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Angiographic findings and embolotherapy in renal arterial trauma.

PURPOSE: To evaluate the angiographic findings and embolotherapy in the management of traumatic renal arterial injury. METHODS: This is a retrospective review of 22 patients with renal trauma who underwent arteriography and percutaneous embolization from December 1995 to January 2002. Medical records, imaging studies and procedural reports were reviewed to assess the type of injury, arteriographic findings and immediate embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians and by clinical chart review. RESULTS: Arteriography was performed in 125 patients admitted to a State Trauma Center with suspected internal bleeding. Renal arterial injury was documented in 22 and was the result of a motor-vehicle accident (10), auto-pedestrian accident (1), gunshot (4) or stab wounds (6) and a fall (1). Percutaneous renal arterial embolization was undertaken in 22 of 125 (18%) patients to treat extravasation (11), arterial pedicle rupture (5), abnormal arteriovenous (3) or arteriocalyceal (2) communication and pseudoaneurysm (3). One of the pseudoaneurysms and one of the arteriovenous fistulae were found in addition to extravasation. All 22 patients (16 men, 6 women) were hemodynamically stable, or controlled during arteriography and embolotherapy. Selective and/or superselective embolization of the abnormal vessels was performed using coils in 9 patients, microcoils in 9 patients and Gelfoam pledgets in 3 patients. In one patient Gelfoam pledgets mixed with polyvinyl alcohol (PVA) particles were used for embolization. Immediate angiographic evidence of hemostasis was demonstrated in all cases. Two initial technical failures were treated with repeat arteriography and embolization. There was no procedure-related death. There was no non-target embolization. One episode of renal abscess after embolization was treated by nephrectomy and 3 patients underwent elective post-embolization nephrectomy to prevent infection. Follow-up ranged from 1 month to 7 years (mean 31 months). No procedure-related or delayed onset of renal insufficiency occurred. CONCLUSION: In hemodynamically stable and controlled patients selective and superselective embolization is a safe and effective method for the management of renal vascular injury.

Abdominal Injuries↗

Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization.

PURPOSE: To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). METHODS: GSPs were separated into four size ranges: A, up to 200 microns (mean 152) as Gelfoam powder; B, 200-500 microns (mean 336) as Gelfoam powder; C, 500-1000 microns (mean 649) as Spongel; and D, 1000-2000 microns (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. RESULTS: The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. CONCLUSION: GSPs of 500 microns are considered optimally effective for tissue necrosis according to this model.

Animals↗

Antiangiogenic and antitumoral properties of a polysaccharide isolated from the seaweed Sargassum stenophyllum.

The potential antiangiogenic and antitumoral properties of SargA, a polysaccharide extracted from the brown marine alga Sargassum stenophyllum, were studied in assays carried out in chick embryos and mice. Gelfoam plugs containing SargA (2-1500 microg/plug) implanted in vivo into fertilized 6-day-old chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). By day 8, the highest dose of SargA alone decreased the vessel number in the CAM by 64%, but coadministered with hydrocortisone (156 microg/plug, which alone caused 30% inhibition) failed to potentiate its antiangiogenic effect. Combined with basic fibroblast growth factor (50 ng/plug), SargA (1500 microg/plug) abolished angiogenesis stimulated by this factor in both chick embryo CAM and in subcutaneous (s.c.) Gelfoam plugs implanted in the dorsal skin of Swiss mice (measured as plug hemoglobin content). Repeated s.c. injections of SargA (1.5 or 150 microg per animal per day for 3 days) close to B16F10 melanoma cell tumors in the dorsal skin of mice markedly decreased tumor growth in a dose-related fashion (by 40% and 80% at 2 weeks after the first injection, respectively), without evident signs of toxicity. SargA caused graded inhibitions of migration and viability of cultured B16F10 cells and also displayed antithrombotic activity in human plasma (5 mg/ml increased thrombin time 2.5-fold relative to saline). Thus, SargA exhibits pronounced antiangiogenic as well as antitumoral properties. Although the latter action of SargA might be related to the inhibition of angiogenesis, the polysaccharide also exerts cytotoxic effects on tumor cells. Because of its chemical characteristics and polyanionic constituents, we postulate that the polysaccharide SargA might modulate the activity of heparin-binding angiogenic growth factors.

Angiogenesis Inhibitors↗

Histopathological changes in rabbit uterus carcinoma after transcatheter arterial embolization using cisplatin.

The effects of chemoembolization with cisplatin on gynecological malignancy were investigated using rabbit uterine tumors. A group of 20 rabbits were subjected to inoculation of the uterus with 5 x 10(7) VX2 carcinoma cells and 4 weeks later were divided into four groups, each consisting of five rabbits: an untreated control group, a group given cisplatin intraarterially (IA), a group subjected to transcatheter arterial embolization (TAE) with Gelfoam particles and a group subjected to transcatheter chemoembolization (TACE) with Gelfoam particles plus 1 mg/kg cisplatin. All groups were examined histologically 2 days after treatment. The untreated control group was further investigated 4 weeks after inoculation. In the untreated control group, the tumor cell nuclei varied in size and were irregular in form, and multiple nuclei and nuclear division were also observed. No necrotic zones were found up to 4 weeks after inoculation. The IA group showed no necrosis, but a few apoptotic cells were scattered throughout the tumor. In the TACE group, necrosis was observed in the center of the tumors, but proliferating cells persisted at the periphery. In the TACE group, necrosis was observed in the central part with many apoptotic cells surrounding the necrotic region in layers. The proliferating cell nuclear antigen (PCNA) index was 95.88% in the untreated control group, 86.6% in the IA group, and 8.62% in the TACE group, indicating a significant reduction in cell proliferation in the TACE group. These findings suggest that TACE results in more effective cytotoxicity than the other two treatments in uterine cancer tumor transplants.

Animals↗

Determining optimal MRI follow-up after transsphenoidal surgery for pituitary adenoma: scan at 24 hours postsurgery provides reliable information.

There is no agreed-upon schedule for MRI follow-up after pituitary adenoma removal via the transsphenoidal approach. Our aim was to establish a plan for MRI follow-up after pituitary surgery. Eighty pituitary adenoma cases (25 microadenomas, 30 macroadenomas that did not infiltrate the cavernous sinus, and 25 macroadenomas with cavernous sinus infiltration) were prospectively studied with MRI following tumor resection via the transsphenoidal approach. Each patient was imaged at 24 hours, at 3, 6 and 9 months, and at 1 year or more postsurgery. The parameters studied were residual tumor, synthetic packing material (Gelfoam) versus fat graft, and normal pituitary, hypophyseal stalk and optic chiasma. The size of the pituitary structure as a whole was also measured. The latter was studied quantitatively, and the findings for the rest of the parameters were evaluated qualitatively, based on the examiners' confidence in their assessment. The final MRI study, done at least 1 year postsurgery in all cases, was considered the reference MRI for all scans. MRI performed 24 hours after surgery was diagnostically accurate for residual tumor and valuable for visualizing normal sellar structures. The findings also showed that fat packing takes longer to resorb than Gelfoam, but produces no potentially confounding contrast enhancement. An algorithm based on the results is presented for postsurgical MRI assessment of pituitary adenoma patients in which the scan at 24 hours postsurgery is the major factor that determines the timing of later rechecks.

Adenoma↗

Gelatin-thrombin-based hemostatic sealant for intraoperative bleeding in vascular surgery.

Vascular surgical procedures may be prolonged because of intraoperative bleeding that is not easily controlled by cautery or suture ligation. This trial compared the ability of a new hemostat, FloSealTM Matrix (FM), with a known hemostat, Gelfoam(R) plus thrombin (GT), to control intraoperative bleeding. Patients undergoing vascular surgery procedures at four institutions were entered in the trial. After a bleeding site was identified, patients were randomized to one of the study agents: (1) FM, a cross-linked gelatin of bovine origin combined with thrombin, or (2) GT. The assigned agent was applied and the site observed for bleeding at 1, 2, 3, 6, and 10 min. The primary end point was cessation of bleeding within 10 min for the first identified site treated. Secondary end points were cessation of bleeding within 10 min for all sites and time to cessation of bleeding. Patients were assessed for morbidity at 30 days and 6-8 weeks after the operation. Analysis was performed on an intent-to-treat basis for analysis of hemostasis at 10 min and on protocol-valid patients for analysis of time to hemostasis. From our results we concluded that for patients undergoing vascular surgery procedures, the new topical hemostat, FloSeal Matrix, provides more rapid and effective hemostasis than Gelfoam plus thrombin.

Aged↗

Selective embolization for control of gastrointestinal hemorrhage.

Transcatheter embolization using Gelfoam plugs or autologous clot is an alternative or adjunct to the conventional management of gastrointestinal hemorrhage. During a 12 month period we successfully treated 10 patients who had massive gastrointestinal hemorrhage with selective embolization; 6 patients had upper gastrointestinal hemorrhage and 4 had bleeding from the colon. Most of these patients were critically ill and were poor surgical candidates. Hemorrhage was controlled by selective catheterization of the bleeding vessel, followed by injection of Gelfoam pledgets. Since the procedure was accomplished with ease and prolonged hemostasis obtained, we recommend it for gastrointestinal hemorrhage, especially in patients who are poor surgical risks or are unresponsive to vasopressin infusion, or both. Operative intervention for the primary disease could subsequently be performed electively, if necessary, days or weeks after transcatheter embolization.

Adult↗

The control of glial populations in brain: changes in astrocyte mitogenic and morphogenic factors in response to injury.

Injury to rat brain induces a 3-10-fold increase in the activity of factors capable of stimulating astrocyte DNA synthesis and cell division in vitro. Maximum mitogenic activity was reached 10-15 days post-lesion in both the tissue surrounding the wound and in the gelfoam filling the wound cavity. Factors capable of transforming the astrocyte morphology from polygonal-flat to fibrous-like (morphogens) could also be observed in brain tissue and showed increased activity beginning at 10 days postlesion. On the other hand, morphogenic activity was very low or absent in gelfoam extracts until 15 days postlesion. Both mitogenic and morphogenic factors were nondiffusible and were partly temperature and trypsin sensitive, i.e. they had the properties of protein-like substances, but seemed different from both epidermal and fibroblast growth factors. As judged by their filtration behavior on Amicon membranes, the molecular weight of mitogens and morphogens ranged from lower than 30,000 to greater than 100,000. Inhibitors of both mitogenic and morphogenic activities with molecular weight lower than 30,000 seemed to be also present in the brain extracts. The factors described here can account for the processes of astrocytosis and astrogliosis observed in vivo in response to CNS injury.

Animals↗

[3H]lysine incorporation into protein of hemisected, cycloheximide-treated spinal cord.

A single application of a protein synthesis inhibitor, puromycin, in the lesion site of a spinal hemisection transiently decreases protein incorporation for less than 24 h and results in axonal sprouting and dendritic and synaptic stability for at least 60 days. In this study we characterized the protein-altering properties of single applications of a different protein synthesis inhibitor, cycloheximide, for comparison. The protein incorporation of [3H] lysine into hemisected rat spinal cord (left side, T2) treated with cycloheximide (100 micrograms/ml in Gelfoam sponge placed in wound at time of lesion) was tested 3 h, 6 h, 12 h, 1, 3, 7, and 14 days later and compared with that in 0.9% saline in Gelfoam implants as normal controls (N = 54). One hour prior to utilization, the animals were injected subcutaneously with 200 mu Ci L-[4,5(n)-3H]lysine monohydrochloride. No treatment-related differences in brain radioactivity were noted at any time postoperation. In spinal cord, inhibition of amino acid uptake by cycloheximide was not demonstrable at 3 h after hemisection, but could be detected from 6 h to 1 day after implantation. During that time, the TCA-soluble radioactivity at the lesion site was greater than in control animals (P less than 0.05). These results suggest that as with puromycin, morphologic effects produced by cycloheximide on spinal cord regeneration may correspond to chemical events which occurred within the first 24 h after cord hemisection and cycloheximide treatment.

Animals↗

Basic fibroblast growth factor prevents neuronal death and atrophy of retrogradely labeled preganglionic neurons in vivo.

We have used retrograde fluorescent tracing (fast blue) both before (prelabeling) and at time points after selective unilateral adrenomedullectomy in vivo (post-labeling) in order to investigate the survival and morphology of sympathoadrenal preganglionic (SAP) neurons located in the lower thoracic intermediolateral (IML) cell column of the adult rat spinal cord. By prelabeling with fast blue it was found that the majority (i.e., more than 85%) of the SAP neurons underwent degeneration and were lost from the IML cell column within 4 weeks after peripheral target lesion and administration of intramedullary gelfoam implants containing a nontrophic control protein cytochrome c. By contrast, atrophy and loss of SAP neurons was largely prevented by local treatment (intramedullary implants) with recombinant basic fibroblast growth factor (bFGF) as determined from counts of large and "healthy-looking" prelabeled neurons within the IML column ipsilateral to the lesioned (i.e., operated) side 4 weeks postimplantation. The time course of withdrawal of preganglionic axons from their lesioned target area was investigated by fast blue injections into intramedullary (control or bFGF) implants at weekly intervals postimplantation (postlabeling) and was documented by counting the number of healthy SAP neurons that retained the label. Without bFGF treatment, progressive numerical loss of SAP neurons was evident within 1 to 4 weeks postlesioning, indicative of pronounced retrograde cell degeneration. Retrograde cell degeneration was insignificant during the first 2 weeks postimplantation after early postlesion treatment with exogenous bFGF; it was apparently postponed to occur after 1 month. Implantation of gelfoam containing neutralizing anti-bFGF-antibodies resulted in accelerated retrograde axon degeneration implying that bFGF is an endogenous trophic factor for SAP neurons. The results are consistent with the idea that SAP neurons actually die following peripheral target lesion and are not supported from other trophic sources. However, these neurons can be prevented from disconnection-induced death by providing exogenous bFGF. Limited amounts of endogenous FGF may also become available to SAP axons by disintegration of nerve terminal-surrounding cells delaying the process of retrograde SAP neuron death.

Adrenal Glands↗

Fatal hemorrhage from an arterio-portal-peritoneal fistula after percutaneous liver biopsy.

Exsanguinating hemorrhage complicated a percutaneous needle biopsy in a 64-yr-old woman with a probable collagen vascular disease. Angiography performed before Gelfoam embolization demonstrated a hepatic arterio-portal venous-peritoneal fistula, a lesion not previously described, to be a cause of the hemorrhage. Although surgery remains the treatment of choice, the role of selective hepatic arteriography and Gelfoam embolization in patients with serious hemorrhage who are poor surgical risks needs evaluation.

Arteriovenous Fistula↗

A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation.

To investigate therapeutic strategies for hepatoma, it is necessary to have a reproducible animal model with a tumor growth pattern allowing accurate assessment of results. Many techniques of intrahepatic tumor implantation (IHTI) have been devised for intrahepatic tumor models. Most of them, however, have the disadvantage of high rates of artificial tumor dissemination during tumor implantation, which interferes with the evaluation of therapy. To overcome this problem, we have developed a technique of IHTI in which a piece of Gelfoam is placed into a small incision in the liver for the purpose of both hemostasis and formation of a tension-free pocket to accept the tumor implant. In 583 ACI rats receiving IHTI with Morris hepatoma 3924A, the tumor take rate was 100%. Resembling the natural course of human hepatoma, the implanted tumor grows locally early in the course of disease and eventually invades the surrounding organs causing ascites and also metastasizes to the lung. Liver microangiography demonstrated that the tumor received blood supply mainly from the hepatic artery. This IHTI technique was also compared to two other methods of IHTI: insertion of fragments without using Gelfoam and implantation with a tumor cell suspension. A significantly lower rate of early lung metastases was achieved with our technique (0%) in comparison with other two techniques (41 and 80%). We conclude that this rat liver cancer model is reproducible and allows efficient evaluation of treatment modalities for liver cancer without interference from tumor at undesirable sites.

Animals↗

Evaluation of therapeutic arterial embolization in renal cell carcinoma using microencapsulated mitomycin C.

The therapeutic arterial embolization in the case of renal cell carcinoma using microencapsulated mitomycin C (MMC) was investigated by an angiographic evaluation in comparison with nonencapsulated MMC. The Gelfoam embolization supplemented with nonencapsulated MMC could not necessarily prevent the recanalization and collateral circulation, while the Gelfoam embolization supplemented with microencapsulated MMC completely or considerably eliminated the revascularization with a distinct advantage in this degree. Moreover, peripheral blood MMC level after the embolization using microencapsulated MMC was reduced to 39 per cent of that after nonencapsulated MMC infusion. The result was consistent with the previous experiments, indicating that the transcatheter infusion of microencapsulated MMC is the therapeutic arterial embolization of the tumor-supplying vessels together with regional anticancer chemotherapy. Further clinical application to various malignancies is in progress.

Aged↗

Transcatheter embolotherapy for congenital renal arteriovenous malformations. Long-term follow-up.

Transcatheter embolization was performed five times in 3 patients with congenital renal arteriovenous malformations (AVM). The patients were followed for one to seven and a half years. Two patients whose AVM were completely occluded with Gelfoam have been asymptomatic with no evidence of hematuria. A third patient, embolized with Gelfoam and Ivalon without complete occlusion of the AVM, bled ten months after the first procedure, was re-embolized, and later had the AVM removed surgically. Superselective transcatheter embolization should be the initial treatment modality for congenital AVM with the aim to control bleeding and occlude those malformations supplied by the terminal portion of interlobar arteries. Large malformations supplied by multiple feeders may require operative ligation and removal of the AVM when vessels cannot be occluded satisfactorily because of massive shunting.

Adult↗

Effects of astrocyte implantation into the hemisected adult rat spinal cord.

Morphological and biochemical methods were applied to assess the effects of implanting cultured astrocytes into the hemisected adult rat spinal cord. Astrocytes were purified from neonatal rat cortex and introduced into the lesioned spinal cord either in suspension injection or cultured on gelfoam first. The control groups were rats which had hemisection with injection of culture media or with gelfoam grafted alone. At various time points after surgery (two weeks to two months), the spinal cord was removed and processed for routine light microscopy, immunofluorescence, gel electrophoresis and immunoblotting. As early as two weeks after surgery, a significantly smaller volume of scar tissue was consistently found in the experimental groups. This reduced scarring was also confirmed by immunofluorescence staining and immunoblotting for glial fibrillary acidic protein in the specimens two months after hemisection. Compared to the control groups, the experimental groups also had more intense staining for neurofilaments, which was confirmed by immunoblotting. However, labelling of the astrocytes with Phaseolus vulgaris leucoagglutinin conjugated with fluorescein showed that the astrocytes migrated at a rate of 0.6 mm/day from the original implanted site. The results therefore suggested that the cultured astrocytes probably exerted their effects over a short time period (less than two weeks) around the lesion site. They could have altered the microenvironment and as a result less scar tissue was formed. Hence, there was less barrier to the regrowth of nerve fibres.

Animals↗

Round window gentamicin application: an inner ear hair cell damage protocol for the mouse.

It is important to develop an inner ear damage protocol for mice that avoids systemic toxicity and produces damage in a relatively rapid fashion, allowing for study of early cellular and molecular mechanisms responsible for hair cell death and those that underlie the lack of hair cell regeneration in mammals. Ideally, this damage protocol would reliably produce both partial and complete lesions of the sensory epithelium. We present a method for in vivo induction of hair cell damage in the mouse via placement of gentamicin-soaked Gelfoam in the round window niche of the inner ear, an adaptation of a method developed to study hair cell regeneration in chicks. A total of 82 subjects underwent the procedure. Variable doses of gentamicin were used (25, 50, 100 and 200 microg). Saline-soaked Gelfoam, sham-operations and the contralateral, non-operated cochlea were used as controls. Survival periods were 1, 3 and 14 days. Damage was assessed on scanning electron microscopy. We found that this method produces relatively rapid hair cell damage that varies with dose and can extend the entire length of the sensory epithelium. In addition, this protocol produces no systemic toxicity and preserves the contralateral ear as a control.

Animals↗

Surgical indications and outcomes of tympanostomy tube removal.

OBJECTIVE: To evaluate factors affecting perforation healing in children with surgical removal of retained tympanostomy tubes. METHODS: We conducted a retrospective chart review of 82 pediatric patients (111 ears) who underwent surgical tube removal at a tertiary care pediatric hospital from 1/1/1999 to 12/31/2001. Patients included 47 males and 35 females with an age range of 2-15 years (average age, 6.8 years and median, 6 years). The length of intubation ranged from 12 months to 108 months (average, 44.6 months). The indications for removal included: prolonged intubation (61.3%), otorrhea or recurrent infection (21.6%), obstruction (7.2%), tube in middle ear (6.3%), enlarging perforation (2.7%), and in preparation for future cochlear implant surgery (9.9%). Interventions included removal of tympanostomy tubes and techniques for encouraging perforation closure. Seventy-six percent of the ears had a technique used to encourage healing. These techniques included freshen edges (11.8%), Gelfoam or Gelfilm (14.1%), Gelfoam and/or Gelfilm with freshened edges (50.6%). The main outcome measure was perforation healing. Chi-square statistical analysis were used to determine the statistical significant of observations. RESULTS: Overall closure rate for all patients available for follow up was 87.0%, regardless of technique used to encourage healing. There was no statistically significant difference between the average intubation time in ears that healed (44 months), versus those with persistent perforation after removal (42 months). There was no statistical significant difference in closure rate based on patient age. When tubes were removed for prolonged intubation, 87.0% closed. If the indication was otorrhea or recurrent infections, 93.0% healed. CONCLUSIONS: The overwhelming majority of patients who undergo surgical removal of tubes will show complete tympanic membrane healing independent of technique at time of removal, duration of intubation, patient age, or indication for removal.

Adolescent↗

Stem cell repair of physeal cartilage.

To evaluate the ability of cultured mesenchymal stem cells (MSC) to repair physeal defects, MSC-matrix constructs with 5% gelatin (group A), 10% gelatin/Gelfoam (Pharmacia, Peapack, NJ) (group B), and MSC grown in the presence of TGF-beta3 with Gelfoam (group C) were implanted in proximal tibial physeal defects created in 20 immature rabbits. Control groups (untreated partial defect and partial defect treated with Gelfoam) showed bony bar formation with varus deformities of 30 degrees and 28 degrees, respectively. Group A had an average 23 degrees varus deformity with bony bridge formation, and group B had mild varus angulation (average 14 degrees) of the proximal tibia. In group C, there was no significant varus deformity (average 9 degrees), and histologic examination showed that some of the columnation areas interspersed with chondrocytes were irregularly arranged in the matrix. These findings suggest that repair of physeal defects can be enhanced by the implantation of MSC cultured with TGF-beta3.

Animals↗