42 results on '"Zoghbi J"'
Search Results
2. A Peptide Fragment of the Actin-binding Protein Gelsolin Attenuates IgE-mediated Mast Cell Degranulation In Vitro and Murine Mast Cell Calcium Oscillations Ex Vivo
- Author
-
Mikami, M., primary, Kanaya, A., additional, Dantzler, K., additional, Perez-Zoghbi, J., additional, and Emala, C.W., additional
- Published
- 2024
- Full Text
- View/download PDF
3. 183 Litifilimab modulates Type I interferon biomarkers in patients with cutaneous lupus erythematosus: Result of the LILAC Part B Phase 2 study
- Author
-
Werth, V., primary, Furie, R., additional, Merola, J., additional, Milliman, E., additional, Ferber, K., additional, Casey, F., additional, Brown, R., additional, Raitcheva, D., additional, Zoghbi, J., additional, Graham, D., additional, Kong, G., additional, Lahoud, Y., additional, Franchimont, N., additional, and Barbey, C., additional
- Published
- 2023
- Full Text
- View/download PDF
4. AB0518 EFFECT OF LITIFILIMAB ON TYPE I INTERFERON (IFN) BIOMARKERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) OR CUTANEOUS LUPUS ERYTHEMATOSUS (CLE): RESULT OF THE LILAC PHASE 2 STUDY
- Author
-
Furie, R., primary, Werth, V., additional, Milliman, E., additional, Ferber, K., additional, Casey, F., additional, Brown, R., additional, Raitcheva, D., additional, Zoghbi, J., additional, Graham, D., additional, Kong, G., additional, Lahoud, Y., additional, Franchimont, N., additional, and Barbey, C., additional
- Published
- 2023
- Full Text
- View/download PDF
5. 590 Litifilimab modulates Type 1 interferon (IFN) biomarkers in patients with cutaneous lupus erythematosus (CLE): Result of the LILAC Part B Phase 2 study
- Author
-
Werth, V.P., primary, Furie, R.A., additional, Milliman, E., additional, Ferber, K., additional, Casey, F., additional, Brown, R., additional, Raitcheva, D., additional, Zoghbi, J., additional, Graham, D., additional, Kong, G., additional, Lahoud, Y., additional, Franchimont, N., additional, and Barbey, C., additional
- Published
- 2023
- Full Text
- View/download PDF
6. Ca2+ handling and sensitivity in airway smooth muscle: Emerging concepts for mechanistic understanding and therapeutic targeting
- Author
-
Koopmans, T., Anaparti, V., Castro-Piedras, I., Yarova, P., Irechukwu, N., Nelson, C., Perez-Zoghbi, J., Tan, X., Ward, J.P.T., and Wright, D.B.
- Published
- 2014
- Full Text
- View/download PDF
7. Fusion between 3D transthoracic echocardiography and computed cardiac tomography: A novel diagnostic approach in congenital heart disease
- Author
-
Pekin, K., primary, Fournier, E., additional, Van Aerschot, I., additional, Guirgis, L., additional, Cohen, S., additional, Belli, E., additional, Zoghbi, J., additional, Batteux, C., additional, Cousergue, C., additional, Foray, C., additional, Provost, B., additional, and Hascoet, S., additional
- Published
- 2022
- Full Text
- View/download PDF
8. Regulation of GPCR-mediated smooth muscle contraction: Implications for asthma and pulmonary hypertension
- Author
-
Wright, D.B., Tripathi, S., Sikarwar, A., Santosh, K.T., Perez-Zoghbi, J., Ojo, O.O., Irechukwu, N., Ward, J.P.T., and Schaafsma, D.
- Published
- 2013
- Full Text
- View/download PDF
9. Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats
- Author
-
Perez-Zoghbi, J. F., Zhu, W., Grafe, M. R., and Brambrink, A. M.
- Published
- 2017
- Full Text
- View/download PDF
10. Echocardiography-computed tomography fusion imaging: a new approach for congenital heart disease
- Author
-
Fournier, E, primary, Batteux, C, additional, Mostefa-Kara, M, additional, Cohen, S, additional, Van Aerschot, I, additional, Meliani, A, additional, Guirgis, L, additional, Sigal-Cinqualbre, A, additional, Provost, B, additional, Roussin, R, additional, Zoghbi, J, additional, Belli, E, additional, and Hascoet, S, additional
- Published
- 2021
- Full Text
- View/download PDF
11. Evolution of practices: Early extubation in high-risk infants after pediatric cardiac surgery
- Author
-
Cressens, S., primary, Boët, A., additional, Decailliot, F., additional, Mirabile, C., additional, Mokhfi, E., additional, Zoghbi, J., additional, and Belli, E., additional
- Published
- 2021
- Full Text
- View/download PDF
12. Anomalous aortic origin of a coronary arteries: Is unroofing procedure always appropriate?
- Author
-
Mostefa Kara, M., primary, Hascoët, S., additional, Tagorti, M., additional, Cohen, S., additional, Zoghbi, J., additional, and Belli, E., additional
- Published
- 2020
- Full Text
- View/download PDF
13. EFFECT OF LITIFILIMAB ON TYPE I INTERFERON (IFN) BIOMARKERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) OR CUTANEOUS LUPUS ERYTHEMATOSUS (CLE): RESULT OF THE LILAC PHASE 2 STUDY.
- Author
-
Furie, R., Werth, V., Milliman, E., Ferber, K., Casey, F., Brown, R., Raitcheva, D., Zoghbi, J., Graham, D., Kong, G., Lahoud, Y., Franchimont, N., and Barbey, C.
- Published
- 2023
- Full Text
- View/download PDF
14. Graph Based Characterization of Microcirculation in Sepsis Using Sidestream Dark Field Imaging
- Author
-
Zoghbi, J. M., primary, De-La-Cruz, L. T., additional, Galarreta, M. A. G. V., additional, Jackowski, Marcel P., additional, Vieira, J. C. F., additional, Liberatore, A. M. A., additional, and Koh, Ivan H. J., additional
- Published
- 2014
- Full Text
- View/download PDF
15. Graph Based Characterization of Microcirculation in Sepsis Using Sidestream Dark Field Imaging.
- Author
-
M., Zoghbi J., T., De La Cruz L., V., Galarreta M. A. G., Jackowski, Marcel P., F., Vieira J. C., A., Liberatore A. M., and H.J., Koh Ivan
- Published
- 2014
- Full Text
- View/download PDF
16. Congenital Mitral Stenosis With or Without Associated Defects : An Evolving Surgical Strategy
- Author
-
Serraf, A., primary, Zoghbi, J., additional, Belli, E., additional, Lacour-Gayet, F., additional, Aznag, H., additional, Houyel, L., additional, Lambert, V., additional, Piot, D., additional, and Planche, C., additional
- Published
- 2000
- Full Text
- View/download PDF
17. Exploration and treatment of carotid stenoses in 1996.
- Author
-
Leseche, G and Zoghbi, J
- Published
- 1998
- Full Text
- View/download PDF
18. Surgical management and indication of left ventricular retraining in arterial switch for transposition of the great arteries with intact ventricular septum.
- Author
-
Lacour-Gayet, F, Piot, D, Zoghbi, J, Serraf, A, Gruber, P, Macé, L, Touchot, A, and Planché, C
- Abstract
Arterial switch is the operation of reference for the surgical treatment of transposition of the great arteries. In cases of late referral, perinatal complications or early left ventricular (LV) dysfunction, the one stage arterial switch is contra indicated. Anatomical repair remains possible in these patients following a LV retraining.
- Published
- 2001
- Full Text
- View/download PDF
19. Surgical management of progressive pulmonary venous obstruction after repair of total anomalous pulmonary venous connection
- Author
-
Lacour-Gayet, F., Zoghbi, J., Serraf, A.E., Belli, E., Piot, D., Rey, C., Marcon, F., Bruniaux, J., and Planche, C.
- Abstract
Background: The occurrence of a progressive pulmonary venous obstruction after the repair of the total anomalous pulmonary venous connection is a severe complication. Objectives: The objectives of this study were to retrospectively review the patients with this condition and to report our experience with a new surgical technique with a sutureless in situ pericardium repair. Methods: Of 178 patients who underwent correction of total anomalous pulmonary venous connection, 16 patients (9%) experienced the development of a progressive pulmonary venous obstruction in a median interval of 4 months (5 weeks-12 years). Three patients had isolated anastomotic stenosis, 4 patients had isolated pulmonary venous ostial stenosis, and 9 patients had both. Pulmonary venous obstruction was bilateral in 7 patients. The surgical procedures used at reoperation included 8 patch enlargements, 5 ostial endarterectomies, 1 intraoperative stenting, and 7 sutureless in situ pericardium repairs. Results: There were 4 deaths after reoperation (4 of 15 patients; 27%). The only significant mortality risk factor was the bilateral location of the pulmonary venous obstruction (P = .045). In patients with isolated anastomotic stenosis or with only 1 pulmonary venous ostial stenosis (n = 5), there was no death, except the patient presenting with a single ventricle. In patients with 2 or more pulmonary venous ostial stenoses (n = 10), there were 3 deaths; 5 of the 7 survivors were successfully treated with the in situ pericardial technique, with normalized pulmonary artery pressure at a mean follow-up of 26 months. Conclusion: Progressive pulmonary venous stenosis after repair of total anomalous pulmonary venous connection remains a severe complication when bilateral. The sutureless in situ pericardial repair offers a satisfactory solution, particularly on the right side. (J Thorac Cardiovasc Surg 1999;117: 679-87)
- Published
- 1999
- Full Text
- View/download PDF
20. [Value of the spiral angio-scanner with three-dimensional reconstruction in the surgical strategy of unifocalization. Apropos of a case]
- Author
-
Le Bret E, Loic MACE, Dervanian P, Bourriez A, Ta, Folliguet, Zoghbi J, Lambert V, Losay J, Martin-Bouyer Y, and Jy, Neveux
- Subjects
Male ,Pulmonary Atresia ,Angiocardiography ,Echocardiography, Three-Dimensional ,Collateral Circulation ,Humans ,Pulmonary Artery ,Child ,Echocardiography, Doppler - Abstract
One of the difficulties of surgical treatment of pulmonary atresia with patent septum by unifocalisation resides in the accurate diagnosis of the different collateral vessels to the lung in order to optimise the surgical approach: anterior or posterolateral thoracotomy, and to determine the type of operation: one or two stages repair. Conventional angiography, even using different views, cannot always give an accurate representation of the anatomy of the different collateral vessels, especially their relationship to the bronchial structures. The authors report the contribution of spiral angioscanner with three dimensional reconstruction in the determination of the operative strategy of a case of pulmonary atresia with patent septum.
21. Is surgical intervention still indicated in recurrent aortic arch obstruction?
- Author
-
ZOGHBI, J
- Published
- 2004
- Full Text
- View/download PDF
22. Brain Charts for the Rhesus Macaque Lifespan.
- Author
-
Alldritt S, Ramirez JSB, Vos de Wael R, Bethlehem R, Seidlitz J, Wang Z, Nenning K, Esper NB, Smallwood J, Franco AR, Byeon K, Alexander-Bloch A, Amaral DG, Amiez C, Balezeau F, Baxter MG, Becker G, Bennett J, Berkner O, Blezer ELA, Brambrink AM, Brochier T, Butler B, Campos LJ, Canet-Soulas E, Chalet L, Chen A, Cléry J, Constantinidis C, Cook DJ, Dehaene S, Dorfschmidt L, Drzewiecki CM, Erdman JW, Everling S, Falchier A, Fleysher L, Fox A, Freiwald W, Froesel M, Froudist-Walsh S, Fudge J, Funck T, Gacoin M, Gale DJ, Gallivan J, Garin CM, Griffiths TD, Guedj C, Hadj-Bouziane F, Hamed SB, Harel N, Hartig R, Hiba B, Howell BR, Jarraya B, Jung B, Kalin N, Karpf J, Kastner S, Klink C, Kovacs-Balint ZA, Kroenke C, Kuchan MJ, Kwok SC, Lala KN, Leopold DA, Li G, Lindenfors P, Linn G, Mars RB, Masiello K, Menon RS, Messinger A, Meunier M, Mok K, Morrison JH, Nacef J, Nagy J, Neudecker V, Neuringer M, Noonan MP, Ortiz-Rios M, Perez-Zoghbi JF, Petkov CI, Pinsk M, Poirier C, Procyk E, Rajimehr R, Reader SM, Rudko DA, Rushworth MFS, Russ BE, Sallet J, Sanchez MM, Schmid MC, Schwiedrzik CM, Scott JA, Sein J, Sharma KK, Shmuel A, Styner M, Sullivan EL, Thiele A, Todorov OS, Tsao D, Tusche A, Vlasova R, Wang Z, Wang L, Wang J, Weiss AR, Wilson CRE, Yacoub E, Zarco W, Zhou Y, Zhu J, Margulies D, Fair D, Schroeder C, Milham M, and Xu T
- Abstract
Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource ( https://interspeciesmap.childmind.org ) supports cross-species comparisons to advance translational neuroscience research.
- Published
- 2024
- Full Text
- View/download PDF
23. Multicentre study on late outcomes of biventricular repair of double outlet right ventricle.
- Author
-
Lacour-Gayet F, Zoghbi J, Gouton M, Roussin R, Bical O, Lucet V, Saint-Pick M, and Leca F
- Subjects
- Child, Humans, Infant, Treatment Outcome, Retrospective Studies, Cardiac Surgical Procedures adverse effects, Double Outlet Right Ventricle surgery, Heart Septal Defects, Pulmonary Valve Stenosis, Transposition of Great Vessels surgery
- Abstract
Objectives: The goal of this retrospective multicentre study was to present late surgical outcomes of the treatment of children with double outlet right ventricle (DORV) coming from emerging countries., Methods: The Mécénat Chirurgie Cardiaque brings to France for surgery selected children with simple and complex congenital diseases, including DORV. The patients are operated on in 9 hospitals that specialize in paediatric cardiac surgery. Data are collected from the Mécénat Chirurgie Cardiaque comprehensive database, with a strict postoperative follow-up. The patients included only those who had biventricular repair of DORV with 2 viable ventricles. According to the classification of the Eleventh Revision of the International Classification of Diseases, DORV was defined as a congenital cardiovascular malformation in which both great arteries arise entirely or predominantly from the morphologically right ventricle., Results: From January 1996 to January 2022, a total of 81 consecutive DORV biventricular repair operations were performed. There were 6 subtypes of DORV divided into 2 groups: DORV-committed ventricular septal defect (VSD): DORV-VSD (n = 25), DORV-Fallot (n = 34), DORV-transposition of the great arteries (n = 5); and DORV-non-committed (nc) VSD: DORV-ncVSD-no pulmonary stenosis (PS) (n = 7), DORV-ncVSD-PS (n = 5) and DORV-atrioventricular septal defect (AVSD)-PS (n = 5). Four Fontan patients were excluded. Three patients were lost to follow-up (3.4%). The overall perioperative mortality was 7.4% ± 2.6%, 6/81 (95% confidence interval: 2.8%-15.4%) ranging from 0% in DORV-AVSD-PS to 14% for DORV-ncVSD-no PS. The overall 10-year survival was 86%. The early mortality of DORV-ncVSD at 5.9% ± 2.4% (1/17) was similar to that of DORV-committed VSD at 7.8% ± 2.7% (5/64) (P = 0.79). There was a trend towards an optimal outcome for the arterial switch operation and the DORV-AVSD-PS repair. VSD enlargement was significantly more frequent in DORV-ncVSD at 42% (5/12) (P = 0.001). There were low numbers in the complex groups. The number of Fontan cases was noticeably low. The aorta located entirely on the right ventricle represents the fundamental anomaly and the surgical challenge of DORV., Conclusions: Overall survival at 10 years was 86%. This study shows a trend towards satisfactory early and late outcomes in BVR of simple DORV with committed VSD, compared to complex DORV with ncVSD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. Multiparametric evaluation of right ventricular function in pulmonary arterial hypertension associated with congenital heart disease.
- Author
-
Fournier E, Selegny M, Amsallem M, Haddad F, Cohen S, Valdeolmillos E, Le Pavec J, Humbert M, Isorni MA, Azarine A, Sitbon O, Jais X, Savale L, Montani D, Fadel E, Zoghbi J, Belli E, and Hascoët S
- Subjects
- Humans, Ventricular Function, Right, Stroke Volume, Pulmonary Arterial Hypertension complications, Atrial Fibrillation complications, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology, Heart Defects, Congenital complications, Heart Defects, Congenital diagnosis, Ventricular Dysfunction, Right diagnostic imaging, Ventricular Dysfunction, Right etiology
- Abstract
Introduction and Objectives: Outcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function., Methods: We prospectively studied 30 patients aged 48±12 years with pretricuspid shunt and PAH and investigated the accuracy of multiple echocardiographic parameters of RV function (tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, RV systolic-to-diastolic duration ratio, right atrial area, RV fractional area change, RV global longitudinal strain and RVESRI) to RV ejection fraction measured by cardiac magnetic resonance., Results: RV ejection fraction <45% was observed in 13 patients (43.3%). RV global longitudinal strain (ρ [Spearman's correlation coefficient]=-0.75; P=.001; R
2 =0.58; P=.001), right atrium area (ρ=-0.74; P <.0001; R2 =0.56; P <.0001), RVESRI (ρ=-0.64; P <.0001; R2 =0.47; P <.0001), systolic-to-diastolic duration ratio (ρ=-0.62; P=.0004; R2 =0.47; P <.0001) and RV fractional area change (ρ=0.48; P=.01; R2 =0.37; P <.0001) were correlated with RV ejection fraction. RV global longitudinal strain, RVESRI and right atrium area predicted RV ejection fraction <45% with the greatest area under curve (0.88; 95%CI, 0.71-1.00; 0.88; 95%CI, 0.76-1.00, and 0.89; 95%CI, 0.77-1.00, respectively). RV global longitudinal strain >-16%, RVESRI ≥ 1.7 and right atrial area ≥ 22 cm2 predicted RV ejection fraction <45% with a sensitivity and specificity of 87.5% and 85.7%; 76.9% and 88.3%; 92.3% and 82.4%, respectively., Conclusions: RVESRI, right atrial area and RV global longitudinal strain are strong markers of RV dysfunction in patients with pretricuspid shunt and PAH., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
25. Cardiac tomography-echocardiography imaging fusion: a new approach to congenital heart disease.
- Author
-
Fournier E, Batteux C, Mostefa-Kara M, Valdeolmillos E, Maltret A, Cohen S, Van Aerschot I, Guirgis L, Azarine A, Sigal-Cinqualbre A, Provost B, Radojevic-Liegeois J, Roussin R, Zoghbi J, Belli E, and Hascoët S
- Subjects
- Child, Adult, Humans, Male, Female, Echocardiography methods, Heart diagnostic imaging, Tomography, X-Ray Computed, Heart Defects, Congenital diagnostic imaging, Heart Defects, Congenital surgery, Echocardiography, Three-Dimensional methods
- Abstract
Introduction and Objectives: Diagnosis, management, and surgical decision-making in children and adults with congenital heart disease are largely based on echocardiography findings. A recent development in cardiac imaging is fusion of different imaging modalities. Our objective was to evaluate the feasibility of computed tomography (CT) and 3-dimensional (3D) transthoracic echocardiography (TTE) fusion in children and adults with congenital heart disease., Methods: We prospectively included 14 patients, 13 of whom had congenital heart disease, and who underwent both CT and 3D TTE as part of their usual follow-up. We described the steps required to complete the fusion process (alignment, landmarks, and superimposition), navigation, and image evaluation., Results: Median age was 9.5 [2.7-15.7] years, 57% were male, and median body surface area was 0.9 m
2 [0.6-1.7]. Congenital heart disease was classified as simple (n=4, 29%), moderate (n=4, 29%), or complex (n=6, 42%). 3D TTE-CT fusion was successful in all patients. Median total time to complete the fusion process was 735 [628-1163] seconds, with no significant difference according to the degree of complexity of the defects. Landmarks were significantly modified in complex congenital heart disease., Conclusions: We established the feasibility and accuracy of 3D TTE-CT fusion in a population of children and adults with a variety of congenital heart diseases. The simultaneous visualization of many intracardiac structures may help to understand the anatomical features of congenital heart disease without limitations regarding age, weight, or complexity of the congenital defects., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
26. 2021 White Paper on Recent Issues in Bioanalysis: ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry ( Part 2 - Recommendations on Biomarkers/CDx Assays Development & Validation, Cytometry Validation & Innovation, Biotherapeutics PK LBA Regulated Bioanalysis, Critical Reagents & Positive Controls Generation).
- Author
-
Hersey S, Keller S, Mathews J, King L, Bandukwala A, Berisha F, Birchler M, Bower J, Clausen V, Duarte J, Garofolo F, Hopper S, Kar S, Mabrouk O, Marshall JC, McGuire K, Naughton M, Saito Y, Schuhmann I, Sperinde G, Teixeira P, Vitaliti A, Wang YM, Wnek R, Zhang Y, Spitz S, Decman V, Eck S, Estevam J, Goihberg P, Alcaide EG, Gonneau C, Hedrick MN, Hopkins G, Junker F, Nuti S, Sommer U, Standifer N, Stevens C, Stevens E, Hendricks C, Wadhwa M, Torri A, Ma M, Harris S, Kumar S, Partridge MA, Caiazzo T, Chilewski S, Cludts I, Coble K, Gorovits B, Grimaldi C, Jordan G, Kamerud J, Leary B, Liang M, Lim H, Mayer A, O'Connor E, Palackal N, Poetzl J, Prior S, Abhari MR, Savoie N, Soo C, Ware M, Wu B, Xu Y, Yang TY, and Zoghbi J
- Subjects
- Biomarkers analysis, Humans, Indicators and Reagents, Liquid Biopsy, Mass Spectrometry, Flow Cytometry methods
- Abstract
The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.
- Published
- 2022
- Full Text
- View/download PDF
27. Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis.
- Author
-
Wasserman E, Gomi R, Sharma A, Hong S, Bareja R, Gu J, Balaji U, Veerappan A, Kim BI, Wu W, Heras A, Perez-Zoghbi J, Sung B, Gueye-Ndiaye S, Worgall TS, and Worgall S
- Subjects
- Animals, Child, Humans, Lung metabolism, Mice, Serine C-Palmitoyltransferase genetics, Serine C-Palmitoyltransferase metabolism, Sphingolipids metabolism, Membrane Proteins metabolism, Rhinovirus
- Abstract
The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of de novo sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis. Children with asthma and 17q21 asthma risk alleles display decreased sphingolipid synthesis in blood cells. Reduced SPT activity results in airway hyperreactivity, a hallmark feature of asthma. 17q21 asthma risk alleles are also linked to childhood infections with human rhinovirus (RV). This study evaluates the interaction of RV with the de novo sphingolipid synthesis pathway, and the alterative effects of concurrent SPT inhibition in SPT-deficient mice and human airway epithelial cells. In mice, RV infection shifted lung sphingolipid synthesis gene expression to a pattern that resembles genetic SPT deficiency, including decreased expression of Sptssa, a small SPT subunit. This pattern was pronounced in lung epithelial cellular adhesion molecule (EpCAM
+ ) cells and reproduced in human bronchial epithelial cells. RV did not affect Sptssa expression in lung CD45+ immune cells. RV increased sphingolipids unique to the de novo synthesis pathway in mouse lung and human airway epithelial cells. Interestingly, these de novo sphingolipid species were reduced in the blood of RV-infected wild-type mice. RV exacerbated SPT deficiency-associated airway hyperreactivity. Airway inflammation was similar in RV-infected wild-type and SPT-deficient mice. This study reveals the effects of RV infection on the de novo sphingolipid synthesis pathway, elucidating a potential mechanistic link between 17q21 asthma risk alleles and rhinoviral infection.- Published
- 2022
- Full Text
- View/download PDF
28. Anti-drug Antibody Validation Testing and Reporting Harmonization.
- Author
-
Myler H, Pedras-Vasconcelos J, Phillips K, Hottenstein CS, Chamberlain P, Devanaryan V, Gleason C, Goodman J, Manning MS, Purushothama S, Richards S, Shen H, Zoghbi J, Amaravadi L, Barger T, Bowen S, Bowsher RR, Clements-Egan A, Geng D, Goletz TJ, Gunn GR, Hallett W, Hodsdon ME, Janelsins BM, Jawa V, Kamondi S, Kirshner S, Kramer D, Liang M, Lindley K, Liu S, Liu Z, McNally J, Mikulskis A, Nelson R, Ahbari MR, Qu Q, Ruppel J, Snoeck V, Song A, Yan H, and Ware M
- Subjects
- Europe, United States, Antibodies, Biological Assay
- Abstract
Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities. Herein, this team provides testing and reporting strategies and tools for the following assessments: (1) pre-study validation cut point; (2) in-study cut points, including procedures for applying cut points to mixed populations; (3) system suitability control criteria for in-study plate acceptance; (4) assay sensitivity, including the selection of an appropriate low positive control; (5) specificity, including drug and target tolerance; (6) sample stability that reflects sample storage and handling conditions; (7) assay selectivity to matrix components, including hemolytic, lipemic, and disease state matrices; (8) domain specificity for multi-domain therapeutics; (9) and minimum required dilution and extraction-based sample processing for titer reporting., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
29. Anomalous aortic origin of coronary arteries: is the unroofing procedure always appropriate?
- Author
-
Mostefa Kara M, Fournier E, Cohen S, Hascoet S, Van Aerschot I, Roussin R, El Zoghbi J, and Belli E
- Subjects
- Adolescent, Aorta, Chest Pain, Coronary Angiography, Humans, Retrospective Studies, Coronary Vessel Anomalies diagnostic imaging, Coronary Vessel Anomalies surgery, Coronary Vessels diagnostic imaging, Coronary Vessels surgery
- Abstract
Objectives: Anomalous aortic origin of the coronary artery (AAOCA) with an interarterial ± an intramural course is a rare anomaly that carries a high risk of ischaemic events and even sudden death. The unroofing of the intramural course has been adopted as the gold standard surgical treatment. However, some anatomical forms need alternative techniques., Methods: We reviewed the surgical cohort with AAOCA managed at our institution between 2005 and 2019 and analysed the anatomical and clinical outcomes., Results: Thirty-nine patients underwent surgical interventions. The median age was 14 years (10-26 years). Twenty-eight patients (72%) had right AAOCA, and 11 (28%) had left AAOCA. Thirty-one (80%) patients presented with symptoms. The symptoms were chest pain in 22 patients (56%), syncope in 5 patients (13%), cardiac arrest during exercise in 2 patients (5%), dyspnoea in 6 patients (15%) and dizziness in 13 patients (33%). An ischaemic test was performed in 32 patients: Only 4 patients (10%) had positive results from the ischaemic test. All patients had computed tomography angiography scans to confirm the precise anatomical features of the anomaly. Repair techniques included 30 unroofing procedures (77%) with an associated translocation of the pulmonary artery for 11 patients in our early experience. In 6 patients the unroofing procedure was not feasible because of the absence of an intramural distinct segment or was judged intraoperatively not appropriate. A reimplantation of the anomalous coronary artery was performed in 2 patients (5%); 3 patients had coronary artery bypass grafting procedures (7%); and 3 (8%) had an isolated translocation of the pulmonary artery. There were no early or late deaths. All patients were free of symptoms. Computed tomography angiography scans performed in 31 cases showed a patent, non-restrictive coronary artery ostium. Seventeen patients underwent postoperative ischaemia testing and showed no evidence of ischaemia., Conclusions: Surgical correction in AAOCA is mandatory both for symptomatic and for asymptomatic patients with evidence of myocardial ischaemia under stress or with a restricted coronary artery segment. Surgical unroofing remains the gold standard but is not appropriate for all forms: alternative techniques should be considered. Surgical results are promising., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
30. Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity.
- Author
-
Heras AF, Veerappan A, Silver RB, Emala CW, Worgall TS, Perez-Zoghbi J, and Worgall S
- Subjects
- Alveolar Epithelial Cells drug effects, Alveolar Epithelial Cells metabolism, Bradykinin pharmacology, Calcium metabolism, Calcium Signaling drug effects, Fenretinide pharmacology, Glycine analogs & derivatives, Glycine pharmacology, Humans, Hydrazines pharmacology, Metabolome drug effects, Methacholine Chloride pharmacology, Muscle Contraction drug effects, Serine C-Palmitoyltransferase metabolism, Bronchial Hyperreactivity metabolism, Sphingolipids biosynthesis
- Abstract
Impaired sphingolipid synthesis is linked genetically to childhood asthma and functionally to airway hyperreactivity (AHR). The objective was to investigate whether sphingolipid synthesis could be a target for asthma therapeutics. The effects of GlyH-101 and fenretinide via modulation of de novo sphingolipid synthesis on AHR was evaluated in mice deficient in SPT (serine palmitoyl-CoA transferase), the rate-limiting enzyme of sphingolipid synthesis. The drugs were also used directly in human airway smooth-muscle and epithelial cells to evaluate changes in de novo sphingolipid metabolites and calcium release. GlyH-101 and fenretinide increased sphinganine and dihydroceramides ( de novo sphingolipid metabolites) in lung epithelial and airway smooth-muscle cells, decreased the intracellular calcium concentration in airway smooth-muscle cells, and decreased agonist-induced contraction in proximal and peripheral airways. GlyH-101 also decreased AHR in SPT-deficient mice in vivo . This study identifies the manipulation of sphingolipid synthesis as a novel metabolic therapeutic strategy to alleviate AHR.
- Published
- 2020
- Full Text
- View/download PDF
31. Surgery of single ventricles in humanitarian practice: surgery for which patients?
- Author
-
Gouton M, Bical OM, Zoghbi J, Roussin R, Lucet V, and Leca F
- Subjects
- Child, Child, Preschool, Developing Countries, Female, Follow-Up Studies, Fontan Procedure statistics & numerical data, France, Heart Defects, Congenital mortality, Humans, Male, Palliative Care methods, Relief Work, Retrospective Studies, Risk Factors, Survival Rate trends, Treatment Outcome, Fontan Procedure methods, Heart Defects, Congenital surgery, Heart Ventricles abnormalities, Heart Ventricles surgery
- Abstract
Objectives: To analyse the feasibility and effectiveness in humanitarian practice of surgical management of children with single-ventricle heart condition., Methods: Retrospective study of children with a single ventricle, managed by the association Mécénat-Chirurgie Cardiaque since 1996, with long-term follow-up after their return home., Results: Of the 138 children in our cohort, 119 had one or more surgeries (180 procedures): palliative surgery alone (systemic-pulmonary anastomosis or banding), 41; partial cavo-pulmonary connection, 47; total cavo-pulmonary connection (mean age 8.5 years), 31. Operative mortality is 5.5%. After a mean follow-up of 5.6 years, 18 children (13%) were lost to follow-up. Survival at 10 years is 79% in children receiving surgery (palliative only, 72%; partial cavo-pulmonary connection, 77%; total cavo-pulmonary connection, 97%) versus 29% in children with no surgical intervention. The prognosis is better for tricuspid atresia and double-inlet left ventricle (86 and 83% survival at 10 years) than for double-outlet right ventricle or complete atrio-ventricular canal defect (64 and 68% at 5 years)., Conclusion: The surgery of the single ventricle in humanitarian medicine allows a very satisfactory survival after one or more surgeries tending towards a total cavo-pulmonary connection as soon as possible.
- Published
- 2019
- Full Text
- View/download PDF
32. Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats.
- Author
-
Perez-Zoghbi JF, Zhu W, Grafe MR, and Brambrink AM
- Subjects
- Anesthetics, Inhalation adverse effects, Animals, Animals, Newborn, Apoptosis drug effects, Disease Models, Animal, Hypnotics and Sedatives pharmacology, Rats, Rats, Wistar, Brain drug effects, Dexmedetomidine pharmacology, Neuroprotection drug effects, Neurotoxicity Syndromes prevention & control, Sevoflurane adverse effects
- Abstract
Background: Exposure of infant animals to clinically used anaesthetics is associated with acute structural brain abnormalities and development functional alterations. The α 2 -adrenoceptor agonist dexmedetomidine (DEX) induces sedation, analgesia, and provides neuroprotection in experimental brain injury models. However, it is unknown whether DEX also affords protection in the developing brain against anaesthesia using sevoflurane (SEVO), which is commonly used in paediatric anaesthesia., Methods: Infant rats were exposed on postnatal day seven for six h to 2.5% SEVO and were given i.p. injections of saline or DEX (1-50 µg kg -1 ) three times during the exposure. Level of anaesthesia, respiratory rates, and arterial blood gasses were assessed for each animal. Apoptosis was determined in brain slices immunostained for activated caspase-3 (AC-3) using a computerised approach., Results: SEVO alone induced a surgical plane of anaesthesia, and all animals survived the study. SEVO induced an approximately 10-fold increase in AC-3 positive cells in several cortical and subcortical brain regions compared with untreated control animals. Co-administration of DEX 1 µg kg -1 with SEVO significantly reduced apoptosis in all brain areas, affording the highest protection in the thalamus (84% reduction) and lowest in the hippocampus and cortical areas (∼50% reduction). DEX 5-25 µg kg -1 plus SEVO dose-dependently increased infant rat mortality., Conclusions: SEVO anaesthesia induced widespread apoptosis in infant rat brain. Co-administration of DEX (1 µg kg -1 ) provided significant protection, whereas DEX (5 µg kg -1 or higher) plus SEVO increased mortality. Our findings suggest that DEX could be an attractive therapeutic for future studies investigating its neuroprotective potential in a translational animal model., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)
- Published
- 2017
- Full Text
- View/download PDF
33. 2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 3--LBA, biomarkers and immunogenicity).
- Author
-
Amaravadi L, Song A, Myler H, Thway T, Kirshner S, Devanarayan V, Ni YG, Garofolo F, Birnboeck H, Richards S, Gupta S, Luo L, Kingsley C, Salazar-Fontana L, Fraser S, Gorovits B, Allinson J, Barger T, Chilewski S, Fjording MS, Haidar S, Islam R, Jaitner B, Kamerud J, Katori N, Krinos-Fiorotti C, Lanham D, Ma M, McNally J, Morimoto A, Mytych D, Nogueira da Costa A, Papadimitriou A, Pillutla R, Ray S, Safavi A, Savoie N, Schaefer M, Shih J, Smeraglia J, Skelly MF, Spond J, Staack RF, Stouffer B, Tampal N, Torri A, Welink J, Yang TY, and Zoghbi J
- Subjects
- Humans, Antibodies, Neutralizing immunology, Biological Assay, Biomarkers analysis, Biopharmaceutics organization & administration, Biotechnology organization & administration
- Abstract
The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5 day, week-long event - A Full Immersion Bioanalytical Week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS and LBA approaches, including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 3 discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Part 1 (small molecule bioanalysis using LCMS) and Part 2 (hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in volume 7, issues 22 and 23 of Bioanalysis, respectively.
- Published
- 2015
- Full Text
- View/download PDF
34. A breakthrough novel method to resolve the drug and target interference problem in immunogenicity assays.
- Author
-
Zoghbi J, Xu Y, Grabert R, Theobald V, and Richards S
- Subjects
- Antibodies, Anti-Idiotypic blood, Antibodies, Monoclonal, Humanized blood, Antibody Formation immunology, Antigen-Antibody Complex immunology, Biomarkers analysis, Chemical Precipitation, Drug Tolerance immunology, Humans, Antibodies, Anti-Idiotypic immunology, Antibodies, Monoclonal, Humanized immunology, Antigen-Antibody Complex blood, Immunoassay, Pharmaceutical Preparations blood
- Abstract
Biological matrix interference in detection and quantitation immunoassays remains a major challenge in the field of bioanalysis. For example, circulating drug may interfere with the detection of anti-drug antibodies (ADA) and drug target, or ADA may interfere with quantitation of drug levels in PK/TK analysis. Monoclonal antibody drug interference, especially for human IgG4 drugs, presents an additional challenge for ADA analysis due to its longer half-life and higher dose. Assay tolerance to such interference may depend on assay platform and reagents. Various approaches have been used to improve drug tolerance in ADA analysis but limited success was observed. We have developed a breakthrough novel method that uses Precipitation and Acid dissociation (PandA) to overcome drug interference in the ADA assay. The method principle is based on four components for detection of total ADA (free ADA and drug bound ADA) in the presence of drug in patient samples: (1) use excess drug to saturate free ADA to form drug bound ADA as drug:ADA complexes, (2) precipitate the complex using an agent such as PEG, (3) acid dissociate ADA from drug and immobilize (capture) free ADA (and free drug) under acidic conditions (without neutralization) onto a large capacity surface, and (4) detect free ADA (not the captured drug) using specific anti-human Ig detection reagent. In this manuscript, we are describing case studies for three humanized monoclonal antibodies (an IgG1 and two IgG4 drugs). The three drug specific PandA ADA assays resulted in complete recovery of ADA in samples containing drug levels in excess of those expected in patients, in contrast to the commonly used acid dissociation approach in ECL bridging assays. This breakthrough novel method shows significant improvement over the current approaches. In fact, the drug interference or under detecting of ADA in all three cases was eliminated. This assay principle could be used not only for ADA assays but also PK and biomarker (drug target) analysis in the presence of interference factors., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
35. Antagonists of the TMEM16A calcium-activated chloride channel modulate airway smooth muscle tone and intracellular calcium.
- Author
-
Danielsson J, Perez-Zoghbi J, Bernstein K, Barajas MB, Zhang Y, Kumar S, Sharma PK, Gallos G, and Emala CW
- Subjects
- Animals, Anoctamin-1, Cell Line, Transformed, Chloride Channels antagonists & inhibitors, Guinea Pigs, Humans, Intracellular Fluid drug effects, Intracellular Fluid metabolism, Lung drug effects, Male, Mice, Mice, Inbred C57BL, Muscle Contraction drug effects, Muscle Contraction physiology, Muscle Relaxation drug effects, Muscle Relaxation physiology, Muscle, Smooth drug effects, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle physiology, Neoplasm Proteins antagonists & inhibitors, Organ Culture Techniques, Trachea drug effects, Calcium metabolism, Calcium Channel Blockers pharmacology, Chloride Channels physiology, Lung physiology, Muscle, Smooth physiology, Neoplasm Proteins physiology, Trachea physiology
- Abstract
Background: Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux., Methods: Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells., Results: Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of benzbromarone. In human ASM, benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12)., Conclusion: TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.
- Published
- 2015
- Full Text
- View/download PDF
36. Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling.
- Author
-
Gallos G, Yocum GT, Siviski ME, Yim PD, Fu XW, Poe MM, Cook JM, Harrison N, Perez-Zoghbi J, and Emala CW Sr
- Subjects
- Animals, Bradykinin metabolism, Bronchial Spasm drug therapy, Bronchoconstriction drug effects, Calcium metabolism, Cells, Cultured, Diazepam pharmacology, Guinea Pigs, Humans, Ion Channel Gating drug effects, Male, Methacholine Chloride pharmacology, Myocytes, Smooth Muscle drug effects, Patch-Clamp Techniques, Respiratory System drug effects, Bronchodilator Agents pharmacology, Diazepam analogs & derivatives, GABA-A Receptor Agonists pharmacology, Imidazoles pharmacology, Muscle, Smooth metabolism, Receptors, GABA-A metabolism
- Abstract
The clinical need for novel bronchodilators for the treatment of bronchoconstrictive diseases remains a major medical issue. Modulation of airway smooth muscle (ASM) chloride via GABAA receptor activation to achieve relaxation of precontracted ASM represents a potentially beneficial therapeutic option. Since human ASM GABAA receptors express only the α4- and α5-subunits, there is an opportunity to selectively target ASM GABAA receptors to improve drug efficacy and minimize side effects. Recently, a novel compound (R)-ethyl8-ethynyl-6-(2-fluorophenyl)-4-methyl-4H-benzo[f]imidazo[1,5-a][1,4] diazepine-3-carboxylate (SH-053-2'F-R-CH3) with allosteric selectivity for α5-subunit containing GABAA receptors has become available. We questioned whether this novel GABAA α5-selective ligand relaxes ASM and affects intracellular calcium concentration ([Ca(2+)]i) regulation. Immunohistochemical staining localized the GABAA α5-subunit to human ASM. The selective GABAA α5 ligand SH-053-2'F-R-CH3 relaxes precontracted intact ASM; increases GABA-activated chloride currents in human ASM cells in voltage-clamp electrophysiology studies; and attenuates bradykinin-induced increases in [Ca(2+)]i, store-operated Ca(2+) entry, and methacholine-induced Ca(2+) oscillations in peripheral murine lung slices. In conclusion, selective subunit targeting of endogenous α5-subunit containing GABAA receptors on ASM may represent a novel therapeutic option to treat severe bronchospasm., (Copyright © 2015 the American Physiological Society.)
- Published
- 2015
- Full Text
- View/download PDF
37. Matrix effect in ligand-binding assay: the importance of evaluating emerging technologies.
- Author
-
Crisino RM, Luo L, Geist B, Zoghbi J, and Spriggs F
- Subjects
- Antibodies analysis, Humans, Immunoassay instrumentation, Immunoassay standards, Inventions, Pharmaceutical Preparations analysis, Immunoassay methods
- Published
- 2014
- Full Text
- View/download PDF
38. Ca(2+) oscillations regulate contraction of intrapulmonary smooth muscle cells.
- Author
-
Sanderson MJ, Bai Y, and Perez-Zoghbi J
- Subjects
- Acetylcholine pharmacology, Animals, Humans, Muscle Contraction drug effects, Muscle Relaxation drug effects, Muscle Relaxation physiology, Myocytes, Smooth Muscle cytology, Potassium Chloride pharmacology, Pulmonary Circulation physiology, Ryanodine Receptor Calcium Release Channel metabolism, Serotonin pharmacology, Calcium metabolism, Calcium Signaling physiology, Muscle Contraction physiology, Myocytes, Smooth Muscle physiology, Pulmonary Artery cytology, Pulmonary Artery drug effects, Pulmonary Artery physiology, Pulmonary Veins cytology, Pulmonary Veins drug effects, Pulmonary Veins physiology
- Abstract
Pulmonary blood pressure is a function of the resistance of the intrapulmonary blood vessels. Consequently, the mechanisms controlling blood vessel smooth muscle cell (SMC) contraction serve as potential sites for hypertension therapy. To explore these mechanisms, access to the intrapulmonary vessels is required and this is provided by the observation of a unique lung slice preparation with microscopy. There are 2 major processes that determine SMC tone; the intracellular Ca(2+) concentration and the sensitivity of the SMCs to Ca(2+). Agonist-induced increases in Ca(2+) occur in the form of propagating Ca(2+) oscillations that predominately utilize internal Ca(2+) stores and inositol trisphosphate receptors. The frequency of these Ca(2+) oscillations correlates with contraction. Agonists also increase Ca(2+) sensitivity of SMCs to enhance contraction. Changes in membrane potential mediated by KCl also stimulate contraction via slow Ca(2+) oscillations and increased sensitivity. However, these slow Ca(2+) oscillations rely on Ca(2+) influx to drive the cyclic release of over-filled Ca(2+) stores via the ryanodine receptor. The relaxation of SMC tone can be induced by the reduction of the frequency of the Ca(2+) oscillations and the Ca(2+) sensitivity by b(2)-adrenergic agonists or nitric oxide.
- Published
- 2010
- Full Text
- View/download PDF
39. Biventricular repair of transposition of the great arteries and unbalanced ventricles.
- Author
-
Serraf A, Piot D, Belli E, Lacour-Gayet F, Touchot A, Roussin R, Zoghbi J, Bruniaux J, and Planché C
- Subjects
- Cardiac Surgical Procedures methods, Follow-Up Studies, Heart Defects, Congenital diagnostic imaging, Heart Defects, Congenital mortality, Humans, Hypoplastic Left Heart Syndrome diagnostic imaging, Hypoplastic Left Heart Syndrome mortality, Hypoplastic Left Heart Syndrome surgery, Infant, Infant, Newborn, Retrospective Studies, Time Factors, Transposition of Great Vessels mortality, Ultrasonography, Heart Defects, Congenital surgery, Transposition of Great Vessels surgery
- Abstract
Background: It is well established that the arterial switch operation is the surgical procedure of choice in patients with transposition of the great arteries and balanced ventricular anatomy. The surgical approach of choice in patients with transposition but unbalanced ventricular size is unknown., Objectives: Since the beginning of the arterial switch operation program, patients with transposition of the great arteries and unbalanced ventricles underwent biventricular repair by means of the arterial switch operation and repair of any associated lesions, either through a single or staged surgical procedure. The aim of this retrospective study is to analyze whether this approach can be proposed to such patients., Methods: Forty-four patients with transposition of the great arteries and unbalanced ventricles underwent this surgical approach since 1984. Two groups were defined: group I had transposition with a dominant right ventricle (n = 28), and group II had transposition with a dominant left ventricle (n = 16). In group I the median age and weight at the arterial switch operation were 8.5 days (range, 5-70 days) and 3.1 kg (range, 1.5-3.7 kg), respectively. The median end-diastolic left ventricular volume, mass, and long-axis ratio were 15 mL/m2 (range, 11-16 mL/m2), 31.5 g/m2 (range, 20-66 g/m2), and 0.85 (range, 0.9-0.7), respectively. The mitral valve diameter was slightly hypoplastic, with a median z value of -1.22 (range, -0.3 to 3.7). In group 2 the median age and weight at the arterial switch operation were 42 days (range, 8 days-15 years) and 3.5 kg (range, 2.8-35 kg), respectively. Associated lesions in this group were coarctation in 9 and single (n = 12) or multiple (n = 4) ventricular septal defects. The median long-axis ratio and tricuspid z value were 0.6 (range, 0.3-0.8) and -0.9 (range, -0.5 to 3.3), respectively. In this group 9 patients had a single-stage procedure with fenestrated ventricular defect patches, atrial septal defect patches, or both; 7 patients underwent the staged approach., Results: In group I there was 1 early death from sepsis after weaning from postoperative extracorporeal membrane oxygenation. Three patients had severe pulmonary hypertension, one of whom died 1 year later. All survivors demonstrated, at discharge from the hospital, equilibrated ventricular size, with a median left ventricular end-diastolic volume of 25 mL/m2 (range, 21-30 mL/m2). In group II there were 2 early and 1 late deaths. All early deaths occurred in patients without voluntary residual intracardiac shunts. Median early postoperative long-axis ratio and tricuspid z value were 0.8 (range, 0.7-1) and -0.2 (range, 0.74 to 1.2), respectively., Conclusion: This study demonstrates that the arterial switch operation in patients with transposition of the great arteries and unbalanced ventricles remains a good surgical option.
- Published
- 2001
- Full Text
- View/download PDF
40. [Enlarging angioplasty of the aortic arch with an pulmonary artery autograft patch. Interest in a single-stage repair of the syndrome of coarctation and interruption of the aortic arch].
- Author
-
Serraf A, Roussin R, Belli E, Zoghbi J, al Chare W, Aupecle B, Bruniaux J, and Planché C
- Subjects
- Anastomosis, Surgical methods, Aorta, Thoracic surgery, Aortic Coarctation pathology, Female, Humans, Infant, Newborn, Male, Syndrome, Angioplasty methods, Aorta, Thoracic abnormalities, Aorta, Thoracic pathology, Aortic Coarctation surgery, Cardiovascular Surgical Procedures methods, Pulmonary Artery transplantation
- Abstract
Single stage repair of syndromes of coarctation and interruption of the aortic arch is a routine procedure in many surgical centres with good immediate results. The classical technique of aortic repair is based on the principles of Crafoord's extended resection anastomosis. Recoarctation is not an unusual long-term complication. A technique of enlarging angioplasty of the aorta using a patch of pulmonary artery has been developed and used in 22 neonates with obstruction of the aortic arch associated with ventricular septal defect with an average age and body weight of 15 days and 2.9 Kg respectively. The ventricular septal defect was closed surgically during the same procedure. Total circulatory arrest was not used in these children and all had aortic repairs with selective cerebral perfusion with moderate hypothermia (28-30 degrees C). This technique was used without any procedure-related early morbidity. No early or late deaths were observed in this series. Two patients were reoperated during the first year after the initial procedure: one for residual ventricular septal defect and the other for supraventricular pulmonary stenosis. Two patients, one of whom was reoperated, developed supraventricular pulmonary stenosis with a gradient of over 60 mmHg. These stenoses were observed in the first cases operated and were essentially due to the technique of pulmonary artery reconstruction. Over a median follow-up period of 10 months, no recoarctations were observed: the Doppler ultrasound study showed an isolated mean systolic gradient of 6 +/- 12 mmHg. The authors conclude that angioplasty of the aortic arch with an enlarging patch of pulmonary artery autograft during single stage surgery of syndromes of coarctation and interruption of the aortic arch provides a harmonious and durable repair of the aortic arch.
- Published
- 2001
41. Biventricular repair for double-outlet right ventricle.
- Author
-
Serraf A, Belli E, Lacour-Gayet F, Zoghbi J, and Planché C
- Abstract
Double-outlet right ventricle (DORV) is a heart malformation that describes an anomalous ventriculoarterial connection which can be associated with considerable variant of associated lesions. When this malformation is present with two ventricles, biventricular repair is feasible in the vast majority of cases. This report describes the surgical techniques for biventricular repair in all forms of encountered DORV, as well as the surgical strategy employed at our institution. Copyright 2000 by W.B. Saunders Company
- Published
- 2000
- Full Text
- View/download PDF
42. [Value of the spiral angio-scanner with three-dimensional reconstruction in the surgical strategy of unifocalization. Apropos of a case].
- Author
-
Le Bret E, Macé L, Dervanian P, Bourriez A, Folliguet TA, Zoghbi J, Lambert V, Losay J, Martin-Bouyer Y, and Neveux JY
- Subjects
- Angiocardiography methods, Child, Collateral Circulation, Echocardiography, Doppler, Echocardiography, Three-Dimensional, Humans, Male, Pulmonary Artery diagnostic imaging, Pulmonary Atresia surgery, Pulmonary Atresia diagnostic imaging
- Abstract
One of the difficulties of surgical treatment of pulmonary atresia with patent septum by unifocalisation resides in the accurate diagnosis of the different collateral vessels to the lung in order to optimise the surgical approach: anterior or posterolateral thoracotomy, and to determine the type of operation: one or two stages repair. Conventional angiography, even using different views, cannot always give an accurate representation of the anatomy of the different collateral vessels, especially their relationship to the bronchial structures. The authors report the contribution of spiral angioscanner with three dimensional reconstruction in the determination of the operative strategy of a case of pulmonary atresia with patent septum.
- Published
- 1998
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.