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Important factors influencing the strength of autologous fibrin glue; the fibrin concentration and reaction time--comparison of strength with commercial fibrin glue.

Fibrin glue was prepared from citrated plasma of human donors by means of ethanol. The outcome was a fibrinogen concentrate with a mean concentration of 43 mg/ml. The fibrinogen was converted to fibrin by the addition of 0.3 part of thrombin solution, 150 NIH U/ml, containing 100 mM calcium chloride. In a rat model full-thickness skin grafts were sealed with the glue, and the adhesive strength was measured at different fibrin concentrations, and after a variable reaction time, and compared to commercial fibrin glue (Tisseel). The strength of ethanol-prepared glue was directly proportional to the fibrin concentration, and increased rapidly within the first minutes of the reaction time. The strength of the commercial glue could be obtained with autologous fibrin glue at the same fibrin concentration.

Animals↗

A comparison of keratinocyte cell sprays with and without fibrin glue.

Fibrin glue is an excellent template for cellular migration and has been shown to be an effective delivery system for cultured autologous keratinocytes. We have investigated whether fibrin glue has any benefit on the percentage of epithelial cover when cultured autologous keratinocytes are sprayed onto a freshly debrided wound bed. Three pigs were used for this study. This provided a total of 18 full thickness, vertically orientated wounds, each 4cm in diameter and isolated in PTFE chambers to prevent re-epithelialisation from the wound margins. Eight wounds were sprayed with cultured autologous keratinocytes suspended in 2ml culture medium and eight wounds were sprayed with cultured autologous keratinocytes suspended in 1ml of the fibrin/aprotinin component of Tisseel fibrin glue (Baxter) mixed with 1ml of culture medium. In the latter group the thrombin component of the fibrin glue kit was applied to the wound bed immediately prior to grafting. The remaining two wounds were used as controls and sprayed with either culture medium or fibrin glue without cells. Epithelial cover was calculated in whole-wound biopsies at 3 weeks using image analysis, histology and immunohistochemistry. The cell suspension in fibrin glue appeared to spread more evenly over the wound surface, with no pooling in the inferior aspect of the wound. However, mean epithelial area at 3 weeks in the fibrin group was 1.6cm(2) per wound compared with 1.8cm(2) for the non-fibrin group, as measured by image analysis of digital photographs. There was no statistically significant difference between the two groups (P=0.802). This surprising result was confirmed by histological analysis of the wound biopsies, with a good correlation between histological and image analysis data (R=0.967). There was no observable difference in the quality of the epithelium on histological and immunohistological analysis of either group.

Aerosols↗

Fibrin glue.

Fibrin glue is a topical biological adhesive, the effect of which imitates the final stages of coagulation. The glue consists of a solution of concentrated human fibrinogen which is activated by the addition of bovine thrombin and calcium chloride. The resultant clot aids haemostasis and tissue sealing and is completely absorbed during wound healing without foreign body reaction or extensive fibrosis. The fibrinogen component of fibrin glue can be produced from fresh frozen plasma obtained from single unit donations thereby reducing the risks of transfusion transmitted infections encountered by exposure to pools from large numbers of donors. Methods involving precipitation of fibrinogen by cryoprecipitation, polyethylene glycol or ammonium sulphate have been described and evaluated. The risk of transmission of infection can be further reduced by using plasma from 'accredited donors' who are plasma donors regularly tested for ALT and markers of viral infection or by use of fibrinogen prepared in advance of surgery from autologous blood. The second component, a mixture of thrombin and CaCl2, is quantitatively and qualitatively well defined and commercially available (Armour Pharmaceutical Co., Thrombinar (bovine thrombin]. Thrombin is applied to the operation site simultaneously and in equal volume to the fibrinogen but from a separate syringe. In the UK a commercial heat treated fibrin glue prepared from pooled plasma is available on a doctor/named patient basis (Tisseel, Immuno, Vienna). The haemostatic and adhesive properties of fibrin glue can be employed in virtually every surgical specialty. The usefulness of the glue is particularly well documented in the fields of cardiovascular surgery, ENT and neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Disorders↗

Control of intraoperative hemorrhage in gynecology with the use of fibrin glue.

Fibrin glue, a biodegradable tissue adhesive, is a valuable topical hemostatic agent and an effective tissue sealant. We describe the use of fibrin glue in controlling life-threatening hemorrhage in three gynecology patients. Simultaneous injection of equal amounts of cryoprecipitate and bovine thrombin at bleeding sites results in formation of the glue, which effectively controls the bleeding. When used in conjunction with good surgical technique, fibrin glue may decrease the need for blood transfusions and may shorten operating room time.

Adult↗

The addition of antibiotics to fibrin glue.

Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these two solutions mimic the final stages of the clotting cascade to form a fibrin clot. Because the resulting fibrin patch is a good medium for microbial growth, the addition of antibiotics to one of the components of fibrin glue has been shown to reduce postoperative infections. Seventeen different antibiotics have been investigated in vitro. Of the 17, cefotaxime, mezlocillin, gentamicin, neomycin, and polymixin B, when added to fibrin glue, can decrease the rate of clot formation or the strength of the resultant fibrin clot. Further work is necessary to characterize the effect the addition of antibiotics has on the rate and strength of fibrin clotting and to determine what effect low systemic levels of antibiotics might have on antibiotic resistance patterns.

Anastomosis, Surgical↗

Long-term results of vein grafts interposed in arterial defects using the telescoping anastomotic technique and fibrin glue.

Fibrin glue has been applied in the anastomosis of vein grafts placed in rat femoral arteries using the telescoping technique at both ends of the graft. 34 out of 35 grafts which were patent 1 to 3 weeks post-operatively were kept for 3 months to assess the long-term patency, and the effect of the glue on the diameters of the graft and femoral artery. All 34 grafts were patent 3 months post-operatively. Excessive enlargement of the graft diameter was alleviated by the fibrin glue without affecting the diameter of the femoral artery. The diameter at the proximal anastomosis was 66% and that at the distal anastomosis was 87% of the diameter of the femoral artery.

Anastomosis, Surgical↗

Hemostasis of solid viscus trauma by intraparenchymal injection of fibrin glue.

Fibrin glue (FG) is an effective hemostatic agent applied topically to the spleen. In this study, FG was found to be an effective hemostatic agent when applied topically in standardized wounds of the canine liver, spleen, and pancreas. It was markedly more effective, however, when injected intraparenchymally. In a case of severe blunt trauma in a patient with acute alcoholic hepatitis, intraparenchymal FG was lifesaving. Fibrin glue is a useful adjunct in the management of trauma to all the abdominal solid viscera. Intraparenchymal injection is the preferred mode of FG application.

Administration, Topical↗

[Surgical repair of left ventricular free wall rupture using layered fibrin glue sheet and fibrin glue; report of a case].

A 57-year-old man with acute myocardial infarction (#13:90%, #6-#8:75%) was admitted to our hospital after the administration of tissue plasminogen activator. Three hours' after emergent percutaneous transluminal coronary angioplasty, he developed left ventricular free wall rupture in the left circumflex artery area. After bleeding was completely controlled by aortic cross clamping, a three-layered of fibrin glue sheet (TachoComb) with fibrin glue was extensively applied to the ruptured site including the infarcted area. He was discharged on the 25th postoperative day and underwent coronary artery bypass grafting to the left anterior descending artery three weeks later. This experience suggests that the layered TachoComb and fibrin glue are effective for left ventricular free wall rupture.

Coronary Artery Bypass↗

[Dura mater healing after repair with aponeurotic plasty. Comparison of results between classical sutures and fibrin adhesive glue. Fibrin adhesive in frontobasal injuries. An experimental study].

The aim of the present experimental study was to compare the quality of the healing obtained with fibrin glue or with classical sutures to repair post-traumatic fronto-basal fistulae. The anterior part of the cranial base and a piece of dura mater are removed. The first group of rabbits (n = 26) is repaired with fibrin glue; the second group with separate sutures. The postoperative controls are realised by injection of 1 ml patent blue in the cisterna magna to detect C.S.F. rhinorrhea, x-ray study of the cranial bases and histological samples of transversal slices of the cranial base. The different biological findings seem to be important arguments to confirm the useability and trustworthiness of human origin fibrin glues to close meningeal wounds.

Animals↗

Techniques of splenic preservation using fibrin glue.

Fibrin glue (FG) was used to achieve hemostasis of 16 splenic injuries in 14 patients. The etiologies of injury included five gunshot wounds, two stab wounds, four iatrogenic injuries, and five patients with blunt splenic trauma. The intraoperative blood loss averaged 1.8 +/- 2.4 (SD) liters and patients were transfused 3 +/- 2 units of blood perioperatively. The amount of FG required to achieve splenic hemostasis averaged 11 +/- 8 ml and varied directly with the grade of injury. One patient with a splenic hilar vascular injury (Grade V) underwent splenectomy following failure to achieve complete hemostasis despite the use of 25 ml of FG. All other splenic injuries were successfully managed using less than 25 ml of FG. Postoperative computerized tomographic (CT) scanning, performed in ten patients, was negative for rebleeding or abscess formation. The overall splenic salvage rate was 86%. FG was effective in achieving hemostasis of both superficial and deep splenic injuries. Its use as an adjunct in trauma surgery should result in increased splenic salvage rates compared with that obtained using conventional surgical techniques.

Adult↗

[Local chemotherapy for malignant brain tumors using methotrexate-containing fibrin glue].

Fibrin glue (FG) is an agent developed for achieving hemostasis and the adhesion of living tissue during surgical operations. Incorporation of a drug into FG may be expected to have a sustained local release. In the present study, methotrexate (MTX) included in FG (FG-MTX) was used. The release of MTX into human plasma and cerebrospinal fluid was studied by in vitro study to confirm the sustained release effect of this preparation, by in vivo study, in which the antitumor effect of FG-MTX was assessed in rats bearing 9L-gliosarcoma subcutaneously; and clinically, FG-MTX therapy was attempted in patients with malignant brain tumors. The in vitro study showed that MTX levels rapidly decreased over 1 to 3 days, but was still detected on days 7 and 14. The results showed the sustained release effect of MTX. The in vivo study showed that in the FG-MTX group, all tumors began to decrease soon after administration and disappeared in four out of five animals (80%) on about day 10. In the clinical study, sustained release for more than one week was found, and tumor decrease occurred in the case of a malignant brain tumor. Thus, FG-MTX appears to provide an effective local chemotherapy.

Animals↗

Autologous Fibrin Glue in Pterygium Surgery as an Alternative to Commercial Fibrin Glue.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of autologous fibrin glue in pterygium surgery, comparing it with commercial fibrin glue in terms of postoperative complications, graft stability, and recurrence rate. METHODS: A prospective, randomized, double-blind study was conducted, involving 42 patients with primary pterygium who underwent autologous conjunctival-limbal transplantation. The graft was fixed using autologous fibrin glue (Group 1, G1) or commercial fibrin glue (Group 2, G2). All patients underwent surgery performed by the same surgeon and were reevaluated on postoperative days 7, 30, 90, and 180 by an independent observer, assessing clinical parameters in the preoperative, intraoperative, and postoperative periods. RESULTS: No cases of severe adverse events were reported. Complete graft dehiscence occurred in 1 patient from G1. The G2 group had more cases of subconjunctival hemorrhage ( P = 0.0355). Pyogenic granuloma was observed in 1 patient from G2 and 2 patients from G1. There was no significant difference in recurrence rates between the groups (15% in G1 vs. 5% in G2; P = 0.2918). In both groups, graft dimensions tended to decrease slightly in the early postoperative period, followed by stabilization. CONCLUSIONS: Autologous fibrin glue demonstrated efficacy and safety comparable to commercial fibrin glue, making it a viable alternative to conjunctival graft fixation in primary pterygium surgery.

Humans↗

[Tissue glues and the fibrin glue system].

The authors submit a report on the present state of development of tissue glues and their use in medicine. They characterize synthetic glues and the fibrin gluing system. They draw attention to the advantages and shortcomings of both systems. The composition of the fibrin glue is analyzed and its properties are analyzed, incl. the relation to treated tissue. Attention is drawn to the favourable properties of fibrin tissue glue in the treatment of tissues, the authors evaluate its sole use as well as its use in combination with traditional suture. They also mention preparations used in the production of the glue and compare the costs of their preparation. Principles for the production of the two components and prerequisites of their wider use in future are emphasized.

Fibrin Tissue Adhesive↗

Closure of blepharoplasty incisions with autologous fibrin glue.

Autologous fibrin glue was prepared from individual patients and used as a surgical adhesive. Sixteen patients undergoing elective eyelid operations were studied. The fibrinogen was prepared from autologous blood by a cryoprecipitate technique. When mixed with commercially available thrombin, a fibrin clot develops with sufficient adhesive strength that the need for extensive suturing is obviated. Complications were few, and due to technical factors in the initial cases, all patients were followed up for at least 1 year. Problems associated with suture closure of wounds (eg, cysts, granulomas, milia) were not seen. The fibrin glue not only sealed the wound but also acted as a hemostatic agent. The autologous preparation is superior to commercial products since it avoids the problem of transfusion-transmitted disease. The fibrin glue and minimal suture technique is an alternative to eyelid incision closure and may be useful in many other types of operative procedures.

Aged↗

Management of experimental pneumothorax in weanling rabbits with the use of fibrin glue sclerosant.

Fibrin glue pleurodesis successfully sealed surgically created pneumothoraxes in 12 (92.3%) of 13 New Zealand white rabbits, an animal model chosen for its similarity to the thoracic configuration of the human neonate. All chest tubes were removed at 24 hours; there were no recurrences. Two rabbits, in whom human cryoprecipitate was used, died of an immunologically mediated pneumonitis. This reaction would not be expected in the human setting. Four months' follow-up revealed nearly total fibrin glue resorption. This "biodegradability" is well suited to the neonate, since alveolar barotrauma, not congenital emphysematous blebs, is the usual initiator of pneumothorax. Time-limited adhesions created by fibrin glue pleurodesis should be adequate for treatment of the acute event, while avoiding persistent pleural adhesions that could interfere with subsequent thoracic surgery or cause long-term deleterious effects on pulmonary function.

Animals↗

Biochemical and physical properties of a solvent-detergent-treated fibrin glue.

A fibrin glue preparation has been obtained from pooled human plasma using a procedure which includes a solvent-detergent (SD) treatment to inactivate lipid-enveloped viruses. The SD treatment inactivated greater than or equal to 5.5 log10 of HIV in less than 45 min, and greater than or equal to 5 log10 and greater than or equal to 6.5 log10 of VSV and Sindbis virus, respectively, in less than 2 h. The product was found to contain high quantities of fibrinogen (116 +/- 2.49 g/l; n = 12), factor XIII (35 +/- 2.88 U/ml) and von Willebrand factor (23 +/- 1.9 U/ml ristocetin cofactor activity), and relatively low levels of fibronectin (5.9 +/- 0.51 g/l). Plasminogen, the precursor of plasmin, which may play a negative role by decreasing the resistance of the fibrin clot, was at only 0.03 g/l. Cellulose acetate electrophoresis showed 95% gamma-proteins and 5% alpha-2-beta proteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions detected three main protein bands with apparent molecular weights of 65, 56 and 47 kilodaltons, probably corresponding to the alpha, beta, and gamma fibrinogen subunits. Other characteristics of the product included (1) high clottability of fibrinogen (over 85%); (2) absence of low molecular weight fibrin degradation products; (3) rapid solubilization at room temperature (less than 10 min); (4) high tensile strength (202 +/- 27 g/cm2 after 2 h of application), and (5) high elasticity of the fibrin clot. In addition, scanning electron microscopy revealed a highly organized structure showing tridimensional arrangement of the fibrin fibers. SD treated fibrin glue should efficiently replace autologous fibrinogen or cryoprecipitate preparations for surgical application.

Antiviral Agents↗

Evolution of fibrin glue applicators.

Fibrin glue (FG) is used worldwide as a potent surgical tool, which establishes hemostasis in wounds and also bonds tissue. The standard FG applicator is based on a dual-syringe system. This review, based mainly on the patent literature, describes the development of the quasi-standard dual syringe system as well as the rise of other FG applicator designs based on mechanical force (ratchet systems), Bernoulli gas flow, positive gas pressure, or electro-servo devices. The packaging of commercial FG components is reviewed within the context of "loading" the FG applicators and the need to minimize the number of needles required to access the packaged (vials) components. Parameters such as internal clogging, homogeneity of spray, the requirement for gas or vacuum house lines, the number of parts that must be handled, and the time required to assemble the applicator, load it, and have it ready for use are also discussed. A rating system is proposed that permits one to use such parameters to rank the various applicator designs, relative to the dual-syringe system. Hopefully, this review will stimulate the design of better FG applicators and packaging required for elective surgery, emergency treatments, and tissue engineering in the 21st century.

Equipment Design↗

Mitogenicity and release of vascular endothelial growth factor with and without heparin from fibrin glue.

PURPOSE: Fibrin glue (FG) has been used for local cytokine delivery on both vascular grafts and angioplasty sites. We measured the diffusive release of vascular endothelial growth factor (VEGF) and heparin from FG and the mitogenic activity of VEGF with and without heparin in FG on canine endothelial cells (ECs) and smooth muscle cells (SMCs). METHODS: Release of VEGF labeled with iodine 125 and tritiated heparin from FG into the overlying media was serially measured over 96 hours, and the data are reported as the mean percent released +/- SD. Proliferation assays measuring tritiated thymidine incorporation were performed for ECs and SMCs plated in media with 10% serum on FG containing various concentrations of VEGF and heparin. Media was placed on the FG for 24 hours and removed before plating cells to minimize the effect of the released, soluble VEGF and heparin. RESULTS: At 24 hours, 54% +/- 1% and 58% +/- 1% of the radioactive VEGF and heparin were released, respectively, with minimal release thereafter (58% +/- 1% and 66% +/- 1% at 96 hours). The ECs, SMCs, or media only (no cells) was plated on FG containing radioactive VEGF in an immediate or 24-hour delayed fashion for 72 hours to determine the percent release of VEGF into the media with the two different methods of plating. Cell type and the presence or absence of cells did not affect VEGF release, but there was three times more VEGF in the media for the immediate versus delayed plating (P <.001). Without heparin, VEGF at 100 ng/mL or more in the FG was needed to induce EC proliferation. Heparin at 5 U/mL enhanced EC proliferation at the VEGF dose of 100 ng/mL as compared wtih no heparin (P <.001), but not at the VEGF dose of 1000 ng/mL, which likely represents a maximal response. With heparin at 500 U/mL, the ECs died. In contrast, VEGF, in the presence or absence of heparin, did not affect SMC proliferation. CONCLUSIONS: We conclude that FG with VEGF at 1000 ng/mL and heparin at 5 U/mL is the optimal concentration for in vivo use because this may encourage EC, but not SMC, proliferation. The VEGF at 1000 ng/mL should leave mitogenic concentrations of VEGF intact after the initial, diffusive loss, and the addition of heparin at 5 U/mL may enhance VEGF mitogenic activity.

Animals↗