1.Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions
Dhanani A. JAYESH ; Parker L. SUZANNE ; Lipman JEFFREY ; Wallis C. STEVEN ; Cohen JEREMY ; Fraser JOHN ; Barnett ADRIAN ; Chew MICHELLE ; Roberts A. JASON
Journal of Pharmaceutical Analysis 2018;8(6):407-412
Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycinwas lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.
2.Failure of Dermal Allograft Repair of Massive Rotator Cuff Tears in Magnetic Resonance Imaging and Clinical Assessment
Conor James Craig GOUK ; Ryan Mark SHULMAN ; Craig BUCHAN ; Michael John Evan THOMAS ; Fraser James TAYLOR
Clinics in Orthopedic Surgery 2019;11(2):200-207
BACKGROUND: Massive retracted rotator cuff tears represent a therapeutic dilemma, particularly in the young and middle-aged patients who are not appropriate for a reverse total shoulder replacement. Interposition grafting using human dermal allograft offers an alternative treatment. METHODS: A retrospective review of all patients who underwent interposition grafting using human dermal allograft between December 2013 and May 2015 for massive rotator cuff tears at our tertiary referral center was performed. Preoperative and 6 month postoperative magnetic resonance imaging (MRI) assessments were performed in all patients, with postoperative graft integrity being the primary outcome measure. Clinical evaluation was performed using the Oxford shoulder score, Constant score, and Disabilities of the Arm, Shoulder and Hand (DASH) score. RESULTS: The mean age at the time of follow-up was 54 years. On MRI, 84% of grafts were seen to have failed at 6 months. Strength was grossly reduced on the operative side when supraspinatus and subscapularis were tested; despite this, Constant score (mean, 48.2) was comparable to that in the previous reports. DASH and Oxford scores were a mean of 24.94 and 37.16, respectively. CONCLUSIONS: Based on these results, in particular the MRI findings, we cannot advocate the use of dermal allograft as an interposition graft for the repair of massive rotator cuff tears.
Acellular Dermis
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Allografts
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Arm
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Follow-Up Studies
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Hand
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Humans
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Magnetic Resonance Imaging
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Outcome Assessment (Health Care)
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Retrospective Studies
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Rotator Cuff
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Shoulder
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Surgical Procedures, Operative
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Tears
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Tertiary Care Centers
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Transplants
3.Ex Vivo Expansion and Clonality of CD34 Cells from Bone Marrow, Umbilical Cord Blood and Mobilized Peripheral Blood in Serum-free Media.
Soon Ki KIM ; Moon Whan IM ; Chung Hyun NAHM ; Chul Soo KIM ; Ju Young SEO ; John K FRASER
Korean Journal of Pediatric Hematology-Oncology 2001;8(1):101-109
PURPOSE: Umbilical cord blood is increasingly being used in the setting of allogeneic marrow transplantation. However, while neutrophil engraftment is comparable to that of marrow transplants, delayed platelet engraftment is often a concern for cord blood transplant recipients. This delay may be due to relative weakness of the megakaryocyte lineage in cord blood. We evaluated the potential of ex vivo expansion and clonality from different stem cell sources. METHODS: The CD34 cells from bone marrow (BM), umbilical cord blood (CB), and mobilized peripheral blood (PB) were cultured for burst-forming unit of erythrocyte (BFU-E), colony-forming unit of granulocyte and monocyte (CFU- GM) and colony-forming unit of megakaryocyte (CFU-MK) at day 0, day 4, day 7, and day 14 under the combination of growth factors, with cell counts. Cytokines included recombinant human megakaryocyte growth and development factors (100 ng/mL), interleukin-3 (10 ng/mL), stem cell factor (100 ng/mL), and flt-3 ligand (50 ng/mL). RESULTS: CB-derived CD34 cells had significantly higher total cell proliferation than either BM or PB at day 7 (1.6 to 18.2 fold) and day 14 (1.2 to 17.2 fold). The colony count of BFU-E was in general more plentiful in CB than in BM and PB at day 4, day 7 and day 14, among which the difference was the most distinct at day 7 culture. Also, CB CD34 cells produced more CFU-Mk colonies than did BM or PB at day 4 and day 7. There were no differences in colonies count of BFU-E and CFU-Mk between BM and PB. CONCLUSION: Ex vivo expansion of CB cells may be most promising in producing total cellular expansion, CFU-Mk and BFU-E compared with BM and PB, especially at day 7, because the former was the most productive hematopoietic source on a per volume basis.
Blood Platelets
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Bone Marrow*
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Cell Count
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Cell Proliferation
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Culture Media, Serum-Free*
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Cytokines
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Erythrocytes
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Erythroid Precursor Cells
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Fetal Blood*
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Granulocytes
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Hematopoietic Stem Cells
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Humans
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Intercellular Signaling Peptides and Proteins
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Interleukin-3
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Megakaryocytes
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Monocytes
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Neutrophils
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Stem Cell Factor
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Stem Cells
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Thrombopoietin
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Transplantation
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Umbilical Cord*