Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Modifier”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources

Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymer-modified poly(ether urethane) surfaces.

A tri-block-coupling polymer of stearyl poly(ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide) (MSPEO), was used as a surface modifying additive (SMA) and the MSPEO-modified poly(ether urethane) (PEU) surfaces were prepared by the process of dip-coating. The surface analysis by XPS revealed the surface enrichment of poly(ethylene oxide) (PEO). On the coating-modified surfaces, the bovine serum albumin (BSA) adsorption, respectively, from the low and high BSA bulk concentration solutions was correspondingly characterized by the methods of radioactive 125I-probe and ATR-FTIR. The bovine serum fibrinogen (Fg)-adsorption from the Fg bulk solution and the BSA-Fg competing adsorption from the BSA-Fg binary solutions were also characterized by radioactive 125I-probe. The reversible BSA-selective in situ adsorption on MSPEO-modified PEU surfaces were achieved, and the performance of blood compatibility on the coating-modified surfaces was also confirmed, respectively, by plasma recalcification time (PRT) and prothrombin time (PT) tests.

Adsorption↗

Improved blood compatibility and decreased VSMC proliferation of surface-modified metal grafted with sulfonated PEG or heparin.

Although the technique of coronary stenting has remarkably improved long-term results in recent years, (sub)acute thrombosis and late restenosis still remain problems to be solved. Metallic surfaces were regarded as thrombogenic, due to their positive surface charges, and stenosis resulted from the activation and proliferation of vascular smooth muscle cells (VSMCs). In this study, a unique surface modification method for metallic surfaces was studied using a self-assembled monolayer (SAM) technique. The method included the deposition of thin gold layers, the chemisorption of disulfides containing functional groups, and the subsequent coupling of PEG derivatives or heparin utilizing the functional groups of the disulfides. All the reactions were confirmed by ATR-FTIR and XPS. The surface modified with sulfonated PEG (Au-S-PEG-SO3) or heparinized PEG (Au-S-PEG-Hep) exhibited decreased static contact angles and therefore increased hydrophilicity to a great extent, which resulted from the coupling of PEG and the ionic groups attached. In vitro fibrinogen adsorption and platelet adhesion onto the Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces decreased to a great extent, indicating enhanced blood compatibility. This decreased interaction of the modified surfaces should be attributed to the non-adhesive property of PEG and the synergistic effect of sulfonated PEG. The effect of the surface modification on the adhesion and proliferation of VSMCs was also investigated. The modified Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces also exhibited decreased adhesion of VSMCs, while the deposited gold layer itself was effective. The enhanced blood compatibility and the decreased adhesion of VSMCs on the modified metallic surfaces may help to decrease thrombus formation and suppress restenosis. It would therefore be very useful to apply these modified surfaces to stents for improved functions. A long-term in vivo study using animal models is currently under way.

Animals↗

Macrophage behavior on surface-modified polyurethanes.

Adherent macrophages and foreign body giant cells (FBGCs) are known to release degradative molecules that can be detrimental to the long-term biostability of polyurethanes. The modification of polyurethanes using surface modifying endgroups (SMEs) and/or the incorporation of silicone into the polyurethane soft segments may alter macrophage adhesion, fusion and apoptosis resulting in improved long-term biostability. An in vitro study of macrophage adhesion, fusion and apoptosis was performed on polyurethanes modified with fluorocarbon SMEs, polyethylene oxide (PEO) SMEs, or poly(dimethylsiloxane) (PDMS) co-soft segment and SMEs. The fluorocarbon SME and PEO SME modifications were shown to have no effect on macrophage adhesion and activity, while silicone modification had varied effects. Macrophages were capable of adapting to the surface and adhering in a similar manner to the silicone-modified and unmodified polyurethanes. In the absence of IL-4, macrophage fusion was comparable on the modified and unmodified polyurethanes, while macrophage apoptosis was promoted on the silicone modified surfaces. In contrast, when exposed to IL-4, a cytokine known to induce FBGC formation, silicone modification resulted in more macrophage fusion to form foreign body giant cells. In conclusion, fluorocarbon SME and PEO SME modification does not affect macrophage adhesion, fusion and apoptosis, while silicone modification is capable of mediating macrophage fusion and apoptosis. Silicone modification may be utilized to direct the fate of adherent macrophages towards FBGC formation or cell death through apoptosis.

Apoptosis↗

The immobilization of glucose oxidase onto radio-frequency plasma-modified poly(etherurethaneurea).

Glucose oxidase was covalently immobilized onto a radio-frequency plasma-modified poly(etherurethaneurea). Thin (90-100 nm) plasma-polymerized N-vinyl-2-pyrrolidone films were deposited onto poly(etherurethaneurea) films. Active sites for the immobilization were obtained via reduction with aqueous sodium borohydride and activation with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate. Modified poly(etherurethaneurea) films were assayed for binding and activity of the immobilized glucose oxidase layer. The results of a modified radioimmunoassay and an 'immunochemical stain' indicated that washing in 900 ml of continuously stirred 2% sodium dodecyl sulfate, 2% Triton X-100, and 20 mM sodium phosphate, pH 7.0, for 24 h each at 4 degrees C was necessary to remove physically adsorbed glucose oxidase from the solid supports. An amperometric activity determination in 9 ml of well-stirred 20 mM sodium phosphate-0.1 M sodium chloride, pH 7.4, gave a qualitative demonstration of the activity of the immobilized enzyme on 18.75 cm2 of modified poly(etherurethaneurea) film. A colorometric activity determination using the coupled reaction with o-dianisidine and peroxidase indicated that glucose oxidase covalently immobilized on approximately 2.4 cm2 of modified poly(etherurethaneurea) film had an activity approximately equal to that of 13.4 nM glucose oxidase in 50 mM sodium acetate, pH 5.1, with a specific activity of approximately 32.0 U/mg at pH 5.1 and room temperature.

Biocompatible Materials↗

Trial of standard versus modified expiration to achieve end-of-test spirometry criteria.

To assess whether satisfying American Thoracic Society (ATS) end-of-test spirometry criteria can be enhanced by modifying the patient's expiratory technique, we conducted a cross-over trial of two expiratory techniques in 48 patients with a range of pulmonary functions (Group 1, n = 12: FEV1/FVC < 0.45; Group 2, n = 11: FEV1/FVC, 0.45 to 0.60; Group 3, n = 16: FEV1/FVC, 0.61 to 0.74; Group 4, n = 9: FEV1/FVC > or = 0.75). After randomizing the order of testing, each patient performed three exhalations using a "standard" forced expiratory maneuver and a modified expiratory technique consisting of an initial maximal expiratory effort followed by a "relaxed expiration" for as long as possible. Patients initiated "relaxed expiration" when instructed by the supervising technician, who issued the instruction to relax when expiratory airflow fell to < or = 200 ml/s (as determined by flow-volume loop analysis). ATS end-of-test criteria were satisfied significantly more often using the modified expiratory technique (58.3% of testing sessions) than using the standard technique (18.7% of sessions, p = 0.001) because of prolongation of the forced expiratory time (FET) with the modified technique in all patient groups. In the 38 patients with FEV1/FVC < or = 0.75, the largest FVC and FET rose significantly using the modified expiratory technique, without compromising the largest FEV1 in any group. In patients with FEV1/FVC > or = 0.75, FET increased without concomitant changes in FVC or FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of complement.

Cigarette smoking is associated with significant increases in the number of pulmonary mononuclear phagocytes and neutrophils. A potent chemoattractant for these cells is C5a, a peptide generated during complement (C) activation. We, therefore, investigated the possibility that cigarette smoke could activate the complement system in vitro. Our results show that factor(s) (mol wt less than 1,000) present in an aqueous solution of whole, unfiltered cigarette smoke can deplete the hemolytic capacity of whole human serum in a dose-dependent manner. The particle-free, filtered gas phase of cigarette smoke is inactive. The smoke factor(s) do not activate serum C1, but do deplete serum C4 activity. Treatment of purified human C3 with whole smoke solution modifies the molecule such that its subsequent addition to serum (containing Mg/EGTA to block the classical pathway) results in consumption of hemolytic complement by activation of the alternative pathway. Smoke-modified C3 shows increased anodal migration in agarose electrophoresis, but this is not due to proteolytic cleavage of the molecule as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast to methylamine-treated C3, C3 treated with smoke is only partially susceptible to the action of the complement regulatory proteins Factors H and I. In addition, smoke-modified C3 has diminished binding to Factor H as compared with methylamine-treated C3. Finally, smoke-modified C3 incorporates [14C]methylamine which suggests that the thiolester bond may be intact. These data indicate that aqueous whole cigarette smoke solution can modify C3 and activate the alternative pathway of complement, perhaps by a previously unrecognized mechanism. Should this occur in vivo, complement activation might partly account for the extensive pulmonary leukocyte recruitment observed in smokers.

Complement Activation↗

Variability in cytotoxicity and fluoride release of resin-modified glass-ionomer cements.

New-generation glass-ionomer cements contain resin to improve their restorative properties. These resin-modified glass-ionomer cements vary considerably in their chemistry, which could result in corresponding variability in their physical and biological properties. This study investigated the cytotoxicity and the fluoride release of two resin-modified glass ionomers, a conventional glass-ionomer cement, and a resin composite. Samples were prepared and extracted in distilled water for 1, 4, and 7 days; eluates were filtered and tested by means of 3T3 mouse fibroblasts. Cytotoxicity (MTT assay) values were low for all materials and extraction times, indicating minimal cytotoxicity of all materials (less than 30% inhibition). Cytotoxicity of one resin-modified glass ionomer was significantly higher than for the other materials (p < 0.001). One resin-modified glass ionomer and the conventional glass-ionomer cement released significantly more fluoride at each time interval (p < 0.001) than the other resin-modified glass-ionomer cement and the resin composite. Fluoride release and cytotoxicity were correlated (r2 = 0.60; p < 0.001), although the fluoride release does not account for the cytotoxicity observed. Cytotoxicity and fluoride release suggest that one hybrid behaved more like a conventional glass ionomer, and the other like a resin composite. These differences may have implications for material selection in specific clinical situations.

3T3 Cells↗

Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome.

BACKGROUND: Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid, electrolytes, and other nutrients. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings, and parenteral nutrition is required to prevent dehydration, electrolyte disturbances, and malnutrition. Substances such as growth hormone, glutamine, and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption. This study was undertaken to determine whether the co-administration of exogenous growth hormone, supplemental glutamine, and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection. METHODS: Ten patients (5 men, 5 women, aged 43 +/- 4 years) with short bowel syndrome were studied 6 +/- 1 years after surgical resection. All patients were admitted to the Clinical Research Center for a 28-day period; the first week served as a control period when nutritional (enteral and parenteral) and medical management simulated usual home therapy. Thereafter, eight patients received exogenous growth hormone, supplemental glutamine, and a modified high-carbohydrate, high-fiber diet. Two patients were treated with the modified diet alone. The efficiency of net nutrient absorption (percent absorbed) for total calories, protein, fat, carbohydrate, water, and sodium was calculated from the measured nutrient intake and stool losses. RESULTS: Three weeks of treatment with growth hormone, glutamine, and a modified diet increased total caloric absorption from 60.1 +/- 6.0% to 74.3 +/- 5.0% (p < or = .003), protein absorption from 48.8 +/- 4.8% to 63.0 +/- 5.4% (p < or = .006), and carbohydrate absorption from 60.0 +/- 9.8% to 81.5 +/- 5.3% (p < or = .02). Fat absorption did not change (61.0 +/- 5.3% to 60.3 +/- 7.9%, p = NS). Water and sodium absorption increased from 45.7 +/- 6.7% to 65.0 +/- 7.3% (p < or = .002) and from 49.0 +/- 9.8% to 69.6 +/- 6.5% (p < or = .04), respectively. These absorptive changes resulted in a decrease in stool output (1,783 +/- 414 g/d control period vs 1,308 +/- 404 g/d third week of treatment, p < or = .05). Treatment with diet alone did not influence nutrient absorption or stool output. CONCLUSIONS: The combined administration of growth hormone, glutamine, and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection. These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients. This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome.

Adult↗

A modified prognostic score for patients with curatively resected gastric cancer.

AIMS AND BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide; the risk of dying depends on several patient and disease characteristics. An existing prognostic score predicts survival in gastric cancer patients undergoing curative resection based on patient age, tumor site, extent of wall invasion and nodal status, categorized as simply as negative or positive. METHODS: Our aim was to modify the original prognostic score by incorporating information on nodal stage according to the latest TNM classification (number of involved nodes), based on a retrospective series of 610 chemotherapy-naive gastric cancer patients recruited to a surgical clinical trial. We then tested the modified score on an independent series of 136 gastric cancer patients. RESULTS: Nodal stage added significant prognostic information to the nodal status classification (P < 0.001), and was therefore included in the modified score. With the latter, we were able to identify three risk groups with overall five-year survival varying from more than 70% to less than 30%. The prognostic performance of the modified score was better than that achieved with the AJCC-UICC TNM staging. CONCLUSIONS: The modified score, based on established prognostic factors, is proposed as a simple tool for prognostic grouping of gastric cancer patients undergoing curative surgery.

Female↗

Detection of cytopathic bovine viral diarrhea virus in the ovaries of cattle following immunization with a modified live bovine viral diarrhea virus vaccine.

Economic loss from infection with bovine viral diarrhea virus (BVDV) is of worldwide concern. The unique pathogenesis and antigenic variability of BVDV have made this virus challenging to control. Vaccination programs are a major component of control and prevention strategies. Both killed and modified live vaccines are commercially available. Choice between killed and modified live vaccines is controversial. Of major concern is the safety of modified live vaccines. Little information is available on their tissue tropism and potential for causing pathology, especially with respect to the reproductive system. The objective of this study was to determine if BVDV could be detected in the ovary of cattle following immunization with a modified live BVDV vaccine. In 2 separate trials, 6 heifers and 4 mature cows were immunized with a modified live BVDV vaccine and ovaries were removed between 7 and 30 days postvaccination. Cytopathic BVDV was isolated from ovaries removed on days 8, 10, and 12. BVDV antigen was detected using immunohistochemistry on days 10-30. These findings are significant because replication of virus in the ovary could cause ovarian dysfunction, resulting in reduced fertility.

Animals↗

Clinical results of modified Mitchell's osteotomy for hallux valgus augmented with oblique lesser metatarsal osteotomy.

PURPOSE: To evaluate postoperative results of modified Mitchell's osteotomy and its combination with oblique metatarsal osteotomy for the treatment of hallux valgus. METHODS: A total of 93 feet of 53 patients (2 men and 51 women) with hallux valgus underwent modified Mitchell's osteotomy and were followed up for at least 5 years. Patients' age ranged from 17 to 83 years, and the duration of follow-up ranged from 5 years one month to 18 years 4 months. Modified Mitchell's osteotomy was performed on 53 feet in 31 patients (group A), whereas modified Mitchell's osteotomy augmented with oblique lesser metatarsal osteotomy was performed to the remaining 40 feet in 22 patients (group B). Postoperative results were assessed using a clinical assessment system developed by the Tokyo Medical University based on 5 categories: pain in the first metatarsophalangeal, deformity of the metatarsophalangeal, plantar callosity and/or metatarsalgia of lesser metatarsals, the use of commercially available shoes, and local inflammatory symptoms. RESULTS: Mean total score improved from 3.8 to 7.9 on a 10-point scale. Scores for 2 categories--plantar callosity and/or metatarsalgia and the use commercially available shoes--were significantly higher in group B at postoperative 5 years. Before surgery, at postoperative 3 weeks, and at postoperative 5 years, respectively, the mean hallux valgus angles were 34.2, 12.0, and 17.1 degrees; mean M1-M2 angles were 16.7, 7.4, and 8.7 degrees; mean M1-M5 angles were 34.9, 25.8, and 26.6 degrees; and mean sesamoid bone shifts were 8.7 mm, 4.3 mm, and 5.9 mm. CONCLUSION: Modified Mitchell's osteotomy shortens the length of the first metatarsal bone and thus relieves tension in soft tissues such as the adductor hallucis. Nonetheless, the procedure can induce metatarsophalangeal joint malalignment and metatarsalgia, and plantar callosity may develop or persist after surgery. Combining oblique metatarsal osteotomy of the lesser metatarsal bones is useful in patients with uneven metatarsal bone lengths and metatarsophalangeal joint malalignment.

Adolescent↗

Hypochlorous acid-modified low-density lipoprotein inactivates the lysosomal protease cathepsin B: protection by ascorbic and lipoic acids.

Unregulated uptake of oxidized LDL by the scavenger receptor(s) of macrophages is thought to be an early event in atherosclerotic lesion development. Accumulation of oxidized LDL within macrophages may result from resistance of the modified LDL to enzymatic hydrolysis or from direct inactivation of lysosomal enzymes by reactive LDL-associated moieties. Since HOCl-modified LDL has been detected in vivo, the effects of HOCI-modified LDL on the activities of the cysteine protease cathepsin B and the aspartyl protease cathepsin D were investigated. LDL (0.5 mg protein/ml), which had been exposed to HOCl (25-200 microM), caused rapid dose-dependent inactivation of cathepsin B, but not of cathepsin D. Exposure of LDL to HOCl results primarily in the formation of LDL-associated chloramines, and the model chloramine N(alpha)-acetyl-lysine chloramine also caused dose-dependent inactivation of cathepsin B. Incubation of HOCl-modified LDL with ascorbic and lipoic acids (25-200 microM) resulted in dose-dependent reduction of LDL-associated chloramines and concomitant protection against cathepsin B inactivation. Thus, the data indicate that HOCl-modified LDL inactivates cathepsin B by a chloramine-dependent mechanism, most likely via oxidation of the enzyme's critical cysteine residue. Furthermore, small molecule antioxidants, such as ascorbic and lipoic acids, may be able to inhibit this potentially pro-atherogenic process by scavenging LDL-associated chloramines.

Amines↗

Reliability of sickness certificates in detecting potential sick leave reduction by modifying working conditions: a clinical epidemiology study.

BACKGROUND: Medical sickness certificates are generally the main source for information when scrutinizing the need for aimed intervention strategies to avoid or reduce the individual and community side effects of sick leave. This study explored the value of medical sickness certificates related to daily work in Norwegian National Insurance Offices to identify sick-listed persons, where modified working conditions might reduce the ongoing sick leave. METHODS: The potential for reducing the ongoing sick leave by modifying working conditions was individually assessed on routine sickness certificates in 999 consecutive sick leave episodes by four Norwegian National Insurance collaborators, two with and two without formal medical competence. The study took place in Northern Norway in 1997 and 1998. Agreement analysed with differences against mean, kappa, and proportional-agreement analysis within and between groups of assessors was used in the judgement. Agreements between the assessors and the self-assessment of sick-listed subjects were additionally analysed in 159 sick-leave episodes. RESULTS: Both sick-listed subjects and National Insurance collaborators anticipated a potential reduction in sick leave in 20-30% of cases, and in another 20% the potential was assessed as possible. The chance corrected agreements, however, were poor (k < 0.20) within and between groups of National Insurance collaborators. The agreement between National Insurance collaborators and the sick-listed subjects was no better than chance. Neither extended medical information nor formal medical competence increased agreement in cases where modified working conditions might have reduced sick leave. CONCLUSION: Information in medical sickness certificates proved ineffective in detecting cases where modified working conditions may reduce sick leave, and focusing on medical certificates may prevent identification of needed interventions. Strategies on how to communicate directly with sick-listed subjects would enable social authorities to exploit more of the sick leave reduction potential by modifying the working conditions than strategies on improving medical information.

Adult↗

Modified ultrafiltration in surgical correction of congenital heart disease with cardiopulmonary bypass.

The surgical correction of congenital heart disease using haemodilution and hypothermia with cardiopulmonary bypass (CPB) may expose patients to tissue ischaemia and initiate a systemic inflammatory response, increasing the total body water and inducing impairment, especially of heart, lung and brain function. It is possible to use ultrafiltration during CPB in the rewarming phase to remove water accumulation in the third space (conventional ultrafiltration). The reduced volume of prime used in children and the ability only to filter the reservoir blood during CPB led the Great Ormond Street Group to modify the method of ultrafiltration with regards to the placement of the filter and the timing of filtration (post-CPB). The main advantage of the modified technique is the ultrafiltration of the patient. A prospective nonrandomized study has been conducted to compare conventional with conventional + modified ultrafiltration. From January 1996 to March 1998, 41 patients underwent correction of congenital heart disease and were submitted to a comparative study (homogeneous groups), using either the conventional or the conventional + modified ultrafiltration techniques. There were no technical complications, no patient required mediastinal re-exploration due to bleeding and it was possible to close all the chests. There were significant differences in the ultrafiltrate volume balance (143.3 +/- 54.3 versus 227 +/- 71.4 mL; P < 0.001) but there were no significant differences in clinical postoperative evolution between the conventional and the conventional + modified ultrafiltration.

Blood Transfusion↗

Electromyography characterization of stretch responses in hemiparetic stroke patients and their relationship with the Modified Ashworth scale.

OBJECTIVES: To determine the validity of the Modified Ashworth Scale as a measure of spasticity by determining its relationship to surface electromyography activity and contracture. DESIGN: A controlled study of hemiparetic stroke patients with spasticity. SETTING: A physiotherapy department in a secondary care hospital. SUBJECTS: Thirty-one stroke patients and 20 healthy volunteers. MAIN MEASURES: The resistance to passive movement around the knee and ankle of the affected and unaffected legs was rated using the Modified Ashworth Scale. Passive range of movement was measured with a goniometer. Surface electromyography recordings of four lower limb muscles were taken during passive stretches of the knee and ankle. RESULTS: Hemiparetic patients produced surface electromyography responses to stretch that were of greater amplitude (unaffected limbs: mean = 25.82 mV (43.85), affected limbs: mean = 24.77 mV (35.46)) than those of healthy volunteers (mean = 15.85 (29.96)). The affected muscles of hemiparetic patients were more likely to produce surface electromyography responses to stretch of a sustained duration (45% of cases) compared with unaffected limbs (24% of cases) and those of healthy volunteers (16% of cases). The Modified Ashworth Scale showed a positive correlation with the magnitude (p < 0.05) and duration (p < 0.001) of the surface electromyography response. High scores on the Modified Ashworth Scale were associated with contracture (p < 0.001). Contracted muscles produced significantly greater surface electromyography reflex responses compared with noncontracted muscles (p < 0.05). CONCLUSION: The Modified Ashworth Scale reflects spasticity in terms of surface electromyography stretch responses produced by passive movement, but the relationship of spasticity to contracture remains unclear.

Aged↗

High-dose cisplatin in hypertonic saline: reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in non-small-cell lung cancer.

Although increased efficacy has been described with a five-day schedule of high-dose cisplatin (CDDP) in hypertonic saline, severe myelosuppression and cumulative neurotoxicity have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in non-small-cell lung cancer (NSCLC), 17 patients with metastatic disease were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per patient and a median total cumulative dose of 600 mg/m2. Nine of 17 patients received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and peripheral neuropathy were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe peripheral neuropathy developed in only one patient (6%). The overall response rate was 47% (eight of 17 patients). Plasma platinum pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate platinum occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced toxicity of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in NSCLC remains to be defined. In view of reduced myelosuppression and neurotoxicity, further trials with this modified schedule are indicated.

Adult↗

Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine.

PURPOSE: We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up. PATIENTS AND METHODS: Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guérin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials. RESULTS: The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P <.001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P <.001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program. CONCLUSION: This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.

Adjuvants, Immunologic↗

Preparation and characterization of gelatin surface modified PLGA microspheres.

This study optimized conditions for preparing and characterizing gelatin surface modified poly (lactic-co-glycolic acid) (PLGA) copolymer microspheres and determined this system's interaction with fibronectin. Some gelatin microspheres have an affinity for fibronectin-bearing surfaces; these microspheres exploit the interaction between gelatin and fibronectin. PLGA copolymer microspheres were selected because they have reproducible and slow-release characteristics in vivo. The PLGA microspheres were surface modified with gelatin to impart fibronectin recognition. Dexamethasone was incorporated into these microspheres because dexamethasone is beneficial in chronic human diseases associated with extra fibronectin expression (eg, cardiovascular disease, inflammatory disorders, rheumatoid arthritis). The gelatin surface modified PLGA microspheres (prepared by adsorption, conjugation, and spray coating) were investigated and characterized by encapsulation efficiency, particle size, in vitro release, and affinity for fibronectin. The gelatin-coated PLGA microspheres had higher interaction with fibronectin compared with the other gelatin surface modified PLGA microspheres (adsorption and conjugation). Dexamethasone was released slowly (over 21 days) from gelatin surface modified PLGA microspheres.

Anti-Inflammatory Agents↗