Clinical protocol: phase I study of an adenovirus/prostate-specific antigen vaccine in men with metastatic prostate cancer.
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This study investigates a gelfoam disc device as an alternative topical ophthalmic drug delivery system for pupillary dilation in humans. Gelfoam (Pharmacia & Upjohn) discs were impregnated with 0.60 mg of tropicamide racemate and 1.7 mg of 1-phenylephrine hydrochloride by an ethanol solvent evaporation method. Twenty randomly selected human subjects received baseline examinations, including blood pressure, pulse rate and biomicroscopy of the ocular surface. One impregnated gelfoam disc was placed in the inferior fornix of a randomly selected eye. Simultaneously, the fellow eye was treated with two topically administered drops, one from a phenylephrine hydrochloride 2.5% solution and one from a tropicamide 1% solution. A single, masked observer measured the pupillary diameter in both eyes at various time intervals under constant ambient conditions. Administration of the topical drops was repeated in the fellow eye. At maximum pupillary dilation, the disc was removed, and a post-dilation biomicroscopic exam was performed. Blood pressure and pulse rate were rechecked. The gelfoam-treated eyes' median change in dilation diameter was approximately 25% greater (a two-fold increase in pupillary area) (p< 0.001) at 15.2 min (median time to maximum dilation) than the topically treated fellow eyes. The median change in systolic blood pressure (+1.0 mmHg) and diastolic blood pressure (-1.0 mmHg) was not statistically significant (p>0.1). The average pulse rate was decreased 7 beats per minute (p=0.004). A gelfoam disc may serve as an ophthalmic drug delivery system for pupillary dilation or as a model for other multiple-dose topical drugs.
A body of evidence has surfaced documenting the ability of endothelial cells cultured on monolayers to phagocytose but not kill bacteria. Several years ago, a new three-dimensional endothelial cell culturing model was developed, which simulated the morphology of the endothelium in small vessels and capillaries. Given that endothelial cells may be derived from the same pluripotent stem cells as macrophages, the question of whether endothelial cells might phagocytose and kill bacteria was explored. Endothelial cells grown on Gelfoam blocks exhibited bactericidal activity towards Staphylococcus aureus, reaching maximal killing of > 90% after 2 h. Evidence documents the involvement of bacterial adherence to the plasma membrane of the endothelial cell. This is followed by phagocytosis of S. aureus, leading to intracellular killing. Penicillin G, included in the endothelial cell growth medium, was found to be a critical factor in the bactericidal activity demonstrated by Gelfoam blocks laden with endothelial cells.
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Conventional methods of endothelial cell culture on monolayers and beads require enzymatic digestion, traumatic scraping, or centrifugation to transfer cells to other experimental systems. Gelfoam, a porous gelatin block, not only supports the growth of bovine pulmonary artery endothelial cells but also allows the rapid transfer of cell-laden blocks from one experimental system to another with minimal intervention. This property has been shown to be especially useful for the rapid fixation of endothelial cells for microscopy using standard histologic methods. Histology confirmed that the trabecular nature of the substrate allows endothelial cells to line the interstices of the sponge matrix and grow in a configuration that simulates the appearance of the endothelium in small vessels and capillaries. The inoculation of 1 x 10(5) endothelial cells on 7.5 mg Gelfoam (24 x 8 x 2 mm blocks) was enhanced by fibroblast growth factor and resulted in cell attachment by day 2 with a cell doubling time of 1.7 days. In addition, endothelial cells completely infiltrated 1, 5 and 7.5 mg Gelfoam blocks, as verified by histology. Assays to quantify cell number and protein were easily performed. To facilitate cell counting, the Gelfoam matrix was rapidly removed by the addition of 0.05 mg/ml collagenase, a concentration that interfered minimally with the assay for cellular protein concentration. The data demonstrate that Gelfoam is a suitable support growth matrix for the in vitro culture of bovine pulmonary artery endothelial cells.
Recently the calvarium has become a popular site for harvesting bone grafts because of its low incidence of morbidity, its proximity to the operative site, and the decreased amount of resorption as a result of its membranous nature. However, information regarding the phenomenon of repair at the donor site itself remains lacking. This investigation was initiated in 40 adult white New Zealand rabbits as an experimental model to study the process of repair at the donor site and to examine the possible use of hydroxyapatite to reconstruct the residual donor site deformity. Our experimental protocol closely followed our clinical procedure for the harvesting of split calvarial bone grafts. Our conclusions in the rabbit model were: (1) each of the commonly used hemostatic agents (bone wax and gelfoam) inhibit osteoneogenesis to varying degrees, (2) hydroxyapatite shows promise in the reconstruction of the donor site defect, and (3) if the periosteum comes in direct contact the defect repairs itself.
Previous work has shown improved wound healing after the administration of systemic vitamin A in patients on chronic steroids. In contrast there have been mixed reports on the effect of topical vitamin A on wound healing in steroid-treated patients. Previous laboratory work has suggested that the topical application of vitamin A may be beneficial to wound healing in a sutured wound in a steroid-treated rat. Due to some inconsistencies in previous studies and steroid animal models, we sought to develop a better wound-healing model in a steroid-treated rat and to assess the effect of topical vitamin A as part of the wound closure. With preliminary studies, we developed a consistent and reliable wound-healing model in a steroid-treated rat using dexamethasone in contrast to cortisone acetate, which had been used in previous studies. Next, rats were randomized into 8 groups, some of which received steroids. Wounds were treated with saline or vitamin A topically or via a soaked gelfoam sponge. Rats were wounded 1 week after the commencement of steroid administration. Wounds were repaired and allowed to heal for 2 weeks. Strips of the wounds were then harvested and tested for tensile strength and breaking strength using a tensiometer. Wound edges were then fixed and wound surface area was measured using digital planimetry. Steroid treatment resulted in consistent weight loss and failure to gain weight as well as decreased breaking strength. Tensile strength was not decreased. Vitamin A applied for 10 minutes before wound closure and a gelfoam sponge alone placed before wound closure both resulted in an increased breaking strength and tensile strength.(ABSTRACT TRUNCATED AT 250 WORDS)
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Demineralized bone matrix (DBM) has been successfully used as a substitute for bone grafting. Autogenous bone grafts may cause site morbidity and undergo significant resorption. DBM may overcome these problems, but it has no mechanical stability until bone formation has occurred. We tested various alloplastic implants (i.e., Surgicel, polydioxanone [PDS], porous polyethylene [Medpor], and Gelfoam) in combination with DBM and compared it with DBM alone in a 9 x 9 mm rat cranial defect model. Histological and biomechanical measurements were performed at postoperative month 2. Among the study groups, Gelfoam/DBM inhibited bone formation to varying degrees and was the only group that displayed an inflammatory response. Mechanical pushout tests using a servohydraulic testing frame were conducted. The Medpor/DBM implant displayed the strongest support at 2 months; maximum load was 95% of intact skull. Surgicel/DBM and DBM alone were comparable; maximum load was 66% of intact skull. Gelfoam/DBM and PDS/DBM displayed the weakest support (48% of intact skull). We conclude that, after 2 months of implantation, alloplastic/DBM composites provide osseous structural integration. Gelfoam/DBM is not an effective delivery system for DBM in our model.
Demineralized bone allografts in the repair of calvarial defects are compared with other common bone fillers. This study uses a video-digitizing radiographic analysis of calvarial defect ossification to determine calcification of bone defects and its relation to postoperative clinical examination and regional controls. The postoperative clinical results at 3 months demonstrated that bony healing was greatest in bur holes filled with demineralized bone and hydroxyapatite. Radiographic analysis demonstrated calcification of demineralized bone-filled defects compared to bone wax- and Gelfoam-filled regions. Hydroxyapatite granules are radiographically dense, thus not allowing accurate measurement of true bone healing. The results suggest that demineralized bone and hydroxyapatite provide better structural support via bone healing to defined calvarial defects than do Gelfoam and bone wax.
For bone defect reconstruction, locally administered cytokine plasmid was examined. Leukemia inhibitory factor (LIF) can bind to the osteoblast cell surface and induce bone formation both in vitro and in vivo. The authors investigated the local mouse LIF complementary deoxyribonucleic acid (cDNA) plasmid in the pcDNA 3 expression vector, which is promoted by cytomegalovirus and is stabilized by bovine growth hormone polyadenylation, with a gelatin sponge carrier. A total of 150 male Wistar rats were used. They were divided into three groups. Group 1 (N = 30) was treated with the gelatin carrier of the pcDNA 3 vector, group 2 (N = 90) was treated with three different doses of LIF cDNA (0.1, 1, and 10 micrograms) in the pcDNA 3-vector plasmid along with the gelatin carrier, and group 3 (N = 30) was treated with recombinant human bone morphogenetic protein -2. Ten animals in each group were euthanized at 1, 3, and 5 weeks postoperatively. Animals treated with LIF cDNA showed significantly enhanced bone mineral density (p < 0.05), as confirmed by dual-energy X-ray absorptiometry (DEXA), in 3 weeks compared with the control vehicle. By 3 weeks, the number of fibroblast-like cells and collagen fibers decreased, whereas the osteoblast-like cells increased inversely, as revealed during histological examination. LIF messenger ribonucleic acid demonstrated by in situ hybridization was observed most markedly in osteocytes of the LIF cDNA-treated group. Also, LIF peptide was detected in the same cell type by immunohistochemistry. Locally administered LIF cDNA plasmid in a gelatin carrier can increase bone density significantly, with subsequent bone formation, probably via osteocyte activation.
Complications associated with temporomandibular joint (TMJ) replacement surgery may include injury to nerves, blood vessels, and otologic structures. Vascular injuries can be associated with trauma to the carotid artery and its terminal branches, the superficial temporal artery, and the internal maxillary artery. Suggested management to control hemorrhage has included uniand bipolar electrocautery, laser ablation, local anesthetics with vasoconstrictors, direct pressure, embolization, and ligation. In this case report, the iatrogenic injury to both the middle meningeal and superficial temporal arteries during total TMJ replacement surgery controlled by using a gelatin-based hemostatic agent is discussed.
Radionuclide blood flow studies were employed to evaluate the success or failure of preoperative Gelfoam embolization in two patients with intracranial meningiomas. In both cases, the initial radionuclide blood flow study showed tumor visualization during the arterial phase. Immediately following the embolization procedure, the radionuclide blood flow study showed no visualization of the meningioma during the arterial phase, indicating a successful embolization procedure in preparation for removal of the tumor in a relatively bloodless field.
Superselective transcatheter arterial radioembolization with radioiodinated lipiodol and gelatin sponges was evaluated in 11 patients with nodular hepatocellular carcinoma. Thirteen tumor nodules were treated using 3-5 ml of lipiodol labeled with 259 to 2220 MBq of I-131 followed by gelatin sponge with the following results: 1) there was elevated uptake in 12 tumor nodules with high tumor-to-background ratios: 2) there was excellent clinical tolerance to the treatment (stable cirrhosis in 5 patients and cirrhosis progression in 2 cases); 3) there was good disease control with size reduction in five tumor lesions (41%) and no increase in seven lesions (59%) followed for 2 years; 4) there was a 2-year survival rate of 70%; and 5) three deaths due to hepatic failure at 2, 3, and 20 months after therapy. Superselective arterial radioembolization with I-131 lipiodol is a useful palliative approach to inoperable hepatocarcinoma, providing long-term local control without severe complications in the progression of cirrhosis.
Artificial splenic trauma was created and treated with embolic material injected selectively into the splenic artery in 10 dogs. The bleeding was controlled by the original or a repeat embolization within the first 3 hours in all dogs. Seven dogs survived for 2 months. On angiograms performed prior to sacrifice, the arteries supplying the infarcted section of the spleen were again patent. Although both the arterial branches and the amount of splenic parenchyma in the area of infarction were smaller, the area of artificial trauma could not otherwise be identified. The histologic examination of the area of injury indicated healing of the injury and resolution of the infarct. The results of the study would indicate that selective embolization is a feasible method of controlling bleeding from splenic injury. Although embolism would not replace splenectomy as the generally used method, it could be used in patients who were not otherwise candidates for operative splenectomy.
Transcatheter embolization of the distal gastrosplenic artery as well as the distal right renal artery or one of its bifurcational branches was performed in 9 domestic swine. The animals were embolized with fresh autologous clot, oxycel or gelfoam in groups of 3. The embolic material was opacified with tantalum in several animals. At 4 months, none of the initial occlusions was sustained and recanalization without residuals was found in the left gastroepipolic artery with only one minor exception. Organized thrombi as sole vascular residuals regardless of embolic substance were found in both the terminal splenic artery as well as in the right renal artery distribution in various degrees together with infarcts in both organs. No trace of either oxycel or gelfoam remained, nor tissue reaction against either material. All 3 agents are therefore regarded equivalent in their long term effects and are not suitable for permanent vascular occlusion.
The feasibility of control of traumatic hepatic hemorrhage by angiographic transcatheter embolization was investigated. Bleeding sites were created in the livers of each of twelve dogs, and the hepatic artery was occluded with Gelfoam. Successful control of bleeding was demonstrated by postembolization angiography in all twelve animals. Initial elevations in alkaline phosphatase and serum glutamic pyruvic transaminase values returned to their baseline in four weeks. Recanalization of the hepatic artery in the five surviving animals was shown by follow-up angiograms. Transcatheter embolic control of traumatic hepatic hemorrhage may be a useful adjunct to surgical therapy.
An episode of disseminated intravascular coagulation following therapeutic gelfoam embolization to control bleeding from esophageal varices in a patient with liver disease is presented. We have since followed 13 patients prospectively (six control and seven gelfoam/autologous clot) to determine the effect of this procedure on clotting. We were unable to show significant differences between the two groups as measured by the prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and platelet count. However, fibrin (ogen) degradation products were significantly elevated (p less than .01) in the gelfoam/autologous clot group. We suspect this occurred secondary to clot lysis at the site of embolization. No subsequent bleeding diathesis attributable to this abnormality occurred in any of the patients.