Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: A 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study

The aim of this study was to evaluate whether a prevalent vertebral deformity predicts mortality and fractures in both men and women. In the city of Malmö, 598 individuals (298 men, 300 women; age 50–80 years) were selected from the city's population and were included in the Swedish part of the European Vertebral Osteoporosis Study (EVOS). At baseline the participants answered a questionnaire and lateral spine radiographs were performed. The prevalence of subjects with vertebral deformity was assessed using a morphometric method. The mortality during a 10-year follow-up period was determined through the register of the National Swedish Board of Health and Welfare. Eighty-five men and 43 women died during the study period. The subsequent fracture incidence during the follow-up period was ascertained by postal questionnaires, telephone interviews and by a survey of the archives of the Department of Radiology in the city hospital. Thirty-seven men and 69 women sustained a fracture during the study period. Data are presented as hazard ratios (HR) with 95% confidence interval (95% CI) within brackets. Prevalent vertebral deformity, defined as a reduction by more than 3 standard deviations (SD) in vertebral height ratio, predicted mortality during the forthcoming decade in both men [age-adjusted HR 2.4 (95% CI 1.6–3.9)] and women [age-adjusted HR 2.3 (95% CI 1.3–4.3)]. In men there was an increased mortality due to cardiovascular and pulmonary diseases and in women due to cancer. Prevalent vertebral deformity predicted an increased risk of any fracture during the forthcoming decade in both men [age-adjusted HR 2.7 (95% CI 1.4–5.3)] and women [age-adjusted HR 1.8 (95% CI 1.1–2.9)]. Prevalent vertebral deformity predicted an increased risk of any subsequent fragility fracture in women [age-adjusted HR 2.0 (95% CI 1.1–3.5)]; however, in men the increased risk was nonsignificant [age-adjusted HR 1.9 (95% CI 0.7–5.1)]. In summary, a prevalent vertebral deformity can predict both increased mortality and increased fracture incidence during the following decade in both men and women. We conclude that prevalent vertebral deformity could be used as a risk factor in both genders for mortality and future fracture.     

Bacterial components regulate the expression of Toll-like receptor 4 on human mast cells

Objectives and design: The aim of this study was to investigate whether the exposure of mast cells (MCs) to bacterial components affects the expression of Toll-like receptor (TLR) 4, and to elucidate the behavior of MCs during the early response to infection. Materials: Two human MC lines, HMC-1 and LAD2, were employed. Messenger RNA expression was observed by RT and real-time PCR. TLR4 expression was determined by Western blotting. TNF-α secretion was analyzed with ELISA. The degranulation ratio was measured with betahexosaminidase assay. Results: Although bacterial components increased TLR4 mRNA, only lipopolysaccharide (LPS) augmented the TLR4 protein expression. LAD2 pre-treated with LPS for 8 h resulted in 2-fold increased TNF-α secretion on LPS restimulation. Conclusion: These results suggest that the exposure of MCs to LPS may reinforce the innate immune system due to up-regulation of MC TLR4, followed by increased TNF-α release. Received 20 April 2006; returned for revision 14 July 2006; accepted by G. Wallace 11 August 2006     

Wachstumsretardierung durch A.-iliaca-Verschluss nach Herzkatheteruntersuchung

Cardiac catheterisations in newborns and infants are being performed routinely in increasing numbers for diagnostic and therapeutic purposes. Rarely, the femoral artery or the iliac artery will be completely occluded after such a procedure, and growth retardation of the lower extremity can result. We report on a case of iliofemoral artery occlusion following cardiac catheterisation in an infant. Twelve years later, a difference of 5.5 cm in leg length was noted, as well as a difference in shoe size and intermittent claudication. Following operative reconstruction, the child’s leg pain ceased. Two years after surgery, differences in leg lengths and shoe sizes are no longer significant. Vascular complications should not be underestimated despite the juvenile potential for collateral vessels. Even in the absence of signs of ischaemia, these complications necessitate further investigation and adequate treatment in due course.     

Reelin expression is upregulated following ocular tissue injury

Purpose Reelin is important in the guidance of neuronal stem cells in the central nervous system during normal development. We wished to determine whether reelin is expressed in the retina and cornea after injury. Methods Mice underwent laceration of their retina as well as corneal epithelial debridement. The mice were sacrificed at 3 days, and eyes were fixed and stained for reelin expression and reelin messenger ribonucleic acid (mRNA). Results In normal eyes, reelin was expressed only at very low levels in the ganglion cell layer of the retina and the endothelial cell layer of the cornea. In injured eyes, there was marked expression in reelin immunoreactivity in the retina and cornea. Reelin gene expression was seen in the retina and cornea. Conclusions Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis. For consideration of publication in Graefe’s Archive for Clinical and Experimental Ophthalmology.     

Recombinant α2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation

Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies. BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.