Delayed recovery and late development of complex regional pain syndrome in patients with an isolated fracture of the distal radius: prediction of a regional inflammatory response by early signs.

We studied prospectively the regional inflammatory response to a unilateral distal radial fracture in 114 patients at eight to nine weeks after injury and again at one year. Our aim was to identify patients at risk for a delayed recovery and particularly those likely to develop complex regional pain syndrome. In order to quantify clinically the inflammatory response, a regional inflammatory score was developed. In addition, blood samples were collected from the antecubital veins of both arms for comparative biochemical and blood-gas analysis. The severity of the inflammatory response was related to the type of treatment (Kruskal-Wallis test, p = 0.002). A highly significantly-positive correlation was found between the regional inflammatory score and the length of time to full recovery (r(2) = 0.92, p = 0.01, linear regession). A regional inflammatory score of 5 points with a sensitivity of 100% but a specificity of only 16% also identified patients at risk of complex regional pain syndrome. None of the biochemical parameters studied correlated with regional inflammatory score or predicted the development of complex regional pain syndrome. Our study suggests that patients with a distal radial fracture and a regional inflammatory score of 5 points or more at eight to nine weeks after injury should be considered for specific anti-inflammatory treatment.

Subareolar breast abscesses: characteristics and results of surgical treatment.

Our objective was to describe the characteristics of subareolar breast abscesses and to analyze the results of surgical treatment in relation to the prevention of recurrences. Almost 70% of patients smoked more than 10 cigarettes a day. The recurrence rate after excision of the lactiferous ducts was 28% and after management without excision of the lactiferous ducts was 79% (p < 0.001). Gram-positive bacteria were isolated more frequently in primary subareolar breast abscesses (not significant). Anaerobic microorganisms were more frequently cultured in recurring subareolar breast abscesses (p = 0.02). Definitive treatment of subareolar breast abscesses should consist of excision of the affected lactiferous ducts.

Pentoxifylline does not improve outcome in a murine model for the multiple-organ dysfunction syndrome.

OBJECTIVE: To investigate the effects of pentoxifylline (PTX) administration in a murine model for the multiple-organ dysfunction syndrome (MODS). DESIGN AND SETTING: Prospective double-blind randomized animal study in a university research laboratory. INTERVENTIONS AND MEASUREMENTS: Sixty C57BL/6 mice were given an aseptic intraperitoneal injection of lipopolysaccharide followed after 6 days by zymosan (day 0) at a dose of either 0.9 or 1.0 mg/g body weight. Starting on day 0 mice were administered PTX at a dose of 80 mg/kg body weight or saline per os every 8 h. On day 17 surviving animals were killed, and their liver, lungs, spleen, and kidneys were collected. RESULTS: Mortality, course of body temperature, body weight, and macroscopic lung damage were similar between zymosan-treated groups. Administration of PTX did not significantly alter survival, body temperature, body weight, or macroscopic lung damage. In addition, there were no significant differences in organ weights between mice that received PTX and mice that received PBS. Although PTX inhibited the lipopolysaccharide-induced increase in tumor necrosis factor alpha and interleukin 6 expression (but not interleukin 1beta expression) at both mRNA and protein level in a murine macrophage cell line, tumor necrosis factor alpha mRNA expression in the livers of PTX-treated mice was not significantly inhibited. CONCLUSIONS: The results reported here do not support the hypothesis that PTX improves outcome in zymosan-induced multiple-organ dysfunction in mice.

Increased expression of matrix metalloproteinases in the murine zymosan-induced multiple organ dysfunction syndrome.

Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue damage in several inflammatory diseases. Since the multiple organ dysfunction syndrome (MODS) is thought to result from systemic inflammation, overactivation of MMPs could contribute to the organ damage observed. The expression and activity of several MMPs were studied in a murine model for MODS. Sixty mice were given an aseptic intraperitoneal injection of lipopolysaccharide, followed, after 6 days, by zymosan. At days 2, 5, 8, 12, and 16 after the injection of zymosan, the liver, lungs, spleen, and kidneys were collected from groups of mice for either RNA extraction, gelatinase zymography and collagenase (MMP-1 and -13) assays (six mice per time point), or immunohistochemistry (three mice per time point). A group of nine mice did not receive zymosan and acted as controls. The expression of MMP-2 mRNA in zymosan-treated mice was strongly up-regulated in liver tissue only. For MMP-9, this was the case in all organs examined. Quantitative gelatin zymography demonstrated the near complete absence of any gelatinase activity in tissues from control mice. However, in the liver, lungs, and especially the spleen of zymosan-treated animals, significantly increased activity of proform and active MMP-2 and -9 was observed with time. Overall, MMP-1 and -13 activities were very low in all samples from the liver and lungs. In the spleen, however, high levels of MMP-1 and -13 were observed in zymosan-treated animals. Immunohistochemical staining for MMP-2 was detected in the liver and spleen, but not in lung and kidney tissue of zymosan-treated animals. Staining for MMP-9 could be detected in liver, lung, and spleen tissues of zymosan-treated mice. For both MMPs, staining appeared to be limited to phagocytes. In conclusion, the data suggest a role for MMPs, especially MMP-9, in the pathogenesis of MODS.

Capillary blood gas analysis in complex regional pain syndrome: a pilot study.

BACKGROUND: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) is still a matter of debate. An inflammatory reaction may cause the syndrome. Increasing evidence points to a role for impairment of oxygen metabolism in the affected limb. METHODS: In this pilot study (16 patients) we performed capillary blood gas analysis in extremities with acute CRPS 1, in order to assess oxygen saturation and lactate concentrations. Comparison was made with the unaffected limb for capillary blood pH, pO(2), SaO(2), and lactate and glucose concentrations. RESULTS: No statistically significant differences could be found. CONCLUSIONS: Capillary blood gas analysis is not useful to detect changes in oxygen saturation and lactate concentrations in CRPS 1.

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

BACKGROUND: open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. OBJECTIVE: to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. METHOD: forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. RESULTS: WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). CONCLUSION: multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation.

[One hundred years of the Association of Surgeons in the Netherlands. V. Traumatology]. / Honderd jaar Nederlandse Vereniging voor Heelkunde. V. Traumatologie.

Traumatology in the Netherlands gained considerable momentum during the last years of the twentieth century. This breakthrough was due to the creation of ten trauma care centres, each with its own 'mobile medical team'. Additionally, four of these centres dispose of a helicopter for rapid transport of this team. Furthermore, within the field of medical education and training, new courses on advanced trauma and life support (ATLS) and advanced pediatric life support (APLS), for example, not only offer more practical knowledge, but also provide a 'common language' for all those involved in the medical and organisational aspects of trauma care. Surgical treatment of trauma injuries is becoming increasingly oriented towards minimally invasive techniques. Assessment of the quality of care provided requires a broad and reliable registration system for injuries.

[Optimizing antibiotics policy in the Netherlands. V. SWAB guidelines for perioperative antibiotic prophylaxis. Foundation Antibiotics Policy Team]. / Optimaliseren van het antibioticabeleid in Nederland. V. SWAB-richtlijnen voor perioperatieve antibiotische profylaxe.

The Stichting Werkgroep Antibioticabeleid (SWAB, Foundation Antibiotics Policy Team) has issued guidelines for perioperative antibiotic prophylaxis in Dutch hospitals. Antibiotic prophylaxis is generally recommended for surgical procedures with relatively high postoperative infection rates and those in which consequences of infection are really serious. Studies have revealed that prophylaxis given within two hours before incision is most effective. Short-term, preferably single-dose prophylaxis, is as effective as multiple-dose prophylaxis in most procedures. For reasons of cost effectiveness and prevention of induction of resistance, single-dose prophylaxis is recommended. The antimicrobial agent of choice for perioperative prophylaxis should not be widely used as a therapeutic agent, should be selectively active against micro-organisms most frequently isolated from surgical site infections, and should have a plasma-half-life that makes single-dosing possible for most operations. Therefore cefazoline is an agent that is widely used for perioperative prophylaxis.

Role of neutrophils in burn-induced microvascular injury in the intestine.

The present study evaluated burn-induced vascular permeability alterations of rat small intestine in vivo and assessed the effect of neutrophil depletion in burn-injured rats on the altered intestinal microvascular permeability. 125I-labeled bovine serum albumin (125I-BSA) was injected intravenously, and its leakage from circulation into the intestinal tissue was determined by measuring tissue counts of 125I-BSA. Compared with sham, vascular albumin permeability increased 1.7-fold on day 1 post-burn and 3.0-fold on day 3 post-burn in ileum. In the jejunum, albumin permeability increased 1.8- and 2.5-fold on day 1 and day 3 post-burn, respectively. Intestinal tissue edema, determined as increases in tissue water contents, was noted in both intestinal segments on day 1 post-burn; no further increase in edema was found on day 3 post-burn. Neutrophil depletion before burn injury prevented the vascular leakage of albumin and edema in the ileum and jejunum on day 1 post-burn. On day 3 post-burn, the effect of prior neutrophil depletion on vascular permeability was less marked, and edema formation was not affected at all. These findings indicate that an absence of neutrophils prevents the loss of intestinal vascular barrier properties only in the initial periods after burns.

Evaluation of three methods to rate impairment in patients with complex regional pain syndrome I of one upper extremity.

OBJECTIVE: To gain insight into the best way of obtaining an impairment rating in complex regional pain syndrome I (CRPS I) of the upper extremity. This syndrome can potentially result in permanent impairment. DESIGN: Comparison of three evaluation methods to obtain impairment scores. Each patient was seen by one tester; two testers in total participated in the research. SETTING: Outpatient clinic of a university hospital. SUBJECTS: Seventy-four patients (27 men, 47 women, mean age 52 years) with CRPS I of one upper extremity. MAIN OUTCOME MEASURES: Methods I and II were conducted according to the American Medical Association's Guides to the evaluation of permanent impairment method I according to the general guidelines, and method II according to the methodology specificially described for CRPS I. Method III was developed by the Dutch Association of Neurologists. For comparison, differences between methods were plotted against their mean ratings, with the limits of agreement. Also the paired t-statistics were calculated (alpha = 0.05/3). RESULTS: The mean difference between methods I and II was -0.7% whole body impairment, between methods II and III 8.1% and between methods I and III 7.3%. Outcomes obtained with method III differed significantly from the other outcomes. CONCLUSIONS: Method I most accurately and objectively reflected the permanent impairment level resulting from CRPS I.

The Radboud skills questionnaire: construction and reliability in patients with reflex sympathetic dystrophy of one upper extremity.

PURPOSE: To construct a questionnaire to measure skills in which notably both hands are active, which is suitable for patients with a disease of one or both hands and to research its response stability and possible improvements. METHOD: Using the Dutch elaboration of the ICIDH and then experts in a Delphi round, the questionnaire was constructed. Thereafter, test-retest and inter-observer reliability was examined. Fifty-four patients with RSD in one upper extremity and a normal contralateral extremity participated in the study, the first twenty to evaluate the construction of the questionnaire and the others to test reliability. RESULTS: The constructed Radboud skills questionnaire was reliable in terms of response stability (median coefficients of variation 2.2% to 6.6%). Correlation's between categories of items were fair to good. CONCLUSIONS: A useful questionnaire was constructed to map alterations in the level of disability in patients with a disease of one hand or both hands.

Leg muscle reflexes mediated by cutaneous A-beta fibres are normal during gait in reflex sympathetic dystrophy.

OBJECTIVES: Reflex sympathetic dystrophy (RSD) is, from the onset, characterized by various neurological deficits such as an alteration of sensation and a decrease in muscle strength. We investigated if afferent A-beta fibre-mediated reflexes are changed in lower extremities affected by acute RSD. METHODS: The involvement of these fibres was determined by analyzing reflex responses from the tibialis anterior (TA) and biceps femoris (BF) muscles after electrical stimulation of the sural nerve. The reflexes were studied during walking on a treadmill to investigate whether the abnormalities in gait of the patients were related either to abnormal amplitudes or deficient phase-dependent modulation of reflexes. In 5 patients with acute RSD of the leg and 5 healthy volunteers these reflex responses were determined during the early and late swing phase of the step cycle. RESULTS: No significant difference was found between the RSD and the volunteers. During early swing the mean amplitude of the facilitatory P2 responses in BF and TA increased as a function of stimulus intensity (1.5, 2 and 2.5 times the perception threshold) in both groups. At end swing the same stimuli induced suppressive responses in TA. This phase-dependent reflex reversal from facilitation in early swing to suppression in late swing occurred equally in both groups. CONCLUSIONS: In the acute phase of RSD of the lower extremity there is no evidence for abnormal A-beta fibre-mediated reflexes or for defective regulation of such reflexes. This finding has implications for both the theory on RSD pathophysiology and RSD models, which are based on abnormal functioning of A-beta fibres.

The gut: the 'motor' of multiple organ dysfunction syndrome?

Abnormal colonization, gut-origin infections, and bacterial translocation are all signs of gut dysfunction that may be implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). This review summarizes and updates relevant experimental and clinical data that have attempted to correlate these phenomena with the development of MODS and to answer whether or not the gut is the 'motor' of MODS. The presented data suggest that, in some patients, gut dysfunction may precede the development of MODS. However, in most patients, this relationship is less obvious. The gut may still be one of the motors of MODS; however, it does not appear that this motor is fueled by the systemic spread of bacteria. Bacteria may play a role on a local gut-associated level in initiating and perpetuating the production of local inflammatory mediators that may produce distant organ injury.

Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy.

There are no adequate comparative studies on physical therapy (PT) versus occupational therapy (OT) in patients with complex regional pain syndrome I (CRPS I). Therefore, we conducted a prospective randomised clinical trial to assess their effectiveness. The outcomes regarding reducing pain and normalising active range of motion (AROM) are discussed. Included in the study were 135 patients who had been suffering from CRPS I of one upper extremity for less than one year. They were randomly assigned to one of three groups: PT, OT, or control (social work, CT). Measurements were taken at base-line (t0), after 6 weeks, and after 3, 6 and 12 months (t1 to t4). Pain was measured on four visual analogue scales (VAS) and the McGill Pain Questionnaire, Dutch Language Version (MPQ-DLV). The AROM was recorded relative to the contralateral side. Explorative statistical evaluations were performed (Wilcoxon; alpha=0.05). PT and to a lesser extent OT, resulted in more rapid improvement in the VAS scores than CT, especially for the VAS during or after effort (P<0.05 at t1 to t3). PT was superior to CT and OT according to the MPQ-DLV particularly at t4. Improvement on the MPQ-DLV over the year was significantly greater for PT than for OT and CT (P<0.05). PT -and to a lesser degree OT- led to better results than CT for the AROM of the wrist, fingers and thumb at t1 to t3 (most-times P<0.05 for PT), but the improvements over the year were not significantly different. Our results indicated that PT, and to a lesser extent OT, were helpful for reducing pain and improving active mobility in patients with CRPS I of less than one year duration, localised in one upper extremity.

Signs and symptoms in complex regional pain syndrome type I/reflex sympathetic dystrophy: judgment of the physician versus objective measurement.

OBJECTIVE: To assess the relation between the subjectively assessed and objectively measured diagnostic signs and symptoms in complex regional pain syndrome type I (CRPS I) and to quantify their severity. DESIGN: Diagnostic signs and symptoms were recorded in patients suffering from CRPS I of one upper extremity for less than 1 year. Independent assessors measured (a) pain by using four visual analog scales (VAS) and the McGill Questionnaire list of adjectives (MPQ), (b) edema with a hand volumeter, (c) skin temperature with an infrared thermometer, and (d) active range of motion (AROM) with goniometers. SETTING: Two university hospitals. PATIENTS: Ninety-five women and 40 men with CRPS I of one upper extremity. RESULTS: Four signs and symptoms were diagnosed in 50 patients, and five in the remaining 85 patients. The mean score for present pain intensity was 31.5 mm and that for pain resulting from exertion of the affected extremity was 71.9 mm. A median of 11.5 words was chosen from the MPQ, with the highest number from its evaluative part. The difference in volume between both hands was 30.4 ml. The mean difference in temperature between the two hands was 0.78 degrees C dorsally and 0.66 degrees C palmarly. The largest decrease in mobility was seen in the wrist and fingers; the thumb was relatively less affected and the little finger relatively more affected than the other fingers. CONCLUSIONS: Bedside evaluation of CRPS I with Veldman's criteria was in good accord with psychometric or laboratory testing of these criteria.

Interleukin 10 mitigates the development of the zymosan-induced multiple organ dysfunction syndrome in mice.

We investigated the effect of interleukin 10 on the development of zymosan-induced multiple organ dysfunction syndrome (MODS) and on plasma concentrations and production capacity of tumour necrosis factor (TNF)-alpha by peritoneal cells. Groups of C57BL/6 mice received a single intraperitoneal injection with zymosan, a cell wall component of Saccharomyces cerevisiae, at day 0. Daily doses of human recombinant interleukin 10 (IL-10: 10 or 50 microg/kg) were given intraperitoneally either starting directly before administration of zymosan (day 0), or 5 or 8 days after administration of zymosan. The animals were monitored for survival, condition, body weight and temperature. On day 12 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 registered as an indicator for organ damage. IL-10 improves survival and clinical condition and also reduces organ damage, but only at the highest dose used and only when started simultaneously with the administration of zymosan. Circulating TNF-alpha concentrations 12 days after zymosan are not affected by any of the IL-10 schedules used. However, lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells is increased, in a dose- and time-dependent fashion. The anti-inflammatory cytokine IL-10 is able to attenuate the development of MODS in this model, but only when given simultaneously with zymosan, and in high dosages.

Objective and subjective assessments of temperature differences between the hands in reflex sympathetic dystrophy.

OBJECTIVE: A difference in temperature between the affected and normal extremity is one of the signs or symptoms of reflex sympathetic dystrophy (RSD). These temperature differences are scored anamnestically, by palpation, or by measurements. We investigated the relationship between objective and subjective differences in skin temperature between the hands. SUBJECTS AND DESIGN: Fifty-one patients with RSD of one upper extremity participated (mean age 55 years, range 18-80). In the first 16 we investigated the reliability of the visual analogue scale (VAS) for recording perceived differences in skin temperature. In the remaining 35 patients the relationship between the VAS and objective infrared radiometry of the hands was investigated. SETTING: Outpatients clinics of two university hospitals. RESULTS: The VAS was found to be reliable in terms of response stability. There was no significant correlation between the objective and subjective outcomes. CONCLUSIONS: There is lack of correspondence between objective and subjective temperature measurements, which may be due to a normal discrepancy between objective and perceived temperature, and/or to alterations in perception due to RSD.