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Biomedical subjects

S Gabbay

Publications and source records attributed to S Gabbay.

At least 19 recordsLinked to original sources

Shelhigh No-React porcine pulmonic valve conduit: a new alternative to the homograft.

BACKGROUND: The Shelhigh No-React pulmonic valve conduit is a new porcine conduit that is glutaraldehyde-treated and detoxified using a proprietary heparin process. In our institution it has been implanted in 25 patients. The aim of this present contribution is to evaluate the short-term follow-up after its implantation. METHODS: From November 1997 to August 1999, 25 patients (mean age, 20.2 years; range, 0.6 to 28.3 years) were operated on using this conduit. Seventeen patients underwent a Ross procedure for aortic valve disease, with the conduits implanted in anatomic position; 6 patients underwent right ventricular outflow tract reconstruction; 2 patients underwent the Rastelli operation. The follow-up was complete. Preoperative and postoperative two-dimensional echocardiography data were collected. RESULTS: There were two non-conduit-related deaths. Two conduits needed to be exchanged because of an increase in the gradient. Overall, all patients were improved in terms of New York Heart Association class. Comparison of preoperative and postoperative two-dimensional echocardiography gradient showed significant improvement. At the 30-month follow-up, no calcification was seen on the explanted conduits or on the two-dimensional echocardiography, although many of the patients are children. CONCLUSIONS: The Shelhigh conduits seem to be an alternative to homograft especially in infants. These experiences are preliminary, and longer follow-up is required.

Adolescent↗

Mitochondria-rich cells in anuran amphibia: chloride conductance and regional distribution over the body surface.

The distribution and density (D(mrc)) of mitochondria-rich cells (MR cells) in skin epithelium, were determined over the whole body surface in nine species of anuran Amphibia that live in a variety of habitats. It was found that the more terrestrial species (beginning with Hyla arborea) have a higher density of MR cells in their pelvic region. In the skin of aquatic (Xenopus laevis) or fossorial (Pelobates syriacus) species, D(mrc) is evenly distributed over the whole body surface. In dorsal skin pieces of H. arborea that lack detectable MR cells, transepithelial voltage activation did not induce Cl(-) conductance as it did in ventral pieces. Skins from Bufo viridis and X. laevis, both have MR cells in their skin, differ markedly in their biophysical properties: a Cl(-) specific current conductance is predominant in the skin epithelium of B. viridis, and is absent in X. laevis. In the latter, anionic conductance is due to glandular secretion. The biophysical properties cannot therefore be related solely to the presence or density of MR cells. Mitochondria-rich cells are sites of Cl(-) conductance across the skin of those amphibians that show this property, but must have different function(s) in other species. It is suggested that the specific zonal distribution of MR cells in the species that were examined in this study could be due to ion exchange activity and water conservation in more terrestrial environments.

Animals↗

Chloride conductance across toad skin: effects of ionic acclimations and cyclic AMP and relationship to mitochondria-rich cell density.

The anionic conductance across toad (Bufo viridis) skin was studied using the voltage-clamp technique following long-term (more than 10 days) acclimation to NaCl and KCl solutions. The non-specific baseline conductance was approximately 0.6 mS cm(-)(2) and was similar in skins from all acclimation conditions. The voltage-activated Cl(-) conductance (G(Cl)) was maximal in skins from distilled-water- and KCl-acclimated toads (>3 mS cm(-)(2)) and was greatly reduced following acclimation to NaCl solutions. Cyclic AMP (EC(50)=13 micromol l(-)(1)) and isobutylmethyl xanthine (IBMX) (EC(50)=69 micromol l(-)(1)) exerted different effects on the activated conductance. IBMX only sensitized the activated conductance, whereas cyclic AMP (CPTcAMP) at high concentrations induced an increase in anionic conductance that was insensitive to electrical potential. Furthermore, external Cl(-) was not required for the stimulatory effect of cyclic AMP, and the conductive pathway had low selectivity. The effects of the two agonists were reversible and depended on the acclimation conditions. Following electrical measurements, the skin of the toads was removed and stained with silver to measure mitochondria-rich cell density (D(mrc)). There was no correlation between D(mrc) and Cl(-) conductance in the present study.

1-Methyl-3-isobutylxanthine↗

Lectin binding patterns in amphibian skin epithelium.

Seven lectins (PNA, DBA, WGA, UEA-I, RCA, SBA, Con A) were used to localize glycoconjugates in the skin of 10 species of Amphibia, 7 anurans (Bufo marinus, Bufo bufo, Rana ridibunda, Rana pipiens, Hyla arborea, Pelobates syriacus and Xenopus laevis) and 3 urodeles (Salamandra salamandra, Triturus vulgaris and Ambystoma mexicanum). It was found that every lectin has a specific binding pattern in the skin of each species. No common pattern could be established, either among frogs or toads, nor for a particular lectin. Each lectin bound specifically and selectively to a particular epithelial component, which differed from one species to the other. A number of lectins showed selective binding to mitochondria-rich cells, but, again, a pattern in positivity could not be found. It is concluded that lectin histochemistry does correlate with cellular function. Our data can be applied in studies of epithelium and skin development, and of changes that occur during adaptation to the environment by amphibian species.

Animals↗

Lectin binding pattern and band 3 localization in toad skin epithelium and the effect of salt acclimation.

Seven lectins were employed to localize glycoconjugates in the skin of a toad (Bufo viridis). Each of the lectins exhibited a particular, specific and selective binding pattern. Peanut lectin (PNA) and WGA bound to mitochondria-rich (MR) cells, but WGA bound also abundantly, in the dermis. Band 3-like protein, as indicated by the reaction with polyclonal anti band 3 antibody, was localized exclusively in MR cells. Ionic acclimation (200 mmol/L NaCl, or 50 mmol/L KCl) affected profoundly the binding pattern of the lectins. High NaCl acclimation resulted also in diminishing anti band 3 antibody binding, whereas in skins of KCl-acclimated toads the staining remained similar to the control. The binding of WGA but not PNA, corresponded with the same cells that stained with anti band 3 antibody. PNA in concentration of > 10 micrograms/mL reduced reversibly, both the resting and activated Cl- conductance by 25-30%. Based on differential binding of band 3, WGA and PNA, these observations provide conclusive verification of the presence of at least two populations of MR cells in the toad skin epithelium. It is suggested that the PNA positive MR cells may correspond to a beta-type MR cell. The information can be used to study molecular mechanisms that are involved in ionic acclimation.

Adaptation, Physiological↗

Calcification of bovine pericardium: glutaraldehyde versus No-React biomodification.

BACKGROUND: Calcific degeneration is the most frequent cause of clinical dysfunction of glutaraldehyde (GA)-pretreated bioprosthetic heart valves. The No-React (NR) process has been shown to be a promising anticalcification treatment. In this comparative study, our objective was to delineate the advantages of the NR treatment over GA. METHODS: Bovine pericardial strips pretreated with GA and NR were individually incubated in calcium phosphate solution for 21 days at 37 degrees C. The pretreated bovine pericardium then was implanted subcutaneously in rats and retrieved at 14, 21, and 35 days after-implantation. Mineral and morphologic analyses were performed on each specimen. RESULTS: The NR-treated pericardium revealed significantly reduced in vitro calcification compared with the GA-treated tissue (mean tissue calcium content 1.3 +/- 0.2 versus 5.9 +/- 0.7 micrograms/mg; p < 0.001). Mineral analysis showed progressive calcification of the GA-pretreated pericardium over the period of implantation (calcium content increasing from 49.6 +/- 9.6 micrograms/mg after 2 weeks to 134.3 +/- 9.1 micrograms/mg at 5 weeks after-implantation). The NR-treated implants had calcified significantly less (p < 0.05) at each corresponding interval. Moreover, morphologic examinations demonstrated a protracted inflammatory response in the form of giant cell and mononuclear cell infiltration associated with intrinsic collagen disruption in the GA-treated tissue; the NR-treated pericardium maintained morphologic integrity with a mild inflammatory response. CONCLUSIONS: The NR biochemical process appears not only to attenuate pericardial calcification, but also to abort the host's destructive inflammatory response to the xenograft.

Animals↗

No-react detoxification process: a superior anticalcification method for bioprostheses.

BACKGROUND: Glutaraldehyde pretreatment of bioprosthetic heart valves is the major pathogenic factor in their calcific degeneration. This comparative study investigates the merit of the No-React aldehyde detoxification process as an alternative modifier of xenograft tissues. METHODS: Glutaraldehyde- and No-React-pretreated porcine aortic valve cusps were implanted subcutaneously in 6-week-old rats (n = 20). At 3, 6, and 14 weeks, randomly selected animals were sacrificed and the explants underwent mineral and morphologic analyses. Glutaraldehyde- and No-React-treated bovine pericardium and porcine aortic valve cusp were incubated in fibroblast cell culture plates. Cell viability was observed under reversed microscope at 6, 24, 48, and 96 hours. Erythrosin B dye exclusion test was used to validate percent cell death. RESULTS: Pretreatment with No-React significantly inhibited calcification of aortic cusp subcutaneous implants throughout the 14-week period (mean tissue Ca2+ content = 1.3 +/- 0.7 micrograms/mg at 14 weeks.) Glutaraldehyde-treated cusps underwent protracted calcification (Ca2+ content = 190.6 +/- 89.5 micrograms/mg; p < 0.01). Morphologic findings correlated with mineral analyses. One-hundred percent of fibroblast cells survived in the presence of No-React-treated tissue, with a growth pattern indistinguishable from control cell culture (ie, in the presence of no tissue). The cells incubated with glutaraldehyde-treated tissue showed signs of nonviability by 6 hours, with 100% cell death by 48 hours. Dye exclusion tests validated these findings. CONCLUSIONS: The No-React detoxification process completely abolishes the cytotoxicity of the xenograft tissue and inhibits calcific degeneration.

Animals↗

Developmental changes in the heterocellular epidermis of Pelobates syriacus integument.

Changes in characteristic components of the skin epidermis of the large tadpole of Pelobates syriacus were studied throughout its development. The fate of two specific cells in the skin epidermis was followed, from the young tadpole to the adult was studied. It was found that flask-shaped type cells in the tadpole epidermis which are PAS-positive, stain with peanut lectin (PNA). There is no detectable band 3 in the premetamorphosed stages, and mitochondria-rich cells are very rare. This pattern of staining changes completely upon metamorphosis: the PAS-positive cells, specific to the tadpole epidermis disappear, and the mitochondria-rich (MR) cells in the adult skin epithelium react with polyclonal anti-band 3 antibody. Western blot analysis showed the presence of a band 3-like protein of about 95 kDa, only in the adult epithelial extract, corroborating the immunocytochemical observations. The finding of the presence of band 3-like protein in the MR cells of Pelobates, is similar to the observations made in the skin of other amphibian species. On the other hand, the binding of peanut lectin to MR cells is species-specific, since it does not react with the MR cells in the skin epithelium of Pelobates syriacus.

Animals↗

New outlook on pericardial substitution after open heart operations.

The difficulties of reoperation owing to adhesions are well known. Clinical attempts to solve this problem using synthetic materials or glutaraldehyde-fixed pericardial xenograft have been less than satisfactory. Although experimental animal results have been good, they have not considered the influence of cardiopulmonary bypass (CPB) on adhesion formation. This study addressed the influence of CPB on the formation of adhesions and evaluated biodegradable polyglycolic acid as a material to reduce adhesions and as a pericardial substitute. Forty-five weanling sheep received implants of pericardial xenograft and polyglycolic acid with and without CPB. The pericardial xenograft showed no adhesions when implanted without CPB, but severe adhesions formed and a thick fibrinous layer covered the heart when CPB was used, making identification of coronary arteries at reoperation very difficult. The polyglycolic acid mesh implanted without CPB was absorbed and replaced with newly formed host collagen. With CPB, the polyglycolic acid was more rapidly absorbed, and a thinner layer of host collagen formed. Therefore, future animal studies must include CPB. In agreement with reported clinical results, glutaraldehyde-fixed pericardial tissue implanted with CPB resulted in severe epicardial reaction and therefore is not an ideal pericardial substitute.

Animals↗

Controversies in management of sternal tumors.

The rarity of sternal tumors makes a good comparative study a difficult task. Controversies exist on questions of method of surgical diagnosis, the extent of the surgical procedure, and the different ways and means of reconstruction. We describe a case that was believed to be a clear case of chondrosarcoma but was actually a plasmacytoma. From the evidence of this case and a review of the literature we conclude that almost any plasmacytoma should be considered generalized multiple myeloma. Biopsy should be performed in all cases of sternal tumor before any surgical action is taken.

Bone Neoplasms↗

Mitochondria-rich cells and carbonic anhydrase content of toad skin epithelium.

The density and carbonic anhydrase (CA) content of the mitochondria-rich cells (MRCs) in the skin epithelium of the toad, Bufo viridis, were studied under conditions of acclimation to various chlorinities. Long-term (days to weeks) acclimation to chloride-free solutions induced a great increase in the MRC density and the area occupied by the apical portion of these cells on the surface of the epithelium. The CA content of the epithelium, and individual MR cells, showed a 5- to 10-fold reduction after acclimation to solutions containing high chloride levels. The MRC density and their relative apical surface area correlated with the chloride permeability of the skin in acclimated (long-term) toads. It is concluded that the MRCs are the principal site of chloride permeability across the amphibian skin, and they respond in an adaptive manner to long-term changes in environmental chloride levels.

Animals↗

Do heart valve bioprostheses degenerate for metabolic or mechanical reasons?

Although heart valve bioprostheses provide a normal quality of life, their durability is still of great concern. Their durability failure is defined as "degeneration," which is considered to be a consequence of metabolic factors. In this study, we demonstrate that mechanical and design factors can also be responsible for bioprosthesis failure. Large numbers of porcine and pericardial bioprostheses were tested in a fatigue-testing system in which the test conditions were proved to be reproducible and accurate by a laser Doppler anemometer. The results have allowed us to define causes of failure, previously insufficiently stressed, in each type of valve tested. There is a clear difference in factors influencing tissue disruption between porcine and pericardial valves. We have compared these in vitro results with in vivo clinical findings. The main inferences are as follows: (1) Bioprostheses rupture and fail in the same fashion in both in vitro and in vivo studies. (2) Mechanical and design factors are involved in tissue failure. (3) The in vitro/in vivo durability ratio is not 1:1. This ratio depends on the test conditions. (4) Pericardial valves fail because of damage during closure, whereas porcine valves are damaged during both opening and closing (mostly opening) because of design features. (5) Once one cusp fails and prolapses, the other cusps will fail in an accelerated fashion. (6) In vitro durability of 100 X 10(6) cycles can be considered excellent and is an achievable goal. (7) Variability is the key impediment to predicting the durability of bioprostheses. Valves can fail within 2 to 3 million cycles or can last more than 100 million cycles. Similarly, bioprostheses may require explantation within a few months or can last 10 to 13 years in patients. (8) Fatigue testing is an excellent and valuable tool to elucidate the mechanical factors responsible for this variability.

Bioprosthesis↗

Left ventricular relaxation in the filling and nonfilling intact canine heart.

We studied left ventricular relaxation in the filling and transiently nonfilling working hearts of seven open-chest pentobarbital-anesthetized dogs by totally occluding the mitral annulus during one systole. In the completely isovolumic nonfilling cycle, the ventricle relaxes to a lower pressure minimum (usually negative) than in the normal filling cycle. By clamping the ventricle at end systole, we determined the pressure asymptote (Poo) under dynamic conditions. With this information, we evaluated the validity of a monoexponential characterization of relaxation. P = (P0 - Poo) exp(-t/T) + Poo (T, time constant, P0, pressure at t = 0). Plots of In(P-Poo) versus t are nonlinear and concave to the origin, thereby revealing that late relaxation is more rapid than predicted by a monoexponential relation. Nevertheless, the monoexponential T remains a useful index of relaxation and correlates well with other temporal indexes (isovolumic relaxation time and relaxation half-time). When T is calculated from a filling cycle by assuming a zero pressure asymptote, i.e., the conventional way, there is no significant difference with the true value based on the nonfilling cycle.

Animals↗

The Meadox unicusp pericardial bioprosthetic heart valve: new concept.

To obtain a valve with better hemodynamic performance and longer durability than the currently available bioprostheses, a single-cusp pericardial xenograft has been developed. This valve has been tested extensively both in vitro, in a pulse duplicator and in a fatigue-testing system, and in vivo, in a series of dogs and sheep. Hemodynamic studies showed improved hemodynamic performance compared with other biological and mechanical valves. Effective orifice areas were larger and performance indexes higher, especially in the small sizes. Accelerated fatigue testing showed durability significantly superior to that of other biological devices. Animal experiments have established that the single cusp remains pliable even after more than two years of insertion. There is a low incidence of calcification and good preservation of the collagen matrix. This preliminary experience demonstrates that the unicusp pericardial xenograft has superior hemodynamics, increased resistance to fatigue-induced lesions, and a low incidence of calcification. These results might indicate an extended in vivo durability for this device.

Actuarial Analysis↗

Replacement of mitral valve chordae with autologous pericardium in dogs.

Glutaraldehyde-tanned autogenous pericardium was compared with untreated autogenous pericardium as a tissue for replacement of anterior chordae tendinae of the mitral valve. Tanned autogenous pericardial chordae have a marked fibrous reaction at their healing ends but retain central pliability. Untreated autogenous pericardial chordae become uniformly fibrosed and stiff. Both retain their length, heal well to the papillary muscle and cusp, and are considered as potentially useful chordal substitutes in the right circumstances. Some of the response of the host to implanted tanned xenograft tissue must be related to the consequences of tanning rather than a reaction to foreign tissue.

Animals↗

Haemodynamics and durability of mitral bioprostheses--an in vitro study.

The haemodynamic characteristics and durability of mitral bioprostheses were evaluated and compared in vitro in a pulse duplicator and in a fatigue test system. Porcine xenografts were shown to be the most stenotic of all bioprostheses, studied at rates simulating both rest and exercise; on the other hand the new generation of biological valves showed a clear improvement in haemodynamics compared with the standard porcine and pericardial prostheses so far used clinically. Durability tests performed at a rate of 1600 to 1800 beats per minute and with a closing pressure ranging from 80 to 100 mmHg showed that the Ionescu-Shiley and Edwards pericardial xenografts last significantly longer than the Hancock and Carpentier Edwards porcine valves and Hancock pericardial bioprosthesis. Correlation between the mode of failure of pericardial and porcine valves in vitro and in vivo clearly demonstrates that a major role in valve failure is played by mechanical stress. This can be either a consequence of the continuous trauma sustained by the tissue hitting against the bare dacron cloth of the sewing ring during the movements of the cusps. or a result of fatigue occurring and the bending points of the leaflets. The results of this study underline the importance of a continued in vitro evaluation of both haemodynamics and durability of bioprostheses, since some of the pericardial valves which had the best haemodynamic performance showed the worst resistance to fatigue-induced failure. A careful selection of the tissue, modification of the stent design and avoidance of a dacron covered frame are suggested to improve long-term durability of biological prostheses.

Bioprosthesis↗