High-resolution HLA matching in double-umbilical-cord-blood reduced-intensity transplantation in adults

BACKGROUND: Double-cord-blood transplantation (DCBT) offers an option for patients receiving reduced-intensity transplants. These unique transplants have two donors, both of whom are usually HLA mismatched at one to two loci.
STUDY DESIGN AND METHODS: Fifty-three patients were recipients of a reduced-intensity DCBT. Cords were at least 4/6 allele-level HLA-A, -B, and -DR match with the patient and each other with a minimum combined cell dose of more than 3.7 × 10⁷ total nucleated cells per kg. Twenty-one patients received cyclosporine/mycophenolate mofetil and 32 patients received sirolimus/tacrolimus (SIR/TAC) for graft-versus-host disease prophylaxis. The effect of allele level HLA typing on clinical endpoints of overall survival (OS), disease-free survival (DFS), engraftment, and acute graft-versus-host disease (aGVHD) were assessed.
RESULTS: Neutrophil (p = 0.001) engraftment and platelet engraftment (p = 0.027) were significantly faster in patients who have closer Class I (HLA-A, -B, -C) matching. Neutrophil engraftment was faster in patients who had closer HLA-B matching to their combined cords (p = 0.007). There was a low incidence of aGVHD overall, especially in the SIR/TAC group. Class I HLA matching had no effect on aGVHD. HLA-DR and -DQ had no effect on engraftment or aGVHD.
CONCLUSION: Class I allele matching, and HLA-B matching specifically, were associated with faster neutrophil engraftment. High-resolution HLA matching did not affect OS or DFS.     

医学催眠术治疗颞下颌紊乱

颞下颌紊乱的患者有咀嚼肌系统或颞下颌关节的功能障碍或二者兼有,典型症状为咀嚼肌疼痛,常伴有耳痛、头痛、面痛并向颈部或肩部放射,发病率约为5％左右。目前普遍认为心理压力是其主要原因,对该病的保守治疗方法主要包括对牙齿的治疗、理疗和抗炎治疗等。本研究目的是探讨医学催眠术对减轻颞下颌紊乱疼痛症状的作用。     

Rheumatoid arthritis: explanatory power of specific radiographic findings for patient clinical status

Radiographs of the hands and wrists of 201 patients with rheumatoid arthritis (RA) were scored for erosion, joint space narrowing, and malalignment. The explanatory power of these findings for measures of clinical status was studied with stepwise multiple linear regression analyses. Radiographic scores explained 59.2% of variation in physical joint count deformity scores, 58.5% of variation in limited motion scores, 22.5% of variation in grip strength scores, 20.5% of variation in button test scores, and 13.5% of variation for the American Rheumatism Association (ARA) Functional Class. Malalignment scores best explained variation in physical deformity, limited motion, and button test scores; joint-space-narrowing scores best explained variation in grip strength; erosion scores best explained variation in ARA Functional Class. When age, duration of disease, erythrocyte sedimentation rate, and rheumatoid factor titer were included in the regression analyses, results were similar to those without these variables. Therefore quantitative scores of specific radiographic findings are in themselves explanatory for measures of clinical status.     

Effect of Mn Doping on the Optical and Electrical Properties of Double Perovskite Sr2TiCoO6

A new series of Sr₂TiCo_1−xMn_xO₆ (0.0 ≤ x ≤ 0.7) materials has been synthesized using the conventional solid-state method. In this research, X-ray diffraction (XRD) results showed that Mn was successfully doped at the Co site in a cubic structure with monoclinic P2₁/n space group. The effect of Mn cation substitution on the structural, optical and electrical performance of Sr₂TiCo_1−xMn_xO₆ double perovskite was investigated. The optical study revealed a nonlinearity pattern of the band gap that is referred to as the band gap bowing trend. Results from optical and Rietveld refinement supports that the band gap bowing trend is correlated with the charge distribution that produces unique effects on structural and size changes due to the Co-Mn compositions. The morphological scanning electron microscopy studies also showed that larger crystallite sizes were developed when dopant was added. Furthermore, increases in the conductivities support the lowering band gap of Mn-doped samples. Here, the intermixing of the atomic orbitals of Co-Mn provides an efficient interlink electrical pathway to improve conductivity and exhibits a high dielectric property at room temperature. These values are strong evidence that STCM material will be suitable for applications in the semiconductor industry.     

Relation between regional and global systolic function in patients with ischemic cardiomyopathy after β-Blocker therapy or revascularization

Background

To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or revascularization.

Materials and methods

Cardiovascular Magnetic Resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 ± 2 months after therapy. Patients were assigned clinically to β-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation.

Results

Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the β-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05).

Conclusion

In patients with chronic ischemic LV dysfunction, β-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after β-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.     

The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha

The chemokine stromal-derived factor-1alpha (SDF-1alpha) is a chemoattractant for CD34(+) progenitor cells, in vitro and in vivo. The receptor for SDF-1alpha, CXCR-4, is a 7 transmembrane domain receptor, which is also a coreceptor for human immunodeficiency virus (HIV). Here we show that transformation of hematopoietic cell lines by BCR/ABL significantly impairs their response to SDF-1alpha. Three different hematopoietic cell lines, Ba/F3, 32Dcl3, and Mo7e, were found to express CXCR-4 and to respond to SDF-1alpha with increased migration in a transwell assay. In contrast, after transformation by the BCR/ABL oncogene, the chemotactic response to SDF-1alpha was reduced in all 3 lines. This effect was directly due to BCR/ABL, because Ba/F3 cells, in which the expression of BCR/ABL could be regulated by a tetracycline-inducible promoter, also had reduced chemotaxis to SDF-1alpha when BCR/ABL was induced. The reduced response to SDF-1alpha was not due to an inability of BCR/ABL-transformed cell lines to migrate in general, as spontaneous motility of BCR/ABL-transformed cells was increased. In mice, injection of SDF-1alpha into the spleen resulted in a transient accumulation of untransformed Ba/F3 cells, but not Ba/F3. p210(BCR/ABL) cells administered simultaneously. The mechanism may involve inhibition of CXCR-4 receptor function, because in BCR/ABL-transformed cells, CXCR-4 receptors were expressed on the cell surface, but SDF-1alpha calcium flux was inhibited. Because SDF-1alpha and CXCR-4 are felt to be involved in progenitor cell homing to marrow, the abnormality decribed here could contribute to the homing and retention defects typical of immature myeloid cells in chronic myelogenous leukemia.     

Cerebral vasculitis--recognition, diagnosis and management

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.