Nimrod Rozen

Expression of vascular antigens by bone cells during bone regeneration in a membranous bone distraction system

Abstract. An in vivo system of membranous bone formation during distraction has been investigated in order to follow cells that express vascular markers with the objective of understanding the neovascularization process. Concomitantly, sustained proliferation of preskeletal cells was achieved through the application of mechanical force. New capillaries and leading edges that arose by angiogenesis from the periosteal and mucosal surfaces and invaded the central zone of the regenerating distraction tissue temporally preceded the growth of delicate woven bone trabeculae from both edges of the cut bone. Concentrically arranged onion-like configurations were abundant in paracentral zones and in association with mesenchymal condensations, suggesting their de novo formation in situ. Vascular specific markers, the angiopoietin receptor Tie-2 and factorxa0VIII-related antigen (FVIIIrAg), were localized immunohistochemically in order to follow cells of vascular origin. Endothelial cells of the new capillaries, centrally located cells of the concentric configurations, pericytes, and most of the adjacent polygonal mesenchymal cells stained positively with specific antibodies to both antigens. Moreover, preosteoblasts and osteoblasts that lie adjacent to or already embedded in the osteiod of the newly formed trabeculae were also FVIIIrAg and Tie-2 immunopositive. As the source of the bone-forming cells in regenerating tissue during distraction is not yet fully understood, this observation might support the possibility of their vascular origin.

The effect of hindlimb immobilization on acid phosphatase, metalloproteinases and nuclear factor-κB in muscles of young and old rats

Age-associated muscle wasting (sarcopenia of old age) is a major problem in elderly people, however, the mechanisms of muscle proteolysis in aging remain obscure and enigmatic. Possible reasons for loss of skeletal muscle mass with aging may be attributed to multiple and complex proteolytic systems. The purpose of the present study was to explore the kinetics of activation of extracellular hydrolytic and proteolytic systems in muscles of hindlimbs immobilized by external fixation of 24-month-old female Wistar rats, in comparison with those of 6-month-old rats. Results show that elevated acid phosphatase activities (lysosomal hydrolytic enzyme activated mainly in macrophages) in immobilized limb muscles of young animals, differ from old animals. In young rats external fixation resulted in significantly elevated acid phosphatase activities (50-55%; p<0.05) after 4 weeks of immobilization, whereas in old animals similar increases were observed already during the first and second weeks of immobilization. The extracellular proteolytic enzymes, matrix metalloproteinases (MMP-2 and -9), were also differentially activated in old animals compared to young animals. In young animals, as shown in previous studies, both MMP-2 and -9 activities were elevated significantly in immobilized muscles. In this study of old animals, only MMP-2 activity was detected, with no significant elevation in the immobilized muscles of old animals. In addition, the levels of the transcription factor Nuclear Factor-kappaB (NF-kappaB) in nuclear extracts of old rat muscles, as detected by ELISA, showed a biphasic pattern after immobilization, suggesting that NF-kappaB could be activated by different processes in the atrophy process, at least in the old age. In conclusion, it seems that the kinetics of activation of extracellular hydrolytic and proteolytic systems differ in muscles of old animals compared to young animals.

Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation

A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.

Ulnar Nerve Injury Following Midshaft Forearm Fractures in Children

We report three cases of ulnar nerve deficit in children following closed fractures of the forearm bones. Significant anterior angulation and displacement of the ulna was noted in all patients. Two patients were operated on at a later stage when no evidence of recovery was demonstrated; the ulnar nerve was found to be embedded in dense scar tissue. One patient was operated on at the time of injury; entrapment of the nerve on the anterior spike and partial transection was found. Early exploration is indicated in such cases and may result in full recovery.

Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults.

CONTEXTnPuberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty.nnnOBJECTIVESnTo investigate duodenal 25-hydroxy vitamin D-1α-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and adults.nnnDESIGN AND METHODSnCYP27B1a nd IGF1 mRNA expression and 1,25(OH)2D3 production were determined in duodenal biopsies. CYP27B1 expression was also determined after IGF1R inhibitor treatment of human and mice duodenal explants. mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by incubating duodenal explants with 25(OH)D3 and measuring 1,25(OH)2D3 production by radioimmunoassay.nnnRESULTSnCYP27B1 mRNA expression was 13.7 and 10.4 times higher in biopsies from adolescents compared to adults and children, respectively. IGF1 mRNA expression was 30% and 45% higher in explants from adolescents and children, respectively, compared to adults. Inhibition of IGF1 receptor activity decreased CYP27B1 expression in explants from both mice (85%) and humans (24%). 1,25(OH)2D3 production reached a maximum velocity of 768 ± 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 in children and adolescents, whereas the maximum velocity was 86.4 ± 43.2 pmol/l/mg protein in adults. The substrate concentration at which the enzyme shows half of its maximum activity was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D3.nnnCONCLUSIONSnIncreased CYP27B1 expression and local duodenal 1,25(OH)2D3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.

Upper extremity fractures among hospitalized road traffic accident adults

BACKGROUNDnUpper extremity fractures (UEFs) associated with road traffic accidents (RTAs) may result in long-term disability. Previous studies have examined UEF profiles with small patient populations. The objective of this study was to examine the injury profiles of UEFs in all mechanisms of injury related to RTAs.nnnMETHODSnData on 71,231 RTA adult patients between 1997 and 2012 whose records were entered in a centralized country trauma database were reviewed. Data on UEFs related to mechanism of injury (car, motorcycle, bicycle, and pedestrian) including associated injuries, multiple UEFs, and frequency of UEF were analyzed.nnnRESULTSnOf 71,231 adult RTA cases recorded in 1997-2012, 12,754 (17.9%) included UEFs. Motorcycle (27%) and bicycle riders (25%) had the greater risk for UEF (P<.0001). Of 12,754 patients with UEFs, 9701 (76%) had other injuries. Pedestrians (86%) and car occupants (81%) had the greater risk for associated injuries (P<.0001). Most of the injuries were head/face/neck (52%), lower extremities (49%), and chest (46%) injuries (P<.0001). Twenty-two percent of all cases had multiple UEFs. The motorcycle riders (27%) had the greater risk for multiple UEFs (P<.0001). Of 12,754 patients with UEFs we found 16,371 UEFs. Most of the fractures were in the radius (22%), humerus (19%), and clavicle (17%) (P<.0001).nnnCONCLUSIONSnThis study contributes the largest database on reported adult UEFs related to all mechanisms of injury in RTAs and finds the comparative epidemiology of associated injuries, multiple UEFs, and frequency of UEFs. It is important that the treating surgeon is aware of the complexity of the UEF patient, the strong possibility for associated injury, the possibility for multiple fractures in the upper limbs, and the most common fractures associated with each mechanism of accident.

Nail Puncture Wound Through a Rubber-Soled Shoe: A Retrospective Study of 96 Adult Patients

Nail punctures through rubber-soled shoes expose the foot to the possibility of deep infection and foreign body retention. In this article, we describe characteristics of adult patients who sustained nail puncture wounds through a rubber-soled shoe and were treated at our institution from January 1, 2000, to January 8, 2008. Of the 96 patients, 36 (37.5%) were treated conservatively and 60 (62.5%) were treated surgically in the operating room. Of those treated surgically, 15 (25%) had a foreign body extracted during the operation. The operated group had a longer duration of time from injury to hospital admission than did the nonoperated group (5.0 +/- 6.8 days versus 2.7 +/- 3.8 days, P < .05). Treatment success was observed in 91 (94.8%) of the patients, and the median lag time before admission for the less successfully treated group was longer than that for the successfully treated group (10 days versus 2 days, P < .002); and, the less successfully treated group was more likely to receive antibiotics in the community before hospitalization (100.0% versus 47.2%, P < .06), and was more likely to be diabetic (40.0% versus 9.9%, P < .10). Fever, white blood cell count, and erythrocyte sedimentation rate were not significantly associated with treatment outcome. Success of the treatment did not depend on white blood cell count, erythrocyte sedimentation rate, or fever. Ultrasonography was useful in detecting the presence of a foreign body.

Low-Grade Fibromyxoid Sarcoma of the Hand: A Case Report

We report a case of low-grade fibromyxoid sarcoma with giant collagen rosettes in the hand of a 21-year-old female. This is a clinically and radiological benign appearing tumor that has a high rate of recurrence and metastasis.

The use of prophylactic antibiotics in treatment of fingertip amputation: a randomized prospective trial

PURPOSEnFingertip amputation is a common injury. Considerable controversy exists as to whether prophylactic antibiotics are necessary for this injury. Our goal was to compare the rate of infections among subgroups with and without prophylactic antibiotic treatment. The study hypothesis was that infection rates were similar in the 2 groups.nnnMETHODSnThis was a prospective randomized control trial of adult patients presenting with fingertip amputation with bone exposed, requiring surgical treatment. Patients were randomized to 2 groups: group 1 received no antibiotics, and group 2 received 1 g intravenous antibiotics (cefazolin) for 3 days. The 2 groups were matched for age, time to surgery, injury mechanism, and type of surgery. All surgical treatments were performed in the operating room, and all patients were reevaluated in our outpatient clinic after 10 days and again after a month. The primary outcome measure was the rate of infection.nnnRESULTSnFifty-eight patients were initially enrolled in the study; 2 patients withdrew before study completion, 29 subjects were randomized to the no-antibiotic group, and 27 subjects were randomized to the antibiotic group. No statistically significant differences on any baseline values were found between the 2 treatment groups. There was no infection in either group at the end of follow-up.nnnCONCLUSIONSnThis study suggests that routine prophylactic antibiotics do not reduce the rate of infection after fingertip amputations with bone exposed treated surgically in the operating room.

Upper extremity fractures among hospitalized pediatric road traffic accident victims

BACKGROUNDnUpper extremity fractures (UEFs) associated with road traffic accidents (RTAs) may result in long-term disability. Previous studies have examined UEF profiles with small patient populations. The objective of this study was to examine the injury profiles of UEFs in all mechanisms of injury related to RTAs in the pediatric population.nnnMETHODSnData on 27 831 RTA hospitalized pediatric patients between 1997 and 2012 whose records were entered in a centralized country trauma database were reviewed. Data on UEFs related to mechanism of injury (car, motorcycle, bicycle, and pedestrian) including associated injuries, multiple UEFs, and frequency of UEF were analyzed.nnnRESULTSnOf 27 831 pediatric RTA cases recorded in 1997-2012, 3666 (13.2%) included UEFs. Motorcycle (18%) and bicycle riders (18%) had a greater risk for UEF (P < .0001). Of 3666 patients with UEFs, 2047 (56%) had other injuries. The pedestrians (82%) and the motorcycle riders (78%) had a greater risk for associated injuries (P < .0001). Most of the injuries were head/face/neck (70%), lower extremities (36%), and chest (28%) injuries (P < .0001). Twenty-two percent of all cases had multiple UEFs. The bicycle riders (28%) had a greater risk for multiple UEFs (P < .0001). Of 3666 patients with UEFs, we found 4612 UEFs. most of the fractures in the radius (27%), humerus (25%), ulna (18%) and clavicle (17%) (P < .0001).nnnCONCLUSIONSnThis study contributes the largest database on reported pediatric UEFs related to all mechanisms of injury in RTAs and finds the comparative epidemiology of associated injuries, multiple UEFs, and frequency of UEFs.