[Probiotics for the prevention of antibiotic-induced diarrhea]. / Probiotika in der Prävention der Antibiotika-induzierten Diarrhö.

Between 5 and 49% of patients treated with antibiotics suffer from diarrhoea. Principally all microbial agents can cause diarrhoea, especially oral agents like cephalosporines, clindamycin, broad-spectrum penicillins, and quinolones of the 3  rd and 4th generation. Manifestations of antibiotic-associated diarrhoea range from mild self-limiting forms to severe life-threatening courses. The potentially most severe form of antibiotic-associated diarrhoea is caused by Clostridium diffcile accounting for approx. 25  % of antibiotic-associated diarrhoea. In the past two decades a broad spectrum of different probiotic strains has been evaluated for the primary prevention of antibiotic-associated diarrhoea in children and adults. Based on their efficacy and clinical data, different levels of evidence and recommendations are emerging on the preventive use of probiotics in antibiotic-associated diarrhoea.

Automated data acquisition by confocal laser scanning microscopy and image analysis of triple stained immunofluorescent leukocytes in tissue.

The aim of the study was to develop a novel system permitting automated analysis of multicolor immunofluorescence-staining of cells in solid tissues which would be comparable to the analytical capacity of flow cytometry. In the user friendly automated data acquisition and image processing system which was established, the software includes a set of pre-defined processing steps for improved object identification and can be either interactive or fully automatic. As with multi color flow cytometry, stained cells can be analyzed in a fully automated manner regardless of tissue type. The software organizes computerized sample movement, autofocus, laser readjustment, data capture and storage as well as calculation. Data are presented as histograms indicating the staining intensity and frequency of each antigen, and in dotplots with each channel plotted against the other. The calculated statistics give information about how many of the cells are single-, double- or triple-reactive and how intensely they react with the respective antibodies. Comparison of data generated by this automated fluorescence confocal laser scanning microscopy (AF-CLSM) with flow cytometry using triple stained peripheral blood lymphocytes revealed a highly significant correlation between the methods (P<0.001). A correlation was also observed when sections triple stained for anti-CD45, -CD3 and -CD8 were analyzed by AF-CLSM and the data were compared to visual/manual cell counting (P<0.01). The AF-CLSM system permits for the first time, fast (online) and reproducible analysis of immunofluorescence staining of an unlimited number of cells in tissue sections. The software, including a manual, is available for a small fee to cover the costs of printing and postage.

High-dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome.

OBJECTIVE: To investigate erythropoietin (EPO) production and the erythropoietic potency of recombinant human EPO in the multiple organ dysfunction syndrome. DESIGN: Randomized, prospective, controlled clinical trial. MATERIALS AND METHODS: Patients received either 600 IU/kg intravenous EPO three times weekly (n = 9) or saline (control, n = 10). MEASUREMENTS: EPO levels, circulating soluble receptors for tumor necrosis factor and interleukin-2, levels of interleukin-6 and intercellular adhesion molecule, and early peripheral blood cell progenitors. RESULTS: EPO production in the control group remained low. Pharmacologic EPO blood levels were associated with increased reticulocyte counts compared with both controls (p < 0.04) and baseline (p < 0.006). Increased levels of soluble receptors for tumor necrosis factor in the treatment group compared with the controls did not prevent this effect. Interleukin 6 inhibited reticulocyte production. CONCLUSION: Despite increased cytokine levels, pharmacologic EPO blood levels were associated with increased reticulocyte counts in patients with multiple organ dysfunction syndrome.

Assessing coronary stenosis. Quantitative coronary angiography versus visual estimation from cine-film or pharmacological stress perfusion images.

UNLABELLED: Visual judgment of stenosis severity from cine-film or single-photon emission computed tomographic dipyridamole perfusion images was compared to assessment of stenosis severity as measured with digital quantitative coronary angiography. Thirty patients with angiographically verified single-vessel disease underwent dipyridamole thallium stress testing within 90 days of angiography. RESULTS: A percent diameter stenosis of > or = 50%, a percent area stenosis of > or = 75%, and a stenotic flow reserve of < 3.75 measured by quantitative coronary angiography (CMS, version 1.1, Medis Inc.) corresponded to haemodynamically significant stenosis as evaluated by visual estimates from cine-film or perfusion images. Quantitative coronary angiography percent diameter stenosis (51.2% +/- 12.6%) correlated closely (r = 0.74) but underestimated significantly visual assessment of stenosis severity from cine-film (69.3% +/- 21.2%; P = 0.0001). However, quantitative coronary angiography percent area stenosis (74.7% +/- 11.7%) more closely reflected visual estimates from cine-film (P = 0.19). Quantitative coronary angiography stenotic flow reserve showed the highest positive and negative predictive value regarding visual estimates from cine-film (88%, 86%) or perfusion images (88%, 64%) followed by percent diameter stenosis (86%, 75% 86%, 56%) and percent area stenosis (87%, 80%, 87%, 60%), respectively. CONCLUSION: Evaluation of coronary lesions by quantitative coronary angiography corresponds closely with visual estimates from cine-film and haemodynamic significance as evaluated by dipyridamole perfusion images.

Outcome prediction for patients with cirrhosis of the liver in a medical ICU: a comparison of the APACHE scores and liver-specific scoringsystems.

OBJECTIVE: To find the most adequate prognostic scoring system for predicting ICU-outcome in patients with decompensated liver cirrhosis in a medical intensive care unit (ICU). DESIGN: Retrospective analysis of patients' records over a 10-year period. SETTING: A medical ICU at the university medical center of Vienna. PATIENTS AND PARTICIPANTS: 94% (n = 198) of all patients with cirrhosis admitted to our medical ICU throughout the 10-year study period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: From data obtained at admission and at 48 h after admission, scores were calculated using the following scoring systems: Acute Physiology and Chronic Health Evaluation (APACHE) II and III, Scale for Composite Clinical and Laboratory Index Scoring (CCLI), Mayo Risk Score, and Child's Classification. Statistical analysis for the prognostic variables was performed using the chi-square test, t-test, Youden index, and area under a receiver operating characteristic (ROC) curve. APACHE III was found to be the most reliable outcome predictor at admission and after 48 h for patients with decompensated liver cirrhosis (AUC = 0.75 and 0.8, respectively). CONCLUSIONS: To predict the outcome for patients with decompensated cirrhosis of the liver admitted to a medical ICU liver failure alone is not decisive. Liver-specific scoring systems (Mayo Risk Score, CCLI) are adequate, but the APACHE II and III proved to be more powerful, because they include additional physiologic parameters and therefore also take into account additional complications associated with this liver disorder.

Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study.

OBJECTIVE: To investigate the safety, biological effects, and efficacy of the anti-tumor necrosis factor (TNF) antibody fragment, MAK 195F, in a phase II trial in patient with severe sepsis. DESIGN: Prospective, randomized, open label, placebo-controlled, dose-ranging, multicenter, multinational clinical trial. SETTING: Sixteen academic medical centers' intensive care units in six European countries. PATIENTS: One hundred twenty-two patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Patients received one of three different doses of the anti-TNF antibody (0.1 mg/kg, 0.3 mg/kg, or 1.0 mg/kg) or placebo; the antibody or placebo was given in nine doses at 8-hr intervals over 3 days. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in mortality rates among the groups receiving various doses of the anti-TNF antibody or placebo, but patients with baseline serum interleukin (IL)-6 concentrations of > 1000 pg/mL appeared to benefit from MAK 195F in a dose-dependent fashion. Increased circulating IL-6 concentrations, but not TNF concentrations, were found to be important prognostic indicators for mortality for the patients in the placebo and the two lower dosage groups but not in the high dosage group (1 mg/kg). IL-6 concentrations decreased during the first 24 hrs of treatment in all three anti-TNF groups but not in the placebo group. MAK 195F was well tolerated by all patients. Human antimurine antibodies developed in 40% of the patients receiving the antibody. CONCLUSIONS: There was no increase in survival from sepsis for the patients receiving anti-TNF treatment in the overall study population. Retrospective stratification of patients by IL-6 concentrations suggests beneficial effects of the drug for patients with baseline circulating IL-6 concentrations of > 1000 pg/mL. This hypothesis requires validation in a larger, blinded, prospective study.

Beneficial effect of renal transplantation on cognitive brain function.

Cognitive brain dysfunction is a common complication of end-stage renal disease. To investigate the cerebral effect of renal transplantation, we studied P300 event-related potentials--an objective marker of cognitive brain function--trailmaking test and Mini-mental state in 15 chronic hemodialysis patients and 45 matched healthy subjects. Before transplantation, patients showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude (15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and Mini-mental state as compared to healthy subjects. Following renal transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating improved cognitive brain function. The trailmaking test and Mini-mental state tended to improve. Following transplantation, P300 findings, trailmaking test and Mini-mental state were not different from healthy subjects. Additional studies following erythropoietin treatment in 6 of the 15 hemodialysis patients revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) with further decrease following transplantation (341 ms, P = 0.06). Our findings indicate that cognitive brain dysfunction in hemodialysis patients may be fully reversed by successful renal transplantation.

Prevention of chemotherapy-induced anemia by the use of erythropoietin in patients with primary malignant bone tumors (a double-blind, randomized, phase III study).

BACKGROUND: Patients undergoing chemotherapy for treatment of malignancy frequently experience clinically significant anemia. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been effectively introduced in anemic patients suffering from chronic renal failure. The present study was designed to assess, first, whether rHuEPO treatment decreases transfusion requirements in chemotherapy-induced anemia and, second, whether high-dose rHuEPO application is safe. STUDY DESIGN AND METHODS: Thirty consecutive anemic patients (hemoglobin <11 g/dl) receiving combination chemotherapy for primary malignant bone tumors were studied in a prospective, double-blind, randomized, Phase III trial. Patients received chemotherapy according to one of two German protocols, depending on histologic diagnosis. All subjects enrolled were randomly assigned either to receive 600 IU of rHuEPO per kg of body weight intravenously twice a week or to receive a placebo during chemotherapy. To obtain comparable data, an observation period of 20 weeks was chosen. Twenty-nine patients fulfilled the criteria and were eligible for statistical evaluation. RESULTS: Transfusion requirements were significantly decreased from Week 8 of therapy (p<0.05) in the treatment group. Therapeutic benefits were even more evident with continuation of therapy (Week 12, p = 0.03; Week 16, p = 0.016; Week 20, p = 0.002). The blood required was 2.1 units of red cells in the treatment group and 8.4 units of red cells in the placebo group. All patients tolerated rHuEPO with no serious side effects. CONCLUSION: These findings suggest that rHuEPO is an effective and well-tolerated therapeutic option for decreasing the transfusion requirements in chemotherapy-induced anemia.

Anemia and erythropoietin levels in lung transplant recipients.

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin < 11 g/L for women, < 14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1-41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1-66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation < 20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels < 15 micrograms/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1-41 mU/ml, vs. 53 mU/ml, 15-88 mU/ml; P < 0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1-21 mU/ml, vs. 5 mU/ml, 3-32 mU/ml; P < 0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128-1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (+/- azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1-41 mU/ml, vs. 1 mU/ml, 1-16 mU/ml; P > 0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.

[Change in the patient profile in coronary heart disease at the time of initial evaluation with coronary angiography between 1975 and 1989]. / Veränderung des Patientenprofils mit koronarer Herzkrankheit zum Zeitpunkt der Erstevaluierung mittels Koronarangiographie zwischen 1975 und 1989.

BACKGROUND AND METHOD: After the introduction of coronary angioplasty in the late 1970s, diagnostic coronary angiography has been performed for reasons other than to evaluate patients for bypass surgery. The aim of this study was to evaluate the change of the patient-profile at the time of the first angiographic evaluation of coronary artery disease. Therefore, 6456 patients in the period from 1975 to 1989 were included. RESULTS: The observation period of 15 years was divided into three parts of 5 years each (group 1 1975-79, N = 1130); group 2 1980-84, N = 2412; and group 3 1984-89, N = 2914). The mean age (53.3 +/- 7.4 vs. 54.4 +/- 8.4 vs. 57.8 +/- 9.3; p < 0,0001) as well as the number of patients of age > 64 years (6.4% vs. 9.6% vs. 25.9%, p < 0.0001) increased significantly over the 15 years. Women were found twice as often in group 3 vs. group 1 (10% vs. 16% vs. 19%; p < 0.0001). In the observation period the left ventricular ejection fraction (51.1 +/- 15.9 vs. 53.8 +/- 14.4 vs. 55.4 +/- 16.2) and one-vessel disease (37.2% vs. 38.2% vs. 42.4%) increased significantly (p < 0.0001), whereas multi-vessel disease decreased (57.7% vs. 56.6% vs. 52.6%). CONCLUSION: Between 1975 and 1989 significantly more women, more patients over 64 years of age, and more patients with lower degree of coronary disease were first evaluated with coronary angiography. The change of patient-profile may have been influenced by increased risk-factors among women and the possibility to offer patients an alternative therapy to bypass surgery.

The use of recombinant human erythropoietin in lung transplantation.

Recombinant human erythropoietin (r-HuEPO) was administered in 4 lung transplant recipients to treat chronic anemia beyond the immediate postoperative period. There were 2 males and 2 females with a mean age of 38 years (range 22-49). None of the patients had major infection or rejection problems, and no blood products were used. Because of different individual responses duration of therapy was 1 to 17 weeks (median 5) with a total dosage ranging from 8 to 36 x 10(3) IU (mean 21 x 10(3)). The median single dose was 58 IU/kg (range 36-100). Hemoglobin levels increased significantly from 9.1 +/- 0.2 to 12.7 +/- 0.3 g/dl (mean +/- SE; p < 0.01). There were no side effects. r-HuEPO is recommended in treatment of chronic anemia in lung transplant patients to save blood products and to exclude the potential risk of transfusion-transmitted viral infections.

Folic acid supplementation improves erythropoietin response.

Therapy with recombinant human erythropoietin (rhEPO) has become most valuable for the treatment of renal anemia in patients with various chronic renal diseases. For the first time this study presents data showing that rhEPO affects the metabolism of folic acid. There were 13 patients enrolled; they suffered from different chronic renal diseases and showed an impaired responsiveness to rhEPO therapy. Before starting rhEPO therapy the mean corpuscular volume of erythrocytes (MCV) was measured; MCV was 90.4 fl. During rhEPO therapy the MCV increased significantly by 14.8 fl (p < 0.05). The developing macrocytic anemia was overcome when folic acid was administered additionally for a mean period of 3.14 +/- 3 months. Hematocrit (Hct) also responded accordingly. Whereas Hct did not increase adequately during the exclusive treatment with rhEPO, an increase in Hct from 23 +/- 3.3 to 30 +/- 4.2% (p < 0.01) was observed after the addition of folic acid. These results are rather remarkable as folic acid serum levels were clearly within the normal range during the whole study period. So it can be concluded that rhEPO therapy results in an increased demand for folic acid. Even if serum concentrations are within the normal range, the administration of folic acid will enhance the effectiveness of rhEPO therapy so that the rhEPO dosage can be reduced.

Serial recording of sensory evoked potentials: a noninvasive prognostic indicator in fulminant liver failure.

Sensory evoked potentials are markedly changed in patients with fulminant liver failure. It is unknown, however, whether serial recordings of sensory evoked potentials provide useful prognostic informations for patient management in fulminant liver failure. Ninety recordings of bilateral median nerve-stimulated short- and long-latency sensory evoked potentials were performed in 25 patients with fulminant liver failure (9 patients spontaneously recovered and survived, 8 patients were referred to emergency liver transplantation and 8 patients died). In all nine survivors the cortical long-latency sensory evoked potential N70 peak was constantly detectable between 74 and 162 ms. In all eight patients who subsequently underwent liver transplantation and in seven of eight patients who died, loss of the N70 peak developed during the course of fulminant liver failure. In 4 of 15 patients who were selected for liver transplantation according to the King's College criteria, the N70 peak was constantly detectable. All four transplantation candidates spontaneously recovered and survived without transplantation. In contrast, eight patients never did fulfill the criteria for liver transplantation. Five of them with constantly detectable N70 peak recovered spontaneously. However, in the remaining three patients loss of the N70 peak developed, and they ultimately died. The probability of correct outcome prediction by sensory evoked potentials is superior to that based on clinical criteria alone (0.96 vs. 0.72). Therefore serial recording of sensory evoked potentials may help identify (a) a subgroup among liver transplantation candidates who may spontaneously recover without transplantation and (b) a subgroup of patients with severe brain dysfunction who should undergo early liver transplantation even though they do not fulfill King's College criteria.

Increased serum concentrations of adhesion molecules after coronary angioplasty.

1. Reocclusion is still a significant complication after percutaneous transluminal coronary angioplasty. The injury of coronary arteries resulting from PTCA plays an important role in the pathophysiology of both abrupt closure and late restenosis after an initially successful procedure. Cytokines play a pivotal role in the accumulation of circulating blood cells at the endothelium and are known to regulate their interaction with the vessel wall. 2. To obtain further information about this interaction, serum concentrations of soluble endothelial leukocyte adhesion molecule 1 (sELAM-1), leucocyte endothelial cell adhesion molecule 1 (sL-selectin), intercellular adhesion molecule 1 (sICAM-1), interleukin 2 receptor (sIL-2R) and interleukin 8 (IL-8) detected by enzyme-linked immunosorbent assay were monitored in 30 consecutive patients referred for elective PTCA. Fifteen patients who underwent elective coronary angiography without PTCA served as controls. 3. All patients underwent successful first PTCA. Within 24 h the serum concentrations of sELAM-1 increased gradually from 21.7 (SD 7.1) to 48.2 (SD 8.6) ng/ml (P < 0.01); levels of sL-selectin rose from 982.1 (SD 128.7) to 1541.3 (SD 104.6) ng/ml after 48 h (P < 0.01). Serum levels of IL-8 remained stable initially, but peaked at the end of the observation time of 72 h (9.4, SD 3.8, versus 16.1, SD 4.9 ng/ml; P < 0.05). A positive correlation was found between the number of dilatations and the rise in these parameters (P < 0.01). No significant changes were found in the serum concentrations of sICAM-1 and sIL-2R after PTCA or in any of the parameters in patients after coronary angiography. 4. We conclude that PTCA induces a significant rise in the concentration of certain adhesion molecules in serum. Thus, we provide preliminary data on the potential role of cytokines for blood cell-endothelium interaction after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired erythropoietin responsiveness in anaemic rheumatoid arthritis patients: potential relation to immune mechanisms.

1. Serum levels of erythropoietin and the immune parameters tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-2, interleukin-6 and interferon-gamma were measured in patients with rheumatoid arthritis. 2. Out of 69 patients, 44 had anaemia with serum haemoglobin concentrations of 10.8 (SD 1.2) g/dl. In these patients erythropoietin levels were significantly higher than in non-anaemic patients [51.97 (SD 23.9) versus 26.06 (SD 11.9) m-units/ml; P < 0.0001; control patients: 18.1 (SD 13.8) m-units/ml]. Mean soluble interleukin-2 receptor activity was elevated in all patients with rheumatoid arthritis [1324 (SD 715) units/ml; control patients: 480 (SD 75) units/ml; P < 0.001] and was significantly higher in the anaemic group than in the non-anaemic group [1562 (SD 662) versus 696 (SD 402) units/ml; P < 0.0001]. The serum activity of soluble interleukin-2 receptor showed an inverse correlation with haemoglobin (r = 0.79; P < 0.0001) and a positive correlation with erythropoietin (r = 0.70, P < 0.0001). 3. Elevated serum tumour necrosis factor-alpha levels were found in 19 anaemic patients [20.6 (SD 9.1) pg/ml]. Concentrations of tumour necrosis factor-alpha in serum showed an inverse correlation with haemoglobin (r = 0.57, P < 0.001) and a positive correlation with erythropoietin (r = 0.46, P < 0.05). Interleukin-6 was detected in seven anaemic patients [21 (SD 14) pg/ml] and interleukin-2 activity in three anaemic patients (12, 16 and 14 units/ml, respectively). Interferon-gamma was not detected in any of the patients investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of serum soluble tumour necrosis factor concentrations in the diagnosis and prognosis of renal graft rejection.

Up to the present the histological diagnosis of rejection through biopsy is still the only possibility for a definite rejection diagnosis. We searched for a reliable non-invasive marker of renal graft rejection. By means of a highly sensitive enzyme-linked immunosorbent assay we investigated the changes in the concentration of serum soluble TNF receptor in kidney graft recipients with different clinical courses according to their graft tolerance. sTNF-R in 19 patients with stable graft function (5.3 +/- 3.2 ng/ml) did not differ significantly from those detected in 22 healty volunteers (4.1 +/- 2.2 ng/ml). In contrast 17 patients suffering from acute graft rejection showed highly significantly increases (23 +/- 8.3 ng/ml, P < 0.0001). These elevated concentrations returned to prerejection rejection values after a 3-day anti-rejection therapy with high-dose methylprednisolone. In 18 patients with an irreversible, chronic kidney graft rejection we could demonstrate significantly increased sTNF-R values (20 +/- 7.9 ng/ml); eight of those patients did not reflect on the anti-rejection therapy, so that the elevated concentrations remained even after the administration of high-dose corticosteroids and ATG. Additionally we found soluble TNF receptor concentrations to be increased earlier than other commonly used biochemical parameters such as creatinine. Soluble TNF-R also proved to be useful for the differentiation of cyclosporin nephrotoxicity. Therefore we believe that the soluble TNF-R and its concentration course may be of diagnostic and prognostic value in kidney graft rejection, as it supports the diagnosis of transplant rejection, indicates the rejection event very early, and reflects the response to anti-rejection therapy.

Serum concentrations of immune parameters during acute cardiogenic pulmonary edema.

OBJECTIVE: To evaluate the effect of acute cardiogenic pulmonary edema on the concentrations of immune parameters in serum. DESIGN: Prospective, controlled study. SETTING: Medical ICU. PATIENTS: Twenty-four consecutive patients with acute pulmonary edema who had significant clinical improvement within 30 mins and did not show any evidence of either tissue damage or infection. For comparison, 25 healthy, age-matched controls and 25 patients with mild chronic heart failure were also studied. INTERVENTIONS: Treatment with oxygen, nitrates, and loop diuretics. MEASUREMENTS: Lymphokines, acute-phase reactants, and cortisol concentrations were measured in serial serum and plasma samples. MAIN RESULTS: Serum concentrations of soluble CD-8 antigen (soluble CD-8) decreased from 928 +/- 124 (SEM) U/mL on admission to 712 +/- 112 and 579 +/- 67 U/mL after 2 and 6 hrs, respectively (p less than .05, p less than .01), and returned to baseline values within 48 hrs (853 +/- 109 U/mL). Concentrations of soluble interleukin-2 receptor increased from 721 +/- 71 to 1078 +/- 112 and 1226 +/- 128 U/mL 12 and 36 hrs, respectively, after admission (p less than .05, p less than .01). Plasma cortisol concentrations were markedly increased on admission (56.9 +/- 4.7 vs. 13.1 +/- 1.3 micrograms/dL after recovery, p less than .001). Increased cortisol concentrations coincided with the nadir of soluble CD-8. Tumor necrosis factor-alpha remained within normal limits in all patients. Neither acute-phase reactants nor angiotensin converting enzyme activity showed significant changes during the observation period. CONCLUSION: The present results indicate significant alterations in the serum concentrations of immune parameters as an effect of an uncomplicated acute cardiogenic pulmonary edema.

Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity.

1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension.