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Results for “Infusions, Intralesional”

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At least 73 records · Page 4Linked to original sources
PubMed2006

Tumor-selective gene expression in a hepatic metastasis model after locoregional delivery of a replication-competent retrovirus vector.

PURPOSE: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been tested previously, particularly in an immunocompetent tumor model. EXPERIMENTAL DESIGN: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via locoregional infusion in a hepatic metastasis model of colorectal cancer. RESULTS: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro, with transduction levels reaching >90% in <12 days after virus inoculation at multiplicities of infection of 0.01 to 0.1. In vivo, infusion of RCR supernatant into the portal circulation resulted in progressive and significant transduction of multifocal intrahepatic CT26 tumors in syngeneic mice, averaging about 30% but with up to 60% transduction in some tumors within 4 weeks. However, immunohistochemistry and quantitative PCR analysis showed no evidence of RCR spread to adjacent normal liver or to any other normal tissues. CONCLUSIONS: Our results thus show that locoregional infusion of RCR vectors can be used to deliver therapeutic genes selectively to tumor cells in the liver while sparing normal hepatocytes and without dissemination to extrahepatic normal tissues.

Adenoviridae↗
PubMed2003

Role of p44/p42 MAP kinase in the age-dependent increase in vascular smooth muscle cell proliferation and neointimal formation.

OBJECTIVE: Age-dependent increase in vascular smooth muscle cell (VSMC) proliferation is thought to contribute to the pathology of atherosclerotic diseases. In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) on VSMC proliferation and neointimal formation in the context of aging. METHODS AND RESULTS: VSMCs were isolated from the aorta of young and old rabbits. The proliferative index after serum stimulation was significantly increased in old versus young VSMCs. This was associated with a significant and specific age-dependent increase in p44/p42 MAPK activation. Treatment with MEK inhibitor PD98059 successfully inhibited p44/p42 MAPK activities and VSMC proliferation. These results were confirmed in vivo using a model of balloon injury in rabbit iliac arteries. p44/p42 MAPK activities were rapidly induced by angioplasty in young and old animals. However, the levels of p44/p42 MAPK activities achieved in arteries of old rabbits were significantly higher than those of young rabbits. This was associated with a higher cellular proliferative index and a significant increase in neointimal formation in old animals. Local delivery of PD98059 in old rabbits successfully inhibited p44/p42 MAPK activities after angioplasty, which led to a significant reduction in cellular proliferation and neointimal formation in treated animals. CONCLUSIONS: Our study suggests for the first time that increased p44/p42 MAPK activation contributes to augmented VSMC proliferation and neointimal formation with aging. p44/p42 MAPK inhibition could represent a novel therapeutic avenue against atherosclerotic diseases.

Age Factors↗
PubMed2001

Pulmonary candidiasis caused by Candida albicans in a Greek tortoise (Testudo graeca) and treatment with intrapulmonary amphotericin B.

An adult female Greek tortoise (Testudo graeca) presented with dyspnea, lethargy, and anorexia. Severe unilateral pulmonary candidiasis was diagnosed and confirmed by histologic and microbiologic evaluations. Initial treatment with ketoconazole resulted in plasma elevations of aspartate aminotransferase, lactate dehydrogenase, and bile acids consistent with imidazole-induced hepatotoxicity. Plasma chemistry abnormalities resolved upon withdrawal of the drug. Temporary osteotomy permitted access to the diseased lung and facilitated intrapulmonary catheterization. Intrapulmonary amphotericin B therapy at 0.1 mg/kg s.i.d. for 34 days proved to be both safe and effective in this case.

Amphotericin B↗
PubMed2006

Treatment with continuous intrasynovial antimicrobial infusion for septic synovitis in horses: 31 cases (2000-2003).

OBJECTIVE-To determine clinical findings, complications, and outcome of septic synovitis in which continuous intrasynovial antimicrobial infusion (CIAI) was used for local antimicrobial delivery in horses. DESIGN-Retrospective case series. Animals-22 adult horses and 9 foals (horses<1 year of age). PROCEDURES-Records of horses with septic synovitis that had CIAI during treatment were reviewed. The association between clinical variables and whether horses performed their intended use following treatment was determined. RESULTS-42 synovial cavities were treated via CIAI. Twenty-nine cases were chronic (>7 days) in nature, 15 had been refractory to standard treatments, and 13 synovial infections had associated osteomyelitis. Mean duration from infection to initiation of CIAI was 19.7 days, and mean duration of CIAI was 6.1 days. Temporary discharge from the catheter site at the time of removal was evident in 8 horses. Dysfunction of the infusion system occurred in 2 horses and was corrected during the course of treatment. No long-term complications were reported. Thirty-nine (93%) synovial infections in 29 (94%) horses were resolved. Twenty adult horses and 8 foals were discharged from the hospital, and 19 of 24 horses with long-term follow-up performed their intended use. CONCLUSIONS AND CLINICAL RELEVANCE-CIAI was a useful adjunctive treatment for septic synovitis and allowed intrasynovial antimicrobial delivery into a variety of synovial cavities.

Animals↗
PubMed2006

Evaluation of a balloon constant rate infusion system for treatment of septic arthritis, septic tenosynovitis, and contaminated synovial wounds: 23 cases (2002-2005).

OBJECTIVE-To determine clinical findings and outcome in horses treated by means of a balloon constant rate infusion system. DESIGN-Retrospective case series. ANIMALS-23 horses. PROCEDURES-Medical records of horses examined at The Ohio State University veterinary teaching hospital from 2002 to 2005 that had septic arthritis, septic tenosynovitis, or penetration of a synovial structure and in which treatment involved a balloon constant rate infusion system were searched. Information pertaining to signalment, history, physical examination findings, clinicopathologic data, treatment, and duration of hospitalization was recorded. RESULTS-Mean+/- SD duration of hospitalization was 11.5+/-5.26 days. No correlation between duration of clinical signs and duration of hospitalization or duration of infusion pump use was detected, but correlations between WBC count and duration of hospitalization and WBC and duration of infusion-pump use were observed. All horses survived to discharge. Follow-up information was obtained on 17 horses, 16 of which were alive at the time of follow-up. Twelve of 13 horses for which followup information was available for at least 5 months were alive 5 months or longer after discharge. Thirteen of the 16 horses alive at follow-up were reported by owners as not lame, whereas the remaining 3 were mildly lame or intermittently moderately lame or had developed angular limb deformity in the contralateral limb. CONCLUSIONS AND CLINICAL RELEVANCE-Balloon constant rate infusion systems may be used effectively in treatment of septic arthritis, septic tenosynovitis, and contaminated synovial wounds. Clinical response and long-term outcome appeared to be comparable to results obtained with other techniques.

Animals↗
PubMed2003

Convection-enhanced delivery in clinical trials.

The poor prognosis associated with the current management of malignant gliomas has led investigators to develop alternative treatments such as targeted toxin therapy. The optimal method for administering these agents is under development but appears to be convection-enhanced delivery (CED). The direct intratumoral infusion of targeted toxins was first performed in nude mouse flank tumor models of human malignant glioma. After the demonstration of in vivo efficacy, these potent cytotoxic compounds were tested in Phase I and Phase II clinical trials. Using a high-flow microinfusion technique, volumes of up to 180 ml were infused by CED through catheters placed directly into brain tumors. Minor systemic toxicity was seen in the form of hepatic enzyme elevation. Neural toxicity manifested as seizure activity and hemiparesis resulted from peritumoral edema that followed the completion of the infusion. Peritumoral toxicity was believed to be more related to the concentration of the infused immunotoxin than to the infusion volume. In approximately half of patients treated with CED a stable disease course, a partial response, or a complete response was demonstrated in some clinical trials. Targeted toxin therapy has clinical efficacy in patients with malignant gliomas. Convection-enhanced delivery appears to represent an effective method for administering these agents in patients with malignant brain tumors.

Adolescent↗
PubMed2004

A realistic brain tissue phantom for intraparenchymal infusion studies.

OBJECT: The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery. METHODS: Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 microl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] approximately 690) and gadodiamide (MW approximately 573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10-20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution. CONCLUSIONS: Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

Animals↗
PubMed2005

Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma.

OBJECT: Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. METHODS: Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL1 3-PE38QQR, patients were followed up without instituting new antitumor therapy. CONCLUSIONS: As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

ADP Ribose Transferases↗
PubMed2003

Treatment of inoperable pancreatic carcinoma using a cell-based local chemotherapy: results of a phase I/II clinical trial.

BACKGROUND: The use of ifosfamide for conventional chemotherapy of pancreatic tumors is limited by systemic toxicity caused, in part, by its activation by liver-specific cytochrome enzymes and the subsequent systemic distribution of metabolites. Activation at the tumor site, on the other hand, should reduce systemic toxicity and provide more effective local therapeutic concentrations. The results of a phase I/II open, single-arm clinical trial of local intratumor activation of ifosfamide are presented. METHODS: Treatment involved angiographic implantation of encapsulated allogeneic cells, genetically modified to overexpress the enzyme cytochrome P-450 2B1, into the vasculature leading to the tumor. The cells are protected from immune rejection and locally activate systemically administered ifosfamide to antitumor metabolites. RESULTS: Of the 14 patients treated, 4 showed tumor regression and the other 10 patients showed stable disease, i.e., no further tumor growth. The median survival of the patient cohort was twice that of the control group. The 1-year survival was 36%, i.e., threefold that of the control group (twice that reported for gemcitabine). As far as clinical benefit was concerned, 4 of the 13 evaluable patients reported improvements in pain assessment at the last observation, with 6 remaining unchanged (4 of these experienced no pain) and 3 patients experiencing slightly greater pain. Using a worst case scenario, 50% experienced a clinical benefit, which rose to 71% of patients if a best case scenario was applied. The best predictor of clinical benefit was lack of pain, whereas significant weight loss possibly predicts a poor clinical benefit. CONCLUSIONS: The data obtained from this phase I/II clinical trial are promising and suggest that further clinical trials are warranted.

Adenocarcinoma↗
PubMed2003

A surgical technique for safely placing a drug delivery catheter into the pons of primates: preliminary results of carboplatin infusion.

OBJECTIVE: We sought to develop a neurosurgical procedure to access the pons with a drug delivery device for chronic therapy and collect preliminary data on the toxicity of direct infusions of carboplatin in primates. METHODS: We made midline incisions on five cynomolgus monkeys, identified the inion, made a burr hole 2.5 cm below the inion, and inserted a catheter through the cerebellum into the roof of the pons. Pumps that infused saline for 90 days or carboplatin solutions for 30 to 35 days at 10 microl/d were placed subcutaneously in the low cervical/high thoracic region. Monkeys were assessed by computed tomography and magnetic resonance imaging, laboratory studies, daily neurological observation, postmortem examinations, and histopathology. RESULTS: Monkeys infused with saline and 82 microg of carboplatin remained neurologically intact throughout the infusion periods. Serial imaging showed that the catheter tip was in the pons and revealed no evidence of hemorrhage, edema, or migration. Two monkeys infused with up to 850 microg of carboplatin showed hyperintense magnetic resonance imaging signals at Days 15 and 18 and neurological deficits at approximately Week 3. Platinum levels greater than 10 ng/mg tissue were detected over a distance of 1 cm in tissue slices. Histopathology demonstrated significant tissue necrosis around the tip of the catheter. CONCLUSION: The pons of monkeys is safely accessed with a catheter for drug delivery by using a posterior midline approach. Clinical observations, radiographic imaging, and laboratory tests of animals infused with saline for 3 months or 0.26 mg/ml of carboplatin for 1 month were unremarkable. Neurotoxicity was seen with dose levels of 2.6 mg/ml of drug for 1 month. This procedure offers opportunities for examining the toxicity of brainstem antitumor therapy in primates.

Animals↗
PubMed2003

Selective hippocampal lesions do not increase adrenocortical activity.

It has been proposed that the hippocampus exerts a tonic inhibitory influence on the hypothalamic-pituitary-adrenal (HPA) stress axis. This claim rests, in particular, on the upregulation of corticosterone secretion and other measures of HPA activity after nonselective lesions of the hippocampal formation. We measured plasma corticosterone concentrations after selective neurotoxic damage to the hippocampus and the subiculum in rats. Concentrations were estimated during rest in the rat's home cage and at several time points after varying degrees of stress. Lesions of the hippocampus did not increase the concentration of corticosterone relative to control rats in any condition. Temporary inactivation of the hippocampus or the ventral subiculum by infusion of the GABAA receptor agonist muscimol also failed to induce hypersecretion, although hippocampal infusions did impair spatial memory. These results suggest that the hippocampus is not necessary for tonic inhibition of adrenocortical activity and imply that the HPA axis receives efficient negative feedback inhibition from other brain systems too.

Adrenal Cortex↗
PubMed2003

[Current diagnostics and therapy of focal liver lesions].

Increasing number of tumorous diseases, the extension of Hepatitis B and C infection, and growing frequency of cirrhotic patients have emphasized the importance of treatment of primary and secondary liver tumors. On the other hand the development in imaging procedures have been resulted in diagnosis of different focal liver lesion with unknown origin, and had to decide whether the patient should be treated or only observation is indicated. First the author gives a review about the most frequent focal liver lesions and their therapeutic consequence. He discusses in detail the indication, risk factors, technics, contraindications and complications of surgical interventions. The possibilities and results of ablative and minimal invasive procedures are analysed, and the author underlines the necessity of combined therapy. The results of different therapeutic modalities are presented according to literary data, and the author summarizes the therapeutic tactics accepted today.

Antineoplastic Agents↗
PubMed2004

[Intratympanic dexamethasone injections for intractable Meniere's disease].

OBJECTIVE: To investigate the efficacy of intratympanic dexamethasone injections (IDI) for 15 patients with intractable Meniere's disease (MD). METHOD: Dexamethasone (2.5 mg/0.5 ml) was injected into the middle ear and followed by a second injection 15 minutes later. The injection was repeated the next day and weekly for 3 weeks. Total dose of dexamethasone was 17.5 mg. RESULT: The 15 patients were followed up for 18 months (average). Complete relief of vertigo was maintained in 10 cases, improved in 2 case, injection wos repeated 3 patients with recurrent vertigo resulted in control of vertigo. Tinnitus disappeared in 5 cases, reduced in 5 cases, unchanged in 5 cases. Hearing was improved in 10 cases, unchanged in 5 cases. CONCLUSION: IDI is effective for intractable MD. The benefits of IDI are avoidance of systemic use of steroids, lower cost, easy application. IDI can be used as an initial surgical treatment for persistent vertigo in MD and indicated for bilateral MD.

Adult↗
PubMed2005

[Intrathoracic infusion with a combination of low-dose minocycline, OK-432 and cisplatin for malignant pleural effusion].

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.

Adenocarcinoma↗
PubMedDate not supplied

Effect of the intraperitoneal paclitaxel on the healing of colonic anastomoses.

The effect of the antiangiogenic agent paclitaxel on the healing of colonic anastomoses was studied in a rat model. Ninety-six rats underwent end-to-end colonic anastomoses, and healing was evaluated by measuring bursting pressure, hydroxyproline content, and number of newly formed vessels. The rats with end-to-end anastomoses were randomized into control and study groups (n = 48). The rats in the control group were administrated 5 ml physiologic saline intraperitoneally, and those in the study group were given 4.5 mg/kg paclitaxel in 5 ml physiologic saline intraperitoneally. One-half of the rats in both groups were killed on day 4, and the other half were killed on day 7 after surgery with high doses of ether anesthesia. There were no deaths. No detectable improvement in anastomoses bursting pressure was observed in the paclitaxel group on day 4 after surgery. On postoperative day 7, a statistically significant difference was found between the groups (P < 0.05). On day 4 after surgery, there was no statistically significant difference in hydroxyproline levels and vessel density between the two groups (P > 0.05; hydroxyproline: 26.25 versus 16 microg/mg tissue; vessel contents: 110.8 versus 118.2 vessels/x 100 fields for control and study groups, respectively). On postoperative day 7, a significant difference was detected between the two groups (P < 0.0001; hydroxyproline: 40.5 versus 9.6 microg/mg tissue; P < 0.05; vessel contents: 105 versus 85.3 vessels/x 100 fields for control and study groups, respectively). Neovascularization and hydroxyproline levels in rats receiving paclitaxel were significantly reduced on postoperative day 7 (P < 0.05 and P < 0.0001, respectively). These findings suggest that the antiangiogenic efficiency of paclitaxel, and thus, negative impact on wound healing, is more prominent on postoperative day 7. Experimentally, paclitaxel may inhibit and delay healing of colonic anastomoses.

Anastomosis, Surgical↗