OBJECTIVE: To find out if there was any local activation of complement in the vicinity of a colonic cancer, and any fluctuation in the function of the complement system during operation. DESIGN: Prospective study. SETTING: One university and two district hospitals in Denmark. SUBJECTS: 29 selected patients undergoing emergency and elective operations for colonic cancer. INTERVENTIONS: Measurements of systemic and local complement fixation capacity and complement activation in samples of serum or plasma taken before, during, and after operation. MAIN OUTCOME MEASURES: Changes in complement fixation capacity and complement activation during operation. RESULTS: Haemodilution during operation caused a significant reduction in the complement fixation capacity of serum and in the activation of the complement system as measured by generation of C3c. We were unable to confirm the presence of complement inhibitors during operation. Haemodilution caused a 30% reduction in fixation capacity of C3b (12/29 samples of serum had values more than 2SD below the mean of the reference range compared with 4/29 before operation). The activity of C4 was reduced by 25% during operation and the capacity of the complement system to fix C3b and C4b was restored to baseline nine days postoperatively. Concentration of C3d was significantly higher in serum from tumour venous blood compared with that from peripheral blood during operation. CONCLUSION: The presence of complement activation products in the general circulation reflects local activation of the complement system in the vicinity of the tumour, but this may have been influenced by tissue necrosis or subclinical infection. Haemodilution causes a significant reduction in the capacity of the complement system during operation, whereas inhibitory factors associated with the cancer or operation and anaesthesia could not be demonstrated. We found no correlation between complement activity and clinical data.
To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by brain pathology. Here we investigated whether changes in these kidney measures are linked to development of new MRI-detected infarcts and microbleeds, and progression of white matter hyperintensity volume. The study included 2671 participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7% women). GFR was estimated from serum creatinine, and albuminuria was assessed by urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002-2006) and 5 years later (2007-2011). New MRI-detected infarcts and microbleeds were counted on the follow-up scans. White matter hyperintensity progression was estimated as percent change in white matter hyperintensity volumes between the two exams. Participants with a large eGFR decline (over 3 ml/min/1.73m2 per year) had more incident subcortical infarcts (odds ratio 1.53; 95% confidence interval 1.05, 2.22), and more marked progression of white matter hyperintensity volume (difference: 8%; 95% confidence interval: 4%, 12%), compared to participants without a large decline. Participants with incident albuminuria (over 30 mg/g) had 21% more white matter hyperintensity volume progression (95% confidence interval: 14%, 29%) and 1.86 higher odds of developing new deep microbleeds (95% confidence interval 1.16, 2.98), compared to participants without incident albuminuria. The findings were independent of cardiovascular risk factors. Changes in kidney measures were not associated with occurrence of cortical infarcts. Thus, larger changes in eGFR and albuminuria are associated with increased risk for developing manifestations of cerebral small vessel disease. Individuals with larger changes in these kidney measures should be considered as a high risk population for accelerated brain pathology.
Immunogenic properties of TVGRGDPHQ nonapeptide which is correspondent to the region 1094-1102 of B. pertussis filamentous hemagglutinin (FHA) were studied. The conjugate of bovine serum albumin with nonapeptide was used for immunization of BALB/c and CBA mice. Antisera of the both lines of mice cross-reacted with a number of antigens, but using affinity chromatography peptide and FHA specific antibodies were extracted. Affinity purified rabbit antibodies to TVGRGPHQ which recognize FHA were also obtained. Therefore the antibodies to the peptide which placed RGD-containing region responsible for macrophage CR3-integrin interaction are capable to distinguish the native antigen. Thus these data are an additional evidence for the nonapeptide use as a component of synthetic vaccine against whooping-cough.
Analytical performance specifications can be based on three different models: the effect of analytical performance on clinical outcome, based on components of biological variation of the measurand or based on state-of-the-art. Models 1 and 3 may to some degree be combined by using case histories presented to a large number of clinicians. The Norwegian Quality Improvement of Primary Care Laboratories (Noklus) has integrated vignettes in its external quality assessment programme since 1991, focusing on typical clinical situations in primary care. Haemoglobin, erythrocyte sedimentation rate (ESR), HbA1c, glucose, u-albumin, creatinine/estimated glomerular filtration rate (eGFR), and Internationl Normalised Ratio (INR) have been evaluated focusing on critical differences in test results, i.e., a change from a previous result that will generate an "action" such as a change in treatment or follow-up of the patient. These critical differences, stated by physicians, can translate into reference change values (RCVs) and assumed analytical performance can be calculated. In general, assessments of RCVs and therefore performance specifications vary both within and between groups of doctors, but with no or minor differences regarding specialisation, age or sex of the general practitioner. In some instances state-of-the-art analytical performance could not meet clinical demands using 95% confidence, whereas clinical demands were met using 80% confidence in nearly all instances. RCVs from vignettes should probably not be used on their own as a basis for setting analytical performance specifications, since clinicians seem "uninformed" regarding important principles. They could rather be used as a background for focus groups of "informed" physicians in discussions of performance specifications tailored to "typical" clinical situations.