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The palliative role of hepatic arterial infusion and arterial occlusion in colorectal carcinoma metastatic to the liver.

Fifty-five patients with metastatic colorectal carcinoma confined to the liver were treated with hepatic arterial infusion of floxuridine and mitomycin C. Tumour response rate was 43.4% and median overall survival was 11 months. Prolonged survival was associated with intentional or inadvertent occlusion of the hepatic artery. The median survival of twenty-four patients with arterial occlusion (15 months) was significantly higher than that of thirty-one patients without arterial occlusion (8 months).

Antineoplastic Agents↗

Implants for sustained drug release over the somatosensory cortex of the newborn rat: a comparison of materials and surgical procedures.

Drugs that interfere with neural transmission are an important tool in assessing the role of specific neurotransmitters in the development of the nervous system. Systemic drug treatments often produce neurodevelopmental effects with questionable specificity. Furthermore, many compounds of interest do not cross the blood-brain barrier. To overcome these limitations, either elvax or gelfoam implants have been previously employed to produce sustained drug release over specific brain regions. In this paper, stereotaxic coordinates are provided for reproducible insertion of drug-delivery systems over the rat somatosensory cortex at birth (P0), prior to the appearance of the cortical barrel pattern; a novel and simpler method for preparation of elvax 40p sheets is described; a new implantation technique is provided. Furthermore, we compare the efficiency and tolerability of elvax vs gelfoam implants, showing that gelfoam, but not elvax, significantly disrupts cortical cytoarchitecture. Finally, successful destruction of serotonin-containing terminals in layer IV of the primary somatosensory cortex of the newborn rat is demonstrated by application of parachloroamphetamine-containing elvax implants.

Acetylcholinesterase↗

Are free radicals responsible for endothelial cell killing of Staphylococcus aureus?

We have recently demonstrated that endothelial cells cultured on Gelfoam blocks, but not monolayer matrices can phagocytose and kill Staphylococcus aureus. Experiments determined that penicillin G, included in the endothelial cell growth medium, induces these cells to exhibit the observed bactericidal activity. In this communication, we report on studies aimed at elucidating the mechanism by which penicillin G-induced endothelial cells, cultured on Gelfoam blocks, kill S. aureus. Despite the fact that there is a substantial literature that demonstrates neutrophilic killing of bacteria can be mediated through free radical-dependent and free radical-independent mechanisms, considerably less is known about pathways by which endothelial cells can catalyze similar microbicidal activities. Studies described herein point to the fact that superoxide and products derived from this free radical were not responsible for endothelial killing of S. aureus. Likewise, a possible role for nitric oxide in bacterial killing was explored. As part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into endothelial cells cultured on Gelfoam blocks in the absence of penicillin G. Even though these cells secreted nitric oxide at a rate of 0.5 microM/h per 1 x 10(6) cells, similar to what has been reported for murine macrophages induced with gamma-interferon, in our model, nitric oxide was not found to kill S. aureus. Data presented demonstrate that the microbicidal activity of endothelial cells is mediated through free radical-independent pathways.

Animals↗

Roles of acid/base nature and molecular weight in drug release from matrices of gelfoam and monoisopropyl ester of poly(vinyl methyl ether-maleic anhydride).

Ophthalmic drug inserts are usually placed in the conjunctival sac. Being in contact with the conjunctiva, they may provide means to deliver large and hydrophilic molecules, such as peptides and oligonucleotides into the eye. We evaluated Gelfoam and monoisopropyl ester of poly(vinyl methyl ether/maleic anhydride) (PVM/MA) as potential polymers for ocular inserts. Matrices were solvent cast with model drugs that had different pKa, molecular weight and hydrophilicity. Drug release from the matrices as well as charge and swelling of Gelfoam(R)-matrix were studied. The release of drugs from PVM/MA-matrices was by erosion of the polymer matrix. The molecular weight and other variants of the releasing compound did not affect their release. In Gelfoam(R)-matrices the release was diffusion controlled and it was affected by the pH of the external solution as well as the charge and molecular weight of the studied compound.

Buffers↗

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Aged↗

Triple semicircular canal occlusion in the guinea pig.

Hearing preservation is possible with translabyrinthine procedures, but the optimal means of sealing the remaining labyrinth has not been determined. The purpose of this study was to compare the effects of mechanical and nonmechanical (CO2 laser-assisted) triple semicircular canal occlusion on hearing in the guinea pig. All three semicircular canals of 19 guinea pigs were treated with one of four techniques: fenestration without packing (control), fenestration with packing, CO2 laser coagulation of the membranous canal without packing, or laser coagulation with packing. Six weeks postoperatively, electrocochleographic thresholds were significantly elevated in one of five ears treated with packing alone, in one of five ears treated with laser and packing, in two of five ears treated with the laser alone, and in all four control ears. Thresholds were significantly elevated in control versus occluded ears (p < 0.05). There were no significant differences between the ears treated with laser or packing. These findings suggest that hearing can be preserved in triple canal occlusion by means of sealing the membranous labyrinth with either CO2 laser coagulation or mechanical packing. Further study on the feasibility of hearing preservation with complete labyrinthectomy is warranted.

Animals↗

Therapeutic arterial embolisation of vascular lesions in the maxillofacial region.

The technique of therapeutic arterial embolisation involves the introduction of a thrombus-inducing material into the lumen of a blood vessel to occlude the vessel and reduce the blood supply to a lesion or to a specific part of the body. It is particularly useful in the maxillofacial region in the management of vascular lesions where marked diminution in blood flow can be achieved. This paper reviews the procedure and the materials for embolisation, and describes four patients for whom it was of considerable assistance.

Adolescent↗

Excision of the trapezium and interposition arthroplasty with gelfoam for the treatment of trapeziometacarpal osteoarthritis.

Excision of the trapezium with Gelfoam interposition was performed in 35 thumbs, 34 of which were evaluated after an average 5 years. Twenty-four patients had unilateral procedures. The follow-up examination included a standardized questionnaire and clinical and radiological examinations. Pain relief was achieved in all cases. The patients considered that 32 of their operated hands had improved function, while two had not improved. All patients were satisfied with the final postoperative result. Adduction of the thumb to the index finger, and opposition to the tip of the little finger was possible in all cases. Weakness, in comparison to the other thumb, of lateral pinch (71%; P=0.0001), tip pinch (74%; P=0.007), and grip strength (85%; P=0.006) were observed. The first web span was preserved in all hands. Calculation of the trapezial space ratio demonstrated only slight, insignificant shortening (7%; P=0.06) of the thumb ray. No significant correlations between the postoperative trapezial space ratio and lateral pinch strength, tip pinch strength, and grip strength were observed. We conclude that excision of the trapezium and Gelfoam interposition has no specific complications and is a reliable surgical treatment for osteoarthritis of the trapeziometacarpal joint.

Aged↗

Clinical evaluation of antibiotic-supplemented bone allograft.

Antibiotic-supplemented bone allograft (ASBA) was originally developed for treatment of combat-acquired, avulsive defects of the oral and maxillofacial skeleton. Earlier findings in experimental wound models showed that ASBA resulted in significantly improved wound repair of infected osseous defects when compared with conventional treatment. In this study, ASBA was evaluated in paired, comparable, mandibular third molar sockets and compared with the findings following conventional surgical removal. The results of this assessment showed that wound healing was significantly improved with the use of ASBA. Evidence produced by this clinical evaluation of ASBA suggests its potential use for other surgical bone defects when grafting is precluded by the risk of infection as a result of contamination by oral flora.

Adult↗

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Adult↗

The preparation and characterisation of drug-loaded alginate and chitosan sponges.

Sponges composed of sodium alginate and chitosan were prepared via a freeze drying process in order to assess the utility of mixed sponges as potential wound dressings or matrices for tissue engineering. Sponge preparation involved dissolving both polymers (either individually or mixed) in 1% acetic acid and freeze-drying the corresponding solutions. The mechanical properties of the sponges were assessed using texture analysis and the microstructure examined using scanning electron microscopy. The dissolution of a model drug (paracetamol) from the sponges was assessed as a function of polysaccharide composition. It was noted that the sponges had a flexible yet strong texture, as assessed macroscopically. Measurement of the resistance to compression ('hardness') indicated that the chitosan sponges were the 'hardest' while the alginate sponges showed the least resistance to compression, with all sponges showing a high degree of recovery. In contrast, the breaking force (tensile force) of the sponges were greatest for the single component systems, while the elongation prior to breaking was similar for each material. SEM studies indicated that the mixed systems had a less well-defined microstructure than the single component sponges. This was ascribed to the two polysaccharides interacting in aqueous solution via coulombic forces, leading to a more randomly ordered network being formed on freezing. Dissolution studies indicated that systems containing chitosan alone showed the slowest release profile, with the mixed systems showing a relatively rapid dissolution profile. The use of chitosan and alginates together, therefore, appears to allow the formulator to manipulate both the mechanical properties and the drug release properties of the sponges.

Alginates↗

Ocular devices for the controlled systemic delivery of insulin: in vitro and in vivo dissolution.

Both in vitro flow-through and in vivo device removal methods were utilized to determine the dissolution rate of insulin from a Gelfoam(R) based eye device. The dissolution profiles generated by these two methods are comparable. The in vivo data suggests that there is a direct relationship between blood glucose lowering and the rate of release of insulin from the device. The in vitro dissolution results indicate that the release of insulin from the device is flow-rate dependent. The prolonged activity of the insulin is due to the gradual release of insulin from the device which results from the lachrymal system's slow and constant tear production.

Animals↗