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Biomedical subjects

G A Ksander

Publications and source records attributed to G A Ksander.

At least 37 records · Page 2Linked to original sources

Capsule contracture in animals can be characterized by gross deformation of prostheses and surrounding tissue.

Gel-filled miniprostheses were implanted in rats, recovered, and reimplanted in fresh animals. Experimental contracture characterized by severe, visually detectable distortion of hemispherical prosthesis mounds into pointed ovoid structures oriented laterally was observed. This finding confirms the existence in rats of a phenomenon similar in appearance to clinical contracture in humans. The incidence of contracture was higher than in the first implantation of these prostheses, which suggests that some property of the prosthesis is critical in the occurrence of contracture, and that this property can be altered by prolonged implantation in the tissue so that contracture is more likely. Implants that were overfilled by injection of extra fluid into the gel showed no contracture, but capsules around these implants did not differ from contracted capsules in protein, collagen, glycosaminoglycan composition, weight, thickness, histological appearance, or incidence of myofibroblasts.

Animals↗

An in-depth look at pressure sores using monolithic silicon pressure sensors.

Three-dimensional scalar pressure distributions were measured in solid tissue near bony prominences in vitro in meat and in vivo in pigs using silicon pressure sensors. Data are in accord with previous theoretical models and indicate that pressure is three to five times higher internally near a bony prominence than it is at the skin over the prominence. Pressure sores are thus thought to begin internally; by the time they are evident at the skin, the sore has worked its way completely from bone to skin. This conclusion is in accord with previous clinical data. Future measurement of local vector forces is needed to fully characterize the force distribution in vivo.

Animals↗

Effect of implant location on compressibility and capsule formation around miniprostheses in rats, and experimental capsule contracture.

Our study of experimental contracture in rats confirms the existence in laboratory animals of a phenomenon very much like human capsule contracture. The ultrastructural features of capsules in rats are essentially identical to those for humans and rabbits. Macrophages with silicon-containing material were present. Star-shaped myofibroblasts with extended processes appeared in contracted and noncontracted capsules. The myofibroblasts contained bundles of 60 to 80 A microfilaments with included dense bodies, convoluted nuclei, and extensive peripheral vesiculation. The myofibroblasts tended to be associated with more extensive ground substance and smaller diameter extracellular fibrils than were normal synthetic fibroblasts. The incidence of contracture was similar for implants beneath different amounts of overlying soft tissue dorsally and sternally, while compressibility and subjective softness were greater for implants beneath lesser amounts of overlying tissue. A greater mass of capsule formed beneath the heavier covering, however, suggesting that in clinical experience, cosmetically more acceptable results from submuscular prosthesis placement are probably due to a padding effect. Capsule glycosaminoglycans were primarily hyaluronic acid and dermatan sulfate. The occurrence of myofibroblasts in these capsules at a relatively late period (26 weeks) implicates myofibroblasts in the contracture mechanism, but details are still unknown. Contracture is a property of the capsule tissue; preliminary observations suggest that its occurrence is independent of species, anatomical site, surgical procedure, presence of extruded gel, presence of myofibroblasts, capsule thickness, or protein, collagen, or glycosaminoglycan composition. Cells within the capsule were geometrically asymmetrical, being extremely flattened in the plane parallel to the prosthesis surface.

Animals↗

Proteolytic activity of blowfly larvae secretions in experimental burns.

Secretions of larvae of the blowfly Calliphora erythrocephala digested experimental rat skin burn eschar in vivo and in vitro when applied topically in a vanishing cream base. Debridement was characterized by de-epithelialization and digestion of dermal collagen to a subfollicular level over a 3-day period. Analytic investigation of the secretions demonstrated the presence of enzymes with activities characteristic of trypsin, leucine aminopeptidase, and carboxypeptidases A and B. These were partially characterized. There was no evidence of chymotrypsin, elastase, or collagenase. Preparation of a suitable therapeutic form could result in a preparation useful for enzymatic debridement.

Animals↗

Effects of diffused soluble steroid on capsules around experimental breast prostheses in rats.

Saline-filled miniprostheses were implanted beneath the dorsal panniculus carnosus of rats. The control prostheses contained only saline, while the experimental prostheses contained soluble methylprednisolone sodium succinate. At 10-day intervals the in situ compressibility of the tissue mound around the implants was measured mechanically. At 60 and 120 days, the control mounds were harder than those around the steroid prostheses, and the control prostheses were surrounded by a thicker capsular membrane. The control capsules contained more non-collagenous protein than the steroid modified capsules. We suggest that this non-collagenous protein may be related to the proteopolysaccharide cement which binds the fibers of immature scar together--and that the effect of our steroid treatment was to reduce this proteopolysaccharide component of the capsule membrane and thereby cause its dissolution.

Amino Acids↗

A microarchitectural model of regional variations in hypodermal mobility in porcine and human skin.

In this paper, we focus on the hypodermal component of the integument and its functional contribution to properties of skin mobility. A specially designed mechanical apparatus was used to measure hypodermal extensibility in vivo of 6-mm "island" punches at selected anatomical sites in anesthetized pigs. Representative regional hypodermal force displacement curves were found to differ statistically in magnitude of acceleration, slope, and extensions at breaking point. A vertically oriented "lattice network" of hypodermal fibrous elements arranged in geometric subunits is consistently seen in sample specimens. Microarchitectural differences in network configuration, geometric unit size, fat infiltration, and intrinsic collagen fiber length can be correlated directly to the biomechanical data. These findings are corroborated by light microscopy, scanning electron microscopy, and quantitative hydroxyproline concentrations. A similar network is confirmed in human cadaver biopsies. Clinically, our data suggest that skin mobility is at least partially allowed by unfolding and stretching of the hypodermal vertical collagen network, and that regional variations in fibrous network architecture satisfy specific functional requisites (e.g., joint mobility, skin stabilization), as well as serving as an expansile retractile reservoir for the deposition and absorption of fat.

Adipose Tissue↗

Study of encapsulation of silicone rubber implants in animals. A foreign-body reaction.

It has long been known that the formation of a fibrous capsule around an implant is a general phenomenon in nature, an inevitable result of the tissue defense mechanism called the foreign body reaction. We have investigated this reaction in animals and find it consists of a series of interrelated processes in which the final result may vary, depending on the susceptibility of the foreign material to phagocytosis, incorporation by giant cells, or isolation by fibrosis. This susceptibility depends, in turn, on the physical and chemical properties of the implant. The process of capsule formation, as well as the structure of the final capsule, is similar in animal models and in humans--so that investigations of human encapsulation may be done in animals. The cause of abnormal induration around human breast implants is still unknown, and the question of whether normal induration in the animal model can be used to elucidate abnormal clinical induration depends on further investigation of both phenomena.

Animals↗

Effects of local instillation of triamcinolone on the capsules around silicone bag-gel prostheses in animals.

"Soft" silicone bag-gel miniprostheses were implanted in 103 rats. The experimental animals had periprosthetic instillations of zero, 0.2, or 2 mg of triamcinolone acetonide at implantation. The compressibility, the architecture, and the chemical composition of the surrounding tissues were observed at 10 and at 120 days. The compressibility was also measured by mechanical means at 10 day intervals. At 120 days all capsules were similar. All the capsules gradually became firmer with time after the implantation. After 60 days, the steroid-treated capsules were very slightly more compressible (softer) than the controls. This slight difference in compressibility could not be correlated with the other changes in the capsule properties we examined. It is suggested that the structure of these capsules may be similar to that of immature scar, and that it is kept in this condition by the continued stimulus of the foreign implant.

Animals↗

Experimental effects on surrounding fibrous capsule formation from placing steroid in a silicone bag-gel prosthesis before implantation.

Soft-gel miniprostheses of silicone were implanted subcutaneously into 75 male rats. Groups of prostheses were preinjected with saline, a commercial form of triamcinolone acetonide, or a suspension of crystalline triamcinolone acetonide. The softness of the prosthesis mound later was measured objectively, and the capsules surrounding the implants were analyzed by histology, SEM, and chemistry, at various intervals up to 120 days after implantation. The control implants developed a normal laminar capsule. With an incidence increasing up to 100 percent at 120 days, the steroid-treated implants were surrounded by capsules lacking an inner membrane. The inner membrane of the laminar capsule had a high protein content (relative to normal tissue) and a relatively reduced collagen content, while the diffuse capsule resulting from the TA treatment had a high protein content and a high collagen content (about the same as normal tissue). No differences were found in the softness of the mounds of the implanted prostheses. The effect of the TA treatment was explained on the basis of its collagenolytic effect, which could gradually erode the normal capsule membrane. Capsule firmness could not be related to the architecture or the protein or collagen content in our findings. We hypothesize that normal capsule firmness may be related to the amount and kind of interconnection between the loose outer zone of connective tissue and the surrounding tissue.

Animals↗

The panniculus carnosus in the domestic pig.

The panniculus carnosus arises from the superficial fascia of the midlateral back, inserts into the medial skin of the forelimb, and fuses ventrally with the contralateral cutaneous muscle. In the midback, forelimb, thigh, and groin the panniculus carnosus is lacking; there, superficial fascia alone is present. Both the panniculus carnosus and the superficial fascia divide the panniculus adiposus into a superficial compact layer and a less compact deep layer. The firm attachment of the dermis to the panniculus carnosus, and of the panniculus carnosus to the deep fascia, makes pigskin a more suitable model for comparison with human integument than the usual laboratory animals with loosely draped skin. When using the pigskin model, however, care must be exercised to define the level of incisions and the location of flaps or grafts, with respect to the panniculus carnosus.

Animals↗

Excisional wound biomechanics, skin tension lines, and elastic contraction.

Confusion surrounding the concept of Langer's lines can be reduced by careful distinction among the operational definitions of the phenomenon, the empirical descriptions, and the theoretical explanations. An experimental analysis of the mechanical parameters of excisional wounds in pigskin shows that the marginal retraction, the elastic modulus at the wound midline, and the closing tension are higher for wounds oriented at right angles to tension lines--but the elastic modulus of the terminal segment of the force displacement curve is independent of orientation. The regional distribution of these values shows two patterns. The modulus parameters and the closing tension share a common distribution related to the steepness of regional force-displacement curves, while retraction has a qualitatively different distribution. On the basis of similarities in the behavior of retracting wound margins and in the distortion of punch holes which define tension lines, we hypothesize that the same mechanism may be responsible in both cases.

Animals↗

Skin tension lines in the domestic pig.

The skin tension lines of the domestic pig have been mapped. With a 6mm punch biopsy, local relative skin forces can be determined. The influence of various factors (such as age, fat deposition, gascial attachments, and previous scarring) on the direction of the skin tension lines is discussed.

Animals↗

Evaluation of a prototype therapeutic system for prolonged, continuous topical delivery of homosulfanilamide in the management of Pseudomonas burn wound sepsis.

The ability of homosulfanilimide (HS) delivered from two different dressing vehicles to limit bacterial proliferation was evaluated in burned animals deliberately infected with virulent Pseudomonas organisms. Treatment consisted of once daily topical application of one of two vehicles: (1) an experimental prototype system that utilized micronized HS in a hydrophobic, bioerodible, polymeric matrix, impregnated on a fabric backing; or (2) a commercially available dressing that contained the same mass of drug in a hydrophilic cream base impregnated on the same backing. Wounds on control animals were covered with fabric backing with or without the bioerodible matrix. The experimental system was designed to maintain a finite local concentration of HS on the burn wound for at least 24 hours. It is known that the cream base presents a rapidly decreasing concentration of drug to the burn surface. HS delivered from the experimental system produced a significant reduction in deaths compared with the HS delivered from the cream base. In addition, the new method of delivering HS provided better control of local and systemic infection, and better wound hydration and also promoted earlier eschar separation. The experimental system was at least as convenient to apply as the cream and had an advantage with respect to inspection of the wound, since it could be removed and reapplied easily.

Administration, Topical↗

Safety and effect of transforming growth factor-beta(2) for treatment of venous stasis ulcers.

Transforming growth factor-beta(2) promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor-beta(2) purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open-label trial comparing transforming growth factor-beta(2) purified from bovine bone (0.5 microg/cm(2)) with a placebo consisting of lyophilized collagen vehicle-without active drug. After no safety issues arose in that trial, a prospectively randomized, closed-label, observer-blinded, three-armed trial was conducted to compare bovine transforming growth factor-beta(2) (2.5 microg/cm(2)) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety-related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor-beta(2). In both studies, treatment with bovine transforming growth factor-beta(2) appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open-label study, the mean rate of closure of ulcers treated with bovine transforming growth factor-beta(2) was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor-beta(2) in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 microg/cm(2), bovine transforming growth factor-beta(2) is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor-beta(2) in accelerating closure of chronic dermal ulcers.

Journal Article↗