Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

Sutureless bowel anastomosis using Nd:YAG laser

Small bowel anastomoses were performed without sutures by using the Nd:YAG laser to produce welded enterotomies. Optimal energy levels for contact and noncontact laser were determined. Anastomoses produced using five target energy levels between 100 and 500 J were examined. Short-term anastomotic strength of these enterotomies was measured 1 min after the welding. Bursting pressure of the laser welded enterotomies was compared to the bursting pressure of traditional two-layer, inverting, interrupted sutured bowel anastomoses. The overall mean bursting pressure of non-contact-welded enterotomies was 50.6 mmHg. Optimal laser settings determined in this initial phase were then used to produce anastomoses in rabbits which are recovered postoperatively for 1 or 2 weeks in order to examine long-term viability and integrity of the anastomoses. All chronic rabbit preparations recovered without complication. The mean bursting pressure was 200 mmHg, not significantly different from that of uncut bowel or two-layer sutured anastomosis.     

A role for decorin in cutaneous wound healing and angiogenesis

Decorin is known to influence tissue tensile strength and cellular phenotype. Therefore, decorin is likely to have an impact on tissue repair, including cutaneous wound healing. In this study, cutaneous healing of both excisional and incisional full‐thickness dermal wounds was studied in decorin‐deficient (Dcn^?/?) animals. A statistically significant delay in excisional wound healing in the Dcn^?/? mice occurred at 4 and 10 days postwounding and, in incisional wounds at 4, 10, and 18 days when compared with wild‐type (Dcn^?/?) controls. Fibrovascular invasion into polyvinylalcohol sponges was significantly increased by day 18 in Dcn^?/? mice relative to Dcn^+/+ mice. The 18‐day sponge implants in the Dcn^?/? mice showed a marked accumulation of biglycan when compared with the corresponding implants in Dcn^+/+ mice. Thus, regulated production of decorin may serve as an excellent therapeutic approach for modifying impaired wound healing and harmful foreign body reactions.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

Renal transplantations from the same kidney donor: outcome of diabetic and non-diabetic patients.

Diabetic (DM) nephropathy is an indication of renal transplantation in 30% of all cases in our hospital. We assessed retrospectively the outcome of these diabetics (DM) in comparison with their non-diabetic (NDM) controls. Each diabetic (n = 24) had a control (n = 24) receiving a kidney from the same donor. There was no difference in the stage of uraemia preoperatively. Anaesthesia and fluid therapy were standardized. Peroperative hypotension occurred more often in diabetics (NS). All operating parameters including cold ischaemia were comparable. Kidney function started immediately in 14/24 in the DM group and 13/24 in the NDM group and was delayed in 10/24 and 11/24, respectively. One diabetic patient rejected the transplant as did two non-diabetic patients. Postoperatively diuretics could be discontinued more often in the DM than in the NDM group (p < 0.05). Antihypertensives had to be started in the NDM more often (NS) than in the DM group. In conclusion, the outcome of diabetic patients after renal transplantation was comparable to their NDM controls.     

Lynestrenol induced therapeutic amenorrhea: effects of dose reduction on serum sex-hormones and lipids.

The effect of reducing the dose of peroral lynestrenol by half on serum sex-hormone, lipid and lipoprotein status was studied in 21 mentally retarded women with therapeutic amenorrhea (TA). They had previously received 5 or 10 mg peroral lynestrenol daily for periods ranging from 32 to 196 months. Dose halving of lynestrenol resulted in an increase in serum total testosterone (T) by 16% (p less than 0.05), sex-hormone binding globulin (SHBG) by 39% (p less than 0.01) and high-density lipoprotein cholesterol (HDL-C) by 28% (p less than 0.001). Both the mean serum total and free concentrations of norethisterone (NET and fNET) decreased by 60% (p less than 0.001). The serum concentrations of 17-beta-estradiol (E2), its free fractions (fE2) and free T (fT) were not significantly altered. Significant correlations were observed between the change in HDL-C and the change in T (r = 0.45, p less than 0.05), between the change in SHBG and the change in T (r = 0.62, p less than 0.01), fT (r = 0.43, p less than 0.05) and E2 (r = 0.51, p less than 0.05). The elevation of HDL-C was probably caused by the reduced serum NET concentrations. This also resulted in an increase in serum SHBG concentration, which is regarded as an indicator of the overall estrogen/androgen ratio.     

Measuring radiation exposure during percutaneous drainages: can shoulder dosemeters be used to estimate finger doses?

Some previous studies have shown remarkably high finger doses to radiologists performing percutaneous drainage under fluoroscopy. To assess the possible need for extra finger dosemeters in addition to the general dosemeter, radiologists' and assistants' radiation exposure at both shoulders and at the third fingers of both hands were recorded using thermoluminescent dosemeters during 27 interventional drainage procedures. Under couch screening was used. Mean dose rates were calculated by dividing the doses by the screening time. The dose rates for the sites measured were correlated with each other. The radiologists' bilateral finger dose rates did not correlate with each other; nor did dose rates between the left shoulder and the right hand. The radiologists' dose rates at both shoulders, however, correlated with each other, as did the shoulder dose rates with the dose rates at the ispilateral hand. The right shoulder dose rates correlated with the left hand dose rates. The assistants' dose rates at the places of measurement all showed significant correlations with each other. It is therefore concluded that radiologists involved in percutaneous drainages should use finger dosemeters on both hands; for assistants this may not be necessary.