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Results for “Infusions, Intralesional”

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PubMed1995

[Therapy of malignant hepatic tumors using percutaneous hot saline injections. Feasibility study and preliminary results].

PURPOSE: To investigate the feasibility and the results of percutaneous hot saline injection therapy (PSIT) of liver tumors. MATERIAL AND METHODS: Eight patients with hepatocellular carcinoma (11 nodules), 1 with cholangiocarcinoma and 1 with a metastasis from colon cancer underwent PSIT. The patients were selected according to variable criteria; thus, each patient was considered apart. A boiling saline solution was injected into the hepatic lesions through a needle like those commonly used for percutaneous ethanol injection (PEI). The results were assessed with US, CT, angiography, the measurement of tumor marker levels, the histopathologic examination of needle biopsy material, resected specimens, explanted liver material and follow-up. RESULTS: PSIT was more easily performed and altogether better accepted than PEI; in particular, pain immediately regressed upon infusion interruption. For this reason and for the atoxicity of the injected liquid, relatively large lesions could be treated with a greater volume per session and fewer sessions than with PEI. Treatment outcome was positive in all patients, except for the cholangiocarcinoma patient who required surgery. The only major complication was moderate peritoneal bleeding in a patient with severe coagulopathy. CONCLUSION: PSIT can be considered a useful tool for the local treatment of hepatic tumors. Its systematic use to treat hepatocellular carcinoma must be proceeded by further comparative studies with PEI.

Aged↗

PubMed2000

Controlling malignant pericardial effusion by intrapericardial carboplatin administration in patients with primary non-small-cell lung cancer.

Malignant pericarditis, when associated with massive pericardial effusion, presents a critical condition in lung cancer patients. Because this condition often arises in terminally ill patients, intensive therapy such as multi-drug combination chemotherapy is rarely appropriate. This study evaluated the clinical relevance of intrapericardial administration of carboplatin for controlling malignant pericardial effusions associated with non-small-cell lung carcinoma (NSCLC). The method used for 10 eligible patients consisted of draining the pericardial effusion and infusing 300 mg/body of carboplatin in 50 ml of saline through an in-place catheter into the pericardial space and clamping the catheter for 40 min. Nine of the 10 patients showed satisfactory results, and 8 experienced complete regression of the effusion. No major or minor adverse effects were observed. Pharmacokinetics analysis revealed that the concentration of free platinum in the pericardial fluid was very high while that of total platinum in the circulating plasma was very low, assuring the usefulness of the intrapericardial instillation of carboplatin in terminally ill patients for controlling malignant pericardial effusion when the systemic delivery of cytotoxic agents is inappropriate.

Adenocarcinoma↗

PubMed2001

[A new development in interventional radiology for hepatocellular carcinoma].

In Japan, interventional radiology (IVR) treatments such as transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), and intraarterial infusion chemotherapy play an important role in the treatment of hepatocellular carcinoma because of the associated cirrhosis (impairment of liver function) and occasional multicentricity. With progress in catheters, embolic materials, and imaging equipment such as the so-called "IVR-CT", superselective TAE and precise evaluation of tumor lesions has become feasible. However, the impact of TAE on survival in patients with hepatocellular carcinoma remains to be determined because no survival benefit was seen in four of five randomized controlled trials (RCTs) in Europe and Eastern countries, in which TAE was compared with no treatment (3 trials), i.v. 5-fluorouracil (1 trial), or tamoxifen (1 trial). To resolve questions arising from these results, a fair number of trials, particularly RCTs are needed in Japan.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Evaluation of intratumoral administration of tumor necrosis factor-alpha in patients with malignant glioma.

BACKGROUND: This study assessed safety and efficacy for intratumoral administration of tumor necrosis factor-a (TNF-SAM2) into the post-operative tumor cavity through an Ommaya reservoir for patients with malignant glioma. MATERIALS AND METHODS: Seven patients with malignant glioma, comprising 3 cases with glioblastoma multiforme (GBM), 3 cases with anaplastic astrocytoma (AA) and 1 case with malignant ependymoma (ME) were included in the study. All patients were pathologically diagnosed and initially treated with adjuvant therapy (radiation and/or ranimustine and/or systemic TNF-SAM2 infusion) following surgical resection. TNF-SAM2 was administrated into the post-operative tumor cavity through a reservoir at a concentration of 1x10(4) U/body when recurrence was detected, or as initial induction therapy concomitant with radiotherapy. RESULTS: Partial response to this regional immunotherapy was seen in 4 out of 7 patients, and 1 patient with GBM has remained clinically stable for >184 weeks without tumor progression. With AA, 2 cases appeared to display slowed advance and longer times to tumor recurrence or regrowth. No serious adverse effects, such as brain edema, hemorrhage or seizure were observed, nor systemic toxicities. CONCLUSION: Local immunotherapy with TNF-SAM2 may safely contribute to therapeutic efficacy in some patients with malignant glioma.

Adult↗

PubMed1989

[A case of sigmoid carcinoma successfully treated with endoscopic topical infusion of OK-432 and UFT oral treatment].

A 78-year-old man had a tumor of Borrmann type II affecting about one third the circumference of sigmoid colon, which was diagnosed as well-differentiated adenocarcinoma from biopsy. Although surgical intervention was recommended and the radical operation seemed possible from preoperative examination, the patient first refused it. Of necessity, systemic administration (s.c) and single endoscopic topical infusion of OK-432 and oral treatment of UFT were performed for 1 month. Since the patient agreed to receive an operation later, sigmoidectomy and lymph node dissection (R 2) were performed, resulting in the disappearance of tumor cells histologically. One week before endoscopic infusion, oral UFT and subcutaneous OK-432 were initiated. Although no macroscopic change was found during the topical infusion as compared with the time of first examination, the bulging disappeared, showing a polypoid change and IIc-like findings after 3 weeks. The operation was performed after an additional week, after which a benign tumor was found macroscopically and the disappearance of tumor cells histologically. Although many reports have dealt with the effect of endoscopic treatment for gastric carcinoma, there have been fewer reports describing the endoscopic treatment performed in patients with colon carcinoma, making it difficult to evaluate its therapeutic effect. However, this endoscopic therapy was suggested to be capable of becoming a useful treatment for inoperable colon carcinoma from the present case, whereas chemotherapy was found to have almost no effect on colon carcinoma in general.

Adenocarcinoma↗

PubMed1998

5-[125I]iodo-2'-deoxyuridine in the radiotherapy of brain tumors in rats.

UNLABELLED: Glial neoplasms of the human central nervous system have defied treatment, in part because of the limited selectivity of available cytotoxic agents. The thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter 125I (125IUdR) is highly toxic to dividing cells when it is deoxyribonucleic acid incorporated, but it is relatively innocuous when located outside the nucleus. Previous studies have shown that 125IUdR has significant antineoplastic potential against mammalian cells in vitro and direct administration of 125IUdR is effective therapy for ovarian ascites tumors in mice and neoplastic meningitis in rats. Studies using external gamma imaging and autoradiography have also shown that direct intratumoral administration of 123IUdR/125IUdR into intracerebral 9L gliosarcomas in rats results in selective uptake of the radionuclide into tumor cells. Based on these encouraging results, we have evaluated the therapeutic potential of 125IUdR in rats bearing intracerebral 9L gliosarcomas. METHODS: Iodine-125-IUdR was infused intracerebrally over a 2-day period into rats bearing 1-day-old 9L tumors and over a 6-day period into animals with 9-day-old 9L tumors; equimolar concentrations of 127IUdR were infused into control animals. Tumor growth was monitored by contrast-enhanced 1H MRI and animal survival was followed over time. RESULTS: Intracerebral tumors (3-7 mm) were readily detected by MRI. Tumor-bearing rats treated with 127IUdR succumbed within 17-24 days, whereas tumor-bearing animals treated with 125IUdR survived significantly longer, and 10%-20% of the animals were cured of tumors. CONCLUSION: These data substantiate the antineoplastic potential of 5-[125I]iodo-2'-deoxyuridine and indicate that it may be a useful agent for the therapy of solid tumors that are accessible to direct radiopharmaceutical administration.

Animals↗

PubMed2004

Percutaneous ablation of VX2 carcinoma-induced liver tumors with use of ethanol versus acetic acid: pilot study in a rabbit model.

PURPOSE: Acetic acid has been employed as a chemical ablation agent for liver tumors because of its superior diffusion characteristics compared with ethanol and the resulting requirement for smaller volumes and fewer injection sessions. Early tissue changes were compared after injection of acetic acid and ethanol in a rabbit model of hepatocellular carcinoma. MATERIALS AND METHODS: VX2 tumors were created in the left lobe of the liver in 11 male New Zealand White rabbits. Each animal underwent a midline minilaparotomy to expose the tumor-laden left lobe, followed by injection of 1.0 mL of 100% ethanol (n = 5) or 50% acetic acid (n = 6) with use of a 20-gauge infusion needle. Animals were killed 30 minutes after surgery; explanted livers were sectioned and examined for gross and microscopic changes. RESULTS: Injection of each agent produced rapid diffusion through tumor and surrounding hepatic parenchyma, with immediate protein precipitation manifested by blanching as a result of coagulation effect. The sizes of coagulation zones, expressed as mean products of the maximum perpendicular diameters of tumoral diffusion, were 13.0 cm(2) +/- 9.4 and 1.3 cm(2) +/- 1.8 for acetic acid and ethanol, respectively (P =.049). No differences in histologic changes were seen between agents. CONCLUSIONS: In this animal model, acetic acid produced significantly larger zones of tumor coagulation compared with ethanol when injected into VX2 carcinoma in equal volumes. Further evaluation is necessary before these findings can be extrapolated to a clinical setting.

Acetic Acid↗

PubMed2002

Sources of intra-oesophageal nitric oxide production following intraluminal acid exposure.

BACKGROUND: The aim of the present study was to assess luminal nitric oxide (NO) levels in the oesophagus during baseline and acidic conditions and to clarify the sources of such oesophageal NO formation. METHODS: Healthy volunteers received an intra-oesophageal infusion of either HCl (100 mM) or NaCl (50 mM) on two separate study days. After a low nitrate diet, nitrate load or no dietary restrictions/pretreatment, direct intraluminal measurements of NO formation were performed using a tonometric technique. Endoscopy was performed and mucosal biopsies were taken and analysed by means of immunohistochemistry, Western blot and RT-PCR. RESULTS: No intra-oesophageal NO was detected during baseline conditions with pH neutrality. During the infusion of HCI the NO levels rose dramatically to around 12000 ppb. This high rate of NO formation fell by 95% following deviation of saliva. NO formation after an acute nitrate load was almost doubled during acid perfusion compared to control. Immunohistochemistry demonstrated distinct staining for iNOS in the oesophageal squamous epithelial cells, and Western blot and RT-PCR confirmed the presence of iNOS. CONCLUSION: Two sources exist for intra-oesophageal NO formation, both dependent on the luminal acidity: 1) chemical reduction of salivary nitrite, a mechanism related to dietary intake of nitrate, and 2) NO formation within the oesophageal mucosal epithelium by enzymatic degradation of L-arginine. In the latter case, the NO synthase has antigenic characteristics, indicating the inducible isoform, although a functional behaviour suggests an unconventional subtype.

Adolescent↗

PubMed1998

Tumor devascularization by intratumoral ethanol injection during surgery. Technical note.

Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection. Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.

Blood Loss, Surgical↗

PubMed1991

Dissolution of cholesterol gall stones using methyltertbutyl ether: a safe effective treatment.

Methyltertbutyl ether (MTBE) administered by percutaneous transhepatic catheter rapidly dissolves radiolucent cholesterol gall bladder stones. However, complete dissolution and clearance of non-cholesterol debris is essential to prevent recurrence. In this study we analysed 25 consecutive patients with reference to efficacy and recurrence based on the presence or absence of non-cholesterol stone fragments after dissolution. Placement of the catheter was successful in 24 patients, one patient requiring cholecystectomy for bile peritonitis. MTBE was infused and aspirated continuously, four to six cycles per minute, resulting in rapid stone dissolution (median six hours; range 4-23 hours for solitary stones and median seven hours, range 4-30 hours for multiple stones). In 18 patients who had complete dissolution, four (22%) had recurrent stones within six to 18 months. Five patients had residual debris which failed to clear completely despite bile acid treatment. One patient with an incomplete rim of calcium in a large stone did not respond to MTBE treatment. A further patient required cholecystectomy for symptomatic recurrence. There were no serious side effects observed. MTBE treatment is a rapid, safe, and effective treatment for patients who refuse surgery or who for medical reasons cannot undergo cholecystectomy. The results of this study confirm that complete dissolution of all fragments is essential and may prevent recurrence.

Adult↗

PubMedDate not supplied

Hepatic chemoembolization: clinical and experimental correlation.

Chemoembolization has become the preferred treatment for patients with inoperable, hypervascular hepatic malignancies in the Far East, but controversial elsewhere. In vivo microscopy in addition to other experimental procedures are used in this presentation to better understand the mechanisms involved in chemoembolization. In chemoembolization Lipiodol acts as a contrast material, a vehicle for chemotherapy and an embolic agent. Although not optimal, Lipiodol injected into the hepatic artery, traverses the peribiliary plexus to the portal veins resulting in a dual embolization. Chemoembolization creates ischemia, slows arterial flow and increases the contact time between the infusate and the neoplasms, increasing the tumor cell kill. However, the vascular occlusion also produces infarction and fibrosis compounding the already existing cirrhosis frequently associated with hepatocellular carcinoma. Lipiodol/ethanol (3:1) injected into the segmental or lobar hepatic artery supplying the neoplasm also gains access to the associated portal venous branches causing focal ablation. This preoperative approach is easier to perform than direct portal vein occlusion, with less parenchymal damage and comparable hypertrophy of the remnant liver frequently necessary for adequate hepatic function following resection. Polymer-drug conjugates, e.g. PG-TXL, have considerable potential for intra-arterial delivery especially with the dramatic increase in concentration of the drug in the tumor and its efficacy. Using in vivo microscopy especially with green fluorescent protein (GFP) gene as an efficient and non-toxic tumor cell marker, the events leading to hepatic metastases can be documented which will serve to better evaluate these varied techniques of chemoembolization.

Animals↗

PubMed1997

Electrical activity of corpus cavernosum in vasculogenic and non-vasculogenic erectile dysfunction.

We aimed to compare the electrical activity of corpus cavernosum before and after intracavernous papaverine injection and to determine the blood lipid profile in vascular and non-vascular erectile dysfunction, and also to assess whether vascular pathology and abnormal blood lipid levels impair cavernosal smooth-muscle relaxation. We determined total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) levels in peripheral and cavernosal blood in 39 patients with erectile dysfunction. Electromyography of the corpus cavernosum was performed before and after an intracavernous injection with 60 mg of papaverine in all patients. Thirty-nine impotent patients have been divided into two groups: vasculogenic erectile dysfunction (VED) and non-vasculogenic erectile dysfunction (NVED), according to colour Doppler ultrasonic flowmetry, dynamic infusion cavernosometry and the pressure difference between the brachial arterial systolic pressure and cavernosal arterial systolic pressure measurements. Biochemical values and amplitude changes were compared in both groups. The TC level was higher in both peripheral and cavernosal samples of the VED group than in the NVED group (p = 0.000), with no differences between peripheral and cavernosal blood levels within the same groups (p > 0.05). There were no significant changes in TG and HDL levels in any of the groups (p > 0.05). The mean amplitude differences before and after papaverine injection (delta A) were found to be 2.05 +/- 0.78 microV in the VED group and 4.68 +/- 2.53 microV in the NVED group, showing that the relaxation response to papaverine was more significant in the NVED than in the VED group (p = 0.003). The moderate decreases in the amplitude of electrical activity of corpus cavernosum and the higher TC levels found in the VED group can be accepted as the parameters of impairment in the relaxation of corpus cavernosum, showing the role of hypercholesterolaemia and vascular pathologies in erectile dysfunction.

Adult↗

PubMed2000

Can blood taken from intraosseous cannulations be used for blood analysis?

Intraosseous infusion is increasingly finding application for venous access to infuse drugs and fluids in paediatric resuscitation including burns. The aim of this study was to determine the feasibility of using blood samples taken from the bone marrow cavity for routine blood analysis. In paediatric resuscitation where alternative venous access is not available this could prove valuable. Peripheral venous blood samples were compared with blood obtained from the bone marrow cavity in patients undergoing bone marrow aspiration for the investigation of possible medical pathology. Haemoglobin, haematocrit, sodium, urea, creatinine, and calcium levels values were sufficiently similar to be clinically useful. The potassium level was elevated in most bone marrow samples and the difference from peripheral venous samples variable. Great caution should be exercised in their interpretation. Glucose levels should also be interpreted with care. In conclusion, blood samples obtained intraosseously may give a useful guide to peripheral blood levels of some haematological and biochemical variables. This is potentially useful where a peripheral venous sample cannot be obtained. The values must be interpreted with care. Whether these findings can be extended to paediatric patients who are not haemodynamically stable has not been assessed.

Blood Chemical Analysis↗

PubMed1999

Survival impact of chemotherapy in patients with colorectal metastases confined to the liver: a re-analysis of 1458 non-operable patients randomised in 22 trials and 4 meta-analyses. Meta-Analysis Group in Cancer.

BACKGROUND: Metastases confined to the liver is a frequent situation in patients with advanced colorectal cancer. For non-operable patients, 5-FU-based chemotherapy is often proposed but the importance of the choice of first line 5-FU regimen remains debatable. DESIGN: In four previously performed meta-analyses, our group had compared bolus intravenous fluoropyrimidines (bolus FU group) with experimental fluoropyrimidines (experimental FU group), consisting of 5-FU plus leucovorin, 5-FU plus methotrexate, continuous infusion 5-FU, or hepaticartery infusion FUDR. We re-analysed this data set to focus on 1458 patients with non-operable colorectal metastases confined to the liver, randomised in 22 trials. All analyses were stratified by trial and used individual patient data. RESULTS: Median survival times were 11.3 months in the bolus FU group (95% CI: 10.5-12.0 months) compared to 12.7 months in the experimental FU group (95% CI: 120-13.1 months). This difference, although clinically small, was statistically significant, with an overall survival hazard ratio of 0.88 (95% CI: 0.79-0.99, P = 0.037). In a multivariate analysis, performance status was the only significant predictor of survival (P < 10(-4)), whereas the statistical significance of allocated treatment was borderline (P = 0.058). CONCLUSIONS: The outcome of patient with non-operable colorectal metastases confined to the liver is poor, and mainly driven by their initial performance status. Experimental chemotherapy schedules yield a small improvement in their overall survival, indicating the importance of the choice of first-line chemotherapy.

Adenocarcinoma↗

PubMedDate not supplied

The efficacy of treatment with triamcinolone acetonide in calcinosis cutis following extravasation of calcium gluconate: a preliminary study.

Neonatal hypocalcemia is not an uncommon condition, especially in the premature neonate. It is effectively treated by intravenous administration of calcium gluconate. Complications of extravasation during intravenous infusion include localized calcification and occasionally necrosis. When this occurs, however, there is no specific mode of treatment except supportive management and skin graft. This experiment was designed to evaluate the efficacy and safety of treatment with triamcinolone acetonide in calcinosis cutis following extravasation of calcium gluconate. Initially, 2 cc of 10% calcium gluconate was injected subcutaneously into two rabbits at seven sites on the shaved skin of the back. Another two rabbits were injected at the same sites with 0.5 cc of triamcinolone acetonide (10 mg/dl) after injection of 2 cc of 10% calcium gluconate. As a control, 2 cc of normal saline was injected into another rabbit in the same manner. These five rabbits were observed over the next 7 weeks and underwent pathologic examination at various intervals (on days 1, 3, 8, 15, 30, 37, 45). In the 10% calcium gluconate injected rabbits, nodules and large ulcerated lesions developed after 15 days. Multiple, linear, ulcerative and indurated masses were noted on day 37. The lesions healed progressively with a decrease in ulceration, and after 2 months, the masses disappeared gradually. Histologically, on day 15 calcium deposits were seen in the walls of the arteries, veins, dermis, and muscle fibers and epidermal necrosis was seen at the injection sites. From day 37 discharge of calcium deposits began to take place by means of transepidermal elimination. After 2 months, the calcium and mucin deposition was observed focally in the dermis. In the rabbits injected with 10% calcium gluconate and triamcinolone acetonide, mild erythema and induration were seen after day 15 at the injection sites; this gradually disappeared. After 30 days the injection sites were normal in appearance. Histologically, at day 15 calcium deposition was seen in the upper dermis, but after 1 month the injection sites were histologically normal. We suggest that intralesional injection of triamcinolone acetonide for the treatment of calcinosis cutis following extravasation of calcium gluconate is effective, probably due to its antiinflammatory effect and its role in facilitating the resorption of calcium in the tissue.

Administration, Topical↗

PubMedDate not supplied

Modified PAIR technique for percutaneous treatment of high-risk hydatid cysts.

PURPOSE: This paper presents a modification of the known method for percutaneous treatment of hydatid cyst, the PAIR technique. It aimed to achieve safe aspiration of large symptomatic cysts and cysts with a danger of impending rupture. METHODS: We designed a coaxial catheter system to achieve concomitant evacuation of cyst contents while infusing scolicidal agent. Hypertonic saline is used to wash out cyst contents and to kill protoscolices. This was followed by injection of a sclerosant (ethyl alcohol 95%) into the residual cyst cavity to prevent formation of a cyst collection after the procedure. Seventeen cysts in 14 patients were successfully aspirated. Follow-up plain radiographs, ultrasonography and CT were performed weekly in the first 4 weeks and then at 3, 6 and 12 months for all patients. Seven patients (9 drained cysts) were followed up for 2 years and 1 patient for 3 years. RESULTS: All cysts were successfully aspirated. The following morphologic changes were noticed: a gradual decrease in cyst size (17 cysts, 100%), thickening and irregularity of the cyst wall due to separation of endocyst from pericyst (7 cysts, 41%), development of a heterogeneous appearance of the cyst components (8 cysts, 47%) and development of pseudotumor (2 cysts, 12%). None of the treated cysts disappeared completely. No significant procedure-related complications were encountered. CONCLUSION: This modified PAIR technique is a reliable method for percutaneous treatment of risky and symptomatic hydatid cysts.

Anticestodal Agents↗

PubMed1996

Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter.

The efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25 U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissue-type plasminogen activator (t-PA; Tisokinase, 50,000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30,000 U/kg) was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.

Angioscopy↗

PubMed2006

Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model.

UNLABELLED: DO was used in an aged mouse model to determine if systemically and/or locally administered rhIGF-I improved osteoblastogenesis and new bone formation. Local and systemic rhIGF-I treatment increased new bone formation. However, only systemic delivery produced measurable concentrations of rhIGF-I in the circulation. INTRODUCTION: Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model. MATERIALS AND METHODS: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouse IGF-I, human IGF-I, and osteocalcin were determined at the end of the study. RESULTS: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of human IGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhIGF-I-treated groups. CONCLUSIONS: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.

Aging↗