45 results on '"Hoffmann WH"'
Search Results
2. Nationwide Outcomes of Octogenarians Following Open or Endovascular Management After Ruptured Abdominal Aortic Aneurysms
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Anna J. Alberga, Jorg L. de Bruin, Frederico Bastos Gonçalves, Eleonora G. Karthaus, Janneke A. Wilschut, Joost A. van Herwaarden, Jan J. Wever, Hence J. M. Verhagen, Van den Akker PJ, Akkersdijk GJ, Akkersdijk GP, Akkersdijk WL, van Andringa de Kempenaer MG, Arts CH, Avontuur JA, Bakker OJ, Balm R, Barendregt WB, Bekken JA, Bender MH, Bendermacher BL, van den Berg M, Berger P, Beuk RJ, Blankensteijn JD, Bleker RJ, Blok JJ, Bode AS, Bodegom ME, van der Bogt KE, Boll AP, Booster MH, Borger van der Burg BL, de Borst GJ, Bos-van Rossum WT, Bosma J, Botman JM, Bouwman LH, Brehm V, de Bruijn MT, de Bruin JL, Brummel P, van Brussel JP, Buijk SE, Buijs MA, Buimer MG, Burger DH, Buscher HC, Cancrinus E, Castenmiller PH, Cazander G, Coester AM, Cuypers PH, Daemen JH, Dawson I, Dierikx JE, Dijkstra ML, Diks J, Dinkelman MK, Dirven M, Dolmans DE, van Doorn RC, van Dortmont LM, Drouven JW, van der Eb MM, Eefting D, van Eijck GJ, Elshof JW, Elsman BH, van der Elst A, van Engeland MI, van Eps RG, Faber MJ, de Fijter WM, Fioole B, Fokkema TM, Frans FA, Fritschy WM, Fung Kon Jin PH, Geelkerken RH, van Gent WB, Glade GJ, Govaert B, Groenendijk RP, de Groot HG, van den Haak RF, de Haan EF, Hajer GF, Hamming JF, van Hattum ES, Hazenberg CE, Hedeman Joosten PP, Helleman JN, van der Hem LG, Hendriks JM, van Herwaarden JA, Heyligers JM, Hinnen JW, Hissink RJ, Ho GH, den Hoed PT, Hoedt MT, van Hoek F, Hoencamp R, Hoffmann WH, Hogendoorn W, Hoksbergen AW, Hollander EJ, Hommes M, Hopmans CJ, Huisman LC, Hulsebos RG, Huntjens KM, Idu MM, Jacobs MJ, van der Jagt MF, Jansbeken JR, Janssen RJ, Jiang HH, de Jong SC, Jongbloed-Winkel TA, Jongkind V, Kapma MR, Keller BP, Khodadade Jahrome A, Kievit JK, Klemm PL, Klinkert P, Koedam NA, Koelemaij MJ, Kolkert JL, Koning GG, Koning OH, Konings R, Krasznai AG, Krol RM, Kropman RH, Kruse RR, van der Laan L, van der Laa n MJ, van Laanen JH, van Lammeren GW, Lamprou DA, Lardenoye JH, Lauret GJ, Leenders BJ, Legemate DA, Leijdekkers VJ, Lemson MS, Lensvelt MM, Lijkwan MA, Lind RC, van der Linden FT, Liqui Lung PF, Loos MJ, Loubert MC, van de Luijtgaarden KM, Mahmoud DE, Manshanden CG, Mattens EC, Meerwaldt R, Mees BM, von Meijenfeldt GC, Menting TP, Metz R, Minnee RC, de Mol van Otterloo JC, Molegraaf MJ, Montauban van Swijndregt YC, Morak MJ, van de Mortel RH, Mulder W, Nagesser SK, Naves CC, Nederhoed JH, Nevenzel-Putters AM, de Nie AJ, Nieuwenhuis DH, Nieuwenhuizen J, van Nieuwenhuizen RC, Nio D, Noyez VJ, Oomen AP, Oranen BI, Oskam J, Palamba HW, Peppelenbosch AG, van Petersen AS, Petri BJ, Pierie ME, Ploeg AJ, Pol RA, Ponfoort ED, Post IC, Poyck PP, Prent A, ten Raa S, Raymakers JT, Reichart M, Reichmann BL, Reijnen MM, de Ridder JA, Rijbroek A, van Rijn MJ, de Roo RA, Rouwet EV, Saleem BR, Salemans PB, van Sambeek MR, Samyn MG, van ‘t Sant HP, van Schaik J, van Schaik PM, Scharn DM, Scheltinga MR, Schepers A, Schlejen PM, Schlosser FJ, Schol FP, Scholtes VP, Schouten O, Schreve MA, Schurink GW, Sikkink CJ, te Slaa A, Smeets HJ, Smeets L, Smeets RR, de Smet AA, Smit PC, Smits TM, Snoeijs MG, Sondakh AO, Speijers MJ, van der Steenhoven TJ, van Sterkenburg SM, Stigter DA, Stokmans RA, Strating RP, Stultiëns GN, Sybrandy JE, Teijink JA, Telgenkamp BJ, Teraa M, Testroote MJ, Tha-In T, The RM, Thijsse WJ, Thomassen I, Tielliu IF, van Tongeren RB, Toorop RJ, Tournoij E, Truijers M, Türkcan K, Tutein Nolthenius RP, Ünlü Ç, Vaes RH, Vafi AA, Vahl AC, Veen EJ, Veger HT, Veldman MG, Velthuis S, Verhagen HJ, Verhoeven BA, Vermeulen CF, Vermeulen EG, Vierhout BP, van der Vijver-Coppen RJ, Visser MJ, van der Vliet JA, Vlijmen—van Keulen CJ, Voorhoeve R, van der Vorst JR, Vos AW, de Vos B, Vos CG, Vos GA, Voute MT, Vriens BH, Vriens PW, de Vries AC, de Vries DK, de Vries JP, de Vries M, van der Waal C, Waasdorp EJ, Wallis de Vries BM, van Walraven LA, van Wanroij JL, Warlé MC, van de Water W, van Weel V, van Well AM, Welten GM, Welten RJ, Wever JJ, Wiersema AM, Wikkeling OR, Willaert WI, Wille J, Willems MC, Willigendael EM, Wilschut ED, Wisselink W, Witte ME, Wittens CH, Wong CY, Wouda R, Yazar O, Yeung KK, Zeebregts CJ, van Zeeland ML, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Surgery
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Radiology, Nuclear Medicine and imaging ,Surgery ,Cardiology and Cardiovascular Medicine - Abstract
Purpose: Octogenarians are known to have less-favorable outcomes following ruptured abdominal aortic aneurysm (rAAA) repair compared with their younger counterparts. Accurate information regarding perioperative outcomes following rAAA-repair is important to evaluate current treatment practice. The aim of this study was to evaluate perioperative outcomes of octogenarians and to identify factors associated with mortality and major complications after open surgical repair (OSR) or endovascular aneurysm repair (EVAR) of a rAAA using nationwide, real-world, contemporary data. Methods: All patients that underwent EVAR or OSR of an infrarenal or juxtarenal rAAA between January 1, 2013, and December 31, 2018, were prospectively registered in the Dutch Surgical Aneurysm Audit (DSAA) and included in this study. The primary outcome was the comparison of perioperative outcomes of octogenarians versus non-octogenarians, including adjustment for confounders. Secondary outcomes were the identification of factors associated with mortality and major complications in octogenarians. Results: The study included 2879 patients, of which 1146 were treated by EVAR (382 octogenarians, 33%) and 1733 were treated by OSR (410 octogenarians, 24%). Perioperative mortality of octogenarians following EVAR was 37.2% versus 14.8% in non-octogenarians (adjusted OR=2.9, 95% CI=2.8–3.0) and 50.0% versus 29.4% following OSR (adjusted OR=2.2, 95% CI=2.2–2.3). Major complication rates of octogenarians were 55.4% versus 31.8% in non-octogenarians following EVAR (OR=2.7, 95% CI=2.1–3.4), and 68% versus 49% following OSR (OR=2.2, 95% CI=1.8–2.8). Following EVAR, 30.6% of the octogenarians had an uncomplicated perioperative course (UPC) versus 49.5% in non-octogenarians (OR=0.5, 95% CI=0.4–0.6), while following OSR, UPC rates were 20.7% in octogenarians versus 32.6% in non-octogenarians (OR=0.5, 95% CI=0.4–0.7). Cardiac or pulmonary comorbidity and loss of consciousness were associated with mortality and major complications in octogenarians. Interestingly, female octogenarians had lower mortality rates following EVAR than male octogenarians (adjusted OR=0.7, 95% CI=0.6–0.8). Conclusion: Based on this nationwide study with real-world registry data, mortality rates of octogenarians following ruptured AAA-repair were high, especially after OSR. However, a substantial proportion of these octogenarians following OSR and EVAR had an uneventful recovery. Known preoperative factors do influence perioperative outcomes and reflect current treatment practice.
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- 2022
3. A FINANCIAL EVALUATION OF CROP ROTATION IN THE SWARTLAND
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Hoffmann, WH and Laubscher, J
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Agricultural Finance ,Farm Management ,Crop Production/Industries - Abstract
This research focuses on the profitability of crop rotation systems in the Middle Swartland region. Crop rotation present a possible alternative to wheat monoculture production, of which profitability decreased since 1996. The advantage of crop rotation is mainly increasing yields and savings on inputs like fertilizers, herbicides and pesticides. Information was obtained by making use of the Delphi technique and group discussions whereby a multi dissiplinary team of experts were involved. The internal rate of return (IRR) was used as financial criterium in calculating the expected profitability of each of the eight crop rotation systems being researched. Of the eight systems the most profitable one is expected to be one consisting of wheat being rotated with medic and clover mixtures as grazing for livestock. The profitability analysis of the alternative crop rotation systems as well as the financial implications of the implementation thereof in the practical farming situation was performed with the aid of typical farming models of the region.
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- 2002
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4. 'N FINANSIËLE EVALUASIE VAN WISSELBOU IN DIE SWARTLAND / A FINANCIAL EVALUATION OF CROP ROTATION IN THE SWARTLAND
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Hoffmann, WH and Laubscher, J
- Abstract
AbstractThis research focuses on the profitability of crop rotation systems in the Middle Swartland region. Crop rotation present a possible alternative to wheat monoculture production, of which profitability decreased since 1996. The advantage of crop rotation is mainly increasing yields and savings on inputs like fertilizers, herbicides and pesticides. Information was obtained by making use of the Delphi technique and group discussions whereby a multi dissiplinary team of experts were involved. The internal rate of return (IRR) was used as financial criterium in calculating the expected profitability of each of the eight crop rotation systems being researched. Of the eight systems the most profitable one is expected to be one consisting of wheat being rotated with medic and clover mixtures as grazing for livestock. The profitability analysis of the alternative crop rotation systems as well as the financial implications of the implementation thereof in the practical farming situation was performed with the aid of typical farming models of the region.
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- 2002
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5. Long-term Follow-up of a Randomized Clinical Trial Comparing Endovascular Revascularization Plus Supervised Exercise With Supervised Exercise Only for Intermittent Claudication.
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Klaphake S, Fakhry F, Rouwet EV, van der Laan L, Wever JJ, Teijink JA, Hoffmann WH, van Petersen A, van Brussel JP, Stultiens GN, Derom A, den Hoed TT, Ho GH, van Dijk LC, Verhofstad N, Orsini M, Hulst I, van Sambeek MR, Rizopoulos D, van Rijn MJJE, Verhagen HJM, and Hunink MGM
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- Humans, Follow-Up Studies, Walking, Exercise Therapy methods, Treatment Outcome, Intermittent Claudication surgery, Quality of Life
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Objective: The goal of this study was to assess the long-term effectiveness of combination therapy for intermittent claudication, compared with supervised exercise only., Background: Supervised exercise therapy is recommended as first-line treatment for intermittent claudication by recent guidelines. Combining endovascular revascularization plus supervised exercise shows promising results; however, there is a lack of long-term follow-up., Methods: The ERASE study is a multicenter randomized clinical trial, including patients between May 2010 and February 2013 with intermittent claudication. Interventions were combination of endovascular revascularization plus supervised exercise (n = 106) or supervised exercise only (n = 106). Primary endpoint was the difference in maximum walking distance at long-term follow-up. Secondary endpoints included differences in pain-free walking distance, ankle-brachial index, quality of life, progression to critical limb ischemia, and revascularization procedures during follow-up. This randomized trial report is based on a post hoc analysis of extended follow-up beyond that of the initial trial. Patients were followed up until 31 July 2017. Data were analyzed according to the intention-to-treat principle., Results: Median long-term follow-up was 5.4 years (IQR 4.9-5.7). Treadmill test was completed for 128/212 (60%) patients. Whereas the difference in maximum walking distance significantly favored combination therapy at 1-year follow-up, the difference at 5-year follow-up was no longer significant (53 m; 99% CI-225 to 331; P = 0.62). No difference in pain-free walking distance, ankle-brachial index, and quality of life was found during long-term follow-up. We found that supervised exercise was associated with an increased hazard of a revascularization procedure during follow-up (HR 2.50; 99% CI 1.27-4.90; P < 0.001). The total number of revascularization procedures (including randomized treatment) was lower in the exercise only group compared to that in the combination therapy group (65 vs 149)., Conclusions: Long-term follow up after combination therapy versus supervised exercise only, demonstrated no significant difference in walking distance or quality of life between the treatment groups. Combination therapy resulted in a lower number of revascularization procedures during follow-up but a higher total number of revascularizations including the randomized treatment., Trial Registration: Netherlands Trial Registry Identifier: NTR2249., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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6. Measuring the refractive index and sub-nanometre surface functionalisation of nanoparticles in suspension.
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Mulkerns NMC, Hoffmann WH, Ramos-Soriano J, de la Cruz N, Garcia-Millan T, Harniman RL, Lindsay ID, Seddon AM, Galan MC, and Gersen H
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Direct measurements to determine the degree of surface coverage of nanoparticles by functional moieties are rare, with current strategies requiring a high level of expertise and expensive equipment. Here, a practical method to determine the ratio of the volume of the functionalisation layer to the particle volume based on measuring the refractive index of nanoparticles in suspension is proposed. As a proof of concept, this technique is applied to poly(methyl methacrylate) (PMMA) nanoparticles and semicrystalline carbon dots functionalised with different surface moieties, yielding refractive indices that are commensurate to those from previous literature and Mie theory. In doing so, it is demonstrated that this technique is able to optically detect differences in surface functionalisation or composition of nanometre-sized particles. This non-destructive and rapid method is well-suited for in situ industrial particle characterisation and biological applications.
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- 2022
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7. An Analysis of Semicircular Channel Backscattering Interferometry through Ray Tracing Simulations.
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Mulkerns NMC, Hoffmann WH, Lindsay ID, and Gersen H
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- Interferometry, Microfluidics
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Recent backscattering interferometry studies utilise a single channel microfluidic system, typically approximately semicircular in cross-section. Here, we present a complete ray tracing model for on-chip backscattering interferometry with a semicircular cross-section, including the dependence upon polarisation and angle of incidence. The full model is validated and utilised to calculate the expected fringe patterns and sensitivities observed under both normal and oblique angles of incidence. Comparison with experimental data from approximately semicircular channels using the parameters stated shows that they cannot be explained using a semicircular geometry. The disagreement does not impact on the validity of the experimental data, but highlights that the optical mechanisms behind the various modalities of backscattering interferometry would benefit from clarification. From the analysis presented here, we conclude that for reasons of ease of analysis, data quality, and sensitivity for a given radius, capillary-based backscattering interferometry affords numerous benefits over on-chip backscattering interferometry.
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- 2022
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8. Determining nanorod dimensions in dispersion with size anisotropy nanoparticle tracking analysis.
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Hoffmann WH, Gao B, Mulkerns NMC, Hinton AG, Hanna S, Hall SR, and Gersen H
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Control over nanorod dimensions is critical to their application, requiring fast, robust characterisation of their volume and aspect ratio whilst in their working medium. Here, we present an extension of Nanoparticle Tracking Analysis which determines the aspect ratio of nanoparticles from the polarisation state of scattered light in addition to a hydrodynamic diameter from Brownian motion. These data, in principle, permit the determination of nanorod dimensions of any composition using Nanoparticle Tracking Analysis. The results are compared with transmission electron microscopy and show that this technique can additionally determine the aggregation state of the nanorod dispersion if single nanorod dimensions are determined with a complementary technique. We also show it is possible to differentiate nanoparticles of similar hydrodynamic diameter by their depolarised scattering. Finally, we assess the ability of the technique to output nanorod dimensions and suggest ways to further improve the approach. This technique will enable rapid characterisation of nanorods in suspension, which are important tools for nanotechnology.
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- 2022
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9. Shedding Light on Capillary-Based Backscattering Interferometry.
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Mulkerns NMC, Hoffmann WH, Lindsay ID, and Gersen H
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- Algorithms, Interferometry methods, Refractometry methods
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Capillary-based backscattering interferometry has been used extensively as a tool to measure molecular binding via interferometric refractive index sensing. Previous studies have analysed the fringe patterns created in the backscatter direction. However, polarisation effects, spatial chirps in the fringe pattern and the practical impact of various approximations, and assumptions in existing models are yet to be fully explored. Here, two independent ray tracing approaches are applied, analysed, contrasted, compared to experimental data, and improved upon by introducing explicit polarisation dependence. In doing so, the significance of the inner diameter, outer diameter, and material of the capillary to the resulting fringe pattern and subsequent analysis are elucidated for the first time. The inner diameter is shown to dictate the fringe pattern seen, and therefore, the effectiveness of any dechirping algorithm, demonstrating that current dechirping methods are only valid for a subset of capillary dimensions. Potential improvements are suggested in order to guide further research, increase sensitivity, and promote wider applicability.
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- 2022
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10. Laser-induced convection shifts size distributions in nanoparticle tracking analysis.
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Hoffmann WH, Mulkerns NMC, Hall SR, and Gersen H
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This work discusses the effects of increasing laser power on the size data derived from NTA for particles of known size and scatterers in solutions of flufenamic acid in ethanol. We find that whilst a higher laser power reveals more particles as expected, their residence time changes due to laser-induced convection. This reduced residence time decreases the number of tracks available for individual particle size determination, shifting the size distribution to smaller values. This problem is overcome by using a shutter to inhibit the development of convection currents, increasing particle residence time and reducing the error on the size distribution. The detailed understanding of laser-induced convection permits more robust size characterisation of mesoscopic organic clusters, which play a key role in two-step nucleation theory., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
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- 2021
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11. Endovascular Revascularization Plus Supervised Exercise Versus Supervised Exercise Only for Intermittent Claudication: A Cost-Effectiveness Analysis.
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Fakhry F, Rouwet EV, Spillenaar Bilgen R, van der Laan L, Wever JJ, Teijink JAW, Hoffmann WH, van Petersen A, van Brussel JP, Stultiens GNM, Derom A, den Hoed PT, Ho GH, van Dijk LC, Verhofstad N, Orsini M, Hulst I, van Sambeek MRHM, Rizopoulos D, Moelker A, and Hunink MGM
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- Cost-Benefit Analysis, Humans, Quality of Life, Treatment Outcome, Exercise Therapy, Intermittent Claudication diagnosis, Intermittent Claudication therapy
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[Figure: see text].
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- 2021
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12. Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.
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Jalalzadeh H, Indrakusuma R, Koelemay MJW, Balm R, Van den Akker LH, Van den Akker PJ, Akkersdijk GJ, Akkersdijk GP, Akkersdijk WL, van Andringa de Kempenaer MG, Arts CH, Avontuur JA, Baal JG, Bakker OJ, Balm R, Barendregt WB, Bender MH, Bendermacher BL, van den Berg M, Berger P, Beuk RJ, Blankensteijn JD, Bleker RJ, Bockel JH, Bodegom ME, Bogt KE, Boll AP, Booster MH, Borger van der Burg BL, de Borst GJ, Bos-van Rossum WT, Bosma J, Botman JM, Bouwman LH, Breek JC, Brehm V, Brinckman MJ, van den Broek TH, Brom HL, de Bruijn MT, de Bruin JL, Brummel P, van Brussel JP, Buijk SE, Buimer MG, Burger DH, Buscher HC, den Butter G, Cancrinus E, Castenmiller PH, Cazander G, Coveliers HM, Cuypers PH, Daemen JH, Dawson I, Derom AF, Dijkema AR, Diks J, Dinkelman MK, Dirven M, Dolmans DE, van Doorn RC, van Dortmont LM, van der Eb MM, Eefting D, van Eijck GJ, Elshof JW, Elsman BH, van der Elst A, van Engeland MI, van Eps RG, Faber MJ, de Fijter WM, Fioole B, Fritschy WM, Geelkerken RH, van Gent WB, Glade GJ, Govaert B, Groenendijk RP, de Groot HG, van den Haak RF, de Haan EF, Hajer GF, Hamming JF, van Hattum ES, Hazenberg CE, Hedeman Joosten PP, Helleman JN, van der Hem LG, Hendriks JM, van Herwaarden JA, Heyligers JM, Hinnen JW, Hissink RJ, Ho GH, den Hoed PT, Hoedt MT, van Hoek F, Hoencamp R, Hoffmann WH, Hoksbergen AW, Hollander EJ, Huisman LC, Hulsebos RG, Huntjens KM, Idu MM, Jacobs MJ, van der Jagt MF, Jansbeken JR, Janssen RJ, Jiang HH, de Jong SC, Jongkind V, Kapma MR, Keller BP, Khodadade Jahrome A, Kievit JK, Klemm PL, Klinkert P, Knippenberg B, Koedam NA, Koelemay MJ, Kolkert JL, Koning GG, Koning OH, Krasznai AG, Krol RM, Kropman RH, Kruse RR, van der Laan L, van der Laan MJ, van Laanen JH, Lardenoye JH, Lawson JA, Legemate DA, Leijdekkers VJ, Lemson MS, Lensvelt MM, Lijkwan MA, Lind RC, van der Linden FT, Liqui Lung PF, Loos MJ, Loubert MC, Mahmoud DE, Manshanden CG, Mattens EC, Meerwaldt R, Mees BM, Metz R, Minnee RC, de Mol van Otterloo JC, Moll FL, Montauban van Swijndregt YC, Morak MJ, van de Mortel RH, Mulder W, Nagesser SK, Naves CC, Nederhoed JH, Nevenzel-Putters AM, de Nie AJ, Nieuwenhuis DH, Nieuwenhuizen J, van Nieuwenhuizen RC, Nio D, Oomen AP, Oranen BI, Oskam J, Palamba HW, Peppelenbosch AG, van Petersen AS, Peterson TF, Petri BJ, Pierie ME, Ploeg AJ, Pol RA, Ponfoort ED, Poyck PP, Prent A, Ten Raa S, Raymakers JT, Reichart M, Reichmann BL, Reijnen MM, Rijbroek A, van Rijn MJ, de Roo RA, Rouwet EV, Rupert CG, Saleem BR, van Sambeek MR, Samyn MG, van 't Sant HP, van Schaik J, van Schaik PM, Scharn DM, Scheltinga MR, Schepers A, Schlejen PM, Schlosser FJ, Schol FP, Schouten O, Schreinemacher MH, Schreve MA, Schurink GW, Sikkink CJ, Siroen MP, Te Slaa A, Smeets HJ, Smeets L, de Smet AA, de Smit P, Smit PC, Smits TM, Snoeijs MG, Sondakh AO, van der Steenhoven TJ, van Sterkenburg SM, Stigter DA, Stigter H, Strating RP, Stultiëns GN, Sybrandy JE, Teijink JA, Telgenkamp BJ, Testroote MJ, The RM, Thijsse WJ, Tielliu IF, van Tongeren RB, Toorop RJ, Tordoir JH, Tournoij E, Truijers M, Türkcan K, Tutein Nolthenius RP, Ünlü Ç, Vafi AA, Vahl AC, Veen EJ, Veger HT, Veldman MG, Verhagen HJ, Verhoeven BA, Vermeulen CF, Vermeulen EG, Vierhout BP, Visser MJ, van der Vliet JA, Vlijmen-van Keulen CJ, Voesten HG, Voorhoeve R, Vos AW, de Vos B, Vos GA, Vriens BH, Vriens PW, de Vries AC, de Vries JP, de Vries M, van der Waal C, Waasdorp EJ, Wallis de Vries BM, van Walraven LA, van Wanroij JL, Warlé MC, van Weel V, van Well AM, Welten GM, Welten RJ, Wever JJ, Wiersema AM, Wikkeling OR, Willaert WI, Wille J, Willems MC, Willigendael EM, Wisselink W, Witte ME, Wittens CH, Wolf-de Jonge IC, Yazar O, Zeebregts CJ, and van Zeeland ML
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- Aged, Aged, 80 and over, Endovascular Procedures methods, Endovascular Procedures mortality, Endovascular Procedures statistics & numerical data, Female, Guideline Adherence statistics & numerical data, Humans, Iliac Aneurysm epidemiology, Iliac Aneurysm mortality, Iliac Aneurysm pathology, Iliac Artery pathology, Iliac Artery surgery, Male, Netherlands epidemiology, Registries, Retrospective Studies, Sex Factors, Treatment Outcome, Iliac Aneurysm surgery
- Abstract
Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)
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- 2020
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13. Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication: A Randomized Clinical Trial.
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Fakhry F, Spronk S, van der Laan L, Wever JJ, Teijink JA, Hoffmann WH, Smits TM, van Brussel JP, Stultiens GN, Derom A, den Hoed PT, Ho GH, van Dijk LC, Verhofstad N, Orsini M, van Petersen A, Woltman K, Hulst I, van Sambeek MR, Rizopoulos D, Rouwet EV, and Hunink MG
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- Aged, Combined Modality Therapy methods, Female, Health Status, Humans, Intention to Treat Analysis, Male, Quality of Life, Treatment Outcome, Walking, Exercise Therapy methods, Intermittent Claudication therapy, Peripheral Arterial Disease therapy, Vascular Surgical Procedures methods
- Abstract
Importance: Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available., Objective: To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only., Design, Setting, and Participants: Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle., Interventions: A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106)., Main Outcomes and Measures: The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation])., Results: Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions., Conclusions and Relevance: Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only., Trial Registration: Netherlands Trial Registry Identifier: NTR2249.
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- 2015
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14. Evaluation of the Metabolic Activity of Echinococcus multilocularis in Rodents Using Positron Emission Tomography Tracers.
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Rolle AM, Soboslay PT, Reischl G, Hoffmann WH, Pichler BJ, and Wiehr S
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- Animals, Female, Gerbillinae, Magnetic Resonance Imaging, Radiopharmaceuticals pharmacokinetics, Echinococcosis diagnostic imaging, Echinococcosis metabolism, Echinococcus multilocularis metabolism, Positron-Emission Tomography methods, Radiopharmaceuticals metabolism
- Abstract
Purpose: 2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) has been used as a standard clinical positron emission tomography (PET) tracer for the follow-up of the rare but life-threatening parasitic disease alveolar echinococcosis (AE). Given that the disease is endemic in many countries in the northern hemisphere and the diagnosis is still challenging, the aim of our study was to evaluate further clinically relevant PET tracers as possible diagnostic tools for AE in vitro and in vivo., Procedures: Various clinically used PET tracers were evaluated in vitro and assessed in an in vivo AE animal model based on PET/magnetic resonance (MR) measurements., Results: In vitro binding assays displayed high uptake of [(18)F]FDG in a cell suspension of E. multilocularis tissue, whereas 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) and [(11)C]choline were found to be taken up strongly by E. multilocularis vesicles. [(18)F]FDG and [(18)F]FLT displayed an elevated uptake in vivo, which appeared as several foci throughout the parasite tissue as opposed to [(18)F]fluoro-azomycinarabinofuranoside ([(18)F]FAZA) and [(11)C]choline., Conclusions: Our data clearly demonstrate that the clinically applied PET tracer [(18)F]FDG is useful for the diagnosis and disease staging of AE but also has drawbacks in the assessment of currently inactive or metabolically weak parasitic lesions. The different tested PET tracers do not show the potential for the replacement or supplementation of current diagnostic strategies. Hence, there is still the need for novel diagnostic tools.
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- 2015
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15. Lactate as a novel quantitative measure of viability in Schistosoma mansoni drug sensitivity assays.
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Howe S, Zöphel D, Subbaraman H, Unger C, Held J, Engleitner T, Hoffmann WH, and Kreidenweiss A
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- Animals, Drug Evaluation, Preclinical, Lactic Acid analysis, Microscopy, Anthelmintics pharmacology, Lactic Acid metabolism, Schistosoma mansoni drug effects, Schistosoma mansoni metabolism
- Abstract
Whole-organism compound sensitivity assays are a valuable strategy in infectious diseases to identify active molecules. In schistosomiasis drug discovery, larval-stage Schistosoma allows the use of a certain degree of automation in the screening of compounds. Unfortunately, the throughput is limited, as drug activity is determined by manual assessment of Schistosoma viability by microscopy. To develop a simple and quantifiable surrogate marker for viability, we targeted glucose metabolism, which is central to Schistosoma survival. Lactate is the end product of glycolysis in human Schistosoma stages and can be detected in the supernatant. We assessed lactate as a surrogate marker for viability in Schistosoma drug screening assays. We thoroughly investigated parameters of lactate measurement and performed drug sensitivity assays by applying schistosomula and adult worms to establish a proof of concept. Lactate levels clearly reflected the viability of schistosomula and correlated with schistosomulum numbers. Compounds with reported potencies were tested, and activities were determined by lactate assay and by microscopy. We conclude that lactate is a sensitive and simple surrogate marker to be measured to determine Schistosoma viability in compound screening assays. Low numbers of schistosomula and the commercial availability of lactate assay reagents make the assay particularly attractive to throughput approaches. Furthermore, standardization of procedures and quantitative evaluation of compound activities facilitate interassay comparisons of potencies and, thus, concerted drug discovery approaches., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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16. A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.
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Baur S, Rautenberg M, Faulstich M, Grau T, Severin Y, Unger C, Hoffmann WH, Rudel T, Autenrieth IB, and Weidenmaier C
- Subjects
- Animals, CHO Cells, Cell Wall metabolism, Cells, Cultured, Cricetinae, Cricetulus, Host-Pathogen Interactions genetics, Humans, Rats, Scavenger Receptors, Class F metabolism, Sigmodontinae, Staphylococcal Infections genetics, Staphylococcal Infections metabolism, Staphylococcal Infections microbiology, Bacterial Adhesion genetics, Epithelial Cells microbiology, Nasal Cavity microbiology, Scavenger Receptors, Class F physiology, Staphylococcus aureus growth & development, Staphylococcus aureus physiology, Teichoic Acids metabolism
- Abstract
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.
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- 2014
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17. ST2 deficiency does not impair type 2 immune responses during chronic filarial infection but leads to an increased microfilaremia due to an impaired splenic microfilarial clearance.
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Ajendra J, Specht S, Neumann AL, Gondorf F, Schmidt D, Gentil K, Hoffmann WH, Taylor MJ, Hoerauf A, and Hübner MP
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- Animals, Chronic Disease, Female, Filariasis genetics, Filariasis pathology, Interleukin-1 Receptor-Like 1 Protein, Mice, Mice, Mutant Strains, Receptors, Interleukin genetics, Sigmodontinae, Spleen pathology, Filariasis immunology, Filarioidea immunology, Receptors, Interleukin immunology, Spleen immunology, Spleen parasitology
- Abstract
Background: Interactions of the Th2 cytokine IL-33 with its receptor ST2 lead to amplified Type 2 immune responses. As Type 2 immune responses are known to mediate protection against helminth infections we hypothesized that the lack of ST2 would lead to an increased susceptibility to filarial infections., Methodology/principal Finding: ST2 deficient and immunocompetent BALB/c mice were infected with the filarial nematode Litomosoides sigmodontis. At different time points after infection mice were analyzed for worm burden and their immune responses were examined within the thoracic cavity, the site of infection, and systemically using spleen cells and plasma. Absence of ST2 led to significantly increased levels of peripheral blood microfilariae, the filarial progeny, whereas L. sigmodontis adult worm burden was not affected. Development of local and systemic Type 2 immune responses were not impaired in ST2 deficient mice after the onset of microfilaremia, but L. sigmodontis infected ST2-ko mice had significantly reduced total numbers of cells within the thoracic cavity and spleen compared to infected immunocompetent controls. Pronounced microfilaremia in ST2-ko mice did not result from an increased microfilariae release by adult female worms, but an impaired splenic clearance of microfilariae., Conclusions/significance: Our findings suggest that the absence of ST2 does not impair the establishment of adult L. sigmodontis worms, but is important for the splenic clearance of microfilariae from peripheral blood. Thus, ST2 interactions may be important for therapies that intend to block the transmission of filarial disease.
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- 2014
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18. Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia after challenge infection by inhibition of filarial embryogenesis.
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Ziewer S, Hübner MP, Dubben B, Hoffmann WH, Bain O, Martin C, Hoerauf A, and Specht S
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- Adjuvants, Immunologic administration & dosage, Alum Compounds administration & dosage, Animals, Disease Models, Animal, Female, Filariasis immunology, Filarioidea growth & development, Filarioidea isolation & purification, Humans, Mice, Mice, Inbred BALB C, Parasite Load, Vaccination methods, Filariasis prevention & control, Filarioidea immunology, Parasitemia prevention & control, Vaccines administration & dosage, Vaccines immunology
- Abstract
Background: Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines., Methodology/principal Findings: Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden., Conclusions/significance: Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.
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- 2012
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19. Parasite-specific IL-17-type cytokine responses and soluble IL-17 receptor levels in Alveolar Echinococcosis patients.
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Lechner CJ, Grüner B, Huang X, Hoffmann WH, Kern P, and Soboslay PT
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- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Echinococcosis, Female, Humans, Inflammation immunology, Lymphocyte Activation, Male, Middle Aged, Th17 Cells immunology, Young Adult, Echinococcosis, Hepatic immunology, Echinococcus multilocularis immunology, Interleukin-17 blood, Receptors, Interleukin-17 blood
- Abstract
Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.
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- 2012
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20. Schistosoma co-infection protects against brain pathology but does not prevent severe disease and death in a murine model of cerebral malaria.
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Bucher K, Dietz K, Lackner P, Pasche B, Fendel R, Mordmüller B, Ben-Smith A, and Hoffmann WH
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- Animals, Body Weight, Cytokines blood, Disease Models, Animal, Female, Hypothermia parasitology, Malaria, Cerebral mortality, Mice, Mice, Inbred C57BL, Parasitemia, Schistosomiasis mansoni mortality, Brain Diseases, Malaria, Cerebral complications, Malaria, Cerebral pathology, Plasmodium berghei pathogenicity, Schistosoma mansoni pathogenicity, Schistosomiasis mansoni complications, Schistosomiasis mansoni pathology
- Abstract
Co-infections of helminths and malaria parasites are common in human populations in most endemic areas. It has been suggested that concomitant helminth infections inhibit the control of malaria parasitemia but down-modulate severe malarial disease. We tested this hypothesis using a murine co-infection model of schistosomiasis and cerebral malaria. C57BL/6 mice were infected with Schistosoma mansoni and 8-9 weeks later, when Schistosoma infection was patent, mice were co-infected with Plasmodium berghei ANKA strain. We found that a concomitant Schistosoma infection increased parasitemia at the beginning of the P. berghei infection. It did not protect against P. berghei-induced weight loss and hypothermia, and P. berghei-mono-infected as well as S. mansoni-P. berghei-co-infected animals showed a high case fatality between days 6 and 8 of malarial infection. However, co-infection significantly reduced P. berghei-induced brain pathology. Over 40% of the S. mansoni-P. berghei-co-infected animals that died during this period were completely protected against haemorrhaging, plugging of blood vessels and infiltration, indicating that mortality in these animals was not related to cerebral disease. Schistosoma mansoni-P. berghei-co-infected mice had elevated plasma concentrations of IL-5 and IL-13 and on day 6 lower levels of IFN-γ, IL-10, monocyte chemoattractant protein-1 (MCP-1) and monokine induced by IFN-γ (MIG) than P. berghei-mono-infected mice. We conclude that in P. berghei infections, disease and early death are caused by distinct pathogenic mechanisms, which develop in parallel and are differentially influenced by the immune response to S. mansoni. This might explain why, in co-infected mice, death could be induced in the absence of brain pathology., (Copyright © 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2011
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21. Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization.
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Burian M, Rautenberg M, Kohler T, Fritz M, Krismer B, Unger C, Hoffmann WH, Peschel A, Wolz C, and Goerke C
- Subjects
- Adhesins, Bacterial physiology, Animals, Antigens, Bacterial biosynthesis, Antigens, Bacterial physiology, Bacterial Proteins biosynthesis, Bacterial Proteins physiology, Disease Models, Animal, Gene Expression Regulation, Bacterial physiology, Genes, Bacterial physiology, Humans, RNA, Bacterial metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sigmodontinae, Staphylococcus aureus metabolism, Staphylococcus aureus physiology, Trans-Activators physiology, Adhesins, Bacterial biosynthesis, Nasal Mucosa microbiology, Staphylococcal Infections microbiology
- Abstract
The human pathogen Staphylococcus aureus successfully colonizes its primary reservoir, the nasal cavity, most likely by regulatory adaptation to the nose environment. Cotton rats represent an excellent model for the study of bacterial gene expression in the initial phases of colonization. To gain insight into the expression profile necessary for the establishment of colonization, we performed direct transcript analysis by quantitative real-time reverse-transcription polymerase chain reaction on cotton rat noses removed from euthanized animals on days 1, 4, or 10 after instillation of 2 human S. aureus nose isolates. Global virulence regulators (agr, sae) were not active in this early phase, but the essential 2-component regulatory system WalKR seems to play an important role. Accordingly, an elevated expression of walKR target genes (sak, sceD) could be detected. In agreement with previous studies that demonstrated the essential role played by wall teichoic acid (WTA) polymers in nasal colonization, we detected a strongly increased expression of WTA-biosynthetic genes. The expression profile switched to production of the adhesive proteins ClfB and IsdA at later stages of the colonization process. These data underscore the temporal differences in the roles of WTA and surface proteins in nasal colonization, and they provide the first evidence for a regulation of WTA biosynthesis in vivo.
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- 2010
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22. [Individual determinants of dental care utilization among low-income adult and elderly individuals].
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Baldani MH, Brito WH, Lawder JA, Mendes YB, da Silva Fde F, and Antunes JL
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- Adult, Aged, Brazil, Female, Humans, Male, Middle Aged, Poverty, Dental Care statistics & numerical data
- Abstract
The utilization of dental care services results from the interaction of biological determinants with sociocultural, family and community variables, as well as from some characteristics of health systems. The objective of this study was to assess the individual factors associated with the use of dental care services among low-income adult and elderly individuals living in the catchment area of the Family Health Strategy, in Ponta Grossa, PR. The sample included 246 individuals, aged 35 years or over, who answered a questionnaire on socioeconomic conditions, perceived needs, and access to dental care services. Data analysis was performed according to a conceptual framework based on Andersen's Behavioral Model. Non-recent use of dental care services was considered as the dependent variable in the logistic regression analysis models. There were high prevalences of self-reported oral health diseases and teeth loss. About 40% of the adults and 67% of the elderly had not made any dental visit in the past 3 years. Individuals without ownership of the family home, with inadequate oral hygiene habits and who wore complete dentures had higher odds of having gone to the dentist longer ago. The fact of having a regular source of dental care was identified as a protective factor in the analysis. The conceptual framework confirmed the presence of social and psychosocial inequalities in the use of dental services among low-income adult and elderly individuals.
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- 2010
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23. In vivo anti-malarial effect of the beta-amino alcohol 1t on Plasmodium berghei.
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Bahamontes-Rosa N, Bucher K, Held J, Robin A, Hoffmann WH, Flitsch SL, Kremsner PG, and Kun JF
- Subjects
- Amino Alcohols administration & dosage, Amino Alcohols pharmacology, Animals, Antimalarials administration & dosage, Antimalarials pharmacology, Female, Inhibitory Concentration 50, Injections, Intraperitoneal, Male, Mice, Mice, Inbred BALB C, Parasitemia drug therapy, Survival Analysis, Amino Alcohols therapeutic use, Antimalarials therapeutic use, Malaria drug therapy, Plasmodium berghei drug effects
- Abstract
Glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of Plasmodium falciparum in vitro. In the present study, one of these compounds, termed 1t, which had the lowest IC(50) values, was assessed in a murine malarial model. Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium berghei ANKA strain were treated in a 4-day suppressive test. Mice received a once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days. Although no parasitaemia clearance was reached, a slower parasite proliferation and a slightly longer survival time compared with the placebo group were observed.
- Published
- 2009
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24. Does resistance to filarial reinfections become leaky over time?
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Duerr HP, Hoffmann WH, and Eichner M
- Subjects
- Animals, Elephantiasis, Filarial parasitology, Humans, Onchocerciasis parasitology, Recurrence, Vaccines immunology, Elephantiasis, Filarial immunology, Onchocerciasis immunology
- Abstract
Strategies for the control of human parasitic diseases such as onchocerciasis and lymphatic filariasis require an understanding of how the parasite successfully infects and persists in humans. Despite the fact that the vast majority of infective larvae are eliminated after infection, this 'protection' is far from being an all-or-nothing response. The hypothesis presented here, which is based on epidemiological observations, suggests that the resistance against filarial parasites includes a time-dependent component, probably caused by an early immune response with short-term memory. Validating this hypothesis requires experimental studies with a longitudinal component. Such experiments would help to clarify whether the infection can be controlled by vaccination strategies at all.
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- 2008
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25. Of mice, cattle, and humans: the immunology and treatment of river blindness.
- Author
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Allen JE, Adjei O, Bain O, Hoerauf A, Hoffmann WH, Makepeace BL, Schulz-Key H, Tanya VN, Trees AJ, Wanji S, and Taylor DW
- Subjects
- Animals, Anthelmintics pharmacology, Cattle, Disease Models, Animal, Humans, Ivermectin pharmacology, Mice, Models, Biological, Onchocerca drug effects, Onchocerciasis, Ocular parasitology, Anthelmintics therapeutic use, Ivermectin therapeutic use, Onchocerca immunology, Onchocerciasis, Ocular drug therapy, Onchocerciasis, Ocular immunology
- Abstract
River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease.
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- 2008
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26. Microfilariae of the filarial nematode Litomosoides sigmodontis exacerbate the course of lipopolysaccharide-induced sepsis in mice.
- Author
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Hübner MP, Pasche B, Kalaydjiev S, Soboslay PT, Lengeling A, Schulz-Key H, Mitre E, and Hoffmann WH
- Subjects
- Animals, Body Temperature, Cytokines metabolism, Female, Gene Expression Regulation physiology, Granulocytes physiology, Male, Mice, Mice, Inbred C57BL, Monocytes physiology, Parasitemia metabolism, Receptors, Interferon genetics, Receptors, Tumor Necrosis Factor genetics, Interferon gamma Receptor, Filarioidea physiology, Lipopolysaccharides toxicity, Microfilariae physiology, Sepsis chemically induced, Sepsis parasitology
- Abstract
Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than sham-treated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilaria-releasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN-gamma receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN-gamma and TNF-alpha. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood.
- Published
- 2008
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27. Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model.
- Author
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Dittrich AM, Erbacher A, Specht S, Diesner F, Krokowski M, Avagyan A, Stock P, Ahrens B, Hoffmann WH, Hoerauf A, and Hamelmann E
- Subjects
- Allergens immunology, Animals, Antibodies, Blocking pharmacology, Antibodies, Helminth immunology, Asthma complications, Cytokines metabolism, Dendritic Cells immunology, Disease Models, Animal, Filariasis complications, Immunoglobulins immunology, Interleukin-2 Receptor alpha Subunit antagonists & inhibitors, Mice, Mice, Inbred BALB C, Phenotype, Spleen immunology, Transforming Growth Factor alpha antagonists & inhibitors, Asthma immunology, Bronchial Hyperreactivity immunology, Filariasis immunology, Respiratory Hypersensitivity immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Numerous epidemiological studies have shown an inverse correlation between helminth infections and the manifestation of atopic diseases, yet the immunological mechanisms governing this phenomenon are indistinct. We therefore investigated the effects of infection with the filarial parasite Litomosoides sigmodontis on allergen-induced immune reactions and airway disease in a murine model of asthma. Infection with L. sigmodontis suppressed all aspects of the asthmatic phenotype: Ag-specific Ig production, airway reactivity to inhaled methacholine, and pulmonary eosinophilia. Similarly, Ag-specific recall proliferation and overall Th2 cytokine (IL-4, IL-5, and IL-3) production were significantly reduced after L. sigmodontis infection. Analysis of splenic mononuclear cells and mediastinal lymph nodes revealed a significant increase in the numbers of T cells with a regulatory phenotype in infected and sensitized mice compared with sensitized controls. Additionally, surface and intracellular staining for TGF-beta on splenic CD4(+) T cells as well as Ag-specific TGF-beta secretion by splenic mononuclear cells was increased in infected and sensitized animals. Administration of Abs blocking TGF-beta or depleting regulatory T cells in infected animals before allergen sensitization and challenges reversed the suppressive effect with regard to airway hyperreactivity, but did not affect airway inflammation. Despite the dissociate results of the blocking experiments, these data point toward an induction of regulatory T cells and enhanced secretion of the immunomodulatory cytokine TGF-beta as one principle mechanism. In conclusion, our data support the epidemiological evidence and enhance the immunological understanding concerning the impact of helminth infections on atopic diseases thus providing new insights for the development of future studies.
- Published
- 2008
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28. Echinococcus multilocularis metacestodes modulate cellular cytokine and chemokine release by peripheral blood mononuclear cells in alveolar echinococcosis patients.
- Author
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Hübner MP, Manfras BJ, Margos MC, Eiffler D, Hoffmann WH, Schulz-Key H, Kern P, and Soboslay PT
- Subjects
- Adolescent, Adult, Aged, Animals, Biomarkers analysis, CD28 Antigens analysis, CD4-Positive T-Lymphocytes immunology, Case-Control Studies, Cells, Cultured, Chemokine CCL22, Chemokines, CC immunology, Female, Flow Cytometry, Humans, Interferon-gamma immunology, Interleukin-12 immunology, Lipopolysaccharides, Lymphocyte Activation, Male, Middle Aged, Parasitology methods, Tumor Necrosis Factor-alpha immunology, Antigens, Helminth immunology, Chemokines immunology, Cytokines immunology, Echinococcosis, Pulmonary immunology, Echinococcus multilocularis immunology
- Abstract
Infection with the cestode Echinococcus multilocularis causes human alveolar echinococcosis (AE), a life-threatening disease affecting primarily the liver. Despite the severity of AE, clinical symptoms often develop only many years after infection, which suggests that E. multilocularis has developed mechanisms which depress anti-parasite immune response, thus favouring immune evasion. In this study we examined the production of cytokines, chemokines and the expression of CD molecules on peripheral blood mononuclear cells (PBMC) from AE patients and healthy controls in response to E. multilocularis metacestode culture supernatant, viable E. multilocularis vesicles and E. multilocularis vesicle fluid antigen in vitro. After 48 h of co-culture, E. multilocularis metacestode culture supernatant and E. multilocularis vesicles depressed the release of the proinflammatory cytokine interleukin (IL)-12 by PBMC. This effect was dose-dependent and a suppression of tumour necrosis factor (TNF)-alpha and IL-12 was observed even when PBMC were activated with lipopolysaccharide (LPS). Comparing proinflammatory cytokine release by AE patients and controls showed that the release of IL-12 and TNF-alpha was reduced in AE patients, which was accompanied by an increased number of CD4+ CD25+ cells and a reduced release of the Th2 type chemokine CCL17 (thymus and activation regulated chemokine, TARC), suggesting an anti-inflammatory response to E. multilocularis metacestode in AE patients. Instead the production of interferon (IFN)-gamma and the expression of CD28 on CD4+ T cells were increased in PBMC from AE patients when compared to controls. This was accompanied by a higher release of the Th2-type chemokine CCL22 (macrophage derived chemokine, MDC) supporting that E. multilocularis also generates proinflammatory immune responses. These results indicate that E. multilocularis antigens modulated both regulatory and inflammatory Th1 and Th2 cytokines and chemokines. Such a mixed profile might be required for limiting parasite growth but also for reducing periparasitic tissue and organ damage in the host.
- Published
- 2006
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29. Long-term observations on mouse strains experimentally infected with Angiostrongylus costaricensis.
- Author
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Abrahams-Sandi E, Hoffmann WH, Graeff-Teixeira C, Schulz-Key H, and Geiger SM
- Subjects
- Animals, Antibodies, Helminth blood, Aorta parasitology, Disease Models, Animal, Feces parasitology, Heart parasitology, Immunoglobulin A blood, Immunoglobulin E blood, Immunoglobulin G blood, Immunoglobulin M blood, Liver parasitology, Mesenteric Arteries parasitology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Survival Analysis, Time Factors, Angiostrongylus immunology, Angiostrongylus isolation & purification, Strongylida Infections immunology, Strongylida Infections parasitology
- Abstract
BALB/c and C57BL/6 mice were experimentally infected with Angiostrongylus costaricensis and the parasitic parameters and antibody response during the acute and chronic phases of infection were analyzed. Following administration of six third-stage larvae (L3), there was no significant difference in the mean worm recovery or mean larval output. Coinciding with the maturation of worms in infected animals and with the egg output in mesenteric arteries, a strong increase in the humoral immune response was observed in both mouse strains. This response was characterized by a hypergammaglobulinemia, with a predominance of IgA and IgG1 during the acute phase of infection, and IgG1 and total IgE during the patent and post-patent periods. Significantly higher levels of IgM, IgG and IgG1 were found in BALB/c mice compared with C57BL/6 mice. On the other hand, a significantly higher concentration of IgA was detected at 6 and 7 weeks post-infection in C57BL/6 mice compared with BALB/c mice. Specific IgE could not be detected in any of the mouse strains. Our results suggest that immunoglobulins, mainly IgG1, contribute to the outcome of a primary A. costaricensis infection with respect to the period of patency and to mortality during the chronic phase.
- Published
- 2004
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30. Parasite-specific antibody and cytokine profiles in newborns from Plasmodium falciparum and Entamoeba histolytica/dispar-infected mothers.
- Author
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Kirch AK, Agossou A, Banla M, Hoffmann WH, Schulz-Key H, and Soboslay PT
- Subjects
- Adult, Animals, Entamoeba histolytica immunology, Female, Fetal Blood, Humans, Infant, Newborn, Rural Population, Urban Population, Antibodies, Protozoan immunology, Cytokines immunology, Entamoebiasis immunology, Immunity, Maternally-Acquired immunology, Malaria, Falciparum immunology
- Abstract
Passage of parasites and their antigens across the placenta occurs with metazoan as well as protozoan parasites, and this study addressed to which extent exposure to and infection of mothers with Plasmodium spp. and Entamoeba histolytica/dispar has sensitized their offspring for parasite-specific immune responses. While at delivery none of the mothers presented with an acute malaria attack, 42% were seropositive for P. falciparum. In half of the mothers cysts of E. histolytica/dispar were detected in stool specimen, 51% of them were found seropositive for E. histolytica, and E. histolytica-specific immunoglobulin A (IgA) responses were detected in neonates of seropositive mothers as well. Umbilical cord blood cells (UCBC) from neonates, when activated with the mitogen phytohaemagglutinine (PHA) and bacterial streptolysin O (SL-O), released significantly less interferon (IFN)-gamma, interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha into cell culture supernatants than peripheral blood cells (PBMC) of mothers. In response to Plasmodium- and Entamoeba-specific antigens UCBC and PBMC produced equal amounts of IL-1beta, TNF-alpha, IFN-gamma and IL-5, but PBMC from mothers secreted significantly more IL-10. Parasite-specific production of inflammatory and Th(1)- and Th(2)-type cytokines was similar in newborns of Plasmodium and Entamoeba seropositive and seronegative mothers. In summary, repeated exposure and subclinical infection of mothers with E. histolytica or P. falciparum will suffice to prime in utero their children for inflammatory and both Th(1)- and Th(2)-type cytokine responses, and such broad and mixed cytokine spectrum may be of advantage upon secondary parasite challenge in later life.
- Published
- 2004
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31. Impact of parental onchocerciasis and intensity of transmission on development and persistence of Onchocerca volvulus infection in offspring: an 18 year follow-up study.
- Author
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Kirch AK, Duerr HP, Boatin B, Alley WS, Hoffmann WH, Schulz-Key H, and Soboslay PT
- Subjects
- Adolescent, Adult, Africa South of the Sahara epidemiology, Animals, Child, Child, Preschool, Fathers, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Longitudinal Studies, Male, Microfilariae isolation & purification, Mothers, Onchocerca volvulus immunology, Onchocerciasis epidemiology, Onchocerciasis immunology, Pregnancy, Pregnancy Complications, Parasitic parasitology, Prevalence, Onchocerca volvulus growth & development, Onchocerciasis transmission
- Abstract
This study analysed the impact and the extent by which parental Onchocerca volvulus infection, intensity of transmission of O. volvulus infective 3rd-stage larvae (L3) and anthropometric factors may influence the acquisition, development and persistence of O. volvulus infection in offspring. A total of 15290 individuals in 3939 families with 9640 children were surveyed for microfilariae of O. volvulus, and prevalence and level of O. volvulus infection in children aged 0 to 20 years from infected and non-infected parents were followed longitudinally for 18 years. Children from O. volvulus-infected mothers had not only a substantially higher risk to become infected; they also acquired infection earlier in life and developed higher infection levels. Multiple logistic regression analysis showed that maternal O. volvulus infection and children's age are the predominant predictors for patent O. volvulus infection, while the intensity of transmission, measured by the annual transmission potential (ATP) of O. volvulus L3, was less decisive. Longitudinal follow up of children showed that during vector control activities by the Onchocerciasis Control Programme (OCP) and in low-level transmission areas, infection persisted at higher levels in children from O. volvulus-positive mothers. In summary, the dominant risk factor for children to become infected is maternal onchocerciasis, and also age-associated factors will strongly impact on the development of patent O. volvulus infection in offspring.
- Published
- 2003
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32. Angiostrongylus costaricensis infection in C57BL/6 mice: MHC-II deficiency results in increased larval elimination but unaltered mortality.
- Author
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Geiger SM, Hoffmann WH, Soboslay PT, Pfaff AW, Graeff-Teixeira C, and Schulz-Key H
- Subjects
- Animals, Antibodies, Helminth blood, Antigens, Helminth immunology, CD4-Positive T-Lymphocytes immunology, Feces parasitology, Immunoglobulins blood, Interferon-gamma biosynthesis, Interleukins biosynthesis, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitogens, Spleen immunology, Strongylida Infections parasitology, Angiostrongylus immunology, Angiostrongylus physiology, Genes, MHC Class II, Strongylida Infections immunology
- Abstract
During experimental Angiostrongylus costaricensis infections in several inbred mouse strains, genetic factors as well as different cytokine secretion patterns have recently been shown to play a role in the outcome of infection in terms of morbidity and mortality, e.g. BALB/c mice show a high and C57BL/6 mice a low mortality during the acute phase of infection. In this study, C57BL/6 MHC-II knockout mice infected with A. costaricensis did not show increased mortality during the acute phase of infection when compared with wild-type mice. Furthermore, MHC-II knockout mice showed a strongly diminished parasite-specific humoral and cellular immune response, which can be explained by the nearly complete lack of CD4+ T cells in the periphery. This defect in MHC-II genes, the lack of CD4+ T cells, and the resulting cellular and humoral unresponsiveness resulted in a three times higher output of first-stage larvae in feces compared with wild-type animals. The results indicate that during experimental A. costaricensis infection a parasite-specific immune response, directed via MHC-II molecules and CD4+ T cells, is not essential for the survival of C57BL/6 mice during the acute phase of infection, whereas the elimination of first-stage larvae seems to be regulated by a MHC-II- and CD4+ T-cell-dependent mechanism.
- Published
- 2003
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33. Regulatory effects of IL-12 and IL-18 on Onchocerca volvulus- and Entamoeba histolytica-specific cellular reactivity and cytokine profiles.
- Author
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Pfaff AW, Kirch AK, Hoffmann WH, Banla M, Schulz-Key H, Geiger SM, and Soboslay PT
- Subjects
- Adolescent, Adult, Animals, Antigens, Helminth immunology, Chemokine CXCL10, Chemokines, CXC biosynthesis, Chemokines, CXC immunology, Entamoebiasis blood, Enzyme-Linked Immunosorbent Assay, Humans, Interferon-gamma biosynthesis, Interferon-gamma immunology, Interleukin-10 biosynthesis, Interleukin-18 biosynthesis, Interleukin-5 biosynthesis, Interleukin-5 immunology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation immunology, Middle Aged, Onchocerciasis blood, Th1 Cells immunology, Th2 Cells immunology, Entamoeba histolytica immunology, Entamoebiasis immunology, Interleukin-10 immunology, Interleukin-18 immunology, Onchocerca volvulus immunology, Onchocerciasis immunology
- Abstract
In the present study, the cytokines interleukin (IL)-12 and IL-18 were evaluated for their capacity to modulate and to re-direct in vitro parasite antigen-specific cellular responsiveness in patients exposed to Onchocerca volvulus and Entamoeba histolytica infection. We found that IL-18 was highly capable of reducing parasite antigen-induced IL-10 production by PBMC. In contrast, addition or neutralization of IL-12, also in combination with IL-18 and the interferon-gamma-inducible chemokine IP-10 did not affect IL-10 production. Interestingly, the highest IL-10 levels were measured when IL-18 and IP-10 were both neutralized. Although having no effect on IL-10, IL-12 strongly promoted spontaneous and parasite antigen-driven IFN-gamma production by PBMC, whereas IL-18 was only moderately affecting IFN-gamma release by PBMC re-stimulated with E. histolytica- or O. volvulus-specific antigens. Both IL-12 and IL-18 diminished the cellular production of IL-13, and a synergistic effect was observed when the cytokines were combined. Likewise, neutralization of IL-12 enhanced Entamoeba and Onchocerca antigen-driven IL-13 production, but no further increase of IL-13 was observed, when anti-IL-12 and anti-IL-18 were used together. This study disclosed that IL-18 will significantly down-regulate parasite-specific IL-10 production, whereas IL-12 induced IFN-gamma and inhibited IL-13 production by PBMC from humans exposed to O. volvulus and E. histolytica. Such selective immune-regulatory capacity of IL-12 and IL-18 may comprise an important tool to re-direct polarized cytokine responses towards a balanced Th1/Th2 cytokine profile, which may prevent pathology and promote immunity against helminth and protozoan parasite infections.
- Published
- 2003
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34. Litomosoides sigmodontis cystatin acts as an immunomodulator during experimental filariasis.
- Author
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Pfaff AW, Schulz-Key H, Soboslay PT, Taylor DW, MacLennan K, and Hoffmann WH
- Subjects
- Amino Acid Sequence, Animals, Antigens, Helminth immunology, Base Sequence, Blotting, Western, Cystatins genetics, Cystatins isolation & purification, Cystatins pharmacology, Filarioidea genetics, Immunization, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Nitric Oxide biosynthesis, Rats, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Sigmodontinae, Cystatins immunology, Filariasis immunology, Filarioidea immunology
- Abstract
During chronic filariasis, parasite-specific cellular responsiveness is profoundly down-regulated. Cystatins, a group of cysteine protease inhibitors, have been implicated in this suppressive activity. In an attempt to investigate the effects of cystatins in vivo, we isolated and expressed a 14 kDa protein of the rodent filaria Litomosoides sigmodontis with substantial homologies to cystatins from human pathogenic filariae. Cystatin was detected in antigen preparations of several developmental stages of L. sigmodontis, as well as in the supernatants of in vitro cultured adult worms. On closer examination, L. sigmodontis cystatin (Ls-Cystatin) migrated as two separate bands at 14 and 15 kDa. When cystatin was introduced into the peritoneal cavity of C57BL/6 mice via micro-osmotic pumps, the production of nitric oxide was profoundly reduced upon microfilarial challenge and, at the same time, synthesis of TNF-alpha mRNA became up-regulated. Furthermore, antigen-specific proliferative response of spleen cells to circulating L. sigmodontis microfilariae was significantly diminished in the presence of cystatin, whereas the antibody production was not suppressed. In vaccination trials, using the L. sigmodontis/BALB/c mouse model of filariasis, L. sigmodontis cystatin did not generate protective effects in terms of adult worm recovery, however, lower numbers of patent infections, i.e. less infections with microfilaraemia were observed in vaccinated animals. These results suggested that cystatin acts as an immunomodulatory molecule during the course of a filarial infection, and its neutralisation might contribute to generate protective immune responses.
- Published
- 2002
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35. Cellular immune responses and cytokine production in BALB/c and C57BL/6 mice during the acute phase of Angiostrongylus costaricensis infection.
- Author
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Geiger SM, Abrahams-Sandi E, Soboslay PT, Hoffmann WH, Pfaff AW, Graeff-Teixeira C, and Schulz-Key H
- Subjects
- Animals, Antibody Formation, Cells, Cultured, Cytokines analysis, Female, Interferon-gamma analysis, Interferon-gamma biosynthesis, Interleukin-10 analysis, Interleukin-10 biosynthesis, Interleukin-2 analysis, Interleukin-2 biosynthesis, Interleukin-4 analysis, Interleukin-4 biosynthesis, Interleukin-5 analysis, Interleukin-5 biosynthesis, Lymphocyte Activation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mitogens, Strongylida Infections parasitology, Strongylida Infections pathology, Time Factors, Angiostrongylus, Antibodies, Helminth blood, Cytokines immunology, Spleen immunology, Strongylida Infections immunology
- Abstract
In our experimental study we were able to show that the contrasting outcome of Angiostrongylus costaricensis infection in C57BL/6 and BALB/c mice, in respect of morbidity and mortality, can be explained by divergent cellular immune responses and a different cytokine pattern in each strain. In BALB/c mice (i.e. those with high mortality), the initial high proliferation of ConA or LPS stimulated spleen cells dropped to very low levels after 2 weeks post-infection (p.i.), whereas in C57BL/6 mice (i.e. those with low mortality), only a minor reduction in lymphoproliferative responses after mitogenic stimulation was observed. The specific proliferation of spleen cells after stimulation with A. costaricensis adult worm antigen remained low in BALB/c mice throughout the experiment, but showed an augmented proliferation in C57BL/6 mice, especially from 2 weeks p.i. onwards. The mitogen-induced production of Th2-type cytokines (IL-4, IL-5, IL-6, IL-10) in spleen cell cultures remained low in BALB/c mice until 4 weeks p.i., but production of Th1-type cytokines (IL-2, IFN-gamma) was highly elevated at 14 and 28 days p.i. In C57BL/6 mice, an upregulated and balanced production of both Th1- and Th2-type cytokines was measured during the course of infection. In summary, a polarization of the immune response towards cellular hyporesponsiveness and a predominantly Th1 cytokine profile was observed in A. costaricensis infected BALB/c mice, which may contribute to pathogenesis and increased morbidity.
- Published
- 2001
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36. Determinants for resistance and susceptibility to microfilaraemia in Litomosoides sigmodontis filariasis.
- Author
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Hoffmann WH, Pfaff AW, Schulz-Key H, and Soboslay PT
- Subjects
- Animals, Antibodies, Helminth analysis, Cytokines biosynthesis, Female, Filariasis parasitology, Filarioidea growth & development, Genes, MHC Class II immunology, Host-Parasite Interactions immunology, Immunity, Innate genetics, Immunity, Innate immunology, Interleukin-10 biosynthesis, Interleukin-10 immunology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout genetics, Mice, Knockout parasitology, Microfilariae growth & development, Parasitemia parasitology, Spleen parasitology, Filariasis immunology, Filarioidea immunology, Microfilariae immunology, Parasitemia immunology
- Abstract
Filarial infections of humans are chronic diseases. Despite an ongoing immune response, adult filariae continuously produce their offspring, the microfilariae (Mf), which are able to persist in sufficient numbers to ensure transmission. In this study, host- and parasite-derived factors, which contribute to persistence of Mf, were investigated using the filariasis model of Litomosoides sigmodontis in mice. Different strains of mice were found to differ widely in their capability to eliminate circulating Mf. Studies of congenic mouse strains showed that early and rapid clearance of Mf was mediated by activation pathways relevant to innate immunity, whereas late or delayed clearance of Mf was pre-determined by MHC-related factors. Genetic knock-out of genes for the MHC class-II molecules totally abrogated resistance. Most interestingly, the presence of only I adult female, but not male worms, renders all mice susceptible, irrespective of the genetic background, enabling Mf to circulate for extended periods of time. Such prolonged microfilaraemia was also observed in L. sigmodontis-infected animals challenged with heterologous Mf of Acanthocheilonema viteae. The use of cytokine gene knock-out mice showed that persistence of L. sigmodontis Mf was facilitated by IL-10, but not by IL-4 or IFN-gamma. In conclusion, irrespective of a resistant or susceptible host genetic background, survival of Mf of L. sigmodontis in mice is decisively regulated by the presence of adult female L. sigmodontis which will skew and exploit immune responses to facilitate the survival and persistence of their offspring in the infected host.
- Published
- 2001
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37. The role of nitric oxide in the innate resistance to microfilariae of Litomosoides sigmodontis in mice.
- Author
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Pfaff AW, Schulz-Key H, Soboslay PT, Geiger SM, and Hoffmann WH
- Subjects
- Animals, Cells, Cultured, Cytokines biosynthesis, Filariasis parasitology, Filarioidea drug effects, Filarioidea growth & development, Hydrogen Peroxide pharmacology, Immunity, Innate, Leukocyte Count, Mice, Mice, Inbred C57BL, Mice, Knockout, Microfilariae drug effects, Microfilariae growth & development, Microfilariae immunology, Nitric Oxide pharmacology, Nitric Oxide Synthase genetics, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Spleen cytology, Filariasis immunology, Filarioidea immunology, Nitric Oxide metabolism
- Abstract
Nitric oxide (NO) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN-gamma. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN-gamma, may be a target of NO release. In this study, we found that mf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemical NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In-vivo production of NO following injection of mf, in this and previous studies, suggested a central role in the defence to filariae. However, neither pharmaceutical inhibition of nitric oxide synthesis, nor genetic knockout of the gene for inducible nitric oxide synthase (iNOS), abrogated resistance to circulating mf in mice. Interestingly, however, iNOS-KO mice showed higher interleukin (IL)-2 responses and lower IL-10 production, compared to their wild-type counterparts. In conclusion, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an important factor in elimination of mf of L. sigmodontis in vivo. However, it may have a regulatory role in the immune response.
- Published
- 2000
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38. Litomosoides sigmodontis: dynamics of the survival of microfilariae in resistant and susceptible strains of mice.
- Author
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Pfaff AW, Schulz-Key H, Soboslay PT, Geiger SM, and Hoffmann WH
- Subjects
- Animals, Disease Susceptibility, Immunity, Innate, Immunocompetence, Leukocyte Count, Lymphocyte Activation, Mice, Mice, Inbred BALB C immunology, Mice, Inbred C57BL immunology, Microfilariae immunology, Nitric Oxide biosynthesis, Parasitemia immunology, Pleura metabolism, Pleura parasitology, Spleen cytology, Spleen immunology, Disease Models, Animal, Filariasis immunology, Filarioidea immunology, Mice, Inbred BALB C parasitology, Mice, Inbred C57BL parasitology
- Abstract
Litomosoides sigmodontis in the BALB/c mouse is the only model of filariasis which allows the observation of the complete development in an immunocompetent mouse. In this study, we injected microfilariae (mf) intravenously, as well as into the pleural cavity, the site of natural release of mf from adult female worms, and followed the kinetics of elimination within the host. In susceptible BALB/c mice, mf circulated at high levels in the blood. In contrast, in C57BL/6 mice, which are refractory to full development, mf were eliminated rapidly from the peripheral blood. However, 6 days after intrapleural injection, viable larvae could be found in the pleural cavity and lung capillaries of both susceptible and resistant strains. The numbers of mf in the pleural cavity and lung capillaries in individual mice were significantly correlated, but not dependent on strain or peripheral microfilaraemia. Thus, although C57BL/6 mice showed enhanced production of nitric oxide by pleural exudate cells and a faster change in the numbers of circulating leukocytes after injection, rapid killing of mf by cell or nitric oxide-mediated mechanisms were not the reason for the different outcome. Furthermore, 3 h after iv injection, only a small percentage of mf could be recovered from the peripheral circulation, indicating the presence of a reservoir for mf containment. In conclusion, injected mf showed disparate dynamics of persistence within susceptible and resistant hosts, which is similar to the disparate outcome of natural infections with L. sigmodontis. This difference became obvious within 1 day after injection. The lung capillary system plays obviously a crucial part in regulation of microfilaremia. Our model also provides a possible means to explain frequent cases of occult infections in human filariasis., (Copyright 2000 Academic Press.)
- Published
- 2000
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39. Operations that require supracoeliac aortic cross-clamping: perioperative monitoring with gastric tonometry.
- Author
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Geelkerken RH, Zwijsen JH, van Baalen JM, Harinck HI, Hoffmann WH, and van Bockel JH
- Subjects
- APACHE, Aged, Aged, 80 and over, Constriction, Female, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Postoperative Period, Prospective Studies, Aortic Aneurysm, Abdominal surgery, Aortic Aneurysm, Thoracic surgery, Gastric Mucosa chemistry, Monitoring, Intraoperative, Splanchnic Circulation
- Abstract
Objective: To assess the predictive value of a gastric intramucosal pH of less than 7.35 for mortality in surgical patients after supracoeliac aortic cross-clamping., Design: Open prospective clinical study., Setting: University hospital, The Netherlands., Subjects: Six patients who required temporary supracoeliac, and four patients who required temporary infrarenal, cross-clamping of the aorta., Main Outcome Measures: Mortality and conventional measures of organ dysfunction correlated with gastric tonometry., Results: All 6 patients who required supracoeliac cross-clamping underwent a steep, and 5 patients a prolonged, decrease in the gastric intramucosal pH. The mean lowest gastric intramucosal pH in the supracoeliac group was 7.05 and in the infrarenal group 7.28. All patients recovered completely., Conclusion: A pHig value below 7.35 does not seem to be a marker of mortality in patients who have undergone supracoeliac cross-clamping of the aorta.
- Published
- 1999
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40. Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2-12.5 kD.
- Author
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Hoffmann WH, Blanke CH, Maier JM, Lüder CG, Schulz-Key H, and Soboslay PT
- Subjects
- Adolescent, Adult, Animals, Antigens, Helminth isolation & purification, Ape Diseases diagnosis, Electrophoresis, Polyacrylamide Gel methods, Humans, Immunoblotting methods, Middle Aged, Molecular Weight, Onchocerciasis diagnosis, Onchocerciasis veterinary, Pan troglodytes, Peptides isolation & purification, Sensitivity and Specificity, Serologic Tests methods, Serologic Tests veterinary, Togo, Antigens, Helminth blood, Epitopes, Onchocerca volvulus immunology, Peptides blood
- Abstract
Onchocerca volvulus polypeptides in the molecular mass range of 2.2 to 12.5 kD were separated by Tricine-SDS-PAGE and the serological recognition of these very low molecular weight antigens (VLMW-OvAg) was then investigated by immuno-blotting. Sera from 21 onchocerciasis patients as well as from 53 individuals with other filariases were used to determine the sensitivity and specificity of detection of individual VLMW-OvAg. In onchocerciasis patients, up to 16 VLMW-OvAg were recognized predominantly by IgG1 and IgG4, while only few antigens were recognized by IgG2 and IgG3. The antigen recognition pattern varied individually, but 4 VLMW-OvAg of 8.6, 6.2, 5.4, and 5.1 kD, respectively, were bound by IgG4 from more than 90% of the onchocerciasis patients. Six VLMW-OvAg of 7.3, 5.8, 5.4, 4.0, 3.8, and 3.6 kD were recognized exclusively by IgG1 from onchocerciasis patients. In amicrofilaraemic filariasis patients with lymphatic pathology, a strong reactivity of IgG3 to an OvAg of 2.2 kD was observed, indicating a possible contribution of this antigen to the pathogenesis. In the molecular mass range below 13 kD, no specific carbohydrate residues or phosphorylcholine-containing (PC) determinants could be identified by lectin-blotting or PC-specific immunoblotting, respectively. Two-dimensional separation and immunoblotting distinctly resolved more than 40 antigenic polypeptides, the majority focusing at acidic isoelectric points. In O. volvulus-infected chimpanzees the IgG1- and IgG4-reactivity against OvAg below 13 kD appeared concurrently with onset of patent infection. These data suggest that some of these VLMW-OvAg might be associated with the production and release of microfilariae from gravid female worms as well as be involved in immune-mediated pathogenesis during filarial infections.
- Published
- 1997
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41. Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection.
- Author
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Soboslay PT, Lüder CG, Hoffmann WH, Michaelis I, Helling G, Heuschkel C, Dreweck CM, Blanke CH, Pritze S, and Banla M
- Subjects
- Animals, Antibody Specificity, Antigens, Helminth immunology, Female, Humans, Interferon-gamma biosynthesis, Interleukins biosynthesis, Ivermectin pharmacology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Male, Onchocerciasis drug therapy, Skin parasitology, Antibodies, Helminth biosynthesis, Immunity, Cellular drug effects, Ivermectin therapeutic use, Onchocerca volvulus immunology, Onchocerciasis immunology
- Abstract
The present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments. In vitro cellular responses to O. volvulus antigen (OvAg) were highest (P < 0.01) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P < 0.05) at 84 months p.i.t. in amicrofilaridermic than in microfilaria-positive onchocerciasis patients. In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals. Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2, IL-4 and interferon-gamma (IFN-gamma) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-gamma were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients. OvAg-specific production of IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P < 0.05), but they then continuously declined with repeated treatments. Only IgG1 and IgG4 bound to OvAg of mol. wt 2-12 kD at 1 month p.i.t., while recognition of OvAg of mol. wt 10-200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3-6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results suggest that onchocerciasis-associated immunosuppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-gamma in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.
- Published
- 1994
- Full Text
- View/download PDF
42. Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.
- Author
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Soboslay PT, Dreweck CM, Hoffmann WH, Lüder CG, Heuschkel C, Görgen H, Banla M, and Schulz-Key H
- Subjects
- Animals, Bacterial Proteins, Cytokines metabolism, Dermatitis immunology, Eosinophilia drug therapy, Female, Humans, Hypersensitivity, Delayed immunology, Immunity, Cellular drug effects, Ivermectin therapeutic use, Leukocyte Count drug effects, Lymphocyte Subsets cytology, Lymphocyte Subsets drug effects, Male, Microfilariae, Parasite Egg Count, Phenotype, Phytohemagglutinins, Statistics as Topic, Streptolysins pharmacology, Ivermectin pharmacology, Onchocerciasis immunology
- Abstract
A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCR gamma delta + cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.
- Published
- 1992
- Full Text
- View/download PDF
43. Ivermectin-facilitated immunity.
- Author
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Schulz-Key H, Soboslay PT, and Hoffmann WH
- Published
- 1992
- Full Text
- View/download PDF
44. The pandemic endemicity of dengue in warm countries.
- Author
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HOFFMANN WH
- Subjects
- Humans, Biometry, Dengue epidemiology, Dengue statistics & numerical data
- Published
- 1946
45. THE SECOND CAPTURE OF THE WHALE SHARK, RHINEODON TYPUS, NEAR HAVANA HARBOR, CUBA.
- Author
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Gudger EW and Hoffmann WH
- Published
- 1930
- Full Text
- View/download PDF
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