bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repair of chronic osteochondral defects in the rat
Authors: Nishimori M. , Deie M. , Kanaya A. , Exham H. , Adachi N. , Ochi M. 
Published: August 2006

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined. The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.
Polyaxially-locked plate screws increase stability of fracture fixation in an experimental model of calcaneal fracture
Authors: Richter M. , Droste P. , Goesling T. , Zech S. , Krettek C. 
Published: August 2006

Different calcaneal plates with locked screws were compared in an experimental model of a calcaneal fracture. Four plate models were tested, three with uniaxially-locked screws (Synthes, Newdeal, Darco), and one with polyaxially-locked screws (90° ± 15°) (Rimbus). Synthetic calcanei were osteotomised to create a fracture model and then fixed with the plates and screws. Seven specimens for each plate model were subjected to cyclic loading (preload 20 N, 1000 cycles at 800 N, 0.75 mm/s), and load to failure (0.75 mm/s). During cyclic loading, the plate with polyaxially-locked screws (Rimbus) showed significantly lower displacement in the primary loading direction than the plates with uniaxially-locked screws (mean values of maximum displacement during cyclic loading: Rimbus, 3.13 mm (sd 0.68); Synthes, 3.46 mm (sd 1.25); Darco, 4.48 mm (sd 3.17); Newdeal, 5.02 mm (sd 3.79); one-way analysis of variance, p < 0.001). The increased stability of a plate with polyaxially-locked screws demonstrated during cyclic loading compared with plates with uniaxially-locked screws may be beneficial for clinical use.
Extra-axial chordoma
Authors: van Akkooi A. C. J. , van Geel A. N. , Bessems J. H. J. M. , den Bakker M. A. 
Published: August 2006

A chordoma which occurs as a primary tumour outside the axial skeleton is known as an extra-axial chordoma, parachordoma or chordoma periphericum. It is extremely rare and therefore survival, recurrence and the rates of metastasis are not known. Whilst few recurrences have been described, the extra-axial chordoma has the potential for late recurrence at up to 12 years. Metastases are even less frequent. We report the case of a 56-year-old woman who developed an extra-axial chordoma of the right thoracic wall in close relationship with the tenth rib. The tumour was completely removed and the prognosis is excellent.
Simvastatin-Induced Decline in Cognition
Authors: Padala Kalpana P , Padala Prasad R , Potter Jane F 
Published: August 2006

Objective: To describe a case of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy. Case Summary: A 64-year-old man developed cognitive difficulties within one week after starting simvastatin 40 mg/day. There was a 3 point decline from baseline in the Mini-Mental State Exam (MMSE) score 2 weeks after simvastatin was initiated, as well as declines in the Activities of Daily Living and Instrumental Activities of Daily Living scales. Simvastatin was discontinued, and the patient's cognition improved to baseline within 6 weeks. Rechallenge with simvastatin at half the original dose was attempted. His cognition deteriorated over a 2 week period. Simvastatin was stopped, and the patient's MMSE scores returned to baseline within 4 weeks. Discussion: This patient developed new-onset problems with short-term memory, long-term memory, and item misplacement in addition to the baseline problems with names and word-finding that had been present prior to beginning statin therapy. Decreased cognition identified with neuropsychological tests has been shown in clinical trials with simvastatin; however, as of August 23, 2006, this is the first report of cognitive and functional problems that have been documented using standardized instruments. The Naranjo probability scale revealed a highly probable adverse reaction of cognitive decline associated with simvastatin therapy. Conclusions: Statins are commonly used in the older population. Simvastatin appeared to be associated with worsened cognition in our patient, an older person with preexisting memory problems. Statins should be used with caution in this vulnerable population.
Pharmacokinetics of Oseltamivir in Young and Very Elderly Subjects
Authors: Abe Masaichi , Smith James , Urae Akinori , Barrett Joanne , Kinoshita Haruki , Rayner Craig R 
Published: August 2006

Background: Pharmacokinetic studies of oseltamivir in very elderly patients (≥80 y) have not previously been performed. Objective: To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects. Methods: Young (20–35 y, fasting, n = 7) and very elderly subjects (≥80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed. Results: The time to maximum plasma concentration (tmax for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (Cmax) and AUCinf were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, Cmax and AUCinf values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the Cmax values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups. Conclusions: Exposures (AUCinf) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.
Paroxetine Useful for Palmar–Plantar Hyperhidrosis
Authors: Praharaj Samir Kumar , Arora Manu 
Published: August 2006

Objective: To report a case of palmar–plantar hyperhidrosis (PPH) In which paroxetine was found to be helpful. Case Summary: A 32-year-old man with a history of excessive sweating of the palms and soles since childhood was diagnosed with PPH and was prescribed paroxetine 10 mg/day, which was increased to 20 mg/day. After one month, he experienced a marked reduction in sweating and improvement in socio-occupational functioning, which were sustained during follow-up at 6 months without any emergent adverse effects. Discussion: Paroxetine's anticholinergic action may be responsible for its beneficial effect in PPH, as it may override the adrenergic mechanism, which has a minor effect on sweating from eccrine glands. Alternatively, paroxetine's beneficial effect in PPH may be secondary to its antianxiety effect, through central mechanisms. Conclusions: Paroxetine may be a useful option in the treatment of PPH.
Obesity: Low-Dose Orlistat Effects on Body Weight of Mildly to Moderately Overweight Individuals: A 16 Week, Double-Blind, Placebo-Controlled Trial
Authors: Anderson James W , Schwartz Susan M , Hauptman Jonathan , Boldrin Mark , Rossi Maureen , Bansal Vidhu , Hale Cecilia A 
Published: August 2006

Background: Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss. Objective: To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals. Methods: A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels. Results: Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 ± 0.35% (mean ± SE) of baseline weight compared with 3.1 ± 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (–4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (–7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects. Conclusions: The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.
Age- and Sex-Specific Differences in the Factor of Risk for Vertebral Fracture: A Population-Based Study Using QCT
Authors: Bouxsein Mary L , Melton L Joseph , Riggs B Lawrence , Muller John , Atkinson Elizabeth J , Oberg Ann L , Robb Richard A , Camp Jon J , Rouleau Peggy A , McCollough Cynthia H , Khosla Sundeep 
Published: August 2006

Abstract
We used QCT scans obtained in 687 men and women, 21–97 years of age, to estimate the factor of risk for vertebral fracture, Φvert, defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Φvert increased significantly more in women than men. Age- and sex-specific differences in Φvert closely resembled previously reported vertebral fracture incidence.
Introduction: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility.
Materials and Methods: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Φvert) in an age- and sex-stratified population-based sample of 700 women and men 21–97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1–L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Φvert, was computed as the ratio of spinal compressive force to vertebral strength for each activity.
Results: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p &lt; 0.001), the decline was greater in women than men (−43% versus −31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Φvert increased with age, but significantly more so in women than men (p &lt; 0.001). For bending and lifting, Φvert-bending exceeded 1.0 in 30% of women and 12% of men ≥50 years of age, values that are similar to the reported frequency of vertebral fracture.
Conclusion: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.
Vitamin D–Mediated Hypercalcemia in Slack Skin Disease: Evidence for Involvement of Extrarenal 25-Hydroxyvitamin D 1α-Hydroxylase
Authors: Karakelides Helen , Geller Jordan L , Schroeter Arnold L , Chen Hong , Behn Philip S , Adams John S , Hewison Martin , Wermers Robert A 
Published: August 2006

Abstract
A case of granulomatous slack skin disease is presented in which we studied the possible involvement of extrarenal 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. Immunolocalization of 1α-OH in skin showed simultaneous dysregulation in epithelial and granulomatous cells.
Introduction: Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of active 1,25-dihydroxyvitamin D [1,25(OH)2D]. Here we describe a case of granulomatous slack skin disease in which we have studied the possible involvement of extrarenal synthesis of 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. The aim of the study was to clarify the etiology of hypercalcemia in this patient.
Materials and Methods: This was a case study of a 19-year-old man with a T-cell lymphoproliferative disorder diagnosed as granulomatous slack skin disease who presented with hypercalcemia and raised serum 1,25(OH)2D. Analysis of expression of the enzyme 25-hydroxyvitamin D 1α-hydroxylase (1α-hydroxylase), which catalyzes synthesis of 1,25(OH)2D, was carried out by immunohistochemical analysis of involved and uninvolved skin. Approval was granted by the Mayo Foundation Institutional Review Board and Biospecimens Subcommittee.
Results: In uninvolved skin, expression of 1α-hydroxylase was confined to the basal layer of the epidermis, whereas slack skin showed overexpression of the enzyme in dermal granulomata and basal cells of the epidermis.
Conclusions: Hypercalcemia associated with granulomatous slack skin syndrome seems to be caused by dysregulation of 1α-hydroxylase expression in both epidermal and dermal granulomatous cells. This contrasts with psoriasis and sarcoidosis of the skin, in which overexpression of the enzyme is restricted to keratinocytes and granulomata, respectively.
Role of IGF-I Signaling in Regulating Osteoclastogenesis
Authors: Wang Yongmei , Nishida Shigeki , Elalieh Hashem Z , Long Roger K , Halloran Bernard P , Bikle Daniel D 
Published: August 2006

Abstract
We showed that IGF-I deficiency impaired osteoclastogenesis directly and/or indirectly by altering the interaction between stromal/osteoblastic cells and osteoclast precursors, reducing RANKL and M-CSF production. These changes lead to impaired bone resorption, resulting in high BV/TV in IGF-I null mice.
Introduction: Although IGF-I has been clearly identified as an important growth factor in regulating osteoblast function, information regarding its role in osteoclastogenesis is limited. Our study was designed to analyze the role of IGF-I in modulating osteoclastogenesis using IGF-I knockout mice (IGF-I−/−).
Materials and Methods: Trabecular bone volume (BV/TV), osteoclast number, and morphology of IGF-I−/− or wildtype mice (IGF-I+/+) were evaluated in vivo by histological analysis. Osteoclast precursors from these mice were cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF) or co-cultured with stromal/osteoblastic cells from either genotype. Osteoclast formation was assessed by measuring the number of multinucleated TRACP+ cells and pit formation. The mRNA levels of osteoclast regulation markers were determined by quantitative RT-PCR.
Results: In vivo, IGF-I−/− mice have higher BV/TV and fewer (76% of IGF-I+/+) and smaller osteoclasts with fewer nuclei. In vitro, in the presence of RANKL and M-CSF, osteoclast number (55% of IGF-I+/+) and resorptive area (30% of IGF-I+/+) in osteoclast precursor cultures from IGF-I−/− mice were significantly fewer and smaller than that from the IGF-I+/+ mice. IGF-I (10 ng/ml) increased the size, number (2.6-fold), and function (resorptive area, 2.7-fold) of osteoclasts in cultures from IGF-I+/+ mice, with weaker stimulation in cultures from IGF-I−/− mice. In co-cultures of IGF-I−/− osteoblasts with IGF-I+/+ osteoclast precursors, or IGF-I+/+ osteoblasts with IGF-I−/− osteoclast precursors, the number of osteoclasts formed was only 11% and 48%, respectively, of that from co-cultures of IGF-I+/+ osteoblasts and IGF-I+/+ osteoclast precursors. In the long bones from IGF-I−/− mice, mRNA levels of RANKL, RANK, M-CSF, and c-fms were 55%, 33%, 60%, and 35% of that from IGF-I+/+ mice, respectively.
Conclusions: Our results indicate that IGF-I regulates osteoclastogenesis by promoting their differentiation. IGF-I is required for maintaining the normal interaction between the osteoblast and osteoclast to support osteoclastogenesis through its regulation of RANKL and RANK expression.
Low-Level, High-Frequency Mechanical Signals Enhance Musculoskeletal Development of Young Women With Low BMD
Authors: Gilsanz Vicente , Wren Tishya AL , Sanchez Monique , Dorey Frederick , Judex Stefan , Rubin Clinton 
Published: August 2006

Abstract
The potential for brief periods of low-magnitude, high-frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD. Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls.
Introduction: The incidence of osteoporosis, a disease that manifests in the elderly, may be reduced by increasing peak bone mass in the young. Preliminary data indicate that extremely low-level mechanical signals are anabolic to bone tissue, and their ability to enhance bone and muscle mass in young women was investigated in this study.
Materials and Methods: A 12-month trial was conducted in 48 young women (15–20 years) with low BMD and a history of at least one skeletal fracture. One half of the subjects underwent brief (10 minutes requested), daily, low-level whole body vibration (30 Hz, 0.3g); the remaining women served as controls. Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight-bearing skeleton.
Results: Using an intention-to-treat (ITT) analysis, cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1% (p = 0.025) and 3.4% (p &lt; 0.001), respectively, compared with 0.1% (p = 0.74) and 1.1% (p = 0.14), in controls. Increases in cancellous and cortical bone were 2.0% (p = 0.06) and 2.3% (p = 0.04) greater, respectively, in the experimental group compared with controls. Cross-sectional area of paraspinous musculature was 4.9% greater (p = 0.002) in the experimental group versus controls. When a per protocol analysis was considered, gains in both muscle and bone were strongly correlated to a threshold in compliance, where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day (n = 18), as reflected by a 3.9% increase in cancellous bone of the spine (p = 0.007), 2.9% increase in cortical bone of the femur (p = 0.009), and 7.2% increase in musculature of the spine (p = 0.001) compared with controls and low compliers (n = 30).
Conclusions: Short bouts of extremely low-level mechanical signals, several orders of magnitude below that associated with vigorous exercise, increased bone and muscle mass in the weight-bearing skeleton of young adult females with low BMD. Should these musculoskeletal enhancements be preserved through adulthood, this intervention may prove to be a deterrent to osteoporosis in the elderly.
Theoretical Model for the Interpretation of BMD Scans in Patients Stopping Strontium Ranelate Treatment
Authors: Blake Glen M , Fogelman Ignac 
Published: August 2006

Abstract
Strontium ranelate is a new treatment for osteoporosis that results in large increases in BMD, much of which is an artefact caused by high bone strontium content. We used clinical trial data and a model of long-term strontium kinetics to estimate the effect of past strontium treatment on future BMD measurements.
Introduction: The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone. As more patients are treated with strontium ranelate, questions will arise about the correct interpretation of their future BMD measurements. We performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD.
Materials and Methods: The BMD changes measured at the spine and hip during strontium ranelate treatment were interpolated from clinical trial data. The long-term retention of strontium in bone was estimated using the International Commission on Radiological Protection (ICRP) strontium retention function modified for use in postmenopausal women. Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years.
Results: If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively. If pre- and post-therapy BMD measurements are available, these predictions can be tailored to the individual patient. On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation. Ten years after stopping treatment, 28 months of treatment are required for the residual BMD artefact to still exceed the 3% threshold.
Conclusions: Strontium ranelate treatment lasting for &gt;6 months can affect BMD measurements for many years afterward.