from it.

However, the programme's success will depend on the country's ability to import sufficient vaccine and find the money to pay for it. The World Health Organization has committed itself to helping the programme, as has neighbouring South Africa.

The outbreak ended a …
Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: A 56-week, randomized, double-blind study
Authors: B.A. Knorr, O. Kuznetsova, T.F. Reiss, E. Beckford, O. Johnson, S.B. Dass, A.B. Becker
Journal: Journal of Allergy and Clinical Immunology (2005)
Hemodynamic State Early after Prosthetic Replacement of Mitral Valve
Authors: G. C. RASTELLI, JOHN W. KIRKLIN
Journal: Circulation (1966)

Cardiac output, stroke volume, and atrial, pulmonary arterial, left ventricular, and systemic arterial pressures were measured preoperatively, during operation, and for 48 hours thereafter in 14 patients undergoing prosthetic replacement of the mitral valve. Cardiac output was usually abnormally low after repair, being lowest 3 to 6 hours after operation. This pattern was different from that in a patient undergoing plication of the posterior leaflet and very different from that in a patient undergoing removal of a left atrial myxoma, who served as controls. Ventricular filling pressure was high, there was no significant diastolic pressure difference across the Starr-Edwards prosthesis, and there was no pressure difference across the left ventricular outflow tract. Blood gas levels and pH were within satisfactory range. The data are interpreted as indicating that impairment of ventricular performance, particularly left, usually contributes significantly to the low cardiac output in these patients. This is probably related in part to preoperative ventricular function. Possible additional contributing factors are discussed.
Identification of Genes Implicated in Methapyrilene-Induced Hepatotoxicity by Comparing Differential Gene Expression in Target and Nontarget Tissue
Authors: J. Todd Auman, Jeff Chou, Kevin Gerrish, Qihong Huang, Supriya Jayadev, Kerry Blanchard, Richard S. Paules
Journal: Environmental Health Perspectives (2007)

BackgroundToxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest.ObjectivesThe objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes.MethodsMale rats were given the hepatotoxicant methapyrilene at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis. To identify gene changes likely to be related to toxicity, we analyzed genes on the basis of their temporal pattern of change using a program developed at the National Institute of Environmental Health Sciences, termed "EPIG" (extracting gene expression patterns and identifying co-expressed genes).ResultsHigh-dose methapyrilene elicited hepatic damage that increased in severity with the number of doses, whereas no treatment-related lesions were observed in the kidney. High-dose methapyrilene elicited thousands of gene changes in the liver at each time point, whereas many fewer gene changes were observed in the kidney. EPIG analysis identified patterns of gene expression correlated to the observed toxicity, including genes associated with endoplasmic reticulum stress and the unfolded protein response.ConclusionsBy factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, we were able to identify genes likely to not be implicated in toxicity, thereby allowing us to focus on a subset of genes to identify toxicity-related processes.
P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma.
Authors: J E Boers, G P ten Velde, F B Thunnissen
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
Differences in the intrinsic immunogenicity and allergenicity of <scp>B</scp> et v 1 and related food allergens revealed by site‐directed mutagenesis
Authors: A. Roulias, U. Pichler, M. Hauser, M. Himly, H. Hofer, P. Lackner, C. Ebner, P. Briza, B. Bohle, M. Egger, M. Wallner, F. Ferreira
Journal: Allergy (2013)

Background Birch pollen allergies are frequently associated with adverse reactions to various fruits, nuts, or vegetables, described as pollen–food syndrome (PFS) and caused by cross-reactive IgE antibodies primarily directed against Bet v 1. Specific immunotherapy (SIT) represents an effective treatment for inhalant allergies; however, successful birch pollen SIT does not correlate well with the amelioration of concomitant food allergies. Methods As vaccine candidates, apple Mal d 1 as well as hazelnut Cor a 1 derivatives were designed by in silico backbone analyses of the respective allergens. The proteins were produced by site-directed mutagenesis as fold variants of their parental allergens. Because Mal d 1 and Cor a 1 form cysteine-mediated aggregates, nonaggregative cysteine to serine mutants were also generated. The proteins were characterized physicochemically, immunologically, and in in vivo models with or without adjuvant. Results The structurally modified proteins showed significantly decreased IgE binding capacity. Notably, both in vivo models revealed reduced immunogenicity of the hypoallergenic fold variants. When formulated with alum, the monomeric cysteine mutants induced a similar immune response as the aggregated parental allergens, which is in contrast with data published on Bet v 1. Conclusion These findings lead to the suggestion that the Bet v 1 structure has unique intrinsic properties, which could account for its high allergenicity. Obviously, these characteristics are not entirely shared with its food homologues from apple and hazelnut. Thus, it is important to tackle pollen-related food allergies from different angles for the generation of effective vaccine candidates to treat birch PFS.
Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen – results from the BAMSE birth cohort
Authors: A. Asarnoj, E. Östblom, S. Ahlstedt, G. Hedlin, G. Lilja, M. Van Hage, M. Wickman
Journal: Allergy (2009)

Specific IgE tests are sometimes difficult to interpret due to structural similarities between certain food and pollen allergens. This may be the reason why concomitant sensitization to peanut and birch pollen is frequently seen. The aim of this study was to investigate reported symptoms to peanut- and birch pollen in relation to sensitization.The data originate from 1928 children in the BAMSE birth cohort. Background factors and clinical parameters were obtained and the levels of IgE antibodies to peanut and birch pollen measured at 4 and 8 years.IgE antibodies to peanut were found in 5.5% and 7.4% of the children at 4 and 8 years, respectively. The IgE antibody levels to peanut were higher in children sensitized to peanut but not birch than in children sensitized to peanut and birch among both 4- and 8-year-olds (P = 0.093 and P = 0.003, respectively). Eight-year-olds sensitized to peanut but not birch, more often reported symptoms to peanut than children sensitized to both peanut and birch pollen (76%vs 46%, P = 0.002). The probability of reported symptoms to peanut increased significantly with increasing IgE levels to peanut, especially in 8-year-olds not sensitized to birch.Children sensitized to both peanut and birch pollen are less likely to report symptoms to peanut than children sensitized to peanut but not to birch pollen at 8 years. This is likely due to cross reactions between birch pollen and peanut and can explain the high sensitization rate to peanut in areas where birch trees are common.