Biomedical subjects
Publications and source records attributed to R J Goris.
In this article sepsis scoring systems commonly used are presented as regards their results and shortcomings. Furthermore, in a more general context, the direct and indirect effect on the individual patients is discussed and recommendations are given on how to use scoring systems.
OBJECTIVES: To construct a set of instruments to measure the level of impairment in reflex sympathetic dystrophy (RSD), to convert the scores for each instrument into one score and to derive a compounded impairment level sumscore (ISS), and to evaluate reliability, validity, and responsiveness of the ISS. DATA SOURCES AND EXTRACTION: Literature search in Medline (1985 to 1995), non-Medline journals, and references from these reports for measurement parameters and suitable, reliable, responsive, and validated instruments. DATA SYNTHESIS: Four measurement parameters (pain, active range of motion, temperature, and volume) and five measurement instruments were chosen to construct the ISS. All outcomes were converted into one score, resulting in an addable score. RESULTS: Forty-five patients with RSD of one upper extremity were evaluated. As expected for this heterogeneous index, the internal consistency of the ISS was poor to moderate. The ISS seemed to have content and concurrent validity. The responsiveness of the ISS was adequate. CONCLUSIONS: A multicomponent test was constructed to map alterations in the level of impairment in RSD patients. Each of the parameter scores could be translated into a uniform score. Adding the scores yielded the ISS.
OBJECTIVE: To determine the prevalence, type of complication, predisposing factors, and treatment for severe complications in a population of reflex sympathetic dystrophy (RSD) patients. DESIGN: Retrospective analysis of the data from RSD patients collected over a 12-year period, to investigate the involvement of predisposing factors in an RSD population without severe complications compared with an RSD population with severe complications. SETTING: Outpatient clinic of a department of surgery of a university hospital. PATIENTS: A total of 1,006 patients with the diagnosis of RSD established according to prospectively defined criteria. MAIN OUTCOME MEASURES: The signs and symptoms of every RSD patient who visited the department were prospectively documented in the medical history; these data were retrospectively analyzed with special regard to RSD with severe complications-infection, ulcers, chronic edema, dystonia, and/or myoclonus-for prevalence, type of complication, and treatment. RESULTS: Seventy-four RSD patients who were mostly young and female developed severe complications. More than one complication occurred in 91% of the affected extremities. Severe complications developed more frequently in the lower extremity (65%). In patients in whom the acute RSD started with a decreased skin temperature of the affected extremity, severe complications developed significantly more often than in acute RSD patients with a warm skin temperature of the extremity from the onset of the disease (p < .001). CONCLUSIONS: It is important to recognize "cold" RSD immediately at the onset of the disease because this group of RSD patients has a higher risk of developing a severe complication, mostly followed by a severe disability that is resistant to therapy.
OBJECTIVES: Chlorpromazine is a known modulator of tumor necrosis factor (TNF)-alpha production. TNF-alpha is thought to be a key mediator in the development of the multiple organ dysfunction syndrome (MODS). We investigated the effect of chlorpromazine on the development of zymosan-induced MODS in mice and on plasma TNF-alpha concentrations and production capacity of TNF-alpha by peritoneal cells. DESIGN: Prospective, controlled laboratory study on zymosan-induced generalized inflammation in mice. SETTING: Animal research laboratory. SUBJECTS: C57BL/6 mice received daily doses (4 mg/kg body weight) of chlorpromazine, beginning 2 days before or 5 days after zymosan administration. In additional groups, the daily chlorpromazine dose of 4 mg/kg started 5 days after zymosan was increased 2 days later to 8 or 16 mg/kg/day. MEASUREMENTS AND MAIN RESULTS: The animals were monitored for survival, condition, body weight, and body temperature. Twelve days after zymosan was administered, all surviving animals were killed to obtain plasma, organs, and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured. Organ weights were recorded as an indicator for organ damage. Although survival was not improved when the animals were treated with chlorpromazine, the chlorpromazine-treated survivors showed improved body weight and temperature when compared with the animals receiving zymosan only. Also, the organ weights and lung damage improved significantly in the treated group. Chlorpromazine was most effective when started before zymosan administration. When administered afterward, clinical improvement declined with the dose. In all cases, circulating TNF-alpha and production of TNF-alpha by peritoneal macrophages were lowered toward control values. CONCLUSION: Chlorpromazine mitigates the development of zymosan-induced MODS, possibly by reducing macrophage TNF-alpha production.
Explore the source record for details and available documents.
The effect of zymosan-induced generalized inflammation on the microcirculation of distant striated skin muscle was studied for a 12 day period in awake Syrian golden hamsters (n = 18) using the dorsal skinfold chamber model and intravital fluorescence microscopy. Intraperitoneal zymosan exposure (125 mg/100 g body weight) induced significant nutritive perfusion failure in the distant striated muscle tissue at Day 1 without complete recovery over the 12 day observation period, as indicated by the marked reduction of functional capillary density when compared with both baseline values and values of sham-treated control animals. Moreover, intraperitoneal zymosan exposure induced endothelial disintegration, as demonstrated by the continuous increase of macromolecular leakage throughout the 12 days of observation. Strikingly, zymosan did not induce significant leukocyte adherence to the endothelial lining of postcapillary and collecting venules of the striated muscle tissue. Thus, we conclude that in this model of generalized inflammation nutritive perfusion failure and loss of endothelial integrity in distant striated muscle is not mediated by activated leukocytes, but must rather be attributed to direct toxic effects of mediators, elicited by the local (intraperitoneal) zymosan challenge and systemically released.
BACKGROUND: Reflex sympathetic dystrophy (RSD) (recently reclassified as complex regional pain syndrome type I) is a syndrome occurring in extremities and, when chronic, results in severe disability and untractable pain. RSD may be accompanied by neurologic symptoms even when there is no previous neurologic lesion. There is no consensus as to the pathogenic mechanism involved in RSD. To gain insight into the pathophysiology of RSD, we studied histopathology of skeletal muscle and peripheral nerve from patients with chronic RSD in a lower extremity. METHODS: In eight patients with chronic RSD, an above-the-knee amputation was performed because of a nonfunctional limb. Specimens of sural nerves, tibial nerves, common peroneal nerves, gastrocnemius muscles, and soleus muscles were obtained from the amputated legs and analyzed by light and electron microscopy. RESULTS: In all patients, the affected leg showed similar neurologic symptoms such as spontaneous pain, hyperpathy, allodynia, paresis, and anesthesia dolorosa. The nerves showed no consistent abnormalities of myelinated fibers. In four patients, the C-fibers showed electron microscopic pathology. In all patients, the gastrocnemius and soleus muscle specimens showed a decrease of type I fibers, an increase of lipofuscin pigment, atrophic fibers, and severely thickened basal membrane layers of the capillaries. CONCLUSION: In chronic RSD, efferent nerve fibers were histologically unaffected; from afferent fibers, only C-fibers showed histopathologic abnormalities. Skeletal muscle showed a variety of histopathologic findings, which are similar to the histologic abnormalities found in muscles of patients with diabetes.
The acute phase of reflex sympathetic dystrophy (RSD) is characterized by the classical signs and symptoms of inflammation (rubor, calor, dolor, tumor and impaired function). As free radicals are involved in acute inflammation, we studied the effects of free radicals in an animal model, especially as to signs and symptoms found in acute RSD. Awake rats were given continuous intra-arterial infusion (1 ml/h) in the left hindlimb, with saline (n = 6) or the free-radical donor tert-butylhydroperoxide (tert-BuOOH, 25 mM, n = 6). During a 24-h infusion period the skin temperature, volume, skin color, function and pain reactions of the paws were observed. After 24 h the rats were killed and both gastrocnemius muscles were histologically analyzed. Infusion with tert-BuOOH induced in the left paw an increased skin temperature, increased volume, redness of the plantar skin, impaired function and increased pain sensation, while these acute RSD signs and symptoms were absent in the saline infused animals. The alterations in pain sensation (spontaneous, mechanical and thermal pain) were similar to findings in the neuropathic animal model. The gastrocnemius muscles of the saline infused rats and the contralateral gastrocnemius muscle of the tert-BuOOH infused rats showed no histological tissue damage. In the left gastrocnemius muscle free-radical-related damage was visible. Induction of free-radical formation in one hindlimb of awake rats mimics the acute signs and symptoms of acute RSD, with alterations in pain sensation as found in the classical neuropathic animal model of RSD, as well as in acute RSD patients.
OBJECTIVE: To evaluate the role of specific macrophage subpopulations in the development of zymosan-induced multiple-organ dysfunction syndrome by selective elimination of liver, splenic, alveolar, and peritoneal macrophages. DESIGN: Randomized animal trial. SETTING: Central animal laboratory at the University Hospital Nijmegen, Nijmegen, the Netherlands. ANIMALS: Male C57Bl/6 mice. INTERVENTIONS: Elimination of macrophages was accomplished by administration of multilamellar liposomes that contained dichloromethylene bisphosphonate (Cl2MBP). Intravenous, intratracheal, and intraperitoneal administrations induced an elimination of liver and splenic, alveolar, and peritoneal and omental macrophages, respectively. Zymosan (1 mg/g) was injected intraperitoneally at day 0. The liposomes that contained Cl2MBP were administered before and after zymosan challenge. At day 12, all surviving mice were killed. MAIN OUTCOME MEASURES: The body weights, temperatures, and mortality rates of the mice were monitored daily. Relative organ weights (ROWs) were calculated from the lungs, liver, spleen, and kidneys after the mice were killed. RESULTS: The liposomes that contained Cl2MBP, administered intravenously before or after zymosan challenge, did not induce significant changes in the body weight, temperature, or mortality rate. The ROW of the liver was significantly decreased in both treatment groups. Elimination of liver and splenic macrophages after zymosan challenge induced an increased ROW of the lung and a decreased ROW of the liver. The liposomes that contained Cl2MBP, administered intratracheally before zymosan challenge, completely prevented deaths. The body weights, temperatures, and ROWs of the mice were not changed. The liposomes that contained Cl2MBP, administered intraperitoneally, did not change the body weight, temperature, or ROW. The liposomes that contained Cl2MBP, administered intraperitoneally before zymosan challenge, increased the mortality from 50% to 90%. CONCLUSIONS: These data show that the elimination of specific macrophage subpopulations and the elimination on specific time points in this model had differential effects, indicating a differential role of specific macrophage subpopulations, either protective or detrimental, in the development of multiple-organ dysfunction syndrome.
Oxygen-derived free radicals are suspected to play an important role in the pathogenesis of inflammation and ischemia/reperfusion of an extremity. In this study we investigated the repair capacity of a free radical-damaged hindlimb of the rat and the effect of the anti-oxidant N-acetyl-L-cysteine (NAC). In nonanesthetized rats (n = 39), the left hindlimb was continuously infused intra-arterially (1 ml/hr) for 24 hr with the free radical donor tert-butylhydroperoxide (tert-BuOOH, 25 mM). Subsequently the infusion system was disconnected and the repair of soft tissue damage was observed with special attention to various pain tests, vascular permeability ((99m)Tc-IgG scintigraphy), and histology for a maximum period of 6 weeks. In 12 of these tert-BuOOH-infused rats the antioxidant NAC was injected intraperitoneally. Six of the NAC-treated rats were killed after 24 hr of infusion, while the remaining 6 rats were disconnected, reinjected with NAC, and observed for 1 week. Tert-BuOOH infusion for 24 hr led to significantly increased pain sensations, vascular permeability, and histological damage. Treatment with NAC significantly reduced pain sensations and vascular permeability, though not to control levels. One week after disconnection, tissue damage was almost completely repaired in the NAC-treated rats. In the untreated rats, repair took longer but histology and vascular permeability were completely normalized within the observation period. Soft tissue damage, induced by 24-hr infusion of the free radical donor tert-BuOOH, showed spontaneous repair within 6 weeks. The antioxidant NAC significantly reduced the soft tissue damage and shortened the repair period.
Reflex sympathetic dystrophy (RSD) is a syndrome affecting an extremity after a minor trauma or operation. At the moment there is no consensus about the pathogenesis of RSD. In 1942 Paul Sudeck suggested that the signs and symptoms of RSD may be provoked by an exaggerated inflammatory response to injury or operation of an extremity. His theory found no disciples, as most physicians believe that RSD is initiated by an hyperactive sympathetic system. We performed various clinical and experimental investigations, including the effects of antiinflammatory treatment. The results of these studies support the theory of Paul Sudeck.
Explore the source record for details and available documents.
Our objective was to determine the serial evolution of vascular permeability as measured by protein extravasation in various organs during the development of zymosan-induced multiple organ dysfunction syndrome (MODS). We evaluated the biodistribution of 111Indium-labeled nonspecific polyclonal immunoglobulin G (111In-IgG). On days 2, 5, 8, and 12 after intraperitoneal challenge with 1 mg/g zymosan, mice were killed. Heart, liver, spleen, kidneys, and the mesenteric lymph node complex and tissue samples of muscle, ileum, and colon were dissected free and weighed. 24 h before death, 10 micrograms of IgG labeled with 2 MBq 111In was injected i.v. Relative organ weights (ROW), wet to dry weight ratios (WDR), and a permeability index (PI) were calculated. ROW increased gradually until day 12. WDR also increased gradually in most organs. Lung WDR, however, initially increased, with a subsequent return to normal. Splenic WDR did not change over time. Liver, spleen, ileum, and colon PI were the highest on day 2, followed by a decrease toward normal. Lung PI showed a triphasic course with peak values at days 2 and 12. Mesenteric lymph node complex-PI was continuously elevated. WDR (tissue edema) and PI (protein extravasation) have different courses in various organs. Most organs displayed an early increase in PI, followed by a late decrease, while ROW (organ damage) was still increasing. It appears that organ damage is preceded by an increased protein extravasation.
A well defined animal model is a prerequisite to test intervention strategies aimed at preventing the development of the multiple organ dysfunction syndrome. This study compares changes in clinical parameters to histopathologic changes in tissues, observed over a 12 day period after a single intraperitoneal injection of zymosan in C57BL/6 mice. Administration of zymosan induced gradual and progressive changes in wet and dry organ weight of the liver, kidneys, and particularly, lungs and spleen that correlated with increasing histopathology. From 6 days after zymosan injection onwards, hemorrhagic spots were found in the lungs evolving into massive hemorrhages at 12 days, when thickened interstitial walls and loss of the honey comb-like structures were observed. The liver displayed progressive accumulation of macrophage-like and mononuclear cells. After 12 days, numerous granuloma-like structures were disseminated throughout the liver parenchyma. The spleen displayed great changes in red and white pulp with increasing numbers of megakaryocytes and plasma-like cells. In the kidneys, necrosis of the tubular epithelium adjacent to granulomas on the ventral (peritoneal) side was found. In mice, a single intraperitoneal challenge with zymosan leads to progressive multiple organ damage, which becomes apparent at some time after the insult. This animal model displays a number of features encountered in human multiple organ dysfunction syndrome and appears suitable to conduct intervention studies.
We present a novel animal model which allows the continuous intra-arterial infusion in one hindlimb of non-anaesthetized rats, without inducing ischemia. Using this model the effect of continuous infusion (1 ml/h) for 24 h with tert-butylhydroperoxide (tert-BuOOH) at a concentration of 25 mM on soft tissue of the left hind limb was studied and compared to the effect of saline infusion (control group). The tert-BuOOH-infused foot showed increased skin temperature, increased circumference, redness of the plantar skin, impaired function and increased pain sensation, while in the contralateral foot and in rats only perfused with saline these signs of inflammation were absent (p < 0.01). Histological analysis of the left gastrocnemius muscle showed edema, muscle cell degeneration with a patchy distribution pattern and vascular damage. All these features increased in severity from 4 to 24 h tert-BuOOH infusion. After 24 h of tert-BuOOH infusion infiltration of neutrophils in the interstitium was observed. Vascular permeability, expressed as left to right gastrocnemius muscle 99mTc-IgG uptake ratio, was similarly increased after 4 h (2.09 +/- 0.26) and 12 h (2.04 +/- 0.08) of tert-BuOOH infusion compared to saline (1.05 +/- 0.08) (p < 0.001), and further increased after 24 h (3.84 +/- 0.13): (p < 0.001). In this animal model free radical-related soft tissue damage was induced, by continuous infusion of tert-BuOOH, followed by increasing necrosis and vascular permeability in skeletal muscle coinciding with neutrophilic infiltration.
Reflex sympathetic dystrophy (RSD) is a syndrome affecting an extremity after a minor trauma or operation. Currently, there is no consensus about the pathogenesis of RSD. The authors performed various clinical and experimental investigations, including studies of the effects of anti-inflammatory treatment, that support the hypothesis that RSD is the result of an exaggerated inflammatory response to injury or surgery.
Multiple organ dysfunction syndrome and the systemic inflammatory response syndrome are expressions of an inappropriate, generalized inflammatory response to severe inflammatory stimuli, which may be bacterial or nonbacterial in nature. The clinical signs and symptoms, morphologic alterations, and changes in oxygen transport seem to be the direct effect of phagocyte activation. So far, identifying the microorganisms and neutralizing their toxins has not been helpful in improving prognosis. As an essential adjunct to treating the bacterial or nonbacterial causes, finding safe ways of modulating the phagocyte response should be considered.
Reflex sympathetic dystrophy (RSD) is a disease that can appear after minor trauma or operation to an extremity. The injury may vary from a simple contusion to a fracture. The prevalence of burns as a cause of RSD, within a population of 829 patients with RSD, was studied retrospectively. Prospectively, we documented the medical history, signs and symptoms of all patients with RSD, seen by our department during the period from January 1984 to 31 December 1994. Four patients had developed RSD after a burn injury, resulting in a prevalence of 0.5 per cent. Though the clinical signs of early RSD are similar to those of a (thermal) burn, alertness to recognize inflammatory signs, in combination with the increase in complaints after exercise, is necessary for early diagnosis and treatment of the complicating RSD.