[Myxoid liposarcoma with pericardial metastasis].
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Diagnosis, Differential↗
Biomedical subjects
N Friedel
Publications and source records attributed to N Friedel.
Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts.
BACKGROUND: To assess the chamber localization, subtype distribution, and regulation of human myocardial angiotensin II receptors in heart failure, we determined the binding of angiotensin II, Sar1Ile8-angiotensin II, and the subtype-specific antagonists Dup 753 (AT1-specific) and PD 123319 (AT2-specific) in atria from patients with normal (left ventricular ejection fraction > 55%) or moderately impaired (left ventricular ejection fraction 30% to 55%) cardiac function and in atria and ventricles from explanted end-stage failing hearts. Sarcolemmal and combined fractions, the latter including internalized receptors, were studied. In addition, AT1 mRNA content was analyzed by polymerase chain reaction after reverse transcription. METHODS AND RESULTS: The number of angiotensin II binding sites (Bmax) in sarcolemmal fractions was significantly reduced in explanted end-stage failing hearts in comparison with control subjects and moderate heart failure (Bmax 3.9 +/- 0.8 versus 11.2 +/- 1.7 and 9.6 +/- 0.8 fmol/mg protein, respectively). A comparable 65% reduction in receptor numbers was found in combined fractions from end-stage failing hearts, indicating that the loss of binding sites was not due to their internalization. The dissociation constants were comparable in sarcolemmal and combined fractions and in nonfailing and failing hearts, ranging from 0.5 +/- 0.2 to 1.2 +/- 0.5 nmol/L. In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1. In explanted hearts, comparable ratios of 66 +/- 5% AT2 sites and 34 +/- 5% AT1 sites were found. AT1 cDNA amplification signals by polymerase chain reaction were reduced to about one third of the level in control subjects in end-stage failing hearts. CONCLUSIONS: Angiotensin II receptors in human myocardium are present in relatively low numbers, and AT2 is the predominant subtype. A significant loss of angiotensin II receptors occurs in end stage but not in moderate heart failure. The loss of receptors affects both subtypes to a comparable degree. The data suggest that the decrease in receptor density is due to a decrease in steady-state mRNA abundance.
Binding Sites↗
Interleukin-6 and interleukin-8 concentrations as predictors of outcome in ventricular assist device patients before heart transplantation.
OBJECTIVE: To determine whether the serum concentrations of some circulating cytokines (as highly sensitive markers of inflammation) are of value in predicting the outcome of patients with cardiogenic shock and end-stage heart disease, who undergo ventricular assist device implantation until heart transplantation. DESIGN: Cohort study. SETTING: University teaching hospitals. PATIENTS: Twenty patients with cardiogenic shock or end-stage heart disease were consecutively selected for this study, if assist device implantation was performed as a bridge to heart transplantation. MEASUREMENTS AND MAIN RESULTS: The circulating concentrations of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha were monitored from the beginning to the end of assist device support two to three times a week, using commercial enzyme-linked immunosorbent assays (ELISA). In all patients, circulating IL-6 and IL-8 values were increased shortly after assist device implantation. In patients with uncomplicated courses, IL-6 and IL-8 concentrations decreased after an initial increase and were low at the time of transplantation, whereas serum cytokine concentrations increased and remained increased in the nonsurvivors (survivors vs. nonsurvivors, p < .001). Circulating IL-1 beta and TNF-alpha concentrations were rarely detectable. CONCLUSIONS: Monitoring of IL-6 and IL-8 values during ventricular assist device support provides a means of early identification of high-risk patients that may allow optimization of antimicrobial therapy and selection of the appropriate time for transplantation.
Adolescent↗
Coronary artery bypass grafting and heart transplantation in end-stage coronary artery disease: a comparison of hemodynamic improvement and ventricular function.
Heart transplantation has now become an accepted treatment for end-stage coronary heart disease (CAD). However, the limited supply of suitable donor organs imposes constraints upon the decision of whether patients are selected for transplantation or for coronary artery bypass grafting (CABG). From April 1986 until the end of March 1992, 265 patients with end-stage CAD involving left ventricular ejection fraction (LVEF) 10% to 30% and predominant angina pectoris underwent CABG. All patients received an average of 2.9 +/- 0.3 venous grafts. Intraaortic balloon pumps were implanted in 30 patients (11.3%) who began to develop low cardiac output syndrome intraoperatively. The actuarial survival rate was 87.8% after 2 years and 86.9% after 3 years. LVEF was measured in 35 patients via left heart catheterization 12 months after their operations and was found to have increased from a mean of 23.8% to 38.1%. Left ventricular end-diastolic pressure had decreased from 16.2 mmHg to an average of 12.1 mmHg. Swan-Ganz catheterization was performed on 120 patients 6 months postoperatively. The pulmonary wedge pressure had reduced significantly from 18.1 mmHg to a mean of 12.7 mmHg (p < 0.01). From 1990 until the end of March 1992, 55 patients with CAD and predominant heart failure received transplants. Their 2-year survival rate was 66.3%. Mean LVEF was 55.6% postoperatively. We conclude that CABG is adequate for patients who have end-stage CAD and angina pectoris symptoms, and that it significantly improves hemodynamic functions. Patients suffering predominantly from heart failure (NYHA Class IV) can be transplanted and subsequently regain normal heart function.
Actuarial Analysis↗
Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation.
Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD-support as a bridge to heart transplantation. This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD-support. Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart). We did not find significant differences in preoperative values of immune parameters between groups of survivors (n = 14) and non-survivors (n = 16). All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T-cell activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T-lymphopenia. Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion. These observations point to the reduced antimicrobial immunity ("immunoparalysis") in the non-survivors and may explain the fatal course of infection in these individuals. The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD-patients.
Adolescent↗
Heart transplantation in Berlin--1993 update.
Heart transplantation has become a routine procedure. Surgical techniques have been standardized and triple-drug immunosuppression has proven to be the most effective posttransplantation medical treatment. A shortage of donor organs has remained the major factor inhibiting extensive application of heart transplantation. Improved techniques of organ protection may eventually contribute to an extension of the donor pool. However, it seems to be more important to develop alternative procedures further (artificial heart, xenotransplantation, extended use of conservative surgical or medical treatment). The patient population undergoing heart transplantation will undoubtedly include more older, severely ill, polymorbid patients who are not suitable for alternative procedures. Pediatric heart transplantation may increase in the coming years and mechanical circulatory support will surely gain in importance for both adult and pediatric patients awaiting heart transplantation.
Adolescent↗
Survival predictors in patients with a left ventricular ejection fraction of 10-30% receiving a coronary bypass: analysis of preoperative variables.
A total of 224 patients with angina pectoris and a left ventricular ejection fraction in the range of 10-30% (mean 24.2%) underwent coronary artery bypass grafting between April 1986 and August 1991. These patients received a mean (s.d.) of 2.9 (0.3) aortocoronary vein grafts. The overall operative mortality rate was 8.9%. The 1-, 2- and 3-year survival rates were 87.7%, 86.7% and 85.2%, respectively. Analysis of operative risk factors showed that patients with an end-diastolic left ventricular pressure > 24 mmHg were significantly more at risk (mortality rate 20.0%, P < 0.05) than those with an end-diastolic left ventricular pressure < or = 24 mmHg (mortality rate 6.2%). Patients with a perioperative cardiac index < 2.5 l min-1m-2 had higher mortality (25.4%) than those with a cardiac index > or = 2.5 l min-1m-2 (mortality 1.9%, P < 0.001). The operative mortality rate of patients with a cardiac index < 2.5 l min-1m-2 and an end-diastolic left ventricular pressure > 24 mmHg was 40.5%. Patients with a left ventricular ejection fraction of 10-20% were not significantly more at risk (P > 0.05) than those with a left ventricular ejection fraction of 21-30%.
Adult↗
Local regulation of vascular tone by bradykinin and angiotensin converting enzyme inhibitors.
Part of the vasodilator response to angiotensin converting enzyme (ACE) inhibitors depends on stimulation of bradykinin receptors, but in most studies the anticipated increase in plasma kinin concentration during ACE inhibition was not detected. We investigated the role of local ACE inhibition on endothelial control of vascular tone. Rings of bovine coronary, renal and tail arteries, as well as human coronary arteries, were mounted in organ chambers so that the isometric force could be recorded. The ACE inhibitors, captopril, fosinoprilat, enalaprilat, lisinopril, and ramiprilat alone had no affect on the vascular tone of bovine coronary arteries with endothelium. However, these ACE inhibitors did potentiate relaxations to bradykinin and the slowly degradable bradykinin derivative [Hyp3-Tyr(Me)8]-bradykinin (3 x 10(-11) M). A similar response was observed in human coronary arteries. The response was not observed in rings of any vessel without endothelium, or after incubation with nitro-L-arginine (10(-4) M), or the bradykinin2-receptor antagonists Hoe 140 (10(-8) M). The sensitivity to bradykinin was higher and the potentiating effect of ACE inhibition larger in the bovine coronary artery than in the renal and tail artery. Thus, ACE inhibition causes selective coronary vasodilation by potentiating the bradykinin-induced release of nitric oxide from the endothelium. The related mechanism underlying these effects must occur at the surface or within the arterial wall and seems to be independent of the degradation of the kinins.
Angiotensin-Converting Enzyme Inhibitors↗
[Detectability of pulmonary coin lesions: a comparative assessment of the image quality of a storage phosphor system and a conventional film screen system].
The object of this study was to compare the prototype of a storage phosphor digital radiography system (Siemens) which allows postprocessing image data adjustment with the stored information, with an optimised conventional film system with respect of image quality and diagnostic accuracy. The test objects were pulmonary coin lesions as the search for primary or secondary lung tumours is one of the most frequent clinical requests and the detectability of coin lesions depends very much on their relative contrast against the surrounding area. In order to achieve reproducible results, an anthropomorphic lung phantom was used. Besides the conventional film radiograms the unprocessed digital radiograms and twelve series with variations of the processing parameters were evaluated. To achieve a homogeneous radiation image an anatomically shaped lead-loaded acrylic glass compensation filter was used. With regard to the true-positive demonstration of coin lesions there were no significant differences between the chosen film system and all digital radiograms. Image processing had no recognisable influence on the demonstration of the findings. Coin lesions of 3 mm diameter were detected only by chance; the detectability of lesions of 5 mm and 10 mm in diameter respectively depended mainly on their localisation. Lesions of 15 mm diameter were detected independent of their localisation. The results indicate that the storage phosphorus radiography system is already comparable to an optimised conventional film system concerning the conspicuity of coin lesions. If the image is homogenised by means of an anatomically shaped lead-loaded acrylic glass compensation filter, selective postprocessing adjustment of the digital radiograms for the evaluation of the mediastinum or the lung parenchyma is unnecessary.
Humans↗
Recovery of end-organ failure during mechanical circulatory support.
To evaluate organ recovery during mechanical assistance, respiratory, hepatic and renal function parameters of 40 patients who underwent bridge-to-transplant procedures were reviewed retrospectively. Mechanical circulatory support was indicated if the hemodynamic and clinical status deteriorated despite pharmacotherapy with catecholamines, vasodilators, and intravenous use of the phosphodiesterase inhibitor enoximone. Sequelae of cardiogenic shock such as renal, hepatic and respiratory insufficiency were not considered a contraindication for mechanical support. The analysis of preimplant data such as serum creatinine, liver enzymes and pulmonary gas exchange did not identify any predictive indicator of irreversible organ damage. Functional recovery of preexisting respiratory, hepatic and renal dysfunction was found in 91%, 90%, and 85%, respectively. Subsequent transplantation, however, was affected by the number of failing organs prior to mechanical support. Of 17 patients with isolated organ failure prior to assist, 14 (82%) were transplanted. By contrast, 9 (75%) of 12 with combined failure of two organs, and only 6 (54%) of 11 patients with clinical patterns of three failing organ systems received transplants. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within 10 to 15 days after initiating mechanical assistance.
Adolescent↗
Enoximone in newborns with refractory postoperative low-output states (LOS).
Enoximone was administered to 16 newborns with postoperative, catecholamine-refractory cardiac low-output states in addition to high-dose catecholamine treatment. Haemodynamic changes were assessed at baseline and during treatment. Haemodynamic parameters were improved in 12 newborns ("responders"), 9 of these survived. Three responders died; one from cardiac low-output and 2 from uncorrectable congenital heart disease verified by autopsy. Four newborns did not respond to enoximone therapy ("non-responders") and died. The haemodynamic effects of enoximone were characterized by an increase in cardiac index (+160%, P less than 0.0008), and a fall in right (-26%, P less than 0.0004) and left (-34%, P less than 0.003) atrial pressures. It is concluded that enoximone can be an effective agent in the treatment of cardiac low-output states refractory to high-dose catecholamines in neonates up to 7 months old.
Cardiac Output, Low↗
The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function.
The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.
Adrenergic Agonists↗
Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery.
We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2-adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (1, 2, 4 and 6 micrograms.kg-1.min-1), the dose producing the optimal response was infused for up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean blood pressure was reduced but did not fall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac output following cardiac surgery.
Adrenergic Agonists↗
[Heart transplantation--indications and results].
Heart transplantation has become a standard procedure in the treatment for irreversible heart failure. Criteria for both recipients and donors have been extended. One year survival now reaches 81%. In the immediate postoperative course patients are endangered by infection. In the long-term course coronary artery disease of the transplanted heart becomes the most serious problem. Alteration of liver and kidney function due to chronic medication as well as malignancies and hypertension also occur. In case of chronic transplant failure retransplantation may be indicated. Acute cardiac failure before transplantation nowerdays can be treated by mechanical circulatory assist devices.
Follow-Up Studies↗
[Progress in heart transplantation].
Within the past 10 years, heart transplantation has become established as a standard procedure in heart surgery. Improvements in immunosuppressive therapy and diagnosis of graft rejection have been crucial. The criteria for transplantation have been broadened for recipients as well as for donors. Newborns, pediatric patients, diabetics, and patients with impaired renal function will no longer be excluded from transplantation due to improved postoperative therapy. Furthermore, progress has been made with assisted circulation. Patients with acute heart failure can now be bridged to transplantation.
Adult↗
Skin microcirculation and laser Doppler blood flow in patients supported by the Berlin heart biventricular assist device.
Microcirculatory forearm cutaneous blood flow was monitored continuously and non-invasively by laser-doppler-flowmetry (LDF) in 10 patients treated with the Berlin Heart biventricular assist device (BVAD) system for end-stage heart failure (BVAD-pts). Ten normal human subjects served as controls (C). The cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the postocclusive reactive hyperemia (PORH) as a standardized response. To examine micro-vasculatory responses to macro-hemodynamic changes the cardiac output (CO) was decreased by reducing the BVAD-pump rate by 20%. No significant differences in base-line LDF measurements were ascertained in the two groups. After sudden cuff pressure release (1 min later) a statistically significant (p less than 0.004) three- to fourfold blood flow increase (PORH) occurred in both groups. The period of the PORH response was altered in all BVAD-pts. The time to peak PORH values were significantly diminished (p less than 0.05) A markedly delayed return to base-line level occurred in the BVAD-pts. The 20% reduction in the BVAD-pump rate significantly decreased CO (p 0.05) and increased systemic vascular resistance (SVR) (p less than 0.01), whereas LDF levels remained unchanged.
Adult↗
[Imaging procedures prior to the extracorporeal shockwave lithotripsy of gallstones].
In order to determine whether cholecystography and computed tomography (CT) are capable of better gallstone characterization than conventional radiography alone, 91 patients (76 females, 15 males; mean age 47 +/- 12 years) with symptomatic single gallstones were studied prospectively prior to extracorporeal shock-wave lithotripsy with concomitant oral stone dissolution therapy. In addition, the value of oral cholecystography in demonstrating patency of the cystic duct was compared with ultrasound assessment of gallbladder function. Despite "negative" plain gallbladder radiographs in all patients, oral cholecystography showed significant stone calcification in 8 of the 91 patients and CT showed stone calcifications in 52 of the 91 patients. In 12 patients the maximum stone density was between 50 and 90 Hounsfield units, and in 40 patients it was more than 90 Hounsfield units. CT revealed ring-like calcification in the majority (79%) of these stones. Oral cholecystography showed satisfactory concentration of contrast medium in all patients, while ultrasonography of the gallbladder following a chemically defined test meal demonstrated contractility of more than 50% of initial volume in 69 patients and of less than 30% in 9 patients. Although oral cholecystography is a simple, readily available complication-free method, ultrasound assessment of gallbladder contraction is better for selecting patients for extracorporeal shock-wave lithotripsy. CT allows significantly better characterization of gallstones than oral cholecystography and conventional plain gallbladder radiography.
Adult↗
Significance of computed tomography for shock-wave therapy of radiolucent gallbladder stones.
One hundred eleven symptomatic patients (91 women, 20 men) with solitary "radiolucent" stones (proved by a plain radiograph) underwent examination with computed tomography for stone analysis before extracorporeal shock-wave lithotripsy with a second-generation piezoelectric lithoptripter. The aim of the study was to assess the importance of computed tomography as a diagnostic pretreatment procedure compared with the plain abdominal radiograph: computed tomography density values greater than 50 Hounsfield units (HU) were found in 64 of 111 patients with radiolucent stones (58%). Of these 64, 50 patients even had values greater than 90 HU (50/111;45%). The majority of the stones with density values greater than 50 HU had a hyperdense rim (43 of 64) with a mean maximum attenuation of 134 +/- 68 HU. A significantly higher degree of stone disintegration was achieved with stones of group A (less than or equal to 50 HU) than with those in group B (greater than 50 HU and less than or equal to 90 HU) and group C (greater than 90 HU) with respect to the mean maximum fragment size after the first (P less than 0.001) and last (P less than 0.01) lithotripsy and with respect to the total number of shock waves applied (P less than 0.001) and the number of treatments (P less than 0.001). No difference was observed between groups B and C. After all follow-up periods, the rate of complete stone disappearance was higher in group A than in group B (NS for 1, 2, and 4 months of follow-up; P less than 0.01 for month 8; P less than 0.05 for month 12) and group C (P less than 0.05 for 1, 2, and 4 months of follow-up; P less than 0.001 for months 8 and 12). The authors conclude that computed tomographic analysis of gallstones before lithotripsy is more sensitive in detecting nonradiolucent stones than in the plain radiograph. Computed tomographic stone analysis seems to provide a better selection of patients suitable for biliary lithotripsy and could become a standard diagnostic pretreatment procedure to improve stone disintegration and complete stone disappearance after shock-wave lithotripsy and adjuvant chemolitholysis.
Adult↗