Biomedical subjects

Georg Gradl

Publications and source records attributed to Georg Gradl.

11 recordsLinked to original sources

PubMed2006

Exaggeration of tissue trauma induces signs and symptoms of acute CRPS I, however displays distinct differences to experimental CRPS II.

As CRPS I frequently develops after tissue trauma, we proposed that an exaggerated inflammatory response to tissue trauma may underlie CRPS I. Therefore, we studied the vascular inflammatory, nociceptive and apoptotic sequelae of (i) soft tissue trauma and (ii) exaggerated soft tissue trauma in comparison to those of (iii) sciatic nerve chronic constriction injury, modeling CRPS II. Standardized soft tissue trauma (TR) was induced by means of a controlled impact injury technique in the hind limb of pentobarbital-anesthetized rats. Additional animals received soft tissue trauma and femoral arterial infusion of mediator-enriched supernatant achieved by homogenization and centrifugation of traumatized muscle tissue in order to provoke an exaggerated trauma response (ETR). Infusion of supernatant of non-traumatized muscle served as control intervention (STR, sham trauma response). Neuropathy was induced by chronic constriction injury of the sciatic nerve (CCI). Untreated animals served as controls (CO). Detailed nociceptive testing showed temporarily decreased mechanical pain thresholds in ETR animals that resolved within 14 days, while TR and STR animals, i.e. those with singular limb trauma, and controls remained free of pain. Neither cold- nor heat-evoked allodynia developed in post-traumatic animals, whereas CCI animals presented the well-known pattern of ongoing neuropathic pain. Using high-resolution in vivo multifluorescence microscopy, muscle tissue of traumatized animals revealed an enhanced inflammatory response that was found most pronounced in ETR animals. CCI of the sciatic nerve was not accompanied by tissue inflammation; however, induced myocyte apoptosis. Collectively, these data indicate that exaggeration of trauma response induces signs and symptoms of acute CRPS I. Pain perception displays differences to that in CRPS II. Apoptosis turns out to be a distinctive marker for CRPS, warranting further evaluation in clinical studies.

Acute Disease↗

PubMed2006

Partial weight bearing after surgery for fractures of the lower extremity--is it achievable?

Partial weight bearing is a generally accepted principle of rehabilitation following trauma or reconstructive surgery of the lower extremity. Individual dynamic loads during partial weight bearing to a given load level of 200 N were compared in 23 patients who had sustained a fracture of the lower extremity and 11 healthy volunteers using dynamic sole pressure measurements. Excessive dynamic loading compared with the statically pre-tested 200 N level was observed in all groups. Maximum force levels were up to 690 N in young patients and up to 580 N elderly patients beyond the prescribed static load. None of the healthy volunteers was able to keep within the given load of 200 N. The set load level was exceeded by at least 38 N (119%) in the elderly patient group. In comparison, elderly patients showed statistically significantly higher maximum forces than young patients during the first two test days (p=0.007 and 0.013). On the 3rd test day the maximum ground contact forces were on average 71 N higher than in the young patients group. Analysis of the force time integrals (impulses transferred to the ground) displayed higher values in the older again than in young patients. The differences were statistically significant during the first two test days (p=0.006 and 0.037). This study implies that the conventional concept of postoperative partial weight bearing starting from 200 N and a stepwise increase of the load level until full weight bearing is not valid during clinical practice.

Adolescent↗

PubMed2006

Detection of fibular torsional deformities after surgery for ankle fractures with a novel CT method.

BACKGROUND: Substantial fibular torsional deformities were detected after surgery for ankle fractures combined with a lesion of the syndesmotic complex using a novel CT analyzing method. METHODS: In a prospective study, 61 patients with ankle fracture dislocations were treated with trans-syndesmotic screw fixation of the distal tibiofibular joint. Postoperative axial CT scans of both lower legs under standardized leg positioning conditions were made and analyzed with three different methods. Method 1 (M1) used proximal and distal CT planes of the lower leg for detection of the fibular torsional angle, method 2 (M2) considered only the angle at the distal tibiofibular joint, and method 3 (M3) measured the angles between the fibular and tibial tangents at the distal tibiofibular joint. Twenty patients with fibular torsional asymmetries of more than 10 degrees were evaluated clinically 6 to 34 months postoperatively with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. RESULTS: Thirty-five of the 61 patients had torsional side-to-side differences of more than 10 degrees. M1 and M2 showed statistically significant differences compared to M3 (p = 0.001). Validity was controlled by interobserver data, variation coefficients were low for M1 and M2. Clinically, six of 20 patients with torsional differences of more than 10 degrees had excellent results, while seven had good results and seven had moderately functional results. Six of the seven with moderate results had fibular torsional differences of more than 15 degrees, two of the seven patients with good outcomes. Torsional results of M1 and M2 correlated with the AOFAS score (r = -0.506). CONCLUSIONS: Of the 61 ankle fractures with ruptures of the syndesmotic complex, 25% showed torsional side-to-side differences of more than 10 degrees on proximal and distal CT planes. This CT technique correlated with the AOFAS score and could help determine when early operative revision is indicated.

Adolescent↗

PubMed2005

Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis.

A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor alpha1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis.

Animals↗

PubMed2005

Sympathetic dysfunction as a temporary phenomenon in acute posttraumatic CRPS I.

OBJECTIVE: Sympathetic testing was carried out in patients in the acute phase of "complex regional pain syndrome type I" (CRPS I) shortly after trauma to the upper limb. Repeated measurements were used to detect changes in peripheral sympathetic function during the course of the disease. MATERIAL AND METHODS: In a busy trauma center, 10 consecutive patients who developed CRPS I following trauma or surgery of the upper limb were diagnosed according to the 1999 modified IASP diagnostic criteria for CRPS I. Clinical signs and symptoms and bilateral hand temperature (infrared thermometry) were recorded. Vasoconstrictor response to sympathetic provocation (inspiratory gasp, contralateral cooling) at the tip of the middle finger of both hands was measured employing laser Doppler flowmetry (LDF). Sympathetic reaction was quantified by the magnitude of blood flow decrease after provocation (SRF parameter). RESULTS: The diagnosis CRPS I could be established 63 days (46-72 days) post-injury. The mean follow-up time after diagnosis was 83+/-15 days. Pain measured by a visual analog scale (VAS 0-10) showed an average of 5.0+/-2.0 at the time of diagnosis and decreased to 1.7+/-1.9 at the last examination. Edema and active range of motion improved substantially during the follow-up period. On the ipsilateral hand marked sympathetic dysfunction was seen early after the onset of CRPS I (mean SRF parameter: 0.14+/-0.01), slowly returning to normal sympathetic reaction three months after the onset of symptoms (mean SRF parameter: 0.42+/-0.21). Diminished sympathetic function was seen even on the contralateral hand. CONCLUSIONS: Sympathetic dysfunction is regularly seen at the onset of CRPS I and normalizes during the course of the disease. This temporary phenomenon suggests a posttraumatic sympathetic deficit playing a decisive role in the genesis of CRPS I.

Acute Disease↗

PubMed2005

Fractures of the distal radius treated with a nonbridging external fixation technique using multiplanar k-wires.

PURPOSE: Joint-bridging external fixation is a minimally invasive treatment option for distal radius fractures. Although radial length can be restored easily the anatomic reduction of articular fragments and restoration of the normal volar tilt proves to be more difficult. A method of nonbridging hybrid fixation of distal radius fractures facilitates fracture reduction and allows for free wrist movement. METHODS: Twenty-five consecutive patients with fractures of the distal radius were treated with nonbridging external fixation for 6 weeks. The stepwise surgical technique comprised a preliminary joint-bridging construction for reduction purposes, the subsequent insertion of 3 to 4 K-wires in the distal fragment, the assembling of wires to a bar nearly parallel to the fracture line, and lastly the removal of the joint-bridging part. Clinical and radiologic evaluation was performed on the first and seventh days and at 6 weeks and 2 years after surgery. RESULTS: All fractures united. Palmar tilt (> or =0 degrees ) and articular surface (articular step-off < 2 mm) were restored in all patients whereas loss of radial length occurred in 4 patients having the distal fracture fragment secured with 3 K-wires. No radial shortening was seen in fractures with 4 K-wires inserted in the distal fragment. Functional results at 2 years after surgery showed an average extension of 55 degrees and flexion of 64 degrees without significant differences between extra-articular and intra-articular fractures. There was no extensor tendinitis or pin loosening in the distal fragment; however, 3 pin track infections of proximal pins occurred. CONCLUSIONS: This surgical technique of nonbridging external fixation is a good treatment option for distal radius fractures: it permits wrist movement. We recommend the insertion of 4 K-wires in the distal fracture fragment.

Aged↗

PubMed2005

Supernatant of traumatized muscle induces inflammation and pain, but not microcirculatory perfusion failure and apoptotic cell death.

Soft tissue trauma induces an inflammatory response locally and in remote organs. Although remote organ failure is attributed to the systemic action of locally released mediators, it is so far unclear to what extent a direct cell injury and the consequences of ischemia or a secondary injury due to locally released mediators contribute to the manifestation of tissue damage at the primary site of trauma. Soft tissue trauma was induced by means of a controlled impact injury technique in the hind limb of pentobarbital-anesthetized rats. Additional animals received a femoral arterial infusion of supernatant of traumatized muscle tissue, of nontraumatized muscle, or 0.9% NaCl. Tissue injury was assessed by determining microcirculatory perfusion failure, inflammatory response, apoptotic cell death, and nociceptive pain behavior. Muscle tissue of traumatized animals revealed perfusion failure, tissue hypoxia, and inflammation. Nociceptive testing showed a decrease in mechanical pain thresholds of the affected hind paw. Infusion of supernatant of traumatized tissue induced local inflammation and pain comparable with that of directly traumatized tissue; however, it failed to cause nutritive perfusion failure. Supernatant of nontraumatized muscle did not affect muscle microcirculation and integrity. Only animals that underwent direct trauma presented with apoptotic cell death, as given by in vivo fluorescence microscopy, caspase 3 protein cleavage, and transferase-mediated dUTP nick-end labeling histology. Trauma-associated humoral factors cause post-traumatic hyperalgesia and inflammation, but not microvascular perfusion failure and apoptotic cell death. This finding may prompt future efforts in the therapy of closed soft tissue trauma to focus not only on antimediator strategies, but to add regimens targeting perfusion failure and tissue apoptosis.

Animals↗

PubMed2005

Selective cyclooxygenase-2 inhibition reverses microcirculatory and inflammatory sequelae of closed soft-tissue trauma in an animal model.

BACKGROUND: Despite the common use of nonsteroidal anti-inflammatory drugs in the treatment of closed soft-tissue injuries, our understanding of the effect of these medications on tissue healing is incomplete. Using high-resolution multifluorescence microscopy, we investigated the efficiency of preinjury and postinjury treatment with the selective cyclooxygenase (COX)-2 inhibitor parecoxib to improve compromised perfusion of traumatized muscle tissue and to minimize secondary tissue damage. METHODS: With use of a pneumatically driven and computer-controlled impact device, closed soft-tissue trauma of the left hindlimb was induced in anesthetized rats that had had intravenous administration of 10 mg/kg of either parecoxib sodium (seven rats) or an equal volume of saline solution (seven rats). Seven additional animals received parecoxib two hours after the trauma, and seven animals without trauma served as controls. RESULTS: Time-course studies with use of both Western blot protein analysis and immunohistochemistry demonstrated a transient upregulation of COX-2 protein expression with peak levels eight to twelve hours after trauma and a return to near baseline level at eighteen hours. Regardless of whether parecoxib was administered before or after the injury, it completely restored microcirculatory impairment within the injured muscle. This was indicated by the mean values (and standard error of the mean) for nutritive perfusion (434 +/- 15 cm/cm(2) in animals treated before the injury and 399 +/- 8 cm/cm(2) in those treated after injury), nicotinamide adenine dinucleotide (NADH) levels (73 +/- 2 aU and 74 +/- 1 aU, respectively), and inflammatory cell interaction (184 +/- 36 and 186 +/- 32 n/mm(2), respectively, for leukocytes, and 1.0 +/-0.1 and 0.8 +/- 0.1 n/mm(2), respectively, for platelets) at eighteen hours after trauma, which were not different from those found in noninjured muscle tissue of controls. In contrast, skeletal muscle in saline solution-treated animals revealed persistent perfusion failure (296 +/-30 cm/cm(2)) with tissue hypoxia (NADH, 100 +/- 4 aU), and enhanced endothelial interaction of both leukocytes (854 +/- 73 mm(-2)) and platelets (2.3 +/- 0.5 n/mm(2)) at eighteen hours after trauma. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of skeletal muscle soft-tissue trauma with parecoxib before as well as after injury is highly effective in restoring disturbed microcirculation. Moreover, a reduced inflammatory cell response helps to prevent leukocyte or platelet-dependent secondary tissue injury. These results deserve further investigation to prove that selective COX-2 inhibitors improve performance and promote healing following closed soft-tissue injury.

Animals↗

PubMed2004

Quantification of C2 cervical spine rotatory fixation by X-ray, MRI and CT.

Atlanto-axial rotatory displacement is known to be a cause of childhood torticollis and may as well be responsible for chronic neck pain after rear-end automobile collisions. The objective was to determine whether quantification of C2 malrotation is possible by plain radiographs in comparison to CT as the golden standard. MR imaging was evaluated as to whether it was of equal value in the detection of bony landmarks. C2 vertebra of five human cadaveric cervical spine specimens, ligamentously intact, were rotated using a Steinmann pin in steps of 5 degrees up to 15 degrees right and 15 degrees left. Plain radiographs, CT and MRI images were taken in each rotational step. Data were analyzed for quantification of C2 rotation by three independent examiners. A rotation of 5 degrees led to a spinous process deviation (SPD) from the midline of 3 mm as measured on an a.p. plain radiograph. A coefficient of rotation was calculated (1.62 degrees mm(-1)). Data analyzed by three examiners revealed a small coefficient of variation (0.03). MRI and CT measurements showed comparable results for the quantification of rotation; however, in both techniques the 15 degrees rotation was underestimated. Quantification of upper cervical spine malrotation was possible on plain radiographs using the SPD and a rotation coefficient. MRI and CT were equally successful in the assessment of C2 malrotation.

Adult↗

PubMed2004

In vivo evidence for apoptosis, but not inflammation in the hindlimb muscle of neuropathic rats.

Loose ligation of the rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in complex regional pain syndrome (CRPS) patients. Neurogenic inflammation is a purported cause of neuropathic pain despite inconsistent evidence to support this hypothesis. To clarify this issue, we examined effects of CCI on microcirculation, inflammatory cell-cell interaction and cell integrity in muscle tissue using intravital fluorescence microscopic, molecular and immunohistochemical techniques. CCI-rats, but not sham-operated animals developed symptoms of neuropathic pain and oedema on the ipsilateral hindpaw. Despite signs of neuropathic pain, high resolution in vivo multifluorescence microscopy revealed physiological values for functional capillary density, leukocyte-endothelial cell interaction and microvascular permeability in muscle tissue of CCI-animals, similarly as found in controls, indicating absence of perfusion failure and inflammatory cell reaction. However, CCI-animals represented with marked apoptosis of bisbenzimide-stained muscle tissue cells, as given by in vivo fluorescence microscopic assessment of cell death-associated condensation, fragmentation and/or crescent-shaped formation of their nuclear chromatin. Apoptosis was further confirmed by increased caspase 3 protein levels and positive terminal deoxyuridine nick end labeling histochemistry. The present study demonstrates that sciatic nerve ligation-induced neuropathy causes cell apoptosis without concomitant inflammation-associated microcirculatory dysfunction in muscle tissue. Beside the well-known pattern of neuropathic pain, the CCI-model has now additionally been shown to reflect the response of muscle tissue to impaired innervation, i.e. prompting muscle cells to undergo non-inflammatory apoptotic cell death. This finding deserves further investigation in that apoptosis may contribute to neuropathic pain conditions like CRPS.

Animals↗

PubMed2003

Efficiency of small-volume resuscitation in restoration of disturbed skeletal muscle microcirculation after soft-tissue trauma and haemorrhagic shock.

BACKGROUND AND AIMS: Despite advances in primary care, trauma in conjunction with shock remains the leading cause for morbidity and mortality of young adults in western countries. Herein, we report on the efficiency of small-volume resuscitation to improve compromised perfusion of traumatised skeletal muscle tissue in shock. METHODS: In pentobarbital anaesthetised, mechanically ventilated rats, closed soft-tissue trauma of the right hind limb was induced, followed by induction of haemorrhagic shock [mean arterial blood pressure (MAP) 40 mmHg for 1 h]. For resuscitation, animals received saline (four-times the shed blood volume/20 min), 10% hydroxyethyl starch (HES) 200/0.5 (equal to shed blood volume/5 min) or 7.2% sodium chloride/6% hydroxyethyl starch 200/0.5 (HyperHES; 10% of shed blood volume/2 min). At 2 h of resuscitation, traumatised skeletal muscle tissue was analysed by in vivo microscopy. Non-resuscitated animals served as shock controls. RESULTS: Despite incomplete restoration of systemic blood pressure, HyperHES was superior to saline, but not to HES, with respect to amelioration of nutritive perfusion. Inflammatory cell response within the traumatised skeletal muscle tissue escaped from the anti-adhesive properties of HyperHES when applied for resuscitation from hypovolaemic shock, and did not differ from values in HES-treated and saline-treated animals. CONCLUSION: Resuscitation with HyperHES is as effective as HES in improving capillary perfusion in traumatised skeletal muscle during haemorrhagic shock. However, because values of functional capillary density in the HyperHES-treated and HES-treated animals were still markedly below those reported in traumatised skeletal muscle of normovolaemic animals, further tools are needed to enhance efficiency in treatment of local skeletal muscle tissue injury during haemorrhagic shock.

Animals↗