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Biomedical subjects

G Pilz

Publications and source records attributed to G Pilz.

At least 19 recordsLinked to original sources

Reversible cerebral hyperperfusion syndrome after stenting of the carotid artery - two case reports.

Hyperperfusion syndrome can complicate carotid revascularization, be it endarterectomy or carotid artery stenting (CAS). Although extensive effort has been devoted to reducing the incidence of ischemic stroke complicating CAS, little is known about the incidence, etiology, and prevention strategies for hyperperfusion following CAS. We report two cases (female patients 72 and 81 years) presenting severe internal carotid stenosis (> 90%), who underwent presurgical and therapeutic intervention with CAS. Both patients developed hyperperfusion symptoms at 2 hours and at 30 minutes, respectively, following stenting, in both cases unilateral hyperperfusion was CCT confirmed. Case 1 was presenting with acute edema of the right hemisphere, case 2 with distended focal edema (left fronto-temporoparietally). Hyperperfusion syndrome and neurological symptoms retroceded in both cases (conservative therapy) and both patients returned to full activity (case 2 within 48 hours).

Aged↗

Improved outcome of APACHE II score-defined escalating systemic inflammatory response syndrome in patients post cardiac surgery in 1996 compared to 1988-1990: the ESSICS-study pilot project.

OBJECTIVE: Cardiac surgery using extracorporeal circulation leads to the release of cytokines and subsequently to a systemic inflammatory response syndrome, which is thought to be a negative prognostic factor for patients' outcome. A stratification for the risk of an escalating systemic inflammatory response syndrome had been achieved in a monocenter study carried out in 1988-1990, using APACHE II scoring on the morning of the 1st postoperative day. We now re-evaluated this concept prospectively in three independent centers. METHODS: The APACHE II based risk stratification was put to test in three independent heart surgery centers in the period from June to December 1996. Nine hundred and forty-five patients after elective cardiac surgery (excluding heart transplantation) with the assistance of the cardiopulmonary bypass were prospectively monitored. RESULTS: We found an increase in mortality with higher APACHE II score values determined on the 1st postoperative day. The mortality rose to nearly 50% with an APACHE II score of > or = 28. Patients at high risk for the development of a systemic inflammatory response syndrome (APACHE II score > or = 24) significantly differed from patients at lower risk (APACHE II score < 19) in the duration of mechanical ventilation and extracorporeal circulation, age and New York Heart Association (NYHA) classification (P < 0.05). CONCLUSION: The APACHE II score determined on the morning of the 1st postoperative day helps identifying the subgroup of patients with escalating systemic inflammatory response syndrome. Comparison with the data obtained in the years 1988-1990, suggests a better prognosis in the current trial for patients at high risk with a similar degree of escalating systemic inflammatory response syndrome.

APACHE↗

Conservative treatment of a paracardial abscess following post-infarct patch grafting.

A patient with previous patch grafts at the site of a ventricular aneurysm and over an ischaemic septal defect presented with an oval hypodense mediastinal mass consistent with a mediastinal abscess with blood cultures positive for Staphylococcus aureus. Surgical re-operation in this region was considered to be too risky and conservative treatment was pursued. Antibiotics were continued for a total of nearly 5 months of treatment. A computed tomographic scan prior to discharge indicated that the abscess was completely resolved.

Abscess↗

Association of serum tumor necrosis factor levels with decrease of cholesterol during septic shock.

Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation.

Aged↗

A post-receptor defect of adenylyl cyclase in severely failing myocardium from children with congenital heart disease.

The aim of this study was to determine whether a defect at the post-receptor level of adenylyl cyclase may also contribute to the decreased effectiveness of cAMP-increasing agents in severely failing patients with congenital heart disease. The severity of congestive heart failure in 31 patients with congenital heart disease was graded by a scoring system which included a description of historical and clinical variables. Patients were divided into a group with no or mild heart failure (score < or = 6) and a group with severe heart failure (score > 6). beta-Adrenoceptor-stimulated adenylyl cyclase activity was significantly decreased by 65% in patients with severe heart failure in comparison to the group of patients with no or mild heart failure. In addition, receptor-independent adenylyl cyclase stimulation by forskolin was reduced by 52% in patients with score > 6 compared to patients with score < or = 6. This post-receptor defect of adenylyl cyclase was apparently due to a decrease in the activity of catalytic subunit of adenylyl cyclase as adenylyl cyclase stimulation by forskolin in the presence of Mn2+ which uncouples catalytic subunit from the G proteins, G(s) and G(i), was also significantly diminished in the patients with severe heart failure. In contrast, the level of inhibitory G protein alpha-subunits was apparently not different in the two groups. In summary, the data indicate that a defect at the catalytic subunit of adenylyl cyclase apparently contributes to the decreased effectiveness of cAMP-increasing agents in severely failing patients with congenital heart disease.

Adenosine Diphosphate↗

[Systemic inflammatory reactions to extracorporeal therapy measures (II): Cardiopulmonary bypass].

About 65,000 cardiac patients undergo surgery annually in Germany with the assistance of cardiopulmonary bypass. The "post pump inflammatory response" (the systemic and myocardial inflammatory response syndrome post cardiac surgery), triggered at least in part by the cardiopulmonary bypass, contributes substantially towards morbidity (e.g., myocardial depression) and mortality in these patients. The main mechanisms underlying this inflammatory response are the complement cascade, the activation of blood cells, the release of cytokines and the induction to nitric oxide synthesis. The relative importance of each individual factor, however, is still a matter of debate. Scoring systems and measurements of tumor necrosis factor-alpha, as well as soluble tumor necrosis factor receptors, allow the early detection of an "escalating inflammatory response" in 2-10% of all patients, which is associated with a worse prognosis. Therapeutic attempts to suppress these systemic and myocardial inflammatory reactions focus on blockade of the complement system, coating of CPB membranes with heparin, leucocyte depletion and attenuation of leucocyte function, elimination of toxins and mediators by means of hemofiltration, as well as on the administration of antiproteases, antioxidants, oxygen radical scavengers and also of immune globulins.

Cardiopulmonary Bypass↗

Comparison of early IgM-enriched immunoglobulin vs polyvalent IgG administration in score-identified postcardiac surgical patients at high risk for sepsis.

STUDY OBJECTIVE: To address the relevance of the IgM component in polyvalent immunoglobulins in sepsis treatment by comparison of the clinical course under polyvalent IgG vs IgGMA therapy in postcardiac surgical patients at high risk for sepsis and to reassess the prognostic validity of sequential changes in acute physiology and chronic health evaluation (APACHE II) scores during treatment. DESIGN: Prospective, randomized clinical trial. SETTING: Cardiac surgical ICU in a university hospital. PATIENTS: Among 870 consecutive patients after elective open-heart surgery, 29 (3.3%) met the previously validated high-risk criterion (APACHE II score > or = 24 on the first postoperative day) with a mean APACHE II score-predicted mortality risk of 63%. INTERVENTIONS: In addition to standard therapy, 27 of these patients were randomized to receive commercially available IV IgG (Polyglobin N, n = 14, total dosage: 18 mL/kg) or IgGMA (Pentaglobin, n = 13, total dosage: 15 mL/kg). MEASUREMENTS AND RESULTS: The two groups were comparable in baseline disease severity and concurrent therapy. The extent of score-quantified improvement in disease severity during treatment was similar in both groups (mean fall in APACHE II scores within 4 days; IgG, -6.9; IgGMA, -5.2), as were score-defined improvement rates (rate of patients with score decrease > or = 7 within 4 days: IgG, 57%; IgGMA, 54%) and in-hospital mortality (IgG, 29%; IgGMA, 31%) (all p = NS). There was a strong association between the decrease over time in APACHE II scores during therapy and prognosis (mortality rates in patients with vs without score-assessed improvement: 0% vs 67%, p = 0.0002). CONCLUSIONS: IgG and IgGMA were associated with a comparable improvement in disease severity in score-identified postcardiac surgical patients at high risk for sepsis. Given the design as an efficacy rather than an equivalence study, this hypothesis derived from our results needs independent validation in larger trials. Sequential APACHE II score changes were reconfirmed as a prognostically valid quantitative measure of disease progress during sepsis therapy.

APACHE↗

Early prediction of outcome in score-identified, postcardiac surgical patients at high risk for sepsis, using soluble tumor necrosis factor receptor-p55 concentrations.

OBJECTIVE: To investigate the prognostic value of increased serum concentrations of soluble tumor necrosis factor (TNF) receptors in patients at high risk for sepsis. DESIGN: Prospective study. SETTING: Cardiac surgical intensive care unit in a University Hospital. PATIENTS: Those 27 of 870 consecutive postcardiac surgical patients who met a previously validated high-risk criterion for imminent sepsis (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 24 on the first postoperative day [day 1]). In this population, systemic inflammatory response syndrome was present in 96% of the patients and the in-hospital mortality rate was 30%. In addition, ten postcardiac surgical patients with an uncomplicated course (mortality rate 0%) were studied for comparison. INTERVENTIONS: Blood sampling for measurements of serum concentrations of TNF and soluble TNF receptors 55 kilodalton (TNF receptor-p55) and 75 kilodalton (TNF receptor-p75) on days 1, 2, 3, and 5. MEASUREMENTS AND MAIN RESULTS: Compared with the ten patients with an uncomplicated course (group A), the high-risk patients had significantly higher baseline (day 1) serum concentrations of soluble TNF receptor-p55 (9.2 vs. 4.2 ng/mL) and soluble TNF receptor-p75 (9.2 vs. 5.5 ng/mL). These high-risk patients could be further differentiated into two subgroups: one (B) with a prompt decrease in APACHE II score and a good prognosis (mortality rate 0%) and another (C) with a persisting high risk of sepsis and mortality rate (40%, p < .05). Although baseline APACHE II score was similar in both high-risk subgroups, soluble TNF receptor-p55 concentrations were significantly higher in subgroup C compared with subgroup B already at baseline (10.7 vs. 4.7 ng/mL). The receiver operating characteristic curve for subgroup classification by soluble TNF receptor-p55 was in a discriminating position with an area (0.773 +/- 0.096), confirming soluble TNF receptor-p55 as a predictor of mortality. TNF and soluble TNF receptor-p75 concentrations were less predictive at baseline. CONCLUSIONS: This study suggest that increased soluble TNF receptor-p55 concentrations in the serum of postcardiac surgical patients allow earlier prognostication of subsequent hospital course than APACHE II scores alone. This study further suggests that the combination of physiologic scores and cytokine receptor measurements could improve the predictive power of early postoperative risk stratification.

APACHE↗

Supplemental immune globulins in sepsis: a critical appraisal.

For 'the total population of patients with sepsis, sepsis syndrome or SIRS', the question of whether intravenous immune globulin (IVIG) reduces mortality is neither proved nor disproved. For the sepsis subgroups 'postoperative sepsis with a sepsis score more than 19' and 'endotoxaemic, early septic shock', a significant reduction in mortality by IVIG has been documented in a single, placebo-controlled, small trial of each subgroup; subsequent studies are needed for confirmation. The incidence of some severe infections in defined 'patients at risk' and 'operations at risk' is lowered by IVIG prophylaxis. Postoperative APACHE II-score identification of high-risk cardiac surgery patients prone to sepsis and severe SIRS may represent one approach to optimize individual, early therapy. Applying this concept to immune globulin treatment in a pilot study, the administration of IgG-IVIG and IgGMA-IVIG yielded similar results.

Humans↗

Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure.

This study focuses on the role of platelet membrane glycoproteins and platelet-leucocyte adhesion in patients with sepsis and multiple organ failure (MOF). Specifically, the study raises the following issues: (1) the influence of sepsis and MOF on platelet activation as assessed by surface expression of platelet membrane glycoproteins GPIIb-IIIa and thrombospondin; and (2) the effect of sepsis and MOF on platelet adhesion to circulating leucocytes. In addition, platelet activation and platelet-leucocyte adhesion are evaluated according to clinical outcome. Forty-five patients with suspected sepsis or MOF were evaluated by intensive care scoring systems (APACHE II and Elebute) to assess severity of disease. Flow cytometric techniques were used to examine platelet membrane expression of various adhesion molecules on circulating platelets and the appearance of platelet specific antigen (CD41) on leucocytes as an index of platelet-leucocyte adhesion. The results were compared with severity of disease and according to outcome in patients. Twenty-eight patients of the total study population were septic and 17 were non-septic. Twenty-two of the 28 septic patients suffered from severe MOF (APACHE II > or = 20) whereas in six septic patients MOF was absent. Eleven of the non-septic group suffered from moderate MOF whereas in six, severe MOF was present. In septic patients fibrinogen receptor activity on platelets was significantly above normal values (P < 0.001). When MOF was present, thrombospondin surface expression on circulating platelets also increased significantly (P < 0.05). Concomitantly, platelet-leucocyte adhesion was increased in sepsis (P < 0.05) and decreased in patients with MOF (P < 0.05). Significant lower levels of circulating platelet-leucocyte aggregates occurred in non-survivors (P < 0.05). We conclude that sepsis is associated with increased surface expression of platelet adhesion molecules and an increased occurrence of circulating platelet-leucocyte aggregates. The decrease in circulating platelet-leucocyte peripheral sequestration. An increased platelet-leucocyte adhesion and sequestration might account for development of MOF in the course of sepsis.

Adolescent↗

Early sepsis treatment with immunoglobulins after cardiac surgery in score-identified high-risk patients.

In patients at risk for sepsis after cardiac surgery, the efficacy of intravenous immunoglobulin (Ig) treatment was compared with a historical control population, equivalent in patient characteristics and disease severity. Using APACHE II scores, especially in the high-risk group (IgG), we could discriminate between low-risk patients (score < 19; mortality 1 percent) and the small groups at risk (score 19 to 23) and high risk (score > or = 24) with a significantly higher mortality (14 percent and 76 percent, respectively) [corrected]. Subsequently, among 1,341 consecutive patients we prospectively identified and treated (IgG n = 41 IgGMA: n = 25) these at-risk groups. In contrast to controls (risk: n = 21; high-risk; n = 21), we found a marked fall in APACHE II scores, especially in the high-risk group (IgG, n = 26: p < 0.05; IgGMA, n = 13: p = 0.08) [corrected]. In this group, Ig therapy produced higher (p < 0.05) response rates (score decrease 7 within 4 days: IgG: 54 percent, IgGMA: 62 percent; controls: 19 percent) and reduced mortality (IgG: 46 percent, IgGMA: 46 percent; controls: 76 percent), statistically significant (p < 0.05) for Ig treatment overall. Thus, early Ig treatment improves disease severity and may improve prognosis in prospectively score-identified high-risk postcardiac surgical patients.

Aged↗

Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels.

In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well tolerated in all patients without signs of toxicity and without development of anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6) and hemodynamics there was no evidence that the higher dosage of the anti-TNF alpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1 mg/kg per dose). Comparison of our data with recent data from phase I or II trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.

Adult↗

Pseudomonas sepsis does not cause more severe cardiovascular dysfunction in patients than non-Pseudomonas sepsis.

To evaluate the clinical relevance of the experimental findings of a more severe cardiac depression in Pseudomonas (P.) than in non-P. sepsis, we retrospectively compared the hemodynamic data in 26 patients with P. sepsis (20 cases, single pathogen; six cases, more positive cultures with P. than with non-P. species), and 102 with non-P. sepsis. As in other studies, the left ventricular stroke work index (LVSWI) was used to assess cardiac performance. The two groups (all numbers are means) had a similar disease and sepsis severity profile (P. vs. non-P: septic shock, 81% vs. 87%; APACHE II scores, 29.1 vs. 29.2; Elebute sepsis scores, 18.1 vs. 18.1; mortality, 58% vs. 62%). Preload (pulmonary capillary wedge pressure 15.0 vs. 16.3 mm Hg) and systemic vascular resistance (588 vs 572 dyn.cm-5.sec) were comparable. Cardiac performance displayed no significant difference (LVSWI, 42.8 vs. 38.3 g.m/m2), a result reproduced in the subgroups with culture-proven bacteremia, with or without preexisting cardiovascular disease or septic shock. Thus, our data suggest that there is no difference in the degree of cardiovascular dysfunction in patients with Pseudomonas compared to non-Pseudomonas sepsis of otherwise equivalent disease severity.

Cardiovascular System↗

Desensitization of rat cardiomyocyte adenylyl cyclase stimulation by plasma of noradrenaline-treated patients with septic shock.

The purpose of this study was to test the possibility that the mechanisms of catecholamine-induced desensitization of cardiac beta-adrenoceptor stimulation are modified in septic shock. Exposure of neonatal rat cardiomyocytes for 48 hr to plasma of noradrenaline-treated patients with septic shock led to a down-regulation of beta-adrenoceptors by 35%, an increase in the level of inhibitory G protein alpha-subunits by 60%, and a decrease in isoproterenol-stimulated adenylyl cyclase activity by 50% in membranes prepared from the rat cardiomyocytes. Similar alterations were observed following pretreatment of the cells with plasma of adrenaline-treated patients with cardiogenic shock. In contrast, exposure of the cardiomyocytes to plasma of intensive care patients without shock, and to plasma of dopamine-treated patients with septic shock did not induce alterations of the cardiomyocyte adenylyl cyclase system. The dosage of the catecholamines had to be increased within the first two days of treatment in the noradrenaline-treated patients, but not in the dopamine-treated patients with septic shock. Thus, this observed tolerance to noradrenaline in the treatment of septic shock may, in part, be due to a desensitization of cardiac beta-adrenoceptor stimulation induced by the beta-adrenoceptor stimulatory effect of noradrenaline.

Adenylyl Cyclases↗