DAS181 treatment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation.

Parainfluenza infection is a cause of significant morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) patients. DAS181 is a novel antiviral agent with activity against influenza and parainfluenza. We report the first 2 cases, to our knowledge, of successful DAS181 use in ventilated HSCT patients with severe parainfluenza lung disease.

The effects of anti-resorptive therapies and estrogen withdrawal in adult scoliosis measured by sub-segmental vertebral BMD analysis.

The sub-segmental analysis of dual energy X-ray absorptiometry (DXA) scans from scoliotic vertebrae has established that there are differences in bone mass between the concave and convex sides of the vertebrae. Furthermore, these differences persisted in patients with low bone mass and were related to the geometry and applied loads, suggesting that this is a good model of bone adaptation in response to external stimuli. The goal of this study was to characterize the response of the human scoliotic spine to anti-resorptive treatments and estrogen withdrawal on the concave and convex sides of the spine. A total of 576 vertebrae (199 no treatment, 214 bisphosphonate, 69 estrogen and 94 estrogen withdrawal) were analyzed from 167 postmenopausal, Caucasian women. An analysis of variance (ANOVA) was used in conjunction with post-hoc Tukey tests to examine the effects of concavity, treatment group, and age. We found that the average change in BMD per year was greater than zero on the concave and convex sides with the exception of the estrogen withdrawal group. Discontinuing estrogen therapy caused patients to maintain bone mass on the concave side, but lose substantial bone density on the convex side. A differential response was also observed with respect to age. Patients younger than 60 exhibited a decrease in total BMD per year concomitant with a small degree of straightening, while those who were 60 or over demonstrated an increase in bone mass and a slight increase in the deformity. Based on these data, it is clear that the differences in BMD between the concave and convex sides of the vertebrae are not simply a result of the deformity, but more likely due to bone accretion. Further study is needed to elucidate the relationship between biomechanical forces and the adaptive response in the spine as a function of time.

Aggregate morphology and aggregation rate constants for silica dispersions in the presence of salt and polyelectrolyte.

It is shown that the addition, over suitable concentration ranges, of mixtures of (nonadsorbing) sodium poly(styrene sulfonate) and potassium chloride, to dispersions of silica particles in water, can lead to very large changes in the sediment height of the resulting aggregates, reflecting similarly large changes in particle packing density within the aggregates. It can also lead to aggregation rates which are considerably faster than the diffusion-controlled rates (by as much as a factor of 2.5), although this enhancement is reduced as the dispersion particle concentration is reduced.

The relationship between bone mineral density and biomechanics in patients with osteoporosis and scoliosis.

Nearly one-third of all women and one-sixth of all men over age 65 have osteoporosis, and this condition is often accompanied by lumbar scoliosis. Previous work has shown that, in a group of postmenopausal women with scoliosis and osteoporosis, both the bone mineral content (BMC) and bone mineral density (BMD) were greater on the concave side than the convex side. The goal of this study was to examine the structure-function relationships in the spines of patients with low bone mass and scoliosis using a patient-specific biomechanical model. We compared the percent change in BMC and the percent change in BMD with axial force, F(a), shear force, F(s), moment, M, local curvature, theta(rel), and the patient's age, A. We found that the percent change in BMC depended on the applied moment and the local curvature. The same dependence was observed for the percent change in BMD, but in this case, the shear force was also significantly inversely correlated. A population with femoral neck BMD with a T-score greater than -2.0 was similarly evaluated and yielded similar results. The percent change in BMD was related to M, theta(rel), A and negatively to the shear force. These results indicate that the osteoporotic spine is still able to respond to changes in the mechanical environment and provides a useful comparison between patients with osteoporosis and those with normal bone mass. In addition, this model may be a useful tool for the in vivo assessment of bone density changes in response to mechanical stimuli and drug treatments.

Assessment of bone quantity and distribution in adult lumbar scoliosis: new dual-energy x-ray absorptiometry methodology and analysis.

STUDY DESIGN: In this study, we elucidated the bone quantity and distribution in lumbar spines of a group of 176 postmenopausal women (average age 72 years) with scoliosis. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis is associated with a low bone mineral density, but the bone mineral density in adult lumbar scoliosis has not been well-characterized. METHODS: Dual-energy x-ray absorptiometry analysis of the femoral neck and lumbar spines of 176 postmenopausal women were used to assess the bone mineral density and bone mineral content at both anatomic sites. Subsegmental analysis was used to determine the bone distribution within the lumbar vertebrae. RESULTS: The lumbar spine bone mass was greater than the femoral neck as evidenced by the average lumbar spine and femoral neck T-scores, -0.493 and -1.81, and Z-scores, 1.70 and 0.12, respectively. There was also a significant correlation between the lumbar spine bone mineral density and femoral neck bone mineral density (r2 = 0.24, P < 0.0001). Individual analysis of 655 vertebrae after bisection and trisection showed that the bone mineral density of the concave side was 15% to 20% higher than the convex, and the difference between the 2 sides was at least as great for patients with low femoral neck bone mineral density as those with high femoral neck bone mineral density. CONCLUSIONS: The quantity and distribution of bone in adult scoliosis is markedly different from adolescent scoliosis. The lumbar spine bone mass is much greater than the femoral neck, and the concave side bone mass is greater than the convex. Finally, subsegmental vertebral dual-energy x-ray absorptiometry analysis may have wider applications in research and clinical settings.

The glutamine/glutamate couplet and cellular function.

All cells require glutamine as a nitrogen donor as well as an energy source for cell-specific functions. Understanding how glutamine utilization is metered to these demands is fundamental to basic cell processes as well as to therapeutic manipulation of regulatory mechanisms. The regulatory role of the glutamine/glutamate couplet in cellular function is illustrated for acid-base homeostasis and for production of the extracellular matrix.

Troglitazone halts diabetic glomerulosclerosis by blockade of mesangial expansion.

BACKGROUND: Renal complications of long-term, poorly controlled type 2 diabetes mellitus include glomerulosclerosis and interstitial fibrosis. The onset and progression of these complications are influenced by underlying pathophysiologies such as hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. Troglitazone, a thiazolidinedione, has been shown to ameliorate these metabolic defects. However, it was not known whether therapeutic intervention with troglitazone would prevent the onset and progression of glomerulosclerosis. METHODS: Sixty male ZDF/Gmitrade mark rats and 30 age-matched Zucker lean rats were in the study. The ZDF/Gmitrade mark rats were divided into two groups, one in which blood glucose levels were uncontrolled (30 animals) and another (30) in which blood glucose was controlled via dietary administration of troglitazone. Ten animals from each group were sacrificed at one, three, and six months into the study. The kidneys were harvested and processed for immunostaining with BM-CSPG, a marker for mesangial matrix. Images of 200 glomeruli per animal were captured using digital imaging microscopy, and the index of mesangial expansion (total area mesangium/total area of tuft) per glomerular section was measured. RESULTS: The administration of troglitazone ameliorated the metabolic defects associated with type 2 diabetes mellitus. Moreover, the glomeruli from tissue sections of animals given troglitazone showed no mesangial expansion when compared with normoglycemic control animals, whereas the uncontrolled diabetic animals showed significant mesangial expansion at all time intervals. CONCLUSIONS: Therapeutic intervention with the thiazolidinedione troglitazone halts the early onset and progression of mesangial expansion in the ZDF/Gmitrade mark rat, preventing the development of glomerulosclerosis in this animal model of type 2 diabetes mellitus.

Regulation of osteoblast levels during bone healing.

OBJECTIVE: To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1beta (IL-1beta) in regulating osteoblast concentration. STUDY DESIGN: Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1beta administered continuously for three days. METHODS: A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1beta was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS: Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1beta significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1beta treatment. CONCLUSION: The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1beta mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.