Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

Spinal fluid dynamics during thoracic- and thoracoabdominal aortic surgery.

AIM: The intention was to investigate cerebrospinal fluid pressure (CSFP) and volume of cerebrospinal fluid (CSF) drained during and after thoracic- and thoracoabdominal aneurysm repair. The findings were related to the occurrence of postoperative neurologic deficits. METHODS: Twenty-nine patients (12 with thoracic and 17 with thoracoabdominal aortic aneurysm) were operated without shunting or extracorporeal circulation. For monitoring of CSFP an intrathecal catheter was placed in all patients. The volume of CSF withdrawn intraoperatively, on the day of operation as well as on the 1st and 2nd postoperative day was recorded. RESULTS: Twenty-six patients had no postoperative neurologic sequelae. One patient had postoperative paraplegia while 2 had paraparesis. The three patients with neurologic sequelae had higher CSFP intraoperatively than those without neurologic symptoms (P=0.04). Median CSFP during aortic cross-clamping was 19 mmHg and 10 mmHg and the median volumes of CSF drained on the day of operation 210 and 85 mL in the two groups, respectively. There was a significant positive correlation between CSFP and central venous pressure. CONCLUSIONS: A higher intraoperative CSFP was observed in patients with neurologic sequelae following thoracic- and thoracoabdominal aneurysm repair. Further, there was a tendency of higher volumes of CSF drained in this group of patients. Although, the series is too small to allow firm conclusions, it supports the view that CSFP monitoring and drainage is beneficial during thoracic- and thoracoabdominal aneurysm repair.     

Fetal growth patterns in fetuses of women with pregestational diabetes mellitus.

OBJECTIVE: To assess the effect of glucose control on the rate of growth of fetuses in women with pregestational diabetes mellitus (Types 1 and 2). METHODS: All pregestational diabetic women booked at Mater Mothers' Hospital, Brisbane, Australia, between 1 January 1994 and 31 December 2002, were included. Pregnancies with congenital fetal anomalies, multiple pregnancies, and pregnancies terminated prior to 20 weeks' gestation were excluded. Dating scans were performed before 14 weeks' gestation and serial scans were performed at 18, 24, 28, 32 and 36 weeks. Fetal parameters, including biparietal diameter, femur length and abdominal circumference, were recorded. The daily growth rates for biparietal diameter, femur length, and fetal abdominal area were calculated and compared with those in a low-risk (non-diabetic) population. The growth rates in fetuses of women with satisfactory diabetic control (HbA1c < 6.5%) and unsatisfactory control (HbA1c > or = 6.5%) in the three trimesters were compared. RESULTS: A total of 174 diabetic pregnancies were included and a total of 997 ultrasound scans were performed. The growth rates for fetuses of mothers with diabetes mellitus were significantly higher than for those in the low-risk population. The z-scores for biparietal diameter, femur length, and fetal abdominal area were 0.18, 0.59 and 1.44, respectively. Fetuses of diabetic mothers with high HbA1c in the first trimester had significantly greater fetal abdominal area growth rate than those with normal HbA1c (fetal abdominal area z-score of 1.7 vs. 0.75, P = 0.009). Although the fetal abdominal area z-scores in fetuses of diabetic mothers with high HbA1c in the second or third trimesters were also higher than those with normal HbA1c levels, the differences did not reach statistical significance. Maternal obesity did not influence the fetal growth rate. CONCLUSION: The rate of growth of fetuses of diabetic mothers differs from that of the normal population. Growth acceleration persists until the late third trimester. Moreover, periconceptional glucose control appears to have a significant effect on accelerated growth of the fetal abdominal area.     

Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.