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At least 127 records · Page 7Linked to original sources

Covering the percutaneous endoscopic gastrostomy (PEG) tube prevents peristomal infection.

BACKGROUND: Because oropharyngeal bacteria can be brought through the abdominal wall during percutaneous endoscopic gastrostomy (PEG), peristomal infection is one of the most frequent complications in patients who undergo the procedure. This study aimed to determine whether covering the PEG tube with a sheath that could be detached in the stomach could help prevent peristomal infection. METHODS: In three community hospitals in Japan, data from 449 patients with swallowing dysfunction were prospectively collected between March 2000 and February 2002 for non-covered PEG (n=206) and between March 2002 and February 2004 for covered PEG (n=243). RESULTS: After adjusting for hospital, age, gender, and underlying diseases, covering the PEG significantly reduced peristomal purulent infection compared with non-covered PEG (odds ratio: 0.05; 95% confidence interval: 0.02-0.13). Body temperature, white blood cell count, and C-reactive protein at day 3 after PEG placement, as well as duration of antibiotics usage, were significantly lower or shorter in patients treated with covered PEG than non-covered PEG. In spite of the same frequencies in the two groups of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in oropharyngeal cultures before PEG placement, these organisms were detected significantly less frequently in peristomal lesions of patients who underwent covered PEG. Moreover, 28 patients treated with covered PEG received no antibiotic therapy, and 27 of them had no signs of peristomal infection. CONCLUSIONS: These results suggest that covering the PEG tube, with or without providing antibiotic therapy, may prevent peristomal infection in spite of the presence of oropharyngeal bacterial flora after percutaneous endoscopic gastrostomy.

Aged↗

Does the presence of esophagitis prior to PEG placement increase the risk for aspiration pneumonia?

The aim of this study is to determine if the endoscopic presence of esophagitis predicts aspiration pneumonia after the initiation of enteral feedings in a newly placed PEG tube. A retrospective analysis of 278 patients who received a PEG tube from November 1999 to June 2002 was performed. All PEG procedures performed by a single endoscopist were reviewed from the GI Trac database at the Medical University of South Carolina. Eleven of the procedures were aborted due to technical difficulties. Nine patients received the PEG for gastric decompression only. Seven patients died within 14 days of PEG placement from non-PEG-related complications and were excluded. The resulting 251 patients included for our analysis successfully had PEG tube placement and had at least 14 days of enteral feeding. Esophagitis was defined macroscopically by the endoscopic presence of mucosal edema, friability, or obscurity of the normal vascular pattern in the distal esophagus. Aspiration was defined as the witnessed regurgitation of or tracheal suctioning of PEG feedings. Pneumonia as a consequence of aspiration was defined by development of fever and new infiltrate on chest radiograph within 14 days of PEG placement. Two hundred fifty-one patients had PEG placement (M, 127; F, 124; average age, 62.4 year; age range, 18-95 years) performed by a single endoscopist over a 32-month period. Fourteen (5.6%) of these patients had clinically evident pulmonary aspiration, with seven of them developing pneumonia. Thirteen (93%) of these patients had normal esophageal mucosa. One of the 24 patients (4%) with esophagitis or esophageal ulceration present endoscopically had an aspiration event with subsequent pneumonia. None of the 20 patients found to have some other form of esophageal pathology had an aspiration event. The overall incidence of aspiration pneumonia after the initiation of PEG feedings was 2.7% (7/251). The odds ratio that the presence of esophagitis would predict the development of aspiration pneumonia was 1.60, with a 95% confidence interval of 0.18 to 13.89. This study argues that the presence of esophagitis alone does not increase the risk of aspiration pneumonia from PEG feedings. Other factors apart from esophagitis play an important role in the incidence of aspiration pneumonia with PEG feeding

Adolescent↗

Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer.

The aim of this study was to elucidate the effect of various mole percentages (0-25 mol%) of 2000 Da polyethylene glycol-disteroylphosphoethanolamine (PEG-DSPE) in the presence or absence of 40 mol% cholesterol and the effect of degree of saturation of phosphatidylcholine (PC) on the size and the lipid bilayer packing of large unilamellar vesicles (LUV). Egg PC (EPC, unsaturated) LUV and fully hydrogenated soy PC (HSPC, saturated) LUV partial specific volume, specific compressibility, size, and packing parameter (PP) of lipids were characterized by measurements of density, ultrasonic velocity, specific turbidity, and dynamic light scattering. Liposome size and specific turbidity decreased with increase in temperature and PEG-DSPE mol%, except at 7+/-2 mol%. At this PEG-DSPE mol%, an anomalous peak in liposome size of 15+/-5 nm was observed. We attribute this effect mainly to the change in the spatial structure of the PEG-DSPE molecule, depending on whether the grafted PEG is in the mushroom or brush configuration. In the mushroom regime, i.e., when the grafted PEG is up to 4 mol% in LUV, the PEG moiety did not affect the additive PP of the lipids in the bilayer, and the PP value of PEG-DSPE is 1.044; while in the brush regime, i.e., when the grafted PEG is higher than 4 mol%, the PP of PEG-DSPE decreases exponentially, reaching the value of 0.487 at 30 mol% of grafted lipopolymer. The specific compressibility and additive PP values for the mixture of matrix lipid (EPC or HSPC), cholesterol, and PEG-DSPE for all liposome compositions investigated reached their maximum at 7+/-2 mol% PEG-DSPE, the concentration of PEG-DSPE at which the highest biological stability of the LUV is achieved.

Compressive Strength↗

Novel PEG-matrix metalloproteinase-2 cleavable peptide-lipid containing galactosylated liposomes for hepatocellular carcinoma-selective targeting.

In order to obtain an HCC-selective drug delivery system, a novel functional lipid, which is cleaved by the protease activity of matrix metalloproteinase-2 (MMP-2), was developed. The amino group of dioleoylphosphatidylethanolamine (DOPE) was conjugated with PEGylated MMP-2 substrate peptide (Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln), and MMP-2-cleavable PEG-Peptide-DOPE (PEG-PD) was synthesized. When PEG-PD was incorporated in galactosylated liposomes (Gal-PEG-PD-liposomes), we expected that Gal-PEG-PD-liposomes would not be taken up by normal hepatocytes due to the steric hindrance effect, but would be activated around HCC cells by secreted MMPs. In the pretreatment by hMMP2 (1, 5, and 10mug/ml), an hMMP2 concentration-dependent higher uptake of Gal-PEG-PD-liposomes was observed in HepG2 cells, suggesting PEG-PD cleavage. In the presence of an excess of galactose, the uptake of Gal-PEG-PD-liposomes with hMMP2 was significantly inhibited, suggesting asialoglycoprotein receptor-mediated uptake of Gal-PEG-PD-liposomes following the PEG-PD cleavage. Pretreatment of Gal-PEG-PD-liposomes with the conditioned medium of B16BL6, which contained secreted MMPs, enhanced the binding to HepG2 cells, as in the case of hMMP-2 treatment. Moreover, the cytotoxicity of N(4)-octadecyl-1-beta-d-arabinofuranosylcytosine (NOAC) incorporated Gal-PEG-PD-liposomes was enhanced by hMMPs (5mug/ml) and its cytotoxicity was significantly reduced by the presence of an excess of galactose in HepG2 cells. In conclusion, Gal-PEG-PD-liposomes were successfully developed for novel HCC-selective targeting.

Antineoplastic Agents↗

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Animals↗

Effects of the molecular weight of peg molecules (8, 20 and 35 KDA) on cell function and allograft survival prolongation in pancreatic islets transplantation.

The normopotassic solution SCOT (Macopharma, France) used for the isolation of the islets of Langerhans may improve both graft function and survival. We believe that this is due to the immunoprotective properties of polyethyleneglycol (PEG) (20 kDa; 1.5 mM/L), which is contained in this solution. However, the optimal PEG chain length remains to be determined. Three extracellular type solutions (SCOT without PEG) containing various PEG-8 kDa, 20 kDa, or 35 kDa- at 1.5 mM/L were compared in vitro for viscosity and osmolarity as well as in vivo using a murine model of pancreatic islet allotransplantation. We compared the effects of the various solutions on functional cell recovery (primary nonfunction rate, PNF) and immunoprotection (allograft survival time). We showed that the viscosity of PEG 35 kDa solutions was too high for physiological use. PEG 20 kDa solution provided the best graft function (0% PNF, P < .05). PEG 8 kda and 20 kDa solutions significantly increased allograft survival time compared to the PEG 35 kDa solution (P < .05). Graft survival was similar with PEG 20 kDa and PEG 8 kDa solutions: 27.50 +/- 3.70 days versus 23.13 +/- 4.39 days (NS). However, the number of PNF with PEG 8 kDa solution (50%) was significantly higher (P < .01) than that with the PEG 20 kDa solution (0%). These preliminary results indicated that the optimal chain length at 1.5 mM/L of PEG is 20 kDa.

Animals↗

Complications in motility PEG placement for hydroxyapatite orbital implant in anophthalmic socket.

PURPOSE: In a retrospective study, we evaluated the complications in using the motility peg system (nonsleeved and sleeved) for hydroxyapatite orbital implants in an anophthalmic socket. METHODS: Drilling for motility peg placement was performed in 265 patients with hydroxyapatite implantation: nonsleeved peg system (n = 191), sleeved peg system (n = 74). A statistical analysis was performed using the chi-square test. RESULTS: Extrusion rates were significantly lower in the sleeved peg system (10.8%) compared to the nonsleeved peg system (27.2%) (P =.005). The other complications related to motility peg placement were granulation tissue overgrowth (4.2%), hydroxyapatite exposure around peg head (3.0%), and decentered peg (1.9%). CONCLUSIONS: To minimize peg extrusion, the sleeved peg was better than the nonsleeved peg for use in primary motility peg placement.

Adult↗

PEG-variant biomaterials as selectively adhesive protein templates: model surfaces for controlled cell adhesion and migration.

Our study focused on the role of poly(ethylene glycol) (PEG) in actively regulating the biological responsiveness of protein-adsorbed biomaterials. To this end, we designed PEG-variant biomaterials from a family of tyrosine/PEG-derived polycarbonates to present surfaces ranging from low to intermediate levels of PEG concentration, below the PEG level requisite for complete abolition of protein adsorption. We analyzed the effect of PEG concentration on the amount, conformation and bioactivity of an adsorbed model protein, fibronectin, and on the attachment, adhesion strength and motility of L929 fibroblasts. Our results demonstrate that low levels of PEG can regulate not only the extent but also the conformation and specific bioactivity of adsorbed fibronectin. As the PEG concentration was increased from 0 to 6 mol%, the amount of adsorbed fibronectin decreased linearly yet the fibronectin conformation was altered such that the overall bioactivity of adsorbed fibronectin was uncompromised. We report that the degree of cell attachment varied with PEG concentration in a manner similar to the dependence of fibronectin bioactivity on PEG. In contrast, the nature of cell adhesion strength dependence on PEG paralleled the pattern observed for fibronectin surface concentration. Our studies also indicated that the rate of cell migration was inversely correlated with PEG concentration over a narrow range of PEG concentration. Overall, these results highlight the striking ability of PEG-variant biomaterials to systematically regulate the behavior of adsorbed cell adhesion proteins and, consequently, effect cell functions.

Adsorption↗

Audit of percutaneous endoscopic gastrostomy (PEG): a questionnaire survey of hospital consultants.

One of the commonest indications for PEG is nutritional support in dysphagia. We investigated the current practice of PEG insertion in South Wales (UK). A postal questionnaire was sent to hospital consultants with responsibility for acute medical/geriatric intake in the South Wales area. Eighty-eight of 114 (78.5%) responded. In 69 of 107 (65%) responses (Radiologists and Geriatricians also performed PEG in some hospitals) Gastroenterologists performed the insertion of PEG. Seventy-one (87%) always involved speech therapists before PEG insertion. Forty-five (55%) and 47 (57%) always involved dieticians and nurses, respectively. Eighty (92%) involved carers before PEG. Sixty-three (76%) used nasogastric feed for nutritional support before PEG. Thirty-six of 80 (45%) responses would wait more than 2 weeks before inserting PEG (range less than 7 days to more than 6 weeks). Five (6.5%) preferred long-term nasogastric feed to PEG. Twenty-five (30%) had definite knowledge of a PEG clinic in their hospital and 38 of 77 (49%) who responded to this question said there was no routine follow-up or were not aware about follow up of PEG patients. There is wide variation in the timing of PEG insertion and involvement of paramedical staff. More research needs to be undertaken to provide evidence so guidelines can be developed in this area. Follow up of patients with PEG is poor but current evidence suggests follow up of these patients may be worth while as some patients with dysphagic stroke can regain their swallow late.

Journal Article↗

Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity.

BACKGROUND: Novel antithrombotic agents such as hirudin have shown promise in the therapy of acute coronary syndromes. PEG-hirudin (polyethyleneglycol conjugated hirudin) has been developed to provide a longer plasma half-life and more stable antithrombotic plasma levels. Privious trials indicated a narrow therapeutic window for hirudin and a number of aPTT (activated partial thromboplastin time)-monitored trials investigating hirudin in acute coronary syndromes had to be stopped because of intracranial bleeding complications. OBJECTIVES: The present study evaluates the ecarin clotting time (ECT), a parameter based on the conversion of prothrombin by the snake venom enzyme ecarin, for the monitoring of PEG-hirudin therapy. METHODS: Plasma from either healthy volunteers (n=20) or from patients (n=10) suffering from unstable angina pectoris (UAP) was spiked with increasing PEG-hirudin concentrations. In a prospective randomized clinical trial patients with UAP were treated with intravenous PEG-hirudin or heparin over 72 hours. Patients were randomized to the following treatment groups: (1) heparin control group, n=15; (2) PEG-hirudin low dose (0.1 mg/kg bolus, 0.01 mg/kg/h infusion), n=19; (3) intermediate dose (0.15 mg/kg and 0.015 mg/kg/h), n=17; 4) high-dose (0.2 mg/kg and 0.02 mg/kg/h), n=16. Spiked plasma samples and plasma from UAP patients treated with i.v. PEG-hirudin were analyzed for aPTT, ECT, and PEG-hirudin levels. RESULTS: A linear correlation up to the highest therapeutic concentrations could be observed between PEG-hirudin plasma concentrations and the ECT. This was true for both plasma samples spiked with PEG-hirudin in vitro as well as for samples taken from patients treated with i.v. PEG-hirudin (correlation coefficient 0.9, respect.) In contrast the aPTT did not show a reliable linear correlation to PEG-hirudin concentrations. CONCLUSION: Monitoring of PEG-hirudin therapy by ECT may help to avoid inadequate anticoagulation or overdosing. Thus, the safety and efficacy profile of PEG-hirudin therapy is likely to be enhanced by ECT monitoring.

Angina, Unstable↗

In vivo efficacy of folate-targeted lipid-protamine-DNA (LPD-PEG-Folate) complexes in an immunocompetent syngeneic model for breast adenocarcinoma.

Gene therapy utilizing lipid-based delivery systems holds tremendous promise for the treatment of cancer. However, due to the potential adverse inflammatory and/or immune effects upon systemic administration, treatments thus far have been predominantly limited to intratumoral or regional treatment. Previous studies from our group have demonstrated the antitumor efficacy of systemically administered, folate-targeted, lipid-protamine-DNA complexes (LPD-PEG-Folate) against breast cancer using an immunodeficient xenogenic murine model. In the current study, the antitumor efficacy of LPD-PEG-Folate in a syngeneic, immune competent, murine model of breast cancer was examined. In this model, the potential inflammatory or immune responses and their effects on systemic delivery can be addressed. The 410.4 murine breast adenocarcinoma cell line was initially evaluated in vitro for its interactions with LPD-PEG-Folate and control LPD-PEG formulations. Utilizing fluorescently labeled formulations and fluorescence-activated cell sorting (FACS) analysis, a 1.6-fold enhancement of binding and internalization of LPD-PEG-Folate over LPD-PEG formulations was observed, suggestive of specific receptor interaction. Increased binding was manifested as 5-26-fold increases in luciferase gene expression in 410.4 cell transfection when comparing LPD-PEG-Folate to LPD-PEG. Moreover, in vivo treatment of 410.4 breast tumors in BALB/c mice with i.v. injected LPD-PEG-Folate delivering the HSV-1 thymidine kinase (TK) gene, in combination with gancyclovir treatment, resulted in a significant reduction in mean tumor volume (260.1 mm3) compared to the LPD-PEG-TK (914.1 mm3), as well as the vehicle (749.7 mm3) and untreated (825.3 mm3) control groups (day 25, P<.019). In addition to a reduced tumor volume, LPD-PEG-Folate-TK treatment also increased median survival from 25 days in the nontargeted LPD-PEG-TK groups to 31 days (P=.0011), which correlated with the termination of treatment. Together, these results demonstrate that in the context of a fully functional immune system, LPD-PEG-Folate-TK treatment possesses significant specific antitumor efficacy and the potential for further preclinical development.

Adenocarcinoma↗

Possible involvement of CS-ACS1 and ethylene in auxin-induced peg formation of cucumber seedlings.

BACKGROUND AND AIMS: Cucumber (Cucumis sativus) seedlings develop a peg on the concave side of the gravitropically bending transition zone between the hypocotyl and the root after seed germination. Peg initiation occurs in response to auxin when its levels in the concave side of the transition zone exceed a particular threshold through the graviresponse. Ethylene also plays an important role in peg formation, but its relationship to auxin in this event is not understood. Here, the role ethylene plays in auxin-induced peg formation is studied. METHODS: Peg formation of cucumber seedlings exposed to ethylene at different stages of growth or during exogenous auxin treatment was observed. In addition, ethylene evolution from the concave and convex sides of the transition zone was compared and their transcription of CS-ACS (1-aminocyclopropane-1-carboxylic acid synthase) genes was analysed by RT-PCR and in situ hybridization. KEY RESULTS: Seedlings treated with ethylene after peg initiation produced an enlarged peg, whereas ethylene treatment before peg initiation inhibited peg formation. Ethylene also promoted the development of the peg in the auxin-treated seedlings. Furthermore, the concave side of the transition zone at peg initiation produced more ethylene and CS-ACS1 mRNA than the convex side. CONCLUSIONS: Since CS-ACS1 is an auxin-inducible gene, the greater abundance of auxin in the concave side of the transition zone causes peg initiation and increases CS-ACS1-mediated ethylene biosynthesis, which then facilitates peg development.

Amino Acids, Cyclic↗

[Characterization and cytotoxicity of mixed PEG-DSG modified liposomes].

It is known that polyethyleneglycol (PEG) modification of the liposome surface leads to the formation of a fixed aqueous layer around the liposomes due to interaction between the PEG polymer and water molecules, which prevents the attraction of opsonins. When a combination of PEG-distearolyglycerol (PEG-DSG) whose characteristics are remarkably different is used, interaction between molecules occurs, leading to increased fixed aqueous layer thickness (FALT). From this speculation, we studied the effect of both modification of PEG900-DSG and PEG2000-DSG modified liposome on FALT, cell uptake and biodistribution. The FALT of mixed PEG modified liposome increased, compared to that of each single PEG modified liposome. In this mixed modification, maximum FALT was shown at liposome modified by added PEG-2000:PEG-900=2:1. This most suitable additional ratio was equal to actual incorporated ratio. On the other hand, cell uptake of mixed modified liposome containing doxorubicin (DOX) was similar with that of PEG2000 modified liposome. Furthermore, mixed PEG modification of liposome was tendency to increase cytotoxicity, compared to that of other modifications. After DOX contained liposome treatment, DOX distribution in the tumor and antitumor activity of DOX increase by mixed PEG modification. In conclusion, it was suggested that mixed PEG liposome (PEG-2000:PEG-900=2:1) was useful for cancer chemotherapy.

Animals↗

The uses and properties of PEG-linked proteins.

Poly(ethylene glycol) (PEG) is a water soluble polymer that when covalently linked to proteins, alters their properties in ways that extend their potential uses. PEG-modified conjugates are being exploited in many different fields. The improved pharmacological performance of PEG-proteins when compared with their unmodified counterparts prompted the development of this type of conjugate as a therapeutic agent. Enzyme deficiencies for which therapy with the native enzyme was inefficient (due to rapid clearance and/or immunological reactions) can now be treated with equivalent PEG-enzymes. PEG-adenosine deaminase has already obtained FDA approval. PEG-modified cytokines have been constructed and, interestingly, one of the conjugates, PEG-modified granulocyte-macrophage colony-stimulating factor, showed dissociation of two biological properties. This novel observation may open new horizons to the application of PEGylation technology. The biotechnology industry has also found PEG-proteins very useful because PEG-enzymes can act as catalysts in organic solvents, thereby opening the possibility of producing desired stereoisomers, as opposed to the racemic mixture usually obtained in classical organic synthesis. Covalent attachment of PEG to proteins requires activation of the hydroxyl terminal group of the polymer with a suitable leaving group that can be displaced by nucleophilic attack of the epsilon-amino terminal of lysine residues (other nucleophilic groups can also interact). Several chemical groups have been exploited to activate PEG, thereby giving rise to a variety of PEG-proteins. Some of these varieties retain part of the activating group as a coupling moiety between PEG and protein and others provide a direct linkage. For each particular application, different coupling methods provide distinct advantages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: effects of PEG chain length and PC incorporation.

Sterically stabilized micelles (SSM) composed of poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) and sterically stabilized mixed micelles (SSMM) composed of DSPE-PEG and egg-phosphatidyl choline (PC) have recently been introduced as novel lipid based carriers for water-insoluble drugs. However, factors that affect the solubilization behavior of these phospholipid micelles are not well understood. This study investigates the effect of PEG chain length and PC content on physical properties and solubilization potential of PEGylated phospholipid micelles. Critical micelle concentrations (CMC) determined for DSPE-PEG with different PEG chain lengths (2000, 3000, and 5000) using a fluorescent probe were in the micromolar range (0.5-1.5 microM) with higher CMC for longer PEG chain length. The size of micelles determined by quasi-elastic light scattering (QELS) showed that micellar systems became heterogeneous when PC was added at > or =25% for DSPE-PEG 2000 and > or = 40% for DSPE-PEG 5000, respectively. Above these critical PC ratios a significant increase in aggregation number and formation of rodlike particles were observed by small angle neutron scattering (SANS). Solubilization of diazepam was greater with DSPE-PEG 2000 than DSPE-PEG 5000 simple micelles as determined by RP-HPLC. However, DSPE-PEG 5000 micelles showed greater improvement in solubilization of the water-insoluble drug with an increase in PC content. In conclusion, phospholipid micelle size and solubilization potential varied with PEG chain length and PC content in the mixed micelle. Aggregation number and shape of the micelles did not significantly change until the critical PC concentrations.

Diazepam↗

Long-term follow-up of consequences of percutaneous endoscopic gastrostomy (PEG) tubes in nursing home patients.

PEG (percutaneous endoscopic gastrostomy) tubes are frequently placed in nursing home patients. The aim of this study was to assess retrospectively the long-term changes in functional and nutritional statuses, tube-related complications, and factors influencing survival in 46 nursing home residents, mean age 73.6 years (range 19-96). Functional status was evaluated by a standard rehabilitation medicine scale. Nutritional status was evaluated by serum albumin and cholesterol concentrations and by weight. PEG-related complications requiring hospitalization or emergency room or clinic evaluations were noted. Additionally, changes in resuscitation status were noted. The predominant indication for PEG placement was dementia (52%). At PEG placement, 48% of patients had total functional impairment. Regardless of the severity of impairment, no patient's functional status improved after PEG. Nutritional status did not improve significantly. Mortality approached 50% and 60% at 12 and 18 months, respectively, and was significantly related to age, resuscitation status, and serum albumin concentration. All patients under 40 years of age at PEG survived, in contrast to 41.3% of patients over 40 years of age (P < 0.001). Sixty-three percent of patients who were "full code" at PEG placement survived, in contrast to 10% of "no code" patients (P < 0.001). Albumin > or = 3.5 g/dl at PEG or thereafter was associated with improved survival (P < 0.001) as compared to albumin < 3.5 g/dl. PEG-related complications occurred in 34.7% of patients, and the first occurred four months after PEG. We conclude that realistic expectations of what PEG can accomplish be a factor in the decision to place a PEG tube in nursing home patients.

Adult↗

Binding and uptake of liposomes containing a poly(ethylene glycol) derivative of cholesterol (stealth liposomes) by the macrophage cell line J774: influence of PEG content and its molecular weight.

The binding and intake of liposomes containing a different molar content and chain length of a PEG-Chol derivative had been studied in cultured macrophage cell line J774. The decrease in binding and endocytosis of the liposomes containing PEG-Chol is dependent on (i) the PEG chain length, (ii) the molar content of the surfactant, (iii) the liposome concentration in the external medium. The best results in reducing the uptake of liposomes were obtained by a PEG-Chol liposome suspension with a high molar content (25%) which presents a non negligible amount of free PEG-Chol. Moreover, we could show an increase by 2 for binding and by about 5 for endocytosis of filtrated-liposomes containing 25 mol% of 8800PEG-Chol, in the absence of free PEG-Chol in the suspension. Binding and intake of control liposomes was also inhibited in the presence of free PEG-Chol. Fluid phase endocytosis of SRh was inhibited up to 45% of control in the presence of liposomes containing PEG-Chol or free PEG-Chol. Based on the comparison of 4400PEG-Chol with the most commonly used PEG derivative 5000PEG-PE, PEG-Chol is more powerful in terms of reducing their binding and endocytosis by J774 cells. Inhibition of the fluid phase endocytic process is attributed to the binding of PEG-Chol to the cells' plasma membrane inducing a decrease in surface hydrophobicity of the cells, resulting in a marked decrease in the extent of phagocytic ingestion.

Animals↗

Stabilized plasmid-lipid particles containing PEG-diacylglycerols exhibit extended circulation lifetimes and tumor selective gene expression.

Stabilized plasmid lipid particles (SPLP) consist of a single copy of DNA surrounded by a lipid bilayer. The particles are small ( approximately 100 nm), stable, monodisperse and have a low surface charge. A diffusible polyethylene glycol (PEG) coating attached to a lipid anchor is critical to the SPLP's functionality. The PEG-lipid exchanges out of the bilayer at a rate determined by the size of the lipid anchor. Here we show that SPLP can be prepared using a series of PEG-diacylglycerol lipids (PEG-S-DAGs). SPLP were prepared incorporating PEG-dimyristoylglycerol (C14), PEG-dipalmitoylglycerol (C16) or PEG-distearoylglycerol (C18) and the rate of PEG-lipid diffusion from the bi-layer determined using a FRET assay. SPLP pharmacokinetics confirm a correlation between the stability of the PEG-lipid component and circulation lifetime. PEG-S-DAGs with longer lipid anchors yield more stable SPLP particles with longer circulation half-lives yielding an increase in tumor delivery and gene expression. PEG-distearoylglycerol (C18) containing SPLP bypass so-called 'first pass' organs, including the lung, and elicit levels of gene expression in distal tumor tissue 100- to 1000-fold greater than that observed in any other tissue. The incorporation of PEG-S-DAG in SPLP confirms that small size, low surface charge and extended circulation lifetimes are prerequisite to the accumulation and tumor selective expression of plasmid DNA following systemic administration.

Diglycerides↗