Evaluation of 99mtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction.

Serial 99mTc pyrophosphate scintigrams were obtained 7 hr to 15 days after experimental acute myocardial infarction produced by permanent or transient coronary occlusion. Scintigrams were interpreted visually and the increased radioactivity in the precordial image was quantitated and compared to extent of infarction found histologically. Results of these studies indicate: 1) 99mTc pyrophosphate imaging is an extremely sensitive for detection of acute myocardial infarction, i.e., infarction in excess of 1% of the left ventricular mass was detected. 2) Early detection of acute infarction is a function of blood flow since 7 hr after infarction scans were negative after permanent occlusion but were strongly positive after transient occlusion. 3) Radioactivity in the precordial image was inversely related to extent of infarction after permanent occlusion and directly related to extent of infarction after transient occlusion. 4) 99mTc pyrophosphate localized in areas with significant histologic infarction but the distribution of radioactivity was not proportional to extent of infarction.     

Donation after cardiac death as a strategy to increase deceased donor liver availability

OBJECTIVE: This study examines donation after cardiac death (DCD) practices and outcomes in liver transplantation. SUMMARY BACKGROUND DATA: Livers procured from DCD donors have recently been used to increase the number of deceased donors and bridge the gap between limited organ supply and the pool of waiting list candidates. Comprehensive evaluation of this practice and its outcomes has not been previously reported. METHODS: A national cohort of all DCD and donation after brain-death (DBD) liver transplants between January 1, 2000 and December 31, 2004 was identified in the Scientific Registry of Transplant Recipients. Time to graft failure (including death) was modeled by Cox regression, adjusted for relevant donor and recipient characteristics. RESULTS: DCD livers were used for 472 (2%) of 24,070 transplants. Annual DCD liver activity increased from 39 in 2000 to 176 in 2004. The adjusted relative risk of DCD graft failure was 85% higher than for DBD grafts (relative risk, 1.85; 95% confidence interval, 1.51-2.26; P < 0.001), corresponding to 3-month, 1-year, and 3-year graft survival rates of 83.0%, 70.1%, and 60.5%, respectively (vs. 89.2%, 83.0%, and 75.0% for DBD recipients). There was no significant association between transplant program DCD liver transplant volume and graft outcome. CONCLUSIONS: The annual number of DCD livers used for transplant has increased rapidly. However, DCD livers are associated with a significantly increased risk of graft failure unrelated to modifiable donor or recipient factors. Appropriate recipients for DCD livers have not been fully characterized and recipient informed consent should be obtained before use of these organs.     

Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

Optimizing the environment of complex bone healing and improving treatment of catastrophic bone fractures and segmental bone defects remains an unmet clinical need both human and equine veterinary medical orthopaedics. The objective of this study was to determine whether scAAV‐equine‐BMP‐2 transduced cells would induce osteogenesis in equine bone marrow derived mesenchymal stem cells (BMDMSCs) in vitro, and if these cells could be cryopreserved in an effort to osteogenically prime them as an “off‐the‐shelf” gene therapeutic approach for fracture repair. Our study found that transgene expression is altered by cell expansion, as would be expected by a transduction resulting in episomal transgene expression, and that osteoinductive levels could still be achieved 5 days after recovery, and protein expression would continue up to 14 days after transduction. This is the first evidence that cryopreservation of genetically modified BMDMSCs would not alter the osteoinductive potential or clinical use of allogeneic donor cells in cases of equine fracture repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1310–1317, 2019.     

Current and novel injectable hydrogels to treat focal chondral lesions: Properties and applicability

Focal chondral lesions and early osteoarthritis (OA) are responsible for progressive joint pain and disability in millions of people worldwide, yet there is currently no surgical joint preservation treatment available to fully restore the long term functionality of cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. Toward improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Injectable hydrogels have emerged as a promising scaffold due to their wide range of properties, the ability to encapsulate cells within the material, and their ability to provide cues for cell differentiation. Some of these advances include the development of improved control over in situ gelation (e.g., light), new techniques to process hydrogels (e.g., multi‐layers), and better incorporation of biological signals (e.g., immobilization, controlled release, and tethering). This review summarises the innovative approaches to engineer injectable hydrogels toward cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:64–75, 2018.     

IMMUNOHEMATOLOGY: Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment

BACKGROUND: Donor white blood cells (WBCs) present in transfusion products can lead to immune sequelae such as production of HLA antibodies or graft‐versus‐host disease in susceptible transfusion recipients. Eliminating the immunogenicity of blood products may prove to be of clinical benefit, particularly in patients requiring multiple transfusions in whom allosensitization is common. This study examines a method of pathogen reduction based on ultraviolet light illumination in the presence of riboflavin. In addition to pathogens, WBCs treated with this system are affected and fail to stimulate proliferation of allogeneic peripheral blood mononuclear cells (PBMNCs) in vitro. STUDY DESIGN AND METHODS: This study sought to determine the mechanisms regulating this loss of immunogenicity. Treated cells were examined for surface expression of a number of molecules involved in activation and adhesion, viability, cell‐cell conjugation, and ability to stimulate immune responses in allogeneic PBMNCs. RESULTS: Compared with untreated controls, ultraviolet (UV)‐irradiated antigen‐presenting cells showed slightly reduced surface expression of HLA Class II and costimulatory molecules and had more significant reductions in surface expression of a number of adhesion molecules. Furthermore, treated cells had a severe defect in cell‐cell conjugation. The observed loss of immunogenicity was nearly complete, with UV‐irradiated cells stimulating barely measurable interferon‐γ production and no detectable STAT‐3, STAT‐5, or CD3‐ε phosphorylation in allospecific primed T cells. CONCLUSION: These results suggest that defective cell‐cell adhesion prevents UV‐irradiated cells from inducing T‐cell activation.     

Enhanced uptake of taurine by basolateral plasma membrane vesicles isolated from developing rat liver

Inasmuch as taurine biosynthesis is decreased during early postnatal life, an efficient mechanism for taurine uptake by the liver must be present to maintain intracellular stores of this beta-amino acid. Therefore, basolateral liver plasma vesicles prepared from 14-day and adult rats were used to examine taurine transport during development. For both age groups, the presence of an inwardly directed Na+ gradient stimulated the initial rate of taurine uptake and caused a transient accumulation of taurine above equilibrium. For all time points before equilibrium, taurine uptake was significantly greater with membrane vesicles from 14-day compared to adult rat livers. In contrast, no age-related differences in Na+-independent uptake as measured with a K+ gradient were detected. With equal intravesicular and extravesicular Na+ concentrations, taurine uptake remained significantly greater in the younger age group. For both age groups, Na+-dependent taurine uptake was saturable but the apparent Km and Vmax for Na+-dependent taurine uptake were significantly greater in membrane vesicles from 14-day compared to adult rats. These findings suggest that an increased number of functional carriers for taurine are present in developing compared to adult basolateral plasma membrane perhaps reflecting the needs of the immature liver for this essential nutrient.     

Modified radical hysterectomy in the treatment of early squamous cervical cancer

OBJECTIVE: The aim of this study was to evaluate the results of modified radical hysterectomy in the treatment of early cervical cancer. MATERIAL AND METHODS: A retrospective chart review of 56 patients with stage I (IA in 35, IB in 21) squamous cervical carcinoma treated with modified radical hysterectomy and followed for a minimum of 5 years (mean, 12 years; range, 5.1-29) was conducted. All pathology slides were reviewed for tumor size, grade, depth of invasion, and lymph-vascular permeation. RESULTS: The mean depth of invasion was 0.5 cm (range, 0.1-2.5 cm), and the mean tumor size was 1.1 cm (range, 0.1-7 cm). Only 3 patients (5.4%) had positive nodes. None of the patients with tumors 2 cm or less in size had positive nodes, whereas 33.3% of the patients with tumors more than 2 cm in size had positive nodes. A recurrence developed in 2 patients (5-year recurrence rate of 3.6%). There were 10 deaths during the entire follow-up period, but only 2 were related to cervical cancer. The disease-specific and overall 5-year survival rates were 96.4 and 94.6%, respectively. The disease-specific 5-year survival rate was 100% among the 47 patients with tumors 2 cm or less and 75% for the 9 patients with tumors larger than 2 cm. Univariate analysis identified stage, lymph node status, and tumor size as statistically significant prognostic factors for overall survival. Tumor grade, lymph-vascular permeation, and depth of invasion (1-3 mm vs >3 mm) were not statistically significant for overall survival. CONCLUSIONS: Modified radical hysterectomy appears to be effective surgical therapy for patients with squamous cervical carcinoma 2 cm or less in size.