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Introduction: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data. Materials and methods: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated. Results: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality. Conclusion: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy.

Introduction: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data. Materials and methods: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated. Results: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality. Conclusion: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy.

Objective To evaluate the diagnostic accuracy of observers with different levels of experience in reading F-18-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. Methods Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. Results Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. Conclusion Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

Background: The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies.Purpose: To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy.Material and Method: A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated.Results: 210 of 215 biopsies (98%; 95% CI 0.94-0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001-0.03), and three were equivocal (lack of imaging description).Conclusion: Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

Background: The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies.Purpose: To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy.Material and Method: A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated.Results: 210 of 215 biopsies (98%; 95% CI 0.94-0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001-0.03), and three were equivocal (lack of imaging description).Conclusion: Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels > 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level < 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort.

Purpose: To evaluate the inclusion of radiologists or nuclear medicine physicians (imaging specialists) as authors of systematic reviews (SRs) on imaging and imaging-guided diagnostic procedures and to determine the impact of imaging specialists' presence as authors on the overall quality of the reviews. Materials and Methods: A MEDLINE and EMBASE search was performed for SRs of diagnostic and interventional image-guided procedures that were published from January 2001 to December 2010. SRs about procedures primarily performed by nonimaging specialists were excluded. The inclusion of imaging specialists among the SR authors and the frequency of publication in imaging journals were evaluated. The quality of a subset of 200 SRs (100 most recent SRs with imaging specialists as authors and 100 most recent SRs without imaging specialists as authors) was rated by using a 12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman, chi(2), and Mann-Whitney statistics were used. Results: From among 3258 retrieved citations, 867 SRs were included in the study. Neuroimaging had the largest number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic performance, and 26% (228 of 867) of SRs were published in imaging journals. Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging specialists as authors were more often published in imaging journals than in nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median number of modified AMSTAR quality indicators was nine in SRs with imaging specialists as authors, while that in SRs without imaging specialists as authors was seven (P = .003). Conclusion: Only 38% (330 of 867) of SRs on radiology or nuclear medicine-related imaging published from January 2001 to December 2010 included imaging specialists as authors. However, the inclusion of imaging specialists as authors wa

Background/AimsThe purpose of the present pilot study was to investigate the feasibility of combining large pore dermal microdialysis with shotgun proteomic analysis in human skin. MethodsDialysate was recovered from human skin by 2000 kDa microdialysis membranes from one subject at three different phases of the study; trauma due to implantation of the dialysis device, a post implantation steady-state period, and after induction of vasodilatation and plasma extravasation. For shotgun proteomics, the proteins were extracted and digested with trypsin. Peptides were separated by capillary and nanoflow HPLC systems, followed by tandem mass spectrometry (MS/MS) on a Quadrupole-TOF hybrid instrument. The MS/MS spectra were merged and mapped to a human target protein database to achieve peptide identification and protein inference. ResultsResults showed variation in protein amounts and profiles for each of the different sampling phases. The total protein concentration was 1.7, 0.6, and 1.3mg/mL during the three phases, respectively. A total of 158 different proteins were identified. Immunoglobulins and the major classes of plasma proteins, including proteases, coagulation factors, apolipoproteins, albumins, and complement factors, make up the major load of proteins in all three test conditions. ConclusionShotgun proteomics allowed the identification of more than 150 proteins in microdialysis samples from human skin. This highlights the opportunities of LC-MS/MS to study the complex molecular interactions in the skin.

Background/AimsThe purpose of the present pilot study was to investigate the feasibility of combining large pore dermal microdialysis with shotgun proteomic analysis in human skin. MethodsDialysate was recovered from human skin by 2000 kDa microdialysis membranes from one subject at three different phases of the study; trauma due to implantation of the dialysis device, a post implantation steady-state period, and after induction of vasodilatation and plasma extravasation. For shotgun proteomics, the proteins were extracted and digested with trypsin. Peptides were separated by capillary and nanoflow HPLC systems, followed by tandem mass spectrometry (MS/MS) on a Quadrupole-TOF hybrid instrument. The MS/MS spectra were merged and mapped to a human target protein database to achieve peptide identification and protein inference. ResultsResults showed variation in protein amounts and profiles for each of the different sampling phases. The total protein concentration was 1.7, 0.6, and 1.3mg/mL during the three phases, respectively. A total of 158 different proteins were identified. Immunoglobulins and the major classes of plasma proteins, including proteases, coagulation factors, apolipoproteins, albumins, and complement factors, make up the major load of proteins in all three test conditions. ConclusionShotgun proteomics allowed the identification of more than 150 proteins in microdialysis samples from human skin. This highlights the opportunities of LC-MS/MS to study the complex molecular interactions in the skin.

Udgivelsesdato: 2009-Mar-6, BACKGROUND: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear. PURPOSE: The objectives of this trial were to study histamine release in human skin during the acute phase of a standardized thermal injury in healthy volunteers. METHODS: Histamine concentrations in human skin were measured by skin microdialysis technique. Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. A standardized superficial thermal injury was elicited by a heating thermode (49 degrees C) applied to the skin for 5 min. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods. RESULTS: Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20 min (n = 6) and 5-10-min samples over 120 min (n = 8). The histamine values were at the limits of the quantification limit of the spectrofluorometric assay. Confirmatory studies using a sensitive radioimmunoassay confirmed no histamine release within the first hour of a thermal injury (baseline 11.6 +/- 1.8 nM vs. post-burn values of 14.8 +/- 1.8 nM, n = 8). CONCLUSIONS: Histamine is not released in human skin during the acute phase of a thermal injury.

Udgivelsesdato: 2009-Apr, BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. RESULTS: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. CONCLUSIONS: Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.

Udgivelsesdato: 2009-Mar-6, BACKGROUND: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear. PURPOSE: The objectives of this trial were to study histamine release in human skin during the acute phase of a standardized thermal injury in healthy volunteers. METHODS: Histamine concentrations in human skin were measured by skin microdialysis technique. Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. A standardized superficial thermal injury was elicited by a heating thermode (49 degrees C) applied to the skin for 5 min. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods. RESULTS: Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20 min (n = 6) and 5-10-min samples over 120 min (n = 8). The histamine values were at the limits of the quantification limit of the spectrofluorometric assay. Confirmatory studies using a sensitive radioimmunoassay confirmed no histamine release within the first hour of a thermal injury (baseline 11.6 +/- 1.8 nM vs. post-burn values of 14.8 +/- 1.8 nM, n = 8). CONCLUSIONS: Histamine is not released in human skin during the acute phase of a thermal injury.

Udgivelsesdato: 2009-Apr, BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. RESULTS: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. CONCLUSIONS: Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.

Interleukin-15 (IL-15) is a proinflammatory, innate response cytokine that mediates pleiotropic effector function in rheumatoid arthritis (RA) inflammatory synovitis. Our objective was to study the ability of HuMax-IL15, a human IgG1 anti-IL-15 monoclonal antibody, to neutralize exogenous and endogenous IL-15 activity in vitro and to perform a phase I-II dose-escalation trial with HuMax-IL15 in patients with active RA.

Interleukin-15 (IL-15) is a proinflammatory, innate response cytokine that mediates pleiotropic effector function in rheumatoid arthritis (RA) inflammatory synovitis. Our objective was to study the ability of HuMax-IL15, a human IgG1 anti-IL-15 monoclonal antibody, to neutralize exogenous and endogenous IL-15 activity in vitro and to perform a phase I-II dose-escalation trial with HuMax-IL15 in patients with active RA.

Background: Patients with atopic dermatitis may experience exacerbations of eczema triggered by various inflammatory stimuli. One mechanism may be IgE-mediated reactions to dermatophytes since these patients are more likely to acquire skin infections with dermatophytes and may become sensitized. Objective: This study investigates IgE-sensitization to fungi in patients with atopic dermatitis and compares the biologic activity of culture filtrates and cellular fungal extracts. The following allergen extracts were provided as culture filtrates and cellular extracts: Candida albicans, Fusarium moniliforme, and Penicillium notatum. In addition, Pityrosporum ovale and Trichophyton rubrum cultures were included in the test panel. Methods: Fifteen patients with clinical findings suggesting dermatophytosis and 11 controls were selected. Each subject was tested by leukocyte histamine release and skin prick test to each fungal extract. The extracts were separated and reduced by sodium dodecylsulfate polyacrylamide gel electrophoresis and analyzed by IgE-immunoblotting with sera from all study subjects. Results: Fourteen patients (93%) reacted to one or several fungal extracts by releasing histamine when challenged in vitro. By immunoblotting experiments, patient sera showed binding to a wide range of components in all extracts. Patient sera recognized allergenic components shared by culture filtrates and cellular extracts but with higher frequent and greater intensity in culture filtrates. Although culture filtrates generated more frequent and potent IgE-reactions than the cellular extracts, the difference was not statistically significant. Biologic potency was similar when evaluated by skin prick tests and leukocyte histamine release. Conclusion: Patients with atopic dermatitis may develop specific IgE-antibodies to a number of fungi as demonstrated by IgE-immunoblotting. In selected patients, fungi may trigger an IgE-mediated reaction that may contribute to the exacerbati

Background: Patients with atopic dermatitis may experience exacerbations of eczema triggered by various inflammatory stimuli. One mechanism may be IgE-mediated reactions to dermatophytes since these patients are more likely to acquire skin infections with dermatophytes and may become sensitized. Objective: This study investigates IgE-sensitization to fungi in patients with atopic dermatitis and compares the biologic activity of culture filtrates and cellular fungal extracts. The following allergen extracts were provided as culture filtrates and cellular extracts: Candida albicans, Fusarium moniliforme, and Penicillium notatum. In addition, Pityrosporum ovale and Trichophyton rubrum cultures were included in the test panel. Methods: Fifteen patients with clinical findings suggesting dermatophytosis and 11 controls were selected. Each subject was tested by leukocyte histamine release and skin prick test to each fungal extract. The extracts were separated and reduced by sodium dodecylsulfate polyacrylamide gel electrophoresis and analyzed by IgE-immunoblotting with sera from all study subjects. Results: Fourteen patients (93%) reacted to one or several fungal extracts by releasing histamine when challenged in vitro. By immunoblotting experiments, patient sera showed binding to a wide range of components in all extracts. Patient sera recognized allergenic components shared by culture filtrates and cellular extracts but with higher frequent and greater intensity in culture filtrates. Although culture filtrates generated more frequent and potent IgE-reactions than the cellular extracts, the difference was not statistically significant. Biologic potency was similar when evaluated by skin prick tests and leukocyte histamine release. Conclusion: Patients with atopic dermatitis may develop specific IgE-antibodies to a number of fungi as demonstrated by IgE-immunoblotting. In selected patients, fungi may trigger an IgE-mediated reaction that may contribute to the exacerbati

Background: Patients with atopic dermatitis may experience exacerbations of eczema triggered by various inflammatory stimuli. One mechanism may be IgE-mediated reactions to dermatophytes since these patients are more likely to acquire skin infections with dermatophytes and may become sensitized. Objective: This study investigates IgE-sensitization to fungi in patients with atopic dermatitis and compares the biologic activity of culture filtrates and cellular fungal extracts. The following allergen extracts were provided as culture filtrates and cellular extracts: Candida albicans, Fusarium moniliforme, and Penicillium notatum. In addition, Pityrosporum ovale and Trichophyton rubrum cultures were included in the test panel. Methods: Fifteen patients with clinical findings suggesting dermatophytosis and 11 controls were selected. Each subject was tested by leukocyte histamine release and skin prick test to each fungal extract. The extracts were separated and reduced by sodium dodecylsulfate polyacrylamide gel electrophoresis and analyzed by IgE-immunoblotting with sera from all study subjects. Results: Fourteen patients (93%) reacted to one or several fungal extracts by releasing histamine when challenged in vitro. By immunoblotting experiments, patient sera showed binding to a wide range of components in all extracts. Patient sera recognized allergenic components shared by culture filtrates and cellular extracts but with higher frequent and greater intensity in culture filtrates. Although culture filtrates generated more frequent and potent IgE-reactions than the cellular extracts, the difference was not statistically significant. Biologic potency was similar when evaluated by skin prick tests and leukocyte histamine release. Conclusion: Patients with atopic dermatitis may develop specific IgE-antibodies to a number of fungi as demonstrated by IgE-immunoblotting. In selected patients, fungi may trigger an IgE-mediated reaction that may contribute to the exacerbati