Tissue adhesiveness and host response of in situ photopolymerizable interpenetrating networks containing methylprednisolone acetate

Interpenetrating networks (IPNs) of varying formulations were investigated as candidates for an in situ photopolymerizable drug delivery matrix containing poly(ethylene glycol) diacrylate and gelatin. The anti-inflammatory agent methylprednisolone acetate was loaded into the IPN. Bond strength between the IPN and tissue (i.e., muscle, dermis, skin) was determined by a modified American Society for Testing and Materials peel test at constant peel rate. The IPNs provided adhesion values of up to 5.7N, which were three- to fivefold lower than that of the commercial tissue bioadhesive. The subcutaneous cage implant system was utilized to assess material host response and drug efficacy in vivo. IPN formulations elicited a more intense acute inflammatory response than the empty cage controls. Methylprednisolone acetate loaded within the IPNs lowered the level of inflammatory response to levels that were comparable to the empty cage baseline controls. In conclusion, a methodology was developed to quantify the tissue adhesiveness of an in situ photopolymerized IPN matrix containing anti-inflammatory agents. The efficacy of drug-loaded IPN in affecting the host inflammatory response was demonstrated in vivo.     

Ionic currents in the uterine smooth muscle.

1. Short segments of isolated longitudinal myometrium from the pregnant rate uterus have been studied in a double sucrose-gap voltage-clamp arrangement. The clamped segment averaged 65 mum times 240 mum times 100 mum, has an average total capacitance of 0-14 muF, and may contain 50-200 individual myometrial cells. 2. A significant resistance exists in series with the membrane, and limits theprecision of the quantitative information. However, it is argued that some qualitative and some comparative information is useful. 3. In Krebs-bicarbonate solution, depolarizing steps produced initial transient inward currents followed by delayed outward currents. 4. When [Na+]o was reduced by 50%, the equilibrium potential Ea shifted by an average of -17-6 mV, the maximum inward current was reduced to 0-5, the time to peak of the early current was delayed by 1-1 msec, and the maximum chord conductances for the early(Ga) and late (GK) currents remained unchanged as compared with those in normal [Na+]o. 5. When [Ca2+] was reduced to 25% of normal, Ea shifted by an average of -20-3 mV, the maximum inward current was reduced to 0-5, the time to peak was delayed 3-1 msec, and Ga was significantly reduced, while GK was unaffected. 6. The early current, and its tail when repolarization was imposed, reversed direction from inward to outward when [Na+]o was reduced from 143 mM to zero, with [Ca2+]o remaining constant at 1-9 mM. 7. From the observations in 4, 5 and 6, it was concluded that Na+ is the main charge carrier for the early current, and that Ca2+ is important in regulating Ga. 8. The late current is outwards when [K+]o equals 5-9 mM, but inwards in some voltage range when [K+]o was elevated to 120 or 148 mM. K+ is the main charge carrier for the late current. 9. The equilibrium potential for the late current, EK, is about 15 mV more negative than the natural resting potential. 10. Prolonged holding of the preparations at voltages that differ significantly from the natural resting potential tends to shift EK in a way consistent with passive changes in [K+]i by the holding current. 11. The steady-state inactivation of the early current, h, is unusual. Inward current is macimum around the resting potential, and declines with both hyperpolarizing and depolarizing changes. Half-inactivation occurred with about 9 mV depolarization and 15 mV hyperpolarization. 12. The instantaneous current-voltage relations of both early and late currents are linear. The chord conductances Ga and GKare similar in form to those in other tissues.     

Evolution of precore/core promoter mutations in hepatitis B carriers with hepatitis B e antigen seroreversion

The evolution of precore stop codon mutation (A1896) and dinucleotide mutation (T1762/A1764) in the basic core promoter (BCP) of hepatitis B virus (HBV) genome during transient seroconversion and seroreversion of hepatitis B e antigen (HBeAg) remains unclarified. Five HBeAg-positive HBV carriers who experienced transient seroconversion followed by seroreversion of HBeAg (Group I, 3.3%) and 3 HBeAg-negative HBV carriers with documented reversion of HBeAg (Group II, 2.5%) in a prospective cohort of 272 patients with chronic hepatitis B were thus identified. The sequential changes at the precore nucleotide 1896 and BCP dinucleotide 1762/1764 were determined by polymerase chain reaction and direct sequencing. At enrollement, precore A1896 and BCP T1762/A1764 were noted in 4 (50%) and 1 (13%) of the eight patients. During a median follow-up period of 58 months (range: 31-76 months), 12 episodes of transient HBeAg seroconversion followed by seroreversion were encountered in Group I patients and 3 episodes of HBeAg seroreversion in Group II patients. Accompanying acute exacerbations were found in two-thirds of patients with either HBeAg seroconversion or seroreversion. Overall, precore nucleotide A1896 remained identical in 73% and 83% of the seroconversion and seroreversion events, respectively. BCP dinucleotide T1762/A1764 remained unchanged in 94% and 92% of the seroconversion and seroreversion events, respectively. At the end of follow-up, only one had both precore and BCP mutations. In conclusion, these data suggested that HBeAg seroreversion might be due to the lack of sustained precore and BCP mutations after HBeAg seroconversion. Although uncommon, HBeAg seroreversion can be associated with hepatitis exacerbation.     

Anatomic Locking Plate for Displaced Intraarticular Calcaneal Fracture: Design and Application

Calcaneal fracture can lead to long-term disability and have a considerable economic effect. Most calcaneal fractures are intraarticular fractures involving the posterior facet of the subtalar joint. Treating displaced intraarticular calcaneal fractures is complicated because of the lack of an optimal treatment option. Internal fixation typically involves screw-and-plate implants, which can be unfavorable owing to the lack of an anatomic design and the intraoperative bending required for the plate to contour to the irregular surface of the calcaneus. We assessed the outcomes of 30 patients treated using innovative, anatomically designed calcaneal locking plates and the perceived advantages for surgeons. Postoperative computed tomography images of the affected feet were obtained, and the functional performance was recorded. The mean average Böhler angle had increased significantly from 16.8° ± 14.9° to 28.5° ± 9.4° (p < .001). The mean average maximal fracture gap and maximal step-off in the posterior facet of the subtalar joint in the coronal computed tomography images also decreased significantly from 2.8 ± 3.7 mm to 0.8 ± 1.3 mm (p < .01) and from 3.3 ± 2.8 mm to 0.8 ± 1.2 mm (p < .001), respectively. The mean average American Orthopaedic Foot and Ankle Ankle-Hindfoot scale score was 93.9 ± 7.1 at the final follow-up visit. In addition, the surgical time was reduced because bending the plate was not required and the quality of reduction could be assessed easily by examining the gap between the cortex and the plate. The results were promising, revealing that the anatomic locking plate can be used effectively in the treatment of displaced intraarticular calcaneal fractures using simple reduction techniques with a potentially shortened operating time.     

Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage

Background

Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan.