Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison with healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patient-reported outcomes, and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FCs) not fulfilling the CRPS diagnostic criteria. We included upper-extremity FCs, acute CRPS I patients within 1 year after trauma, a second disease control group (painful diabetic polyneuropathy), and healthy controls. Fracture controls were not symptoms-free, but reported some pain, disability, anxiety, and cold pain hyperalgesia in quantitative sensory testing. Patients with CRPS had higher scores for pain, disability, and all patient-reported outcomes. In quantitative sensory testing, ipsilateral and contralateral sides differed significantly. However, on the affected side, patients with CRPS were more sensitive in only 3 parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors that distinguish CRPS and FC. Fracture control as a control group can assist to discover resolution factors after trauma.
The implantation of antibiotic-containing cement beads became standard adjuvant local antibiotic therapy of chronic osteomyelitis. The new developed bioabsorbable drug carrier system of polyglycolic acid with the antibiotic Ciprofloxacin was tested in vitro and in vivo. The goal of this study was to determinate the penetration depth of Ciprofloxacin into bone cortex and marrow. Two monofil, PGA cylinders, 3.2 x 5 mm in size, containing 3 mg of Ciprofloxacin each, were implanted into the proximal part of both femora of 18 rabbits (New Zealand white). After sacrifice, the concentration of Ciprofloxacin in micrograms/g cortex and marrow was measured with high-performance liquid chromatography in relation to the distance from the test material at day 2, as well as at 1, 2, 3, 4, and 6 weeks postimplantation. For a distance up to 5 mm, marrow levels of the drug exceeded cortical levels at day 2 (5000 to 240 micrograms/g). At a distance of 5-10 mm, cortex levels were similar to marrow levels after 2 weeks and were higher than marrow levels at week 3. This observation could be made at a distance between 10 and 15 mm only after 2 days. Later, marrow concentrations again exceeded that in cortex. At a distance of more than 15 mm, antibiotic levels were low and approximated. After 6 weeks, at 5 mm distance, a bactericidal drug concentration of about 2 micrograms/g in bone marrow could be measured. Drug penetration into cortical bone in bactericidal concentrations of about 2 micrograms/g was achieved at up to 30 mm in the first few days.(ABSTRACT TRUNCATED AT 250 WORDS)
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