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Biomedical subjects

I Brandslund

Publications and source records attributed to I Brandslund.

At least 55 records · Page 3Linked to original sources

Is a low serum concentration of alpha 1-antitrypsin associated with an increased susceptibility for byssinosis in cotton mill workers? Considerations regarding analytical quality requirements and economical consequences.

We have previously demonstrated an association between development of the cotton lung disease byssinosis and endotoxin concentrations in the work environment. Endotoxin has been shown to exert its effects through granulocyte activation and hence release of elastase and other proteases at the bronchoalveolar surface. alpha 1-Antitrypsin is a protease inhibitor, and hence, alpha 1-Antitrypsin concentrations in the blood and then on the alveolar surface might be important for the protection against endotoxin effects. Airborne endotoxin concentrations in the work place and S-alpha 1-Antitrypsin (a1A) was measured in 226 workers in cotton mills in Vejle and of these 206 were further phenotyped. The following models were considered: Model 1. The S-a1A concentration is determining the risk for development of byssinosis. The lower the concentration, the higher the risk. Model 2. The degree of exposure to endotoxin is determining. The higher the airborne concentration and the longer time working in that, the higher is the risk. Model 3. The phenotype of a1-A is determining. Only MS and/or MZ phenotypes represent a risk disposition. The goals for analytical quality for a1-A measurements were estimated in the two relevant models. The specifications are: Regarding model 1: analytical coefficient of variation CVA < 3% and analytical bias--1 mumol/L < BA < +1 mumol/L. Model 2: a1-A is not of significant importance and specifications cannot be evaluated. Regarding model 3: There is a direct relationship between cut-off point and analytical performance, e.g. an imprecision of SA 3 mumol/L and cut-off of 38 mumol/L will allow for a BA of -1 mumol/L.

Byssinosis↗

[Quality assurance in a medium-sized central laboratory].

In the article are described the procedures and materials used at a medium-sized Danish central laboratory, vis-à-vis current trends in quality assurance. There is a tendency toward stricter control procedures. The development of bedside and office tests will entail a shift in the onus of quality assurance to individual physicians in the future.

Blood Chemical Analysis↗

[Costs and prices of laboratory services].

Cost accounting is performed in private and public laboratories. Guidelines for these activities are required and with this objective in mind, the Board of the Danish Society of Clinical Chemistry commissioned a working group to produce a position paper which is presented now in this report. The report discusses the objectives, the principles and the general requirements for cost accounting. The significance of information on costs for the clinicians' rational use of the laboratory is also illustrated. The working group points out that prerequisites for lucid and appropriate costing guidelines are clarification of which purposes information on costs are meant to serve, identification of the relevant cost centers and quality assurance of laboratory services to a defined extent. It is common practice to express laboratory costs as costs per test. The report advocates calculation of the cost per patient contact, i.e. the overall costs for laboratory service in a given investigative situation.

Accounting↗

Specificities of monoclonal antibodies against the complement C3d split product.

The only specific method at present for the quantification of the complement split product C3d, the double-decker rocket immunoelectrophoretic assay, is work intensive and expensive. We investigated the possibilities for developing an ELISA for the direct quantification of C3d in plasma. Available antibodies were examined for their specificity for C3 and its degradation products by the PAGE immunoblotting method. None of the antibodies were specific for C3d, as cross-reactivities against C3 and/or C3b and C3bi were demonstrable.

Animals↗

Metabolism of C3 and factor B in patients with congenital factor I deficiency.

The metabolism of complement factor B and C3 was analyzed in three previously described patients with congenital deficiency of factor I (C3b/C4b inactivator). Samples taken at steady state contained elevated levels of Ba and Bb, whereas native factor B was not detectable. Following plasma infusion in two of the patients Ba was rapidly cleared (within 8-12 hr) from the circulation and native factor B increased transiently, reaching normal levels within 22-24 hr. In parallel with the increase in Ba, factor B decreased during the following days, reaching preinfusion level after seven days. This was in contrast to a continued increase in C3 concentration, which was still within the normal range 15 days after infusion, despite the presence of only trace amounts of native B. In vitro complement activation experiments, employing purified C3Nef IgG as alternative pathway activator and aggregated IgG as classical pathway activator, were performed on selected serum samples (base-line, 12 hr and 15 days postinfusion samples) from the plasma infusion series. It was demonstrated that (a) C3Nef could not induce alternative pathway C3-conversion in factor B depleted samples and (b) C3-degradation by CP-activation could still occur in B-depleted samples, although at a much slower rate compared to normal human serum. These results may partly explain the difference in kinetics of factor B and C3 metabolism seen after plasma infusion in patients with factor I deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Lumbar disc surgery and variations in C-reactive protein, erythrocyte sedimentation rate and the complement split product C 3 d.

Lumbar disc surgery was performed in fifty consecutive patients and variation in erythrocyte sedimentation rate (ESR), complement C 3 d, and C-reactive protein (CRP) levels before and after surgery were recorded. Preoperative values were within normal limits in all patients. Postoperatively, CRP increased immediately, with a maximum of 28.5 mg/l on the 2nd day and were normalized within 6 days. The maximum ESR elevation occurred after the 6th day and was followed by a slow decrease. After 12 weeks some patients still had an elevated ESR. Plasma C 3 varied pari passu with the ESR. Uncomplicated recovery after lumbar disc surgery seems to be indicated by a normalization of CRP, regardless of ESR values. Therefore, ESR may not be so useful as an indicator of disc space inflammation as previously accepted.

Adult↗

Neutrophil lysosomal enzyme release and complement activation during cardiopulmonary bypass.

Complement activation and neutrophil degranulation were concomitantly studied during uncomplicated cardiopulmonary bypass (CPB). Plasma concentrations of complement factor C4, complement split product C3d, the neutrophil lysosomal enzyme elastase complexed with alpha 1-proteinase inhibitor (PI) and fibronectin were measured in 12 patients, C3d and elastase/PI increased significantly during CPB (volume-corrected results). The C3d rise was almost linear, whereas elastase/PI showed exponential increase. Mean elastase/PI and mean C3d concentrations at different times during CPB covaried closely. The study showed that during CPB neutrophil lysosomal enzyme release is intimately related to complement activation, although activation of the two systems may be caused by a common third activator within the extracorporeal circuit.

Adult↗

Screening for complement deficiencies in unselected patients with meningitis.

Two hundred and nine patients consecutively admitted to hospital with a tentative diagnosis of meningitis were screened for complement deficiency by measuring classical and alternative pathway serum haemolytic complement activity and the plasma concentration of C3d. Abnormal test results were followed up by quantitative immunochemical measurements of individual complement components. No patients with homozygous complement deficiency were found in our material. One patient with pneumococcal meningitis with probable heterozygous C2-deficiency was identified. Patients with purulent meningitis of various etiologies or meningococcal disease had significantly increased plasma C3d concentration at admission compared to patients with serous meningitis or without meningitis. Furthermore, increased plasma level of C3d at admission in patients with purulent meningitis or meningococcal disease was associated with an increased lethality. Our findings do not support the hypothesis that complement deficiency is commonly associated with sporadically occurring meningococcal disease or purulent meningitis.

Adolescent↗

Plasma concentrations of complement split product C3d and immune complexes after procainamide induced production of antinuclear antibodies.

Seventeen patients treated with procainamide for cardiac ventricular arrhythmias were followed for up to 40 weeks. Immunological data as a clue to developing the systemic lupus erythematosus (SLE)-like syndrome was emphasized. Ten patients developed antinuclear antibodies (IgG or IgM), but no increase in the plasma concentration of the complement split product C3d or immune complexes, measured by two different methods, was demonstrated. This finding is in contrast to the high levels of both C3d and immune complexes in SLE. The discrepancy may be caused by a lack of immune complex mediated complement activation by the procainamide induced antibodies, or may be due to a difference in severity of disease. The acetylator phenotype of the patients was determined but due to the low frequency of fast acetylators no comparison of the immunological response of the two phenotypes could be done.

Aged↗

A family with complement factor I deficiency.

A family with inherited factor I deficiency is described. The proband was a 19-year-old Caucasian female with one episode of meningococcal meningitis and one episode of suspected septicaemia of unknown cause. Two obligate and two probable heterozygotes with factor I levels below the lower limit of the reference range were identified. None of these exhibited increased susceptibility to infectious diseases. The inheritance was autosomal codominant. In addition, molecular heterogeneity of factor H in plasma from the proband but not from any other family members was demonstrated by crossed immunoelectrophoresis. The migration of factor H component of fast electrophoretic mobility was retarded by antibodies to C3c and C3d, suggesting the presence of a fluid-phase complex between factor H and excess C3b generated by the uncontrolled activity of the amplification loop.

Adult↗

Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis.

Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate the need to collect blood specimens and perform clinical examinations of patients at a fixed time of day.

Adult↗

Low plasma fibronectin after drowning.

The plasma concentrations of fibronectin were zero for 8 days in a 53-year-old male who was submersed for 5 min, but conscious at the time of admission to hospital. The patient developed multiple organ failure, disseminated intravascular coagulation and finally died after 15 days. The low fibronectin values indicate prolonged severe reticulo-endothelial failure, and may be a prognostic sign in cases of drowning or asphyxia of other etiologies.

Combined Modality Therapy↗

Steroids reduce complement activation in rheumatoid arthritis.

Patients with seropositive, classical rheumatoid arthritis (RA) with severe active disease have raised plasma concentrations of the complement C3 split product C3d. These values display little diurnal or circadian variation in the individual patient. During a 3-month period the variation was within 10 mU/l in 45 patients (ref. range 20-52 mU/l, RA patients up to 120 mU/l.) Six RA patients were treated with steroids on clinical indication, and the plasma C3d, Ritchie index and pain score before and during the treatment (30 mg prednisolone per day) were measured. The variables showed a steady decrease during the next 14 days. Plasma C3d fell 2/3 of the total fall within the first 48 hours, while the serum total haemolytic complement activity, complement C3 and C4 did not change significantly. This shows that the anti-inflammatory effect of steroids is accompanied by a reduction of complement activation.

Arthritis, Rheumatoid↗

The third complement factor (C3) and its in vivo cleavage products: interaction with lectins and precipitation with polyethylene glycol.

Five molecular forms of C3 expressing D but not C epitopes were identified following in vivo activation of the complement system. Examination of concanavalin A (Con-A) reactivity in crossed immunoelectrophoresis revealed that native C3, C3c and the beta mobile form 4 of C3d were completely precipitated by 100 micrograms Con A/cm2. The alpha-1 mobile form 1 of C3d did not interact with Con A, whereas the alpha-2 mobile forms 2 and 3 were retarded in electrophoretic migration by Con A. Native C3, C3c, and forms 4 and 5 of C3d were precipitated by 12% (w/v) polyethylene glycol (PEG). Form 1 of C3d was soluble in these PEG concentrations, whereas forms 2 and 3 were partially precipitated.

Antigen-Antibody Reactions↗

Factor I deficiency and C3 nephritic factor: immunochemical findings and association with Neisseria meningitidis infection in two patients.

The complement system was examined in two patients with systemic Neisseria meningitidis infections, both of whom had reduced or nondetectable CH50 as analysed by both pathways. C3 measured by conventional technique revealed 19% anti-C3c-reactive protein in the plasma of patient 1 and 3% in patient 2. Patient 1 had circulating C3b but no detectable C3c, C3d, or C4d, whereas patient 2 had normal levels of C3c and C4d and strongly elevated levels of C3d. Factor B analysis revealed no demonstrable native factor B and small amounts of Bb in patient 1 and normal concentration of native factor B plus trace amounts of Bb in patient 2. The depletion of C3 in both patients was due to uncontrolled activation caused by complete factor I deficiency (patient 1) and circulating C3 nephritic factor (patient 2). Both parents of patient 1 had factor I concentrations below (mean-2 SD) that seen in normal healthy individuals (n = 20). Circulating immune complexes (IC) were demonstrated in patient 1 only, whereas serum from both patients had strongly reduced capacity to solubilize preformed IC.

Adolescent↗