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Biomedical subjects

P Späth

Publications and source records attributed to P Späth.

At least 37 records · Page 2Linked to original sources

Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals.

Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.

Antibodies, Monoclonal↗

Serum concentrations of immunoglobulins and of antibody isotypes in bone marrow transplant recipients treated with high doses of polyspecific immunoglobulin or with cytomegalovirus hyperimmune globulin.

The kinetics of immunoglobulins (Ig) and antibodies were followed in 10 bone marrow transplant recipients who received either high doses (0.5 g/kg body weight) of polyspecific intravenous Ig (HD-IVIG) weekly or cytomegalovirus hyper-Ig (CMV-IVIG, 0.1 g/kg body weight) every 3 weeks. In the HD-IVIG group, the mean total IgG concentration more than tripled and similar significant increases were seen for IgG1 and IgG2. IgG antibodies to CMV showed a marked increase in the HD-IVIG and a less pronounced rise in the CMV-IVIG group. IgM antibodies to CMV were present initially or became detectable in five patients, unrelated to the IVIG preparation. HD-IVIG induced a significant increase of IgG antibodies to streptococcal group A carbohydrate (A-CHO) and to smooth strain lipopolysaccharides (LPS) but not of antibodies against lipid-A. When the Ig treatment was discontinued, levels of total IgG and of IgG antibody to CMV decreased with an apparent half-life of 30 days. Both IVIG preparations were well tolerated and had no negative feedback on total Ig and on specific antibody production or other antimicrobial defence mechanisms. In patient nos. 4 and 10 who developed severe graft-versus-host-disease, transient serum Ig peaks including several Ig isotypes appeared after day 14. In patient no. 10 this peak contained an IgG antibody to H. influenzae type b (Hib), and IgM antibodies to CMV, Hib, A-CHO and LPS. This study clearly shows that serum concentrations of Ig isotypes, subtypes and specific antibodies, depend on at least four factors: total amount and composition of Ig infused, consumption, catabolism and endogenous production.

Adult↗

Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass.

The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.

Antithrombin III↗

[Chronic urticaria and acquired complement deficiency due to a nephritic factor (C3NeF)].

Several studies have suggested that complement activation processes are frequently involved in the pathogenesis of urticaria. We report clinical evolution and studies of complement-mediated functions in a 47-year-old previously described patient presenting with chronic urticaria, in whom we found persistent low complement hemolytic activity (65-75% of normal values), depressed levels of third complement component (C3, between 55% and 65%) and of factor B (between 60% and 75%), together with C1, C4, C2, C5, C5b neoantigen and fluid phase terminal complement (SC5b-9) complex within the normal range, pointing to activation of the alternative pathway. A circulating low affinity C3 nephritic factor (C3NeF), known to enhance cleavage of human serum C3, was detected. The urticarial lesions, which were initially pruritic and persisted for less than 24 hours, became subsequently fixed and burning, and were accompanied by fever and arthralgia. Skin biopsy specimens showed moderate leukocytoclastic vasculitis. Response to varied treatment regimens, including antihistamines and colchicine, was poor. Therapy with oral corticosteroids produced some improvement. The association of chronic urticaria with C3NeF without clinical and biological signs of membranoproliferative glomerulonephritis and partial lipodystrophy has not to our knowledge been reported before. This observation raises the question of a possible role of C3NeF in the pathogenesis of urticaria.

Chronic Disease↗

[Efficacy of prophylactic nifedipine therapy during aortocoronary vein bypass interventions. Drug concentration with oral or intravenous nifedipine administration; hemodynamics and plasma catecholamines].

To assess the usefulness of prophylactic nifedipine in coronary artery surgery, in this study nifedipine plasma concentrations were determined in patients, who had been given 10 mg nifedipine orally before operation. Furthermore, plasma and tissue concentrations of nifedipine were measured in patients receiving a nifedipine infusion. In this group of patients the efficacy of nifedipine, based on changes in hemodynamics and plasma catecholamines was also investigated. Patients with normal global left ventricular function (LVEDP less than 15 mm Hg, EF greater than 0.5) undergoing coronary artery bypass grafting (CABG) operations were included in this study. The preoperative antianginal therapy was continued until the time of surgery, the last beta-adrenoceptor blocker was given on the day of surgery. A standardized premedication and anesthesia (fentanyl-flunitrazepan infusion) was given to all patients. Hemodynamic parameters were obtained using indwelling arterial, venous and pulmonary artery thermodilution catheters. The high-pressure-liquid-chromatography (HPLC) method was used to measure plasma catecholamines as well as plasma and tissue nifedipine concentrations. Eight patients received 10 mg nifedipine orally one hour prior to anesthetic induction. Plasma nifedipine concentration (Figure 1) showed a wide interindividual scattering at anesthetic induction (25 +/- 38 ng/ml) in this group and they decreased to low, noneffective levels during surgical stimulation (12 +/- 12 ng/ml) and aortic cannulation (8 +/- 8 ng/ml). 24 patients with a nifedipine infusion of 0.30 micron/kg/min prior to extracorporeal circulation (start: following intubation, termination: at aortic cannulation) were compared to a control group of 24 patients with respect to hemodynamics, plasma catecholamines, anesthetic requirements and need for additional vasodilator and vasopressor therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Angioedema caused by enalapril (Reniten)].

Two cases of enalapril(Reniten)-induced angioedema are described. In both patients the time lag between the first manifestation of angio-edema and diagnosis was more than one year, during which several bouts of edema occurred. One patient developed life-threatening swelling of the tongue and the larynx followed by asystole and apnea. The second patient had recurrent edema of the tongue and dyspnea. In general, enalapril-induced edema is not thought to be based on immunological mechanisms. However, in both patients we found elevated titres of antinuclear antibodies, which were reversible upon cessation of enalapril medication. The possible pathomechanisms are discussed.

Angioedema↗

The influence of rapid potassium administration on hemodynamics and endogenous catecholamine production during extracorporeal circulation.

In a prospective randomized double-blind study, the peripheral vascular effects of potassium chloride (KCl) and potassium-magnesium-aspartate (KMA) were compared. Twenty patients undergoing coronary artery bypass graft surgery received either 12 mmol of KCl (n = 10) or 12 mmol of KMA (n = 10) into the oxygenator of the heart-lung machine during extracorporeal circulation (ECC). The most striking difference between these two solutions was vasoconstriction following KCl administration and vasodilation after KMA injection. In the KMA group, decreases of perfusion pressure (MAP) and systemic vascular resistance (SVR), as well as changes in the oxygenator volume (dV), were significant (P less than 0.01) between the first and the fifth minutes. Maximal changes of MAP, from 72 +/- 13 to 59 +/- 12 mmHg (mean +/- SD), and SVR were recorded in the first and second minutes. Oxygenator volume changes reached their maximum (285 +/- 163 mL) in the tenth minute. In the KCl group, maximal increases in MAP, from 70 +/- 16 to 81 +/- 20 mmHg (mean +/- SD), and SVR were found in the fourth minute. Maximal changes in dV (300 +/- 315 mL) were measured in the tenth minute. Plasma epinephrine levels, which were already elevated during ECC, showed further increases in all cases in the KCl group and in most of the cases in the KMA group. The change in plasma epinephrine concentration following KCl injection was significant (P less than 0.01). No characteristic change in plasma norepinephrine was found in either of the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Sufentanil-N2O2/O2 or halothane-N2O/O2 anesthesia in surgery of infants and children with congenital heart defects. Hemodynamics and plasma catecholamines].

Sufentanil-nitrous oxide/oxygen anesthesia was compared to halothane-nitrous oxide/oxygen anesthesia in 44 infants and children undergoing cardiac surgery. Patients were randomly assigned to one of the two techniques studied, with 22 patients in each group. The mean weight was 8.3 (4.4-15.8) kg in the sufentanil (S) group and 11.7 (5.2-18) kg in the halothane (H) group. All patients were premedicated with IM atropine 0.01 mg/kg, morphine 0.2 mg/kg, and flunitrazepam 0.04 mg/kg. In the S group 1 micrograms/kg S was given intravenously for induction, followed by a cumulative dose of 4 micrograms/kg S until the beginning of surgery. In the H group anesthesia was induced with H 0.5-1.0 vol.% and for deepening of anesthesia increasing H concentrations of 0.5-1.0-1.5 vol.% were applied. Following intubation all patients were ventilated with nitrous oxide/oxygen (1:1). There were no significant differences between the two groups in systolic, diastolic and mean arterial blood pressures or in heart-rate response to induction and intubation. Peripheral arterial oxygen saturation increased significantly in cyanotic patients in both groups following induction. There were dose-dependent decreases in heart rate and small but significant decreases in mean and diastolic arterial pressure in the S group during deepening of anesthesia. There was a significantly greater decrease in systolic, diastolic and mean blood pressures during the same period in the H group whereas the reduction in heart rate was minimal. In addition, in 5 of 22 patients receiving H there were episodes of nodal rhythms with dramatic decreases in systemic arterial pressure and peripheral arterial oxygen saturation in cyanotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

[Meningococcal meningitis in isolated familial deficiency of the 7th complement component, C7].

Based on recent reports of a hereditary disposition to neisserial infections in subjects deficient in one of the hemolytic components of the complement system, we have studied 2 siblings who had had "sporadic" meningococcal meningitis in 1976 and 1977 respectively. In neither was C7 detectable, which suggested a homozygous deficiency. The two children of the first propositus showed values compatible with a heterozygous state.

Adult↗

Dysfunctional C8 beta chain in patients with C8 deficiency.

Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.

Adult↗

Purified fibronectin administration to patients with severe abdominal infections. A controlled clinical trial.

Subnormal plasma fibronectin (Fn) levels are found in patients with severe abdominal infections (SAI). The repletion of Fn has been postulated to have therapeutic benefit by virtue of its opsonic, reticuloendothelial system (RES) stimulating effects. A controlled, prospective trial of Fn administration was performed in patients with SAI to assess its use as an adjunct to standard procedures of intensive care. Thirty-three SAI patients were given daily doses of 0.8 g of purified Fn on days 1-5 following admission to the ICU, whereas 34 control patients received no Fn. All patients received the clinical care, antibiotics, and pharmacologic agents appropriate to their individual needs. The admission status and laboratory profiles of the two patient groups (+ and -Fn) were comparable on admission to the study. No side effects of the Fn preparation were observed. As judged by subgroup averages, the Fn replacement regimen was effective in elevating Fn levels to within normal range from day 2 onwards, as measured by immunological and functional assays. The estimated intravascular recovery of Fn averaged 82% in those patients who survived, yet only 52% in the nonsurvivors. Ultimate hospital mortality was 9/33 (27.3%) in the +Fn group versus 13/34 (38.2%) in the -Fn group (p = 0.244, Fisher's exact test). Although ultimate mortality was not significantly changed by the administration of Fn, the Fn treated patients appeared to survive longer than did the control patients. This trend was confirmed through the analysis of expected survival curves (D = 3.12, 0.1 greater than p greater than 0.05). When compared to the survivors, the ultimate nonsurvivors entered the study with statistically higher group averages of bilirubin and creatinine concomitant with lower averages of Fn, antithrombin III, C4, C3, C3b-INH, and transferrin. These differences persisted throughout the 11-day monitoring period; differences between survivors and nonsurvivors with respect to platelets, plasminogen, B-1-H, alpha-2-macroglobulin, and prealbumin appeared during the same period. Dramatic differences between the +Fn and -Fn treatment groups were not seen. Other than Fn, the Fn recipients only developed higher levels of the acute phase reactants C4, C3b-INH, B-1-H and alpha-1-antitrypsin (p less than 0.05) than did their non-Fn treated counterparts. In the present study, we again found a highly significant pattern of correlations between the absolute levels as well as the changes of Fn and other plasma proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗

[Experiences with Swan-Ganz-catheter placement in the external jugular vein].

Clinical experience concerning the placement of Swan-Ganz catheters (SGC) via the external jugular vein is presented. After puncture of either the right or left external jugular vein, placement of SGC was possible in 90 per cent of patients. Compared to techniques involving puncture of the internal jugular vein this method has less complications. The placement of 167 SGC could be done without any problems, thus proving that the external jugular vein is a safe way of insertion. The external jugular vein as a primary route can be recommended if the vein is visible, especially in cases where puncture of the internal jugular vein may be difficult and could only be performed with an increased risk of complications.

Anesthesia, Intravenous↗