Patient outcomes following wrist ganglion excision surgery.

We present patient outcomes following surgical excision of primary wrist ganglia over a 5 year period. Patients (48 of 59; 81%) responded to a questionnaire by post or telephone, with a mean time to follow-up of 44 (range 21-77) months. There was a statistically significant reduction in all reported symptoms, including pain, paraesthesia, weakness, stiffness, and cosmesis. The recurrence rate was 8%. In total, 98% of patients were satisfied or very satisfied with treatment. Surgical excision of primary wrist ganglia may have advantages over aspiration and reassurance alone, particularly in reducing recurrence and hastening resolution of symptoms.

Decellularized human valve allografts.

BACKGROUND: Variable performance of allograft tissues in children and some adults may be linked to an immune response and could be mitigated by reducing implant antigenicity. METHODS: As endothelial and fibroblast cells are the likely source of valve antigenicity, human (CryoValve SG) and sheep pulmonary valves were decellularized using the SynerGraft treatment process. Treated valves were evaluated in vitro using histochemical, biomechanical, and hydrodynamic methods, and compared with standard cryopreserved valves. Four SynerGraft-treated and two cryopreserved sheep pulmonary valves were implanted as root replacements in the right ventricular outflow tract of growing sheep and monitored echocardiographically and histologically at 3 and 6 months. CryoValve SG human pulmonary valves were implanted in 36 patients. RESULTS: SynerGraft treatment reduced tissue antigen expression but did not alter human valve biomechanics or strength. Decellularized sheep allograft valves were functional during the implantation period, and, they became progressively recellularized with recipient cells. In humans, CryoValve SG pulmonary valves did not provoke a panel reactive antibody response. CONCLUSIONS: SynerGraft decellularization leaves the physical properties of valves unaltered and substantially diminishes antigen content. Reduction in implant cellularity enables host recellularization of the matrix, which should favorably impact long-term graft durability.

Failure strengths of suture vs. biodegradable arrow and staple for meniscal repair: an in vitro study.

A study was performed to determine the in vitro biomechanical behaviour of two 'all inside' meniscal repair techniques (Meniscal Arrow [Bionx Implants Inc.] and Meniscal Staple [Surgical Dynamics Inc.]) and compare these directly with both a horizontal and vertical suture repair. Using 30 fresh bovine medial menisci, vertical 'bucket handle' tears were created 4 mm from the meniscus periphery. Repairs were subsequently performed, using four techniques, with 15 repairs in each group, a horizontally placed 3-metric Ethibond suture, a vertically placed 3-metric Ethibond suture, a single 13-mm arrow and a single 7-mm staple. A tensile test was performed to determine the force at failure for each technique. The mean force at failure of the horizontal and vertical suture groups was 63.2 and 73.9 N, respectively, 44.3 N for the arrow group and 17.8 N for the staple group. The mean forces at failure were significantly different (P < 0.005). The mean tensile strength of the meniscal staple was significantly lower than that of both suture and arrow groups. The 7-mm staple design may not allow adequate interdigitation between the barbed legs and the semicircular collagen fibres of the meniscus.

Recellularization of heart valve grafts by a process of adaptive remodeling.

The objective of this study was to investigate if function and durability of connective tissue grafts stems from in vivo revascularization and recellularization. Viability is important for durable valve performance, demonstrated by pulmonary autografts. A pattern of in vivo recellularization occurs in xenogeneic or allogeneic heart valves decellularized prior to implantation, dictated by the tissue matrix and functional biomechanics. Porcine or sheep heart valves were decellularized with the SynerGraft antigen reduction process (a common treatment process to remove all histologically demonstrable leaflet cells), and implanted as pulmonary (n = 11) or aortic valve (n = 9) replacements in sheep. Sheep allograft pulmonary valves (n = 4) were implanted as pulmonary valve replacements. Recellularization was evaluated histologically after 3, 4, 5, 6, and 11 months, with cell phenotypes identified using specific antibodies. SynerGraft heart valves were progressively recellularized beginning with an initial cellular infiltrate, and subsequent repopulation with mature interstitial cells. This process occurs in the conduit and then in the leaflet, and is associated with revascularization of the graft. Functional, fully developed fibrocytes, actively synthesizing type I procollagen (antibody probe) were present within 3 months. As the process matured cell density and distribution became similar to native valve leaflets with localization of smooth muscle actin positive cells at the ventricularis/spongiosa interface. After 11 months, leaflet explants had no detectable inflammatory cells, were as much as 80% repopulated, and had a distribution of smooth muscle actin positive cells similar to that of the natural leaflet. SynerGraft- treated heart valve implants are repopulated by a process typical of adaptive remodeling following implantation. This antigen reduction treatment is the first successful tissue engineering effort obtaining an implant with mature recipient cells capable of matrix protein synthesis. Normal early valve function and durability is maintained.

Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis (OB), chronic allograft rejection of the lung, is a major cause of morbidity and mortality after lung transplantation. Previous studies using the heterotopic mouse trachea model of chronic airway rejection have shown a T cell infiltrate composed of CD4+ and CD8+ T cells. The goal of these experiments was to characterize the pattern of T lymphocyte cytokines during chronic airway rejection using the heterotopic mouse trachea model. METHODS: Isografts (BALB/c into BALB/c) and allografts (BALB/c into C57BL/6) were implanted into cyclosporin-treated animals and harvested 2, 4, 6, and 10 weeks posttransplant. Cytokine mRNA expression in these grafts was determined using reverse transcription polymerase chain reactions. Expression of Th1 cytokines, interleukin- (IL) 2 and gamma-interferon, and Th2 cytokines, IL-4, and IL-10 were analyzed, as well as the cytotoxic lymphocyte product granzyme B and expressed relative to beta-actin gene expression. RESULTS: In allografts, expression of IL-2 (P=0.002), gamma-interferon (P=2x10(-6)), granzyme B (P=0.003), IL-4 (P=0.06), and IL-10 (P=8x10(-6)) were 2- to 10-fold higher compared to isografts throughout the time-course of graft injury. Th1 and cytotoxic lymphocyte gene expression were increased to a greater extent than Th2 cytokines in allografts compared with isografts, and both Th1 and Th2 cytokine gene expression persisted at 6-10 weeks. CONCLUSIONS: These data suggest that Th1, Th2, and cytotoxic lymphocyte subtypes all contribute to the development of obliterative bronchiolitis in the heterotopic mouse trachea model. Efforts to reduce the development of obliterative bronchiolitis may require the antagonism of multiple T cell pathways.

Transpecies heart valve transplant: advanced studies of a bioengineered xeno-autograft.

BACKGROUND: Tissue engineering approaches utilizing biomechanically suitable cell-conductive matrixes should extend xenograft heart valve performance, durability, and growth potential to an extent presently attained only by the pulmonary autograft. To test this hypothesis, we developed an acellular, unfixed porcine aortic valve-based construct. The performance of this valve has been evaluated in vitro under simulated aortic conditions, as a pulmonary valve replacement in sheep, and in aortic and pulmonary valve replacement in humans. METHODS: SynerGraft porcine heart valves (CryoLife Inc, Kennesaw, GA) were constructed from porcine noncoronary aortic valve cusp units consisting of aorta, noncoronary aortic leaflet, and attached anterior mitral leaflet (AML). After treatment to remove all histologically demonstrable leaflet cells and substantially reduce porcine cell-related immunoreactivity, three valve cusps were matched and sewn to form a symmetrical root utilizing the AML remnants as the inflow conduit. SynerGraft valves were evaluated by in vitro hydrodynamics, and by in vivo implants in the right ventricular outflow tract of weanling sheep for up to 336 days. Cryopreserved allograft valves served as control valves in both in vitro and in vivo evaluations. Valves were also implanted as aortic valve replacements in humans. RESULTS: In vitro pulsatile flow testing of the SynerGraft porcine valves demonstrated excellent valve function with large effective orifice areas and low gradients equivalent to a normal human aortic valve. Implants in sheep right ventricular outflow tracts showed stable leaflets with up to 80% of matrix recellularization with host fibroblasts and/or myofibroblasts, and with no leaflet calcification over 150 days, and minimal deposition at 336 days. Echocardiography studies showed normal hemodynamic performance during the implantation period. The human implants have proven functional for over 9 months. CONCLUSIONS: A unique heart valve construct has been engineered to achieve the equivalent of an autograft. Short-term durability of these novel implants demonstrates for the first time the possibility of an engineered autograft.

Rolipram, a specific type IV phosphodiesterase inhibitor, is a potent inhibitor of HIV-1 replication.

OBJECTIVE: To determine the effects of rolipram, a specific type IV phosphodiesterase inhibitor, on tumor necrosis factor (TNF)-alpha production and HIV-1 replication. DESIGN: TNF-alpha enhances HIV-1 replication in vitro; blocking TNF-alpha and thereby inhibiting HIV-1 replication may therefore potentially delay progression of HIV disease. Pentoxifylline is a non-specific phosphodiesterase inhibitor that blocks TNF-alpha synthesis and HIV-1 replication in vitro and has been shown in preliminary clinical studies to decrease viral replication in HIV-1-infected patients. Rolipram, which selectively inhibits the predominant phosphodiesterase isoenzyme of monocytes, inhibits lipopolysaccharide (LPS)-induced TNF-alpha with 500-fold greater potency than pentoxifylline. We, therefore, hypothesized that rolipram would be a powerful inhibitor of HIV-1 replication. METHODS: The effects of rolipram and pentoxifylline on TNF-alpha production and HIV-1 replication were determined in infected and uninfected peripheral blood mononuclear cells (PBMC), in a chronically infected promonocytic cell line (U1) and in an acutely infected monocytic cell line (BT4A3.5). TNF-alpha was determined by specific radioimmunoassay and HIV-1 replication was measured by p24 antigen and HIV-1 mRNA production. RESULTS: Rolipram inhibited TNF-alpha production in LPS- and phorbol myristate acetate (PMA)-stimulated PBMC and in PMA-stimulated U1 cells. Rolipram also inhibited HIV-1 replication in the U1 cell line, as well as in acutely infected PBMC and BT4A3.5 cells. Depending on the experimental conditions, rolipram was 10-600 times more potent, on a molar basis, than pentoxifylline. CONCLUSION: Rolipram is a potent inhibitor HIV-1 replication and therefore deserves further investigation as a potential therapeutic agent in the treatment of HIV-1-infected patients.

Effects of hydrogen peroxide oxidation and calcium channel blockers on the equatorial potassium current of the frog lens.

Hydrogen peroxide, in concentrations of 10-1000 microM, produces two major changes in the current-voltage relationships associated with the equatorial potassium current of the lens. First, the resting and reversal potentials become more negative than they were prior to treatment with hydrogen peroxide and second, the membrane resistance related to the equatorial current is decreased. The shift in the resting and reversal potentials is in the opposite direction from that produced by ouabain. Based on the Nernst equation, the shift in the reversal potential suggests that there is an increase in the concentration of potassium in the lens. The 86Rb uptake and efflux are increased. These observations suggest that hydrogen peroxide stimulates the Na,K-pump. The decrease in membrane resistance is inhibited by 100 microM of quinine, a calcium-dependent potassium channel blocker, and does not decrease in a calcium-free medium. This suggests that the decrease in resistance may be secondary to an increase in lenticular calcium. These effects of hydrogen peroxide are similar to those of p-chloromercuriphenylsulfonate (pCMPS), a nearly impermeant sulfhydryl binding agent, and suggest that permeant hydrogen peroxide may increase calcium influx by acting on sulfhydryl groups on the outer surface of lens membranes. Verapamil, a calcium channel blocker, is reported to prevent cataract formation. D600, the methoxy analogue of verapamil, is a calcium channel blocker that increases the resistance associated with the equatorial current in the presence and absence of hydrogen peroxide. The gadolinium ion has a similar effect. Thus, D600 and Gd3+ partially counteract the reduction in membrane resistance produced by 50 microM hydrogen peroxide.

Topical norepinephrine, isoproterenol, terbutaline, forskolin and 8-bromo cyclic AMP increase lens equatorial current.

The equatorial current of the frog lens was studied with microelectrodes and a vibrating probe. Norepinephrine, isoproterenol and terbutaline applied topically at the surface of the cornea as a 1% solution increased the equatorial current of the lens about 80%. This increase was blocked by timolol. Topical forskolin increased the equatorial current by over 80%. This effect of forskolin was not blocked by timolol. These substances did not affect the equatorial current of the lens when the lens was suspended in a frog Ringers solution. 8-Bromo cyclic AMP increased the equatorial current when it was applied topically but not when it was added directly to the medium bathing an isolated lens. The results suggest that beta-adrenergic agonists, applied topically to the cornea, increase the equatorial current of the lens by a mechanism that is mediated by cyclic AMP. The finding that 8-bromo cyclic AMP did not act directly on the lens suggests that a currently unknown substance or process is active at the level of the lens.

D600 increases the resistance associated with the equatorial potassium current of the lens.

The effects of D600, the methoxy analog of verapamil, on a pCMPS system were studied. A major effect of D600 is to increase the resistance associated with the equatorial potassium current of the lens. The increase in resistance is statistically significant at concentrations above 200 microM. At concentrations of 25-50 microM, D600 counteracts the decrease in resistance produced by binding sulfhydryl groups with 1 microM pCMPS. This effect is similar to that produced by quinine and by a calcium-free medium, and is attributed to the prevention of an increase in the calcium-dependent conductance produced by pCMPS.

Link between the ciliary process and lens equatorial current.

Circadian and seasonal rhythmic changes in the intraocular pressure are modulated by the nervous system and expressed in the eye by the release of norepinephrine at adrenergic nerve endings. This study links seasonal changes and the effects of the topical application of norepinephrine with changes in the equatorial current of the lens in frogs. A vibrating probe and microelectrodes were used to study the segment of the K+ electrical loop extending between the internal microelectrode, used for measuring potential difference (PD), and the external vibrating electrode, measuring the equatorial current (J). Changes were noted in the electrophysiological parameters of 270 normal frog lenses (Rana pipiens) at different times of the year. Threefold seasonal variations were observed in the amplitude of equatorial current (J) and the resistance associated with the equatorial current (RJ). J was greatest in the winter and RJ was greatest in late spring. Norepinephrine applied directly to the lens did not affect the equatorial current. Norepinephrine applied topically, increased the equatorial current of the lens. It is concluded that the magnitude of the equatorial current of the lens is mediated in part by the ciliary process epithelium.