Urography in preoperative evaluation of abdominal aortic aneurysms

Ultrasound is a commonly used and accurate method to diagnose abdominal aortic aneurysms. A case of abdominal aortic aneurysm, diagnosed by ultrasound, which at surgery was found to have an overlying horseshoe kidney with multiple renal vessels is reported. The clot surrounding the aneurysm most likely prevented demonstration of the isthmus of the horseshoe kidney by echography. Since preservation of renal blood supply is crucial, urography should routinely be performed prior to surgery to discover such anomalies.     

Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis

PRO70769 is a humanized IgG1 monoclonal antibody against the CD20 molecule that is present on normal and malignant B cells. PRO70769 is being evaluated for treatment of B-cell-mediated diseases and is in a phase 1 trial for rheumatoid arthritis. As part of the preclinical toxicology evaluation, B-cell depletion profiles and safety of PRO70769 were assessed in cynomolgus monkeys. Animals were administered drug (IV) on days 1 and 15 with 10, 50, or 100 mg/kg PRO70769 and killed 2 weeks after the second dose and after a 3-month recovery period. In a parallel study, animals were not necropsied but instead were retreated with a second cycle of PRO70769 administered under an identical regimen. PRO70769 suppressed B cells in the blood to undetectable levels and significantly reduced B cells in lymphoid tissues. Splenic B cells were depleted to a greater extent compared with lymph node B cells. A second cycle of treatment resulted in a greater extent of depletion in lymphoid tissues compared with the depletion observed after one cycle of treatment; however, residual B cells in lymphoid tissues were still detectable, even at the highest dose. The rate of B-cell recovery in peripheral blood appeared similar between one and two cycles of treatment. Upon depletion there was a change in the profile of lymph node B-cell subsets. After recovery, B-cell subsets were reconstituted to normal levels. Depletion of CD20-expressing cells and lymphoid follicular atrophy were the only treatment-related effects.     

Preliminary evaluation of sodium hypochlorite for pulpotomies in primary molars

PURPOSE: The purpose of this study was to compare the effectiveness of 5% sodium hypochlorite (NaOCl) to that of ferric sulfate (FeSO4) as a pulpotomy medicament in decayed primary molars. METHODS: Healthy subjects between 4 and 9 years with at least 2 primary molars needing pulpotomy consented to receive either NaOCl or FeSO4 and restoration with IRM base/stainless steel crown in a prospective, randomized design. Clinical and radiographic signs/symptoms were recorded at 0, 6, and 12 months. RESULTS: Twenty-three subjects were recruited. Six-month results are based on the first 32 teeth in the NaOCl group and 28 teeth in the FeSO4 group. Twelve-month results are based on 13 teeth in the FeSO4 group and 14 in the NaOCl group. Results show 100% restoration retention in both groups and no signs/symptoms of pain at 6 and 12 months. At 6 months, 100% clinical success was found with both FeSO4 and NaOCl. Radiographic success for FeSO4 was 68%, with internal resorption being the most common finding. The NaOCl group showed 91% radiographic success, P = .050. At 12 months, FeSO4 had 85% clinical success and 62% radiographic success. NaOCl had 100% clinical success and 79% radiographic success. CONCLUSION: Preliminary evidence shows that NaOCl can be used successfully as a pulpotomy medicament.     

Evaluation of novel injectable hydrogels for nucleus pulposus replacement

Branched copolymers composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) are being investigated as an in situ forming replacement for the nucleus pulposus of the intervertebral disc. A family of copolymers was synthesized by varying the molecular weight of the PEG blocks and molar ratio of NIPAAm monomer units to PEG branches. Gel swelling, dissolution, and compressive mechanical properties were characterized over 90 days and stress relaxation behavior over 30 days immersion in vitro. It was found that the NIPAAm to PEG molar ratio did not affect the equilibrium swelling and compressive mechanical properties. However, gel elasticity exhibited a dependency on both the PEG block molecular weight and content. The equilibrium gel water content increased and compressive modulus decreased with increasing PEG block size. While all of the branched copolymers showed significant increases in stress relaxation time constant compared to the homopolymer (p < 0.05), the high PEG content PNIPAAm-PEG (4600 and 8000 g/mol) exhibited the maximum elasticity. Because of its high water content, requisite stiffness and high elastic response, PNIPAAm-PEG (4600 g/mol) will be further evaluated as a candidate material for nucleus pulposus replacement.     

The effect of dehydration history on PVA/PVP hydrogels for nucleus pulposus replacement

The feasibility of the use of a copolymer gel prepared from blends of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) for endoscopic replacement of the nucleus pulposus of a lumbar intervertebral disc was examined in this study. Hydrogels were processed with the use of three freeze/thaw cycles to induce crystallinity. As-prepared samples were dehydrated to various levels: 70.4, 46.3, 25.1, and 10.3% of their as-prepared masses and subsequently rehydrated. The dehydration history controlled the dimensions upon swelling and caused distortion of the material, with major distortion occurring when the hydrogel reached around 25% of the initial hydrated mass. The dehydration history affected the mechanical behavior of the rehydrated gels. Increased dehydration resulted in increased compressive modulus for the reswollen gels. Experiments were performed to investigate the formation of a skin layer that was found on the hydrogels during the dehydration process. The skin was found to dehydrate quickly and form a barrier to further dehydration from the core. Rubber elasticity theory was used to describe the differences in the network characteristics between the skin and the core of a drying hydrogel. The dehydration/rehydration process used in this study and an implantation of a cadaver model demonstrate the feasibility of endoscopic nucleus replacement.     

Therapeutic anti-VEGF antibodies

Vascular endothelial growth factor (VEGF-A) is a key cytokine in the development of normal blood vessels as well as the development of vessels in tumors and other tissues undergoing abnormal angiogenesis. Here, we review the molecular engineering of two humanized antibodies derived from a common mouse anti-VEGF antibody--bevacizumab, a full-length IgG1 approved for the treatment of specified cancer indications, and ranibizumab, an affinity-matured antibody Fab domain approved for use in age-related macular degeneration (AMD). In clinical trials and as FDA-approved therapeutics, these two anti-VEGF antibodies, bevacizumab (Avastin anti-VEGF antibody) and ranibizumab (Lucentis anti-VEGF antibody), have demonstrated therapeutic utility in blocking VEGF-induced angiogenesis.     

Uptake and release of budesonide from mucoadhesive, pH-sensitive copolymers and their application to nasal delivery.

Microparticles of novel, bioadhesive graft copolymers of polymethacrylic acid and polyethylene glycol (P(MAA-g-EG)) were prepared. The aims of this study were to investigate the uptake and release kinetics of budesonide from P(MAA-g-EG) in vitro as well as the pharmacokinetics following nasal administration of the polymer contained budesonide. The loading of budesonide into the pH-sensitive polymers was examined using various ethanol solutions. Ethanol was required for drug solubilization but hindered hydrogel swelling at pH 7.2. Maximum loading of the drug in the polymer was obtained using 25% ethanol solutions. The release of budesonide from the polymer swollen in 25% ethanol solutions obeyed classical Fickian release behavior after an initial rapid drug burst. For nasal administration of budesonide-containing P(MAA-g-EG) the plasma concentration of budesonide was kept constant following a peak concentration of the drug approximately 45 min after administration.     

Hydrogels for the repair of articular cartilage defects

The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair.