bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientation of the acetabular component
Authors: Honl M. , Schwieger K. , Salineros M. , Jacobs J. , Morlock M. , Wimmer M.
Published: September 2006

We compared the orientation of the acetabular component obtained by a conventional manual technique with that using five different navigation systems.

Three surgeons carried out five implantations of an acetabular component with each navigation system, as well as manually, using an anatomical model. The orientation of the acetabular component, including inclination and anteversion, and its position was determined using a co-ordinate measuring machine.

The variation of the orientation of the acetabular component was higher in the conventional group compared with the navigated group. One experienced surgeon took significantly less time for the procedure. However, his placement of the component was no better than that of the less experienced surgeons. Significantly better inclination and anteversion (p < 0.001 for both) were obtained using navigation. These parameters were not significantly different between the surgeons when using the conventional technique (p = 0.966).

The use of computer navigation helps a surgeon to orientate the acetabular component with less variation regarding inclination and anteversion.
Combined femoral and Chiari osteotomies for reconstruction of the painful subluxation or dislocation of the hip in cerebral palsy
Authors: Debnath U. K. , Guha A. R. , Karlakki S. , Varghese J. , Evans G. A.
Published: September 2006

In order to treat painful subluxation or dislocation secondary to cerebral palsy, 11 patients (12 hips) underwent combined femoral and Chiari pelvic osteotomies with additional soft-tissue releases at a mean age of 14.1 years (9.1 to 17.8). Relief of pain, improvement in movement of the hip, and in sitting posture, and ease of perineal care were recorded in all, and were maintained at a mean follow-up of 13.1 years (8 to 17.5). The improvement in general mobility was marginal, but those who were able to walk benefited the most.

The radiological measurements made before operation were modified afterwards to use the lateral margin of the neoacetabulum produced by the pelvic osteotomy. The radiological migration index improved from a mean of 80.6% (61% to 100%) to 13.7% (0% to 33%) (p < 0.0001). The mean changes in centre edge angle and Sharp’s angle were 72° (56° to 87°; p < 0.0001) and 12.3° (9° to 15.6°; p < 0.0001), respectively. Radiological evidence of progressive arthritic change was seen in one hip, in which only a partial reduction had been achieved, and there was early narrowing of the joint space in another. Painless heterotopic ossification was observed in one patient with athetoid quadriplegia. In seven hips the lateral Kawamura approach, elevating the greater trochanter, provided exposure for both osteotomies and allowed the construction of a dome-shaped iliac osteotomy, while protecting the sciatic nerve.
Incomplete discoid glenoid labrum combined with a ganglion cyst of the spinoglenoid notch
Authors: Rhee K. J. , Kim K. C. , Lee J. K. , Hwang D. S. , Shin H. D. , Yang J. Y. , Kim Y. M.
Published: September 2006

In a 41-year-old man, right-sided infraspinatus muscle weakness was associated with compression of the suprascapular nerve caused by a spinoglenoid ganglion cyst. The lesion was confirmed using electromyography and MRI. In addition, arthroscopy showed an incomplete discoid labrum. The free inner edge of the labrum was removed as in a meniscectomy of a discoid meniscus in the knee joint. Arthroscopic decompression of the cyst was performed through a juxtaglenoid capsulotomy which was left open. Neurological function recovered completely.
Calcium Channel TRPV6 Expression in Human Duodenum: Different Relationships to the Vitamin D System and Aging in Men and Women
Authors: Walters Julian RF , Balesaria Sara , Chavele Konstantia-Maria , Taylor Vivienne , Berry Jacqueline L , Khair Umma , Barley Natalie F , van Heel David A , Field Jennifer , Hayat Jamal O , Bhattacharjee Abhik , Jeffery Rosemary , Poulsom Richard
Published: September 2006

Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women.

Introduction: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system.

Materials and Methods: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)2D].

Results: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)2D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)2D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)2D, but there was a significant decrease with age (r = −0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively).

Conclusions: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women.
Change in Lumbar Spine BMD and Vertebral Fracture Risk Reduction in Teriparatide-Treated Postmenopausal Women With Osteoporosis
Authors: Chen Peiqi , Miller Paul D , Delmas Pierre D , Misurski Derek A , Krege John H
Published: September 2006

Increases in lumbar spine BMD account for 30–41% of the vertebral fracture risk reduction with teriparatide treatment. The remaining fracture risk reduction is caused by improvements in non-BMD determinants of bone strength.

Introduction: Changes in BMD account for a small percentage of the fracture risk reduction seen in patients treated with antiresorptive drugs. The relationship between changes in lumbar spine BMD and vertebral fracture risk reduction with teriparatide treatment has not been assessed.

Materials and Methods: The relationship between spine BMD and the risk of new vertebral fractures after teriparatide treatment was assessed using data from the Fracture Prevention Trial. Postmenopausal women with osteoporosis (n = 1637) were randomized to placebo or teriparatide 20 or 40 μg/day for a median of 19 months. Spine BMD was assessed at baseline and 18 months. Vertebrae whose fracture status changed during the trial were removed from the calculation of BMD. Baseline and endpoint lateral spine radiographs were assessed using a visual semiquantitative technique.

Results: Both the baseline and change in spine BMD were contributors to vertebral fracture risk. The mean spine BMD increase in teriparatide-treated patients was 0.09 g/cm2 across tertiles of baseline spine BMD. Compared with placebo, teriparatide significantly reduced the risk of new vertebral fracture for all endpoint BMD values. Teriparatide-mediated increases in spine BMD accounted for 30% (in the low baseline spine BMD tertile) to 41% (in the high baseline spine BMD tertile) of the reduction in vertebral fracture risk.

Conclusions: Increases in BMD account for approximately one third of the vertebral fracture risk reduction seen with teriparatide. The majority of the risk reduction, however, results from improvements in non-BMD determinants of bone strength.
25-Hydroxyvitamin D Deficiency and Diabetes Predict Reduced BMD in Patients With Chronic Kidney Disease
Authors: Elder Grahame J , Mackun Kenneth
Published: September 2006

In this study of 242 patients with renal failure, women, patients with diabetes, and patients on peritoneal dialysis had the highest risk of 25-hydroxyvitamin D deficiency. Levels correlated positively to BMD Z scores, and hip BMD was inversely related to prevalent fracture. Increasing 25-hydroxyvitamin D levels may benefit these patients.

Introduction: 25-Hydroxyvitamin D deficiency (<37 nM) is common in patients with chronic kidney disease (CKD) stage 5 (glomerular filtration rate < 15 ml/min/1.73 m2 or on dialysis), but it is unclear if this deficiency is associated with bone disease and if supplementation is warranted.

Materials and Methods: Blood samples were collected on 242 patients with CKD stage 5 caused by type 1 diabetes (33%), type 2 diabetes (2%), and other causes (65%), who were about to undergo kidney or kidney pancreas transplantation. Prevalent spinal fracture was assessed by X-ray and BMD by DXA.

Results: 25-Hydroxyvitamin D deficiency was present in 28% of patients with diabetes versus 12% without (p < 0.0001). Patients on peritoneal dialysis (PD) had lower levels of 25-hydroxyvitamin D than patients on hemodialysis (HD; 49 ± 26 versus 77 ± 34 nM; p < 0.0001), and women had lower levels than men (51 ± 25 versus 77 ± 35 pM; p < 0.0001). BMD Z scores were within 1 SD of the mean at all sites, except in patients with diabetes (femoral neck Z score, −1.07 ± 1.2; p < 0.0001) and patients who had undergone parathyroidectomy (lumbar spine Z score, 1.03 ± 1.34, femoral neck Z score, 1.24 ± 1.35; p < 0.001 and p < 0.0001, respectively). In multiple stepwise linear regression analysis, levels of 25-hydroxyvitamin D correlated positively and intact PTH (iPTH) correlated negatively to Z scores at the lumbar spine and wrist. Time on dialysis correlated positively to Z scores at the femoral neck and lumbar spine. Diabetes and serum alkaline phosphatase levels correlated negatively with Z scores at the femoral neck. Lower femoral neck BMD was associated with an increased prevalence of vertebral fracture and fragility fracture at any site (p = 0.03 and p < 0.03, respectively).

Conclusions: This study of patients with CKD stage 5 identifies women, patients with diabetes, and patients on PD as being at particular risk of 25-hydroxyvitamin D deficiency. We describe positive associations of 25-hydroxyvitamin D levels and BMD Z scores and an association between femoral neck BMD and fragility fracture at any site. Treatment to improve 25-hydroxyvitamin D levels may benefit these patients.
Decreased Fracture Risk in Users of Organic Nitrates: A Nationwide Case-Control Study
Authors: Rejnmark Lars , Vestergaard Peter , Mosekilde Leif
Published: September 2006

In a nationwide population-based pharmaco-epidemiological case-control study, including 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls, we found an ∼15% reduced risk of fractures in users of organic nitrates. Thus, organic nitrates may protect against osteoporosis.

Introduction: Organic nitrates are widely used in the treatment of ischemic heart diseases. In addition, nitrates may affect bone. In vitro studies have shown that nitrates are able to inhibit bone resorption, and recent studies in humans have shown a positive effect on BMD and bone turnover.

Materials and Methods We studied the effect of organic nitrates on risk of fracture. We performed a population-based pharmaco-epidemiological case-control study with fracture in 2000 as outcome and use of nitrates (isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin) during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of nitrates and related these data to individual fracture data and information on potential confounders. In the study, we included 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls.

Results: After confounder adjustment, use of nitrates was associated with an 11% reduced risk of any fracture (OR = 0.89; 95% CI, 0.86–0.92) and a 15% reduced risk of hip fracture (OR = 0.85; 95% CI, 0.79–0.92). Risk of any fracture was reduced in both men and women, but risk of hip fracture was only reduced in women. Hip fracture risk was reduced dose-dependently. Use of nitrates with a short duration of action was associated with lower risk estimates than use of slow release preparations.

Conclusions: Treatment with nitrates is associated with a decreased risk of fracture. Further studies should determine whether a causal relationship exists.
QTL With Pleiotropic Effects on Serum Levels of Bone-Specific Alkaline Phosphatase and Osteocalcin Maps to the Baboon Ortholog of Human Chromosome 6p23-21.3
Authors: Havill Lorena M , Rogers Jeffrey , Cox Laura A , Mahaney Michael C
Published: September 2006

Bone ALP and OC are under partial genetic control. This study of 591 pedigreed baboons shows a QTL corresponding to human 6p23–21.3 that accounts for 25% (bone ALP) and 20% (OC) of the genetic variance. A gene affecting osteoblast activity, number, or recruitment likely resides in this area.

Bone ALP and OC are under partial genetic control. This study of 591 pedigreed baboons shows a QTL corresponding to human 6p23–21.3 that accounts for 25% (bone ALP) and 20% (OC) of the genetic variance. A gene affecting osteoblast activity, number, or recruitment likely resides in this area.

Introduction: Serum levels of bone alkaline phosphatase (ALP) and osteocalcin (OC) reflect osteoblast activity. Both of these measures are under partial genetic control. Genetic effects on bone ALP have not been previously localized to chromosomal regions in primates, nor has the degree to which genetic effects are shared (pleiotropic) between bone ALP and OC been studied.

Materials and Methods: We applied variance components methods to a sample of 591 adult pedigreed baboons to detect and quantify effects of genes that influence bone ALP and that have pleiotropic effects on bone ALP and OC. A univariate linkage analysis was conducted for bone ALP. Bivariate linkage analyses were conducted in areas for which the bone ALP results presented here and a previous univariate OC linkage analysis showed evidence for linkage on the same chromosome for both bone ALP and OC.

Results: A quantitative trait locus (QTL) for serum levels of bone ALP is evident on the baboon ortholog of human chromosomal region 6p (LOD 2.93). Thirty-seven percent (genetic correlation [ρG] =0.61) of the genetic variance in bone ALP and OC is caused by pleiotropic effects of the same gene(s). Bivariate linkage analysis revealed a QTL in the region corresponding to human chromosome 6p23–21.3, with the strongest evidence for bivariate linkage near D6S422 (LOD =2.97 at 22 cM from our pter-most marker). D6S422 maps to 20.4 Mb in the human genome. The QTL-specific heritability (h2) is 0.25 and 0.20 for bone ALP and OC, respectively.

Conclusions: This first formal test for shared genetic effects on two serum markers of osteoblast activity indicates that a significant pleiotropic effect on bone ALP and OC levels, and thus on bone formation, is detectible. The fact that this region corresponds to one on mouse chromosome 13 that has repeatedly yielded QTLs for BMD should encourage more intensive study of the effect of genes in this region on bone maintenance and turnover.
Leptin Is a Negative Independent Predictor of Areal BMD and Cortical Bone Size in Young Adult Swedish Men
Authors: Lorentzon Mattias , Landin Kerstin , Mellström Dan , Ohlsson Claes
Published: September 2006

The association between leptin and areal BMD has been controversial, and the predictive role of leptin on cortical volumetric BMD and bone size has not previously been studied. We show that leptin is a negative independent predictor of aBMD (DXA), at several measured sites, and of cortical bone size (pQCT) in a large population of young men.

Introduction: Recent findings suggest that both adipose tissue (AT) and bone mass are regulated by leptin. Previous reports studying the association between leptin and areal BMD (aBMD) have yielded conflicting results. The role of leptin on volumetric BMD (vBMD) and bone size of the cortical and trabecular bone compartments has not previously been studied.

Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based study of 1068 men (age, 18.9 ± 0.6 [SD] years). aBMD of the total body, lumbar spine, femoral neck, both radii, and trochanter, as well as total body AT and lean mass (LM) were measured using DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT.

Results: Total body LM could explain a larger magnitude of the difference in the variation in aBMD and cortical bone size than what total body AT could (total body aBMD: LM 37.4% versus AT 8.7%; tibia cross-sectional area [CSA]: LM 46.8% versus AT 5.6%). The independent role of leptin on bone parameters was studied using a multiple linear regression model, including age, total body LM and AT, height, present physical activity, calcium intake, and smoking as covariates. Leptin was found to be a negative independent predictor of aBMD (total body: β =−0.08, p =0.01; lumbar spine: β =−0.13, p < 0.01; trochanter: β =−0.09, p =0.01), as well as of the cortical bone size (CSA and thickness) of both the radius (CSA: β =−0.12, p < 0.001) and tibia (CSA: β =−0.08, p < 0.01), but not of the cortical or trabecular vBMD of these bones.

Conclusion: Our results indicate that LM has a greater impact on bone mass than AT. Our findings further show that leptin is a negative independent predictor of aBMD at several measured sites and of bone parameters reflecting cortical bone size, but not vBMD, in a large population of young Swedish men.
On the Increasing Fragility of Human Teeth With Age: A Deep-UV Resonance Raman Study
Authors: Ager Joel W , Nalla Ravi K , Balooch Guive , Kim Grace , Pugach Megan , Habelitz Stefan , Marshall Grayson W , Kinney John H , Ritchie Robert O
Published: September 2006

UV resonance Raman spectroscopy (UVRRS) using 244-nm excitation was used to study the impact of aging on human dentin. The intensity of a spectroscopic feature from the peptide bonds in the collagen increases with tissue age, similar to a finding reported previously for human cortical bone.

Introduction: The structural changes that lead to compromised mechanical properties with age in dentin and bone are under intense study. However, in situ analyses of the content and distribution of the mineral phase are more highly developed at present than equivalent probes of the organic phase.

Materials and Methods: Thirty-five human molars were divided into three groups: young/normal (23.3 ± 3.8 years); aged/transparent (74.3 ± 6.0 years), which had become transparent because of filling of the tubule lumens with mineral deposits; and aged/nontransparent (73.3 ± 5.7 years). Control experiments were performed by demineralizing normal dentin.

Results: Spectral features caused by both the amide backbone and resonance-enhanced side-chain vibrations were observed. This finding contrasts with reported Raman spectra of proteins in solution excited with similar UV wavelengths, where side chain vibrations, but not strong amide features, are observed. The strong intensity of the amide features observed from dentin is attributed to broadening of the resonance profile for the amide π → π* transition caused by the environment of the collagen molecules in dentin. With increasing age, the height of one specific amide vibration (amide I) becomes significantly higher when comparing teeth from donors with an average age of 23 years to those of 73 years (p < 0.001). This trend of increasing amide I peak height with age is similar to that previously reported for human cortical bone. The amide I feature also increased in dentin that had been demineralized and dehydrated.

Conclusions: The similar trend of increasing amide I peak height with age in the UVRR spectra of both teeth and bone is surprising, given that only bone undergoes remodeling. However, by considering those observations together with this study of demineralized/dehydrated dentin and our prior work on dentin dehydrated with polar solvents, a consistent relationship between changes in the UVRR spectra and the collagen environment in the tissue can be developed.
Bone Fragility: Failure of Periosteal Apposition to Compensate for Increased Endocortical Resorption in Postmenopausal Women
Authors: Szulc Pawel , Seeman Ego , Duboeuf François , Sornay-Rendu Elisabeth , Delmas Pierre D
Published: September 2006

The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength.

Introduction: Bone loss from the inner (endocortical) surface contributes to bone fragility, whereas deposition of bone on the outer (periosteal) surface is believed to be an adaptive response to maintain resistance to bending.

Materials and Methods: To test this hypothesis, changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius, bone turnover markers, and fracture incidence were measured annually in 821 women 30–89 years of age for 7.1 ± 2.5 years. The analyses were made in 151 premenopausal women, 33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women receiving hormone replacement therapy (HRT).

Results: In premenopausal women, periosteal apposition increased the radius width, partly offsetting endocortical resorption; therefore, the estimated cortical thickness decreased. Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength. Estimated endocortical resorption accelerated during perimenopause, whereas periosteal apposition decreased. Further cortical thinning occurred, but estimated bending strength was maintained by modest outward cortical displacement. Endocortical resorption accelerated further during the postmenopausal years, whereas periosteal apposition declined further; cortices thinned, but because outward displacement was minimal, estimated cortical area and bending strength now decreased. Women with highest remodeling had the greatest loss of bone mass and strength. Women with low remodeling lost less bone and maintained estimated bone strength. In HRT-treated women, loss of bone strength was partly prevented. These structural indices predicted incident fractures; a 1 SD lower section modulus doubled fracture risk.

Conclusions: Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.
Does Reduced Skeletal Loading Account for Age-Related Bone Loss?
Authors: Melton L Joseph , Riggs B Lawrence , Achenbach Sara J , Amin Shreyasee , Camp Jon J , Rouleau Peggy A , Robb Richard A , Oberg Ann L , Khosla Sundeep
Published: September 2006

A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21–97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging.

Introduction: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail.

Materials and Methods: In a stratified random sample of Rochester, MN, women and men 21–97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (Ho) that bone strength per unit load did not vary with age.

Results and Conclusions: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p =0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.
Missionary Ridge Fire Cost Assessment
Authors: Mackes Kurt H. , Lynch Dennis L. , Kelly Stephen K. , Eckhoff Mike
Published: September 2006

Capturing the true cost of wildland fire events is critical for providing a sound basis for public policy. Recently, Lynch [1] suggested additional factors to consider in addition to suppression costs as a means for gaging a fire’s total cost. In this study a similar evaluation was done for the second largest fire in Colorado during the 2002 wildland fire season. The Missionary Ridge fire burned 70 475 acres of land in southwestern Colorado in June and July of 2002. Costs associated with the fire were analyzed and separated into three categories: (1) direct costs, (2) rehabilitation costs, and (3) impact costs. Direct costs during the fire were $90 276 323, rehabilitation costs totaled $8 732 608, and impact costs that occurred after fire containment through 2003 amounted to $50 499 849. Impact costs were still accruing at the time this study was completed. In addition, special values were also considered, including the death of a firefighter, wilderness acreage burned, and loss of sensitive species habitat. These costs were estimated to be $3 404 410. The total cost of the fire to date was estimated at $152 803 785 or more than $2168 per acre.
Placental Growth Factor-1 Potentiates Hematopoietic Progenitor Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor in Mice and Nonhuman Primates
Authors: Carlo-Stella Carmelo , Di Nicola Massimo , Longoni Paolo , Cleris Loredana , Lavazza Cristiana , Milani Raffaella , Milanesi Marco , Magni Michele , Pace Virgilio , Colotta Francesco , Avanzini Maria A. , Formelli Franca , Gianni Alessandro M.
Published: September 2006

The complex hematopoietic effects of placental growth factor (PlGF) prompted us to test in mice and nonhuman primates the mobilization of peripheral blood progenitor cells (PBPCs) elicited by recombinant mouse PlGF-2 (rmPlGF-2) and recombinant human PlGF-1 (rhPlGF-1). PBPC mobilization was evaluated by assaying colony-forming cells (CFCs), high-proliferative potential-CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). In mice, both rmPlGF-2 and rhPlGF-1 used as single agents failed to mobilize PBPCs, whereas the combination of rhPlGF-1 and granulocyte colony-stimulating factor (rhG-CSF) increased CFCs and LTC-ICs per milliliter of blood by four- and eightfold, respectively, as compared with rhG-CSF alone. rhPlGF-1 plus rhG-CSF significantly increased matrix metalloproteinase-9 plasma levels over rhG-CSF alone, suggesting a mechanistic explanation for rhPlGF-1/rhG-CSF synergism. In rhesus monkeys, rhPlGF-1 alone had no mobilization effect, whereas rhPlGF-1 (260 μg/kg per day) plus rhG-CSF (100 μg/kg per day) increased rhG-CSF-elicited mobilization of CFCs, HPP-CFCs, and LTC-ICs per milliliter of blood by 5-, 7-, and 15-fold, respectively. No specific toxicity was associated with the administration of rhPlGF-1 alone or in combination. In conclusion, our data demonstrate that rhPlGF-1 significantly increases rhG-CSF-elicited hematopoietic mobilization and provide a preclinical rationale for evaluating rhPlGF-1 in the clinical setting.
Do realistic reverberation levels reduce auditory distraction?
Authors: Perham Nick , Banbury Simon , Jones Dylan M.
Published: September 2006

Acoustically treated ceilings and wall panels can be used as part of a strategy to reduce the impact of background sound on the health and performance of employees by decreasing the reverberation times of the office noise. In this article we examine the impact of two reverberation times upon task performance. A cognitive task known to be a sensitive index of auditory distraction (serial recall) was used to assess the degree of distraction associated with two types of ceiling: a hard ceiling, such as plasterboard, and a soft ceiling, such as an acoustically treated ceiling. Office noise (in the range 65–75 dB (A)) was found generally to be disruptive relative to a quiet control condition but there was no difference in performance with regard to the ceiling types. Copyright © 2006 John Wiley & Sons, Ltd.
Glycosyl‐phosphatidyl‐inositol‐defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction
Authors: Cacciapuoti Carmela , Terrazzano Giuseppe , Barone Lucia , Sica Michela , Becchimanzi Cristina , Rotoli Bruno , Ruggiero Giuseppina , Alfinito Fiorella
Published: September 2006

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the emergence of a GPI‐defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI‐defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial‐dependent intracellular ingestion and the consequent activation of oxidative burst in GPI‐defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI‐defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N‐formyl‐MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI‐defective granulocytes was maintained after treatment with phorbol 12‐myristate 13‐acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab
Authors: Cheung Winnie W. , Tse Eric , Leung Anskar Y.H. , Yuen Kwok‐Yung , Kwong Yok‐Lam
Published: September 2006

Ten patients with refractory lymphomas or autoimmune cytopenias were treated with alemtuzumab, and monitored prospectively for cytomegalovirus (CMV) reactivation by antigenemia and polymerase chain reaction. All patients showed virologic CMV reactivation. Two patients developed pneumonitis and hepatitis respectively, necessitating alemtuzumab withdrawal. Eight patients were asymptomatic, and with pre‐emptive anti‐CMV treatment, alemtuzumab therapy was uninterrupted. All patients ultimately achieved virologic remission. The frequent CMV reactivation was due to a high background seropositivity rate for CMV, severely immunocompromized patients, a sensitive detection method, and the diligence of surveillance. Frequent monitoring for and early treatment of CMV reactivation is necessary during alemtuzumab therapy. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Titelbild: Isostructural Coordination Capsules for a Series of 10 Different d5–d10 Transition‐Metal Ions (Angew. Chem. 39/2006)
Authors: Hiraoka Shuichi , Harano Koji , Shiro Motoo , Ozawa Yoshiki , Yasuda Nobuhiro , Toriumi Koshiro , Shionoya Mitsuhiko
Published: September 2006

Einen isolierten Raum für die größen‐ oder formselektive dynamische molekulare Erkennung und metallvermittelte chemische Reaktionen bietet das Innere von Nanokapseln. In ihrer Zuschrift auf S. 6638 ff. beschreiben M. Shionoya et al. eine Reihe von isostrukturellen oktaedrischen Kapseln, die aus einem einzigen dreizähnigen Liganden und zehn verschiedenen zweiwertigen Übergangsmetallionen (in Grün auf dem Titelbild hervorgehoben) hergestellt wurden, und belegen den ortsspezifischen Austausch der Anionen, die im Hohlraum an die Metallzentren koordiniert sind.
Epidemiologic surveillance of upper‐extremity musculoskeletal disorders in the working population
Authors: Roquelaure Yves , Ha Catherine , Leclerc Annette , Touranchet Annie , Sauteron Marine , Melchior Maria , Imbernon Ellen , Goldberg Marcel
Published: September 2006

Objective

Since 2002, an epidemiologic surveillance system of work‐related, upper‐limb musculoskeletal disorders (MSDs) has been implemented in France's Pays de la Loire region to assess the prevalence of MSDs and their risk factors in the working population.

Methods

The surveillance was based on a network of occupational physicians (OPs) and used the recommendations of a group of European experts (criteria document consensus). In 2002–2003, 80 of 400 OPs volunteered to participate. All underwent a training program to standardize the physical examination. Health status was assessed by self‐administered questionnaire and physical examination. Occupational risk factors were assessed by self‐administered questionnaire. Exposure scores were computed for each anatomic zone by summing the risk factors taken into account by the criteria document.

Results

More than 50% of the 2,685 men and women randomly included in 2002–2003 experienced nonspecific musculoskeletal symptoms during the preceeding 12 months and ∼30% experienced them in the preceeding week. The prevalence of clinically diagnosed MSDs was high: ∼13% of workers experienced at least 1 of the MSDs. The most frequent disorder was rotator cuff syndrome followed by carpal tunnel syndrome and lateral epicondylitis. The prevalence of MSDs increased with age and varied widely across economic sectors and occupations. More than half of the workers were exposed to at least 2 risk factors of MSDs. Exposure varied according to industrial activity and occupation. According to the criteria document, a high percentage of MSD cases could be classified as probably work related (95% in men and 89% in women age <50, and 87% in men and 69% in women age >50).

Conclusion

Nonspecific upper‐limb symptoms and specific upper‐limb MSDs are common in the working population. These results show the need to implement prevention programs in most sectors to reduce the prevalence of MSDs.
Disability, social support, and distress in rheumatoid arthritis: Results from a thirteen‐year prospective study
Authors: Strating Mathilde M. H. , Suurmeijer Theo P. B. M. , Van Schuur Wijbrandt H.
Published: September 2006

Objective

To examine the strength and stability of the relationships between disease‐related factors (joint tenderness, pain, and functional disability), social support, and distress over time, and to investigate to what extent disease‐related factors and social support can predict distress in short‐term and long‐term rheumatoid arthritis (RA).

Methods

The study was a Dutch extension of the European Research on Incapacitating Diseases and Social Support and started with 292 patients. After 5 waves of data collection, 129 patients remained. Composite measures were computed following the area under the curve approach. Interaction terms were computed between functional disability and social support satisfaction. Correlational and hierarchical regression analyses were performed.

Results

In patients with short‐term RA, disease‐related factors and social support were important in determining distress. Also, a buffering effect of social companionship was found. In total, 51% of the variance in distress in short‐term RA could be explained primarily by mean distress over the previous years. In patients with long‐term RA, disease‐related factors remained important in determining distress, but to a lesser extent. Seventeen percent of the variance in distress in long‐term RA could be explained primarily by mean distress over the years before.

Conclusion

During the course of the disease, patients may learn to adjust to their disease and its consequences and are able to maintain a normal distress level. The effect of the disease on psychological distress decreased over the years. Some support for the buffering hypothesis of social support was found in short‐term RA, but not in long‐term RA.
Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long‐term urate‐lowering therapy: A prospective study
Authors: Perez‐Ruiz Fernando , Atxotegi Joana , Hernando Iñaki , Calabozo Marcelo , Nolla Joan M.
Published: September 2006

Objective

Withdrawal of urate‐lowering therapy (ULT) is associated with recurrence of acute gouty arthritis and tophi, but no data are available about factors associated with recurrence of gouty symptoms. Therefore, life‐long therapy prescription is usually advised, but the prospect of life‐long therapy may contribute to very low compliance rates. Our objective was to ascertain the outcome of ULT withdrawal after long‐term, documented control of serum urate levels.

Methods

We conducted a prospective, long‐term, followup study of patients treated with ULT during a 5‐year period. Both diagnosis and recurrence of gout were determined based on monosodium urate crystal identification in synovial fluid or material aspirated from tophi.

Results

Low average serum urate levels while receiving ULT and during the followup period after ULT withdrawal were statistically associated with the longest period in which patients were free of gouty symptoms, suggesting that depletion and formation of the body's urate pool is dependent on both time and serum urate levels. Patients whose average serum urate levels were <5.05 mg/dl while receiving ULT and <8.75 mg/dl after ULT withdrawal had the longest (>4 years) time to recurrence.

Conclusion

Proper and long‐term reduction of serum urate level is associated with long‐term periods in which patients are free of gouty symptoms, probably due to the reduction of the urate pool. These results suggest that 5‐year intermittent, instead of life‐long, ULT could be offered to patients with good serum urate control during ULT.
Successes and failures in improving osteoporosis care after fragility fracture: Results of a multiple‐site clinical improvement project
Authors: Harrington J. Timothy , Deal Chad L.
Published: September 2006

Objective

To improve osteoporosis diagnosis and treatment of fragility fracture patient populations because osteoporosis care is provided infrequently to those patients, leaving them vulnerable to further fractures and increasing debility.

Methods

Osteoporosis experts from 11 US health systems participated in a clinical improvement project based on previously described successful osteoporosis care process redesigns. Participants were taught rapid cycle process improvement methods that are widely used in clinical improvement projects, and were supported in their efforts by the program coordinator. Measures of successful process development included establishing reliable referral from orthopedic fracture care to osteoporosis diagnosis and treatment, nurse coordination and monitoring of osteoporosis care, and use of process management software for registering patients and organizing work.

Results

Four sites were able to establish these critical referral and osteoporosis management processes. Two sites were partially successful in increasing orthopedic referrals to consultative care, but otherwise continued traditional care processes. Five were unsuccessful due to inability to implement 1 or more of these key process improvements.

Conclusion

Reliable osteoporosis care for fracture patients is possible if traditional practice processes are replaced with more effective, well‐recognized approaches to chronic disease management.
Impact of multiple joint problems on daily living tasks in people in the community over age fifty‐five
Authors: Keenan Anne‐maree , Tennant Alan , Fear Jon , Emery Paul , Conaghan Philip G.
Published: September 2006

Objective

To establish the prevalence of multiple joint problems and their impact on everyday tasks.

Methods

A random sample of the UK population was assessed using a postal questionnaire. Data on overall joint pain, swelling and stiffness, and activities of daily living were obtained from 16,222 individuals >55 years of age (86% response rate). Prevalence estimates of joint problems were established and the impact of multiple joint pathologies on common physical tasks was determined.

Results

Single joint involvement was unusual (median joint involvement 4). Although the knee was the most frequently involved joint (220.30 per 1,000), isolated knee pathology accounted for only 1 in 11 patients with knee pain. Although single joint disorders increased the risk of experiencing functional difficulty, this risk was substantially increased with multiple joint problems: individuals with knee and feet problems were 14 times more likely to experience difficulty standing and walking than those without knee problems (odds ratio [OR] 14.50); knee and hip problems increased the risk >12 times (OR 12.43) whereas knee, back, feet, and hip involvement increased the risk 60 times (OR 62.41).

Conclusion

Multiple‐site joint problems are much more common than single joint problems. Although individual joint problems have a considerable impact on a person's functional ability, this risk is substantially increased when other joints are involved. With the increasing burden associated with the aging population, it is essential that the management of joint pain be considered in light of the impact of multiple, rather than single, joint problems.
Korrosionserscheinungen an Balkonen und Loggien – Ursachen und Vermeidung
Authors: Błaszczyński Tomasz , Łowińska‐Kluge Aldona
Published: September 2006

Für jedes Bauelement, das Zerstörungsanzeichen zeigt, sollten Art und Ursachen der aufgetretenen Korrosionserscheinungen genau bestimmt und dementsprechend die Art und Weise der Reparatur und der Bausicherung gewählt werden. Erst dann werden die ausgeführten Bausicherungen und Reparaturen entsprechend haltbar sein, das wird im Endeffekt dazu beitragen, die Kosten der Instandhaltung der Bauobjekte zu reduzieren. Aufgrund der Untersuchungen an Bauobjekten durch Labor‐ und strukturelle Untersuchungen (Röntgen‐Mikroskopie und ‐Mikroanalyse) werden die Ursachen der Korrosion der Bestandteile von Loggien und Balkonen dargestellt und analysiert. Auf Basis der Ergebnisse werden Hinweise zur Vermeidung derartiger Erscheinungen erarbeitet.
Epinephrine for the treatment of anaphylaxis: do all 40 mg sublingual epinephrine tablet formulations with similar in vitro characteristics have the same bioavailability?
Authors: Rawas‐Qalaji Mutasem M. , Simons F. Estelle R. , Simons Keith J.
Published: September 2006

Epinephrine autoinjectors are underutilized in the first aid emergency treatment of anaphylaxis in the community; so non‐invasive sublingual epinephrine administration is being proposed. In order to determine the effect of changing excipients on the bioavailability of sublingual epinephrine, four distinct fast‐disintegrating epinephrine 40 mg tablet formulations, A, B, C and D, were manufactured using direct compression. All formulations were evaluated for tablet hardness (H), disintegration time (DT) and wetting time (WT). In a prospective 5‐way crossover study, four sublingual formulations and epinephrine 0.3 mg i.m. as a control were tested sequentially in a validated rabbit model. Blood samples were collected before dosing and at intervals afterwards. Epinephrine plasma concentrations were measured using HPLC‐EC. All tablet formulations met USP standards for weight variation and content uniformity, and resulted in similar mean H, DT and WT (n=6). The area under the curve (AUC), maximum concentration (Cmax) and time at which Cmax was achieved (Tmax) did not differ significantly after the sublingual administration of formulation A and epinephrine 0.3 mg i.m. The AUC after B, C and D were significantly lower (p<0.05) than after epinephrine 0.3 mg i.m. These results suggest that the selection of excipients used in these tablet formulations can affect the bioavailability of sublingually administered epinephrine. Copyright © 2006 John Wiley & Sons, Ltd.
Pharmacokinetic interaction between fluvastatin and diltiazem in rats
Authors: Choi Jun‐Shik , Piao Yong‐Ji , Han Hyo‐Kyung
Published: September 2006

The present study aimed to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem in rats. Pharmacokinetic parameters of diltiazem were determined in rats following an oral administration of diltiazem (15 mg/kg) in the presence and absence of fluvastatin (0.6 and 2.0 mg/kg). Compared with the control given diltiazem alone, theCmaxandAUCof diltiazem increased by 30–70% in rats with the concurrent use of fluvastatin, while there was no significant change inTmaxand the plasma half‐life (T1/2) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of fluvastatin were significantly higher (p<0.05) than those from the control group, implying that fluvastatin could reduce the presystemic extraction of diltiazem. In conclusion, the concurrent use of fluvastatin significantly enhanced the oral exposure of diltiazem in rats. Copyright © 2006 John Wiley & Sons, Ltd.