R. Jan A. Goris

Reflex sympathetic dystrophy of the hand : an excessive inflammatory response?

&NA; In 23 patients with reflex sympathetic dystrophy (RSD) of the hand, scintigraphy with indium‐111 labeled human non‐specific polyclonal immunoglobulin G (In‐111‐IgG) was performed to investigate whether inflammatory characteristics are present in RSD. Both blood flow and accumulation over 48 h were assessed. Nineteen patients had increased flow to the affected hand, and 3 had decreased flow. One patient had bilateral RSD. Exercise provoked aggravation of complaints and signs in all patients. The affected/non‐affected hand ratio (target‐to‐background, T/B) immediately before and after exercise did not change significantly. The T/B ratios 48 h after In‐111‐IgG injection were significantly higher in patients with RSD less than 5 months than in patients with RSD existing 5 months or longer. The T/B ratios 24 and 48 h after In‐111‐IgG injection were not correlated with the flow T/B ratios. In fact, 2 of the 3 patients with a decreased flow showed excess accumulation on the late images. Significantly more patients with early RSD, existing less than 5 months, had a positive In‐111‐IgG scintigraphy (14 of 17) than the patients with late RSD (1 of 6). Increased vascular permeability for macromolecules, an important characteristic of inflammation, appears to play a role in the development of RSD. This phenomenon is not flow‐dependent.

Organ damage in zymosan-induced multiple organ dysfunction syndrome in mice is not mediated by inducible nitric oxide synthase.

Objective To examine the role of inducible nitric oxide synthase (iNOS) in the development of the multiple organ dysfunction syndrome (MODS) in a murine model by using either a selective iNOS inhibitor or iNOS knockout mice. Design Prospective randomized laboratory study. Setting Central animal laboratory and experimental laboratory. Subjects Fifty inbred C57BL/6 mice, 39 iNOS knockout (−/−) mice, and 30 wild-type (+/+) mice, 7–9 wks old, weighing 20–25 g. Interventions Mice received an aseptic intraperitoneal injection of 40 &mgr;g of lipopolysaccharide followed by zymosan at a dose of 1 mg/g of body weight 6 days later (day 0). In experiment 1, C57BL/6 mice additionally received intraperitoneal injections with 5 mg of aminoguanidine or saline every 12 hrs, from 4 days after the injection of zymosan onward. In experiment 2, both iNOS−/− mice and corresponding wild-type (iNOS+/+) mice were treated with lipopolysaccharide and zymosan. Measurements and Main Results In all animals, the injection of zymosan induced an acute peritonitis, followed by an apparent recovery. From approximately day 6 onward, animals entered the third—MODS-like—phase, indicated by weight loss, a decrease in body temperature, and significant mortality rates. Quantitative reverse transcriptase polymerase chain reaction and immunochemistry revealed a strongly increased expression of iNOS messenger RNA and iNOS protein in livers of mice in the last phase. However, neither the in vivo administration of aminoguanidine to C57BL/6 mice nor the complete absence of iNOS enzyme (iNOS−/− mice) had a beneficial effect on survival rate, body temperature, or body weight. In addition, relative lung, liver, and spleen weights and lung scores were not different between experimental groups. Conclusions The current results strongly argue against an essential and causative role of iNOS in the development of organ damage in our murine model of MODS.

The Oxidative Response in the Chronic Constriction Injury Model of Neuropathic Pain

BACKGROUND In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model observed (indirect) signs of inflammation. We, therefore, investigated the level of oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat hind paw and (jugular vein) plasma at d 7 after nerve injury. MATERIALS AND METHODS The level of reactive oxygen and nitrogen species (RONS) was determined as a measure of oxidative stress. Reduced GSH levels and the ceruloplasmin/transferrin ratio were determined as measures of overall antioxidant activity. RONS and overall antioxidant activity were measured in skeletal muscle tissue of the hind paw and jugular vein plasma. The level of RONS in muscle was determined using spin trapping combined with electron paramagnetic resonance spectroscopy. Using electron paramagnetic resonance spectroscopy, we also determined plasma levels of transferrin and ceruloplasmin. GSH levels were determined using high-performance liquid chromatography. RESULTS In skeletal muscle tissue, the level of RONS was lower in nerve-injured hind paws than in controls. The plasma level (jugular vein) of RONS did not differ between nerve-injured and control rats. In skeletal muscle tissue, the level of GSH was higher in nerve-injured hind paws than in controls. The ceruloplasmin/transferrin ratio tended to be higher in (jugular vein) plasma of nerve-injured rats as compared to controls. CONCLUSIONS This study shows that, at d 7 after nerve injury, oxidative stress-induced changes are present also in skeletal muscle tissue of the rat hind paw. Our findings of a decreased level of RONS in combination with an increased level of the antioxidant GSH suggest that an overshoot of antioxidant activity overrules initial oxidative stress.

Tissue- and Time-Dependent Upregulation of Cytokine mRNA in a Murine Model for the Multiple Organ Dysfunction Syndrome

Objective:We sough to quantitate the course of specific cytokine mRNA expression in tissues that exhibit increasing histopathological changes in time in an animal model for the multiple organ dysfunction syndrome (MODS). Summary Background Data:The development of treatment protocols for MODS requires elucidation of the mechanisms and mediators involved. To devise logical interventions, it is necessary to collect data on cytokine expression at tissue level during the development of MODS. Methods:Ninety-four C57BL/6 mice were given an intraperitoneal injection of 40 μg of lipopolysaccharide (LPS), followed by zymosan at a dose of 0.8 mg/g body weight 6 days later (day 0). Six additional animals did not receive zymosan and acted as controls. At several time points after zymosan injection, 6 randomly assigned, zymosan-treated animals were killed, and their livers, lungs, spleens, and kidneys were collected. mRNA expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, macrophage migration inhibiting factor, IL-12, interferon-γ, and IL-10 was measured using a real-time reverse transcription-polymerase chain reaction assay. Results:The injection of zymosan induced an acute peritonitis, followed by an apparent recovery. From approximately day 6 onwards, animals started to display MODS-like symptoms. During the peritonitis phase, up-regulation of cytokine mRNA was limited. During the period of apparent recovery, cytokine mRNA expression strongly increased, mostly reaching its maximum at day 9 when deterioration of the clinical condition had already set in. The up-regulation of tumor necrosis factor-α mRNA was most pronounced, especially in the lungs and liver. Conclusions:Interventions should preferentially be targeted against multiple cytokines and, at least in this model, there may be a treatment window well after the initial challenge.

Impaired Oxygen Utilization in Skeletal Muscle of CRPS I Patients

BACKGROUND The purpose of this study was to evaluate oxygen extraction and utilization in end stage chronic complex regional pain syndrome type I (CRPS I) patients undergoing amputation and to relate these to muscle histology of the amputated limb. MATERIALS AND METHODS In 25 patients with severe CRPS I requiring amputation of the affected limb venous blood samples and in 11 patients skeletal muscle specimens were analyzed. RESULTS The mean venous oxygen saturation (S(v)O(2)) value (94.3% ± 4.0%) of the affected limb was significantly higher than S(v)O(2) values found in healthy subjects (77.5% ± 9.8%) pointing to a severely decreased oxygen diffusion or utilization within the affected limb. Histologic analysis showed a significant decrease of type I fibers and a significant increase of type IIB fibers. Ultrastructural investigations of soleus skeletal muscle capillaries revealed thickened endothelial cells and thickened basement membranes. Muscle capillary densities were decreased in comparison with literature data. High venous oxygen saturation levels were partially explained by impaired diffusion of oxygen due to thickened basement membrane and decreased capillary density. CONCLUSION This study shows that venous oxygen saturation is significantly increased in chronic end stage CRPS I patients corresponding with impaired oxygen diffusion. The abnormal skeletal muscle findings points to severe disuse but only partially explain the impaired diffusion of oxygen; mitochondrial dysfunction seems a likely explanation in addition.

Reflex Sympathetic Dystrophy – Another View

Reflex sympathetic dystrophy is a potentially incapacitating syndrome occurring in an extremity, usually after minor injury operation. This manuscript summarizes the current theory on the pathophysiological mechanisms and some new data as to prevention and treatment.

Sod in Rat Models of Shock and Organ Failure

Posttraumatic or postoperative (multi) organ failure is the result of a multitude of reactions similar to (generalized) inflammatory situations. The fuel for this reaction cascade is either derived from continuous activation of humoral cascades (e.g. complement), continuous overshooting phagocytosis or toxic products of bacterial cells (e.g. endotoxin).

Trauma Research in Europe

AbstractBackground: Publishing in journals with the highest possible Impact Factor and Citation Index is of paramount importance for a researcher and his research group. In this respect, European trauma researchers may be in a disadvantaged position, as the citation index of European trauma journals is relatively low, as compared to Anglo-American trauma journals. Material and Method: This article analyses relative differences observed in original studies published in a continental European and several Anglo-American trauma journals. Aspects analysed include the number, (source of) funding, country of origin, type and topic of study of the publications. Conclusion: It is concluded that the quality of original trauma publications from Europe is high, that the larger subsidized studies are published outside continental Europe, while relatively few European studies have received (substantial) funding. Obtaining substantial financial support for trauma research, i. e. to appoint and train dedicated trauma researcher, is of capital importance to promote the cause of trauma research in Europe.