Clinical,instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10–50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10–50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.     

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls

Objective

One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer’s disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls.

Methods

We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only.

Results

The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate.

Conclusions

The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.     

Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjögren's syndrome

Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p = 0.42), seroprotection (83.3 vs. 72.2%, p = 0.26) and FI-GMT (p = 0.85). Disease duration, prednisone (2.1 ± 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p > 0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p > 0.05) and only mild side effects were reported in comparable rates to controls (p > 0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p = 0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p = 0.0001) and anti-La/SSB (p = 0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.     

Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation.

BACKGROUND: Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection. METHODS: The incidence and severity of acute rejection and the number of steroid pulses were analyzed in 20 lung recipients who were converted from a cyclosporine- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven acute rejection. RESULTS: Tacrolimus was started 12.0 +/- 13.0 months after transplantation, and the mean follow-up was 25.0 +/- 13.7 months. After shifting to tacrolimus, a significant decline was observed in both the number of acute rejections per patient (3.0 +/- 1.56 to 0.85 +/- 1.14, p < 0.0001), and the incidence of acute rejection per 100 patient-days (1.52 +/- 0.99 to 0.14 +/- 0.21, p < 0.0001). Furthermore, the average histologic grade of rejection decreased from 1.9 +/- 0.8 to 0.4 +/- 0.5 (p < 0.0001). Methylprednisolone pulses similarly decreased from 1.9 +/- 1.3/patient to 0.3 +/- 0.7/patient (p < 0.0001). During cyclosporine immunosuppression, the mean forced expiratory volume in 1 second decreased to 84.4% +/- 13.3% of individual best value. The average lung function parameters were stable 3 months after the change of medication, and then began to improve. After an average follow-up of 36.5 +/- 19.2 months, 2 patients have developed bronchiolitis obliterans syndrome (one has Stage 1 and one has Stage 3). CONCLUSION: Conversion to a tacrolimus-based immunosuppressive regimen for refractory acute lung rejection is associated with reduced incidence and severity of acute rejection episodes, steroid sparing, and stabilization or improvement of pulmonary function.     

Cervical cancer and herpes simplex virus type 2: Case-control studies in Spain and Colombia,with special reference to immunoglobulin-G sub-classes

Two casecontrol studies, including 449 histologically confirmed cases of cervical intraepithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using typespecific antigens, glycoprotein C for type I (gC-1) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) subclasses, IgG₁ and lgG3_r were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG₁. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG₁ in Spain. The levels of lgG₃ and its ratio to lgG₁, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with lgG₁ was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.     

Running fatiguing protocol affects peak torque joint angle and peak torque differently in hamstrings vs. quadriceps

Sport Sciences for Health - The aim of the current study was to investigate the effects of a running fatiguing protocol on the peak torque joint angle and the peak torque in hamstrings vs....