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Pohlmann, Paula Raffin, Todd W. Miller, David L. Blum, Dipti Pareh, Heping Yan, Cammie R. Sutton, Teresa C. Dugger, et al. "Trastuzumab-reactive antibodies (TR-abs) in serum and trastuzumab (Tzb) benefit prediction in patients with HER2-overexpressing breast cancer." Journal of Clinical Oncology 30, no. 30_suppl (October 20, 2012): 77. http://dx.doi.org/10.1200/jco.2012.30.30_suppl.77.
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77 Background: Trastuzumab (Tzb) is a humanized monoclonal antibody (MAb) approved for treatment of HER2-overexpressing breast cancer. Unfortunately not all patients benefit from it and lack of response cannot be predicted. We detected TR-abs in serum of mice and patients treated with Tzb. We hypothesized that TR-abs would associate with response to therapy. Methods: Direct/competition ELISA, dot blot, and mass spectrometry were used to detect and characterize TR-abs in sera from Tzb treated FVBMMTV/HER2transgenic mice, from hybridoma MAbs stemming from transgenic mice responding favorably to Tzb (992-18 mMAb), and in sera of 22 patients with metastatic breast cancer enrolled in a phase I clinical trial. WST-1 viability assay was used to assess biological activity of 992-18 on SKBR3 or BT474 human breast cancer cell lines. Results: From 12 mice bearing HER2-overexpressing tumors and treated with Tzb, 5 responded to therapy and 7 exhibited progressive disease (PD). All 5 responders had elevated TR-abs, whereas TR-abs were low/undetectable with PD (p=0.002; Mann-Whitney two-tailed). This was confirmed in a second cohort of 16 mice, in which TR-abs were undetectable prior to treatment, but gradually detected with Tzb therapy and tumor regression. TR-MAb 992-18 directly targeted also SKBR3 and BT474 in cell-based ELISAs and immunofluorescence assays. Treatment with 992-18 reduced BT474 and SKBR3 cell viability in comparison to isotype-matched control Ab (p<0.0001). In sera from patients with metastatic breast cancer, higher concentrations of TR-abs were significantly associated with lower risk of disease progression (p=0.023, Cox regression, univariate analysis). Conclusions: Low serum TR-abs are associated with poor response to Tzb in mice and with shorter progression free survival in women with HER2 overexpressing stage IV breast cancer. In addition, TR-abs (e.g. 992-18) produced in response to therapy may be pharmacologically active. Results support prospective evaluation of patients undergoing treatment with therapeutic antibodies to determine if this non-invasive immunoassay detecting anti-therapeutic antibodies would predict benefit to therapy.
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Komariah, Anis, Sriatun Sriatun, and Pardoyo Pardoyo. "Adsorpsi Alkil Benzena Sulfonat Menggunakan Zeolit Termodifikasi Cetyltrimethylammonium." Jurnal Kimia Sains dan Aplikasi 20, no. 1 (April 1, 2017): 13–18. http://dx.doi.org/10.14710/jksa.20.1.13-18.
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Dalam penelitian ini dilakukan modifikasi zeolit alam teraktivasi NH4Cl (H-Zeolit) dengan surfaktan CTAB (Cetyltrimethylammonium Bromide) berbagai konsentrasi yaitu sebesar 0,25 mM (ZMS-1), 1 mM (ZMS-2), dan 100 mM (ZMS-3) sebagai adsorben senyawa ABS (Alkil Benzena Sulfonat). Karakterisasi dilakukan terhadap H-Zeolit dan ZMS menggunakan spektrofotometer FTIR. Parameter utama dalam penelitian ini adalah variasi konsentrasi ABS (50, 75, dan 100 ppm) dan waktu kontak (15, 30, 45, 60, 75, dan 90 menit). Konsentrasi ABS yang teradsorpsi dianalisis dengan spektrofotometer UV-Vis menggunakan metode MBAS (Methylene Blue Active Substance). Hasil spektra FTIR zeolit alam termodifikasi surfaktan (ZMS) menunjukkan puncak pada bilangan gelombang 2931,80 cm-1; 2854,65 cm-1 dan 1404,18 cm-1 yang mengindikasikan keberadaan gugus CTAB pada zeolit. Konsentrasi maksimum dan waktu optimum ABS yang dapat dijerap oleh per 0,1 gram ZMS adalah 50 ppm dalam 25 mL pada waktu 60 menit dengan persen adsorpsi sebesar 84,04% untuk H-Zeolit ; 96,42% untuk ZMS-1; 96,48% untuk ZMS-2; dan 97,29% untuk ZMS-3. Performa ZMS cenderung meningkat dengan konsentrasi CTAB pada zeolit.
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ANYANWU, Madubuike Umunna, and Oluwatosin Ajoke KOLADE. "Veterinarians’ Perception, Knowledge and Practices of Antibiotic Stewardship in Enugu State Southeast, Nigeria." Notulae Scientia Biologicae 9, no. 3 (September 30, 2017): 321–31. http://dx.doi.org/10.15835/nsb9310061.
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A cross-sectional survey utilizing structured questionnaires was used to study the veterinarians’ perception, knowledge and practices of antibiotic stewardship (ABS) in Enugu State, Southeastern Nigeria. Data obtained were analyzed using chi-square on SPSS (Version 15.0) at a significance level of P < 0.05 to determine possible associations between variables and perceptions/knowledge about ABS. Out of 280 respondents, 41 (17.1%) had heard about ABS. Minority of the respondents perceived/knew that using antibiotics only when necessary (6.4%, 18), administering antibiotics at the appropriate dose (6.4%, 18) and administering antibiotics for appropriate duration in every case (4.3%, 12) were among the principles of ABS. The study also showed that age, gender, qualification, years of practice and locations did not exert any influence (P > 0.05) on the awareness of respondents about ABS. More than one-third of the respondents wrongly perceived that increasing the use of broad-spectrum antibiotics (35.4%, 99) is one of the goals of ABS, whereas the minority of the respondents rightly perceived/knew that minimizing toxicity and other adverse effects (16.8%, 47) and reducing antibiotic resistance (ABR) (43.2%, 121) are also goals of ABS. Only 21.4% (60) had overall knowledge of ABS. Prescribing antibiotics without seeing/examining the patient, prescribing antibiotics for any case suspected to be infectious, prescribing broad-spectrum antibiotics despite availability of narrow-spectrum antibiotics, prescribing different classes/types of antibiotics concurrently to ensure therapeutic efficacy, prescribing overdose of antibiotics to ensure efficacy and non-consultation of the veterinary formulary/other resources when in doubt during prescription, are some of inappropriate/untoward ABS practices/behaviors/attitudes amongst the respondents. No significant association (P > 0.05) was found between practices of ABS and age, gender, qualification, years of practice and location. In conclusion, the veterinarians’ awareness/perception and practices of ABS is abysmally poor in the study area, thus education of Nigerian veterinarians about ABS and the teaching of the principles and practices of ABS during veterinary schools are recommended.
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Tagami, Tetsuya, Kaho Hiroshima-Hamanaka, Hironobu Umakoshi, Mika Tsuiki-Naruse, Toru Kusakabe, Noriko Satoh-Asahara, Akira Shimatsu, and Kenji Moriyama. "Experimental Reproduction of Dynamic Fluctuation of TSH Receptor–Binding Antibodies Between Stimulation and Inhibition." Journal of the Endocrine Society 3, no. 12 (September 23, 2019): 2361–73. http://dx.doi.org/10.1210/js.2019-00012.
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Abstract Context Hyperthyroidism in Graves disease (GD) is caused by autoantibody stimulation of the TSH receptor (TSHR). TSHR autoantibody (TSHR-Ab) activity is measured routinely by inhibition of labeled ligand (TSH or M22) binding to the TSHR [TSH-binding inhibitory immunoglobulins (TBIIs)] or by stimulation of cAMP production in isolated cells [TSH receptor–stimulating antibodies (TSAbs)]. Usually, measurements of TSHR-Abs by TBIIs agree reasonably well with TSAb values at least in the setting of hyperthyroidism, and both measurements tend to change in parallel during treatment with some exceptions. In this study, we describe three unusual cases, which illustrate nearly pure stimulating, blocking, or neutral properties of TSHR-Abs. Objective Whether patient serum TSHR-Abs can be reproduced by mixtures of human monoclonal autoantibodies to the TSHR was studied because the sera in most patients show moderate properties having both of TBII and TSAb activities. Design We compared the TBII and TSAb activities of serum from four unusual patients in detail with mixtures of human monoclonal TSHR-Abs (mAbs) M22 (stimulating), K1-18 (stimulating), and K1-70 (blocking). Results Characteristic of a patient’s serum was similar to M22 or K1-18, another was similar to K1-70, whereas another was similar to a mixture of K1-70 and M22 (or K1-18). Additionally, some patients seemed to have neutral TSHR-Abs in their sera. Conclusions Our studies suggest that the characteristics of TSHR-Abs in the patient serum can be mimicked by mixtures of human mAbs to the TSHR, stimulating, blocking, and neutral if any.
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Torii, Masae, and Masakazu Toi. "Performance of fluorine-18 fluorodeoxyglucose (18F-FDG) dedicated breast PET for early breast cancer." Annals of Breast Surgery 2 (November 2018): 19. http://dx.doi.org/10.21037/abs.2018.11.02.
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Jankowiak, Mirosław. "Sprawozdanie z konferencji „Dawne Inflanty Polskie: dziedzictwo i historia (Kraków, 18–19 listopada 2010)." Acta Baltico-Slavica 35 (July 28, 2015): 291–93. http://dx.doi.org/10.11649/abs.2011.022.
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Zubair, Khadija, and Muhammad Fayzan Shakir. "Effect of Polymer Matrix in Polymer/trGO Nano-Composite for EMI Shielding Application in Microwave and Infrared Region." Key Engineering Materials 875 (February 2021): 153–59. http://dx.doi.org/10.4028/www.scientific.net/kem.875.153.
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Thermally reduced graphene oxide (trGO) was successfully prepared and confirmed by XRD then dispersed in polystyrene (PS) and Acrylonitrile-Butadiene-Styrene (ABS) polymers and evaluated for EMI shielding in microwave and infrared (IR) region. Thickness of prepared polymer/trGO composite films were 200-250 micron. It was observed that trGO has more compatibility with PS then ABS and dispersed more easily and uniformly in PS than ABS. This effect was also observed in IR shielding as ABS+15trGO have 3% transmission and PS+1% trGO have 1.5% transmission. Maximum 29 dB and 25 dB shielding effectiveness was measured by vector network analyzer (VNA) in microwave region (9-18 GHz) of PS+2% trGO and ABS+2% trGo composite respectively. These results clearly indicating that trGO is more compatible with PS than ABS and form more stable and mature interconnected network structure in PS at lower concentrations.
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Rose, Gerd. "Sonder-Gewerbesteuer aus § 18 Abs. 4 UmwStG nach Formwechsel vor 1999?" Finanz-Rundschau Ertragsteuerrecht 87, no. 1 (January 1, 2005): 1–6. http://dx.doi.org/10.9785/fr-2005-0103.
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Bartolomé, Maria J., Gonzalo de las Heras, and Marcos López-Hoyos. "Low-Avidity Antibodies to Carbonic Anhydrase-I and -II in Autoimmune Chronic Pancreatitise." Scientific World JOURNAL 2 (2002): 1560–68. http://dx.doi.org/10.1100/tsw.2002.811.
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Antibodies (Abs) to carbonic anhydrase (isoforms CA-I and CA-II) have been considered pathogenic factors in the development of autoimmune pancreatitis. Besides, such autoAbs might accelerate the pancreatic damage in alcoholic chronic pancreatitis (CP). The aim of the present study was to evaluate the presence of serum Abs to CA-I and CA-II in CP and the relative affinity of these Abs.Serum anti-CA-I and -CA-II Abs were measured in 89 patients with CP (48 alcoholic and 41 nonalcoholic) by an ELISA technique. The prevalence of those autoAbs in CP was compared with other autoimmune diseases where they have also been found. The presence of other serological manifestations of autoimmunity, such as hypergammaglobulinemia or antinuclear Abs, was determined in CP patients as well.Elevated serum levels of both anti-CA-I (24%) and -CA-II (18%) Abs were observed in CP, although their prevalence was lower than in autoimmune diseases like rheumatoid arthritis (44 and 25%, respectively) or systemic lupus erythematosus (39% for anti-CA-I Abs). Furthermore, these Abs were of low average avidity. On the other hand, a significantly higher proportion of nonalcoholic CP had anti-CA-II Abs with respect to alcoholic CP (15.2 vs. 2.4%,p< 0.05Anti-CA-I and -CA-II Abs might be helpful in the diagnosis of autoimmune CP, and the detection of the latter Abs seems to discard alcoholic etiology. Although it does not discard any pathogenic role in autoimmune CP, the low-avidity of anti-CA Abs argues against such idea.
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Heldt, Amélie P. "Pflicht zu weltweiter Löschung: konsequente oder ausufernde Auslegung? – Anmerkung zum Urteil des EuGH v. 3.10.2019, Rs. C-18/18 (Glawischnig-Piesczek)." Europarecht 55, no. 2 (2020): 238–45. http://dx.doi.org/10.5771/0531-2485-2020-2-238.
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Im Fall von Glawischnig-Piesczek/Facebook Ireland Ltd. hatte der EuGH über die Reichweite der Löschungspflicht von Hostingplattformen für rechtswidrige Inhalte zu entscheiden. Im Kern ging es um die Frage, ob das Vorliegen der positiven Kenntnis über rechtswidrige Inhalte sich auch auf wort- und sinngleiche Inhalte erstreckt, also ob soziale Netzwerke verpflichtet werden können, nicht nur den ursprünglichen rechtswidrigen Beitrag zu entfernen oder zu sperren, sondern auch inhaltsgleiche Abwandlungen. Diese Fragen hat der EuGH alle bejaht und damit Art. 14 Abs. 1 E-Commerce-Richtlinie als weltweite Pflicht ausgelegt.
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Sangster, Mark Y., Jane Baer, Felix W. Santiago, Theresa Fitzgerald, Natalia A. Ilyushina, Aarthi Sundararajan, Alicia D. Henn, et al. "B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination." Clinical and Vaccine Immunology 20, no. 6 (April 10, 2013): 867–76. http://dx.doi.org/10.1128/cvi.00735-12.
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ABSTRACTThe 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and ≥70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.
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Lotz, Helga, and Giovanni B. Salabè. "Lipoprotein(a) increase associated with thyroid autoimmunity." European Journal of Endocrinology 136, no. 1 (January 1997): 87–91. http://dx.doi.org/10.1530/eje.0.1360087.
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Abstract Conflicting results have been reported regarding serum lipoprotein(a) (Lp(a)) concentrations in patients with hypothyroidism. We addressed the question whether thyroid autoimmunity could be associated with elevated Lp(a) values independent of the thyroid status. Lp(a) was measured by ELISA in 30 males, 29 premenopausal and 30 postmenopausal females positive for thyroid peroxidase- and/or thyroglobulin-antibody (T-Abs) and normolipidemic, screened out respectively from 428 male donors, 162 premenopausal donors and 108 postmenopausal females; they were compared with 65 males, 72 premenopausal and 48 postmenopausal females, negative for thyroid antibodies, normolipidemic and matched for age. T-Abs-positive male donors showed serum Lp(a) concentrations significantly increased compared with males without T-Abs (mean 19·7 ± 15·9 vs 12·7 ± 17·5 mg/dl; median 17·0 vs 4·0 mg/dl; Mann Whitney U test: P = 0·0000). In premenopausal females no difference could be found between T-Abs-positive and T-Abs-negative subjects (mean 13·2 ± 16·1 vs 12·3 ± 13·9 mg/dl; median 5·2 vs 8·7 mg/dl), suggesting an Lp(a) lowering effect of estrogens. The study was, therefore, extended to postmenopausal females. Significantly elevated Lp(a) levels were found in 30 postmenopausal females with T-Abs when compared with 48 postmenopausal females without T-Abs (40·0 ± 34·2 mg/dl vs 20·7 ± 19·3 mg/dl; median 32·0 vs 18·0 mg/dl; Mann Whitney U test: P = 0·0002). Finally, 21 postmenopausal, normolipidemic, autoimmune hypothyroid patients on l-thyroxine and euthyroid compared with 48 postmenopausal females without T-Abs also showed increased serum levels of Lp(a) (mean 27·0 ± 16·8 mg/dl vs 20·7 ± 19·3 mg/dl, median 25·0 vs 18 mg/dl; Mann Whitney U test: P = 0·0024). Thyrotropin levels in all subjects and patients were within the normal range. In conclusion, our results in males and postmenopausal females with T-Abs and euthyroid show an association between thyroid autoimmunity and increased levels of Lp(a), while the results obtained in premenopausal females suggest that estrogens might interfere with the Lp(a) increase related to thyroid autoimmunity. European Journal of Endocrinology 136 87–91
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Cordell, Barbara Jean, Anup Kanodia, and Gregory K. Miller. "Case–Control Research Study of Auto-Brewery Syndrome." Global Advances in Health and Medicine 8 (January 2019): 216495611983756. http://dx.doi.org/10.1177/2164956119837566.
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Background Auto-brewery syndrome (ABS), also known as Gut Fermentation Syndrome and Endogenous Ethanol Fermentation, is afflicting people worldwide, but little is known about ABS patients’ demographics, health history, lifestyle factors, and diet. Method We conducted a broad-based case–control survey study on 52 patients known to have a diagnosis of ABS and their household members. The research compares the symptomatic group (N = 28) to the asymptomatic group (N = 18) regarding lifestyle and health, diet, and medical history. Results With a response rate of 88% and using rank-sum tests, the data demonstrate that patients with ABS have significant differences compared to people without ABS in lower quality bowel movements ( P = .048), more frequent bowel movements ( P = .038), more reports of malodorous breath ( P = .0001), and self-classify as having poorer health ( P = .009). Furthermore, participants with ABS consume more water ( P = .038), consume less tea and coffee ( P = .033), eat fewer dairy products ( P = .0185), eat less candy ( P = .032), eat out less and rely on food prepared at home ( P = .043), have more aversion to starch ( P = .008), and have more food sensitivities ( P = .043) than the group without ABS. The ABS group also reports more diarrhea ( P = .048), higher amounts of yeast in their gastrointestinal tract ( P = .015), and using acne medication for a longer time ( P = .037) than the control group. Conclusion Patients with ABS have significant differences in their lifestyle and health, diet, and medical history compared to non-ABS participants and these differences warrant further research.
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Rasmussen, Mark, Daniel W. Bougie, Gregory H. Denomme, and Richard H. Aster. "Serologic Characterization of Antibodies in Patients Experiencing Piperacillin-Induced Immune Thrombocytopenia." Blood 134, Supplement_1 (November 13, 2019): 1078. http://dx.doi.org/10.1182/blood-2019-130966.
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Beta lactam antibiotics (penicillins, cephalosporins, etc) are relatively common triggers for immune hemolytic anemia, neutropenia and drug-induced thrombocytopenia (DITP) but the mechanism(s) responsible for this side effect are not well understood. The ureidopenicillin, piperacillin, is one of the beta lactam drugs implicated most often as a trigger for immune cytopenia. We characterized drug-dependent reactions of antibodies (abs) identified in 18 patients with piperacillin-associated thrombocytopenia. Each of the 18 patients had an ab that reacted strongly (flow cytometry) with normal platelets but not RBC when soluble piperacillin was present. These reactions were not inhibited by the highest drug concentration that could be achieved in the reaction mixture and similar antibodies were not found in normal serum. These reactions are similar to those obtained with drug-dependent antibodies (DDAbs) found in patients sensitive to quinine, vancomycin, and many other drugs known to cause DITP. Evidence suggests that such drugs promote binding of DDAbs to their targets by reacting with antibody CDR3 and modifying its specificity (Blood 2015;126:2138). Beta-lactam drugs differ from most other medications in their ability to spontaneously link covalently to free amino groups on membrane proteins to produce potentially immunogenic haptens that could induce abs theoretically capable of contributing to thrombocytopenia in piperacillin-treated patients. We optimized conditions for "haptenization" of platelets and RBCs with piperacillin and tested patient and normal sera for abs that recognize piperacillin-coated cells. Complete inhibition of binding by excess soluble drug was a criterion for a "positive" reaction. As shown in Table 1, IgG and IgM abs reactive with piperacillin-coated RBCs were found in each of 18 patient and 20 normal sera tested; IgM abs reactive with piperacillin-coated platelets were found in nearly all of both groups and similar IgG abs were found in about half. Reaction strength of IgM abs against piperacillin-coated RBCs correlated closely with that against piperacillin-coated platelets The findings demonstrate two distinctly different types of piperacillin-specific abs in patients experiencing piperacillin-induced thrombocytopenia. The first is usually IgG, binds to platelets but not RBCs only when soluble drug is present, is not inhibited by excess drug, even at high concentrations, correlates with exposure to piperacillin and development of thrombocytopenia and is not found in normal persons. This behavior is similar to that of DDAbs induced by quinine, vancomycin and many other drugs. The second is commonly IgM and less often IgG, binds to piperacillin-coated platelets and RBCs, is inhibited by soluble drug and, as the IgM isoform, is found in nearly all normal subjects. Failure of abs that recognize piperacillin-coated cells to distinguish between platelets and RBCs in any consistent way argues against the possibility that they play a role in the pathogenesis of piperacillin-induced DITP. "Naturally-occurring" IgM abs that recognize piperacillin-coated RBC were previously described by Garratty et al (Transfusion 2008;48:2429) and could reflect widespread environmental exposure to beta-lactam antibiotics. Disclosures No relevant conflicts of interest to declare.
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Collacott, Richard A. "The Effect of Age and Residential Placement on Adaptive Behaviour of Adults with Down's Syndrome." British Journal of Psychiatry 161, no. 5 (November 1992): 675–79. http://dx.doi.org/10.1192/bjp.161.5.675.
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Through widespread enquiry, the population of adults with Down's syndrome (aged over 18 years) in Leicestershire was estimated at 376. For 315 of these (83.8%), the immediate carer was invited to complete the Adaptive Behavior Scale (ABS). Completed ABS assessments were obtained on 81.9% of the adult population with Down's syndrome in the county. Additional information concerning residential history was obtained. When the sample was divided into five cohorts on the basis of age when the ABS assessment took place, an exponential decline in ability was observed. Deterioration in most domains of the ABS achieved statistical significance in the cohort aged 50–59, and in all domains in those aged 60 and over. The deterioration in global skills in older cohorts was attributed to ageing (and thereby probably Alzheimer's disease). Institutional placement was associated with low scores in younger groups only.
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Eng, Grith P., Klaus Bendtzen, Henning Bliddal, Michael Stoltenberg, Marcin Szkudlarek, Viktoria Fana, Hanne M. Lindegaard, et al. "Antibodies to Infliximab and Adalimumab in Patients with Rheumatoid Arthritis in Clinical Remission: A Cross-Sectional Study." Arthritis 2015 (February 11, 2015): 1–7. http://dx.doi.org/10.1155/2015/784825.
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Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab or adalimumab, and in clinical remission (DAS28(CRP) < 2.6) were included from 6 out-patient clinics. In blood samples, presence of anti-TNFi Abs was determined by radioimmunoassay, and concentration of bioactive TNFi was measured by a cell-based reporter gene assay. Results. Anti-TNFi Abs were present in 8/44 patients (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (p=0.012). In the former group, anti-TNFi Abs corresponded with low levels of TNFi (p=0.048). Anti-TNFi Ab-positive patients had shorter disease duration at initiation of TNFi therapy (p=0.023) but were similar for the rest of the compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi Abs occur frequently in patients treated with infliximab, while they occur rarely in patients treated with adalimumab. Presence of anti-infliximab Abs is accompanied by low or undetectable levels of infliximab. These data suggest that continued infliximab treatment may be redundant in a proportion of RA patients treated with infliximab and in clinical remission.
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Meeks, Shannon, John F. Healey, Ernest T. Parker, and Pete Lollar. "A Subset of High Titer Acquired Hemophilia Patients May Benefit from Treatment with High Dose Factor VIII." Blood 114, no. 22 (November 20, 2009): 3476. http://dx.doi.org/10.1182/blood.v114.22.3476.3476.
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Abstract Abstract 3476 Poster Board III-413 Approximately 30% of patients with severe hemophilia A will develop inhibitory antibodies (Abs) to factor VIII (fVIII inhibitors). The immune response to fVIII currently is the most significant complication in the management of patients with hemophilia A. In addition, autoimmune Abs to fVIII can develop in non-hemophiliacs, producing acquired hemophilia A, which frequently produces life- or limb-threatening bleeding. Patients with autoimmune hemophilia often have Abs with type II kinetics in which there is incomplete inactivation of fVIII at saturating concentrations of inhibitor. We have characterized the antibody response to the C2 domain of human fVIII in a murine hemophilia model and described 5 structural groups of Abs. Groups A, AB, and B are classical anti-C2 Abs that block fVIII and fVIIIa binding to phospholipid. Groups BC and C consist of non-classical anti-C2 Abs that inhibit the proteolytic activation of fVIII but do not block the binding of fVIII to phospholipid. Subsequently, we identified classical and non-classical anti-C2 Abs in human fVIII inhibitor plasmas. Most murine non-classical Abs have inhibitor titers greater than 10,000 Bethesda units/mg IgG. In a murine in vivo bleeding model, both type I classical C2 Abs, type II non-classical C2 Abs, and a type I anti-A2 Ab produced similar amounts of blood loss that were significantly greater than control mice injected with 180 U/kg of fVIII alone. Increasing the dose of fVIII to 360 U/kg overcame the bleeding diathesis produced by the type II MAbs, but not the type I Abs. These results were consistent with the in vitro Bethesda assay in which a type I anti-A2 Ab, 4A4, completely inhibited both 1 U/mL and 3 U/mL fVIII, while there was 40% residual activity at saturating concentrations of a type II anti-C2 Ab, 2-77, at either concentration of fVIII. To determine if similar in vitro characteristics exist in patients with acquired hemophilia, plasmas from 3 patients with high titer type II inhibitors were studied. All 3 plasmas primarily had C2 domain epitope specificity that included non-classical Abs. Plasma A7 additionally had detectable anti-A2 activity. Recovery of fVIII activity after a 2 h incubation at 37 °C at nominal added concentrations of 1 mL and 3 U/mL fVIII was compared (Table 1). At 3 U/mL added fVIII, recovery of activity in plasmas A4 and A5 was 1.1 U/mL and 0.51 U/mL, respectively, despite the presence of inhibitor titers of 18 and 11 Bethesda units (BU) per mL. The presence of anti-A2 Abs, which typically have type I kinetics, may have contributed to the overall lower recovery of activity in plasma A7. These results suggest that treatment with high-dose fVIII rather than bypassing agents may be warranted in patients with an inhibitor response dominated by non-classical anti-C2 Abs. Table 1 Patient Plasma Inhibitor Titer (BU/mL) Recovered Activity at 1U/mL FVIII (U/mL) Recovered Activity at 3 U/mL FVIII (U/mL) A4 18 0.31 1.1 A5 11 0.18 0.51 A7 62 0.07 0.12 Disclosures: No relevant conflicts of interest to declare.
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Puel, Anne, Rainer Döffinger, Angels Natividad, Maya Chrabieh, Gabriela Barcenas-Morales, Capucine Picard, Aurélie Cobat, et al. "Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I." Journal of Experimental Medicine 207, no. 2 (February 1, 2010): 291–97. http://dx.doi.org/10.1084/jem.20091983.
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Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-γ, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1β, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-β, tumor necrosis factor [α], or transforming growth factor β). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.
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Lee-Gosselin, Martin, Pierre-Sébastien Fournier, and Isabelle Béchard. "Driver Knowledge and Beliefs About Antilock Brake Systems: Have Preconditions for Behavioral Adaptation Been Met?" Transportation Research Record: Journal of the Transportation Research Board 1779, no. 1 (January 2001): 62–67. http://dx.doi.org/10.3141/1779-09.
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Some studies suggest that the benefits of antilock brake systems (ABS) may be offset through behavioral adaptation, such as driving faster or following closer. Whether preconditions for behavioral adaptation exist was examined by investigating driver knowledge and beliefs about ABS. Telephone interviews were conducted throughout Quebec early in 1999 with principal drivers of a stratified random sample of 404 drivers with currently registered light-duty vehicles, registered to the same person for at least 18 months. The response rate was 82 percent of 492 reached. Only medium-range and high-end 1990-1995 vehicles, for which ABS was either standard equipment or unavailable, were selected. The protocol involved mostly open questions that encouraged respondents to reveal their knowledge and beliefs with minimal prompting. The results indicated an important lack of understanding, on the part of a majority of drivers, regarding the functioning and use of ABS. This varied from an inability to identify conditions in which ABS is favorable or unfavorable to serious misconceptions; about 25 percent were wrong about whether their vehicle was ABS equipped. Cognitive preconditions for behavioral adaptations—sometimes increased prudence—were found for a minority of this sample, and there may be a relationship between a low level of knowledge and the perceived possibility of driving faster with these brakes. There appears to be a case for improved public and dealer-delivered information on the advantages and disadvantages of ABS in different driving conditions, which if balanced should not increase unsafe behavioral adaptation.
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Herndon, Caroline N., Sudarvili Shanthalingam, Donald P. Knowles, Douglas R. Call, and Subramaniam Srikumaran. "Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia." Clinical and Vaccine Immunology 18, no. 7 (May 25, 2011): 1133–38. http://dx.doi.org/10.1128/cvi.00044-11.
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ABSTRACTMannheimia haemolyticaconsistently causes fatal bronchopneumonia in bighorn sheep (BHS;Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related speciesOvis aries(domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) againstM. haemolyticaprovides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed againstM. haemolyticain the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens ofM. haemolyticaand approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia.
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Wang, Bai-nian, Ming-yang Chen, and Bao-jun Yang. "Modification and Compounding of CaMgAl-Layered Double Hydroxides and Their Application in the Flame Retardance of Acrylonitrile-Butadiene-Styrene Resin." Polymers 11, no. 10 (October 8, 2019): 1623. http://dx.doi.org/10.3390/polym11101623.
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CaMgAl-layered double hydroxides (CaMgAl-LDHs) were synthesized by a co-precipitation method to prepare sodium oleate-modified, borate-intercalated CaMgAl-LDHs (O-CaMgAl-LDHs) using in-situ intercalation and modification, and the LDHs samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), and thermal gravimetric analysis (TGA). The FESEM observations showed that the as-prepared CaMgAl-LDHs had a lamellar structure with a particle size of 200~500 nm, while the O-CaMgAl-LDHs had a plate-like structure with a particle size of about 100 nm. TGA showed that O-CaMgAl-LDHs resulted in higher thermal stability at high temperature compared to CaMgAl-LDHs. O-CaMgAl-LDHs/ABS composites were prepared by adding O-CaMgAl-LDHs to acrylonitrile-butadiene-styrene resin (ABS) to test the resulting flame retardancy and mechanical properties, and the results showed that the limiting oxygen index (LOI) could increase from 18% to 26%, while the mechanical properties decreased significantly when the added fraction was 40% (relative to ABS). O-CaMgAl-LDHs, ammonium polyphosphate (APP) and expandable graphite (EG) were added into the ABS to prepare ABS composites, and the effects of different compositions on the flame retardancy and mechanical properties of the ABS composites were investigated. The results showed that, when adding 5 g of O-CaMgAl-LDHs, 1 g of APP, and 14 g of EG into 40 g of ABS, the LOI of the ABS composite reached 28.8%, and the composite prepared could meet the V-0 grade requirements of the UL-94 combustion test, while the flexural strength decreased only 21.9% compared to pure ABS, the smallest decrease compared to all of the other composites.
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Beyazit, Yavuz, Tayyar Kart, Ahmet Kuscu, Alper Arslan, Mevlut Kurt, Bora Aktas, Murat Kekilli, and Ibrahim Haznedaroglu. "Successful Management of Bleeding after Dental Procedures with Application of Blood Stopper: A Single Center Prospective Trial." Journal of Contemporary Dental Practice 12, no. 5 (2011): 379–84. http://dx.doi.org/10.5005/jp-journals-10024-1063.
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ABSTRACT Aim Ankaferd Blood Stopper (ABS), as an herbal complementary medicine, has been approved for the management of clinical hemorrhages in Turkey, including dental interventions. Basic, preclinical and clinical studies disclosed the settings of the topical hemostatic use of ABS. The aim of this study is therefore to assess the efficacy and safety of ABS as an antihemorrhagic agent in the bleedings associated with dental procedures in patients with normal and impaired hemostasis. Materials and methods ABS has been topically applied by homogeneously spraying to the 113 patients during dental interventions within its on-label indications. A median of 0.5 ml (IQR:0.5-1 ml) ABS was administered after tooth extraction with prolonged hemorrhages. Results After the administration, bleeding stopped in less than 10 seconds in 59 (52.2%) patients, and below 22.5 seconds (IQR: 18, 8-30) in 54 patients (47.8%). A total of 141 procedures were performed in these 113 patients, and nearly 72.5 ml ABS was used with a total cost of 98 €. Conclusion ABS as a new herbal medicine was found to be an effective method for controlling bleeding related to dental procedures. No patient had wound infection and the healing process appeared to be normal. Topical ABS could be useful for the local hemostasis and wound healing in periodontal surgeries. Clinical significance In this prospective study ABS, for the first time, has demonstrated its potential for being an effective hemostatic agent for the management of bleedings due to dental procedures. How to cite this article Beyazit Y, Kart T, Kuscu A, Arslan A, Kurt M, Aktas B, Kekilli M, Haznedaroglu I. Successful Management of Bleeding after Dental Procedures with Application of Blood Stopper: A Single Center Prospective Trial. J Contemp Dent Pract 2011;12(5):379-384.
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Wong, S. S., D. L. T. Teo, and R. K. W. Chan. "Confirmatory serological testing of blood donors positive on TPHA screening in Singapore." International Journal of STD & AIDS 8, no. 12 (December 1, 1997): 760–63. http://dx.doi.org/10.1258/0956462971919237.
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Summary: Seventy-two blood donors who were tested positive by the Singapore Blood Transfusion Service (SBTS) for Treponema pallidum haemagglutination (TPHA) test, were evaluated at the Department of Sexually Transmitted Diseases Clinic (DSC) between November 1994 to December 1996. All underwent syphilis serological testing, including rapid plasma reagin test (RPR), TPHA test and fluorescent treponemal antibody-absorption (FTA-Abs) test. All except one (98.6%) were confirmed TPHA positive by the DSC. Of the 71 TPHA-confirmed-positive donors, 53 (74.6%) were subsequently tested positive for FTA-Abs and 18 (25.4%) were tested negative for FTA-Abs. Twenty-two (31%) of the 71 TPHA-positive blood donors had reactive RPR and 49 (69%) had non-reactive RPR. Of the 22 TPHA-positive donors who had reactive RPR, 19 (86%) had positive FTA-Abs (13 late latent syphilis, 4 serological scar, one late congenital syphilis, one secondary syphilis), and 3 (14%) had negative FTA-Abs (all late latent syphilis). Of the 49 TPHA-positive donors who had non-reactive RPR, 34 (69%) had positive FTA-Abs (24 late latent syphilis, 9 serological scar, one late congenital syphilis) and 15 (31%) had negative FTA-Abs (12 late latent syphilis, 2 serological scar, one false-positive TPHA). Only one TPHA-positive donor referred by the SBTS subsequently turned out to have negative syphilis serology at the DSC. Overall, 68 (95.8%) TPHApositive donors who had a past history of sexual exposure were managed as treated or untreated syphilis, regardless of their RPR or FTA-Abs results. However, FTAAbs was found to be useful in the management of 3 (4.2%) TPHA-positive blood donors in the absence of a history of sexual exposures.
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Morgan, James F., Glenn M. Gomes, and James M. Owens. "Outsourcing Investigations of Sexual Harassment: The Unexpected Consequences of Good Intentions." Employment Relations Today 27, no. 4 (2001): 65–78. http://dx.doi.org/10.1002/ert.18.abs.
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Shiao, Yaojung, Quang-Anh Nguyen, and Jhe-Wei Lin. "A Study of Novel Hybrid Antilock Braking System Employing Magnetorheological Brake." Advances in Mechanical Engineering 6 (January 1, 2014): 617584. http://dx.doi.org/10.1155/2014/617584.
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A novel hybrid antilock braking system (ABS) with the combination of auxiliary brake and a multipole magnetorheological (MR) brake was proposed in this paper. The MR brake with innovative operation concept can replace existed hydraulic brake system or works as an auxiliary brake. Two simulation models of the MR brakes, inner rotor and outer rotor structures, have been built. The outer rotor design was chosen due to its better braking performance and suitable mechanism for using on motorcycle. After that, motorcycle simulation software was employed to validate the hybrid ABS system under appropriated working condition. Two controllers, the ordinary and self-organizing fuzzy logic controllers (FLC and SOFLC), were evaluated on ABS performance to pick the suitable one. Simulation results confirm the more adaptations to different road conditions of the SOFLC with 18% higher brake performance compared to ones of ordinary FLC. Brake performance can increase 12% more with the combination of SOFLC and road condition estimator (RCE). It is concluded that this hybrid ABS is feasible for actual application by effectively improving the brake performance for ensuring driving stability.
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Lee, Eun-Young, Xilin Zhang, Junki Miyamoto, Ikuo Kimura, Tomoaki Taknaka, Kenichi Furusawa, Takahito Jomori, Kosuke Fujimoto, Satoshi Uematsu, and Takashi Miki. "Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway." Journal of Endocrinology 239, no. 3 (December 2018): 267–76. http://dx.doi.org/10.1530/joe-18-0241.
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Mechanisms of carbohydrate-induced secretion of the two incretins namely glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are considered to be mostly similar. However, we found that mice exhibit opposite secretory responses in response to co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol), stimulatory for GLP-1, as reported previously, but inhibitory for GIP. Gut microbiota was shown to be involved in maltose/miglitol-induced GIP suppression, as the suppression was attenuated in antibiotics (Abs)-treated mice and abolished in germ-free mice. In addition, maltose/miglitol administration increased plasma levels of short-chain fatty acids (SCFAs), carbohydrate-derived metabolites, in the portal vein. GIP suppression by maltose/miglitol was not observed in mice lacking a SCFA receptor Ffar3, but it was normally seen in Ffar2-deficient mice. Similar to maltose/miglitol administration, co-administration of glucose plus a sodium glucose transporter inhibitor phloridzin (glucose/phloridzin) induced GIP suppression, which was again cancelled by Abs treatment. In conclusion, oral administration of carbohydrates with α-glucosidase inhibitors suppresses GIP secretion through a microbiota/SCFA/FFAR3 pathway.
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Benzidi, Younès, Thibault Duburcq, Daniel Mathieu, and Erika Parmentier-Decrucq. "Evaluation of pressure in water-filled endotracheal tube cuffs in intubated patients undergoing hyperbaric oxygen treatment." Diving and Hyperbaric Medicine Journal 50, no. 3 (September 30, 2020): 230–37. http://dx.doi.org/10.28920/dhm50.3.230-237.
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Introduction: Inflating endotracheal tube cuffs using water instead of air before hyperbaric oxygen treatment (HBOT) is common. The objective of this study was to assess cuff pressure (Pcuff), when the cuff was inflated using water, in normobaric conditions and during HBOT. Methods: This was a prospective, observational study taking place in hyperbaric centre and intensive care unit of the University Hospital of Lille. Every patient who required tracheal intubation and HBOT at 253.3 kPa (2.5 atmospheres absolute [atm abs]) was included. Pcuff was measured using a pressure transductor connected to the cuff inflating port. Measurements were performed at 'normobaria' (1 atm abs) and during HBOT at 2.5 atm abs. Results: Thirty patients were included between February and April 2016. Recordings were analysable in 27 patients. Mean Pcuff at normobaria was 60.8 (SD 42) cmH2O. Nineteen (70%) of patients had an excessive Pcuff (higher than 30 cmH2O). Coefficient of variation was 69%. Mean Pcuff at 2.5 atm abs was 51.6 (40.7) cmH2O, significantly lower than at normobaria (P < 0.0001). Coefficient of variation was 79%. In only five (18%) patients was Pcuff < 20 cmH2O at 2.5 atm abs. Conclusions: In normobaric conditions, when the cuff was inflated using water and not specifically controlled Pcuff was not predictable. The cuff was typically over-inflated exceeding safe pressure. During HBOT Pcuff decreased slightly.
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Först, Gesche, Winfried V. Kern, Nadine Weber, Christiane Querbach, Johannes Kleideiter, Holger Knoth, Stefan Hagel, et al. "Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany." Journal of Antimicrobial Chemotherapy 74, no. 12 (August 23, 2019): 3596–602. http://dx.doi.org/10.1093/jac/dkz364.
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Abstract Objectives The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German–Austrian hospital ABS practice guideline. Methods Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. Results Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. Conclusions Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.
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von Drygalski, Annette, Brian Curtis, Dan Bougie, Scott Ahl, Kelty Baker, and Richard H. Aster. "Immune-Mediated Thrombocytopenia in Patients Treated with Vancomycin." Blood 106, no. 11 (November 16, 2005): 1238. http://dx.doi.org/10.1182/blood.v106.11.1238.1238.
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Abstract Numerous drugs are known to cause immune thrombocytopenia (TP) mediated by antibodies (abs) that bind to platelets only when the sensitizing drug is present in soluble form. The widely used antibiotic, vancomycin, has been implicated as a cause of TP only in 8 case reports and little is known about antibodies possibly responsible for this complication. We characterized clinical and serologic aspects of TP occurring in 39 patients during treatment with vancomycin. In this group, TP developed after 1–27 days of treatment (median 6 days) and plt nadirs ranged from 1,000 to 60,000 plts/uL (median 14,000 plts/uL). Bleeding occurred in 14 patients and contributed to a fatal outcome in 3. TP persisted for 1–17 days after discontinuing vancomycin (median 7 days). Platelets eventually returned to baseline in all surviving patients. Serum obtained after the onset of TP was studied for vancomycin-dependent, platelet-reactive abs by flow cytometry and by solid phase ELISA using immobilized plt glycoproteins (GP) as targets. Vancomycin-dependent antibodies detected in patients and normal subjects IgG only IgM only IgG + IgM No antibody Total Patients with TP 21 (54%) 5 (13%) 13 (33%) (0)%) 39 Normal individuals 58 (21%) 4 (1%) 1 (0%) 210 (77%) 273 Results of flow cytometric studies are summarized above. All patients had IgG and/or IgM abs that reacted with normal plts in the presence, but not in the absence of vancomycin. The IgG mean fluorescence intensity (MFI) signal in the presence of drug was 1.6 to 32.0 times stronger (mean ratio 5.7) than that obtained in the absence of drug. Vancomycin-dependent IgG abs were also identified in 59 of 273 normal individuals but were much weaker than abs detected in patients (p = 0.004). IgM abs (mean ratio 5.7, range 1.6 – 34) were found in 18 of 39 patients (46%). Weaker IgM abs were found in only 5 of 273 normal subjects (1.8%) (p = 0.001). Two patient abs studied in ELISA reacted preferentially with GPIIb/IIIa. Studies to determine the frequency of abs in patients given vancomycin who do not develop TP are in progress. These findings provide evidence that TP in patients given vancomycin can be caused by drug-dependent abs specific for GPIIb/IIIa that are stimulated by vancomycin exposure. IgG and IgM abs in patients with TP are generally much stronger than drug-dependent, platelet-reactive immunoglobulins found in some normal subjects. The significance of the latter abs is presently unknown. Drug-dependent IgM abs are found almost exclusively in patients with vancomycin-associated TP and may be diagnostic. Patients treated with vancomycin often have life-threatening bacterial sepsis and may have various reasons for developing TP. Serologic testing for drug-dependent, platelet-reactive IgG and IgM abs may provide a means of identifying those in whom vancomycin should be discontinued.
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Bertrand, Yves, Andre Baruchel, Xavier Thomas, Nicolas Blin, Emmanuelle Tavernier, Stephane Ducassou, Norbert Vey, et al. "Evaluation of the Impact of the Presence of Neutralizing L-Asparaginase Antibodies on the Efficacy and Safety of Graspa in Phase 3 Randomized Trial Versus Native L-Asparaginase in Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)." Blood 126, no. 23 (December 3, 2015): 3734. http://dx.doi.org/10.1182/blood.v126.23.3734.3734.
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Abstract Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (eryaspase - proposed INN) is an L-asparaginase encapsulated into the red blood cells. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the mean duration of asparaginase (ASPA) activity > 100 IU/L and incidence of hypersensitivity reactions during induction phase. Key secondary endpoints were safety, tolerability, complete remission and minimal residual disease rate, PK, and anti-ASPA antibodies (A-Abs) at baseline. Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n=28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C). All pts received COOPRALL protocol as a backbone chemotherapy. Here we report the impact of A-Abs on safety and efficacy of GRASPA. Assessments were performed at Day 4, 13, 18, and 27 (F1/F2 block), Day 6, 15, and 27 (VANDA block), and Day 6, 12 (R2/R1 block). Results At baseline, 23%, 25%, and 58% of pts had +ve A-Abs status in Arms A, B, and C, respectively. The mean duration of total ASPA activity (Days) adjusted for baseline antibody status is presented below, and shows that activity slightly differed with positive status; however, GRASPA maintained higher activity compared to L-ASP: Table 1. GRASPA L-ASP GRASPA L-ASP GRASPA (Arm C) Antibody status Negative Positive Negative Positive N 20 21 6 7 11 15 Mean (SD) 22.4 (3.6) 10.31 (8.1) 14.17 (5.1) 6.5 (4.0) 18.9 (6.8) 18.4 (6.2) Median 22.4 8.3 12.2 7.0 21.8 21.7 Min; Max 10.2; 30.7 0.0; 25.0 9.8; 21.8 1.9; 14.0 9.1; 27.9 6.9; 25.0 The incidence of hypersensitivity reactions were 0%, 7/21 (33%), and 2/11 (18%) in pts with negative A-Abs, compared to 0%, 6/7 (85.7%), and 1/15 (7%) in pts with positive A-Abs, in arms A, B and C, respectively. The CR rate during induction was 75%, 48%, and 64% in pts with negative A-Abs, compared to 33%, 14% and 48% in pts with positive A-Abs, in arms A, B and C, respectively. Conclusion These results show that about one third of pts without evidence of prior hypersensitivity have silent A-Abs activation. Positive A-Abs appeared to attenuate the clinical activity in all treatments arms. GRASPA consistently demonstrated activity and improved hypersensitivity regardless of A-Abs status, and therefore, GRASPA is a suitable option for patients with relapsed ALL. Disclosures Bertrand: ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Thomas:ERYTECH Pharma: Consultancy. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.
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Graczykowska, Tamara. "„Nieaktualna” leksyka ogólnopolska w dwudziestoleciu międzywojennym (na materiale gazety „Trybuna Radziecka” z lat 1927–1938 – litery a–b)." Acta Baltico-Slavica 37 (June 30, 2015): 527–41. http://dx.doi.org/10.11649/abs.2013.036.
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"The outdated" Polish lexis in the interwar period (based on Trybuna Radziecka 1927–1938, letters a–b)This paper discusses 27 lexemes extracted from Trybuna Radziecka, the Polish weekly published in Moscow in 1927–1938 and edited by Polish left-intelligentsia, living in the USSR as political émigrés in the interwar period. The lexical items are listed in the form of a dictionary with examples and comments.The largest group are lexemes whose frequency in Polish is decreasing (18 items); the next group are words becoming obsolete (8 items); 15 lexems still function in the postwar Northern Borderland Polish (e.g. aeroport, akuratnie, arenda, asfaltowany, automobil, automobilowy, awjacja, bezpodstawowy, biust, bizun); one item belongs to the older vocabulary of general Polish and one to already outdated lexis. Apart from these groups, twelve lexemes had been derived from Russian words (e.g. adres, aeroport, akuratnie, arenda, automobile). «Неупотрeбляемая» польская лексика в междувоенный период (на материале газеты «Trybuna Radziecka» за годы 1927–1938, буквы А–Б)В статье проводится анализ лексики, извлеченнoй из газеты «Trybuna Radziecka» (буквы А–Б), издаваемой в Москве польскими коммунистами в период между двумя мировыми войнами (годы 1927–1938). Рассматриваются лишь слова, принадлежащие к лексике, вышедшей из употребления в oбщепольском языке. Доминируют рецессивные слова (18 примеров) и выходящие из упторебления (8 примеров). Мы обнаружили также одно устаревшее слово и один архаизм. Стоит подчеркнуть, что значительная часть слов (12 единиц) нашла поддержку в русском языке, что способствовало их более длительному сохранению в языке поляков, проживающих в Советской России в междувоенный период. Подытоживая, следует сказать, что хотя неупотребляемая лексика занимала незначительную позицию среди всех слов (в пределах букв А–Б), почерпнутых из газеты «Trybuna Radziecka», её наличие в языке источника всё же отражало общие черты советского польского языка послереволюционного периода.
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Riss. "Verfahren nach §§ 18, 19 MRG – keine Auswirkungen auf Präklusivfrist des § 16 Abs 8 MRG." Wohnrechtliche Blätter 20, no. 5 (May 2007): 136–37. http://dx.doi.org/10.1007/s00719-007-0785-6.
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Lupi, Isabella, Luca Manetti, Patrizio Caturegli, Michele Menicagli, Mirco Cosottini, Aldo Iannelli, Giovanni Acerbi, Generoso Bevilacqua, Fausto Bogazzi, and Enio Martino. "Tumor Infiltrating Lymphocytes But Not Serum Pituitary Antibodies Are Associated with Poor Clinical Outcome after Surgery in Patients with Pituitary Adenoma." Journal of Clinical Endocrinology & Metabolism 95, no. 1 (January 1, 2010): 289–96. http://dx.doi.org/10.1210/jc.2009-1583.
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Abstract Context: Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown. Objective: The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome. Design: This was a prevalence case-control study. Patients and Setting: Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center. Intervention: Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72). Main Outcome Measure: Clinical response of pituitary adenoma after surgery was evaluated. Results: Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma. Conclusions: TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.
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Maple, P. A. C., D. Ratcliffe, and E. Smit. "Characterization of Treponema pallidum Particle Agglutination Assay-Negative Sera following Screening by Treponemal Total Antibody Enzyme Immunoassays." Clinical and Vaccine Immunology 17, no. 11 (September 15, 2010): 1718–22. http://dx.doi.org/10.1128/cvi.00102-10.
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ABSTRACT Following a laboratory audit, a significant number of Treponema pallidum particle agglutination assay (TPPA)-negative sera were identified when TPPA was used as a confirmatory assay of syphilis enzyme immunoassay (EIA) screening-reactive sera (SSRS). Sera giving such discrepant results were further characterized to assess their significance. A panel of 226 sera was tested by the Abbott Murex ICE Syphilis EIA and then by the Newmarket Syphilis EIA II. TPPA testing was performed on 223 sera. Further testing by the Venereal Disease Research Laboratory (VDRL) test, the Mercia Syphilis IgM EIA, the fluorescent treponemal antibody (FTA-ABS) assay, and INNO-LIA immunoblotting was undertaken in discrepant cases. One hundred eighty-seven of 223 (83.8%) SSRS were TPPA reactive, while 26 (11.6%) sera which were reactive in both the ICE and Newmarket EIAs were nonreactive by TPPA. The majority (68%) of the TPPA-discrepant sera were from HIV-positive patients and did not represent early acute cases, based on previous or follow-up samples, which were available for 22/26 samples. FTA-ABS testing was performed on 24 of these sera; 14 (58.3%) were FTA-ABS positive, and 10 (41.7%) were FTA-ABS negative. Twenty-one of these 26 sera were tested by INNO-LIA, and an additional 4 FTA-ABS-negative samples were positive. In this study, significant numbers (18/26) of SSRS- and TPPA-negative sera were shown by further FTA-ABS and LIA (line immunoblot assay) testing to be positive. The reason why certain sera are negative by TPPA but reactive by treponemal EIA and other syphilis confirmatory assays is not clear, and these initial findings should be further explored.
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Andrievskaya, I. A., N. A. Ishutina, and O. L. Kutepova. "FREE-RADICAL OXIDATION AND OXYGENATION OF HEMOGLOBIN AT EXACERBATION OF CYTOMEGALOVIRUS INFECTION IN THE SECOND TRIMESTER OF PREGNANCY." Acta Biomedica Scientifica 3, no. 4 (July 28, 2018): 9–14. http://dx.doi.org/10.29413/abs.2018-3.4.1.
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The aim of the study was to assess free radical processes and their effect on oxygenation of hemoglobin in the blood of 18-21 weeks pregnant women with exacerbation of cytomegalovirus infection. We examined 40 pregnant women with exacerbation of cytomegalovirus infection and various levels of specific antibodies (IgM) at 18-21 weeks and 30 pregnant women without cytomegalovirus. The spectrophotometric method was used to determine the content of oxyhemoglobin, methemoglobin, thiobarbituric acid (TBA)-active products, superoxide dismutase in blood erythrocytes; thin layer chromatography – phosphotidylcholine, lysophosphatidylcholine; gas-liquid chromatography – arachidonic acid. Exacerbation of cytomegalovirus infection changes the activity of free radical oxidation processes, the severity of which is determined by the level of IgM antibodies and is manifested by a decrease in superoxide dismutase (p = 0.000) and phosphatidylcholine (p = 0.000), an increase in phospholipase A2 (p = 0.000), lysophosphatidylcholine (p = 0.000), arachidonic acid (p = 0.000) and TBA-active products (p = 0.000). Accumulation of superoxide anion radical and products of lipoperoxidation in erythrocytes decreases oxyhemoglobin (p = 0.000) and increases methemoglobin (p = 0.000). Exacerbation of cytomegalovirus infection at 18-21 weeks is associated with the enhancement of free radical lipid oxidation and a deficiency in the antioxidant activity of superoxide dismutase. It decreases oxygen transport properties and increases phagocytosis by red blood monocytes; and pregnant women develop further hemic hypoxia.
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Markiewicz, Miroslaw, Anna Koclega, Sylwia Mizia, Urszula Siekiera, Alicja Dobrowolska, Monika Dzierzak-Mietla, Patrycja Zielinska, Krzysztof Bialas, and Slawomira Kyrcz-Krzemien. "The Influence Of Anti-HLA Antibodies On Engraftment and Donor’s Chimerism Following Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Mismatched Unrelated Donors." Blood 122, no. 21 (November 15, 2013): 4542. http://dx.doi.org/10.1182/blood.v122.21.4542.4542.
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Introduction Although anti-HLA Antibodies (Abs) are considered an important factor of graft failure in solid organ transplants, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still undiscovered. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define the presence of anti-HLA Abs before allo-HSCT from HLA-mismatched unrelated donors and their impact on engraftment and post-transplant full donor’s chimerism. Material and Methods 70 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL, AML, CML, SAA, PNH, MDS and CLL. Preparative regimen was myeloablative in 68pts (97%) and reduced in 2pts (2.3%). Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (69pts) or Alemtuzumab (1pt). HLA A,B,C,DR,DQ alleles were PCR-typed. Single HLA-antigen was mismatched in 46pts, single HLA-allele in 16pts, double antigens or alleles in 2 pts and another 2 pts had combined antigenic/allelic HLA mismatch. Anti-HLA A,B,C,DR,DQ,DP Abs were identified in sera collected prior to the conditioning treatment with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens. Post-transplant chimerism was analyzed using STR-PCR method at 30, 100-days and 1-year after allo-HSCT. Results Anti-HLA Abs pre-formed before allo-HSCT were detected in 32pts: against class I, II or both in 13(18.6%), 7(10%) and 12(17.1%) pts. Anti-HLA Abs were detected after allo-HSCT in 49pts: against class I, II or both in 22(32.4%), 7(10.3%) and 20(29.4%) pts, respectively. Anti-HLA Abs directed against the mismatched HLA antigens were observed in 4 pts before allo-HSCT. Although no Abs specific to mismatched HLA alleles were detected, Abs belonging to the same Cross-Reactive Groups (CREGs) were present in 5pts. No graft failure has been observed (graft failure was defined as absence of neutrophil recovery by day 30 after allo-HSCT or loss of donor’s chimerism). The detection of anti-HLA Abs before allo-HSCT was associated with decrease of post-transplant donor’s chimerism (18/31 vs 11/35, p=0.03). Anti-HLA Abs had no significant impact on engraftment of platelets and neutrophils. The median time to neutrophils engraftment was 16.9 days (range 7-31 days) in pts with and 18.9 days (range 13-30 days) in pts without anti-HLA Abs (p=0.188). The median time to platelets engraftment was 16.9 days (range 9-31 days) in patients with and 18.3 days (range 10-32 days) in pts without anti-HLA Abs (p=0.274). Conclusions Our preliminary results indicate, that anti-HLA Abs are present before transplantation in mismatched allo-HSCT recipients. They influence the post-transplant full donor’s chimerism, but they did not influence engraftment and graft failure. Disclosures: No relevant conflicts of interest to declare.
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Barger, Troy E., Andy Boshier, Vibha Jawa, June Kim, Daniel T. Mytych, Joseph Park, and David J. Kuter. "Assessment of Romiplostim Immunogenicity in Adult Patients in Clinical Trials and in a Global Registry." Blood 132, Supplement 1 (November 29, 2018): 2427. http://dx.doi.org/10.1182/blood-2018-99-113484.
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Abstract Background: Romiplostim (Nplate®) is a thrombopoietin (TPO) receptor agonist approved for the treatment of adult chronic immune thrombocytopenia (ITP). The formation of antibodies (Abs) against romiplostim may lead to a loss of response, and a theoretical risk exists that an immune response against romiplostim might lead to the formation of Abs that bind both romiplostim and native TPO. We therefore examined Abs against romiplostim and TPO in adult patients (pts) enrolled in clinical trials and in a global postmarketing registry based on spontaneously submitted requests for Ab testing. Methods: The clinical trial population included adult pts (age ≥18 years at screening) with ITP who received ≥1 dose of romiplostim in any of 13 completed romiplostim clinical trials, including phase 1 (n=1), phase 2 (n=3), phase 1/2 (n=1), phase 3 (n=5), and open-label extension (n=3) studies. Duration of romiplostim treatment varied among the trials. The postmarketing global registry population included romiplostim-treated adult pts with ITP who had blood samples sent for Ab testing. Serum samples from the clinical trials and the registry were assessed for romiplostim and TPO binding Abs in a surface plasmon resonance (SPR)-based immunoassay, and samples positive for binding were assessed for neutralizing activity in a cell-based bioassay, as previously described (Jawa et al. Ann Hematol 2010). Pt characteristics were summarized for those who did and did not develop Abs in the clinical trials. Pts in the registry found to have romiplostim neutralizing Abs were to be followed every 3 months for up to 12 months. No formal statistical analyses were conducted. Results: A total of 1046 romiplostim-treated pts from clinical trials were available for analysis. At baseline, 958 pts had romiplostim Ab results: 35 pts (3.7%) were positive for binding Abs and 1 pt (0.1%) was positive for neutralizing Abs. Post-baseline, 961 pts had romiplostim Ab results: 80 pts (8.3%) were positive for binding Abs and 4 pts (0.4%) were positive for neutralizing Abs, independent of the baseline result. Sixty (6.2%) pts negative for anti-drug Abs at baseline developed romiplostim binding Abs during the clinical trials. Characteristics of the pts who did and did not develop romiplostim binding Abs are presented in Table 1. Development of romiplostim binding Abs was more frequent in pts with ITP duration >3 years at baseline (70.0% vs 57.4%), prior splenectomy (48.3% vs 37.5%), and a history of allergies (21.7% vs 8.4%). Pts who developed Abs also had lower baseline TPO levels (84.8 pg/mL vs 104.6 pg/mL), lower baseline platelet counts (12.5× 109/L vs 20.5 × 109/L), and a higher number of previous ITP treatments (median 3 vs 2). Four of the 60 pts with romiplostim binding Abs developed romiplostim neutralizing Abs after treatment (0.38% of 1046 pts overall; Table 2). The emergence of neutralizing Abs did not appear to be related to romiplostim dose or platelet count. The neutralizing Abs were directed against the peptide component of romiplostim and did not bind native TPO. Pts in the clinical trials were also tested for TPO Abs. At baseline, 956 pts had TPO Ab results: 31 pts (3.2%) were positive for TPO binding Abs and 1 pt (0.1%) was positive for neutralizing Abs. Post-baseline, 960 pts had TPO Ab results: 33 pts (3.4%) were positive for TPO binding Abs and no pts were positive for neutralizing Abs. Of the 184 adult pts in the registry, 9 (4.9%) were positive for binding Abs: 5 were positive for romiplostim binding, 2 for TPO binding, and 2 for romiplostim and TPO binding. No predose Ab results were available for these pts. One pt received romiplostim for 11 months at a dose of 2 µg/kg and then experienced an abrupt fall in platelet count even as romiplostim dose was increased to 10 µg/kg. The pt tested positive for romiplostim binding and neutralizing Abs. Romiplostim was discontinued, and the pt was switched to alternative therapy. Conclusions: An analysis of pts in 13 clinical trials shows that pts with indicators of more severe disease (longer duration of ITP, prior splenectomy, and a higher number of previous ITP treatments) may be at increased risk of developing romiplostim binding Abs. Development of romiplostim neutralizing Abs was uncommon in the clinical trials, and these Abs did not bind native TPO. Data from a postmarketing registry showed that the overall risk of clinically significant immunogenicity following exposure to romiplostim is low. Disclosures Barger: Amgen Inc.: Employment, Equity Ownership. Boshier:Sanofi: Other: rents a room to a Sanofi employee; Amgen Inc.: Employment, Equity Ownership. Kim:Amgen Inc.: Employment, Equity Ownership. Mytych:Amgen Inc.: Employment, Equity Ownership. Park:Amgen Inc.: Employment, Equity Ownership. Kuter:Amgen Inc.: Consultancy; Argenx: Consultancy; Rigel: Consultancy, Research Funding; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Principia: Research Funding; Protalex: Research Funding; Pfizer: Consultancy; Bioverativ: Consultancy, Research Funding; ONO: Consultancy; Syntimmune: Consultancy; BMS: Research Funding.
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Terlitza, Ulfried. "Rechtszuständigkeit der Eigentümergemeinschaft abseits des § 18 Abs 2 WEG 2002: Geltendmachung von Schadenersatz- und Beseitigungsansprüchen?" wohnrechtliche blätter 32, no. 2 (2019): 61. http://dx.doi.org/10.33196/wobl201902006101.
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Liu, LX, MA Nardi, JF Casella, and S. Karpatkin. "Inhibition of binding of anti-PLA1 antibodies to platelets with monoclonal antibody LK-4. Evidence for multiple PLA1 receptor sites on platelet GPIIIa." Blood 88, no. 9 (November 1, 1996): 3601–7. http://dx.doi.org/10.1182/blood.v88.9.3601.bloodjournal8893601.
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The PLA1 epitope on platelet GPIIIa has a sulfhydryl-dependent conformation and is dependent on a leucine 33/proline33 polymorphism. Monoclonal antibody LK-4 differentiates PLA1/PLA1 from PLA2/PLA2 platelet lysates on solid phase enzyme-linked immunosorbent assay (ELISA), as well as immunoblot. To determine whether LK-4 reacts at or near the binding site(s) for human anti-PLA1, nine such antibodies (Abs) (six neonatal; three posttransfusion) were examined in the presence and absence of LK-4 for binding to platelets, as well as rGPIIIa 1–66, a recombinant glutathione S-transferase fusion peptide. All nine human Abs bound to rGPIIIa 1–66, as well as platelets, in a saturation-dependent manner, employing both solid phase ELISA, as well as flow cytometry. Binding of all nine Abs to rGPIIIa 1–66 or platelets was inhibited by LK-4. IC50′s for inhibition of binding of anti-PLA1 to rGPIIIa 1–66 varied from 8 to 160 micrograms/mL (5 x 10(-8)- 1 x 10(-6) mol/L). However, IC50′s for LK-4 inhibition of binding to platelets was strikingly different. Six of the nine Abs had IC50′s of 1 to 10 micrograms/mL (8-fold to 16-fold greater inhibition than with rGPIIIa 1–66), whereas three neonatal Abs had IC50′s of 380 to 1,013 micrograms/mL (6-fold to 48-fold less inhibition than with rGPIIIa 1–66). Similar results were noted with intact GPIIIa, rGPIIIa 1–66 blocked the binding of anti-PLA1 Abs to platelets and served to segregate the nine patients into two groups: a sensitive group of anti-PLA1 Abs from six patients in which binding to platelets was progressively inhibited by increasing concentrations of rGPIIIa 1–66 with inhibition at 1 micrograms/mL of 18% and inhibition at 256 micrograms/mL of 78%; a second resistant group of three anti-PLA1 Abs from three patients in which inhibition was first noted at 16 micrograms/mL of 4% with 35% inhibition at 256 micrograms/mL. Thus, LK-4 binds to GPIIIa at the 1–66 N-terminal region, inhibits binding of anti-PLA1 Ab to platelets, and segregates, anti-PLA1 Abs into two groups. These data are compatible with two or more receptor sites for anti-PLA1 Ab: one that is present on rGPIIIa 1–66 and sensitive to LK-4 inhibition, another that is present on rGPIIIa 1–66, as well as other site(s) on platelet GPIIIa and insensitive to inhibition.
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Chatterjee, Diptendu, Maurizio Pieroni, Meena Fatah, Flavien Charpentier, Kristopher S. Cunningham, Danna A. Spears, Dipashree Chatterjee, et al. "An autoantibody profile detects Brugada syndrome and identifies abnormally expressed myocardial proteins." European Heart Journal 41, no. 30 (June 12, 2020): 2878–90. http://dx.doi.org/10.1093/eurheartj/ehaa383.
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Abstract Aims Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients. Methods and results For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates. Conclusion A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.
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Shimizu, Daisuke, Harumi Fujihara, Hiroki Shibata, Chiaki Yamada, Hiroyuki Furumaki, Hiroko Watanabe, Keiko Ishizuka, et al. "Difference In Erythrocyte Alloantibodies After Blood Transfusion In Patients With Hematological and Non-Hematological Diseases." Blood 122, no. 21 (November 15, 2013): 2404. http://dx.doi.org/10.1182/blood.v122.21.2404.2404.
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Abstract Introduction The incidence of irregular erythrocyte allo-antibodies (Abs) increases with the amount of previous erythrocyte transfusions. Blood transfusion has been one of the most important supportive cares in patients with hematological diseases. Therefore, patients with hematological diseases, such as leukemia and myelodysplastic syndrome, have often received considerable amounts of blood transfusion, and have a higher risk for alloimmunization against erythrocyte antigens. On the other hand, patients receiving chemotherapy and immunotherapy exhibit less antibody response than do patients with non-hematological diseases. Several authors reported that the frequency of irregular erythrocyte Abs was unexpectedly low in these patients (Schonewille et al., 2009). In this study, we retrospectively analyzed the frequency and the contents of Abs after blood transfusion in patients with hematological and non-hematological diseases. Materials and Methods We selected patients with hematological or non-hematological diseases, who were transfused in our hospital from 2000 to 2011. We analyzed the patients' profiles including gender, age, the number of blood units previously transfused, and category of transfused products. We also studied the frequencies of irregular erythrocyte Abs. If the same patient was tested more than once, it was counted as one case. If more than two antibodies were detected in the same blood sample, they were tallied separately. If a patient had different antibodies at different times, all of them were summarized. We compared antibody frequencies between the patients with hematological or non-hematological diseases. Statistical analysis was performed by chi-square test and F-test followed by Student's t-test. Results The numbers of patients with hematological or non-hematological diseases were 517 and 4,311 cases, respectively (Table 1). Gender was similar (male / female: 1.35 vs. 1.38, NS). Median age was 64 years (range: 15-93) vs. 75 years (2-82) (p< 0.001). The median amount of transfused erythrocytes was 18 units (2-358) and 8 units (1-182), respectively. Abs were detected in 24 (4.6%) and 129 cases (2.9%), respectively (p< 0.05). Frequently determined Abs were as follows: anti-E (63% vs. 34%), anti-Lea (13% vs. 23%), anti-C (4% vs. 5%), anti-Dia (4% vs. 5%), anti-Jka (4% vs. 6%), and anti-E+c Ab(4% vs. 8%, respectively) (Fig. 1). The amount of erythrocyte transfusions until determination of Abs was 19 units (10-100) and 14 units (2-84), respectively. Discussion The frequency of irregular erythrocyte Abs was significantly greater in patients with hematological diseases than in those with non-hematological diseases. The amount of erythrocyte transfusions was greater and age was younger in those with hematological diseases. Anti-E Ab, whose frequency is reportedly less in Japanese, was more frequently detected in those with hematological diseases, while non-Rh Abs were more frequently detected in those with non-hematological diseases. Analyses after the exclusion of perioperative transfusion showed that the amount of erythrocyte transfusion until determination of Abs was greater in those with hematological diseases. These results showed that irregular Abs were more frequently detected in patients with hematological diseases, but the Abs are poorly productive in these patients after the same amount of transfusion. Further studies will solve the detailed mechanisms. Disclosures: No relevant conflicts of interest to declare.
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Koclega, Anna, Miroslaw Markiewicz, Sylwia Mizia, Urszula Siekiera, Alicja Dobrowolska, Monika Dzierzak-Mietla, Krzysztof Bialas, and Slawomira Kyrcz-Krzemien. "No Influence of Post-Transplant Anti-HLA Antibodies on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Mismatched Unrelated Donors." Blood 126, no. 23 (December 3, 2015): 5538. http://dx.doi.org/10.1182/blood.v126.23.5538.5538.
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Abstract Introduction: Although anti-HLA Antibodies (Abs) are considered an important factor of graft failure in solid organ transplants, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still undiscovered. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define the presence of anti-HLA Abs after allo-HSCT from HLA-mismatched unrelated donors and their impact on outcomes of allo-HSCT. Material and methods: 68 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL, AML, CML, SAA, PNH, MDS and CLL. Preparative regimen was myeloablative in 66(97%)pts and reduced in 2(3%)pts. Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (67pts) or Alemtuzumab (1pt). HLA A,B,C,DR,DQ alleles were PCR-typed. Single HLA-antigen was mismatched in 44pts, single HLA-allele in 16pts, double antigens or alleles in 2 pts and another 2 pts had combined antigenic/allelic HLA mismatches. Anti-HLA A,B,C,DR,DQ,DP Abs were identified in sera collected at +30, +100 days and 1 year post-transplant with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens. Post-transplant chimerism was analyzed using STR-PCR method at 30, 100-days and 1-year after allo-HSCT. Results: Anti-HLA Abs were detected post-transplant in 49(72.1%) patients at least at one of three examined time-points. They were directed against HLA class I, II or both in: 22(32.4%), 7(10.3%) or 20(29.4%) patients, respectively. In 3 (4.4%) patients antibodies for many specificities were detected. Anti-HLA antibodies detected during the first year after transplantation did not impact the donor's chimerism. Full donor's chimerism was observed in 22/48 (46%) patients without versus 7/18 (39%) patients with anti-HLA Abs, p=0.615). Anti-HLA Abs present after transplantation also did not impact the risk of developing aGVHD, grades neither I-IV (36/49, 73% in positive versus 17/19, 89% in negative group, p=0.270), nor II-IV (15/49, 31% in positive versus 8/19, 42% in negative group, p=0.372). Chronic GVHD and extensive cGVHD also were not influenced by anti-HLA Abs detected post-transplant (23/49, 47% versus 10/19, 53%, p=0.676) and (13/49, 27% versus 5/19, 26%, p=0.986), respectively. Post-transplant anti-HLA Abs did not influence the recurrence of the disease, which was observed in 9/49 (18.3%) patients with versus 1/19 (5.2%) patients without anti-HLA antibodies, p=0.323, nor the overall survival at 3-years (54% in anti-HLA Abs positive versus 46% in anti-HLA Abs negative patients, p=0.207). Conclusions: Our results indicate, that anti-HLA Abs can be detected post-transplant in HLA-mismatched allo-HSCT recipients. Presence of anti-HLA antibodies detected after allo-HSCT was not associated with occurrence of aGVHD, cGVHD, relapse nor overall survival. Disclosures No relevant conflicts of interest to declare.
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Murray, John J., Paz Emparanza, Eugenijus Lesinskas, Margaret Tawadrous, and Jeanne D. Breen. "Efficacy and Safety of a Novel, Single-dose Azithromycin Microsphere Formulation Versus 10 Days of Levofloxacin for the Treatment of Acute Bacterial Sinusitis in Adults." Otolaryngology–Head and Neck Surgery 133, no. 2 (August 2005): 194–200. http://dx.doi.org/10.1016/j.otohns.2005.04.020.
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Objective To compare the efficacy and safety of a single 2.0-g dose of a novel azithromycin microsphere formulation with that of 10 days of levofloxacin, 500 mg/d, when used to treat adults with uncomplicated acute bacterial maxillary sinusitis (ABS). Study Design and Setting An international, multicenter, randomized, double-blind, double-dummy trial. Eligible outpatients ≥18 years of age with clinical and radiographic evidence of ABS underwent maxillary sinus aspiration before randomization. Primary endpoint was clinical efficacy at the test-of-cure visit (day 17-24). Results Clinical success rates were 94.5% (242/256) in azithromycin-microspheres-treated patients and 92.8% (233/251) in the levofloxacin group. In patients with documented Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3% (36/37), 96.3% (26/27), and 100% (8/8), respectively, for the azithromycin group and 92.3% (36/39), 100% (30/30), and 90.9% (10/11), respectively, for the levofloxacin group. Conclusions Single-dose azithromycin microspheres provided clinical and bacteriologic efficacy and safety comparable to 10 days of levofloxacin. Significance A novel microsphere formulation of azithromycin given as a single dose was safe and effective for the treatment of ABS.
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Robles, Noemi, Laura Muñoz Ortiz, and Mireia Espallargues. "VP174 Atlases Of Quality: Assessing Integrated Care In Chronic Diseases." International Journal of Technology Assessment in Health Care 33, S1 (2017): 230–31. http://dx.doi.org/10.1017/s0266462317004093.
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INTRODUCTION:The Comprehensive Public Healthcare System of Catalonia (SISCAT) Atlases of Quality aim to evaluate the quality of care in relation to specific diseases or procedures in the Catalan territory with a focus on outcomes of care in order to promote best practices. The first Atlas of Quality aimed to assess the quality of integrated care for chronic patients.METHODS:Methodology was articulated in four stages:(i) Establishment of a conceptual framework of reference specific for each intervention/technology being assessed, (ii) Definition and consensus of the assessment indicators, and (iii) Implementation of indicators using the Basic Health Areas (ABS) of Catalonia as a unit of analysis, comparing ABS with vs without the intervention (such as integrated care for chronicity). Indicators were obtained from the SISCAT databases and implemented through risk adjustment models. For performance assessment, we calculated the observed and expected indicator rates for each ABS, and for the benchmarking analysis, these ratios were represented in funnel plots (Confidence Interval, CI 95 percent and 99.8 percent for exclusion zones). (iv) Evaluation of the intervention and identification of specific success factors.RESULTS:For the assessment of integrated care interventions for chronicity, the defined framework in stage 1 was base on the Kaiser Pyramid (population distribution), and the Porter and the Donabedian's approaches (structure, processes, outcomes) (1). In stage 2 more than 500 experts, using several qualitative techniques, considered 18 indicators as relevants and feasibles for the assessment (2). Ten of them were implemented in stage 3 for congestive heart failure and pulmonary obstructive chronic disease. Significant values were found both in ABS with and without chronicity care programms (phase 3).CONCLUSIONS:The subsequent analysis (phase 4) will allow identification of practices of each ABS that best explain these results. Some limitations must be considered such as the availability of the consensued indicators in the SISCAT databases.
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Shchuko, A. G., E. T. Novozhilova, O. I. Rozanova, and L. F. Sholokhov. "Assessment of Changes in Cyliary Muscle in Patients with Hypermetropy Using Mathematical Modeling Methods." Acta Biomedica Scientifica 4, no. 4 (August 25, 2019): 113–18. http://dx.doi.org/10.29413/abs.2019-4.4.17.
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Background. Age-related decline in accommodation in patients with emmetropia, myopia and hyperopia is characterized by multidirectional changes in the thickness of the ciliary muscle and the configuration of the inner apex of the ciliary body. The structural and functional state of the ciliary muscle and its individual components and the patterns of their change with age in patients with hyperopia remain little studied.Aim: to study the structural and functional state of the ciliary muscle and its components in patients with hyperopia using mathematical modeling methods.Methods. 110 patients (220 eyes) with axial hyperopia were examined. The first group consisted of patients aged 18–30 years – 20 people. The second group consisted of 80 patients aged 45–65 years. The control group consisted of 30 healthy volunteers aged from 18 to 30 years. All patients underwent ultrasound biomicroscopy, on the basis of which a spatial-mathematical model was created using the ImageJ software package.Results and conclusion. In patients with hyperopia, in the aging process there is a transformation of the ciliary body and the restructuring of its muscular components. Structural irido-ciliary relationships in young patients with emmetropia and hyperopia significantly differ in the location and configuration of the inner apex of the ciliary body, the degree of emphasis on the circular portion of the ciliary muscle.
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Moir, Joshua, and Noah Drautzburg. "Das Wahlmindestalter in Art. 38 Abs. 2 GG und die Rechtsprechung des Bundesverfassungsgerichts zum Wahlrechtsausschluss." Recht und Politik 57, no. 2 (April 1, 2021): 198–211. http://dx.doi.org/10.3790/rup.57.2.198.
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Das Bundesverfassungsgericht (BVerfG) hat die kollektiven Ausschlüsse von Betreuten in allen Angelegenheiten und wegen Schuldunfähigkeit untergebrachter Straftäter 2019 für verfassungswidrig erklärt. Der Frage nach der Zulässigkeit des Wahlrechtsausschlusses von Kindern und Jugendlichen bis 18 Jahren ist das Gericht bisher aus dem Weg gegangen.Welche Auswirkung die Entscheidung auf den kollektiven Ausschluss Minderjähriger hat und ob ein Wahlmindestalter bei 18 Jahren (immer noch) mit dem Grundgesetz (GG) vereinbar ist, untersucht dieser Beitrag.
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Kahaly, George J. "Management of Graves Thyroidal and Extrathyroidal Disease: An Update." Journal of Clinical Endocrinology & Metabolism 105, no. 12 (September 14, 2020): 3704–20. http://dx.doi.org/10.1210/clinem/dgaa646.
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Abstract Context Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO). Evidence acquisition Guidelines, pertinent original articles, systemic reviews, and meta-analyses. Evidence synthesis Thyrotropin receptor antibodies (TSH-R-Abs), foremost the stimulatory TSH-R-Abs, are a specific biomarker for GD. Their measurement assists in the differential diagnosis of hyperthyroidism and offers accurate and rapid diagnosis of GD. Thyroid ultrasound is a sensitive imaging tool for GD. Worldwide, thionamides are the favored treatment (12-18 months) of newly diagnosed GD, with methimazole (MMI) as the preferred drug. Patients with persistently high TSH-R-Abs and/or persistent hyperthyroidism at 18 months, or with a relapse after completing a course of MMI, can opt for a definitive therapy with radioactive iodine (RAI) or total thyroidectomy (TX). Continued long-term, low-dose MMI administration is a valuable and safe alternative. Patient choice, both at initial presentation of GD and at recurrence, should be emphasized. Propylthiouracil is preferred to MMI during the first trimester of pregnancy. TX is best performed by a high-volume thyroid surgeon. RAI should be avoided in GD patients with active GO, especially in smokers. Recently, a promising therapy with an anti-insulin-like growth factor-1 monoclonal antibody for patients with active/severe GO was approved by the Food and Drug Administration. COVID-19 infection is a risk factor for poorly controlled hyperthyroidism, which contributes to the infection–related mortality risk. If GO is not severe, systemic steroid treatment should be postponed during COVID-19 while local treatment and preventive measures are offered. Conclusions A clear trend towards serological diagnosis and medical treatment of GD has emerged.
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Schmidt, L., A. S. Nielsen, A. B. Bojesen, and K. Andersen. "Research assessments more important than duration of treatment? A systematic review and meta-analysis of the duration of psychosocial treatments for alcohol use disorders." European Psychiatry 33, S1 (March 2016): S118. http://dx.doi.org/10.1016/j.eurpsy.2016.01.133.
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Background and aimsThe recommendations of duration of treatment for alcohol use disorders (AUD) in clinical guidelines are based on consensus decisions. There is a risk that patients will receive too little or too much therapy. We hypothesize that there is an association between duration and effect up until a point where the effects of treatment diminish.MethodsA systematic review and meta-analysis of randomized controlled trials of psychosocial interventions in the alcohol outpatient treatment centers. Population: adults (> 17 years) suffering from AUD treated with at least two sessions of therapy.StatisticsMultiple linear regression analysis with outcome measured in percentage of days abstinent (PDA), percentage of heavy days drinking (PHD), drinks per drinking day (DDD) and/or proportion of participants abstinent (ABS) as a function of duration of treatment.ResultsForty-four studies with 8485 participants were included. Mean duration: 18 (8–82) weeks and 15 (2–36) sessions. Mean follow-up time: 43 (8–104) weeks with a mean of 5 (2–18) research assessments. Only ABS was significantly associated with duration of treatment; ABS increased with 1.6%-point (P < 0.01) with each additional week in treatment. Surprisingly the analysis showed that each research assessment increased PDA with 11%-point (P < 0.001), decreased PHD with 4%-point (P < 0.05) and decreased DDD with 8%-point (P < 0.001).ConclusionDuration of treatment was associated positively with proportion of participants abstinent but not percentage of days abstinent drinks per drinking day or percentage of heavy drinking days. The three latter outcomes were affected positively by number of research assessments.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Dück, Hermann, and Gerrit Terhorst. "Zentralvermarktung der Fußball-Bundesliga im Lichte neuer kartellrechtlicher Kriterien wie „No-Single-Buyer-Rule“ und alternative Modelle der Rechteverwertung." Zeitschrift für Wettbewerbsrecht 15, no. 1 (March 9, 2017): 50–71. http://dx.doi.org/10.15375/zwer-2017-0105.
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ZusammenfassungDie Diskussion um Einnahmensteigerungen im Rahmen der Rechtevergabe für die Fußball-Bundesliga hat die Zentralvermarktung erneut in die öffentliche Wahrnehmung gerückt. Medial begleitet wurde die vom Bundeskartellamt (BKartA) durchgeführte Prüfung der Zentralvermarktung ab der Saison 2017/18 nicht zuletzt durch den lukrativen TV-Vertrag der englischen Premier League, aber auch durch das Bestreben einzelner Bundesligavereine an einer (stärkeren) Einzelvermarktung oder durch das Plädoyer für einen Ausschluss von Werksclubs bzw. Mäzenvereinen von den gemeinsamen Einnahmen der Zentralvermarktung. Relevant ist die Prüfung durch das BKartA insofern, als die Zentralvermarktung an sich als kartellrechtswidrige Wettbewerbsbeschränkung gem. Art. 101 Abs. 1 AEUV bzw. § 1 GWB eingestuft wird. Dabei stellt sich nicht zuletzt die Frage, wie die Neuerung des Alleinerwerbsverbots kartellrechtlich zu beurteilen ist, so z. B. im Hinblick auf die Möglichkeiten einer Freistellung vom Kartellverbot (Art. 101 Abs. 3 AEUV bzw. § 2 GWB).
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Häublein, Martin, and Hannah Köll. "Die rechtsfähige Eigentümergemeinschaft als Liegenschaftseigentümerin – zu den Grenzen der Verwaltungsangelegenheiten iSv § 18 Abs 1 WEG 2002." wohnrechtliche blätter 132, no. 7-8 (2019): 256. http://dx.doi.org/10.33196/wobl201907025601.
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