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Papers by claudia rodriguez
American Journal of Transplantation, 2004
The study was designed to identify a subset of heart transplant (HT) recipients who could benefit... more The study was designed to identify a subset of heart transplant (HT) recipients who could benefit from the administration of targeted antifungal prophylaxis and to evaluate the efficacy of oral itraconazole as the preventive drug. We have analyzed the risk factors for invasive aspergillosis (IA) in our entire population of HT recipients (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) and also the role of oral itraconazole prophylaxis that was provided to all patients since 1995 [400 mg q.d. of itraconazole oral (PO) for 3-6 months]. There were 24 cases of IA. Our main results indicate that the independent risk factors for IA after heart transplantation are: re-operation (RR 5.8; 95% CI 1.8-18, p = = 0.002), cytomegalovirus (CMV) disease (RR 5.2; 95% CI 2-13.9, p = = 0.001), post-transplant hemodialysis (RR 4.9; 95% CI 1.2-18, p = = 0.02), and the existence of an episode of IA in the HT program 2 months before or after the transplantation date (RR 4.6; 95% CI 1.5-14.4, p = = 0.007). Itraconazole prophylaxis showed an independent protective value against developing IA (RR 0.2; 95% CI 0.07-0.9, p = = 0.03) and also determined a significantly prolonged 1-year survival (RR 0.5; 95% CI 0.3-0.8, p = = 0.01). We believe that antifungal prophylaxis in heart transplant patients should be offered at least to patients with one or more of these predisposing conditions.
Clinical Infectious Diseases, 2005
Tuberculosis is a serious opportunistic infection that may affect transplant recipients. The inci... more Tuberculosis is a serious opportunistic infection that may affect transplant recipients. The incidence of tuberculosis among such persons is 20-74 times higher than that for the general population, with a mortality rate of up to 30%. The most common form of acquisition of tuberculosis after transplantation is the reactivation of latent tuberculosis in patients with previous exposure. Clinical presentation is frequently atypical and diverse, with unsuspected and elusive sites of affection. Manifestations include fever of unknown origin and allograft dysfunction. Coinfection with other pathogens is not uncommon. New techniques, such as PCR and quantification of interferon- gamma , have been developed to achieve more-rapid and -accurate diagnoses. Treatment requires control of interactions between antituberculous drugs and immunosuppressive therapy. Prophylaxis against latent tuberculosis is the main approach to treatment, but many issues remain unsolved, because of the difficulty in identifying patients at risk (such as those with nonreactive purified protein derivative test results) and the toxicity of therapy.
Journal of Lipid Research, 2003
Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptor... more Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptors, lipid transfer protein, lipolytic enzymes and HDL apolipoproteins. In order to better define the role of HDL apolipoproteins in determining plasma HDL concentrations, the aims of the present study were: a ) to compare the in vivo rate of plasma turnover of HDL apolipoproteins [i.e., apolipoprotein A-I (apoA-I), apoC-I, apoC-III, and apoE], and b ) to investigate to what extent these metabolic parameters are related to plasma HDL levels. We thus studied 16 individuals with HDL cholesterol levels ranging from 0.56-1.66 mmol/l and HDL apoA-I levels ranging from 89-149 mg/dl. Plasma kinetics of HDL apolipoproteins were investigated using a primed constant (12 h) infusion of deuterated leucine. Plasma HDL apolipoprotein levels were 41.8 ؎ 1.5, 9.7 ؎ 0.5, 4.9 ؎ 0.5, and 0.7 ؎ 0.1 mol/l for apoA-I, apoC-I, apoC-III and apoE. Plasma transport rates (TRs) were 388.6 ؎ 24.7, 131.5 ؎ 12.5, 66.5 ؎ 9.1, and 31.4 ؎ 3.3 nmol·kg ؊ 1 ·day ؊ 1 ; and residence times (RTs) were 5. respectively. HDL cholesterol and apoA-I levels were significantly correlated with HDL apoA-I RT ( r ؍ 0.69 and r ؍ 0.56), and were not significantly correlated with HDL apoA-I TR. In contrast, HDL apoC-I, apoC-III, and apoB levels were all positively related to their TRs and not their RTs. HDL apoC-III TR was postively correlated with levels of HDL apoC-III ( r ؍ 0.73, P Ͻ 0.01), and with those of HDL cholesterol and apoA-I ( r ؍ 0.54 and r ؍ 0.53, P Ͻ 0.05, respectively). HDL apoC-III TR was in turn related to HDL apoA-I RT ( r ؍ 0.51, P Ͻ 0.05). Together, these results provide in vivo evidence for a link between the metabolism of HDL apoC-III and apoA-I, and suggest a role for apoC-III in the regulation of plasma HDL levels. -Cohn, J. S., R. Batal, M. Tremblay, H. Jacques, L. Veilleux, C. Rodriguez, O. Mamer, and J. Davignon. Plasma turnover of HDL apoC-I, apoC-III, and apoE in humans: in vivo evidence for a link between HDL apoC-III and apoA-I metabolism. J. Lipid Res. 2003Res. . 44: 1976Res. -1983 Supplementary key words apolipoprotein C-I • triglyceride • cholesterol • atherosclerosis • stable isotope • lipoprotein metabolism Abbreviations: CHD, coronary heart disease; HL, hepatic lipase; SR-BI, scavenger receptor class B type I; TR, transport rate; TRL, triglyceride-rich lipoprotein.
Atherosclerosis, 2004
Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabol... more Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabolism. In order to further investigate the plasma metabolism of apoC-III in hypertriglyceridemic subjects, we have studied the plasma kinetics of VLDL apoC-III, HDL apoC-III and total plasma apoC-III with a primed constant intravenous infusion of deuterated leucine in a group of male patients with mixed hyperlipidemia (type IIb hyperlipoproteinemia, HLP, n = 6) and in a group with type III HLP (n = 6). Compared to normolipidemic control subjects (n = 5), patients with type IIb and type III HLP had significantly higher levels of plasma TG (0.89 ± 0.15 mmol/l vs 2.56 ± 0.40 mmol/l vs 8.76 ± 1.39 mmol/l, respectively, P < 0.01), plasma apoC-III (9.5 ± 0.8 mg/dl vs 20.8 ± 2.5 mg/dl vs 41.7 ± 5.6 mg/dl, P < 0.01) and VLDL apoC-III (3.6 ± 0.8 mg/dl vs 14.6 ± 2.2 mg/dl vs 35.4 ± 5.1 mg/dl, P < 0.01). VLDL apoC-III production rates were significantly elevated in type IIb and type III patients (1.35 ± 0.23 mg kg −1 day −1 vs 3.53 ± 0.43 mg kg −1 day −1 vs 5.60 ± 0.78 mg kg −1 day −1 , P < 0.01), as were total plasma apoC-III production rates (1.80 ± 0.22 mg kg −1 day −1 vs 4.16 ± 0.44 mg kg −1 day −1 vs 7.26 ± 0.74 mg kg −1 day −1 , P < 0.01). VLDL apoC-III but not total plasma apoC-III fractional catabolic rates were reduced in type IIb and type III patients. Together with our previous results showing an increase of apoC-III production in patients with type IV HLP, and in overweight subjects with reduced insulin sensitivity, our data suggest that increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia.
Journal of Lipid Research, 2002
ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediate... more ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediated uptake of plasma triglyceride-rich lipoproteins, inhibition of cholesteryl ester transfer activity, and mediation of tissue fatty acid uptake. Since little is known about the rate of production and catabolism of plasma apoC-I in humans, the present study was undertaken to determine the plasma kinetics of VLDL and HDL apoC-I using a primed constant (12 h) intravenous infusion of deuterium-labeled leucine. Data were obtained for 14 subjects: normolipidemics (NL, n ؍ 4), hypertriglyceridemics (HTG, n ؍ 4) and combined hyperlipidemics (CHL, n ؍ 6). Plasma VLDL triglyceride (TG) levels were 0.59 ؎ 0.03, 4.32 ؎ 0.77 ( P Ͻ 0.01 vs. NL), and 2.20 ؎ 0.39 mmol/l ( P Ͻ 0.01 vs. NL), and plasma LDL cholesterol (LDL-C) levels were 2.34 ؎ 0.22, 2.48 ؎ 0.26, and 5.35 ؎ 0.48 mmol/l ( P Ͻ 0.01 vs. NL), respectively. HTG and CHL had significantly ( P Ͻ 0.05) increased levels of total plasma apoC-I (12.5 ؎ 1.2 and 12.4 ؎ 1.3 mg/dl, respectively) versus NL (7.9 ؎ 0.6 mg/dl), due to significantly ( P Ͻ 0.01) elevated levels of VLDL apoC-I (5.8 ؎ 0.8 and 4.5 ؎ 0.8 vs. 0.3 ؎ 0.1 mg/dl). HTG and CHL also had increased rates of VLDL apoC-I transport (i.e., production) versus NL: 2.29 ؎ 0.34 and 3.04 ؎ 0.53 versus 0.24 ؎ 0.11 mg/kg.day ( P Ͻ 0.01), with no significant change in VLDL apoC-I residence times (RT): 1.16 ؎ 0.12 versus 0.69 ؎ 0.06 versus 0.74 ؎ 0.17. Although HDL apoC-I concentrations were not significantly lower in HTG and CHL versus NL, HDL apoC-I rates of transport were inversely related to plasma and VLDL-TG levels ( r ؍ ؊ 0.63 and ؊ 0.62, respectively, P Ͻ 0.05).
American Journal of Transplantation, 2004
The study was designed to identify a subset of heart transplant (HT) recipients who could benefit... more The study was designed to identify a subset of heart transplant (HT) recipients who could benefit from the administration of targeted antifungal prophylaxis and to evaluate the efficacy of oral itraconazole as the preventive drug. We have analyzed the risk factors for invasive aspergillosis (IA) in our entire population of HT recipients (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) and also the role of oral itraconazole prophylaxis that was provided to all patients since 1995 [400 mg q.d. of itraconazole oral (PO) for 3-6 months]. There were 24 cases of IA. Our main results indicate that the independent risk factors for IA after heart transplantation are: re-operation (RR 5.8; 95% CI 1.8-18, p = = 0.002), cytomegalovirus (CMV) disease (RR 5.2; 95% CI 2-13.9, p = = 0.001), post-transplant hemodialysis (RR 4.9; 95% CI 1.2-18, p = = 0.02), and the existence of an episode of IA in the HT program 2 months before or after the transplantation date (RR 4.6; 95% CI 1.5-14.4, p = = 0.007). Itraconazole prophylaxis showed an independent protective value against developing IA (RR 0.2; 95% CI 0.07-0.9, p = = 0.03) and also determined a significantly prolonged 1-year survival (RR 0.5; 95% CI 0.3-0.8, p = = 0.01). We believe that antifungal prophylaxis in heart transplant patients should be offered at least to patients with one or more of these predisposing conditions.
Clinical Infectious Diseases, 2005
Tuberculosis is a serious opportunistic infection that may affect transplant recipients. The inci... more Tuberculosis is a serious opportunistic infection that may affect transplant recipients. The incidence of tuberculosis among such persons is 20-74 times higher than that for the general population, with a mortality rate of up to 30%. The most common form of acquisition of tuberculosis after transplantation is the reactivation of latent tuberculosis in patients with previous exposure. Clinical presentation is frequently atypical and diverse, with unsuspected and elusive sites of affection. Manifestations include fever of unknown origin and allograft dysfunction. Coinfection with other pathogens is not uncommon. New techniques, such as PCR and quantification of interferon- gamma , have been developed to achieve more-rapid and -accurate diagnoses. Treatment requires control of interactions between antituberculous drugs and immunosuppressive therapy. Prophylaxis against latent tuberculosis is the main approach to treatment, but many issues remain unsolved, because of the difficulty in identifying patients at risk (such as those with nonreactive purified protein derivative test results) and the toxicity of therapy.
Journal of Lipid Research, 2003
Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptor... more Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptors, lipid transfer protein, lipolytic enzymes and HDL apolipoproteins. In order to better define the role of HDL apolipoproteins in determining plasma HDL concentrations, the aims of the present study were: a ) to compare the in vivo rate of plasma turnover of HDL apolipoproteins [i.e., apolipoprotein A-I (apoA-I), apoC-I, apoC-III, and apoE], and b ) to investigate to what extent these metabolic parameters are related to plasma HDL levels. We thus studied 16 individuals with HDL cholesterol levels ranging from 0.56-1.66 mmol/l and HDL apoA-I levels ranging from 89-149 mg/dl. Plasma kinetics of HDL apolipoproteins were investigated using a primed constant (12 h) infusion of deuterated leucine. Plasma HDL apolipoprotein levels were 41.8 ؎ 1.5, 9.7 ؎ 0.5, 4.9 ؎ 0.5, and 0.7 ؎ 0.1 mol/l for apoA-I, apoC-I, apoC-III and apoE. Plasma transport rates (TRs) were 388.6 ؎ 24.7, 131.5 ؎ 12.5, 66.5 ؎ 9.1, and 31.4 ؎ 3.3 nmol·kg ؊ 1 ·day ؊ 1 ; and residence times (RTs) were 5. respectively. HDL cholesterol and apoA-I levels were significantly correlated with HDL apoA-I RT ( r ؍ 0.69 and r ؍ 0.56), and were not significantly correlated with HDL apoA-I TR. In contrast, HDL apoC-I, apoC-III, and apoB levels were all positively related to their TRs and not their RTs. HDL apoC-III TR was postively correlated with levels of HDL apoC-III ( r ؍ 0.73, P Ͻ 0.01), and with those of HDL cholesterol and apoA-I ( r ؍ 0.54 and r ؍ 0.53, P Ͻ 0.05, respectively). HDL apoC-III TR was in turn related to HDL apoA-I RT ( r ؍ 0.51, P Ͻ 0.05). Together, these results provide in vivo evidence for a link between the metabolism of HDL apoC-III and apoA-I, and suggest a role for apoC-III in the regulation of plasma HDL levels. -Cohn, J. S., R. Batal, M. Tremblay, H. Jacques, L. Veilleux, C. Rodriguez, O. Mamer, and J. Davignon. Plasma turnover of HDL apoC-I, apoC-III, and apoE in humans: in vivo evidence for a link between HDL apoC-III and apoA-I metabolism. J. Lipid Res. 2003Res. . 44: 1976Res. -1983 Supplementary key words apolipoprotein C-I • triglyceride • cholesterol • atherosclerosis • stable isotope • lipoprotein metabolism Abbreviations: CHD, coronary heart disease; HL, hepatic lipase; SR-BI, scavenger receptor class B type I; TR, transport rate; TRL, triglyceride-rich lipoprotein.
Atherosclerosis, 2004
Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabol... more Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabolism. In order to further investigate the plasma metabolism of apoC-III in hypertriglyceridemic subjects, we have studied the plasma kinetics of VLDL apoC-III, HDL apoC-III and total plasma apoC-III with a primed constant intravenous infusion of deuterated leucine in a group of male patients with mixed hyperlipidemia (type IIb hyperlipoproteinemia, HLP, n = 6) and in a group with type III HLP (n = 6). Compared to normolipidemic control subjects (n = 5), patients with type IIb and type III HLP had significantly higher levels of plasma TG (0.89 ± 0.15 mmol/l vs 2.56 ± 0.40 mmol/l vs 8.76 ± 1.39 mmol/l, respectively, P < 0.01), plasma apoC-III (9.5 ± 0.8 mg/dl vs 20.8 ± 2.5 mg/dl vs 41.7 ± 5.6 mg/dl, P < 0.01) and VLDL apoC-III (3.6 ± 0.8 mg/dl vs 14.6 ± 2.2 mg/dl vs 35.4 ± 5.1 mg/dl, P < 0.01). VLDL apoC-III production rates were significantly elevated in type IIb and type III patients (1.35 ± 0.23 mg kg −1 day −1 vs 3.53 ± 0.43 mg kg −1 day −1 vs 5.60 ± 0.78 mg kg −1 day −1 , P < 0.01), as were total plasma apoC-III production rates (1.80 ± 0.22 mg kg −1 day −1 vs 4.16 ± 0.44 mg kg −1 day −1 vs 7.26 ± 0.74 mg kg −1 day −1 , P < 0.01). VLDL apoC-III but not total plasma apoC-III fractional catabolic rates were reduced in type IIb and type III patients. Together with our previous results showing an increase of apoC-III production in patients with type IV HLP, and in overweight subjects with reduced insulin sensitivity, our data suggest that increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia.
Journal of Lipid Research, 2002
ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediate... more ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediated uptake of plasma triglyceride-rich lipoproteins, inhibition of cholesteryl ester transfer activity, and mediation of tissue fatty acid uptake. Since little is known about the rate of production and catabolism of plasma apoC-I in humans, the present study was undertaken to determine the plasma kinetics of VLDL and HDL apoC-I using a primed constant (12 h) intravenous infusion of deuterium-labeled leucine. Data were obtained for 14 subjects: normolipidemics (NL, n ؍ 4), hypertriglyceridemics (HTG, n ؍ 4) and combined hyperlipidemics (CHL, n ؍ 6). Plasma VLDL triglyceride (TG) levels were 0.59 ؎ 0.03, 4.32 ؎ 0.77 ( P Ͻ 0.01 vs. NL), and 2.20 ؎ 0.39 mmol/l ( P Ͻ 0.01 vs. NL), and plasma LDL cholesterol (LDL-C) levels were 2.34 ؎ 0.22, 2.48 ؎ 0.26, and 5.35 ؎ 0.48 mmol/l ( P Ͻ 0.01 vs. NL), respectively. HTG and CHL had significantly ( P Ͻ 0.05) increased levels of total plasma apoC-I (12.5 ؎ 1.2 and 12.4 ؎ 1.3 mg/dl, respectively) versus NL (7.9 ؎ 0.6 mg/dl), due to significantly ( P Ͻ 0.01) elevated levels of VLDL apoC-I (5.8 ؎ 0.8 and 4.5 ؎ 0.8 vs. 0.3 ؎ 0.1 mg/dl). HTG and CHL also had increased rates of VLDL apoC-I transport (i.e., production) versus NL: 2.29 ؎ 0.34 and 3.04 ؎ 0.53 versus 0.24 ؎ 0.11 mg/kg.day ( P Ͻ 0.01), with no significant change in VLDL apoC-I residence times (RT): 1.16 ؎ 0.12 versus 0.69 ؎ 0.06 versus 0.74 ؎ 0.17. Although HDL apoC-I concentrations were not significantly lower in HTG and CHL versus NL, HDL apoC-I rates of transport were inversely related to plasma and VLDL-TG levels ( r ؍ ؊ 0.63 and ؊ 0.62, respectively, P Ͻ 0.05).