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13 results on '"S. Drinkwater"'

1. First case series of clozapine induced hypogammaglobulinaemia in England

Author

T Tan, A Herwadkar, Ariharan Anantharachagan, S Drinkwater, P Vijayadurai, H. Alachkar, T Garcez, J. Darroch, and Shuayb Elkhalifa

Subjects
Antibody deficiency, Clinical immunology, Immunoglobulin levels, business.industry, General Medicine, North west, Immunology, Medicine, In patient, business, Signalling pathways, Drug toxicity, Clozapine, medicine.drug
Abstract

Evidence is emerging that clozapine can adversely affect immunoglobulin levels. We present a case series of 17 clozapine-treated patients referred to clinical immunology centres in the north west of England with otherwise-unexplained hypogammaglobulinaemia. This adds to existing evidence and suggests that clozapine can cause clinically significant antibody deficiency that will sometimes require specialist intervention. We speculate that this putative drug toxicity could be mediated via interaction with PI3K (phosphatidylinositol-3-kinase) signalling pathways involved in the development and homeostasis of B cells. It may be advisable to monitor immunoglobulin levels in patients being treated with clozapine.

Published
2021
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2. Recovery of Microbial Contamination with Settle Plates Exposed in a Unidirectional Airflow Workstation for 4 Hours

Author

Tim Eaton, Karen Capper, A Nash, S Drinkwater, and J Bright

Abstract

The ability of irradiated 90 mm diameter Tryptone Soya Agar (TSA) settle plates, exposed for 4 hours in a unidirectional airflow (UDAF) workstation (air supply velocity 0.45 m/s), to recover microbial contamination, was investigated. The investigation was completed by inoculation of numerous test plates with a range of different test micro-organisms and then exposure of the plates within a UDAF workstation for 4 hours. Following incubation, the numbers of recovered micro-organisms were compared with the numbers recovered from control plates that had been identically inoculated and incubated but not exposed within the workstation. Investigations of initial settle plate weight variation, loss of weight and water activity levels during exposure were also completed to help understand the influence of plate media water to any loss of microbial recovery. It was determined that the average number of recovered test plate colonies was reduced compared to the control plates and the exposure of the plates reduced the weight by an average of 10.85%. However, the media water activity levels remained consistently higher than the threshold level at which the growth of micro-organisms would be affected and the ability of the plates to recover micro-organisms was reduced but not significantly affected. Key words: Microbiological settle plates, media dehydration, unidirectional airflow (UDAF), 4 hour exposure

Published
2022
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4. Choices of stent and cerebral protection in the ongoing ACST-2 trial: a descriptive study

Author

D.D. de Waard, A. Halliday, G.J. de Borst, R. Bulbulia, A. Huibers, R. Casana, L.H. Bonati, V. Tolva, G. Fraedrich, B. Rantner, E. Gizewski, I. Gruber, J. Hendriks, P. Cras, P. Lauwers, P. van Scheil, F. Vermassen, I. Van Herzeele, M. Geenens, D. Hemelsoet, P. Lerut, B. Lambrecht, G. Saad, A. Peeters, M. Bosiers, E. da Silva, N. de Luccia, J.C. Sitrangulo, A.E.V. Estenssoro, C. Presti, I. Casella, J.A.T. Monteiro, W. Campos, P. Puech-Leao, V. Petrov, C. Bachvarov, M. Hill, A. Mitha, J. Wong, C.-W. Liu, L. Bao, C. Yu, I. Cvjetko, V. Vidjak, J. Fiedler, S. Ostry, L. Sterba, P. Kostal, R. Staffa, R. Vlachovsky, M. Privara, Z. Kriz, B. Vojtisek, P. Krupa, M. Reif, V. Benes, P. Buchvald, L. Endrych, V. Prochazka, M. Kuliha, D. Otahal, T. Hrbac, D. Netuka, M. Mohapl, F. Kramier, M. Eldessoki, H. Heshmat, F. Abd-Allah, V. Palmiste, S. Margus, T. Toomsoo, J.-P. Becquemin, P. Bergeron, T. Abdulamit, J.-M. Cardon, S. Debus, G. Thomalla, J. Fiehler, C. Gerloss, U. Grzyska, M. Storck, E. LaMacchia, H.H. Eckstein, H. Söllner, H. Berger, M. Kallmayer, H. Popert, A. Zimmermann, A. Guenther, C. Klingner, T. Mayer, J. Schubert, J. Zanow, D. Scheinert, U. Banning-Eichenseer, Y. Bausback, D. Branzan, S. Braünilch, J. Lenzer, A. Schidt, H. Staab, M. Ulirch, J. Barlinn, K. Haase, A. Abramyuk, U. Bodechtel, J. Gerber, C. Reeps, T. Pfeiffer, G. Torello, A. Cöster, A. Giannoukas, K. Spanos, M. Matsagkas, S. Koutias, S. Vasdekis, J. Kakisis, K. Moulakakis, A. Lazaris, C. Liapas, E. Brountzos, M. Lazarides, N. Ioannou, A. Polydorou, B. Fulop, E. Fako, E. Voros, M. Bodosi, T. Nemeth, P. Barzo, S. Pazdernyik, L. Entz, Z. Szeberin, E. Dosa, B. Nemes, Z. Jaranyi, S. Pazdernyia, P. Madhaban, A. Hoffman, E. Nikolsky, R. Beyar, R. Silingardi, A. Lauricella, G. Coppi, E. Nicoloci, N. Tusini, F. Strozzi, E. Vecchiati, M. Ferri, E. Ferrero, D. Psacharopulo, A. Gaggiano, A. Viazzo, L. Farchioni, G. Parlani, V. Caso, P. De Rangoy, F. Verzini, P. Castelli, M.L. DeLodovici, G. Carrafiello, A.M. Ierardi, G. Piffaretti, G. Nano, M.T. Occhiuto, G. Malacrida, D. Tealdi, S. Steghter, A. Stella, R. Pini, G. Faggioli, S. Sacca, M.D. Negri, M. Palombo, M.C. Perfumo, G.F. Fadda, H. Kasemi, C. Cernetti, D. Tonello, A. Visonà, N. Mangialardi, S. Ronchey, M.C. Altavista, S. Michelagnoli, E. Chisci, F. Speziale, L. Capoccia, P. Veroux, A. Giaquinta, F. Patti, R. Pulli, P. Boggia, D. Angiletta, G. Amatucci, F. Spinetti, F. Mascoli, E. Tsolaki, E. Civilini, B. Reimers, C. Setacci, G. Pogany, A. Odero, F. Accrocca, G. Bajardi, I. Takashi, E. Masayuki, E. Hidenori, B. Aidashova, N. Kospanov, S. Bakke, M. Skjelland, A. Czlonkowska, A. Kobayashi, R. Proczka, A. Dowzenko, W. Czepel, J. Polanski, P. Bialek, G. Ozkinis, M. Snoch-Ziólkiewicz, M. Gabriel, M. Stanisic, W. Iwanowski, P. Andziak, F.B. Gonçalves, V. Starodubtsev, P. Ignatenko, A. Karpenko, D. Radak, N. Aleksic, D. Sagic, L. Davidovic, I. Koncar, I. Tomic, M. Colic, D. Bartkoy, F. Rusnak, M. Gaspirini, P. Praczek, Z. Milosevic, V. Flis, A. Bergauer, N. Kobilica, K. Miksic, J. Matela, E. Blanco, M. Guerra, V. Riambau, P. Gillgren, C. Skioldebrand, N. Nymen, B. Berg, M. Delle, J. Formgren, T.B. Kally, P. Qvarfordt, G. Plate, H. Pärson, H. Lindgren, K. Bjorses, A. Gottsäter, M. Warvsten, T. Kristmundsson, C. Forssell, M. Malina, J. Holst, T. Kuhme, B. Sonesson, B. Lindblad, T. Kolbel, S. Acosta, L. Bonati, C. Traenka, M. Mueller, T. Lattman, M. Wasner, E. Mujagic, A. Von Hessling, A. Isaak, P. Stierli, T. Eugster, L. Mariani, C. Stippich, T. Wolff, T. Kahles, R. Toorop, F. Moll, R. Lo, A. Meershoek, A.K. Jahrome, A.W.F. Vos, W. Schuiling, R. Keunen, M. Reijnen, S. Macsweeney, N. McConachie, A. Southam, G. Stansby, T. Lees, D. Lambert, M. Clarke, M. Wyatt, S. Kappadath, L. Wales, R. Jackson, A. Raudonaitis, S. MacDonald, P. Dunlop, A. Brown, S. Vetrivel, M. Bajoriene, R. Gopi, C. McCollum, L. Wolowczyk, J. Ghosh, D. Seriki, R. Ashleigh, J. Butterfield, M. Welch, J.V. Smyth, D. Briley, U. Schulz, J. Perkins, L. Hands, W. Kuker, C. Darby, A. Handa, L. Sekaran, K. Poskitt, J. Morrison, P. Guyler, I. Grunwald, J. Brown, M. Jakeways, S. Tysoe, D. Hargroves, G. Gunathilagan, R. Insall, J. Senaratne, J. Beard, T. Cleveland, S. Nawaz, R. Lonsdale, D. Turner, P. Gaines, R. Nair, I. Chetter, G. Robinson, B. Akomolafe, J. Hatfield, K. Saastamoinen, J. Crinnion, A.A. Egun, J. Thomas, S. Drinkwater, S. D'Souza, G. Thomson, B. Gregory, S. Babu, S. Ashley, T. Joseph, R. Gibbs, G. Tebit, A. Mehrzad, P. Enevoldson, D. Mendalow, A. Parry, G. Tervitt, A. Clifton, M. Nazzel, R. Peto, H. Pan, J. Potter, R. Bullbulia, B. Mihaylova, M. Flather, A. Mansfield, D. Simpson, D. Thomas, W. Gray, B. Farrell, C. Davies, K. Rahimi, M. Gough, P. Cao, P. Rothwell, A. Belli, M. Mafham, W. Herrington, P. Sandercock, R. Gray, C. Shearman, A. Molyneux, A. Gray, A. Clarke, M. Sneade, L. Tully, W. Brudlo, M. Lay, A. Munday, C. Berry, S. Tochlin, J. Cox, R. Kurien, and J. Chester

Subjects
Plaque echolucency, Time Factors, medicine.medical_treatment, Practice Patterns, 030204 cardiovascular system & hematology, Severity of Illness Index, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, Occlusion, Carotid artery stenosis, Carotid Stenosis, Practice Patterns, Physicians', Stroke, Endarterectomy, Plaque, Atherosclerotic, Endarterectomy, Carotid, Endovascular Procedures, Plaque, Atherosclerotic, Treatment Outcome, Cerebrovascular Circulation, Stents, Radiology, medicine.symptom, Cardiology and Cardiovascular Medicine, Carotid artery stenting, medicine.medical_specialty, Clinical Decision-Making, education, Cerebral protection devices, Stent design, Surgery, Prosthesis Design, Asymptomatic, Embolic Protection Devices, 03 medical and health sciences, Severity of illness, medicine, Humans, Carotid, Chi-Square Distribution, Physicians', business.industry, Patient Selection, Stent, METANÁLISE, medicine.disease, Asymptomatic Diseases, Cerebrovascular Disorders, Stenosis, business, 030217 neurology & neurosurgery
Abstract

Objectives Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Materials and methods Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90–99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. Results In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90–99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. Conclusions In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

Published
2017

5. Expression of chemokine receptors CXCR4, CXCR5 and CCR7 on B and T lymphocytes from patients with primary antibody deficiency

Author

R Baretto, Daniel Payne, Michael J. Browning, S Drinkwater, and M Duddridge

Subjects
Adult, Male, Receptors, CXCR5, Receptors, CCR7, Receptors, CXCR4, Translational Studies, T-Lymphocytes, Immunology, C-C chemokine receptor type 7, Biology, Statistics, Nonparametric, Chemokine receptor, Humans, Immunology and Allergy, CXCL13, CCL13, CXCL16, B-Lymphocytes, Immunologic Deficiency Syndromes, Middle Aged, Flow Cytometry, CCL20, Common Variable Immunodeficiency, Case-Control Studies, Female, Receptors, Chemokine, CC chemokine receptors, Immunologic Memory, Abnormal Lymphocyte
Abstract

SummaryThe interaction of chemokines and their receptors directs lymphocyte migration, and is involved in the distribution and organization of lymphocytes within lymphoid tissues. We reasoned that abnormal chemokine receptor expression might give rise to defects of lymphocyte migration into and within lymphoid tissues, and consequently be associated with defective antibody production in primary antibody deficiencies. In this study, we have investigated the expression of chemokine receptors CXCR4, CXCR5 and CCR7 on lymphocyte subpopulations (naive and memory B cells; CD4+ and CD8+ T cells) in a cohort of patients with primary antibody deficiency (n = 23), and compared these with a group of healthy controls (n = 19). We show that there were significant differences in both the proportions of lymphocytes expressing, and the levels of expression of, specific chemokine receptors on individual lymphocyte subpopulations between patients and controls. Furthermore, these changes appeared more pronounced in patients with more severe antibody deficiency. These data support the hypothesis that abnormal lymphocyte trafficking may be involved in the pathogenesis of primary antibody deficiencies.

Published
2009
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6. Erratum to 'Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study' [Eur J Vasc Endovasc Surg 53 (2017) 617–625]

Author

D.D. de Waard, A. Halliday, G.J. de Borst, R. Bulbulia, A. Huibers, R. Casana, L.H. Bonati, V. Tolva, G. Fraedrich, B. Rantner, E. Gizewski, I. Gruber, J. Hendriks, P. Cras, P. Lauwers, P. van Scheil, F. Vermassen, I. Van Herzeele, M. Geenens, D. Hemelsoet, P. Lerut, B. Lambrecht, G. Saad, A. Peeters, M. Bosiers, E. da Silva, N. de Luccia, J.C. Sitrangulo, A.E.V. Estenssoro, C. Presti, I. Casella, J.A.T. Monteiro, W. Campos, P. Puech-Leao, V. Petrov, C. Bachvarov, M. Hill, A. Mitha, J. Wong, C.-W. Liu, L. Bao, C. Yu, I. Cvjetko, V. Vidjak, J. Fiedler, S. Ostry, L. Sterba, P. Kostal, R. Staffa, R. Vlachovsky, M. Privara, Z. Kriz, B. Vojtisek, P. Krupa, M. Reif, V. Benes, P. Buchvald, L. Endrych, V. Prochazka, M. Kuliha, D. Otahal, T. Hrbac, D. Netuka, M. Mohapl, F. Kramier, M. Eldessoki, H. Heshmat, F. Abd-Allah, V. Palmiste, S. Margus, T. Toomsoo, J.-P. Becquemin, P. Bergeron, T. Abdulamit, J.-M. Cardon, S. Debus, G. Thomalla, J. Fiehler, C. Gerloss, U. Grzyska, M. Storck, E. LaMacchia, H.H. Eckstein, H. Söllner, H. Berger, M. Kallmayer, H. Popert, A. Zimmermann, A. Guenther, C. Klingner, T. Mayer, J. Schubert, J. Zanow, D. Scheinert, U. Banning-Eichenseer, Y. Bausback, D. Branzan, S. Braünilch, J. Lenzer, A. Schidt, H. Staab, M. Ulirch, J. Barlinn, K. Haase, A. Abramyuk, U. Bodechtel, J. Gerber, C. Reeps, T. Pfeiffer, G. Torello, A. Cöster, A. Giannoukas, K. Spanos, M. Matsagkas, S. Koutias, S. Vasdekis, J. Kakisis, K. Moulakakis, A. Lazaris, C. Liapas, E. Brountzos, M. Lazarides, N. Ioannou, A. Polydorou, B. Fulop, E. Fako, E. Voros, M. Bodosi, T. Nemeth, P. Barzo, S. Pazdernyik, L. Entz, Z. Szeberin, E. Dosa, B. Nemes, Z. Jaranyi, S. Pazdernyia, P. Madhaban, A. Hoffman, E. Nikolsky, R. Beyar, R. Silingardi, A. Lauricella, G. Coppi, E. Nicoloci, N. Tusini, F. Strozzi, E. Vecchiati, M. Ferri, E. Ferrero, D. Psacharopulo, A. Gaggiano, A. Viazzo, L. Farchioni, G. Parlani, V. Caso, P. De Rangoy, F. Verzini, P. Castelli, M.L. DeLodovici, G. Carrafiello, A.M. Ierardi, G. Piffaretti, G. Nano, M.T. Occhiuto, G. Malacrida, D. Tealdi, S. Steghter, A. Stella, R. Pini, G. Faggioli, S. Sacca, M.D. Negri, M. Palombo, M.C. Perfumo, G.F. Fadda, H. Kasemi, C. Cernetti, D. Tonello, A. Visonà, N. Mangialardi, S. Ronchey, M.C. Altavista, S. Michelagnoli, E. Chisci, F. Speziale, L. Capoccia, P. Veroux, A. Giaquinta, F. Patti, R. Pulli, P. Boggia, D. Angiletta, G. Amatucci, F. Spinetti, F. Mascoli, E. Tsolaki, E. Civilini, B. Reimers, C. Setacci, G. Pogany, A. Odero, F. Accrocca, G. Bajardi, I. Takashi, E. Masayuki, E. Hidenori, B. Aidashova, N. Kospanov, S. Bakke, M. Skjelland, A. Czlonkowska, A. Kobayashi, R. Proczka, A. Dowzenko, W. Czepel, J. Polanski, P. Bialek, G. Ozkinis, M. Snoch-Ziólkiewicz, M. Gabriel, M. Stanisic, W. Iwanowski, P. Andziak, F.B. Gonçalves, V. Starodubtsev, P. Ignatenko, A. Karpenko, D. Radak, N. Aleksic, D. Sagic, L. Davidovic, I. Koncar, I. Tomic, M. Colic, D. Bartkoy, F. Rusnak, M. Gaspirini, P. Praczek, Z. Milosevic, V. Flis, A. Bergauer, N. Kobilica, K. Miksic, J. Matela, E. Blanco, M. Guerra, V. Riambau, P. Gillgren, C. Skioldebrand, N. Nymen, B. Berg, M. Delle, J. Formgren, T.B. Kally, P. Qvarfordt, G. Plate, H. Pärson, H. Lindgren, K. Bjorses, A. Gottsäter, M. Warvsten, T. Kristmundsson, C. Forssell, M. Malina, J. Holst, T. Kuhme, B. Sonesson, B. Lindblad, T. Kolbel, S. Acosta, L. Bonati, C. Traenka, M. Mueller, T. Lattman, M. Wasner, E. Mujagic, A. Von Hessling, A. Isaak, P. Stierli, T. Eugster, L. Mariani, C. Stippich, T. Wolff, T. Kahles, R. Toorop, F. Moll, R. Lo, A. Meershoek, A.K. Jahrome, A.W.F. Vos, W. Schuiling, R. Keunen, M. Reijnen, S. Macsweeney, N. McConachie, A. Southam, G. Stansby, T. Lees, D. Lambert, M. Clarke, M. Wyatt, S. Kappadath, L. Wales, R. Jackson, A. Raudonaitis, S. MacDonald, P. Dunlop, A. Brown, S. Vetrivel, M. Bajoriene, R. Gopi, C. McCollum, L. Wolowczyk, J. Ghosh, D. Seriki, R. Ashleigh, J. Butterfield, M. Welch, J.V. Smyth, D. Briley, U. Schulz, J. Perkins, L. Hands, W. Kuker, C. Darby, A. Handa, L. Sekaran, K. Poskitt, J. Morrison, P. Guyler, I. Grunwald, J. Brown, M. Jakeways, S. Tysoe, D. Hargroves, G. Gunathilagan, R. Insall, J. Senaratne, J. Beard, T. Cleveland, S. Nawaz, R. Lonsdale, D. Turner, P. Gaines, R. Nair, I. Chetter, G. Robinson, B. Akomolafe, J. Hatfield, K. Saastamoinen, J. Crinnion, A.A. Egun, J. Thomas, S. Drinkwater, S. D'Souza, G. Thomson, B. Gregory, S. Babu, S. Ashley, T. Joseph, R. Gibbs, G. Tebit, A. Mehrzad, P. Enevoldson, D. Mendalow, A. Parry, G. Tervitt, A. Clifton, M. Nazzel, R. Peto, H. Pan, J. Potter, R. Bullbulia, B. Mihaylova, M. Flather, A. Mansfield, D. Simpson, D. Thomas, W. Gray, B. Farrell, C. Davies, K. Rahimi, M. Gough, P. Cao, P. Rothwell, A. Belli, M. Mafham, W. Herrington, P. Sandercock, R. Gray, C. Shearman, A. Molyneux, A. Gray, A. Clarke, M. Sneade, L. Tully, W. Brudlo, M. Lay, A. Munday, C. Berry, S. Tochlin, J. Cox, R. Kurien, and J. Chester

Subjects
medicine.medical_specialty, Surgery, Cardiology and Cardiovascular Medicine, business.industry, Published Erratum, medicine.medical_treatment, Physical therapy, medicine, MEDLINE, Stent, Descriptive research, business
Published
2017
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7. A case of renal impairment and raised venous pressure

Author

C Backhouse, S Drinkwater, and D F Johnston

Subjects
Male, medicine.medical_specialty, Peripheral edema, Aortic Diseases, Vena Cava, Inferior, Palpation, Epigastric pain, medicine.artery, medicine, Humans, Radiology, Nuclear Medicine and imaging, Vein, Aged, Aorta, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Surgery, medicine.anatomical_structure, Blood pressure, Iliac Aneurysm, Arteriovenous Fistula, Abdomen, medicine.symptom, business, Nuclear medicine, Tomography, X-Ray Computed, Venous Pressure, Kidney disease, Aortic Aneurysm, Abdominal
Abstract

A 68-year-old man presented to the emergency department with a 3 day history of epigastric pain radiating to the back. This was associated with vomiting and light-headedness. On examination, his pulse was 110 and his blood pressure 130/35 mmHg. He had peripheral oedema and a raised jugular venous pressure. Palpation of his abdomen revealed a large tender pulsatile mass. His white cell count was 9.6 6 10 l and his haemoglobin, urea and creatinine levels were 11.5 g dl, 18.4 mmol l and 277 mmol l, respectively. A 16-slice CT scan of his abdomen was performed with image acquisition triggered by the detection of 150 HU in the aorta. Selected images from the scan are shown in Figures 1 and 2. What diagnosis can explain each of these images? Address correspondence to: Diane F Johnston, Colchester General Hospital, 2 Parker Road, Colchester, Essex CO4 5BE, UK. E-mail: dianefjohnston@btinternet.com

Published
2007

11. A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.

Author

Morsi H, Huissoon A, Grammatikos A, Whyte A, Manson A, Ekbote A, Sivadasan A, Boulton APR, Herwadkar A, Anantharachagan A, Price A, Steele C, Stroud C, Chopra C, Arnold D, Eren E, Cleave E, Drewe E, Moon E, Zinser E, Hayman G, Alachkar H, Ghanta H, Bourne H, Abdelhakam I, Dempster J, Townsend K, Sooriyakumar K, Lorenzo L, Dziadzio M, Ahuja M, Prasinou M, Frleta-Gilchrist M, Zhang M, Thomas M, Vijayadurai P, Vaitla PM, Sargur R, Herriot R, Yellon RL, Murng SHK, Drinkwater S, Denness S, Denman S, Elkhalifa S, Savic S, Kiani-Alikhan S, Coulter TI, El-Shanawany T, Rahman T, Garcez T, Yong PFK, and Jain R

Abstract

Background: Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management., Objectives: To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK., Method: Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared., Results: Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients., Conclusion: The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2025
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12. The Use of Amplified ATP Bioluminescence for Rapid Sterility Testing of Drug Product Formulations.

Author

Guest M, Pickard B, Smith B, and Drinkwater S

Subjects
Humans, Sterilization, Bacteria, Adenosine Triphosphate, Adenosine, Infertility
Abstract

The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development. However, sterile material manufactured under Good Manufacturing Practice (GMP) conditions may not always be available, for example, during studies to understand the bacterial retention of sterilizing grade filters. In cases of bactericidal products, the use of surrogates may be justified if they are suitably representative of the final drug product formulation. It may not be possible to secure GMP facility access to prepare such surrogate formulations; in those cases, the principles of GMP may be applied in a controlled laboratory setting. The rapid sterility test was used to provide the sterility assurance of the prepared surrogate material. In this case study, the application of amplified ATP bioluminescence sterility testing enabled a fast response to ensure mitigations could be executed in a timely manner. This meant that overarching project plans could be met. The case study also provides information on the rapid identification technique used to identify the slow growing and difficult to recover organism, which allowed faster indication of a nonsterile material. The example also highlights some of the aspects of the challenges of culturing microorganisms and the value of modern techniques in their ability to indicate a quality drift. Dermacoccus nishinomiyaensis was isolated from the test article, and throughout the investigation, it was not possible to culture this organism on standard tryptic soya agar., (© PDA, Inc. 2023.)

Published
2023
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13. TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis.

Author

Nyirenda MH, Morandi E, Vinkemeier U, Constantin-Teodosiu D, Drinkwater S, Mee M, King L, Podda G, Zhang GX, Ghaemmaghami A, Constantinescu CS, Bar-Or A, and Gran B

Subjects
Adult, Case-Control Studies, Cell Differentiation drug effects, Cytokines biosynthesis, Female, Humans, Immunomodulation, Immunophenotyping, Lipoproteins pharmacology, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting immunology, Multiple Sclerosis, Relapsing-Remitting metabolism, STAT3 Transcription Factor metabolism, T-Lymphocyte Subsets drug effects, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Regulatory cytology, Th17 Cells cytology, Toll-Like Receptor 2 agonists, Young Adult, Multiple Sclerosis immunology, Multiple Sclerosis metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Th17 Cells immunology, Th17 Cells metabolism, Toll-Like Receptor 2 metabolism
Abstract

CD4(+)CD25(hi) FOXP3(+) regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we reported that stimulation of TLR2, which is preferentially expressed by human Tregs, reduces their suppressive function and skews them into a Th17-like phenotype. In this study, we tested the hypothesis that TLR2 activation is involved in reduced Treg function in MS. We found that Tregs from MS patients expressed higher levels of TLR2 compared with healthy controls, and stimulation with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg function and induced Th17 skewing in MS patient samples more than in healthy controls. These data provide a novel mechanism underlying diminished Treg function in MS. Infections that activate TLR2 in vivo (specifically through TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory state in MS, thereby promoting disease activity and progression., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Published
2015
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