Von Willebrand factor: a possible biomarker for disease activity in vasculitis.

OBJECTIVE: Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. METHOD: Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. RESULTS: Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. CONCLUSION: vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Radiological findings of early invasive pulmonary aspergillosis in immune-compromised patients.

Data on the radiological features of invasive pulmonary aspergillosis (IPA) in early stages is scanty. Detection of Aspergillus (ASP) species in broncho-alveolar (BAL) fluid by polymerase chain reaction (PCR) enables early diagnosis of IPA. This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune-compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11-30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs. 67%, p = 0.001). It was concluded that the radiological appearance of early IPA diagnosed with the aid of PCR testing included mainly discrete small nodules with halo and focal ground glass, representing the early stage of the disease.

Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities.

BACKGROUND: Human serum paraoxonase (PON1) exists in two polymorphic forms: one that differs in the amino acid at position 192 (glutamine and arginine, Q and R, respectively) and the second one that differs in the amino acid at position 55 (methionine and leucine, M and L, respectively). PON1 protects LDL from oxidation, and during LDL oxidation, PON1 is inactivated. METHODS AND RESULTS: The present study compared PON1 isoforms Q and R for their effect on lipid peroxide content in human coronary and carotid lesions. After 24 hours of incubation with PON1Q or PON1R (10 arylesterase units/mL), lipid peroxides content in both coronary and carotid lesion homogenates (0.1 g/mL) was reduced up to 27% and 16%, respectively. The above incubation was associated with inactivation of PON1Q and PON1R by 15% and 45%, respectively. Lesion cholesteryl linoleate hydroperoxides and cholesteryl linoleate hydroxides were hydrolyzed by PON1 to yield linoleic acid hydroperoxides and linoleic acid hydroxides. Furthermore, lesion and pure linoleic acid hydroperoxides were reduced to yield linoleic acid hydroxides. These results thus indicate that PON1 demonstrates esterase-like and peroxidase-like activities. Recombinant PON1 mutants in which the PON1-free sulfhydryl group at cysteine-284 was replaced with either alanine or serine were no longer able to reduce lipid peroxide content in carotid lesions. CONCLUSIONS: We conclude that PON1 may be antiatherogenic because it hydrolyzes lipid peroxides in human atherosclerotic lesions.

Impact of PCR-based diagnosis of invasive pulmonary aspergillosis on clinical outcome.

The mortality rate of 60-90% in invasive pulmonary aspergillosis (IPA) is partly explained by diagnostic delay due to the limitation of current diagnostic tests. We assessed the influence of Aspergillus species (ASP) DNA detection by PCR from bronchoalveolar lavage (BAL) fluid, a new tool for diagnosing IPA, on the outcome of this disease in immune-compromised patients. The study population comprised 107 consecutive patients with hematological malignancies from a single medical center with IPA diagnosed between 1998 and 2005. Clinical variables and mortality rates were compared between two groups diagnosed according to traditional criteria without and with PCR-based ASP DNA detection in BAL fluid. The overall mortality rate during the study period was 38.3%. The addition of PCR to the diagnostic criteria shifted 31 patients from possible to probable IPA. Patients diagnosed with probable IPA according to traditional microbiological methods had significantly higher mortality rates compared to their counterparts who had in addition a PCR-based diagnosis (80 vs 35.6%, P=0.003). This study demonstrates that PCR-based ASP DNA detection for a diagnosis of IPA from BAL fluid has a significant effect on the outcome of patients with IPA, probably related to earlier diagnosis.