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[Complement system during hemofiltration in patients with multiple organ failure].

Nine patients (8 men and 1 woman) were treated. Sepsis was diagnosed in 7 of them. All patients were subjected to forced ventilation of the lungs, 6 were in need of inotropic support. The severity of clinical status was 31 +/- 0.8 according to APACHE II score. One patient survived. The main method of substitute renal therapy (SRT) was permanent hemofiltration with spontaneous arteriovenous perfusion. The results indicate manifest depletion of the complement system augmenting with the progress of multiple organ failure (MOF). Extracorporeal perfusion in SRT had no additional negative effects on the complement system damaged by disease. Nonselective penetration of individual complement fractions into the filtrate in the course of perfusion was noted. Therefore, the complement system is severely damaged in patients with MOF; it can modulate the SRT because of penetration of its individual fractions.

APACHE↗

[Abdominal manifestations of hereditary angioneurotic edema. Importance of the exploration of the complement system (apropos of 29 families)].

Abdominal manifestations are almost constantly present (85% of cases) in the current form of hereditary Quincke's disease. In some cases, these abdominal manifestations occur even when cutaneomucosal edema is not present which leads to unwarranted often repeated and sometimes dangerous surgery. Apart from a story of heredity diagnosis of such troubles is possible, provided the total complement has been assayed to note its sharp fall. It can be subsequently explained by a functional defect of the C1 esterase inhibitor or alpha2-neuraminoglycoprotein.

Adolescent↗

Demonstration of reactivity to airborne and food allergens in cutaneous vasculitis by variations in fibrinopeptide A and other blood coagulation, fibrinolysis and complement parameters.

In a 32-year-old woman and a 40-year-old man with cutaneous vasculitis, etiological allergic responses to foods and airborne allergens were found. During provocation tests, observations were made on blood levels of fibrinopeptide A(FPA) and coagulation factors, fibrinogen degradation products (FDP) and serum complement components. Skin biopsies were taken for microscopic and immunofluorescence analysis. In case 1, anaphylactoid allergy to milk and reaginic and anaphylactoid hypersensitivity to grass pollens were found. Dermal provocations with grass pollens gave arthralgia, hematomas, serum C3 fluctuation, factor VII reduction and fibrinolysis. During peroral milk challenge, transient increases in FPA and FDP levels were observed before symptoms appeared. In case 2, anaphylactoid hypersensitivity responses to bacteria, animal danders, foods and pollens were found. Two inhalations with sheep-wool extract resulted in a typical skin eruption. The first also gave an early reduction of C3 and then FPA liberation. Nasal birch-pollen test gave an increase of FPA in the latent period and then typical nodules. At least no low molecular weight FDP were detected during provocations. In patients with vasculitis reactions to exogenous allergens, FPA and FDP estimations after provocations may discriminate harmful from innocuous allergens and reveal individual response patterns in coagulation and fibrinolysis systems.

Adult↗

[Diagnosis of fever of unknown origin: use of Bayes theorem].

Sophisticated tests and time are needed to establish the diagnosis of fever of unknown origin (FUO). Bayes theorem can guide the clinician to early probabilistic diagnosis. The authors had estimated the a priori probabilities in a previous study yet. In this paper the diagnostic probabilities of four clinical signs (arthralgias, myalgias, splenomegaly, multiple micro-lymphoadenopathies) and the probabilities of abnormalities of some routine laboratory tests (neutrophils count, lymphocytes count, platelets count, hemoglobin, lactic-dehydrogenase, C3 and C4 complement subunits and fibrinogen plasma concentrations, erythrocyte sedimentation rate) and of the positive bacterial cultures, were estimated in the main groups of FUO disease (indefinite, aspecific bacteria infections, non-bacterial or specific bacteria infections, neoplasias, connective tissue diseases, miscellaneous group). The data suggest that the a priori probability is not affected by the clinical signs. Arthralgias increase the probability of connective tissue diseases. Normal erythrocyte sedimentation rate and plasma fibrinogen concentrations increase the probability of paraneoplastic and indefinite fever. Thrombocytosis increases the probability of paraneoplastic fever. Over 1200 U/l serum lactic-dehydrogenase serum concentrations guide to non-bacterial or specific bacteria infectious diseases and to malignancies. Neutrophilia decreases the probability of indefinite diagnosis, even though it is not specific. The heterogeneity of the miscellaneous group makes the interpretations of the data very hard.

Arthralgia↗

Alternative pathway of complement is activated during in vitro ventricular assist.

BACKGROUND: Although ventricular assist devices (VAD) have improved survival in selected patients, their use continues to be complicated by thromboembolism and end-organ failure. Complement activation may play a role in the pathogenesis of these complications. Previous studies have found that the complement common terminal pathway is activated during VAD circulation. C3a levels rise dramatically during VAD use. Because the C3a fragment is generated by either the alternative or classical pathway, the purpose of this study is to determine the relative importance of the respective pathways in complement activation during in vitro VAD circulation. METHODS: Six in vitro VAD circuits were simulated for 3 days using 450 mL of human blood. Temperature, activated clotting time, pH, pCO2, pO2, Ca2+, and glucose were maintained at physiologic levels. Enzyme immunoassays were used to measure concentrations of fragment Bb to indicate alternative pathway activation and fragment C4d to indicate classical pathway activation. RESULTS: Fragment Bb concentrations rise from 1.92 to 10.77 micrograms/mL during the first 6 hours of circulation. Thereafter, Bb levels plateau. C4d concentrations slowly rise from a baseline of 1.49 to 6.84 micrograms/mL in 72 hours. CONCLUSIONS: These findings suggest that both the alternative and classical pathways of complement are activated during VAD circulation. Alternative pathway activation precedes classical pathway activation during in vitro VAD circulation and may be of greater clinical importance during clinical VAD circulation.

Assisted Circulation↗

[The immune system and the complement system in low-birth-weight newborns].

Maturing of the immune system is related to the duration of the gestation period. It is essential that immunological processes be closely looked on in extremely low-birth-weight neonates: very high levels of immunoglobulins and components in extremely premature infected newborn babies are an example of the importance of the above recommendation.

Complement C3↗

Peritubular capillary deposition of C4d complement fragment in ABO-incompatible renal transplantation with humoral rejection.

In ABO-incompatible renal transplantation complement activation may be related to antibody-associated humoral rejection. However, immune deposits within the vasculature have been infrequently demonstrated in biopsy specimens. Whether deposition of complement fragment C4d is correlated with graft outcome and pathological findings (as measured by the severity of antibody-associated humoral rejection) is investigated in this study. Nineteen ABO-incompatible and 9 ABO-compatible renal graft biopsy specimens were selected. Four out of 19 ABO-incompatible patients lost their grafts within 1 yr. Ten out of 19 ABO-incompatible and just 1 out of 9 ABO-compatible patients, had prominent C4d deposition in peritubular capillaries. ABO-incompatible patients with predominant C4d deposition showed few tubulitis, accumulation of polymorphonuclear cells and thrombosis in peritubular and glomerular capillaries. The severity of the humoral rejection was correlated to C4d deposition in peritubular capillaries. Three out of four graft losses in ABO-incompatible renal transplantation showed severe humoral rejection and profuse deposition of C4d complement fragments in peritubular capillaries. Immunosuppression therapy was discontinued in the 4th patient, who lost his graft because of his lethal intestinal bleeding. C4d deposition in peritubular capillaries would be helpful for differential diagnosis between humoral rejection and drug-induced nephrotoxicity, and may serve as a sensitive marker of ABO-incompatible humoral rejection for patients with unsatisfactory (no glomeruli) biopsy specimens.

ABO Blood-Group System↗

Complement receptors (C3b, C4b/C3d) unbalance on CLL lymphocytes.

A study of lymphocytes bearing C3b, C4b and C3d complement receptor (CRL) was performed on human peripheral blood from 16 healthy donors and 12 patients affected with Chronic Lymphatic Leukemia (CLL). In the latter group a clear rise of C3dCRL was demonstrated, when compared with immunoadherence receptors bearing lymphocytes. However, when compared with controls, also these latter were slightly augmented. Furthermore in CLL under treatment CRL populations showed the same profile as CLL: so it was suggested that the treatment reduced not selectively all the three types of CRL, within the population of sIg bearing lymphocytes. Here we discuss the hypothesis that, in CLL, the proliferating lymphocytes population is chiefly sIg+, C3d+/C3b-, C4b-, but also sIg+, C3d+/C3b+, C4b+.

Animals↗

Complement activation in nephropathia epidemica caused by Puumala hantavirus.

BACKGROUND AND AIM: Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. There is considerable variability in the clinical severity of NE. Its pathogenesis is largely unknown and data on complement activation in NE are scant. We sought here to establish how the complement system behaves during NE and whether the variation in the clinical outcome is related to the activation of complement. PATIENTS AND METHODS: The complement component levels and complement activation products and the clinical course of 25 hospital-treated acutely ill NE patients were studied. RESULTS: Complement activation was observed in 23 patients. In 10 patients the complement system was activated mainly through the alternative route, in 6 mainly through the classical route and in 5 through both the alternative and the classical route. An elevated soluble terminal complex SC5b-9 was the most sensitive indicator of complement activation (17 out of 25 patients). Two patients had only an elevated SC5b-9 value and 2 had no complement activation. The C4d/C4 maximal ratio was significantly higher in patients with clinically severe NE compared to the mild or moderate disease groups. CONCLUSION: Our results show that complement activation is common in NE. Although both pathways are usually activated, the classical pathway activation by immune complexes or directly by viral components is associated with a severe clinical course of NE.

Adolescent↗

[The chemiluminescence test in the laboratory evaluation of effects of immunostimulatory therapy].

BACKGROUND: Number of patients treated by general practitioners with various immunomodulatory drugs has recently increased. Effects of such medication on the immune system were not usually monitored. The aim of our work was to evaluate effect of selected immunomodulatory drugs on the phagocytic and metabolic activities of the phagocytes. METHODS AND RESULTS: 51 patients (18 males and 33 females) of the average age 36 years with repeating respiratory, mycotic and herpetic infections were investigated. Immunomodulatory treatment included: Decaris (Lavamizolum), Isoprinosine (Methisoprinolum), Imudon (Lysatum bacteriale mixtum), Biostim (Klebsiella pneumoniae), and Immodin (Leukocyti dialysati lyophylysatum). Before and after treatment all patients underwent basic immunological examination IgG, IgA, IgM, C3, C4 complement components, PEG, CD3, CD4, CD8 and CD19). Phagocytotic activity was estimated by means of FAGO MSHP test with HEMA particles and by chemiluminiscence test. Chemiluminiscence was measured using ML 3000 Microtiter Plate Luminometer (Dynex), 26 healthy individuals of the corresponding age were the controls. Results were statistically evaluated by Student's t-test. Significant increase of the cellular metabolic activity was found in Decaris and Immodin treated patients (P < 0.001). CONCLUSIONS: Chemiluminiscence test, which evaluates the metabolic activity of phagocytes, can be used for the accurate laboratory monitoring of the effects of some immunomodulatory drugs on the natural immunity of patients.

Adjuvants, Immunologic↗

Acute poststreptococcal glomerulonephritis associated with thrombotic microangiopathy in an adult.

The simultaneous occurrence of acute poststreptococcal glomerulonephritis and thrombotic microangiopathy is rare. A 47-year-old woman was admitted with acute renal failure, hematuria, edematous nephrotic syndrome and severe hypertension. This acute nephritic syndrome occurred two weeks after left leg erysipelas. The patient also had signs of intravascular hemolysis, low serum levels of C3 and C4 and elevated antistreptolysin-O titer. Kidney biopsy confirmed postinfectious glomerulonephritis with diffuse hypercellularity and humps, and simultaneous subendothelial hyalin deposits and fibrinoid arteriolar thrombi. The patient received four antihypertensive drugs, acetylsalicyclic acid and plasma infusions. Renal function improved, hypertension was controlled and serum levels of C3 and C4 complement components returned to normal within three months. This case illustrates the occurrence of thrombotic microangiopathy in association with acute poststreptococcal glomerulonephritis. This simultaneous appearance supports a role of neuraminidase in this disease.

Acute Disease↗

Hereditary angioedema. Long-term follow-up of 88 patients. Experience of the Argentine Allergy and Immunology Institute.

Since the detection of the first patient with hereditary angioedema (HA) in 1978, 88 new patients belonging to 16 families have been referred to our clinic. Eighty patients had Type I disease, 5 Type II, and 3 Type III (secondary). We describe the clinical onset, frequent complications, diagnostic tests of the complement system, and abnormalities of the coagulation pathway linked to complement activation. Particular attention was paid to family members who could present succedaneum symptoms. The results of danazole and other therapies and protective and preventive treatment for surgery also are discussed.

Adolescent↗