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3. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I., Dunn, David T., Sutherland, Katherine A., Pillay, Deenan, Mbisa, Jean L., Parry, Chris M., Post, Frank A., Sabin, Caroline A., Cane, Patricia A., Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Pillay, Deenan, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, OʼShea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Welch, J., Poulton, M., MacDonald, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Allan, S., Palfreeman, A., Moore, A., and Wakeman, K.

Published
2013
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6. COMMENTARY

Author

Waxman, M A and Abrahamian, F M

Published
2006

8. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

Author

Jose, Sophie, Hamzah, Lisa, Campbell, Lucy J., Hill, Teresa, Fisher, Martin, Leen, Clifford, Gilson, Richard, Walsh, John, Nelson, Mark, Hay, Phillip, Johnson, Margaret, Chadwick, David, Nitsch, Dorothea, Jones, Rachael, Sabin, Caroline A., Post, Frank A., Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Delpech, Valerie, Dunn, David, Gazzard, Brian, Gompels, Mark, Kegg, Stephen, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Sabin, Caroline, Sachikonye, Memory, Schwenk, Achim, Huntington, Susie, Josie, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Churchill, D., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Poulton, M., Taylor, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Gompels, M., Allan, S., Palfreeman, A., Moore, A., Chadwick, D., Wakeman, K., Main, Paul, Mitchell, Hunter, and Dhillon, Mandip

Subjects
Adult, Male, eGFR slopes, kidney, Anti-HIV Agents, Adenine, renal function, Organophosphonates, HIV Infections, highly active antiretroviral therapy, Middle Aged, Viral Load, tenofovir, Drug Administration Schedule, Cohort Studies, Major Articles and Brief Reports, eGFR, HIV/AIDS, Humans, Female, Kidney Diseases, Glomerular Filtration Rate, Proportional Hazards Models
Abstract

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

Published
2014

12. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

Author

May, MT, Gill, MJ, Wittkop, L, Klein, M, Sabin, C, Harrigan, PR, Dunn, D, Vehreschild, JJ, Rubio, R, Mocroft, A, Cavassini, M, Reiss, P, Monforte, AD, Zangerle, R, Ingle, SM, Hill, T, Jose, S, Sterne, JAC, Boulle, A, Stephan, C, Miro, JM, Chene, G-V, Costagliola, D, Dabis, F, Del Amo, J, Van Sighem, A, Vehreschild, J, Gill, J, Guest, J, Haerry, DH-U, Hogg, R, Justice, A, Obel, N, Crane, H, Smith, C, Saag, M, Sterling, T, Teira, R, Williams, M, Sterne, J, May, M, Ingle, S, Trickey, A, Ainsworth, J, Anderson, J, Babiker, A, Chadwick, D, Delpech, V, Fisher, M, Gazzard, B, Gilson, R, Hay, P, Gompels, M, Johnson, M, Kegg, S, Leen, C, Mackie, N, Nelson, M, Orkin, C, Palfreeman, A, Phillips, A, Pillay, D, Post, F, Sachikonye, M, Schwenk, A, Walsh, J, Thornton, A, Huntington, S, Glabay, A, Garrett, N, Lynch, J, Hand, J, De Souza, C, Perry, N, Tilbury, S, Youssef, E, Churchill, D, Waxman, M, Asboe, D, Mandalia, S, Munshi, S, Awosika, D, Korat, H, Taylor, C, Gleisner, Z, Ibrahim, F, Campbell, L, Baillie, K, Cope, E, Gibney, M, Gibson, J, Brima, N, Williams, I, Miller, S, Wood, C, Youle, M, Lampe, F, Chaloner, C, Winston, A, Weber, J, Ramzan, F, Carder, M, Wilson, A, Morris, S, Allan, S, Moore, A, Fox, L, Bojanowski, J, Lewszuk, A, Main, P, Mitchell, D, Hunter, D, Dhillon, M, Martin, F, Douglas, S, Russell-Sharp, S, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, and Global Health

Subjects
Male, 0301 basic medicine, IMPACT, DIVERSITY, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Immunology and Allergy, Medicine, 030212 general & internal medicine, Cooperative Behavior, Viral failure, Hazard ratio, viral failure, 11 Medical And Health Sciences, Middle Aged, Prognosis, Antiretroviral therapy, 3. Good health, Europe, Infectious Diseases, Anti-Retroviral Agents, INFECTIONS, Cohort, Female, Life Sciences & Biomedicine, NAIVE PATIENTS, Cohort study, Adult, Canada, medicine.medical_specialty, Genotype, Epidemiology and Social, antiretroviral therapy, Immunology, 17 Psychology And Cognitive Sciences, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, Humans, TYPE-1 SUBTYPES, Mortality, COMBINATION ANTIRETROVIRAL THERAPY, HIV-1 subtype, Science & Technology, business.industry, DISEASE PROGRESSION, 06 Biological Sciences, medicine.disease, Survival Analysis, mortality, IMMUNOLOGICAL RESPONSE, 030112 virology, Confidence interval, Regimen, HIV-1, prognosis, T-CELL DECLINE, business, RESISTANCE
Abstract

Objectives: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design: Collaborative analysis of data from eight European and three Canadian cohorts. Methods: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4+ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4+ cell count below, or more than, 100 cells/ml, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

Published
2015

13. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

18. 735 Early Success of Ventricular Tachycardia Ablation in Patients With Structural Heart Disease: A Single Centre Experience

Author

Khan, F., primary, Roshan, J., additional, Das, M., additional, Harris, L., additional, Wanounou, L., additional, Spears, D., additional, Chauhan, V., additional, Ing, D., additional, Cameron, D., additional, Waxman, M., additional, Ha, A., additional, Nair, K., additional, Downar, E., additional, and Nanthakumar, K., additional

Published
2012
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40. French Meadows reunion camp.

Author

Ferre C, Ferre J, Stanchich L, McCarty M, Carr B, Loeb K, Chen M, Waxman M, Waxman D, Rubin L, Russell H, Stec L, and Tinling H

Abstract

There is more to French Meadows Summer Camp than any of us can put into words -- yet, we try. This year, in honor of the reunion camp, we asked the presenters to explain why learning at French Meadows is so unique. [ABSTRACT FROM AUTHOR]

Published
2009

41. Right atrial stimulation in the treatment of atrial flutter.

Author

Zeft, Howard J., Cobb, Fred R., Waxman, Menashe B., Hunt, Noel C., Morris Jr., James J., Zeft, H J, Cobb, F R, Waxman, M B, Hunt, N C, and Morris, J J Jr

Subjects
ATRIAL flutter, DIGITALIS (Drug), FLUOROSCOPY, ARRHYTHMIA, LIDOCAINE, QUINIDINE, CARDIAC catheterization, CARDIAC glycosides, CARDIAC pacemakers, ELECTROCARDIOGRAPHY, ELECTRODES, HEART atrium, TIME, THERAPEUTICS
Abstract

The use of right atrial stimulation in the treatment of atrial flutter was evaluated in 10 patients. Atrial flutter was present in these patients from 6 to 96 hr before the procedure. Eight patients were receiving digitalis preparations. In seven patients a unipolar platinum-tipped electrode was positioned in the right atrium by monitoring the intra-atrial electrocardiogram; in three patients a bipolar pacing catheter was positioned in the right atrium under fluoroscopic guidance. Atrial stimulation was performed utilizing either a battery-powered or electrically powered pulse generator. Right atrial stimulation was performed at 180/min in seven patients and 400 to 600/min in three patients. Right atrial stimulation produced conversion to a stable sinus rhythm in seven patients and a transient sinus rhythm in an additional patient. In all but one patient transient unstable atrial fibrillation was observed immediately before conversion to a sinus mechanism. Postconversion arrhythmias or complications directly attributed to the procedure were not observed. In certain patients with atrial flutter--especially those unable to tolerate anesthesia, large doses of antiarrhythmic drugs, or withdrawal from digitalis--atrial stimulation seems to be the initial treatment of choice. [ABSTRACT FROM AUTHOR]

Published
1969
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42. Effect of adrenergic stimulation and blockade on ventricular defibrillation in the rat.

Author

Sharma, A D, Waxman, M B, and Huerta, F I

Abstract

Ventricular fibrillation was electrically induced in 60 rats and the effects of adrenergic stimulation ad blockade on the time taken to spontaneous reversion to sinus rhythm were determined. Alpha adrenergic stimulation by norepinephrine and phenylephrine infusion shortened ventricular fibrillation from 3.21 +/- 0.42 (+/- S.E.M.) to 1.48 +/- 0.17 sec (P less than .001) and from 5.13 +/- 0.77 to 2.18 +/- 0.27 sec (P less than .001), respectively. Nonselective beta adrenergic stimulation with isoproterenol prolonged the time to defibrillation from 1.65 +/- 0.20 to 7.01 +/- 0.95 sec (P less than .001), whereas beta-2 adrenergic stimulation with salbutamol produced no change. Alpha adrenergic stimulation antagonized the effect of a concomitant isoproterenol infusion (P less than .05). Alpha adrenergic blockade with phenoxybenzamine prolonged ventricular fibrillation (P less than .001) whereas beta blockade with propranolol or metoprolol shortened the duration of fibrillation. It was concluded that these effects were due to direct stimulation and blockade of cardiac adrenergic receptors. These actions were associated with changes in ventricular refractoriness. Cardiac alpha adrenergic stimulation prolonged the ventricular effective refractory period and promoted spontaneous defibrillation. Beta adrenergic stimulation shortened the ventricular effective refractory period and prolonged the time to defibrillation.

Published
1983

43. Surface Conductance of Sodium Bentonite in Water

Author

Olphen, H. and Waxman, M.

Abstract

The concept of surface conductance and its role in the interpretation of the formation resistivity factor of reservoir rocks is reviewed. The specific surface conductance of a clay is determined for four narrow particle-size fractions of sodium Wyoming bentonite in conductivity water. The values are derived from the specific conductance of gels of these clays on the basis of the picture of an idealized cubic network structure of the clay plates. The average surface conductance for internal and external surfaces of the bentonites is found to be 3.2 × 10−19ohm−1, which is 0.55 × the value expected when all exchangeable ions are assigned their infinite dilution mobility. The data are independent of particle size. In addition, conductivity data are presented for clay suspensions in a wide range of concentrations. In extremely dilute suspensions, the contribution of the clay to the conductivity when expressed per unit weight of clay (the so-called “weight conductance”) is smaller than expected from an independent movement of particle and counter ions. This is interpreted to be partly a result of both electrophoretic and relaxation retardation, indicating that the electrical double layer on sodium bentonite has a condensed character. Probably part of the counter ions are entirely immobilized by adsorption on the surface. With increasing clay concentration, further compression of the double layer increases the retardation effects and a further decrease of the weight conductance is observed. A minimum is reached at a concentration of a few tenths of one percent clay at which, according to viscosity and light absorption data, particle interaction becomes apparent. At this point, immobilization of the particles and bridging between the electrodes gradually eliminate the retardation effects, and surface conductance takes over. The weight conductance increases gradually until a constant value is reached in a concentration range of 5 to 12 g of clay per 100 ml gel, from which the above value of the specific surface conductance was computed.

Published
1956
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45. Antazoline therapy of recurrent refractory supraventricular arrhythmias--a preliminary report

Author

Downar, E. and Waxman, M. B.

Subjects
Adult, Male, Clinical Trials as Topic, Digoxin, Adolescent, Antazoline, Imidazoles, Arrhythmias, Cardiac, Middle Aged, Procainamide, Propranolol, Quinidine, Recurrence, Chronic Disease, Drug Evaluation, Humans, Female, Research Article, Aged
Abstract

Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.

Published
1975

46. Self-conversion of drug-resistant paroxysmal atrial tachycardia

Author

Waxman, M. B., Felderhof, C. H., Downar, E., Goldman, B. S., and Morch, J. E.

Subjects
Bundle of His, Pacemaker, Artificial, Radio Waves, Electric Countershock, Middle Aged, Coronary Vessels, Electrodes, Implanted, Electrocardiography, Recurrence, cardiovascular system, Humans, Female, Heart Atria, Tachycardia, Paroxysmal, Research Article
Abstract

A 56-year-old woman had paroxysmal atrial tachycardia (PAT) that was recurrent, drug-resistant and required frequent electroversion. The mode of onset and termination of initiated episodes of PAT suggested an AV junctional reentrant mechanism. The problem was successfully managed by a permanent electrode implanted transvenously in the coronary sinus and connected to a subcutaneous radio frequency receiver. For the past 24 months the patient has successfully terminated all episodes of PAT (at least 60) by activating an external radio frequency transmitter that transmits impulses to the implanted receiver and electrode catheter. Conversion to sinus rhythm requires 5 seconds or less of pacing.

Published
1975

47. Neurally mediated syncope: Pathogenesis, diagnosis, and treatment

Author

Kaufmann, H., Savage, D. D., Corwin, L., Mcgee, D. L., Gendelman, H. E., Linzer, M., Gabelman, M., Day, S. C., Cook, E. F., Funkenstein, H., Lewis, T., Ziegler, M. G., Lake, C. R., Kopin, I. J., Bannister, R., Sever, P., Gross, M., Oribe, E., Winters, S., Sneddon, J. F., Counihan, P. J., Bashir, Y., Boudoulas, H., Weissler, A. M., Lewis, R. P., Weiss, S., Baker, J. P., Dehn, T. C., Morley, C. A., Sutton, R., Mathias, C. J., Armstrong, E., Browse, N., Shaw, E. C., Young, H. H., Kapoor, W. N., Peterson, J. R., Karpf, M., Palmer, E. D., Mark, A. L., Abboud, F. M., Oberg, B., Thoren, P., Skarphedinsson, J. O., Carlsson, S., Jarisch, A., Zotterman, Y., Shalev, Y., Gal, R., Tchou, P. J., Scherrer, U., Vissing, S., Morgan, B. J., Fitzpatrick, A. P., Bannder, N., Cheng, A., Maloney, T. D., Jaeger, F. J., Fouad-Tarazi, F. M., Milstein, S., Buetikofer, J., Lesser, J., Sra, J. S., Jazayeri, M. R., Avitall, B., Barcroft, H., Edholm, O. G., Mcmichael, J., Sharpey-Shafer, E. P., Epstein, S. E., Stampfer, M., Beiser, D., Murray, R. H., Thompson, L. J., Bowers, J. A., Wallin, B. G., Sundlof, G., Westerberg, C. E., Sundloff, G., Burke, D., Wallin, G., Oliver, J. A., Miller, M., Glover, W. E., Greenfield, A. D. M., Shanks, R. G., Robinson, B. J., Johnson, R. H., Robertson, D., Johnson, G. A., Robertson, R. M., Palmer, R. M., Ashton, D. S., Moncada, S., Higgs, E. A., Bolotina, V., Najibi, S., Palacino, J., Tolins, J., Palmer, R. M. J., Berman, J., Kenny, R. A., Ingram, A., Bayliss, J., Fitzpatrick, A., Abi-Samra, F., Maloney, J. D., Fouad-Tarazi, F., Almquist, A., Goldenberg, I. F., Strasberg, B., Rechavia, E., Sagie, A., Raviele, A., Gasparini, G., Di Pede, F., Grubb, B. P., Temsey-Armos, P., Hahn, H., Michele Brignole, Menozzi, C., Gianfranchi, L., Anderson, A. J., Sheik, S. H., Sheldon, R., Killam, S., Waxman, M. B., Yao, L., Cameron, D. A., Brant, N., Micieli, G., Cavallini, A., Tasorelli, C., El-Bedawi, K. M., Hainsworth, R., Davies, I. B., Sever, P. S., Balaji, S., Oslizlok, P. C., Allen, M. C., Dacosta, D., Mcintosh, S., Thames, M. D., Abi Samra, F. M., Davison, N. M., Gardner, R. D., O Marcaigh, A. S., Maclellan-Tobert, S. G., Porter, C. J., Dangovian, M. I., Jarandilla, R., Frumin, H., Morillo, C. A., Leitch, J. W., Yee, R., Mclaran, C. J., Gersh, B. J., Osborn, M. J., Nelson, S., Stanley, M., Love, C., Susmano, A., Volgman, A. S., Buckingham, T. A., Strieper, M. J., Campbell, R., Wolfe, D., and Samoil, D.

48. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I., Dunn, David T., Sutherland, Katherine A., Pillay, Deenan, Mbisa, Jean L., Parry, Chris M., Post, Frank A., Sabin, Caroline A., Cane, Patricia A., Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Welch, J., Poulton, M., MacDonald, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Allan, S., Palfreeman, A., Moore, A., and Wakeman, K.

Subjects
Male, Mutation rate, Pyridines, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, THERAPY, Cohort Studies, 0302 clinical medicine, HIV Protease, Mutation Rate, 1108 Medical Microbiology, Genotype, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Treatment Failure, drug resistance mutations, Original Research, 0303 health sciences, virological failure, UK Collaborative HIV Cohort Study (UK CHIC), Proteolytic enzymes, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Female, 1115 Pharmacology and Pharmaceutical Sciences, Life Sciences & Biomedicine, Oligopeptides, medicine.drug, Cohort study, 0605 Microbiology, Microbiology (medical), Adult, medicine.medical_specialty, Anti-HIV Agents, Atazanavir Sulfate, protease inhibitors, Mutation, Missense, RITONAVIR, Biology, Microbiology, Medication Adherence, 03 medical and health sciences, Internal medicine, SCORE, Drug Resistance, Viral, medicine, Humans, 030304 developmental biology, Pharmacology, Science & Technology, HIV, Virology, naive patients, United States, Atazanavir, Regimen, HIV-1, Ritonavir, UK HIV Drug Resistance Database (UKHDRD)
Abstract

Author(s): Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A; UK HIV Drug Resistance Database (UKHDRD); UK Collaborative HIV Cohort Study (UK CHIC) | Abstract: ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P l 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P l 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

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