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PubMed1997

Implants for sustained drug release over the somatosensory cortex of the newborn rat: a comparison of materials and surgical procedures.

Drugs that interfere with neural transmission are an important tool in assessing the role of specific neurotransmitters in the development of the nervous system. Systemic drug treatments often produce neurodevelopmental effects with questionable specificity. Furthermore, many compounds of interest do not cross the blood-brain barrier. To overcome these limitations, either elvax or gelfoam implants have been previously employed to produce sustained drug release over specific brain regions. In this paper, stereotaxic coordinates are provided for reproducible insertion of drug-delivery systems over the rat somatosensory cortex at birth (P0), prior to the appearance of the cortical barrel pattern; a novel and simpler method for preparation of elvax 40p sheets is described; a new implantation technique is provided. Furthermore, we compare the efficiency and tolerability of elvax vs gelfoam implants, showing that gelfoam, but not elvax, significantly disrupts cortical cytoarchitecture. Finally, successful destruction of serotonin-containing terminals in layer IV of the primary somatosensory cortex of the newborn rat is demonstrated by application of parachloroamphetamine-containing elvax implants.

Acetylcholinesterase↗
PubMed1997

Are free radicals responsible for endothelial cell killing of Staphylococcus aureus?

We have recently demonstrated that endothelial cells cultured on Gelfoam blocks, but not monolayer matrices can phagocytose and kill Staphylococcus aureus. Experiments determined that penicillin G, included in the endothelial cell growth medium, induces these cells to exhibit the observed bactericidal activity. In this communication, we report on studies aimed at elucidating the mechanism by which penicillin G-induced endothelial cells, cultured on Gelfoam blocks, kill S. aureus. Despite the fact that there is a substantial literature that demonstrates neutrophilic killing of bacteria can be mediated through free radical-dependent and free radical-independent mechanisms, considerably less is known about pathways by which endothelial cells can catalyze similar microbicidal activities. Studies described herein point to the fact that superoxide and products derived from this free radical were not responsible for endothelial killing of S. aureus. Likewise, a possible role for nitric oxide in bacterial killing was explored. As part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into endothelial cells cultured on Gelfoam blocks in the absence of penicillin G. Even though these cells secreted nitric oxide at a rate of 0.5 microM/h per 1 x 10(6) cells, similar to what has been reported for murine macrophages induced with gamma-interferon, in our model, nitric oxide was not found to kill S. aureus. Data presented demonstrate that the microbicidal activity of endothelial cells is mediated through free radical-independent pathways.

Animals↗
PubMed1996

Repair of chronic tympanic membrane perforations with fibroblast growth factor.

A number of angiogenic growth factors have been shown to accelerate wound healing. Previous work has demonstrated that topical application of epidermal growth factor is effective in healing chronic tympanic membrane perforations in an animal model. Theoretically, fibroblast growth factor may result in a superior healed membrane through preferential stimulation of the fibroblasts within the middle layer of the tympanic membrane. To test this hypothesis, the effects of exogenously applied fibroblast growth factor on the chronically perforated tympanic membrane were evaluated. A buffered solution of fibroblast growth factor (25 microliters of fibroblast growth factor, 0.2 mg/ml) was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in chinchillas. Control ears were treated with Gelfoam and the buffer solution only. Complete closure of the tympanic membrane perforation was observed in 81% (13 of 16) of the fibroblast growth factor-treated ears, but in only 41% (7 of 17) of the controls (p = 0.05). Heading took place gradually, requiring an average of 4 weeks for the fibroblast growth factor-treated and 6.5 weeks for the control ears that healed. The relatively high healing rate for the control group does not imply that the pretreatment perforations were not chronic, rather there appears to be some efficacy to the control protocol of repeated applications of Gelfoam and buffer. A histologic analysis of the fibroblast growth factor-healed eardrums immediately after closure demonstrated hypertrophy of the squamous and fibrous layers of the tympanic membrane. Over time, the eardrum thinned to reach proportions similar to those of the normal tympanic membrane, including the presence of a substantial middle fibrous layer. A screening ototoxicity study revealed no structural damage to the organ of Corti after growth factor treatment. To assess the potential for systemic toxicity, blood and peripheral tissues were analyzed for radioactivity at time points during a 48-hour period after application of 25 microliters of 125I-fibroblast growth factor to the perforated tympanic membrane. More than 78% of the radioactivity remained at the application site. Given the tiny original dosage, the small fraction absorbed systemically is minuscule and highly unlikely to induce adverse effects in light of published toxicity data. On the basis of these promising safety and efficacy data in the chinchilla model, clinical trials of fibroblast growth factor in repair of chronic tympanic membrane perforations in human beings are being initiated.

Administration, Topical↗
PubMed1996

In vitro assessment of neurotrophic activity from the striatum of aging rats.

Neurotrophic factors are produced in the striatum following trauma and have a demonstrable effect on in vitro bioassays and on in vivo graft survival. We have previously measured the in vitro effect of these factors following trauma to the striatum of young rats. However, the effect of age on this neurotrophic response has not been evaluated. In this study we report on the in vitro effects of extracts (obtained from gelfoam) removed from striatal cavities 7 days following trauma. Gelfoam extract from aged rats (18-24 months) had a reduced neurite-promoting response in dorsal root ganglia (DRG) and SH-SY5Y (a dopamine-producing neuroblastoma cell line) assays, compared to gelfoam from young rats (2-3 months). In contrast, extracts from both young and old rats showed significant neuroprotection of SH-SY5Y cells from the dopaminergic neurotoxins N-methy-4phenylpyridinium ion (MPP +) and 6-hydroxydopamine (6-OHDA). The results suggest that the striatum of aged individuals may have (1) a diminished capacity of neurite promotion and/ or (2) that neurite outgrowth and neuroprotection may be influenced by different factors or different levels of the same factors. The direct implication is that aged animals would be the most appropriate models to study experimental therapies for Parkinson's disease.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Effects of columella removal on inner ear morphology in the chick.

We are currently removing the single middle ear bone (columella) in the domestic chick to introduce chemical agents directly into the inner ear. Since we are interested in the effect of these agents on neural structures within the avian basilar papilla (BP), we are concerned about any subtle changes that might result from the surgical procedure of columella removal alone. The purpose of this study was to use light and transmission electron microscopy to analyze morphological changes in the inner ear after columella removal. Fifteen-day-old chicks underwent a unilateral, bilateral or a sham removal of the columella. After columella removal, the oval window was either plugged with Gelfoam or Kimwipe (standard accepted procedure to prevent possible perilymph leak) or left uncovered. After a 5-day survival period, morphological changes were observed in the tegmentum vasculosum (TV) of all ears receiving a columella removal as compared to unoperated ears. Further, ears with Gelfoam plugging the oval window also had damage to the hair cells and support cells of the basilar papilla. In contrast, there were no observable differences in either auditory afferent or efferent nerve terminals on hair cells in the BP from any ears that had the columella removed compared to those from unoperated ears. These results suggest that columella removal alone may produce morphological changes to the TV within 5 days of surgery but not to structures within the BP. On the other hand, columella removal with a Gelfoam plug results in damage not only to the TV but also to cells within the basilar papilla during this same survival time. Despite damage to other structures within the inner ear, cochlear efferent and afferent terminals on surviving hair cells were unaffected by columella removal with or without plugging.

Animals↗
PubMed2004

Subcranial transnasal repair of cerebrospinal fluid rhinorrhea with free autologous grafts by the combined overlay and underlay techniques.

OBJECTIVE: To determine the efficacy of subcranial transnasal repair of cerebrospinal fluid rhinorrhea with free autologous grafts by the combined overlay and underlay techniques using the surgical microscope and/or endoscope. PATIENTS AND METHODS: Twenty patients with CSF rhinorrhea were included in this retrospective study. They were 13 males and 7 females. Their age ranged from 7 to 62 years (mean: 39.35). The etiologies of the leak were iatrogenic in 10 cases, spontaneous in 5 cases, traumatic in 4 cases and one case was associated with meningeo-encephalocele. Preoperative nasal endoscopic examination, computed tomography (CT) with intrathecal non-ionic contrast and magnetic resonance imaging (MRI) were done when indicated. Endoscopic and/or microscopic repair of the CSF fistula was done by a combination of both underlay and overlay repair with free autologous grafts as follows: Gelfoam with fibrin glue, strips of fat, facia lata, Gelfoam with fibrin glue (underlay), septal cartilage, Gelfoam with fibrin glue and strips of fat (overlay). RESULTS: Complete closure of the leak was achieved in all patients. In one case of spontaneous CSF leak which was operated endoscopically, the leak recurred 6 months postoperatively and ceased spontaneously after a month with conservative medical treatment. No major complications were seen and no patients developed meningitis or postoperative anosmia. CONCLUSION: Subcranial transnasal repair with free autologous grafts by the combined overlay and underlay techniques using the endoscope or surgical microscope is a safe and successful method of treating CSF leaks, provided that the CSF leak is precisely located and the site can be reached with the endoscope or surgical microscope.

Adolescent↗
PubMed2001

Cochlear gene delivery through an intact round window membrane in mouse.

Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.

Adenoviridae↗
PubMed1990

Effects of sodium hyaluronate on peridural fibrosis after lumbar laminotomy and discectomy.

Sodium hyaluronate, 1.9% solution, was evaluated for its ability to retard peridural fibrosis after unilateral lumbar hemilaminotomy, anular fenestration, and nuclectomy in dogs. Three materials: fat grafts, gelfoam, and sodium hyaluronate, were compared with empty controls for their ability to inhibit peridural fibrosis. Each dog served as his own internal control and the formation of fibrosis was evaluated at 2, 4, 12, and 26 weeks. Sodium hyaluronate was found to inhibit fibrosis more than the other materials on both a macroscopic and microscopic level. The area of fibrosis and tenacity of the adhesions on dissection were notably less in the sodium hyaluronate group. Microscopically, the thickness of collagen and number of fibroblasts were decreased with the use of 1.9% sodium hyaluronate. The peridural fibrosis occurred equally both anteriorly and posteriorly to the nerve roots and correlated with the area of surgical dissection. Fat grafts were not effective in preventing fibrosis anteriorly, especially in the region of the exiting nerve roots. Gelfoam did not inhibit but actually appeared to increase fibrosis formation. Interposition materials currently used in humans to prevent scar formation such as gelfoam and fat grafts have only addressed the posterior scar formation, which do little to alter the fibrosis anteriorly. The adhesions between the nerve root and the anulus fibrosus bind the nerve root down anteriorly, making it more vulnerable to recurrent disc herniation. Sodium hyaluronate, 1.9% solution, with its viscous semifluid properties, coats the nerve roots and dura anteriorly and posteriorly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed2001

A multicenter, prospective, randomized trial evaluating a new hemostatic agent for spinal surgery.

STUDY DESIGN: A prospective, randomized trial comparing Proceed, a gelatin-based hemostatic sealant (treatment), with Gelfoam-thrombin (control) in stopping intraoperative bleeding during spinal surgery. OBJECTIVES: To determine the effectiveness and safety of Proceed. SUMMARY OF BACKGROUND DATA: Proceed has been tested in animal models to determine its safety and effectiveness as a hemostatic agent. The current study was conducted under a Food and Drug Administration-approved Investigational Device Exemption to evaluate the effectiveness and safety of Proceed in humans. METHODS: For this study, 127 patients undergoing spinal surgery were randomized into either the treatment or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after the hemostatic agent was applied. The application was considered successful if the bleeding stopped within 10 minutes. Follow-up evaluation was performed at 12 to 36 hours, then at 6 to 8 weeks after surgery. RESULTS: Proceed stopped bleeding in 98% of the patients (first bleeding site only) within 10 minutes, as compared with 90% of the control patients (P = 0.001). At 3 minutes, successful hemostasis had been achieved in 97% of the Proceed group, as compared with 71% of the control group (P = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: A significantly larger number of bleeding sites had achieved hemostasis with Proceed than with Gelfoam-thrombin at 1, 2, and 3 minutes after application. Proceed was as safe as Gelfoam-thrombin when used for hemostasis during spinal surgery procedures.

Administration, Topical↗
PubMed2006

How to make the blockage between the nasal cavity and intracranial space using a four-layer sealing technique.

BACKGROUND: Craniofacial surgery for facial advancement or correction of severe craniofacial malformations such as orbital hypertelorism, Crouzon's disease, and Apert's syndrome may carry great risk. Postoperative infection after craniofacial surgery is a life-threatening complication. Ascending infection via nasofrontal communication in frontofacial monobloc advancement, intracranial Le Fort III osteotomy, correction of hypertelorism (intracranial approach), and acute trauma of cribriform plate can lead to life-threatening meningitis and meningoencephalitis. METHODS: A four-layer sealing technique for the closure of nasofrontal communication using Gelfoam, galeopericranial flap, rib bone graft, and Tissel is a very effective method. Until the rib bone graft is taken up, Gelfoam is used to temporarily block bony defects and prevents displacement of the rib bone graft. The authors used galeoperiosteal flap for the sufficient blood supply to the rib bone graft. Tissel is used as a biologic adhesive and for blockage of the surrounding gaps. RESULTS: There were no cases of cerebrospinal fluid rhinorrhea, epidural abscesses due to nasofrontal ascending infection, or meningitis, and no cases underwent débridement due to necrosis of the frontal bone flap. This indicated that the blockage of nasofrontal communication was successful in this series. Moreover, postoperative cosmetic outcomes were satisfactory. CONCLUSION: This study indicated that the blockage using the Gelfoam, galeopericranial flap, rib bone graft, and Tissel application was effective for the thorough management of nasofrontal fistula and the prevention of recurrent episodes.

Adolescent↗
PubMed2005

Endovascular management of pseudoaneurysms of the splenic artery: experience with six patients.

The purpose of this paper was to describe our experience with the endovascular management of splenic artery pseudoaneurysms (SAPA). Seven patients with documented SAPA on CT and/or angiography were considered for endovascular treatment. The pseudoaneurysms were located in the main splenic artery (n = 4) or its branches (n = 3). In one patient in whom the pseudoaneurysm was located in a hilar branch, selective catheterization of splenic artery failed. Metallic coils (n = 1), gelfoam and hydrogel particles (n = 1), metallic coils and gelfoam (n = 2), metallic coil, gelfoam and acrylic glue (n = 2) were used as embolization material in the remaining six patients. These patients were followed for a mean period of 11.3 months. Transcatheter embolization was successful in five patients with no procedure-related complications. In one patient, embolization was incomplete and the patient underwent surgery, but died on the 10th postoperative day because of irreversible shock. Another patient, after successful embolization, underwent surgery for management of an associated pseudocyst. Endovascular treatment is a safe and effective method of management of SAPA.

Adult↗
PubMed2005

Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis.

Interleukin-8 (IL-8) is an angiogenic factor that promotes growth of pancreatic tumors. The purpose of this study was to determine if c-Src, a protein tyrosine kinase frequently overexpressed in pancreatic cancer, regulated IL-8 expression and to elucidate the Src-mediated signaling pathways that contribute to angiogenesis in pancreatic adenocarcinoma cells. In a panel of pancreatic cancer cell lines, expression of total and activated Src correlated with IL-8 production. Furthermore, ectopic expression of activated Src in PANC-1 cells with low endogenous Src activity significantly increased IL-8 production (P < 0.005). In contrast, pharmacologic inhibition of endogenous c-Src kinase activity or small interfering RNA-mediated "knockdown" of c-Src expression in L3.6pl cells with high Src expression and activity caused significant decreases in IL-8 production (P < 0.005). Inhibition of c-Src activity resulted in decreased phosphorylation of Akt, p38, and extracellular signal-regulated kinase (Erk)-1/2. Significant (P < 0.005) dose-dependent decreases were observed in IL-8 expression by inhibiting Src-dependent signaling molecules Erk-1/2 and p38 but not phosphatidylinositol 3-kinase. To assess the relevance of Src inhibition to angiogenesis, in vivo gelfoam assays were done. Robust infiltration of vessels was observed in gelfoam saturated with conditioned medium from pancreatic carcinoma cells. This angiogenesis was nearly abrogated in gelfoams saturated with conditioned medium from cells treated with the Src family kinase inhibitor, PP2 (P < 0.001). Thus, c-Src regulates critical "downstream" signaling pathways that contribute to expression of IL-8 in human pancreatic tumor cells, suggesting c-Src may be a target for therapeutic intervention in pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1980

Preoperative embolization of renal tumors--comparison of different methods.

Different techniques and materials for preoperative embolization of renal carcinoma have been assessed in 26 cases. The different methods used and compared were gelfoam fragments (10 cases), cyanoacrylate (4 cases), Gianturco stainless steel coil (3 cases) and the combination of gelfoam and the Gianturco device (9 cases). The method of choice appears to be the combination of gelfoam and the Gianturco device which allows excellent peripheral ischemia with complete occlusion of the main arterial trunks. Embolization is particularly useful in invading and hypervascularized renal tumors supplied by collateral blood vessels.

Bucrylate↗
PubMed2001

Pre-clinical subdural tissue reaction and absorption study of absorbable hemostatic devices.

SURGIFOAM (Absorbable Gelatin Sponge, USP), a new absorbable hemostatic sponge, GELFOAM (Absorbable Gelatin Sponge, USP) or Avitene (microfibrillar collagen hemostat) were evaluated in a three-month tissue reaction and absorption study in rabbits. Bilateral craniotomy was followed by subdural implantation of each hemostatic device. A sham control group was treated in a similar way except that no material was implanted. Implantation of these hemostatic devices for 15, 43, or 92 days did not result in any deaths or clinical neurobehavioral abnormalities, changes in cerebrospinal fluid, or significant macroscopic observations at necropsy. The tissue reaction to SURGIFOAM sponge was characterized by transient granulomatous inflammation that was slightly less intense than that observed for GELFOAM sponge which correlated to slightly longer absorption. In contrast, the tissue reaction to Avitene hemostat was characterized by moderate to marked granulomatous inflammation with an acute inflammatory component indicating a greater degree of tissue irritancy. Sequelae of this reaction were still observed at 92 days post-implantation. The tissue reaction in humans to SURGIFOAM sponge used as a hemostatic agent for neurologic surgical procedures is expected to be comparable to that observed with GELFOAM sponge, resulting in no significant adverse reactions for patients. This animal model was useful to assess the tissue reaction and absorption of biomaterials implanted in contact with the central nervous system, and it was able to differentiate between materials of biologic origin.

Animals↗
PubMed1988

Utilizing angiogenic agents to expedite the neovascularization process in skin flaps.

The revascularization of a skin flap after flap transposition is an important step in flap survival. This study investigates the efficacy of certain angiogenic agents to expedite the neovascularization process and to increase the viability of skin flaps. Eighty-four island skin flaps were designed on the auricles of 42 New Zealand White rabbits to achieve 90% necrosis over a 7-day period. Thirty-six flaps were treated with Endothelial Cell Growth Supplement (ECGS) or Endothelial Cell Growth Factor (ECGF) at several concentrations topically or immersed in Gelfoam. The remaining flaps were used as normal saline controls. Flap viability and peripheral neovascularization were documented by polar planimetry, angiography, and histological analysis. The flap viability of the ECGS-Gelfoam -treated flaps was 100% greater than their normal saline-Gelfoam controls (p = .021). Flap angiograms demonstrated increased vascular ingrowth among the treated flaps compared to the controls. This study suggests that angiogenic agents can expedite flap neovascularization and have the potential to increase flap viability.

Administration, Topical↗
PubMed1993

Direct application of basic fibroblast growth factor improves tympanic membrane perforation healing.

Topical application of basic fibroblast growth factor (b-FGF) on tympanic membrane (TM) perforations was studied in guinea pigs. One-millimeter simple round TM perforations or 2-mm TM perforations with medially flapped borders were performed. Either b-FGF or placebo was instilled in each ear on the day of surgery and daily thereafter. Treatment was applied either directly to the perforation or to a Gelfoam pledget over the defect. When no scaffolding material was interposed, b-FGF induced a faster healing response characterized by a hyperplastic but linear subepidermal connective tissue reaction compared to the control. When Gelfoam was interposed as a scaffold, a voluminous scar protruding into the middle ear cavity and involving the ossicles was observed in both b-FGF and control animals. Gelfoam-induced scars did not decrease after long-term observation, therefore discouraging its use.

Animals↗
PubMed1994

Cochlear implantation in children: labyrinthitis following pneumococcal otitis media in unimplanted and implanted cat cochleas.

Pneumococcal otitis media is frequent in young children and could lead to labyrinthitis post-implantation. To assess the risk, and methods of minimizing it by a graft to the round window around the electrode entry point, we have used a cat animal model of pneumococcal otitis media. Twenty-one kittens were used in the study. Thirty-two cochleas were implanted when the kittens were 2 months of age. Fourteen cochleas were implanted without using a graft (12 were available for study); 9 had a fascial graft, and 9 a Gelfoam graft (7 were available for study). The implanted kittens had their bullae inoculated with Streptococcus pneumoniae 2 months after implantation and were sacrificed 1 week later. There were also 9 unimplanted control ears which were inoculated when the animals were 4 months of age. Labyrinthitis occurred in 44% of unimplanted control, 50% of implanted ungrafted, and 6% of implanted grafted (fascia and Gelfoam) cochleas. There was no statistically significant difference between the unimplanted control and the implanted cochleas (p < 0.05). There was, however, a difference between the implanted-ungrafted and implanted grafted cochleas, but not between the use of fascia and Gelfoam to graft the round window entry point. As a result, the data indicates that cochlear implantation does not increase the risk of labyrinthitis following pneumococcal otitis media, but it is desirable to use fascia as a graft to the round window around the electrode entry point.

Animals↗
PubMed1975

Infiltrative potentiality of brain tumors in organ culture.

The invasive potential of 15 brain tumors (seven meningiomas, and eight astrocytomas) as studied in cultures with Gelfoam used as a substrate. A three-stage system is introduced to classify in vitro invasiveness according to the depth of Gelfoam infiltration after 2 weeks' culture. This system proved to be simple and accurate. Meningiomas revealed greater activity in culture as compared to astrocytomas and infiltrated deeper into the Gelfoam. Dura mater explants were placed next to the culture of the tumors to study their interaction. Dura mater acted as a relatively strong barrier against tumor cell invasion in culture. In the majority of the explants, tumor cells revealed either contact arrest or spread underneath the dura and rarely spread over it. Tumor cells were seen infiltrating the dural explants in three cases, all of which were meningiomas.

Astrocytoma↗