Bone tissue concentrations of ciprofloxacin released from biodegradable screws implanted in rabbits skull

Previously, ciprofloxacin-releasing polylactide/polyglycolide 80/20 (SR-PLGA) screws have proven to be biocompatible with sufficient strength. However, there has been no information about the local concentrations of ciprofloxacin in bone tissue after their implantation. To measure bone concentrations of ciprofloxacin, two screws were implanted in each rabbit, one on either side of the sagittal suture (n = 28 rabbits). Follow-up periods were 2, 4, 8, 16, 24, 52 and 78 weeks. From each rabbit, bone blocks containing one screw were retrieved and used to measure drug concentration. Ciprofloxacin concentration at 2 weeks follow-up was 4.4 ± 4.2 μg/g, 14.1 ± 2.7 μg/g at 4 weeks and 7.6 ± 4.5 μg/g at 8 weeks. Measured concentrations were very low at 16 weeks (mean 0.09 ± 0.04 μg/g) and 24 weeks (mean 0.04 ± 0.02 μg/g). Surprisingly, the concentration was higher again at 1 year (mean 1.3 ± 1.0 μg/g). At 1.5 years, concentration had decreased again (mean 0.8 ± 0.6 μg/g). The drug concentration in bone tissue was higher than minimal inhibitory concentration of ciprofloxacin (Staphylococcus aureus 0.1–1.0 μg/g) at 2, 4, and 8 weeks. Ciprofloxacin-releasing SR-PLGA 80/20 screws could be used clinically for osteofixation and infection treatment in cranial bone.     

Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR

OBJECTIVE: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis. METHODS: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire. RESULTS: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer. CONCLUSION: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.     

Intervention effectiveness among war-affected children: a cluster randomized controlled trial on improving mental health

We examined the effectiveness of a psychosocial intervention in reducing mental health symptoms among war-affected children, and the role of peritraumatic dissociation in moderating the intervention impact on posttraumatic stress symptoms (PTSS). School classes were randomized into intervention (n = 242) and waitlist control (n = 240) conditions in Gaza, Palestine. The intervention group participated in 16 extracurriculum sessions of teaching recovery techniques (TRT) and the controls received normal school-provided support. Participants were 10- to 13-year-old Palestinian girls (49.4%) and boys (50.6%). Data on PTSS, depressive symptoms, and psychological distress were collected at baseline (T1), postintervention (T2), and 6-month follow-up (T3). Peritraumatic dissociation was assessed only at baseline. Regression analyses that took regression to the mean and cluster sampling into account were applied. The results on intervention effectiveness were specific to gender and peritraumatic dissociation. At T2, the intervention significantly reduced the proportion of clinical PTSS among boys, and both the symptom level (R(2) = .24), and proportion of clinical PTSS among girls who had a low level of peritraumatic dissociation. The results have implications for risk-specific tailoring of psychosocial interventions in war conditions.     

MR monitoring of focused ultrasonic surgery of renal cortex: Experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1- weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby Indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.