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.     

Complement components, C1 activation and disease activity in SLE

Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.     

Bilateral simultaneous tubal sextuplets: pregnancy after in-vitro fertilization--embryo transfer following salpingectomy

The presence of a damaged tube has been suggested in recent studies to have a negative effect on in-vitro fertilization (IVF) outcome. Performing bilateral salpingectomy prior to IVF to maximize pregnancy rates may also result in unnecessary surgery. This case is also an example of the occurrence of interstitial pregnancy after salpingectomy. This unusual type of ectopic pregnancy must be kept in mind when evaluating a patient suspected of a possible early abnormal gestation after assisted reproductive technolologies.      

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.     

Lack of interchangeability between visual analogue and verbal rating pain scales: a cross sectional description of pain etiology groups

Background:  

Rating scales like the visual analogue scale, VAS, and the verbal rating scale, VRS, are often used for pain assessments both in clinical work and in research, despite the lack of a gold standard. Interchangeability of recorded pain intensity captured in the two scales has been discussed earlier, but not in conjunction with taking the influence of pain etiology into consideration.     

Atopic dermatitis in 5-6-year-old Swedish children: cumulative incidence, point prevalence, and severity scoring

Background: This study aimed to evaluate the cumulative incidence, point prevalence, and severity of atopic dermatitis (AD) in a pediatric population. We also aimed to identify differential diagnoses relevant to AD in this population. Methods: Children scheduled for a health visit at 5.5 years of age were selected consecutively during the period October 1997–March 1998 from two cities in southern Sweden (Göteborg and Kristianstad). Schultz Larsen's questionnaire was used to evaluate the cumulative incidence of AD. Clinical examination was performed by dermatologists (A.B. and Å.S.) for those children with active eczema. The UK working party's criteria were used for the clinical diagnosis of AD. The SCORAD index was used to evaluate the severity of eczema. This index includes evaluation of extent, intensity, and subjective symptoms to a maximum score of 103 points. Results: In Göteborg 1219 and in Kristianstad 742 questionnaires were answered regarding 1961 children, 1004 boys and 957 girls. The response rate was 89%. According to the answers to Schultz Larsen's questionnaire, the cumulative incidence of AD in the whole material was 20.7% (406/1961) (CI 95% 18.9–22.5). In Göteborg, 104 of the examined children fulfilled the UK working party's criteria, equivalent to a point prevalence of 8.5% (CI 95% 7.0–10.1). In Kristianstad, the corresponding point prevalence was 11.5% (CI 95% 9.2–13.8). The severity of AD was evaluated in all children with visible eczema. SCORAD evaluation was performed in 155 of the 157 children with visible eczema. The majority of children had mild or moderate eczema; mean value 20.5 (CI 95% 18.7–22.3), median 19.6. Of the 96 children who did not fulfil the criteria of AD, other skin disorders were diagnosed in 51 at the clinical examination. Dry skin was by far the most common differential diagnosis. Conclusions: We have used validated protocols to evaluate the cumulative incidence, point prevalence, and severity of AD in a population‐based study in southern Sweden The present study, involving a rural and urban pediatric population, shows that AD is common, usually classified as mild or moderate, and seems to increase over time.     

A simplified assay for the detection of C3a in human plasma employing a monoclonal antibody raised against denatured C3

A monoclonal antibody raised against SDS-denatured C3 was shown to react with both solid-phase C3a and unfragmented C3. However, in the fluid phase the antibody was found to bind only to C3a and not to native C3. These findings indicated that the antibody could be used in an assay to detect C3a in human EDTA-plasma without prior separation of C3a from native C3. A simple and rapid competition ELISA was developed which monitored soluble C3a. 200 microliter of C3a (8 ng) was absorbed to plastic wells over night at 4 degrees C. Thereafter, 50 microliter of sample and 50 microliter of constant amounts of monoclonal antibody conjugated with beta-galactosidase, were incubated for 60 min at 37 degrees C. After washing, the colour reaction was started by adding nitrophenyl-galactopyridine to the wells. The microtitre plate was incubated at 37 degrees C for 30 min and the staining intensity was quantified at 405 nm. The assay detected both C3a and C3ades arg. A strong correlation was obtained between the new technique and an RIA which used an acid precipitation step for the separation of C3a prior to the determination of C3a (r = 0.9). Significantly higher levels of C3a were detected both in plasma from patients with immune complexes (93 +/- 9 ng/ml; P less than 0.1) and in plasma from patients treated in blood oxygenators (140 +/- 19 ng/ml; P less than 0.05) than in plasma from normal subjects (74 +/- 4 ng/ml). The results were not affected by repeated freezing and thawing of the plasma samples.     

Measurements of dose distributions in small beams of 6 MV x-rays

Dose distributions produced by small circular beams of 6 MV x-rays have been measured using ionisation chambers of small active volume. Specific quantities measured include tissue maximum ratios (TMR), total scatter correction factors (St), collimator scatter correction factors (Sc) and off-axis ratios (OAR). Field sizes ranged from 12.5 to 30 mm diameter, and were defined by machined auxiliary collimators with the movable jaws set for a 4 cm x 4 cm field size. Due to the lack of complete lateral electronic equilibrium for these small fields, the accuracy of the measurements was also investigated. This was accomplished by studying dose response as a function of detector size. Uncertainties of 2.5% were observed for the central axis dose in the 12.5 mm field when measuring with an ionisation chamber with a diameter of 3.5 mm. The total scatter correction factor exhibits a strong field size dependence for fields below 20 mm diameter, while the collimator scatter correction factor is constant and is defined by the setting of the movable jaws. Off-axis ratio measurements show larger dose gradients at the beam edges than those achieved with conventional collimator systems. Corrected profiles measured with an ionisation chamber are compared with measurements made with photographic film and LiF thermoluminescent dosemeters.     

Comparative study of tocainide and lidocaine in patients admitted for suspected acute myocardial infarction

The antiarrhythmic effects of tocainide, administered as a bolus injection of 750 mg followed by oral therapy, and conventional lidocaine therapy were evaluated in 40 patients admitted for suspected acute myocardial infarction (AMI) and showing high-grade premature ventricular complexes (PVCs). The mean hourly PVC rate before therapy was 928 and its reduction was equally significant in the tocainide group, 73%, and in the lidocaine group, 68%. The number of 5-minute periods with multiform, paired and R/T PVCs or ventricular tachycardia was also significantly reduced, by 78% in the tocainide group and by 71% in the lidocaine group. Ten patients in the tocainide group reported moderate side-effects, compared to 13 in the lidocaine group, where the infusion had to be discontinued in 5 patients and the rate had to be reduced in 4. Tocainide, an amine analogue of lidocaine, is considered just as effective as lidocaine in patients with high-grade PVCs and suspected AMI.     

IL-4-deficient mice develop less acute but more chronic relapsing collagen-induced arthritis

Rheumatoid arthritis as well as collagen-induced arthritis (CIA) is thought to involve T cell autoimmunity of the Th1 type and the Th2 cytokine IL-4 has been proposed to play a suppressive role. To exclude a possible skewing role of the mycobacteria used in the complete Freund's adjuvant (CFA) we induced CIA with type II collagen (CII) in incomplete Freund's adjuvant (IFA). Our results show that IL-4 deficiency leads to a lesser susceptibility to arthritis and lower B and T cell responses if induced with CII/IFA but not if induced with CII/CFA. In addition, IL-4-deficient mice were less susceptible to arthritis induced with monoclonal anti-CII antibodies. However, mice immunized with CII/IFA later developed a chronic relapsing disease, which was promoted by IL-4 deficiency. We conclude that IL-4 plays different roles depending on the type of adjuvant used and the phase (acute or chronic) of the clinical disease.