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- Gullestad, Lars, et al.
(author)
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Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial
- 2010
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In: Transplantation. - : Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 89:7, s. 864-872
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Journal article (peer-reviewed)abstract
- Background. The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. Methods. In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate greater than= 20 mL/min/1.73m(2) and less than90 mL/min/1.73 m(2)) greater than1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. Results. Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (Pless than0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). Conclusion. Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.
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- Rundqvist, Håkan Claes, et al.
(author)
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Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise
- 2017
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 123:6, s. 1501-1515
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Journal article (peer-reviewed)abstract
- Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by one month, twelve healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint and blood samples were taken repeatedly during the experiment. Fractional synthetic rate (FSR) was measured by continuous infusion of L-[(2)H5]-phenylalanine up to 200 min postexercise. The mRNA and protein expression of SNAT2 were both 1.4-fold higher (P < 0.05) after nutrient intake compared to placebo at 200 min postexercise. Phosphorylated Akt, mTOR and p70S6k was 1.7- to 3.6-fold higher (P<0.01) 80 min after the last sprint with nutrient ingestion as compared to placebo. In addition, FSR was higher (P<0.05) with nutrients when plasma phenylalanine (FSRplasma) was used as a precursor, but not when intracellular phenylalanine (FSRmuscle) was used. Significant correlations were also found between FSRplasma on the one hand and plasma leucine and serum insulin on the other hand in the nutrient condition. The results show that nutrient ingestion induces the expression of the amino acid transporter SNAT2, stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis following sprint exercise.
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- Selimovic, Nedim, 1960, et al.
(author)
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Assessment of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension.
- 2007
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In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 26:9, s. 927-34
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Journal article (peer-reviewed)abstract
- BACKGROUND: Assessment of pulmonary artery pressures, cardiac output (CO) and pulmonary vascular resistance (PVR) is crucial in the management of patients with pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether Doppler echocardiography can be used to determine PVR in patients with PAH. METHODS: Forty-two patients were included and Doppler echocardiography was performed simultaneously (n = 22) and non-simultaneously (n = 60) with right heart catheterization. The tricuspid regurgitation velocity was used to estimate pulmonary arterial peak systolic and diastolic (PADP) pressures (Bernoulli equation). At the time of pulmonary valve opening, right ventricular pressure equals PADP. The tricuspid regurgitation velocity at the time of pulmonary valve opening was measured by superimposing the time from the QRS to the onset of pulmonary flow on the tricuspid regurgitation velocity envelope. Pulmonary capillary wedge pressure, right atrial pressure and CO were assessed using standard Doppler echocardiography methods. Right heart catheterization was performed using Swan-Ganz catheters and thermodilution for CO determination. RESULTS: The differences (mean +/- SD) between catheter and simultaneous/non-simultaneous Doppler echocardiography were 0.3 +/- 0.8 (p = 0.10)/-0.3 +/- 1.1 (p = 0.06) liter/min for CO, 2.9 +/- 5.1 (p = 0.02)/-1.2 +/- 7.4 (p = 0.2) mm Hg for the transpulmonary gradient (TPG) and 0.3 +/- 2.1 (p = 0.65)/0.8 +/- 2.4 (p = 0.02) Wood unit for PVR. The correlation coefficients between catheter and simultaneous/non-simultaneous Doppler echocardiography were 0.86/0.75 for CO, 0.92/0.90 for TPG and 0.93/0.92 for PVR. CONCLUSIONS: A comprehensive hemodynamic assessment that includes CO, TPG and PVR can be provided by Doppler echocardiography in patients with severe pulmonary hypertension.
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- Selimovic, Nedim, 1960, et al.
(author)
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Endothelin-1 across the lung circulation in patients with pulmonary arterial hypertension and influence of epoprostenol infusion.
- 2009
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In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 28:8, s. 808-14
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Journal article (peer-reviewed)abstract
- BACKGROUND: The endothelin-1 (ET-1) system plays a pathophysiologic role in patients with pulmonary arterial hypertension (PAH). Results from previous studies assessing the transpulmonary gradient of ET-1 have been inconsistent. The influence of an intravenous epoprostenol infusion on the transpulmonary ET-1 gradient is unknown. METHODS: In a prospective investigation, serum concentrations of ET-1 were measured in 39 consecutive patients (31 women; mean age, 20-77 years) with pulmonary hypertension (33 with PAH) and compared with 20 controls. The effect of intravenous epoprostenol administration on the transpulmonary gradient of ET-1 was analyzed in 13 patients with pulmonary hypertension. Blood samples were taken simultaneously from the pulmonary artery and radial artery. RESULTS: The serum levels of ET-1 were significantly higher in the arterial (3.9 +/- 1.28 vs 2.53 +/- 0.24 pg/ml, p < 0.001) and mixed venous blood samples (3.9 +/- 1.21 vs 2.52 +/- 0.29 pg/ml, p < 0.001) in patients with pulmonary hypertension than in controls. The arterial/venous ratio of ET-1 in patients (1.0 +/- 0.1) and in the control group (1.0 +/- 0.05) was similar (p = 0.79). During intravenous epoprostenol infusion, there were no changes in the mean transpulmonary ET-1 gradient (0.98 +/- 0.07 vs 0.96 +/- 0.09, p = 0.52), despite significant hemodynamic changes. CONCLUSION: The ET-1 radial artery/pulmonary artery ratio of unity indicates a balanced release and clearance of ET-1 across the lung circulation in controls and in patients with different forms of pulmonary hypertension. ET-1 levels across the pulmonary circulation did not change during epoprostenol infusion.
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| 6. |
- Selimovic, Nedim, 1960, et al.
(author)
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Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension.
- 2009
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In: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 34:3, s. 662-8
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Journal article (peer-reviewed)abstract
- The aim of our study was to assess the levels of growth factors and interleukin (IL)-6 across the pulmonary circulation in patients with pulmonary arterial hypertension (PAH) and correlate them with clinical and haemodynamic data and outcome. Simultaneous arterial and pulmonary arterial blood samples in patients with PAH (n = 44) and controls (n = 20) were obtained during right heart catheterisation. Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta1 and IL-6 were measured using ELISA. Arterial median (interquartile range) values for VEGF, PDGF-BB, TGF-beta1 and IL-6 were significantly higher in patients (377 (218-588) versus 9.0 pg.mL(-1); 1,955 (1,371-2,519) versus 306 (131-502) pg.mL(-1); 26.42 (11.3-41.1) versus 7.0 (1.8-18.4) ng.mL(-1); and 3.98 (0.7-8.1) versus 0.7 pg.mL(-1), respectively; p<0.001 for all variables). There was a consistent step-up of VEGF, PDGF-BB and TGF-beta1 across the lungs in PAH patients (p<0.001, p = 0.002 and p<0.001, respectively), whereas in controls, arterial and pulmonary arterial serum levels of IL-6 and growth factors were similar (statistically nonsignificant). In multivariate analysis, increased IL-6 levels predicted mortality (hazard ratio 1.08 (95% confidence interval 1.02-1.15); p = 0.012). Our findings indicate increased release and/or decreased clearance of growth factors at the lung vascular level, which may contribute to vascular remodelling in PAH.
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