Value of mycophenolic acid trough level monitoring after lung transplantation.
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Drug Monitoring↗
Biomedical subjects
E Tschernko
Publications and source records attributed to E Tschernko.
Is long-term functional outcome after lung volume reduction surgery predictable?
OBJECTIVE: The aim of this retrospective study was to analyze which preoperative parameters might predict a persistent improvement in forced expiratory volume in 1 s (FeV1) 1 year after surgery. METHODS: Seventy consecutive lung volume reduction surgery (LVRS) patients (age, 56.5+/-1.2 years) with a follow-up period of at least 1 year were analyzed (from September 1994 to September 1997). The patients were described by lung function tests, blood gas analysis, ventilatory mechanics (intrinsic positive endexpiratory pressure (PEEP)) and morphometric data (degree of heterogeneity, DHG; degree of hyperinflation, DHI; severity of parenchymal destruction, SPD) preoperatively. Based on the postoperative course of FeV1 (percentual increase compared with preoperative values, % increase), patients were divided into four groups: group A, (n=21) no improvement (FeV1</=20% increase); group B, (n=10) FeV1>/=20% increase, which declined to preoperative values after 1 year; group C, (n=18) FeV1, 20-40% increase, sustaining at 1 year; group D, (n=21) FeV1>/=40% increase, sustaining at 1 year. The statistics comprised of analysis of variance (ANOVA) and chi-square testing, with values presented as means+/-SEM. RESULTS: No differences were found for lung function parameters (FeV1: 27.7+/-2.7, 26.0+/-2.5, 23. 9+/-2.2 and 23.9+/-1.9% predicted, in groups A, B, C and D, respectively). Arterial blood gas levels preoperatively revealed significant differences between the groups; the arterial pO(2) was 66.2+/-1.2 mmHg in groups A+B compared with 61.8+/-1.5 mmHg in groups C+D (P=0.030). The arterial pCO(2) was 39.2+/-1.1 mmHg in groups A+B compared with 43.3+/-1.5 mmHg in groups C+D (P=0.038). The morphometric data had a strong trend towards higher heterogeneity in groups C and D. Marked DHI was found in 59 and 81% of patients in groups A+B versus C+D, respectively (P=0.121). Marked DHG was present in 22 and 54% of patients in groups A+B versus C+D, respectively (P=0.010). CONCLUSION: Preoperative arterial pO(2) and pCO(2), and the DHG are predictors for long-term benefit after LVRS with regard to the FeV1, 1 year postoperatively.
Analysis of Variance↗
Neural drive to the diaphragm after lung volume reduction surgery.
STUDY OBJECTIVES: The aim of this study was to investigate prospectively the changes in neural drive to the diaphragm in the first year after lung volume reduction surgery (LVRS) in patients with COPD. PATIENTS AND METHODS: In 14 patients with severe emphysema (mean +/- SD; age, 53.7 +/- 8.3 years; FEV(1), 0.64 +/- 0. 18 L; residual volume [RV], 5.33 +/- 1.25 L; PaO(2), 62.3 +/- 9.0 mm Hg; PaCO(2), 39.0 +/- 6.0 mm Hg), we assessed lung function, arterial blood gases, maximal exercise capacity (Wmax), and oxygen uptake (f1.gif" BORDER="0">O(2)max); intrinsic positive end-expiratory pressure (PEEPi); diaphragmatic strength (transdiaphragmatic pressure, Pdisniff) and endurance capacity (tlim); central diaphragmatic drive assessed by root mean square analysis of the esophageal electromyogram (rmsdia); and isotime dyspnea during loaded breathing tests (BS). RESULTS: Despite a significant increase (expressed as a percentage of baseline) in FEV(1) (40.6%) and a decrease in RV (30.0%) and PEEPi (75.7%) 1 month after LVRS, the improvements in Wmax (31.2%) and f1.gif" BORDER="0">O(2)max (13.7%); Pdisniff (25.4%) and tlim (64.9%); rmsdia (34.6%); and BS (21.7%) did not reach statistical significance (p < 0.05) until 6 months after LVRS. Arterial blood gases did not change significantly. Significant correlations were found between decrease in rmsdia and changes in PEEPi (r = 0.69), Wmax (r = -0.56), Pdisniff (r = -0.65), tlim (r = -0.59), and BS (r = 0.71) 6 months after LVRS. CONCLUSIONS: Our results show that LVRS is able to increase the efficacy of the respiratory pump and by this way reduce ventilatory drive and respiratory effort sensation.
Diaphragm↗
Morphologic grading of the emphysematous lung and its relation to improvement after lung volume reduction surgery.
BACKGROUND: The morphologic criteria for lung volume reduction surgery, such as severity and heterogeneity of disease, differ widely between patients, and this makes any comparison of functional results between centers difficult. Here we present a morphologic scoring system and describe its possible relation to functional results after lung volume reduction operations. METHODS: Between September 1994 and December 1996, 47 consecutive patients underwent bilateral lung volume reduction operations. The morphology of emphysema was quantified with standard chest roentgenograms and computed tomographic imaging, which were used to define the following four variables: degree of hyperinflation (grade 0 to 4), degree of impairment in diaphragmatic mechanics, degree of heterogeneity (grade 0 to 4), and severity of parenchymal destruction (range, 0 to 48). RESULTS: All four variables showed good reproducibility. Degree of heterogeneity had a significant influence on functional improvement in terms of forced expiratory volume in 1 second (p = 0.0413, r2 = 0.11). Severity of parenchymal destruction was significantly associated with 30-day mortality: patients who died after operation (n = 4) had a severity of parenchymal destruction of 28.4 +/- 2.1 compared with 21.3 +/- 1.0 for those who survived (n = 43) (p = 0.003). CONCLUSIONS: This morphologic scoring system is easy to use, is reproducible, and allows quantification of the morphology of emphysema, thereby allowing definition of different patient subgroups. Such an exact morphologic quantification may help in the comparison of functional results between centers. Furthermore, the risk factors for certain morphologic subgroups, such as patients with a homogeneous distribution pattern, may be clarified in the future.
Adult↗
Chronic hypercapnia should not exclude patients from lung volume reduction surgery.
OBJECTIVE: Chronic hypercapnia is still considered to increase the risk for perioperative mortality and therefore to be a contraindication for lung volume reduction surgery (LVRS). The aim of this study was to analyse the influences of hypercapnia upon postoperative outcome. METHODS: The functional improvement (preop vs. 3 months postop) and clinical outcome was studied in 22 patients with chronic hypercapnia (preoperative arterial pCO2 > or = 45 mmHg) who underwent LVRS between 9/94 and 2/97 and were compared to all other patients (n = 58) without hypercapnia. Data are expressed as the mean +/- SEM. RESULTS: The 30-day mortality was 9.1% (2/22) in patients with chronic hypercapnia (HC) and 5.2% (3/58) in patients with normal arterial pCO2 levels (control) (P = n.s). The stay on the ICU (3.5 +/- 0.8 vs. 2.1 +/- 0.3 days) and duration of chest drainage (7.3 +/- 1.2 vs. 7.2 +/- 0.8 days) was similar between both groups (HC vs. control) (P = n.s). The preoperative lung function (% of predicted) and blood gas (mmHg) parameters were significantly worse in HC patients compared to control patients. In both groups significant functional improvements were observed: FeV1 in the control group increased by 37% within the first 3 months (29.1 +/- 1.7% of predicted vs. 39.9 +/- 3.1% of predicted, P = 0.0198). In the HC group, FeV1 increased by 73% which was even higher than in the controls (19.5 +/- 1.5% of predicted vs. 33.7 +/- 4.7% of predicted, P = 0.0385). All patients of both groups who died perioperatively had a significantly higher severity of parenchymal destruction than those who survived (P = 0.0277 and 0.0380, respectively). CONCLUSIONS: Patients with chronic hypercapnia alone, had no significantly higher mortality and morbidity, and therefore should not be excluded from LVRS. However, the presence of additional risk factors, such as homogeneity of disease, high degree of parenchymal destruction or pulmonary hypertension should be considered as contraindications for the procedure.
Case-Control Studies↗
Functional improvement after volume reduction: sternotomy versus videoendoscopic approach.
BACKGROUND: Volume reduction has been proved to increase ventilatory mechanics in diffuse, nonbullous lung emphysema. However, the best approach is still controversial. METHODS: We retrospectively compared the perioperative data of and functional results in 15 patients having sternotomy (group I) with those of 15 patients having a videoendoscopic approach (group II). RESULTS: The 30-day mortality was 2 patients in group I and 1 patient in group II. Mean duration of chest tube drainage was 8.7 +/- 1.8 days and 8.0 +/- 1.9 days and mean hospital stay, 12.3 +/- 1.9 and 12.5 +/- 2.1 days in groups I and II, respectively. Work of breathing decreased from 1.89 +/- 0.33 J/L and 1.76 +/- 0.22 J/L preoperatively to 0.75 +/- 0.06 J/L and 0.8 +/- 0.06 J/L (p < 0.01 and p < 0.05, respectively) after 3 months; and intrinsic positive end-expiratory pressure decreased from 7.15 +/- 1.31 cm H2O and 6.24 +/- 1.33 cm H2O to preoperatively 0.79 +/- 0.46 cm H2O and 1.13 +/- 0.44 cm H2O (p < 0.005 and p < 0.01, respectively) after 3 months in groups I and II, respectively. Forced expiratory volume in 1 second increased from preoperative values of 21.6% +/- 2.9% and 25.3% +/- 2.4% of predicted to 34.5% +/- 5.0% and 40.9% +/- 7.5% of predicted after 3 months (p < 0.05 in both groups) in groups I and II, respectively. CONCLUSIONS: Both surgical approaches resulted in similar substantial improvement in lung function and physical fitness. The incidence of air leakage, the duration of chest tube drainage, and the hospital stay were the same for both procedures.
Case-Control Studies↗
Functional improvements in ventilatory mechanics after lung volume reduction surgery for homogeneous emphysema.
OBJECTIVE: Between September 1994 and August 1996 Lung Volume Reduction Surgery (LVRS) was performed through median sternotomy, videoendoscopically or by thoracotomy in 54 consecutive patients (age 34-69 years, mean 48 years). METHODS: The areas with the most destroyed lung parenchyma were resected by means of linear stapling devices. A total of 5 patients died postoperatively due to aspiration pneumonia, multiorgan failure and acute hepatic failure respectively. A marked functional improvement and increase in quality of life was observed in the remaining patients. RESULTS: Residual volume decreased from 317.0 +/- 12.4% of predicted (%p) preoperatively to 226.2 +/- 8.8%p within the first month (P = 0.0001). FeV1 significantly increased from 23.7 +/- 1.3%p preoperatively to 36.3 +/- 4.1%p during the first 6 months postoperatively (P = 0.0016). Radiological signs of hyperinflation and distention of the thorax preoperatively improved to a more dome shaped diaphragm and narrowed intercostal spaces. These morphologic changes resulted in better ventilatory muscle function. The intrinsic PEEP significantly decreased from 5.92 +/- 0.64 cm H2O preoperatively to 1.70 +/- 0.25 cm H2O postoperatively (P = 0.0001). The work of breathing decreased from 1.58 +/- 0.09 J/l preoperatively to 0.99 +/- 0.07 J/l postoperatively (P = 0.0001). CONCLUSIONS: In conclusion, LVRS is an excellent therapeutic option for patients with homogeneous emphysema with additional signs of severe hyperinflation.
Female↗
Renal and ocular hemodynamic effects of insulin.
There is evidence that the vasodilator action of insulin is mediated by the release of nitric oxide (NO). We hypothesized that euglycemic hyperinsulinemia might increase renal and ocular blood flow, and that the vasodilator capacity of insulin might be NO-dependent. Euglycemic insulin clamps were performed in 10 healthy subjects. Sixty minutes after the start of insulin administration, an intravenous coinfusion of N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, or of norepinephrine (NE), an endothelium-independent vasoconstrictor, was started. Renal plasma flow was measured by para-aminohippurate (PAH) clearance method. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. Renal plasma flow and ocular fundus pulsations were increased by insulin. L-NMMA almost completely abolished the vasodilative effects of insulin, whereas the effects of combined infusion of insulin and NE were approximately the sum of the hemodynamic changes induced by each agent alone. The results show that during euglycemic hyperinsulinemia, renal and ocular blood flow are increased, which may be mediated either by a local vasodilator effect or a systemic increase in flow. The hemodynamic effects of insulin in the kidney and the eye are at least partially dependent on NO synthesis. Because the insulin plasma levels we obtained are in the high physiological range, it may be assumed that insulin plays a role in renal and ocular blood flow regulation.
Adult↗
Lung retransplantation: institutional report on a series of twenty patients.
BACKGROUND AND METHODS: Between 1986 and 1995, 124 isolated lung and 29 combined heart-lung transplantations were performed at our institution. Twenty of these procedures were retransplantations. Four different types of reoperations were performed: ipsilateral single lung retransplantation (n = 3), single lung retransplantation after bilateral or heart-lung transplantation (n = 7), bilateral retransplantation after bilateral lung transplantation (n = 5), and bilateral retransplantation after single lung transplantation (n = 5). Nine patients underwent retransplantation while still in the intensive care unit after the primary transplantation. Indications for retransplantation in these patients were primary graft failure in seven and bronchial complications in two patients. In 11 patients a late retransplantation (3 to 30 months after the first transplantation) was performed. The indication was obliterative bronchiolitis in nine and late bronchial complications in two patients. Overall, 13 patients were ventilator-dependent before retransplantations. RESULTS: Overall survival was 52.8% and 36.2% at 1 and 12 months, respectively. For early retransplantation the survival rate at 1 month was only 22.2% with 2 patients alive 5 and 22 months after the retransplantation. For late retransplantation survival at 1 and 12 months was 70.7% and 50.5%, respectively (p = 0.07), and the longest surviving patient was at 47 months after retransplantation at the time this article was written. Patients who were ventilator-dependent before retransplantation had a significantly worse outcome (survival at 1 and 12 months: 33.8% and 25.4% versus 85.7% and 57.1% for all others, p = 0.055). Of those surviving to date, all were in New York Heart Association class I or II. CONCLUSIONS: We conclude that late and elective lung retransplantation achieves acceptable results when offered to patients with chronic pulmonary dysfunction but with otherwise stable conditions. In view of the poor results, early acute retransplantation should be performed much more restrictively.
Adolescent↗
[Lung volume reduction in emphysema--experience and results of the first 2 years].
Between September 1994 and August 1996 Lung Volume Reduction Surgery (LVRS) was performed through median sternotomy, videoendoscopically or by thoracotomy in 60 patients (age 33 to 80 years, mean 56.7 years). All these patients had severe emphysema despite maximal conservative and physical therapy. The areas with the most destroyed lung parenchyma were resected by means of linear stapling devices, 3 patients (20%) out of 15 who were operated via sternotomy died postoperatively due to aspiration pneumonia, multiorgan failure and acute hepatic failure. In the videoendoscopic group with 45 patients, 2 patients (4.4%) died due to multiorgan failure and cardiorespiratory failure. 72.7% of the remaining patients showed a significant functional improvement (postoperative FEV1 > 130% of the preoperative value) with a marked decrease of dyspnea. There was no significant improvement in 23.7% of the patients (postoperative FEV1 = 90 to 110% of the preoperative value) and 3.6% of the patients had a functional deterioration. Residual volume decreased from 317.0 +/- 12.4% of predicted (%p) preoperatively to 226.2 +/- 8.8 %p within the first month (p = 0.0001). FEV1 significantly increased from 23.7 +/- 1.3 %p preoperatively to 36.6 +/- 4.1 %p during the first 6 months postoperatively (p = 0.0016). Radiological signs of hyperinflation and distention of the thorax preoperatively improved to narrowed intercostal spaces and a more shaped diaphragm. These morphological changes resulted in better ventilatory muscle function. The intrinsic PEEP significantly decreased from 5.92 +/- 0.64 cm H2O preoperatively to 1.70 +/- 0.25 cm H2O postoperatively (p = 0.0001). The work of breathing decreased from 1.58 +/- 0.09 J/l preoperatively to 0.99 +/- 0.07 J/l postoperatively (p = 0.0001). In conclusion, LVRS is an excellent therapeutic option for patients with severe emphysema and additional signs of severe hyperinflation with significant postoperative functional improvement and marked increase in quality of life.
Female↗
[Surgical technique and results of bilateral volume reduction in patients with pulmonary emphysema].
Between 9/94 and 3/96 volume reduction was performed on 29 patients by a median sternotomy or videoendoscopic approach. Perioperative mortality occurred in three patients. The residual volume decreased within the first month from preoperative 308.8 +/- 13.4% of predicted (%p) to 217.9 +/- 12.7%p (p < 0.05). FeV1 significantly improved to 37.9 +/- 4.6%p after 3 months, versus 23.5 +/- 1.8%p preoperatively (p < 0.05). Intrinsic PEEP substantially decreased from 6.69 +/- 0.91 cm H2O preop to 0.93 +/- 0.28 cm H2O initially after surgery (p < 0.005). This was paralleled by the work of breathing: 1.78 +/- 0.2 J/l preoperatively versus 0.77 +/- 0.04 J/l postoperatively (p < 0.005). In conclusion, VR is a safe and successful option for patients with pulmonary emphysema, who show signs of marked hyperinflation.
Female↗
Recovery of intraoperatively shed blood in aortoiliac surgery: comparison of cell washing with simple filtration.
To regain blood shed intraoperatively, two different systems are clinically established: washing and centrifuging red blood cells to produce autologous erythrocyte concentrates and devices for immediate reinfusion of whole blood after mere filtration. In a prospective-randomised study to compare both methods regarding their efficiency, adverse effects, and economy, 20 patients of our department undergoing elective aortoiliac surgery received intraoperative autotransfusion by means of either cell-washing (CS) or salvage of whole blood (WB). Patients were preoperatively randomized into one of the two groups and were evaluated with respect to standard metabolic and haematological laboratory parameters preoperatively, during surgery, after transfer into the recovery room, 24 h after surgery, after transfer into the recovery room, 24 h after surgery, and at discharge. Both patient groups were well comparable in demographics, preoperative laboratory data, and indication for operation. Handling was easier, the set-up time was shorter with the whole blood filtration device (10.2 +/- 2.3 versus 21 +/- 1.9 min, p = 0.0023), and no additional personnel was needed to run the system. The whole blood device also allowed a greater percentage of aspirated blood to be returned intraoperatively compared to cell washing (73.5% +/- 7.2 versus 51.1% +/- 6.5, p = 0.03). Thrombocytopenia occurred in 7 (CS) and 3 (WB) patients intraoperatively with a significant difference in platelet count between the two groups (118 +/- 17 [CS] versus 170 +/- 12 [WB]*10(9)/L, p = 0.025). Expected changes in the perioperative course of the clotting parameters such as highly increased PTT levels and moderately prolonged prothrombin times occurred in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Hepatic regulation of renal function.
Despite apparently conflicting reports in the past, the bulk of evidence presently available points to a significant role for the liver in the regulation of renal function. Hepatic regulation of renal function may involve both a hepatorenal reflex and a liver-borne diuretic factor (LBDF and/or 'glomerulopressin'). The hepatorenal reflex is elicited by an increase in intrahepatic pressure, and/or certain amino acids in portal venous blood. It is transmitted by serotonin in the liver and presumably by noradrenaline in the kidney. It leads to a marked decrease in renal blood flow, glomerular filtration and urinary flow rate. The evidence for the LBDF is still circumstantial. The LBDF may be stimulated by glucagon and adenosine. It leads to a marked increase of renal blood flow, glomerular filtration rate and urinary output. Amongst the conditions presumed to be associated with altered hepatic regulation of renal function are postprandial hyperfiltration, and the deterioration of renal function which occurs in liver disease, cardiac insufficiency and cardiovascular shock.
Amino Acids↗
Proteins, the liver and the kidney--hepatic regulation of renal function.
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Animals↗
Cellular mechanisms of bradykinin-induced hyperpolarization in renal epitheloid MDCK-cells.
Previous studies have demonstrated that bradykinin hyperpolarizes the cell membrane of subconfluent MDCK cells by increase of the potassium conductance. The present study has been performed to elucidate the intracellular mechanisms involved. To this end, the effects of bradykinin on the potential difference across the cell membrane (PD), on formation of inositol phosphates, and on intracellular calcium concentration (Cai) have been analyzed in cells without or with pretreatment with pertussis toxin or 12-O-tetradecanoylphorbol 13-acetate diester (TPA). In untreated cells, bradykinin leads to a transient increase of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, increase of Cai, activation of potassium channels and hyperpolarization of the cell membrane. The effects of bradykinin on PD and Cai are still present in the absence of extracellular calcium. In cells pretreated with pertussis toxin the effect of bradykinin on inositol trisphosphate formation is almost abolished but bradykinin still leads to a transient increase of Cai and PD in the presence and absence of extracellular calcium. In cells pretreated with TPA the bradykinin-induced increase of inositol trisphosphate formation is blunted, the bradykinin-induced increase of Cai abolished, but the bradykinin-induced hyperpolarization still present. The observations indicate that bradykinin increases Cai in part by phorbol ester and pertussis toxin sensitive activation of phospholipase C. In addition, bradykinin is capable of enhancing Cai by utilizing pertussis toxin insensitive mechanisms. Furthermore, bradykinin is able to transiently enhance the potassium conductance without a general increase of intracellular calcium.
Animals↗
Serotoninergic hepatorenal reflex regulating renal glomerular filtration rate.
Infusion of glutamine (2 mumol/min) into the superior mesenteric vein leads to a decrease of renal glomerular filtration rate (GFR) and urinary flow rate (V), whereas infusion of identical amounts of glutamine into the jugular vein does not significantly alter GFR or V. The effect of mesenteric glutamine is mimicked by mesenteric infusion of 5 nmol/min serotonin and is abolished in the presence of 20 nmol/min methysergide. The effect of mesenteric serotonin is almost abolished after transection of vagal hepatic nerves. The observations point to a serotoninergic hepatorenal reflex regulating renal function.
Animals↗
Hepatorenal reflex regulating kidney function.
In anesthetized male rats, infusion of glutamine (2 mumol/min) into the superior mesenteric vein at a rate known to induce liver cell swelling leads to marked decreases in renal glomerular filtration rate, renal para-aminohippurate clearance and urinary flow rate. Glutamine infused at identical rates into the jugular vein does not elicit any of these effects. The effect of glutamine is mimicked by serine but not by glutamate. Spinal transection, renal denervation or section of the vagal hepatic nerves abolishes the effect of mesenteric venous glutamine infusion. Mesenteric application of glucagon (1 ng/min) or of both glutamine and glucagon enhances glomerular filtration rate and urinary flow rate. Infusion of 1 ng/min glucagon through the jugular vein does not significantly alter glomerular filtration rate or urinary flow rate. The data disclose a powerful liver-borne mechanism regulating kidney function that is mediated by the hepatorenal innervation.
Animals↗
Ion channels in Madin-Darby canine kidney cells.
Ion channels in Madin-Darby canine kidney cells serve transepithelial chloride transport and probably cell volume regulation. Three distinct potassium channels and one anion channel have been revealed by patch clamp studies in Madin-Darby canine kidney cells. The potassium channels are activated by an increase in intracellular calcium activity. A number of hormones activate the potassium channels by an increase in intracellular calcium activity. However, under certain conditions the hormones hyperpolarize the cell membrane without increasing intracellular calcium activity sufficiently to activate the calcium-sensitive potassium channels. Thus, the hormones may activate potassium channels via another, as yet undefined, intracellular mechanism. The anion channel is stimulated by cAMP. Another factor modifying channel activity is cell volume: cell swelling leads probably to subsequent activation of potassium and anion channels. The net result is a variable transient hyperpolarization followed by a sustained depolarization of the cell membrane.
Animals↗