Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22(Phox) and iNOS expression.

OBJECTIVE: Reactive oxygen species (ROS) are major determinants in the alteration of articular cartilage. Among protective cellular mechanisms, the inducible isoform of haem oxygenase (HO-1) plays a particularly relevant role. On the other hand, the enzymatic activity of the Nicotinamide adenine dinucleotide phosphate (NADPH) system could contribute to the generation of ROS. Glucosamine sulphate (GS) is one of the drugs used in the treatment of osteoarthritis; however, its mechanism of action is still largely unknown. The aim of the present study was to investigate the effects of GS on primary human chondrocytes in vitro, in particular with regard to HO-1, p22(Phox) (a subunit of NADPH complex) and inducible nitric oxide synthase (iNOS) expression. METHODS: Primary human chondrocytes were treated with different concentrations of GS; gene expression of HO-1, p22(Phox) and iNOS was assessed by the reverse transcriptase-polymerase chain reaction method. In a separate set of experiments, the cells were stimulated with human recombinant interleukin (IL)-1beta and simultaneously treated with GS. Moreover, HO-1 protein and total nitrite production were evaluated. RESULTS: HO-1 gene expression was up-regulated (+40% with respect to the controls, P < 0.001) by 10 mmol/l GS at 24 h, while p22(Phox) gene expression was down-regulated by 10 mmol/l GS with a maximum inhibitory effect observed after 48 h treatment. IL-1beta stimulation induced expression of iNOS reverted by 1 and 10 mmol/l GS. Moreover, HO-1 gene expression was down-regulated by IL-1beta and 10 mmol/l GS restored baseline values. These data were confirmed by evaluating HO-1 protein level and nitrite production. CONCLUSIONS: The influence of GS on oxidative stress observed in this study discloses a possible new mechanism of action and seems to be in keeping with a potential protective effect on chondrocyte population.

YKL-40 in human lumbar herniated disc and its relationships with nitric oxide and cyclooxygenase-2.

UNLABELLED: The basic pathophysiology of intervertebral disc degeneration and low back pain remains unclear. It has been hypo-thesized a role of biochemical mediators of inflammation and tissue degradation in intervertebral disc degeneration and herniation. Chitinase 3-like protein 1 (YKL-40) is a glycoprotein mainly secreted by chondrocytes which has been proposed as a possible marker of inflammation and/or cartilage alterations. OBJECTIVE: To investigate the YKL-40 presence in human lumbar disc tissue culture and its possible relationships with some substances relevant in inflammation such as cyclooxygenase-2 (COX-2) and nitric oxide (NO). PATIENTS AND METHODS: We analyzed lumbar discs from 19 patients who underwent surgery for lumbar disc herniation at L4-L5 or L5-S1 levels. The specimens were cultured and incubated for 72 hours. At the end of incubation, the supernatants were assayed for presence and concentration of YKL-40, COX-2 and NO. RESULTS: YKL-40 was detectable in all the samples analyzed. Mean (+/-SD) concentration was 1.54+/-1.29 ng/ml/mg compared to dry weight. COX-2 and NO levels were 25.25+/-11.42 pg/ml/mg and 1.3+/-1.8 microM/mgx10(-2), respectively. A correlation was found between YKL-40 and COX-2 (r=0.579, p<0.05) and YKL-40 and NO (r=0.509, p<0.05). CONCLUSION: To our knowledge, this is the first report demonstrating YKL-40 release by intervertebral disc culture. It may contribute to better clarify the role of this protein in the pathophysiology of discal degeneration and inflammation as confirmed by its relationships with COX-2 and NO in disc tissue culture.

Tendinous muscular insertions onto the deep fascia of the upper limb. First part: anatomical study.

We examined 30 upper limbs in order to study the tendinous muscular insertions into the deep fascia and to verify whether they have a specific anatomical arrangement and to measure their resilience to traction. We have found that the fascia receives many tendinous muscular insertions, which are always present and exhibit a constant anatomical structure. In particular, the pectoralis major fascia always continues with the brachial fascia in two distinct ways: the fascia overlying the clavicular part of pectoralis major had an expansion towards the anterior brachial fascia, whereas the fascia covering its costal part extended into the medial brachial fascia and the medial intermuscular septum. The lacertus fibrosus was also composed by two groups of fibres: the main group was oriented downwards and medially, the second group longitudinally. The palmaris longus opened out into a fan-shape in the palm of the hand and sent some tendinous expansions to the flexor retinaculum and fascia overlying the thenar eminence muscles. In the posterior region of the arm, the fascia of the latissimus dorsi sent a fibrous lamina to the triceps brachial fascia. The triceps tendon inserted partially into the antebrachial fascia, while the extensor carpi ulnaris sent a tendinous expansion to the fascia of the hypothenar eminence. It is hypothesized that the tendinous muscular insertions maintain the fascia at a basal tension and create myofascial continuity between the different muscles actuating flexion and extension of the upper limb, stretching the fascia in different ways according to the different motor directions.

Anatomy of the deep fascia of the upper limb. Second part: study of innervation.

Analysis of specimens taken from different areas of the deep fascia in 20 upper limbs was made in order to establish which kind of nerve fibres and endings are present in the deep muscular fascia. The flexor retinaculum and the lacertus fibrosus were also evaluated because they are anatomically hardly separable from the deep muscular fascia, although they have different functions. In particular, specimens were taken at the level of: (a) the expansion of pectoralis major onto the bicipital fascia, (b) the middle third of the brachial fascia, (c) the lacertus fibrosus, (d) the middle third of the antebrachial fascia, (e) the flexor retinaculum. This study demonstrated an abundant innervation of the fascia consisting in both free nerve endings and encapsulated receptors, in particular, Ruffini and Pacini corpuscles. However, differences in innervation were verified: the flexor retinaculum was resulted the more innervated element whilst lacertus fibrosus and the pectoralis major expansion the less innervated. These results suggest that the retinaculum has more a perceptive function whereas the tendinous expansions onto the fascia have mostly a mechanical role in the transmission of tension. The hypothesis that the fascia plays an important role in proprioception, especially dynamic proprioception, is therefore advanced. In fact, the fascia is a membrane that extends throughout the whole body and numerous muscular expansions maintain it in a basal tension. During a muscular contraction these expansions could also transmit the effect of the stretch to a specific area of the fascia, stimulating the proprioceptors in that area.

Orthopedic resident's learning curve for arthroscopic subscapularis tendon repair: short-term clinical and radiographic outcomes.

BACKGROUND: Arthroscopic subscapularis (SSC) repair is a technically demanding procedure with a long learning curve. As effective completion of resident's practical experience remains controversial, a prospective clinical study was performed to assess the functional and anatomical outcomes of subscapularis (SSC) arthroscopic repair by orthopedic residents. The pathological anatomy of the tears, the surgical approach and the difficulties encountered at the beginning of the learning curve were reported. MATERIALS AND METHODS: Between June 2009 and June 2010, 30 patients with rotator cuff tear were preoperatively evaluated with clinical exam, Constant and UCLA scores. Surgery was performed under arthroscopy by a team of three orthopedic surgeons in training. A SSC tear, if present, was recorded and treated. The same clinical exam and functional scores were repeated at minimum 6 months of follow-up. Subscapularis strength recovery and tendon healing were investigated with arthromagnetic resonance imaging. RESULTS: A SSC tear was observed in 11 cases out of 30 and treated arthroscopically. The clinical scores improved in all patients: the average Constant score increased from 34 ± 14 to 77 ± 11 and the UCLA score from 11 ± 5 to 29 ± 3. The SSC tests were negative in all patients with the exception of one. Tendon healing was observed in 10 out of 11 cases. CONCLUSIONS: Arthroscopic SSC repair performed by educated residents is possible and leads to good clinical and anatomical results. Surgery duration progressively improved as the learning curve advanced. LEVEL OF EVIDENCE: Level 2.

Limb lengthening by diaphyseal corticotomy, callus distraction, and dynamic axial fixation. An experimental study in the ovine femur.

Limb lengthening of the left femur was performed in 12 sheep, 7-8 months of age. After weakening of the cortex by drill holes, a controlled fracture was created in the diaphysis. The bone segments were fixed in reduced position using a unilateral external fixation device. The fixator was left in neutral position for 10 days postoperatively when lengthening started. By means of daily distraction at a rate of 1.0 mm once a day for 3 weeks, an average lengthening of 1.9 cm (11.9%) was obtained. Two weeks after distraction had been discontinued, distinct callus bridging of the lengthening zone was confirmed radiographically in all animals. At this time the rigid state of fixation was converted to a system allowing axial compression by loading in half the animals. The other half of the animals served as controls with the fixator remaining unchanged. The external device was left on until 5 weeks after the end of distraction. At this time the animals were killed. Both femora of all animals were tested mechanically in torsion. The average ultimate torsional strength of the elongated femur compared with control was 71% in the group with dynamic axial fixation and 65% in the control group. No significant difference in relative strength of the tested bones in the two groups was found. We conclude that intermittent axial compression by loading during consolidation had no significant effect on the bone-healing process evaluated by radiography and mechanical testing.

Distraction osteogenesis for lengthening of the tibia in patients who have limb-length discrepancy or short stature.

BACKGROUND: This study was performed to determine the safety and effectiveness of lengthening of the tibia, in patients who have a limb-length discrepancy or a short stature, with use of distraction osteogenesis, a technique based on the principle of distracting the callus that is formed after a subperiosteal osteotomy of the proximal portion of the diaphysis of a long bone. METHODS: A total of 230 tibial lengthening procedures were done in 150 patients. Seventy procedures were performed because of a limb-length discrepancy, which was secondary to trauma (thirty limbs), congenital fibular hemimelia (twenty-six), poliomyelitis (ten), or infection (four). The remaining 160 procedures were performed because of a short stature, which was secondary to achondroplasia (fifty-eight limbs), Turner syndrome (thirty-four), an idiopathic etiology (twenty-two), hypochondroplasia (twenty), achondroplasia (ten), Ellis-van Creveld syndrome (six), rickets (four), or adrenogenital syndrome, Laron syndrome, or pseudoachondroplasia (two limbs each). The age of the patients at the time of the operation was 18.4+/-6.2 years (average and standard deviation), with a range of six to forty-one years. The procedures were performed according to one of three protocols. In Group A (ninety procedures), an Orthofix telescopic fixator and a variable number of screws were used and the tibiofibular syndesmosis was not stabilized; in Group B (ninety-six procedures), an Orthofix reconstruction system was used, the syndesmosis was stabilized, and a tenotomy of the Achilles tendon was performed; and in Group C (forty-four procedures), an Orthofix Garches lengthening device was used, the syndesmosis was stabilized, and a tenotomy of the Achilles tendon was performed. RESULTS: At the time of the latest follow-up (average, five years; range, two to seven years), the average gain in length after the seventy procedures performed because of a limb-length discrepancy was 4.0+/-1.98 centimeters (range, 2.5 to 9.5 centimeters), or 14 percent (range, 7 to 45 percent). The average gain in length after the 160 procedures that were performed because of a short stature was 7.8+/-2.28 centimeters (range, 2.5 to fifteen centimeters), or 33 percent (range, 10 to 78 percent). Ten (14 percent) of the seventy procedures performed because of a limb-length discrepancy and forty-six (29 percent) of the 160 performed because of a short stature were associated with a complication. There was only one permanent sequela in the entire series. CONCLUSIONS: Although the three operative protocols resulted in similar healing indices, the rates of complications differed significantly among the groups (p<0.0001). Group C (the Garches device) had the lowest rate of complications (7 percent). It is important to be aware of potential complications as well as the need for additional procedures in order to avoid predictable problems. These procedures include percutaneous tenotomy of the Achilles tendon and fixation of the distal segment of the fibula to the tibia to maintain the integrity of the tibiotalar articulation and the alignment of the foot.

A chart of anthropometric values.

A chart is presented to assist with the assessment and treatment of patients with growth-related deformities. It is based on anthropometric values from five published sources and relates sitting height to stature, limb length, the radiographic lengths of the leg bones and the lengths of the feet and hands. It has proved useful in the prediction of leg-length discrepancies, in the diagnosis of cases of short stature, and in the assessment of spinal shortening from scoliosis.

Leg lengthening in Turner dwarfism.

We have reviewed 16 patients treated by leg lengthening for various forms of Turner dwarfism with regard to the long period of healing and the complications. We consider that Turner dwarfism is a suitable indication for leg lengthening because of the moderate length deficit and the morphological appearance of the patients, and have introduced an improved programme of management to deal with the problems encountered.

The treatment of fractures with a dynamic axial fixator.

The results obtained with a lightweight dynamic axial fixator in the treatment of fractures are reported. The apparatus comprises a single bar with articulating ends which clamp self-tapping screws and can be locked at an angle appropriate for axial alignment. A telescopic facility allows ready conversion from rigid to dynamic fixation once periosteal callus formation has commenced. Reduction and controlled distraction or compression are achieved by means of a detachable compressor unit. We treated 288 patients with fresh fractures and 50 with ununited fractures. The success rate for fresh fractures was 94%, with average healing times ranging from 3.4 to 6.5 months. In ununited fractures also, the success rate was 94% with average healing times ranging from 4.7 to 6.5 months. Complications were minimal. The device is versatile and can be applied in an average of 15 minutes. It permits ambulatory fracture care without sacrificing a sound anatomical result.

Limb lengthening by distraction of the epiphyseal plate. A comparison of two techniques in the rabbit.

We have compared, in rabbits, two techniques of limb lengthening by distraction of the epiphyseal plate using a unilateral external fixation frame. In all cases, 14 mm of symmetrical lengthening without deviation was achieved. With rapid distraction at rates of 1 mm per day (distractional epiphyseolysis) separation of the epiphysis from the metaphysis occurred by day 7, and by day 70 almost complete ossification of the cartilage and the elongated segment was evident. In contrast, slow distraction at 0.25 mm every 12 hours (chondrodiatasis) produced hyperplasia of growth cartilage without any evidence of detachment at 28 days, the end of the distraction period. By day 70 the epiphyseal plate had returned to normal thickness with normal cellular morphology, while the lengthened segment was occupied by ossified tissue. The significance of these findings is discussed.

Chondrodiatasis-controlled symmetrical distraction of the epiphyseal plate. Limb lengthening in children.

We describe a technique for slow, progressive, symmetrical distraction of the growth plate using a lightweight dynamic axial fixation system. Results are given for the elongation of 40 bony segments in children with limb-length discrepancies and 60 segments in children with achondroplasia or hypochondroplasia. Increases in limb length of up to 36% were obtained in non-achondroplastic and up to 64.5% in achondroplastic patients. There were no nerve or vascular lesions or bony infections and no case required a bone graft. Pin-track complications occurred in only 1.5%.

Lengthening of the lower limbs in achondroplastic patients. A comparative study of four techniques.

We report our experience of lengthening by over 30% a total of 117 lower limbs in achondroplastic patients. We have compared four methods: transverse osteotomy, oblique osteotomy, callotasis of the shaft and chondrodiatasis of the epiphysis. Chrondrodiatasis of the femur and callotasis of the tibia are the techniques which gave fewest complications.

Lower-limb lengthening in short stature. An electrophysiological and clinical assessment of peripheral nerve function.

We assessed peripheral nerve function during and after lower-limb lengthening by callotasis in 14 patients with short stature, using motor conduction studies. Four patients with short stature of varying aetiology showed unilateral and one showed bilateral weakness of foot dorsiflexion. Both clinical and electrophysiological abnormalities consistent with involvement of the peroneal nerve were observed early after starting tibial callotasis. There was some progressive electrophysiological improvement despite continued bone distraction, but two patients with Turner's syndrome had incomplete recovery. A greater percentage increase in tibial length did not correspond to a higher rate of peroneal nerve palsy. The function of the posterior leg muscles and the conduction velocity of the posterior tibial nerve were normal throughout the monitoring period. The F-wave response showed a longer latency at the end of the bone distraction than in basal conditions; this is probably related to the slowing of conduction throughout the entire length of the nerve.

Dynamic axial fixation : A rational alternative for the external fixation of fractures.

Conventional external fixation systems neither inhibit motion at the fracture site sufficiently to permit primary bone healing, nor do they allow sufficient motion to encourage adequate external callus formation. Healing with such systems is therefore prolonged. These methods are usually reserved for the most severe fractures when internal fixation may be contraindicated. A unilateral, dynamic axial fixation system (Orthofix - registered trademark) is described which allows for simple conversion from a rigid to a dynamic mode, and so can be readily adapted to the changing physiological patterns of fracture repair.In 288 fresh fractures a success rate of 94% was achieved, with an average time to healing of 4.4 months. The incidence of pin-track infection was only 0.6%. The contribution which the mechanical and design features of the apparatus make to the results obtained is discussed.It is suggested that the system is capable of extending the range of indications for an externally mounted system to include many cases which would formerly have been treated by internal fixation, plaster cast or traction.

Femoral callotasis.

The procedure for femoral callotasis is explained, and a series of 160 lengthenings is reviewed, 60 for limb length discrepancy and 100 for short stature. Callotasis was performed in 106 subjects with a mean age of 19 years. The mean healing index (HI) of 36 days per centimeter is related more to etiology than to age or extent of lengthening. There were nine complications (15%) among subjects treated for limb discrepancies and 39 (39%) in those treated for short stature. Three permanent sequelae were recorded: necrosis of the head of the femur (two cases) and permanent extension deficit of the knee (one case). The present review assesses the type of results that can be achieved with callotasis in straightforward cases of femoral lengthening when the guidelines proposed by the author are followed. It does not attempt to compare this technique with other methods of limb lengthening.

Limb lengthening in short stature patients.

A series of 140 patients with short stature operated on for limb lengthening (80 had achondroplasia, 20 had hypochondroplasia, 20 had Turner syndrome, 10 had idiopathic short stature due to an undemonstrated cause, 5 regarded their stature as too short, and 5 had a psychopathic personality due to dysmorphophobia that had developed because of their short stature) was reviewed. All patients underwent symmetric lengthening of both femora and tibiae; 10 of these achondroplastic patients underwent lengthening of the humeri. We carried out the 580 lengthening procedures by means of three different surgical techniques: 440 callotasis, 120 chondrodiatasis and 20 mid-shaft osteotomy. In the 130 patients with a disproportionate short stature, the average gain in length was 18.2 +/- 3.93 cm: 43.8% had complications and 3.8% had sequelae; the average treatment time was 31 months. In the 10 patients with proportionate short stature, the average gain in length was 10.8 +/- 1.00 cm: 4 experienced complications and none had sequelae; the average treatment time was 21 months. Patients who underwent lengthening of the upper limbs experienced an average gain in length of 10.2 +/- 1.25 cm: the average treatment time was 9 months and none of them experienced any complications or sequelae. The authors discuss how difficult it is to achieve the benefits of this surgery: they underline the strong commitment on the part of the patients and their families, the time in the hospital, the number of operations and, above all, the severity of those permanent sequelae that occurred.

Nerve conduction changes during lower limb lengthening. Somatosensory evoked potentials (SEPs) and F-wave results.

The effect of lower limb lengthening on nerve conduction was investigated in 5 achondroplastic subjects who underwent callotasis on a "cross-over" basis. Somatosensory evoked potentials (SEPs) and F waves from the posterior tibial nerve (PTN) were studied preoperatively and then after removal of the axial fixators. SEPs at the end of lengthening showed that both the latency of the plexus potential (P9) and, albeit to a lesser extent, the interpeak time between the plexus and the spinal cord (N15) potentials were significantly increased. The central conduction time (N15-P33) and the amplitude of the scalp responses were not modified. The latencies of the F waves were much longer at the end of bone distraction than in basal conditions. The increases in both PTN SEPs and F-wave latencies are consistent with a slowing of conduction The extent of these latency shifts correlated closely with the degree of limb lengthening. We calculated that, on average, each cm of lengthening could produce 0.21 msec and 0.22 msec delays respectively, suggesting a similar effect of the stretching on both sensory and motor fibers. Our findings indicated that the damage could be widely distributed along the whole length of the nerve, affecting both the peripheral (trunk) and proximal (plexus and root) segments. The electrophysiological changes were not associated with any persistent clinical complaint.

Minimally invasive plate osteosynthesis in type B fibular fractures versus open surgery.

BACKGROUND: In traumatology, the search for better surgical access points has led to the increased use of the minimally invasive plate osteosynthesis (MIPO) technique. There are few studies on the treatment of distal fibular fractures with MIPO. Locking compression plates (LCP) for distal fibular fractures is generally applied after open reduction, but may involve complications to the surgical wound. In this study, we compared two groups of patients receiving either ORIF or MIPO, in order to analyse the advantages and disadvantages of the two techniques. MATERIALS AND METHODS: Two homogeneous groups of patients (18 + 18) received LCP for distal fractures of the fibula, type B, according to AO. Group A patients underwent open surgery, whereas Group B patients received plates applied with the MIPO technique. Both groups were examined physically and radiographically 1 and 3 months after the two types of procedure and then 1 year later, with functional assessment according to Olerud and Molander. RESULTS: ROM Group A: 5° reduction in tibiotarsal extension in 8 patients and 5° in supination in 1 patient; Group B: 5° reduction in extension in 7 cases. Mean healing time: 3 months (range 2-4) in Group A and 2.9 (range 2-4) in Group B. Dehiscence of the surgical wound was observed in five Group A patients, but none in Group B. Functional assessment according to Olerud and Molander was 87.4 points in Group A (range 80-100) and 95.6 in Group B (range 82-100). CONCLUSIONS: We believe that the MIPO technique for distal fractures of the fibula should be used more often, especially if soft tissue is in a critical condition. Healing times should be reduced in the more complex cases. It is important that the learning curve should be improved, to minimize exposure to radioscopy and possible damage to the superficial fibular nerve.

Locked antegrade intramedullary nailing of humeral shaft fractures.

This paper reports the results of treating 35 humeral shaft fractures with antegrade nailing in patients between the ages of 25 and 92 (mean 64.5): 14 patients were aged between 25 and 59, and 21 between 66 and 92. The nail was set in place proximally with a spiral blade and distally with 1 or 2 screws. In the first 14 cases, uncannulated humeral nailing (UHN) was carried out, and in the next 21 cannulated humeral nailing (CHN). The latter technique uses a guide wire which, in cases of an error in the length of the nail, is useful in that it allows another nail to be set in place. Main outcome parameters were fracture healing, shoulder discomfort, and radial nerve recovery. The DASH functional scoring system, modified according to Beaton et al. for subjective assessment was used, and range of motion was checked with the constant score. X-rays were used to assess fracture healing time and cases of malunion. Two patients developed non-union, one caused by a UHN which was too short, and the other by a nail blocked distally by a single screw. In 7 patients, consolidation was achieved, but with varus between 3 and 8 degrees (mean 5 degrees), without aesthetic or functional damage. In 33 out of 35 patients, shoulder functionality had mean DASH score results of 21.9, whereas shoulder range of motion reached a mean constant score (CS) of 26.5 (78.8%) with respect to the opposite shoulder. In 5 cases of stiffness, the UHN turned out to be insufficiently buried. Results improved with the CHN. Much better results were seen in the group of patients aged between 25 and 59 (mean age 43), but worse in older ones (66-92 years, mean age 78). Radial nerve palsy after surgery occurred in 2 cases, and the nerve was immediately examined. It did not appear to be trapped in the fracture in either case, and recovery was complete 6 months later. CHN appears to be a valid solution, both in younger patients, thanks to excellent results, and in older ones, who have fewer functional requirements.