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D H Thompson

Publications and source records attributed to D H Thompson.

At least 19 recordsLinked to original sources
PubMed2003

Preparation and electrochemical behavior of gramicidin-bipolar lipid monolayer membranes supported on gold electrodes.

Gramicidin-containing synthetic bolalipid membranes comprised of 2,2'-di-O-decyl-3,3'-O-1,20-eicosanyl-bis-rac-glycero-1,1'-diphosphocholine (C20BAS) have been synthesized and supported on gold electrodes. Supported membranes were prepared by first depositing a partial bolalipid layer on the electrode using a thioctic acid-modified bolalipid (1'-O-omega-thioctamidetetraethylene glycol-2,2'-di-O-decyl-3,3'-di-O-1,20-eicosanyl-bis-rac-glycero-1-phosphate, SSC20BAS) as an anchoring group, followed by a vesicle fusion step using either pure C20BAS or gramicidin-containing C20BAS (C20BAS-GA) vesicles. The latter configuration was designed to immobilize single, continuously-on channels of gramicidin in the C20BAS membrane. Vesicle deposition to form supported bolalipid monolayer membranes was monitored by impedance spectroscopy and cyclic voltammetry. Impedances were observed to increase with vesicle deposition time. Pretreatment of the impedance electrode with SSC20BAS accelerated the supported monolayer membrane deposition rate. Impedances decreased in a gramicidin concentration-dependent manner when gramicidin was incorporated into the C20BAS membrane. These supported bolalipid membranes are also surprisingly inert to organic solvent exposure (CH(3)CH(2)OH;CH(2)Cl(2)), suggesting that they may serve as robust host matrices for integral membrane protein-based sensors.

Biosensing Techniques↗
PubMed2001

Phototriggering of liposomal drug delivery systems.

Over the past several years, photodynamic therapy (PDT) has been approved for the treatment of various cancers. Additional applications of photochemical processes for triggering site-specific drug delivery are in early stages of development at this time. This review focuses on the literature appearing between January 1996-June 2001 that describe new and ongoing studies of phototriggering mechanisms that may ultimately find utility in drug delivery applications.

Animals↗
PubMed2001

Chloroaluminum phthalocyanine tetrasulfonate delivered via acid-labile diplasmenylcholine-folate liposomes: intracellular localization and synergistic phototoxicity.

Folate-diplasmenylcholine (1,2-di-O-(Z-1'-hexadecenyl)-sn-glycero-3-phosphocholine; DPPlsC) liposomes have been shown to greatly enhance the potency of water-soluble antitumor agents via a selective folate-mediated uptake and acid-catalyzed endosomal escape mechanism (Rui et al. J. Am. Chem. Soc., 1998; 120:11213--18). This study describes an adaptation of this strategy for the delivery of chloroaluminum phthalocyanine tetrasulfonate ([AlPcS(4)](4-)), a water-soluble sensitizer used in photodynamic therapy, in a binary targeting scheme designed to enhance both its tumor selectivity and phototoxicity. [AlPcS(4)](4-)/DPPlsC:folate liposomes (9.8 microM bulk concentration, 2.5 mM intraliposomal concentration) were substantially more phototoxic to folate-deficient KB cells than 12.5 microM free [AlPcS(4)](4-) after a 30 min irradiation (630-910 nm). Considerable differences in phototoxicity were observed, however, between the commercially-available AlPcS(4)(4-) and an HPLC purified sample of [AlPcS(4)](4-) due to an increased tendency for the latter to aggregate. Experiments with [AlPcS(4)](4-)/DPPC:folate and folate-free [AlPcS(4)](4-)/DPPlsC liposomes (acid-insensitive and non-targeted controls, respectively) showed significantly reduced phototoxicities under the same illumination conditions. Our results imply that higher concentrations of water-soluble sensitizers can be delivered to target cells using the folate receptor-mediated pathway, which can change both the biodistribution and intracellular localization of the sensitizer when acid-labile DPPlsC liposomes are used as the delivery vehicle. Potential advantages of this approach include the use of lower bulk [AlPcS(4)](4-) concentrations, rapid plasma clearance of free [AlPcS(4)](4-), and better phototoxic responses, due to higher intracellular [AlPcS(4)](4-) concentrations combined with reduced collateral photodamage arising from misguided sensitizer accumulation, thereby enhancing the selective phototoxicity of PDT treatments.

Aluminum↗
PubMed1999

Efficient synthesis of 40- and 48-membered tetraether macrocyclic bisphosphocholines.

An efficient route toward the synthesis of unsaturated (bis-diacetylenic) and saturated 40- and 48-membered macrocyclic biphosphocholines has been developed using 2-phenyl-5-hydroxy-1,3-dioxane as a common glycerol synthon. Ring closure was accomplished using either high-dilution Glaser oxidation of [(Cy3P)2RU==CHPh]Cl2-catalyzed olefin metathesis conditions. Deprotection of benzyl ethers using trimethylsilyl iodide (TMS-I) in the presence of diacetylenic moieties has also been demonstrated for the first time.

Acetylene↗
PubMed1999

Synthesis of acid-labile diplasmenyl lipids for drug and gene delivery applications.

The low pH environments characteristic of endosomal compartments and ischemic tissues provide an intrinsic pathway for triggering site-specific contents release from appropriately designed delivery vehicles. Accordingly, research in this group has focused on the design, synthesis and application of novel acid-sensitive lipids that will undergo facile lamellar (L alpha) to hexagonal (HII) phase transitions within these acidic sites. Previously, it has been demonstrated that plasmenylcholine-type lipids have excellent acid hydrolysis and contents release kinetics (Gerasimov et al., Biochim. Biophys. Acta. 1324 (1997) 200-214; Rui et al., J. Am. Chem. Soc. 120 (1998) 11213-11218). This paper describes the synthesis of three new acid sensitive lipids, based on a chiral 1,2-di-O-(1Z',9Z'-octadecadienyl)-sn-glycerol (6) platform, displaying phosphocholine (7), poly(ethyleneoxide) (8), and O-carbamoyl-N-diethylen-etriamine (10) headgroups. Intermediate 6 was obtained in 28% overall yield via a six step synthesis from (S)-(+)-2,2-dimethyl-1,2-dioxolane-4-methanol. Subsequent conversion to the final products was acheived in moderate (7 and 10) to excellent yields (8).

Acids↗
PubMed1998

Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers: theoretical prediction and experimental verification.

Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1, 2-diacyl-sn-glycerophosphocholines (e.g., egg L-alpha-lecithin, 1, 2-dimyristoyl-sn-glycero-3-phosphocholine, 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1, 2-distearoyl-sn-glycero-3-phosphocholine) and 1, 2-dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e. , 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e glycol)2000]carboxamide and 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e oxide)5000]carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Unusual septoplasty complication: Streptococcus viridans endocarditis.

Infection is an infrequently reported complication following septoplasty and septorhinoplasty. Among the recognized but rare infections are toxic shock syndrome, spinal osteomyelitis, meningitis, septic cavernous sinus thrombosis and endocarditis. A high index of suspicion is required to diagnose these infections early and thereby minimize morbidity and mortality. We present a case of endocarditis following septoplasty in a patient who had no identifiable preoperative risk factors but who experienced recurrent fever and chills postoperatively.

Adult↗
PubMed1997

Acid-catalyzed plasmenylcholine hydrolysis and its effect on bilayer permeability: a quantitative study.

This laboratory has previously shown (Anderson, V.C. and Thompson, D.H. (1992) Biochim. Biophys. Acta 1109, 33-42; Thompson, D.H., Gerasimov, O.V., Wheeler, J.J., Rui, Y. and Anderson, V.C. (1996) Biochim. Biophys. Acta 1279, 25-34), that plasmenylcholine (1-alk-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine; PlsPamCho) liposomes release hydrophilic contents upon photooxidation or acid-catalyzed hydrolysis. We now report the kinetics and chemical mechanism of the acid-catalyzed reaction and its effect on calcein leakage rates. Hydrolysis of the plasmenylcholine vinyl ether linkage generates fatty aldehydes and 1-hydroxy-2-palmitoyl-sn-glycero-3-phosphocholine (lysolipid); HPLC and 1H-NMR experiments establish that the former is readily air-oxidized to fatty acids, while the latter undergoes rapid acid-catalyzed rearrangement to 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine. Lysolipid formation obeys first order kinetics, yielding observed pseudo-first order rate constants that are pH-dependent. Bimolecular hydrolysis rate constants, k(bi), have also been determined. Calcein release rates from plasmenylcholine liposomes are strongly dependent on both the dihydrocholesterol (DHC) content and the extent of PlsPamCho hydrolysis within the bilayer. DHC-free plasmenylcholine liposomes (38 degrees C, pH 2.5) require < 5% PlsPamCho hydrolysis to effect > 50% calcein release within 10 min. The presence of > or = 25 mol% DHC, however, greatly reduces the observed calcein release rate; nearly 30% PlsPamCho hydrolysis is required to effect 50% calcein release over a 70-min period in 6:4 PlsPamCho/DHC liposomes. Bacteriochlorophyll a-sensitized photooxidation of plasmenylcholine liposomes also produces fatty aldehyde and another intermediate, tentatively described as 1-formyl-2-palmitoyl-sn-glycero-3-phosphocholine, that hydrolyzes to form the 1-hydroxy lysolipid. These results have important implications for the quantitative description of lysolipid effects on membrane permeability and on the design of triggerable liposomes for drug delivery.

Acids↗
PubMed1997

Microbiology of otitis externa.

Microbiologic and clinical data from 26 patients with otitis externa were prospectively evaluated. Specimens were processed for aerobic and anaerobic bacteria. Bacterial growth was noted in 23 specimens. A total of 33 aerobic and 2 anaerobic bacteria were recovered. Aerobic bacteria only were isolated in 21 (91%) patients, anaerobic bacteria only in 1 (4%), and mixed aerobic and anaerobic bacteria in 1 (4%). The most common isolates were Pseudomonas aeruginosa (14 instances), Staphylococcus aureus (7), Acinetobacter calcoaceticus (2), Proteus mirabilis (2), Enterococcus faecalis (2), Bacteroides fragilis (1), and Peptostreptococcus magnus (1). One isolate was recovered in 13 (57%) patients, 2 isolates in 8 (35%), and 3 isolates in 2 (9%). These data illustrate the polymicrobial nature of otitis externa in about half of the patients and the role of anaerobic bacteria in 8% of them. Further studies are warranted to evaluate the therapeutic implications of these findings.

Adolescent↗
PubMed1996

Triggerable plasmalogen liposomes: improvement of system efficiency.

A photoactivated liposome release system that is generally applicable for triggered release of encapsulated hydrophilic materials is described. This approach to phototriggered release, derived from the known effects of plasmalogen photooxidation on membrane permeability in whole cells and model membrane systems, relies on producing a lamellar phase change or increase in permeability upon cleaving its constitutive lipids to single-chain surfactants using 630-820 nm light to sensitize the photooxidation of the plasmalogen vinyl ether linkage. Semi-synthetic plasmenylcholine liposomes containing encapsulated calcein and a membrane-bound sensitizer, such as zinc phthalocyanine, tin octabutoxyphthalocyanine, or bacteriochlorophyll a, were prepared by extrusion. Irradiation of air-saturated liposome solutions enhanced membrane permeability toward calcein and Mn2+, and promoted membrane fusion processes compared to non-irradiated or anaerobic controls. Bacteriochlorophyll a sensitization produced the fastest observed photoinitiated release rate from these liposomes (100% calcein release in less than 20 min; 800 nm irradiation at 300 mW); the observed release rate was two orders of magnitude slower for egg lecithin liposomes prepared and irradiated under identical experimental conditions. Liposome aggregation, interlipidic particle formation, and membrane fusion between adjoining liposomes was observed by 31P-NMR, freeze-fracture/freeze-etch TEM, and cryo-TEM as a function of irradiation time. The use of near-infrared sensitizers and the capacity of photolyzed plasmenylcholine liposomes to undergo membrane fusion processes make photodynamic therapy with these liposome-borne sensitizers an attractive adjunct to biochemical targeting methods.

Drug Delivery Systems↗
PubMed1995

Quantitative bacteriology of tonsils removed from children with tonsillitis hypertrophy and recurrent tonsillitis with and without hypertrophy.

The aerobic and anaerobic bacterial species and their numbers were studied in tonsillar specimens from children who had undergone elective tonsillectomy: 6 patients with recurrent tonsillitis (RT), 9 with recurrent tonsillitis with hypertrophy (RTH), and 8 with obstructive tonsillar hypertrophy (OTH). Mixed flora were present in all tonsils, yielding an average of 6.7 isolates (5.6 aerobic or facultative and 1.1 anaerobic bacteria). The highest recovery rate of organisms per tonsil was in patients with OTH (7.7 per tonsil), compared to 6.3 per tonsil in RT and 5.9 per tonsil in RTH. The predominant aerobic and facultative organisms were Haemophilus influenzae (22 isolates), Neisseria sp (16), Staphylococcus aureus (14), and Eikenella corrodens (14), and the predominant anaerobic bacteria were Fusobacterium sp (8), Bacteroides sp (7), and Prevotella melaninogenica (5). The number of bacteria per gram of tonsillar tissue varied between 10(4) and 10(8). A higher concentration of S aureus and H influenzae was found in hypertrophic tonsils (RTH and OTH) as compared to RT. These findings suggest the presence of an increased bacterial load and supports an etiologic role for H influenzae and S aureus in hypertrophic tonsils with and without inflammation (RTH and OTH). Further studies to elucidate the effect of selective antimicrobial therapy directed at these organisms may offer an alternative management of hypertrophic tonsils.

Bacterial Infections↗
PubMed1994

Microbiology and management of chronic maxillary sinusitis.

OBJECTIVE: Assessment of the microbiology and management of patients who suffered from chronic maxillary sinusitis was studied retrospectively. DESIGN: Retrospective analysis of microbiology and antimicrobial therapy of 68 patients who underwent the Caldwell-Luc procedure for chronic sinusitis had not received antimicrobials before surgery and whose cultures showed bacterial growth. SETTING: This study was performed at the Naval Hospital in Bethesda, Md. INTERVENTION: Amoxicillin-clavulanic acid was given to 18 patients, amoxicillin or ampicillin to 25, cefaclor to 17, and erythromycin to eight. RESULTS: A total of 183 isolates (123 anaerobic and 60 aerobic) were recovered. Anaerobic organisms only were recovered from 35 (51%), specimens, and aerobic or facultative bacteria only in 12 (18%), and mixed aerobic and anaerobic flora in 21 (31%). Thirty-four aerobic and anaerobic beta-lactamase-producing bacteria were isolated from 28 patients. The 18 patients who received amoxicillin-clavulanic acid had the most rapid and complete response to therapy, none required a change in therapy, and surgical drainage was required in one case. Of 25 patients who received amoxicillin or ampicillin, eight required a change of therapy due to clinical failure (32%), including three who also had surgical drainage. Of 17 that received cefaclor, five had an antibiotic change (29%), one with surgical drainage. Of the eight who were treated with erythromycin, three needed antibiotic change (38%), two with surgical drainage. Resistant organisms were recovered from most of the patients that required therapeutic change. CONCLUSIONS: These findings indicate the major role of aerobic and anaerobic beta-lactamase-producing bacteria organisms in the polymicrobial etiology of chronic maxillary sinusitis and illustrate the superiority of therapy effective against these bacteria.

Adolescent↗
PubMed1994

Effect of anemia on survival of myocutaneous flaps in the pig.

The decision to transfuse patients after major head and neck reconstructive surgery has been influenced by the dictum that a hematocrit level of 30% or more is necessary for the survival of surgical flaps. Pedicled myocutaneous flaps are among the most frequently used methods of reconstruction after major head and neck oncologic surgery. No studies have addressed the survival of myocutaneous pedicled flaps in anemic animals. In this study survival of latissimus dorsi myocutaneous flaps in pigs was evaluated in anemic and control groups. A total of 26 pigs were randomly divided into two groups. The pigs in the anemic group were exsanguinated to normovolemic anemia (average hematocrit, 19%), followed by elevation of a latissimus dorsi myocutaneous flap. In the control group the same operation was performed without exsanguination. All other variables were kept constant. The flap survival was judged on postoperative days 3, 7, and 14 by two evaluators. Ten pigs from each group were found to have 100% flap survival on post-operative day 14. There was no significant difference in mean flap survival rates between two groups for postoperative days 3, 7, and 14. It is concluded that normovolemic anemia does not adversely affect the survival of the myocutaneous flaps. This finding may save unnecessary transfusions in postoperative patients.

Anemia↗
PubMed1993

Control of early postoperative pain with bupivacaine in adult local tonsillectomy.

Early postoperative pain following tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same-day surgery practices. Although several otolaryngologists anecdotally support intraoperative infiltration with long-acting anesthetic agents for postoperative pain control, to our knowledge, no previous study confirms this claim. In a prior investigation, we found no difference between bupivacaine hydrochloride and saline placebo in pediatric patients undergoing tonsillectomy. In this trial, we performed a similar study in an adult population. Fifty-one patients undergoing tonsillectomy with local anesthesia were randomized into bupivacaine or saline placebo groups. Patients provided the following data: (1) pain level; (2) oral intake; (3) number of pain medication doses; and (4) level of pain on jaw opening, all at 10 hours postoperatively. Bupivacaine administration resulted in no adverse effects. No difference was noted in pain level, amount of oral intake, or pain on full jaw opening. Bupivacaine group patients received fewer though not statistically significant doses of pain medication than placebo group patients. We conclude that bupivacaine is a safe medication but offers no advantage in the control of early postoperative pain in adult patients undergoing local tonsillectomy.

Adult↗
PubMed1993

Control of early postoperative pain with bupivacaine in pediatric tonsillectomy.

Early postoperative pain following pediatric tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same day surgery practices. Several otolaryngologists anecdotally support intraoperative infiltration with a long-acting amide anesthetic, bupivacaine hydrochloride, for postoperative pain control. However, no previous study supports these claims. At the National Naval Medical Center, a prospective, randomized, double-blinded study was undertaken in fifty patients, ages 3 to 16 years old. After tonsil resection, either 0.5% bupivacaine or saline was injected into each fossa. We asked the parents three questions. First, what was the level of pain at 2, 6 and 10 hours postoperatively? Second, what was the amount of oral intake during the first 10 hours after surgery? And third, how many doses of oral acetaminophen elixir were administered over the first 10 postoperative hours? Bupivacaine administration caused no adverse effects. There was no difference in perceived pain level between bupivacaine and saline groups at 2, 6 and 10 hours. Oral intake levels over the first 10 hours were similar. Although bupivacaine group patients received fewer doses of oral acetaminophen, the difference between groups was not statistically significant. We conclude that bupivacaine is a safe medication for infiltration, but offers no advantage over saline in the control of early postoperative pain in pediatric tonsillectomy.

Bupivacaine↗