Degradation of hydroxyapatite coating on a well-functioning femoral component

We carried out a histological study of a proximally hydroxyapatite (HA)-coated femoral component, retrieved after 9.5 years of good function. The HA coating had completely degraded. Bone was in direct contact with the titanium surface in all the areas which had been coated, with no interposing fibrous tissue. There were no signs of particles, third-body wear, adverse tissue reactions or osteolysis. Bone remodelling was evident by the presence of resorption lacunae; tetracycline labelling showed bone laid down six years after implantation. The loss of the HA-coating had no negative effect on the osseo-integration of the stem. We conclude that the HA coating contributes to the fixation of the implant and that its degradation does not adversely affect the long-term fixation.     

Is the response pattern of on- and off-cells in the rostral ventromedial medulla to noxious stimulation independent of stimulation site?

The classification of on- and off-cells in the rostral ventromedial medulla is based on the response pattern to noxious tail heat. It is generally assumed that on- and off-cells respond equally to noxious stimulation anywhere on the body surface, but so far this assumption has not been systematically examined. In the present study the effects of noxious thermal and mechanical stimuli applied to the tail, the extremities and the craniofacial region on the extracellularly recorded activity of 13 on- and 23 off-cells were investigated in lightly anesthetized rats. In 3 out of 13 on-cells and 11 out of 23 off-cells the response pattern evoked by noxious stimulation of the extremities or the craniofacial region differed from the response pattern elicited by noxious tail heat. In comparison with the response pattern to noxious tail heat, stimulation of the extremities or the craniofacial region reproducibly evoked opposite reactions in 2 on- and 9 off-cells and did not change neuronal activity in one on- and 2 off-cells. The results of the present study raise the question of whether the response pattern of on- and off-cells in the rostral ventromedial medulla can be sufficiently predicted by a classification that is exclusively based on the cellular behavior to noxious heat stimulation of the tail.     

Mice with astrocyte-directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels

Gap junctions mediate communication between many cell types in the brain. Gap junction channels are composed of membrane-spanning connexin (Cx) proteins, allowing the cell-to-cell passage of small ions and metabolites. Cx43 is the main constituent of the brain-spanning astrocytic gap junctional network, controlling activity-related changes in ion and glutamate concentrations as well as metabolic processes. In astrocytes, deletion of Cx43-coding DNA led to attenuated gap junctional coupling and impaired propagation of calcium waves, known to influence neuronal activity. Investigation of the role of Cx43 in behaviour has been impossible so far, due to postnatal lethality of its general deletion. Recently, we have shown that deletion of Cx30, which is also expressed by astrocytes, affects exploration, emotionality, and neurochemistry in the mouse. In the present study, we investigated the effects of the astrocyte-directed inactivation of Cx43 on mouse behaviour and brain neurochemistry. Deletion of Cx43 in astrocytes increased exploratory activity without influencing habituation. In the open field, but not in the elevated plus-maze, an anxiolytic-like effect was observed. Rotarod performance was initially impaired, but reached control level after further training. In the water maze, Cx43 deficient mice showed a steeper learning course, although final performance was similar between groups. Cx43 inactivation in astrocytes increased acetylcholine content in the frontal cortex of water maze-trained animals. Results are discussed in terms of altered communication between astrocytes and neurons, possible compensation processes, and differential effects of Cx30- and astrocyte-specific Cx43 deletion.     

Reduced intensity conditioning prior to allogeneic stem cell transplantation in first complete remission is effective in patients with acute myeloid leukemia and an intermediate-risk karyotype

To evaluate the efficacy of reduced intensity conditioning (RIC) prior to allogeneic stem cell transplantation (alloSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1), we retrospectively analyzed the outcome of 93 consecutive patients transplanted at our institution either following RIC (n = 37) or standard myeloablative conditioning (MAC) (n = 56) between 1999 and 2007. Projected overall survival (OS) or disease-free survival (DFS) for all patients at 1, 2, and 5 years was 78 or 70%, 65 or 57%, and 61 or 53% in the RIC group versus 73 or 70%, 68 or 62%, and 56 or 54% in the standard MAC group. In the subgroup of patients with an intermediate-risk karyotype projected OS at 1, 2, and 5 years was 86, 68, and 68% following RIC (n = 21) or 75, 69, and 66% following standard MAC (n = 36). Relapse or treatment-related mortality (TRM) was 15 or 17% (RIC group) and 26 or 14% (standard MAC group). Taken together, these data suggest that RIC-alloSCT may induce stable remissions in patients with AML transplanted in CR1. In particular, patients with an intermediate-risk karyotype ineligible to transplantation following standard MAC may benefit from RIC-alloSCT in CR1 at a low TRM.     

Use of diuretics and risk of implant failure after primary total hip arthroplasty: A nationwide population-based study

IntroductionThiazid and loop diuretics have been associated with changes in bone mineral density and fracture risk. However, data on survival of prosthesis implants are lacking. We evaluated the association between diuretic use and the risk of revision after primary total hip arthroplasty (THA).Materials and methodsWe conducted a nationwide population-based case-control study using medical databases in Denmark. In the Danish Hip Arthroplasty Registry, we identified 2491 cases that were revised after primary THA in the period 1995–2005 and who could be matched on age, gender and year of primary operation with 4943 non-revised THA controls. By means of conditional logistic regression, we estimated the relative risk (RR) of revision due to all causes and due to specific causes according to postoperative use of thiazid and loop diuretic, respectively.ResultsThe 10-year cumulated implant revision rate in the underlying cohort of 57,575 THA procedures from the Danish Hip Arthroplasty Registry was 8.9% (95% CI: 8.4–9.4). Postoperative thiazid diuretic use was not associated with neither the overall risk of revision nor revision due to specific causes compared to non-use. Postoperative loop diuretic use was associated with an adjusted RR of revision of 1.14 (95% CI; 0.98–1.32) compared with non-use. The adjusted RR of revision due to deep infection and periprosthetic fracture in loop diuretic users was 1.71 (1.15–2.55) and 6.39 (1.84–22.21), respectively. Loop diuretic use was not associated with risk of revision due to aseptic loosening, dislocation or miscellaneous causes.DiscussionLoop diuretics but not thiazides may be associated with an increased risk of revision following primary THA. Further studies are warranted in order to confirm this finding and clarify the nature of the association.