Finite element analysis performed on radius and tibia HR‐pQCT images and fragility fractures at all sites in men

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case‐control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)‐pQCT, and finite element (µFE) analysis was based on HR‐pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from ?6% to 15%. µFE‐derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE‐derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27–2.12] (2.21 [1.60–3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00–1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16–2.09] (2.21 [1.59–3.07]), and with PC2, with OR = 1.55 [1.17–2.06] (1.45 [1.06–1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties. © 2011 American Society for Bone and Mineral Research.     

The influence of non‐HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Non‐HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti‐angiotensin II type 1‐receptor‐activating antibodies (anti‐AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti‐AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti‐AT1R antibodies in 117 consecutive renal transplant recipients in pre‐ and post‐transplant screening. Anti‐AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti‐AT1R(+) group. The patients with anti‐AT1R Abs >9 U/ml lost their graft more often. Biopsy‐proven AR was described in 4/27 (15%) pts in the anti‐AT1R(+) group and 13/90 (14.4%) in the anti‐AT1R(?) group, but more severe cases of Banff IIB or antibody‐mediated rejection (AMR) were more often observed in anti‐AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti‐AT1R(+) (P = 0.009). Patients with anti‐AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti‐AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti‐AT1R‐positive ones lost the graft. Our study suggests monitoring of anti‐AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.     

G8363A mitochondrial DNA mutation is not a rare cause of Leigh syndrome - clinical, biochemical and pathological study of an affected child

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, having relatively homogeneous clinical symptomatology and pattern of neuropathological changes, shows remarkable heterogeneity in biochemical and molecular background. G8363A mitochondrial DNA mutation typical for MERRF syndrome and progressive cardiomyopathy may also be associated with LS. Clinical, biochemical and pathological findings in a boy aged 28 months who died with classical COX-deficientLSassociatedwithmtG8363Aisdescribedindetail.Hyperlactataemia,LCHAD-like organic acids profile and respiratory alkalosis(pH7.47,pCO2 4.9 mmHg, HCO3 3.0 mmol/l) were observed. Spectrophotometric assay showed deficit of respiratory chain complexes IVand I. Skeletal muscle biopsy revealed mosaic cytochrome oxidase deficit,lipid accumulation and ultrastructural abnormalities of mitochondria. Postmortem examination confirmed the presence of typical LS central nervous system lesions as well as hypertrophy of the left ventricle of the heart.Conclusion: mtG8363A "MERRF-like" mutation should be included in the differential diagnosis of classical LS in infants. This case is in agreement with our hypothesis that hyperventilation plays a substantial role in progression of central nervous system damage.     

Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II–IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III–IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II–IV astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. These findings suggest that focal radiation may be inadequate for some of these patients. Importantly, we show that clinically classic DIPGs represent a diverse histologic spectrum, including multiple cases which would fit WHO criteria of grade II astrocytoma which nevertheless behave clinically as high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests that the current WHO astrocytoma grading scheme may not appropriately predict outcome for paediatric brainstem gliomas.     

Experience with intraoperative high frequency Doppler sonography in neurosurgical practice

Abstract

The method of blood flow velocity (BFV) evaluation by intraoperative application of the high frequency Doppler is presented. The device is used to estimate BFV changes in small caliber arteries by direct placement of the probe upon the examined vessel. BFVexaminations were performed on the site during aneurysm operations, during transsphenoidal approaches to identify the intracavernous portion of leA embedded in the tumor mass and in patients after encephalodurosynangiosis evaluated on the outpatient basis. Technical characteristics of the flowmeter used are described and examples of the BFV pictures in cerebral arteries are presented. The device allows a precise BFVevaluation in the selected vessel and detection of changes in BFV patterns particularly useful during aneurysms surgery. This method of identifying cerebral vessels may become applicable in other types of neurosurgical operations. [Neural Res 1998; 20: 655–657]     

Serum concentrations of 17β-E2 and 25-hydroxycholecalciferol (25OHD) in relation to all-cause mortality in older men – the MINOS study

Objective To examine the association of serum hormone levels with all‐cause mortality in older community‐dwelling men. Design Single centre cohort study. Subjects Men aged 50 and older, insured by Société de Secours Minière de Bourgogne (Montceau les Mines, France). Among 3400 men invited to participate, 782 volunteers had serum hormone measurements and were followed up for 10 years. No exclusion criteria were used. Results Nonsurvivors (n = 182) were older, had more comorbidities and lower physical performance. The lowest quartile of 25‐hydroxycholecalciferol (25OHD) level predicted mortality [HR = 1·44, 95% confidence interval (CI): 1·03–2·03, P < 0·05] regardless of age, BMI, smoking, physical activity, vitamin D supplementation, and health status; mainly for the first 3 years. The 17β‐E₂ level predicted mortality independent of confounders after the third year (HR = 1·21 per 1 SD increase, 95% CI: 1·09–1·35, P < 0·001). In the fully adjusted models, risk of death increased per quartiles of 17β‐E₂ (trend –P < 0·001) and was higher in the third and the fourth quartiles compared with the lowest quartile (HR = 1·80, 95% CI: 1·09–2·98, P < 0·05 and HR = 2·83, 95% CI: 1·71–4·67, P < 0·001). Concentrations of testosterone and PTH did not predict mortality independent of the model. Conclusions In older men, increased 17β‐E₂ level predicted mortality after 3 years of follow‐up. Thus, high 17β‐E₂ level may reflect presence of risk factors precipitating development of diseases. Low 25OHD level predicted mortality more weakly, mainly for the first 3 years of the follow‐up, and was strongly influenced by the confounding variables. Thus, low 25OHD level may reflect poor current health status and unhealthy lifestyle.