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Biomedical subjects

J T Jacob

Publications and source records attributed to J T Jacob.

15 recordsLinked to original sources

Slow release of the antimetabolite 5-fluorouracil (5-FU) from modified Baerveldt glaucoma drains to prolong drain function.

Drainage devices are routinely placed in the eyes of patients with glaucoma to reduce intraocular pressure (IOP) by providing controlled outflow of fluid (aqueous humor) via a filtering bleb. However, the natural wound healing response often interferes with fluid outflow by thickening the walls of the bleb over time, so that these devices rarely remain functional for more than 5 years. We investigated the use of controlled release of an antimetabolite, 5-fluorouracil (5-FU), within glaucoma drains to determine if the wound healing response could be reduced and the useful life span of the device increased. Collagen plugs containing 1.125 mg of 5-FU were placed in the silicone tubes of modified Baerveldt glaucoma drains. Eight drains with 5-FU and eight drains without 5-FU were implanted in one eye each of 16 New Zealand white rabbits: the contralateral eyes served as unoperated controls. Results were evaluated in terms of IOP, fibrous capsule thickness, macrophage density. and presence of type III collagen surrounding the drain plate, 3 and 6 months after implantation. In general, eyes implanted with antimetabolite-containing drains demonstrated significantly lower values for all evaluated parameters at 3 months and lower or equal values at 6 months, compared with the eyes not receiving 5-FU and the unoperated controls, indicating improved IOP-lowering function, reduced bleb wall thickness, and earlier achievement of a steady-state wound healing response. All eyes remained healthy throughout the 6-month duration of the study with no cytotoxicity complications in any of the eyes. Thus, biodegradable plugs placed within the silicone tubes of glaucoma drains can safely deliver 5-FU to filtering blebs over time, which could prolong the functional life of the bleb by decreasing the thickness of the anterior fibrous capsule and permitting sufficient fluid outflow to reduce IOP to physiological levels.

Animals↗

Porous alloplastic material encasement of gold weights for the treatment of paralytic lagophthalmos.

PURPOSE: To determine if encasing gold weights in a porous alloplastic material would improve their longevity in situ. METHODS: Gold weights used for passive eyelid reanimation in patients with paralytic lagophthalmos were wrapped in either expanded polytetrafluoroethylene (E-PTFE) or porous polyurethane (PPU) to allow cellular infiltration and ingrowth and increase the blood supply to the site of the implant. A total of 14 implants, six encased in E-PTFE, six encased in PPU, and two with no casings (controls), were tested for biocompatibility and stability in rabbit eyelids for 10 months. RESULTS: Two of the PPU-encased gold weights showed some anterior extrusion, one at 3 months and one at 5 months after implantation. All of the E-PTFE-encased gold weights and both control weights were well tolerated for the entire study period. Histology of the alloplastic casings and surrounding tissues showed good tissue compatibility and cellular ingrowth for both alloplastic materials. CONCLUSIONS: Encasing the weights in a biocompatible alloplastic material, such as E-PTFE, may decrease micromovement and improve attachment to the eyelid tissue, as well as increase blood supply to the area, thereby reducing the rates of the major complications--infection and extrusion--associated with these implants.

Animals↗

Biocompatibility response to modified Baerveldt glaucoma drains.

Glaucoma implants are designed to increase fluid outflow from the eye in order to decrease intraocular pressure and prevent damage to the optic nerve. The implant consists of a silicone tube that is inserted into the anterior chamber at one end and is attached at the other end to a silicone plate that is sutured to the outside of the globe beneath the conjunctiva. The glaucoma "implant" becomes a "drain" over the first 3 to 6 postoperative weeks as the silicone plate is enclosed by a fibrous capsule that allows a space to form into which fluid can drain and from which fluid can be absorbed by the surrounding tissues. Ideally, the size and thickness of the capsule (the filtering bleb) that surrounds the plate is such that the amount of fluid that passes through the capsule is identical to the amount of fluid produced by the eye at an intraocular pressure of 8 to 14 mmHg. The most common long-term complication of these implants is failure of the filtering bleb 2 to 4 years after surgery due to the formation of a thick fibrous capsule around the device. Micromovement of the smooth drainage plate against the scleral surface may be integral to the mechanism of glaucoma implant failure by stimulating low-level activation of the wound healing response, increased collagen scar formation, and increased fibrous capsule thickness. To test this hypothesis, we modified seven Baerveldt implants by adding porous cellular ingrowth material to the posterior surface of the drainage plate. Seven modified and five unmodified implants were placed in adult rabbit eyes. After 6 months, we found that the fibrous capsule around the modified implants was significantly thinner than the capsule surrounding the unmodified implants (p < 0.05), particularly on the surface between the porous ingrowth material and the sclera (p < 0.05). Although type I collagen predominated in the fibrous capsules around both types of implants, the amount of type III collagen in the capsules around the modified implants was significantly less than the amount around the unmodified implants (p < 0.05). We believe that these data suggest a reduction in the wound healing response to the modified implants, with greater stability of capsule thickness. Long-term studies are needed to verify that the stability of the capsules around the modified implants persists over a period of years, in which case this type of modification may prove useful in prolonging the functional life of these devices in the surgical treatment of glaucoma.

Animals↗

Efficacy of a novel synthetic material to close exposed fascial defects.

BACKGROUND: After developing a synthetic composite material (TMS-1) made from a porous polypropylene mesh (placed in apposition to fascia) coated on the "visceral" side with solid polyurethane, we compared its efficacy with that of porous polytetrafluoroethylene, polypropylene, and primary fascial closure when the repairs were left exposed to the environment. METHODS: We created 1 cm2 abdominal wall defects in each of the four abdominal quadrants of rats (n = 12). We used porous polytetrafluoroethylene, polypropylene, and TMS-1 to repair three defects; the fourth we primarily closed. The skin was left open in all cases, leaving the fascial closures exposed. A second group of rats (n = 24) had the same operation, except that peritonitis was induced using a standard fecal inoculation technique. When the rats were killed 2 weeks later, a "blinded" observer using a standard scale assessed the surface area and severity of adhesions formed. RESULTS: When compared with the other synthetic materials, the surface area of adhesions formed was significantly less after primary closure in clean conditions; in contaminated conditions, it was less than porous polytetrafluoroethylene, polypropylene, and the same as TMS-1. Furthermore, in contaminated conditions, the severity of adhesions beneath TMS-1 was the same as primary closure and significantly less than those beneath the polypropylene. CONCLUSION: The overall superiority of TMS-1 over porous polytetrafluoroethylene and polypropylene in septic conditions justifies further experiments to define its long-term efficacy in the repair of large defects.

Abdomen↗

Development of a novel synthetic material to close abdominal wall defects.

To compare the efficacy of a novel synthetic material (TMS-2) with polytetrafluoroethylene, polypropylene (Marlex), and primary closure of experimentally fashioned clean and contaminated abdominal wounds, 1-cm2 abdominal wall defects were created in each of the four abdominal quadrants of rats (n = 10). Patches of each material were used to repair three of these defects, the fourth being primarily closed. A second group of rats (n = 7) underwent the same operative protocol; however, peritonitis was induced at the time of surgery using a fecal inoculation technique. Animals were killed 2 weeks later, and surface area and severity of formed adhesions were assessed by a "blinded" observer. All closure techniques were successful insofar as none demonstrated fascial dehiscence. Compared with each synthetic material, the surface area of formed adhesions was smaller after primary closure in clean and in contaminated conditions; however, the three synthetic materials were equally matched regarding surface area of adhesions under both conditions. In the face of fecal contamination, TMS-2 proved identical to primary closure, each generating significantly (P < 0.02) milder adhesions than the other prosthetic materials. It is concluded that the TMS-2 may prove of clinical benefit to repair abdominal wall defects.

Abdominal Muscles↗

Synthetic scleral reinforcement materials. III. Changes in surface and bulk physical properties.

Changes in the physical properties of polymer materials during implantation in the biological environment can directly affect the ultimate performance of the polymer and/or device. We implanted four types of extraocular bands (porous, solid, composite, and patched) made from 11 types of materials in rabbit eyes and examined the changes in the physical strength and polymer structure of the implanted bands in terms of tensile strength measurements, creep analysis, and attenuated total internal reflectance--Fourier transform infrared spectroscopy (ATR-FTIR) at intervals up to 18 months after implantation. Most of the materials showed increases in tensile strength over the first 6 months in situ in the rabbit eye, followed by significant decreases between 6 and 18 months. Polymer bands that had been implanted for 18 months generally exhibited less creep behavior than unimplanted controls; for most of the bands, creep values ranged from 0% to 10% of the original length. ATR-FTIR of the solid bands and surface coatings showed protein deposition on all of the materials examined, with silicone materials and coatings least affected. Thirty-degree ATR-FTIR scans detected significant changes in the polymer structure for two of the band types: one solid (polyether urethane) and one porous (porous polyacrylate). In general, expanded polytetrafluoroethylene was the most stable in terms of tensile strength and creep. The least stable bands (composite bands made with porous polyurethane) were those that had undergone hydrolytic and/or oxidative degradation and chain scission of the polymer or alteration of the bond between the two materials making up the composite. These changes in physical properties and polymer structure observed after 18 months of implantation support the idea that polymer implant materials should be followed closely over several years in vivo to determine their suitability prior to use in humans.

Animals↗

Synthetic scleral reinforcement materials. II. Collagen types in the fibrous capsule.

Attainment of a steady state in fibrous-capsule formation around a polymeric implant is indicative of minimization of the foreign-body response, and is characterized by thin capsule walls, few macrophages, and the replacement of type III collagen with type I collagen within the capsular matrix. We implanted four general types of extraocular band materials (porous, solid, composite, and patched) in rabbit eyes, and examined the proportions of types III and I collagen in the surrounding fibrous-capsule walls at intervals after surgery. Immunohistochemical analysis showed that 18 months after implantation of the band materials, the capsules adjacent to the porous-material surfaces had virtually no type III collagen remaining, while the solid-surface-material capsules still contained more than trace amounts (greater than 5%). In that the bands were implanted around the outside of the globe, which provides a dynamic environment in constant motion, it may be that the cellular ingrowth permitted by the porous materials increased the stability of the implants, thereby lessening the foreign body response and allowing the collagen replacement characteristic of the steady state to be completed. In contrast the solid-surface implants, which had little cellular ingrowth, may have continued to undergo sufficient micromovement within the capsule walls to sustain a low-level activation of the wound-healing response, resulting in thicker capsule walls and residual type III collagen a year and a half after implantation surgery.

Animals↗

Bioavailability and pharmacokinetics of a new, slow-release potassium chloride capsule.

The bioavailability of a new, slow-release potassium chloride product consisting of coated beads in a hard gelatin capsule was compared with the bioavailability of two marketed products, an elixir and a slow-release tablet, by determining the urinary excretion of potassium. Twelve healthy male volunteers were dosed with a total of 80 mEq of potassium, in a single dose for the capsule and tablet and in three 26.6-mEq doses at 6-hr intervals for the elixir. Mean recoveries in 24-hr urine potassium levels from all three dosage forms after subtracting normal urine potassium excretion levels were 50.8% from the capsule, 53.9% from the elixir, and 63.1% from the tablet. Maximum excretion rates were reached at 2.0 hr for the elixir, 6.8 hr for the capsule, and 4.0 hr for the tablet. Fewer side effects were reported with the capsule than with the elixir and tablet.

Adult↗

Ion-pair liquid chromatographic assay of decongestants and antihistamines.

The quantitative determinations of combinations of antihistamine and decongestant drugs including phenylephrine, dl-ephedrine, psi-ephedrine, phenylpropanolamine, pyrilamine, pheniramine, l-ephedrine, chlorpheniramine, brompheniramine, oxymetazoline, naphazoline, and antazoline contained in solid and liquid dosage forms are described. All active ingredients except the ephedrine optical isomers were separated from other ingredients with ion-paired high-pressure liquid chromatography. Manipulation of the mobile phase either by changing the hydroalcoholic ratio or by changing the alkyl chain length of the counterion (sulfonic acid) for achieving optimum separations is discussed. The method is simple, short, accurate, and precise.

Chromatography, Liquid↗

Trace determination of chlorpheniramine in plasma by GLC using a nitrogen-phosphorous (N-P) detector.

A fast, sensitive and specific method for the determination of chlorpheniramine in plasma is described. The drug was extracted with diethylether, back extracted in hydrochloric acid and reextracted in diethylether. The extract was evaporated to dryness and reconstituted in isopropyl alcohol. The isopropyl alcoholic solution was gas chromatographed without any derivatization and the detection was carried out using a nitrogen sensitive detector. The mean recovery of chlorpheniramine was found to be 96% and a drug level as low as 0.5 ng/ml can be accurately measured.

Animals↗

Comparison of novel synthetic materials with traditional methods to repair exposed abdominal wall fascial defects.

Repair of large abdominal wall defects is a challenge, particularly when full-thickness tissue loss prohibits coverage of the fascial repair. Two novel synthetic materials (TMS-1 and TMS-2) have been shown to be better accepted than expanded polytetrafluoroethylene (Gore-Tex), and polypropylene (Marlex) in the closure of clean and contaminated fascial wounds that are immediately covered by skin/soft tissue. Therefore, 1-cm2 abdominal wall defects were created in each of the four quadrants of rat groups. Gore-Tex, Marlex, and TMS-1 or TMS-2 were used to repair three defects, the fourth being primarily closed. To ensure that each repair remained exposed, skin edges were sutured to underlying muscle. Additional animal groups underwent the same protocol; however, peritonitis was induced at surgery using a fecal inoculum technique. Animals were sacrificed 2 weeks later, at which time a blinded observer assessed the surface area and severity of adhesions. In clean wounds, the surface area of formed adhesions was less (p < .004) after primary closure than each synthetic material; among the synthetics, TMS-2 caused significantly (p < .01) less extensive adhesions than Marlex. In addition, the severity of adhesions to TMS-2 was comparable to that of defects closed primarily, and less severe (p < .02) than those formed to Gore-Tex and Marlex. In animals with peritonitis, primary closure caused less extensive (p < .03) adhesions than Marlex and Gore-Tex and significantly (p < .002) less severe adhesions than Marlex, Gore-Tex, and TMS-2. However, the severity of adhesions formed to TMS-1 repairs proved comparable to primarily closed wounds. These experiments reaffirm the tenet that, whenever possible, abdominal wounds should undergo primary fascial closure. When soft tissue coverage over the repair cannot be achieved, TMS-2 is well tolerated in clean wounds. However, the superiority of TMS-1 over the other synthetic materials in contaminated wounds suggests it may also ultimately prove to be of clinical utility.

Abdominal Muscles↗