Michael Soudry

Nicotine modulates bone metabolism-associated gene expression in osteoblast cells

Smoking has a broad range of physiological effects, such as being a risk factor in osteoporosis, bone fracture incidence, and increased nonunion rates. Recent studies showed that nicotine has effects at the cellular level in human osteoblast cells. To identify possible mechanisms underlying nicotine-induced changes in osteogenic metabolism, we defined changes in proliferation and osteocalcin, type I collagen, and alkaline phosphatase gene expression after treating human osteosarcoma cells (MG63), with various concentration of nicotine. Nicotine affects cell proliferation in a biphasic manner, including toxic and antiproliferative effects at high levels of nicotine and stimulatory effects at low levels. Moreover, low levels of nicotine upregulated osteocalcin, type I collagen, and alkaline phosphatase gene expression. The increased cell proliferation and gene upregulation induced by nicotine were inhibited by addition of the nicotinic receptor antagonist d-tubocurarine. High nicotine concentrations downregulated the investigated genes. Our results demonstrate, for the first time, that the addition of nicotine concentrations analogous to those acquired by a light to moderate smoker yields increased osteoblast proliferation and bone metabolism, whereas the addition of nicotine concentrations analogous to heavy smokers leads to the opposite effect. The inhibition of these effects by d-tubocurarine suggests that nicotine acts via the nicotinic acetylcholine receptor (nAChR).

The revised "reconstructive ladder" and its applications for high-energy injuries to the extremities.

In this report, we tried to evaluate the merits of the classic “reconstructive ladder” and other reconstructive tools, such as acute shortening followed by distraction osteogenesis and a vacuum-assisted closure device, for the treatment of high-energy injuries. Thirty-seven patients suffering from high-velocity injuries to the extremities caused by war weapons and blast terror attacks were treated at our institution. The fractures were initially stabilized by the Association for the Study of Internal Fixation (AO/ASIF) unilateral tubular external fixator, which was changed 2–3 days later to a circular Ilizarov frame for 19 patients. Temporary acute shortening was performed for 5 patients. Skin grafts were performed for 21 patients, local or regional flaps for 14 patients, and free flaps for 6. Vacuum-assisted closure was selected for 8 patients. The wounds were successfully closed in all the patients. Two patients with upper-limb injuries had nonunion. Motor nerve injuries recovered in 7/10 patients. Due to hypergranulating tissue, 2 patients treated with vacuum-assisted closure (VAC) had to stop treatment early. Their wounds were closed with skin graft or local flap. The classic reconstructive ladder, starting from direct closure and ending with a free flap, should be extended for limb traumas and include acute shortening with or without angulation, followed by distraction osteogenesis and the VAC system on the same step as the free flap.

Nicotinic modulation of gene expression in osteoblast cells, MG-63.

Exposure to nicotine causes a broad range of biological and molecular effects on osteoblasts which are known to play a crucial role in bone metabolism and fracture healing. Most effects of nicotine on the osteoblasts are long-term adaptations at the genomic level. To identify the nicotine-regulated genes, the Agilent technologies whole human genome gene expression microarray was performed on RNA samples from osteoblast-like cells, MG-63, exposed to 100 μM nicotine. Repeat and cross-controlled microarray analyses revealed 842 genes whose expression was consistently altered at P<0.05 level following nicotine treatment. Gene ontology analysis suggested effects of nicotine on various biological and cellular processes which were associated with survival, proliferation, differentiation and apoptosis processes within the cell. Quantitative real-time reverse transcriptase PCR analysis confirmed altered expression in 7 out of 9 genes tested. The identified genes tested in the current study support our previous report that nicotine regulates the expression of genes that promote osteoblast proliferation and/or anti-apoptosis processes. Furthermore, using nicotinic acetylcholine receptor antagonists blocked the majority of the nicotine effects, indicating that these changes are dependent on nAChR activation. These results established a novel and consistent nicotinic activation of nAChR in osteoblast cells which has a broad role affecting cellular physiology through modulation of gene expression.

Arthrodesis With the Ilizarov Device After Failed Knee Arthroplasty

Thirteen patients with failed total knee arthroplasty (TKA) due to infection (12 patients) or aseptic loosening (1 patient) underwent arthrodesis using the Ilizarov external fixator. Solid fusion was achieved in all patients with an average healing time of 27.6 weeks. Patients spent an average 18.8 weeks in the fixator followed by an average 8.8 weeks in a plaster cylinder cast. Five patients had a pin tract infection and one a superficial wound infection. One patient had 15 degrees recurvatum after surgery that was gradually corrected by adding a hinge system to the fixator. Average shortening of the affected limb was 3.7 cm (range: 1-6 cm). The Ilizarov fixator for knee arthrodesis after failed TKA produced favorable results and should be considered for use by surgeons familiar with the technique.

Shoulder impairment following treatment of diaphysial fractures of humerus by functional brace

IntroductionTreatment of humeral shaft fractures by functional bracing has been reported to be effective in achieving high rate of fracture union and good function of the adjacent shoulder and elbow joints. Since our previous clinical impression indicated an occurrence of shoulder function impairment following this treatment, we investigated the shoulder function in a consecutive series of patients treated by functional bracing for fractures of humeral shaft in order to estimate their residual shoulder function.Materials and methodsWe followed 15 consecutive patients with humeral shaft fractures treated by functional brace. The mean follow up was 30xa0months (range 12–57xa0months); seven patients with midshaft fracture, four patients with proximal third, and four patients with fractured distal third of the humeral diaphysis. All the patients were evaluated by the Constant score of the injured limb in comparison to the contra-lateral not injured shoulder and by the Oxford shoulder score of the injured limb.ResultsWe found that all the fractures were united with mean varus angulation of 13° and with mean angulation in the saggital plane of 9° antecurvatum, Constant scores were significantly lower in the injured shoulders (Pxa0<xa00.001) and the function of the shoulders in the injured extremities were estimated as having mean Oxford shoulder score of 34 (range 17–54).ConclusionsThe evaluation of the present series revealed an impaired functional outcome in the shoulders after humeral shaft fracture. Our results indicate that although the fracture union is usually achieved following the functional bracing of humeral shaft fractures, the shoulder function in the injured limb may remain impaired.

Extreme Bone Lengthening Using Distraction Osteogenesis After Trauma: A Case Report

We are reporting herein the result of a 22 cm tibial lengthening after using an acute shortening technique with acute temporary angulation for salvage of a posttraumatic lower limb injury. The patient was referred to our center 2 weeks after a Gustilo IIIB open complex injury to the lower limb that included bone and soft-tissue loss. After surgical debridement, the tibial gap was 22 cm and the soft-tissue defect on the anterior aspect of the calf measured 12 × 20 cm. An acute shortening using a 50° angulation (apex posteriorly) of the tibia in an Ilizarov frame was done after a full assessment of all reconstructive surgical options. After complete wound healing, a progressive correction of the angulation was done. Bilevel tibial distraction at a rate of 1.75 mm/day restored the original lower limb length. The 22 cm tibial elongation included 17 cm proximal lengthening and 5 cm distal lengthening. The fractures consolidated after 371 days, all wounds had closed, and no signs of osteomyelitis were present. Good aesthetic and functional results were obtained. The patient had no leg discrepancy compared to his normal limb and he returned to his previous occupation as a garage mechanic and to his favorite sport, boxing. To our knowledge, this is the first report in the English literature of tibial lengthening of this magnitude following acute trauma.

Neuropraxis Secondary to Hemorrhage in a Traumatic Dislocation of the Shoulder

A case of traumatic shoulder dislocation associated with a tear of the subscapular artery is presented. The main clinical feature was a dramatic neurologic loss of the brachial plexus, reversed by exploration, evacuation of hematoma, and ligation of the bleeding vessel. Early surgical decompression to achieve neurologic recovery is emphasized.

In vitro mitochondrial effects of PK 11195, a synthetic translocator protein 18 kDa (TSPO) ligand, in human osteoblast-like cells

The role of the TSPO in metabolism of human osteoblasts is unknown. We hypothesized that human osteoblast metabolism may be modulated by the TSPO. Therefore we evaluated the presence of TSPO in human osteoblast-like cells and the effect of its synthetic ligand PK 11195 on these cells. The presence of TSPO was determined by [3H]PK 11195 binding using Scatchard analysis: Bmax 7682xa0fmol/mg, Kd 9.24xa0nM. PK 11195 did not affect significantly cell proliferation, cell death, cellular viability, maturation, [18F]-FDG incorporation and hexokinase 2 gene expression or protein levels. PK 11195 exerted a suppressive effect on VDAC1 and caused an increase in TSPO gene expression or protein levels. In parallel there was an increase in mitochondrial mass, mitochondrial ATP content and a reduction in ΔΨm collapse. Thus, it appears that PK11195 (10−5xa0M) stimulates mitochondrial activity in human osteoblast-like cells without affecting glycolytic activity and cell death.

Comparison of two methods for the evaluation of treatment in medial epicondylitis: pain estimation vs grip strength measurements

IntroductionDetermination of a precise and reproducible diagnostic tool for the evaluation of patients with medial epicondylitis (ME) is important for an effective follow-up. The commonly suggested use of grip strength measurements with a hand dynamometer is not always easily available and may be affected by the patient’s compliance. We propose that pain estimation based on the visual analog scale can be considered for this purpose as well because it addresses the painful degenerative lesion in the common flexor origin, which is the basic pathological process in ME.Materials and methodsWe analyzed and compared 237 different sets of measurements of grip strengths and pain evaluation, according to the visual analog scale, in 79 patients with ME. For the purpose of this comparison, we developed a qualitative grading system based on the statistical data of the grip strength values in the normal population.ResultsHigh dependency between the graded pain evaluation and measured grip strength was found.ConclusionWe suggest that evaluation of patients with ME according to the proposed grading method of pain evaluation is as accurate as grip strength measurements.

Familial recurrent dislocation of patella with autosomal dominant mode of inheritance

Recurrent dislocation of the patella is considered to be a manifestation of generalized joint laxity. An autosomal dominant mode of inheritance was previously suggested in a few instances; however, male‐to‐male transmission has not yet been reported. We report a recurrent dislocation of the patella occurring in five generations of one family with male‐to‐male transmission and without generalized joint laxity.