Wall shear stress in the stented superficial femoral artery in peripheral arterial disease

Objective

Local changes in wall shear stress (WSS) contribute to vascular wall thickening and subsequent stenosis. Restenosis after stenting is a major concern, especially in the superficial femoral artery (SFA) of patients with peripheral arterial disease (PAD). Local alterations in WSS after stenting might contribute to restenosis/reocclusion. To test the hypothesis that WSS is impaired along the stented SFA segment, we studied the profile of WSS along the femoro-popliteal axis after stent placement in a cross-sectional design.

Methods

Eighty-seven patients with PAD (89 limbs) were included one day after stenting of the SFA. Flow velocities (peak and mean) and vessel diameter were measured by duplex ultrasound in five predefined segments along the femoro-popliteal axis, at rest and after exercise (30 toe raises); WSS (peak and mean) was calculated from flow velocities, vessel diameter and whole blood viscosity.

Results

WSS progressively declined along the stented segment at rest (peak WSS, p < 0.0001; mean WSS, p < 0.05); after exercise, WSS increased in all segments (all p < 0.001), but, again, progressively declined along the stent (peak WSS, p < 0.0001; mean WSS, p < 0.05). The internal vessel diameter remained unchanged after exercise in the stented and in the non-stented parts of the femoro-popliteal axis (all p > 0.05).

Conclusion

In PAD patients with SFA stenting WSS is impaired along the femoro-popliteal axis. The consequences of this finding in terms of local effects on the vessel wall that might favor restenosis/reocclusion needs further investigation.     

Impaired polysaccharide responsiveness without agammaglobulinaemia in three patients with hypomorphic mutations in Bruton Tyrosine Kinase—No detection by newborn screening for primary immunodeficiencies

Hypomorphic mutations in the gene encoding Bruton tyrosine kinase (BTK) may result in milder phenotypes and delayed diagnosis of B-cell related immunodeficiencies due to residual BTK function. Newborn screening for kappa-deleting-recombination-excision circles (KRECs) reliably identifies classical X-linked agammaglobulinaemia (XLA) patients with profound B-cell lymphopenia at birth but has not been evaluated in patients with residual BTK function. We aimed to evaluate clinical findings, BTK function and KREC copy numbers in three patients with BTK mutations presenting with impaired polysaccharide responsiveness without agammaglobulinaemia. One patient had an invasive pneumococcal infection at the age of 4 years. All three patients (two brothers) had visible tonsils, normal to slightly decreased immunoglobulin G levels, undetectable pneumococcal antibodies despite pneumococcal conjugate vaccinations, no antibody response after a diagnostic polysaccharide vaccination as well as profound B-cell lymphopenia with residual B-cell differentiation. BTK mutations were identified by Sanger sequencing. BTK staining and phosphorylation assays were performed on peripheral B cells. KREC copy numbers were determined from dried blood spots obtained within the first week of life as well as once at the age of 8, 6 and 3 years, respectively. BTK staining showed residual protein expression. Also, residual BTK activity could be demonstrated. KREC copy numbers from dried blood spots were above the threshold set for detection of patients with profound B-cell lymphopenia. Male patients with impaired polysaccharide responsiveness should be evaluated for B-cell lymphopenia followed by BTK analyses irrespective of immunoglobulin levels or tonsil size.     

Comparative analysis of cathepsin l,cathepsin d,and collagenase messenger rna expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis,by in situ hybridization

Objective. To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin-labeled RNA probes. Results. Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens. Conclusion. Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion of synovial cells to cartilage mediates the invasive destructive process in RA.     

Hematopoietic reconstitution after bone marrow transplantation: Assessment with MR imaging and H-1 localized spectroscopy

Magnetic resonance (MR) studies were performed in 14 patients as early as possible (21–110 days) after bone marrow transplantation (BMT). MR characteristics of lumbar vertebral bone marrow were studied with T1-weighted spin-echo imaging, water- and fatselective imaging with a frequency-selective excitation technique, and point-resolved spatially localized proton spectroscopy. Signals from water and fat protons and their T1 and T2 values were analyzed. Water proton signal intensity correlated well with cellularity within bone marrow, as determined with parallel iliac crest biopsies. The fraction of signal from water in red bone marrow of patients with allogeneic transplants from siblings (four cases) was significantly higher than in four patients with autologous transplants. The latter showed very low cellularity in the period of about 4 weeks after BMT because of the cytotoxic pretreatment of the bone marrow. The MR results in six patients with allogeneic transplants from unrelated donors ranged widely, depending on the complications after BMT. Analysis of data obtained with the different techniques showed that water- and fat-selective MR imaging and spectroscopic methods are useful for noninvasive monitoring of hematopoietic reconstitution after BMT.