11 research outputs found
Chronic Systolic Heart Failure, Guideline-Directed Medical Therapy, and Systemic Hypotension-Less Pressure but Maybe More Risk (Does This Clinical Scenario Need More Discussion?)
No full textMany clinical trials have demonstrated the survival benefit of medication regimens that modulate the neurohormonal activation that occurs with chronic heart failure (HF). These medications, however, also commonly lower systemic blood pressure (BP). Low arterial BP in patients with chronic HF has been shown to be an independent predictor of increased mortality. Given this apparent paradox in therapeutic goals (treat aggressively but keep BP from going too low), how low should we allow systemic BP to go as a result of our medication regimens before we compromise the proven benefits of such drug therapy? Or is the association between the BP-lowering effects of standard therapy and outcomes in HF even meaningful clinically? It is from this perspective that the merits, potential clinical implications, and the relevant published literature pertaining to this patient and practice management issue will be discussed. © 2009 Elsevier Inc. All rights reserved.Aaronson KD, 1997, CIRCULATION, V95, P2660; ADAMS JF, 2006, J CARD FAIL, V12, P10; Anand IS, 2007, J AM COLL CARDIOL, V49, P32, DOI 10.1016-j.jacc.2006.04.109; Anand IS, 2008, CIRC-HEART FAIL, V1, P34, DOI 10.1161-CIRCHEARTFAILURE.107.736975; Canesin Manoel F, 2002, Arq Bras Cardiol, V78, P83, DOI 10.1590-S0066-782X2002000100007; Chobanian AV, 2003, HYPERTENSION, V42, P1206, DOI 10.1161-01.HYP.0000107251.49515.c2; COHN JN, 1973, AM J MED, V55, P351, DOI 10.1016-0002-9343(73)90135-6; Cowie MR, 2000, HEART, V83, P505, DOI 10.1136-heart.83.5.505; CRUICKSHANK JM, 1992, EUR HEART J, V13, P39; De Pasquale CG, 2005, EUR J HEART FAIL, V7, P888, DOI 10.1016-j.ejheart.2004.12.012; FARNETT L, 1991, JAMA-J AM MED ASSOC, V265, P489, DOI 10.1001-jama.265.4.489; Fonarow GC, 2005, JAMA-J AM MED ASSOC, V293, P572, DOI 10.1001-jama.293.5.572; GHALI JK, 1992, AM HEART J, V123, P993, DOI 10.1016-0002-8703(92)90709-5; Gheorghiade M, 2006, JAMA-J AM MED ASSOC, V296, P2217, DOI 10.1001-jama.296.18.2217; Goldenberg I, 2007, J AM COLL CARDIOL, V49, P1427, DOI 10.1016-j.jacc.2006.11.042; GOULD KL, 1985, CIRC RES, V57, P341; Herlitz J, 2002, J CARD FAIL, V8, P8, DOI 10.1054-jcaf.2002.30735; Hunt Sharon Ann, 2005, J Am Coll Cardiol, V46, pe1, DOI 10.1016-j.jacc.2005.08.022; Ingelsson E, 2006, JAMA-J AM MED ASSOC, V295, P2859, DOI 10.1001-jama.295.24.2859; Kannel WB, 2004, AM J CARDIOL, V94, P380, DOI 10.1016-j.amjcard.2004.04.043; Kihara M, 1998, AGE AGEING, V27, P551, DOI 10.1093-ageing-27.5.551; Kikuya M, 2007, CIRCULATION, V115, P2145, DOI 10.1161-CIRCULATIONAHA.106.662254; Koelling TM, 2004, AM HEART J, V147, P74, DOI 10.1016-j.ahj.2003.07.021; Lee J, 2006, WOMEN HIST REV, V15, P83, DOI 10.1080-09612020500440903; LEVINE TB, 1982, AM J CARDIOL, V49, P1659, DOI 10.1016-0002-9149(82)90243-0; Levy WC, 2006, CIRCULATION, V113, P1424, DOI 10.1161-CIRCULATIONAHA.105.584102; Mark DB, 1997, AM J CARDIOL, V80, pH33, DOI 10.1016-S0002-9149(97)00818-7; Messerli FH, 2006, ANN INTERN MED, V144, P884; Metra M, 2005, EUR HEART J, V26, P2259, DOI 10.1093-eurheartj-ehi386; Mosterd A, 2001, EUR HEART J, V22, P1318, DOI 10.1053-euhj.2000.2533; OCONNELL JB, 1994, J HEART LUNG TRANSPL, V13, pS107; Redfield MM, 2003, JAMA-J AM MED ASSOC, V289, P194, DOI 10.1001-jama.289.2.194; Rouleau JL, 2004, J AM COLL CARDIOL, V43, P1423, DOI 10.1016-j.jacc.2003.11.037; Senni M, 1999, ARCH INTERN MED, V159, P29, DOI 10.1001-archinte.159.1.29; Shin J, 2007, J CARD FAIL, V13, P656, DOI 10.1016-j.cardfail.2007.04.013; Taylor AL, 2004, NEW ENGL J MED, V351, P2049, DOI 10.1056-NEJMoa042934; Williams BR, 1999, ANN PHARMACOTHER, V33, P149, DOI 10.1345-aph.1742466
Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report
No full textSuccess of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report
No full textAbstract Background Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. Case presentation Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. Conclusions The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission
Prognostic role of pulmonary arterial capacitance in advanced heart failure
No full textBackground-Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. Methods and Results-We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=-0.64) and wedge pressure (r=-0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P0.0001) and higher PVR (P0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95percent CI: 0.84-1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes.s-1.cm-5, P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL-mm Hg, P0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P0.0001). Conclusions-PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy. © 2012 American Heart Association, Inc.Aronson D, 2011, CIRC-HEART FAIL, V4, P644, DOI 10.1161-CIRCHEARTFAILURE.110.960864; BAKER BJ, 1984, AM J CARDIOL, V54, P596, DOI 10.1016-0002-9149(84)90256-X; Bonderman D, 2011, CHEST, V139, P122, DOI 10.1378-chest.10-0348; Butler J, 1999, J AM COLL CARDIOL, V34, P1802, DOI 10.1016-S0735-1097(99)00408-8; de Groote P, 1998, J AM COLL CARDIOL, V32, P948, DOI 10.1016-S0735-1097(98)00337-4; de Perrot M, 2011, CHEST, V140, P34, DOI 10.1378-chest.10-1263; DISALVO TG, 1995, J AM COLL CARDIOL, V25, P1143, DOI 10.1016-0735-1097(94)00511-N; Ghio S, 2001, J AM COLL CARDIOL, V37, P183, DOI 10.1016-S0735-1097(00)01102-5; HARRIS P, 1965, BRIT HEART J, V27, P651; Juilliere Y, 1997, EUR HEART J, V18, P276; Karatasakis GT, 1998, AM J CARDIOL, V82, P329, DOI 10.1016-S0002-9149(98)00344-0; Lankhaar JW, 2006, AM J PHYSIOL-HEART C, V291, pH1731, DOI 10.1152-ajpheart.00336.2006; Lankhaar JW, 2008, EUR HEART J, V29, P1688, DOI 10.1093-eurheartj-ehn103; MACKAY EH, 1978, THORAX, V33, P335, DOI 10.1136-thx.33.3.335; Mahapatra S, 2006, J AM COLL CARDIOL, V47, P799, DOI 10.1016-j.jacc.2005.09.054; Mahapatra S, 2006, J AM SOC ECHOCARDIOG, V19, P1045, DOI 10.1016-j.echo.2006.03.008; POLAK JF, 1983, J AM COLL CARDIOL, V2, P217; Saouti N, 2009, AM J PHYSIOL-HEART C, V297, pH2154, DOI 10.1152-ajpheart.00694.2009; Tedford RJ, 2012, CIRCULATION, V125, P289, DOI 10.1161-CIRCULATIONAHA.111.051540; Voelkel NF, 2006, CIRCULATION, V114, P1883, DOI 10.1161-CIRCULATIONAHA.106.632208; WESTERHO.N, 1971, J APPL PHYSIOL, V31, P776; Westerhof N, 2009, MED BIOL ENG COMPUT, V47, P131, DOI 10.1007-s11517-008-0359-212
Plasma myeloperoxidase concentration predicts the presence and severity of coronary disease in patients with chest pain and negative troponin-T
No full textBackground: A non-negligible proportion of patients with chest pain with negative cardiac troponin may harbor a disrupted coronary plaque. A marker of plaque rupture upstream from myocardial necrosis may help identify high-risk patients among this patient population. The purpose of this study was to investigate the correlation of plasma myeloperoxidase (MPO) concentration and angiographic coronary disease among patients with suspected troponin-negative coronary syndromes. PATIENTS AND Methods: Patients presenting with chest pain and negative cardiac troponin-T concentration and undergoing coronary angiography were enrolled in our study. Plasma MPO concentration was measured using a single blood sample collected prior to cardiac catheterization. The primary angiographic endpoint was the presence of at least one coronary stenosis causing a 70percent or more diameter reduction; secondary endpoints were number of diseased vessels, presence of coronary thrombus, and lesion ulceration. The main clinical endpoint was coronary revascularization. Results: Three hundred and eighty-nine patients were enrolled. Presence of coronary stenosis causing a 70percent or more diameter reduction increased with increasing quartiles of myeloperoxidase concentration (P0.0001), as did the presence of coronary thrombus (P0.0001) and plaque ulceration (P0.0001). The need for percutaneous coronary revascularization also increased with increasing quartiles of systemic myeloperoxidase levels (P0.0001). Coronary surgical revascularization did not differ among myeloperoxidase quartiles. Conclusion: Among patients with chest pain without troponin elevation, a single measurement of plasma MPO concentration can help identify patients with a higher risk of having significant coronary stenoses and high-risk angiographic features. © 2011 Wolters Kluwer Health | Lippincott Williams and Wilkins.*ACC AHA, 2007, CIRCULATION, V116, P803; AMBROSE JA, 1985, J AM COLL CARDIOL, V5, P609; Antman EM, 1996, NEW ENGL J MED, V335, P1342, DOI 10.1056-NEJM199610313351802; Baldus S, 2003, CIRCULATION, V108, P1440, DOI 10.1161-01.CIR.0000090690.67322.51; Brener SJ, 2000, EUR HEART J, V21, P1117, DOI 10.1053-euhj.2000.2119; Brennan M, 2003, NEW ENGL J MED, V349, P1595, DOI 10.1056-NEJMoa035003; Buffon A, 2002, NEW ENGL J MED, V347, P5, DOI 10.1056-NEJMoa012295; Cavusoglu E, 2007, AM J CARDIOL, V99, P1364, DOI 10.1016-j.amjcard.2006.12.060; Eiserich JP, 2002, SCIENCE, V296, P2391, DOI 10.1126-science.1106830; Fu XY, 2001, J BIOL CHEM, V276, P41279, DOI 10.1074-jbc.M106958200; Hamm CW, 2000, CIRCULATION, V102, P118; Hazen SL, 1997, J CLIN INVEST, V99, P2075, DOI 10.1172-JCI119379; Heslop CL, 2010, J AM COLL CARDIOL, V55, P1102, DOI 10.1016-j.jacc.2009.11.050; Jurlander B, 2000, AM J CARDIOL, V85, P810, DOI 10.1016-S0002-9149(99)00872-3; KLEBANOFF SJ, 1984, METHOD ENZYMOL, V105, P399; Kubala L, 2008, CLIN CHIM ACTA, V394, P59, DOI 10.1016-j.cca.2008.04.001; Lucio ED, 2011, INFLAMM RES, V60, P137, DOI 10.1007-s00011-010-0247-8; Meuwese MC, 2007, J AM COLL CARDIOL, V50, P159, DOI 10.1016-j.jacc.2007.03.033; Mocatta TJ, 2007, J AM COLL CARDIOL, V49, P1993, DOI 10.1016-j.jacc.2007.02.040; Naruko T, 2010, HEART, V96, P1716, DOI 10.1136-hrt.2009.187609; Nicholls SJ, 2005, ARTERIOSCL THROM VAS, V25, P1102, DOI 10.1161-01.ATV.0000163262.83456.6d; Ornato J P, 1999, Clin Cardiol, V22, pIV3; Podrez EA, 2000, J CLIN INVEST, V105, P1095, DOI 10.1172-JCI8574; Pope JH, 2000, NEW ENGL J MED, V342, P1163, DOI 10.1056-NEJM200004203421603; REBEIZ A, 2005, EUR HEART J SUPPL, V26, P442; Sanchis J, 2005, J AM COLL CARDIOL, V46, P443, DOI 10.1016-j.jacc.2005.04.037; Sugiyama S, 2004, ARTERIOSCL THROM VAS, V24, P1309, DOI 10.1161-01.ATV.0000131784.50633.4f; Wainstein RV, 2010, CLIN BIOCHEM, V43, P57, DOI 10.1016-j.clinbiochem.2009.07.02212
Determinants of Self-Care in Patients With Heart Failure: Observations From a Developing Country in the Middle East
No full textIntroduction: Self-care is recognized as a means for improving outcomes of heart failure (HF), yet studies have not addressed what predicts successful self-care in collectivist cultures like Lebanon. Methodology: Self-care was measured, using the Arabic Self-Care of HF index, in 100 participants with HF (76% males; mean age 67.59) recruited from a tertiary medical center. Results: Self-care was suboptimal, with mean scores of 67.26, 66.96, and 69.5 for self-care maintenance, management, and confidence. Better HF knowledge, social support, and self-care confidence and lower New York Heart Association score predicted better self-care maintenance. Better knowledge, social support, and self-care maintenance, no recent hospitalization, and being unemployed predicted better self-care confidence. Better self-care confidence, maintenance, and HF knowledge predicted better self-care management. Discussion: HF self-care in Lebanon is suboptimal. Nurses need to identify facilitators of and barriers to self-care particular to this population. Interventions targeting HF knowledge, confidence, and caregiver support are expected to improve self-care in Lebanese patients. © The Author(s) 2019
Comparison of the systemic levels of inflammatory markers after percutaneous coronary intervention with bare metal versus sirolimus-eluting stents
No full textBackground: Percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment causes plaque disruption and a rise in systemic levels of C-reactive protein (CRP), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Our aim is to study whether PCI with sirolimus-eluting stent (SES) use attenuates this response. Methods: Patients with stable angina undergoing single-vessel PCI were enrolled in a randomized, open-label fashion into a BMS group or an SES group. Blood samples were drawn pre-PCI, 24 hours post-PCI, and 30 days post-PCI. Systemic concentrations of CRP, IL-6, and MCP-1 were measured at all time points. Results: In total, 41 patients were enrolled (21 in the BMS group and 20 in the SES group). The baseline plasma concentrations of all markers were comparable between groups. At 24 hours, the mean plasma CRP concentration in the SES group was 20.21 mg-dL versus 8.95 mg-dL in the BMS group (P = 0.15). The mean plasma IL-6 concentration at 24 hours was 25.41 pg-mL in the SES group versus 17.44 pg-mL in the BMS group (P = 0.17). The mean plasma MCP-1 concentration at 24 hours was 382.38 pg-mL in the SES group versus 329.04 pg-mL in the BMS group (P = 0.2). At 30 days, plasma concentrations of all three markers decreased to similar values between groups. Conclusions: The use of SES did not inhibit the rise in systemic concentrations of CRP, IL-6, and MCP-1 at 24 hours or 30 days post-PCI, compared with BMS. Moreover, at 24 hours, there was a trend for higher systemic levels of all proinflammatory markers in the SES group compared with the BMS cohort. ©2009, Wiley Periodicals, Inc.Bonz AW, 2003, AM HEART J, V145, P693, DOI 10.1067-mhj.2003.65; Brasselet C, 2007, CLIN CHEM LAB MED, V45, P526, DOI 10.1515-CCLM.2007.088; Bruns CJ, 2004, CLIN CANCER RES, V10, P2109, DOI 10.1158-1078-0432.CCR-03-0502; Caixeta AM, 2007, CATHETER CARDIO INTE, V69, P500, DOI 10.1002-ccd.21007; Economou E, 2001, INT J CARDIOL, V80, P55, DOI 10.1016-S0167-5273(01)00454-5; Gogo PB, 2005, J THROMB THROMBOLYS, V19, P87, DOI 10.1007-s11239-005-1378-6; Gomes WJ, 2005, ANN THORAC SURG, V80, P1903, DOI 10.1016-j.athoracsur.2004.05.079; Gurbel PA, 2006, J AM COLL CARDIOL, V48, P2186, DOI 10.1016-j.jacc.2005.12.084; HOFFMA S, 2006, EUR HEART J, V27, P166; Hojo Y, 2000, HEART, V84, P83, DOI 10.1136-heart.84.1.83; Jabs A, 2008, J AM COLL CARDIOL, V51, P2130, DOI 10.1016-j.jacc.2008.01.058; Jeanmart H, 2002, J HEART LUNG TRANSPL, V21, P990, DOI 10.1016-S1053-2498(02)00429-1; Kim JY, 2005, AM J CARDIOL, V96, P1384, DOI 10.1016-j.amjcard.2005.07.042; Kochiadakis GE, 2007, ATHEROSCLEROSIS, V194, P433, DOI 10.1016-j.atherosclerosis.2006.08.029; Lincoff AM, 2001, CIRCULATION, V104, P163; Marx SO, 2001, CIRCULATION, V104, P852; Moses JW, 2003, NEW ENGL J MED, V349, P1315, DOI 10.1056-NEJMoa035071; NIEMI SM, 1985, LAB ANIM SCI, V35, P609; Poon M, 1996, J CLIN INVEST, V98, P2277, DOI 10.1172-JCI119038; Revell PA, 1998, BIOMATERIALS, V19, P1579, DOI 10.1016-S0142-9612(97)00118-X; Rollins BJ, 1996, MOL MED TODAY, V2, P198, DOI 10.1016-1357-4310(96)88772-7; Serrano CV, 1997, J AM COLL CARDIOL, V29, P1276; Stone GW, 2004, NEW ENGL J MED, V350, P221, DOI 10.1056-NEJMoa032441; Suzuki T, 2001, CIRCULATION, V104, P1188, DOI 10.1161-hc3601.093987; Virmani R, 2004, CORONARY ARTERY DIS, V15, P313, DOI 10.1097-00019501-200409000-0000387
Prevalence of coronary artery calcium among asymptomatic men and women in a developing country: Comparison with the USA data
No full textBackground: Coronary artery calcium score (CACS) correlates with atherosclerotic burden and predicts cardiac events. Most of the published data have been derived from the USA population. Objective: To study the prevalence of coronary calcium in an asymptomatic population from the eastern Mediterranean region and compare it to data obtained from a large population study in the USA. Results: A total of 1154 asymptomatic men and women from Lebanon underwent EBCT screening because of the presence of one or more CAD risk factors. Mean CACS as well as the percentile cut-points increased consistently with increasing age and, except for those above 74 years of age, were higher in men than women in each age stratum. Age, hypercholesterolemia, diabetes and smoking showed significant associations with CACS in men, while only age and hypercholesterolemia were significantly associated with CACS in women. Among men, the 75th and 90th percentile distributions were comparable to what is observed in developed countries such as the USA. Conclusion: Findings, from this first study in the region, suggest that despite a higher rate of diabetes and smokers in our study population, the CACS distribution in Lebanon is similar to that observed in the USA. © 2005 Elsevier Ireland Ltd. All rights reserved.AGATSTON AS, 1990, J AM COLL CARDIOL, V15, P827; Berman DS, 2004, J AM COLL CARDIOL, V44, P923, DOI 10.1016-j.jacc.2004.06.042; Bild DE, 2001, ARTERIOSCL THROM VAS, V21, P852; CALLISTER T, 2002, 51 ANN SCI SESS AM C; de Lorgeril M, 1999, CIRCULATION, V99, P779; Detrano R, 1996, J AM COLL CARDIOL, V27, P285, DOI 10.1016-0735-1097(95)00460-2; Esposito K, 2004, JAMA-J AM MED ASSOC, V292, P1440, DOI 10.1001-jama.292.12.1440; Guerci AD, 1997, AM J CARDIOL, V79, P128; Hoff JA, 2001, AM J CARDIOL, V87, P1335, DOI 10.1016-S0002-9149(01)01548-X; Jain T, 2004, J AM COLL CARDIOL, V44, P1011, DOI 10.1016-j.jacc.2004.05.069; JANOWITZ WR, 1993, AM J CARDIOL, V72, P247, DOI 10.1016-0002-9149(93)90668-3; KAJINAMI K, 1995, J AM COLL CARDIOL, V26, P1209, DOI 10.1016-0735-1097(95)00314-2; Knoops KTB, 2004, JAMA-J AM MED ASSOC, V292, P1433, DOI 10.1001-jama.292.12.1433; KRAGEL AH, 1989, CIRCULATION, V80, P1747; MOHLENKAMP S, 2001, ANN SCI SESS AM HEAR; NUWAYHID I, 1997, BEIRUT HLTH PROFILE, P132; O'Rourke RA, 2000, CIRCULATION, V102, P126; ROBERTS WC, 1989, AM J CARDIOL, V64, P324, DOI 10.1016-0002-9149(89)90528-6; Robertson RM, 2001, CIRCULATION, V103, P1821; RUMBERGER JA, 1995, CIRCULATION, V92, P2157; Rumberger JA, 1997, J AM COLL CARDIOL, V29, P1542; RUMBERGER JA, 1995, CIRCULATION, V91, P1363; RUMBERGER JA, 1994, AM J CARDIOL, V73, P1169, DOI 10.1016-0002-9149(94)90176-7; Rumberger JA, 1999, MAYO CLIN PROC, V74, P243; Sangiorgi G, 1998, J AM COLL CARDIOL, V31, P126, DOI 10.1016-S0735-1097(97)00443-9; Schmermund A, 1999, J AM COLL CARDIOL, V34, P777, DOI 10.1016-S0735-1097(99)00265-X; Schmermund A, 1998, J AM COLL CARDIOL, V31, P1267, DOI 10.1016-S0735-1097(98)00082-5; Wayhs R, 2002, J AM COLL CARDIOL, V39, P225, DOI 10.1016-S0735-1097(01)01737-5; Wexler L, 1996, CIRCULATION, V94, P1175; World Health Organization, 1997, OB PREV MAN GLOB EP86
Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of lebanese people
No full textThe authors assessed the impact of CYP2C9*2, CYP2C9*3, and-or VKORC1-1639GA-1173CT single-nucleotide polymorphisms on oral anticoagulants in a Lebanese population. This study recruited 231 Lebanese participants on long-term warfarin or acenocoumarol maintenance therapy with an international normalized ratio (INR) monitored at the American University of Beirut Medical Center. CYP2C9 and VKORC1 variant alleles were screened by real-time PCR. Plasma R-and S-warfarin and R-and S-acenocoumarol levels were assayed using high-performance liquid chromatography. The variant allele frequencies of CYP2C9*2, CYP2C9*3, and VKORC1-1639GA-1173CT were 15.4percent, 7.8percent, and 52.4percent, respectively. Fifty-five participants were excluded from analysis because of nontherapeutic INR values at recruitment, leaving 43 participants taking warfarin and 133 taking acenocoumarol. There was a significant decrease in the weekly maintenance dose of both drugs with CYP2C9 and VKORC1 variants when compared with wild-type patients. CYP2C9*2 had the least impact on the response to both drugs. The concentrations of R-and S-warfarin in plasma were significantly correlated with CYP2C9 genotypes. For acenocoumarol, time to reach target INR was more prolonged in patients carrying any CYP2C9 variant allele but failed to reach statistical significance because of low numbers of patients. There was no association between allelic variants and bleeding events. This is the first pharmacogenetic study of oral anticoagulants in Arabs. 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Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension
No full textBackground: Pulmonary hypertension (PH) remains one of the rarest and deadliest diseases. Pulmonary Capillary Hemangiomatosis (PCH) is one of the sub-classes of PH. It was identified using histological and molecular tools and is characterized by the proliferation of capillaries into the alveolar septae. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of PH. Methods: In our effort to unveil the genetic basis of idiopathic and familial cases of PH in Lebanon, we have used whole exome sequencing to document known and/or novel mutations in genes that could explain the underlying phenotype. Results: We showed bi-allelic mutations in EIF2AK4 in two non-consanguineous families: a novel non-sense mutation c.1672C > T (p.Q558∗) and a previously documented deletion c.560-564drlAAGAA (p.K187Rfs9∗). Our histological analysis coupled with the CT-scan results showed that the two patients with the p.Q558∗mutation have PH. In contrast, only one of the individuals harboring the p.K187Rfs9∗variant has a documented PCH while his older brother remains asymtomatic. Differential analysis of the variants in the genes of the neighboring network of EIF2AK4 between the two siblings identified a couple of interesting missense mutations that could account for this discrepancy. Conclusion: These findings represent a novel documentation of the involvement of EIF2AK4 in the different aspects of pulmonary hypertension. The absence of a molecular mechanism that relates the abrogated function of the protein to the phenotype is still a major hurdle in our understanding of the disease. © 2019 The Author(s)
