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At least 757 records · Page 42Linked to original sources

Control of carcinoid syndrome with hepatic artery embolization.

Eighteen patients with metastatic carcinoid were treated by hepatic artery embolization with Gelfoam or polyvinyl alcohol foam for control of the carcinoid syndrome. Seventeen showed subjective or objective clinical improvement, including less skin flushing, diarrhea, and bronchospasm. Fourteen showed improvement in biochemical indices, including decreased urinary 5-hydroxyindoleacetic acid levels. The mean life span of the treated patients from the first episode of flushing to the time of this report was 5.4 years, and half of the patients are still alive. This survival time compares favorably with previous reports of survival of 3.2 years from the onset of flushing.

Adult↗

Bile duct necrosis: complication of transcatheter hepatic arterial embolization.

Bile duct necrosis because of transcatheter hepatic arterial embolization (THAE) in two patients with hepatocellular carcinoma is reported. Preoperative THAE was performed on 29 patients, and bile duct necrosis was experienced by two of the 29 (7%). In these two patients, gelatin (Gelfoam) powder was used as the embolus. Among the 24 whose embolus was clear, four were embolized with gelatin powder. Therefore, incidence of bile duct necrosis after THAE with gelatin powder was 50%. Because of the hazards of severe complications such as bile duct necrosis, we conclude that gelatin powder should not be used except for the THAE of no more than one segment of the liver.

Bile Ducts↗

Bronchial artery embolization in the management of hemoptysis: technical aspects and long-term results.

Seventy-five patients with hemoptysis were treated with bronchial artery embolization (BAE). The procedure was performed with Hexabrix (sodium methylglucamine ioxaglate), Mikaelson catheters, and Gelfoam particles. Angiographic evaluation of the bronchial artery anatomy revealed ten different configurations, which are described. The embolization attempt failed in three cases (4%); eight additional patients (10.7%) were excluded from the series because of inadequate data. In the remaining 64 patients, 41 underwent BAE alone and 23 underwent either chemotherapy or surgery in addition to embolization. Immediate control of hemoptysis was achieved in 49 of 64 patients (76.6%). Long-term control of hemoptysis was achieved in 46 of the 56 patients included in the long-term follow-up (82.1%). Eight of the 64 patients were lost to follow-up, which ranged from one to 47 months (mean 24.8 months). Hemoptysis recurred in 12 of 56 patients (severe in 10, mild in 2) (21.4%). Twelve patients died (21.4%), five of them due to hemoptysis (8.9%). None of the patients who died of hemoptysis had responded to initial BAE. It is concluded that BAE is an effective treatment for immediate control of life-threatening hemoptysis, allowing long-term control of bleeding in the majority of patients.

Adult↗

Safe splenoportography.

The records of 37 patients who had undergone splenoportography, including one group of 12 who were studied before 1976 and a second group of 25 who were studied after 1977, were reviewed. The primary difference was that in the second group, the tract in the spleen was occluded with absorbable gelatin sponge (Gelfoam) plugs as the needle was withdrawn. In addition, there were minor changes in technique, such as changes in the needle puncture angle and entry site. When the new technique was used, there was a significant decrease in the complications traditionally associated with splenoportography. This procedure is safe and deserves to be considered the procedure of choice in patients in whom precise anatomic information is needed preoperatively that cannot be obtained with noninvasive procedures such as ultrasound or magnetic resonance imaging.

Adolescent↗

Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents.

Thirty-one patients with hepatocellular carcinoma (HCC) were given either an intraarterial injection of iodized poppyseed oil (Lipiodol) alone (group A, n = 6), an emulsion of iodized oil and doxorubicin hydrochloride (Adriamycin) (group B, n = 15), or chemoembolization with the same emulsion followed by gelatin sponge (Gelfoam) particles (group C, n = 10). Hepatic resection was subsequently performed. The frequencies of complete necrosis of tumor in the main lesion, daughter tumors, tumor thrombus, and foci of intracapsular invasion were evaluated in the cut surface of the resected specimen. Group C demonstrated the best therapeutic effects, showing complete necrosis of the main lesion in 83% (P less than .01), daughter tumors in 53% (P less than .01), tumor thrombus in 17%, and foci of intracapsular invasion in 67%. These results are superior to those reported previously for chemoembolization without iodized oil. Group B showed better results than group A, but the difference was not significant. Iodized oil alone (group A) had practically no therapeutic effect but was helpful in differentiating small HCC from regenerative nodules.

Adult↗

Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction.

Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test (n = 5/group) showed that the elastin mesh was more elastic (P < 0.05) and tensile (P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells (Cell group, n = 7) or COS-7 cells with elastin gene (Elastin group, n = 9) or vector (Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls (n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group (P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater (P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.

Animals↗

Cell-based tissue engineering for lung regeneration.

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed "alveolar-like structures" at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

Absorbable Implants↗

Long-term maintenance of mature pulmonary parenchyma cultured in serum-free conditions.

Current concepts of the pathogenesis of lung injury and repair are derived from in vitro cellular and in vivo investigations. Studies with viable ex vivo models may offer additional insights into disease processes, since essential cellular interactions would be maintained. However, a major limiting factor has been the availability of a model that maintains normal parenchymal structure, viability, and homeostasis beyond 4 wk in serum-free conditions. We have succeeded in establishing an ex vivo lung culture system which reproducibly maintains parenchymal architecture for up to 9 wk. Our method is a simple, modified version of previously utilized techniques. Thin slices of mature murine lung were inflated with agar-defined medium and cultured on Gelfoam saturated with serum-free medium. Normal pulmonary parenchyma, with the exception of endothelial cells, was maintained for up to 60 days as assessed chronologically by light and electron microscopy. The integrity of the microvasculature and endothelial cells was lost beyond 7 days. The adult lung ex vivo culture system maintained necessary epithelial and interstitial cellular interactions in the alveolar wall without systemic circulatory influences. Future studies with this model may provide important insights in assessing the pathogenesis of many acute and chronic lung diseases and clarify existing controversies raised from in vitro and in vivo studies.

Animals↗

Antisense oligonucleotides for PDGF-B and its receptor inhibit mechanical strain-induced fetal lung cell growth.

An intermittent mechanical strain regimen, which simulates fetal breathing movements, has been shown to enhance DNA synthesis and cell division of fetal rat lung cells. The signaling mechanism through which the physical stimulus is transduced is unknown. Herein, we report that mechanical strain (5% elongation, 60 cycles/min) of fetal lung cells, cultured in a three-dimensional environment provided by Gelfoam sponges, increased the mRNA levels of platelet-derived growth factor B (PDGF-B) and beta-receptor (PDGF-beta-R) within 5 min of the onset of strain. Both PDGF-BB and PDGF-beta-R proteins were increased after a 24-h intermittent strain (15 min/h). Phosphorothioate antisense PDGF-B oligonucleotides (ON) at 15 microM abolished the strain-enhanced DNA synthesis and cell growth. Scrambled PDGF-B ON had no such effect. A neutralizing PDGF-BB antibody (10 micrograms/ml) also attenuated strain-induced DNA synthesis. Furthermore, the strain-induced stimulatory effect on DNA synthesis of fetal lung cells was blocked by tyrphostin 9 (1 microM), a PDGF receptor-associated tyrosine kinase inhibitor, but not by its inactive structural analogue tyrphostin 1. Antisense but not sense PDGF-beta-R ON (10 microM) also abrogated the strain-enhanced DNA synthesis. These results suggest that physical forces such as fetal breathing movements regulate fetal lung cell growth by controlling PDGF-B and PDGF-beta-R gene expression.

Animals↗

Effect of focal cooling of central chemosensitive areas on cerebral ischemic response.

The ventrolateral medullary surface (VMS) has been shown to have chemosensitive areas that can alter blood pressure and respiration. It has also been shown that lesions near the VMS can affect the intensity of the cerebral ischemic response (CIR). To determine which regions of the central chemosensitive areas of the ventral medullary surface contribute to the pressor response caused by cerebral ischemia, we used focal cooling of the caudal Loescheke's (CL), intermediate Schlaefke's (IS), and rostral Mitchell's (RM) areas of VMS during ischemia of the brain. Experiments were performed on 17 pentobarbital sodium-anesthetized, paralyzed, and artificially ventilated cats after denervation of the vagi and sinoaortic nerves. Bilateral occlusion of the external carotid and vertebral arteries resulted in a significant increase of arterial pressure (from 129 +/- 4 to 174 +/- 8 mmHg, P less than 0.01) and an increase in splanchnic sympathetic activity. However, heart rate and cervical sympathetic activities were not appreciably affected by cerebral ischemia. Bilateral cooling of the IS area to as low as 10 degrees C led to a decrease or disappearance of phrenic activity but failed to affect the magnitude of the pressor response. Also cooling of the CL and RM areas and application of Gelfoam pledgets soaked in lidocaine (4%) to these areas did not affect the CIR. However, covering the whole VMS with 0.2 ml of 4% lidocaine or cold cerebrospinal fluid (10 degrees C) abolished the ischemic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Modulation of motoneuron excitability by brain-derived neurotrophic factor.

The influence of neurotrophins on motoneuron survival and development has been well documented in cell cultures and neonates. In the present study, the role of brain-derived neurotrophic factor (BDNF) in the maintenance of motoneuron electrical properties was investigated. In adult male rats, BDNF- or saline-saturated gelfoam was inserted between the medial and lateral heads of the gastrocnemius muscles. After 5 days survival, in vivo intracellular recordings were obtained, and motoneuron biophysical properties were measured. In BDNF-treated rats, significant decreases in mean rheobase and in total cell capacitance of medial gastrocnemius motoneurons were observed. In addition, a concommitant increase in input resistance and decrease in membrane time constant were noted in BDNF-treated rats but were not statistically significant. No significant treatment effect was observed in motoneuron conduction velocity, action potential amplitude, equalizing time constant, electrotonic length, afterhyperpolarization amplitude and duration, and membrane potential sag during current injection. The observed changes in motoneuron rheobase and total cell capacitance suggest that application of BDNF produces an increase in motoneuron excitability coincident with a reduction in size. These data are discussed with respect to the possible role of BDNF as a muscle-derived trophic factor for the regulation of motoneuron excitability.

Animals↗

Interleukin-1beta regulates angiopoietin-1 expression in human endothelial cells.

Angiopoietin (Ang)-1 is an important regulator of endothelial cell (EC) survival and stabilization. Ang-1 exerts its biological effects by binding to the EC-specific tyrosine kinase receptor Tie-2, and initiates intracellular signaling in ECs. However, regulatory mechanisms for endothelial Ang-1 expression have not been completely elucidated. In this study, we investigated the effects of angiogenic cytokines and growth factors on Ang-1 expression in human umbilical vein ECs (HUVECs). Northern blot analysis was performed after HUVECs were exposed to interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, platelet-derived growth factor-BB, insulin-like growth factor-1, or vascular endothelial growth factor (VEGF). Both IL-1beta and tumor necrosis factor-alpha caused marked down-regulation of Ang-1 mRNA levels at 4 h with a further decrease observed at 24 h. Using signaling inhibitors, we identified the P38 pathway as the pathway that mediates IL-1beta down-regulation of Ang-1. Furthermore, treatment of cells with IL-1beta indirectly (via down-regulation of Ang-1) led to a decrease in Tie-2 autophosphorylation levels in HUVECs. We previously demonstrated that IL-1beta regulates VEGF expression in tumor cells. This observation was confirmed in ECs in the present study. Because pericytes play a role in regulating EC function, we also determined whether IL-1beta would also down-regulate Ang-1 in human vascular smooth muscle cells. Similar to our findings in HUVECs, we found that IL-1beta decreased Ang-1 expression in human vascular smooth muscle cells. Direct effects of IL-1beta on angiogenesis were investigated by use of an in vivo Gelfoam angiogenesis assay in which IL-1beta produced a significant increase in vessel counts (P = 0.0189). These results suggest that IL-1beta indirectly regulates angiogenesis by modulating the expression of Ang-1. IL-1beta may trigger a proangiogenic response by decreasing Ang-1 levels in ECs and pericytes and up-regulating VEGF in ECs and tumor cells.

Angiopoietin-1↗

Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine.

Angiogenesis, a key rate-limiting step in the growth and dissemination of malignant tumors, is regulated by the balance between positive and negative effectors. Recent studies indicate that the pleiotropic cytokine interleukin-6 (IL-6) may contribute to the vascularization of some tumors by disrupting the equilibrium between positive and negative angiogenic regulatory molecules. We determined whether IL-6 participates in the angiogenesis observed during the progression of ovarian carcinoma. We measured IL-6 production by human ovarian cancer cell lines in vitro and in vivo. Not all cell lines secreted IL-6 in vitro; however, when the cell lines were implanted into the peritoneal cavity of female nude mice, every line secreted IL-6. Most human ovarian carcinoma cell lines tested secreted significant levels of the soluble IL-6 receptor (sIL-6R). Endothelial cell lines established from the ovary and mesentery of female H-2K(b)-tsA58 mice were tested for response to IL-6. Both endothelial cell lines expressed the IL-6R and their stimulation with the exogenous ligand significantly enhanced cell migration and activated the downstream signaling molecule signal transducers and activators of transcription 3. Dual immunohistochemical staining for IL-6R and CD31 revealed IL-6R expression on human endothelial cells within normal ovary and carcinoma specimens. Gelfoam sponges containing 0.4% agarose and IL-6 or basic fibroblast growth factor and implanted into the subcutis of BALB/c mice were vascularized to the same extent. Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease.

Animals↗

Origin of innervation in the feline ophthalmic artery.

In this study, we investigate the innervation to the feline ophthalmic artery by the horseradish peroxidase (HRP) tracing method. Five adult cats with body weights ranging between 2.0 and 3.0 kg were used. Under microscopic dissection, the ophthalmic artery was identified and isolated. A gelfoam (Upjohn Co.), 1 x 3 mm in size, containing 0.1 ml of HRP was applied to the prepared artery segment for 2 h. The cat was sacrificed 3 days later. The trigeminal, stellate, superior cervical, middle cervical and nodal ganglia, and oculomotor, trochlear and abducens nuclei were removed, sectioned and stained for HRP-positive cells. HRP-labeled neurons were found in the ipsilateral trigeminal (TRG) and superior cervical ganglia (SCG). The middle cervical, stellate, Edinger-Westphal, trochlear and abducens nuclei were all deemed negative for HRP-labeled cells. In the TRG, HRP-labeled neurons ranged from 21 to 250 (mean +/- SE = 93.8 +/- 42.5/ganglion). The labeled neurons were distributed primarily in the ophthalmic branch. In the SCG, the HRP-labeled neurons were distributed evenly in the ganglion, ranging from 6 to 180 (mean +/- SE = 91.6 +/- 31.5/ganglion). Two additional cats having received a sham operation revealed a negative finding. The feline ophthalmic artery is innervated by the ipsilateral TRG and SCG. Such innervation may play a role in regulating blood flow to the optic nerve.

Animals↗

Current issues in cochlear gene transfer.

Cochlear gene therapy represents a potential experimental and therapeutic tool to understand and treat deafness. In designing cochlear gene transfer studies, the chosen route of delivery of vector and the choice of gene therapy vector have to be given careful consideration. Several different routes of delivery have been tested in our laboratory including infusion with osmotic minipump, direct microinjection into the cochlea and application of vector-transgene complex-soaked Gelfoam((R)) into the direct contact with the round window membrane. In our experience, the latter is an easy, safe and atraumatic technique to deliver gene into the cochlea. A number of different gene transfer vectors have been investigated in vivo for their efficacy, utility and safety in intracochlear gene transfer. Vectors successfully studied include cationic liposomes, adeno-associated virus, adenovirus, lentivirus, herpes simplex virus and vaccinia virus. While the viral vectors offer clear experimental advantages, human gene therapy in the future will likely utilize nonviral vectors to maximize safety. Finally, safety issues regarding dissemination of gene transfer vectors beyond the target cochlea will need to be adequately addressed.

Animals↗

Synaptophysin immunohistochemistry during vestibular hair cell recovery after gentamicin treatment.

In the present study, morphometric and immunohistochemical techniques were used to evaluate the degree of synaptic recovery in the chinchilla crista sensory epithelia during various post-gentamicin-treatment periods of hair cell loss and recovery. For this purpose, two groups of animals were treated with Gelfoam pellets impregnated with 50 micro g of gentamicin implanted in the perilymphatic space within the otic capsule of the superior semicircular canal. Animals were sacrificed 1, 2 and 4 weeks after treatment. The degree of synaptic reinnervation was evaluated in the horizontal crista of the first group of animals using immunohistochemical techniques and antibodies against synaptophysin, a marker for synaptic reinnervation and synaptogenesis. Quantification of immunoreactivity in this group was made in the mid-region of the crista using the NIH 'Image' program. The second group of animals was used for quantification of the number of hair cells and supporting cells in the horizontal crista. In the normal sensory epithelium, synaptophysin immunoreactivity was found in the areas corresponding to the known distribution of afferent and efferent nerve terminals. Immunoreactivity was predominantly located within the afferent calyces of type I hair cells. No immunoreactivity was found in the supporting cells. Seven days after treatment there was a significant loss of hair cells and synaptophysin-stained area (SSA). In the mid-region of the crista the loss of synaptophysin immunoreactivity was quantitatively the greatest within the central zone of this region (93%) while the loss of hair cells was the smallest. These results suggest that afferent and efferent nerve terminals were also severely affected by the ototoxic treatment. Four weeks after treatment corresponding to the end of the recovery phase of gentamicin ototoxicity, there was a proportional increase in the number of hair cells and of the degree of SSA in the mid-region of the crista. The number of hair cells recovered to 58% with a recovery of SSA to 54% of normal. These results suggest that a greater fraction of synaptophysin expression within the sensory epithelium depends on the presence of afferent calyceal endings, which are greatly affected by gentamicin. Also, these results demonstrate a significant level of reinnervation of the newly regenerated hair cells, forecasting the potential for functionality of the regenerated hair cells.

Animals↗

Antiangiogenic effect of ZD1839 against murine renal cell carcinoma (RENCA) in an orthotopic mouse model.

INTRODUCTION: ZD1839 (Iressa) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We evaluated the antitumor and antiangiogenesis activities of ZD1839 in a murine renal cell carcinoma (RENCA) model. MATERIALS AND METHODS: The effect of ZD1839 on the cellular proliferation of RENCA cells in vitro was measured by colorimetric assay. For the in vivo studies, RENCA cells were adsorbed in Gelfoam and implanted into BALB/cJ mouse parenchyma with an agarose bar. Mice were treated with ZD1839 (40 mg/kg/day s.c.), genistein or saline for 14 days. Western blot analysis was performed to observe EGFR expression in RENCA cells and tumor tissues. Microvessel density (MVD) was quantified by immunostaining for factor VIII-related antigens and VEGF level was assayed by ELISA. RESULTS: ZD1839 showed a dose-dependent inhibition of RENCA cellular proliferation. ZD1839 treatment resulted in a marked decrease in tumor growth compared with saline treatment. The MVD and VEGF in the RENCA tumors were decreased significantly by ZD1839 (p<0.01 and p>0.05, respectively). Genistein also suppressed tumor growth and decreased MVD and VEGF level, but the efficacies were less than with ZD1839. CONCLUSION: The suppressive activity of ZD1839 on RENCA tumor growth was accompanied by decreases in the MVD and VEGF production. These results suggest that the antitumor effect of ZD1839 in a RENCA model is mediated partially by the inhibition of tumor angiogenesis.

Animals↗

Urgent superselective segmental renal artery embolization in the treatment of life-threatening renal hemorrhage.

INTRODUCTION: Renal hemorrhage is a major life-threatening condition that can be caused by trauma, operation, biopsy, as well as sudden spontaneous rupture of renal tumors or aneurysms. We report our experience with superselective segmental renal artery catheterization and embolization as therapeutic options for such cases. PATIENTS AND METHODS: Over the last 8 years, 28 patients with severe renal hemorrhage were admitted for evaluation and possible further treatment. Twenty of them had a history of previous biopsy (6 of them one of a transplanted kidney), 1 patient had a recent percutaneous nephrostomy, 4 patients presented with renal mass ruptures (2 patients renal cell carcinoma, 1 patient angiomyolipoma, 1 patient hemorrhagic cysts), 1 patient had rupture of a renal aneurysm during delivery, 1 patient suffered bleeding after partial nephrectomy, and 1 patient was hospitalized after a car accident. They all presented with clinical signs of hemodynamic instability. Angiographic investigation of the kidneys preceded further intervention in all cases. 26 out of the 28 patients underwent superselective embolization of the specific bleeding vessel with the use of microcoils and/or Gelfoam particles. RESULTS: All patients treated by superselective segmental renal artery embolization had a successful outcome, including a steady renal function and a stable clinical course. No complications occurred. CONCLUSION: Superselective segmental renal artery catheterization and embolization is a safe and efficient method for the treatment of patients with severe renal hemorrhage, preserving healthy renal parenchyma and renal function.

Adolescent↗