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Biomedical subjects

J Gillard

Publications and source records attributed to J Gillard.

At least 37 records · Page 2Linked to original sources
PubMed1995

Variations in clinical experience of pre-registration house officers: the effect of London.

A postal questionnaire was used to examine possible differences in clinical experience of pre-registration house officers (PHROs) in eight former English regions, and, within the Thames regions, between teaching hospitals, and non-teaching hospitals in Inner London, Outer London and outside London. The main measurements were the numbers of patients clerked in an average week as emergency, routine or day admissions or as outpatients; the number of patients under the respondents' care at time of reply; the experience of specific clinical conditions gained; the overall adequacy of clinical experience; and the suitability of posts for preparing respondents to work as casualty officers, senior house officers, or general practitioners. The results indicate that less clinical experience was acquired by PRHOs training in the Thames regions. They had fewer admissions per week, fewer patients, and exposure to fewer surgical conditions. Within the Thames regions, there was a gradient of improving educational quality (in all areas of this study) from the teaching hospitals, through the non-teaching hospitals in inner and in outer London, and then to the hospitals outside London. No differences were found between Thames region posts outside London and non-Thames regions.

Attitude of Health Personnel↗
PubMed1993

[Plaster of Paris: a carrier for antibiotics in the treatment of bone infections].

Local antibiotherapy by diffusion from plaster of Paris is a promising method in orthopedic surgery. Nevertheless, the characteristics of this matrix have not yet been extensively studied with respect to regulation of drug-carrier capacity. From the careful comparative investigation of five commercialized plasters of Paris, it appears that the material must be constituted of fine homogeneous crystals devoid of any additive in order to obtain reproducible implants which are sufficiently hard. This condition determines their use as a biodegradable filler of bone cavities. Because of the antimicrobial spectrum, diffusion velocity and synergistic effect of sodium fusidate, amoxicillin trihydrate and sodium amoxicillin, this association of antibiotics with the plaster of Paris appears to be a useful sterilizing delivery system. The plaster of Paris allows a significant release of sodium amoxicillin during the first 3 days. This is followed by an important sustained liberation of sodium fusidate and amoxicillin trihydrate for one week. Finally, the local release of sodium fusidate for at least 2 weeks at concentrations higher than the minimum inhibition concentrations (MIC) of the most frequently infecting pathogens in osteomyelitis, will allow the sterilization of bone cavities.

Anti-Bacterial Agents↗
PubMed1991

The human sigma site, which resembles that in NCB20 cells, may correspond to a low-affinity site in guinea pig brain.

1,3-di(2-[5-3H]tolyl)Guanidine ([3H]DTG) was found to bind to a single saturable population of binding sites in human cerebral cortex and NCB20 cells, a second low-affinity site was apparent in guinea pig brain. Displacement studies were performed to determine the pharmacology of the [3H]DTG binding site in these 3 membrane preparations. In human cortical tissue and NCB20 cell membranes the (+)-stereoisomers of benzomorphans displaced binding with Hill coefficients close to one, displayed similar affinity and did not give the biphasic displacement curve characteristic of guinea pig membranes. The pIC50 of the low-affinity component of the sigma binding site in guinea pig brain correlates best with the affinity of drugs for the binding site in human cortex.

Animals↗
PubMed1991

[Psycho-action of pressurized hydrogen. Apropos of 3 cases].

During research about high pressure, some divers presented an organic syndrome with delirium when the mixed gaz (hydrogen with oxygen) was in a particular level. All the divers were better and mental symptom disappeared during the coming back to normal level of gaz pressure. With the same pressure and mixed gaz animals show a distortion of dopamine's receptors and the authors try to give an explanation for that "hydrogen syndrome" occurrence. Pressure effects and ionizing power of hydrogen could be the beginning of dopamine's distortion.

Animals↗
PubMed1989

Fractional conversion of thromboxane A2 and B2 to urinary 2,3-dinor-thromboxane B2 and 11-dehydrothromboxane B2 in the cynomolgus monkey.

Following the intravenous administration of thromboxane (TX) B2, the stable hydration product of TXA2, to human and nonhuman primates the most abundant urinary metabolites are 2,3-dinor-TXB2 and 11-dehydro-TXB2. However, it is not known whether fractional conversion of TXB2 to its enzymatic metabolites is an accurate representation of TXA2 metabolism. Thus, we have compared the metabolic disposition of synthetic TXA2 and TXB2 via the beta-oxidation and 11-OH-dehydrogenase pathways in vivo in the monkey. TXA2 or TXB2 (20 ng/kg) was intravenously administered to four cynomolgus monkeys pretreated with aspirin in order to suppress endogenous TXA2 production. Urinary TXB2, 2,3-dinor-TXB2 and 11-dehydro-TXB2 were measured before, during and up to 24 h after thromboxane administration by means of reversed-phase high-performance liquid chromatography radioimmunoassay. Aspirin treatment suppressed urinary 2,3-dinor-TXB2 and 11-dehydro-TXB2 by approx. 75%. A similar fractional conversion of TXA2 and TXB2 into 2,3-dinor-TXB2 and 11-dehydro-TXB2 was found. These results suggest that TXA2 is hydrolyzed to TXB2 prior to enzymatic degradation and that metabolites of the latter represent reliable indices of TXA2 biosynthesis. Due to the variability in the conversion of thromboxanes into 2,3-dinor-TXB2 and 11-dehydro-TXB2, the measurement of both metabolites seems to represent a more reliable index of acute changes in TXA2 production.

Animals↗
PubMed1989

L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor.

L-663,536 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2, 2-dimethylpropanoic acid) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human polymorphonuclear leukocytes (PMN) (IC50, 2.5 nM). Similarly, L-663,536 inhibited A23187-induced LTB4 formation by rat peripheral blood and elicited PMN. At concentrations where inhibition of leukotriene biosynthesis occurred in human whole blood (1.1 microM), no effect was seen on cyclooxygenase or 12-lipoxygenase, an effect also observed in washed human platelets. The compound had no effect on rat or porcine 5-lipoxygenase indicating that L-663,536 is not a direct 5-lipoxygenase inhibitor. When administered in vivo L-663,536 was a potent inhibitor of antigen-induced dyspnea in inbred rats pretreated with methysergide (ED50, 0.036 mg/kg p.o.) and of Ascaris-induced bronchoconstriction in squirrel monkeys (1 mg/kg p.o.). The compound inhibited leukotriene biosynthesis in vivo in a rat pleurisy model (ED50, 0.2 mg/kg p.o.), an inflamed rat paw model (ED50, 0.8 mg/kg), a model of leukotriene excretion in rat bile following antigen provocation, and a model in the guinea-pig ear where leukotriene synthesis was induced by topical challenge with ionophore A23187 (ED50, 2.5 mg/kg p.o. and 0.6 micrograms topically). The results indicate that L-663,536 is a potent inhibitor of leukotriene biosynthesis both in vitro and in vivo indicating that the compound is suitable for studying the role of leukotrienes in a variety of pathological situations.

Animals↗
PubMed1989

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist.

L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.

Anesthesia↗
PubMed1989

[Treatment of chronic osteomyelitis in Africa with plaster implants impregnated with antibiotics].

Nineteen African patients with osteomyelitis were treated by curettage of the lesions and packing of the bone cavities with plaster of Paris pellets containing antibiotics (Fucidin and Amoxycillin). Of 18 patients followed, 16 showed wound healing in an average of 3 to 6 weeks. Eight patients had regular roentgenographic examinations during a minimum of two months. In six of these patients, healing of the lesions and a significant osteogenic reaction were observed. The plaster pellets were resorbed in 3 to 6 weeks in all patients, and no signs of rejection were noted. In spite of insufficient follow-up due to medical conditions in Africa (Zaire), the study confirms the advantages of this simple treatment of osteomyelitis in underdeveloped countries.

Adolescent↗
PubMed1988

The affinities of prostaglandin H2 and thromboxane A2 for their receptor are similar in washed human platelets.

Both thromboxane A2 (TXA2) and its precursor prostaglandin H2 (PGH2) are labile and share a common receptor. The affinities of these two compounds for their putative common receptor are unknown. We compared the potencies of TXA2 and PGH2 to aggregate human platelets and bind to the TXA2/PGH2 receptor. TXA2 was more potent than PGH2 in initiating aggregation in platelet-rich plasma, EC50 of 66 +/- 15 nM and 2.5 +/- 1.3 microM, respectively. In washed platelets, however, PGH2 was more potent than TXA2 with EC50 values of 45 +/- 2 nM and 163 +/- 21 nM, respectively. The affinity of these two compounds in washed platelets was determined in radioligand competition binding assays employing [125I]-PTA-OH. The Kd values for PGH2 and TXA2 were 43 nM and 125 nM, respectively. The results demonstrate that the affinity of PGH2 for the platelet TXA2/PGH2 receptor is greater than previously thought. The data raise the possibility that PGH2 may significantly contribute to the responses attributed to TXA2 in vivo.

Binding, Competitive↗
PubMed1987

Pharmacology of L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpro pan oic acid); a potent, selective thromboxane/prostaglandin endoperoxide antagonist.

L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropa noic acid) has been studied in vitro on the guinea-pig tracheal chain, pulmonary artery and thoracic aorta ring and shown to be a potent, competitive antagonist of contractions induced by the prostaglandin endoperoxide analogue, U-44069 (pA2 values 8.0, 8.4 and 8.0 respectively). Selectivity on the guinea-pig trachea was indicated by non-competitive antagonism of contractions induced by prostaglandin D2 and minimal activity against contractions induced by leukotriene D4, prostaglandin F2 alpha, serotonin, histamine and acetylcholine. L-655,240 was a potent inhibitor of the aggregation of washed human platelets induced by U-44069 (IC50 value 7 X 10(-9) M) and inhibited aggregation of human platelet rich plasma induced by U-44069, U-46619, thromboxane A2 and collagen but not ADP or platelet activating factor. In vivo i.v. L-655,240 administered to guinea-pigs inhibited bronchoconstriction induced by i.v. U-44069 and arachidonic acid (ED50 values 0.09 and 0.23 mg kg-1) but not histamine, acetylcholine or serotonin. When administered to rhesus monkeys (3 and 10 mg/kg p.o.), L-655,240 inhibited ex vivo platelet aggregation induced by U-44069 but not ADP. It is concluded that L-655,240 is a potent, selective, orally active thromboxane/prostaglandin endoperoxide antagonist.

Animals↗
PubMed1986

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: a method of assessing the Circle of Willis.

Transcranial pulsed Doppler ultrasound and spectral analysis were used for detection of blood velocities in the basal cerebral arteries. The Doppler transducer was placed superior to the zygomatic arch and during insonation of the middle cerebral artery care was taken to obtain maximum Doppler-shift frequency signals since this allowed a small angle between the ultrasound beam and this artery. Doppler signals were obtained from the middle, anterior, and posterior cerebral arteries in 20 volunteers with the average depth of the Doppler gate at 4.9 (4.6-5.2 cm), 5.2 (4.9-5.4 cm), and 6.3 cm (6.0-6.9 cm), respectively. These measurements were in agreement with those obtained for 15 cadaver studies, in whom the distance from the proposed site of the Doppler transducer to each basal cerebral artery was measured as 4.7 +/- 0.6, 5.3 +/- 0.5, and 5.9 +/- 0.9 cm, respectively. The reproducibility of middle cerebral artery blood velocity values was tested in seven subjects and showed a variation of not more than 8% in any individual. The method was used in combination with common carotid compression to assess four patients who had occlusive extracranial carotid disease; in three the disease was more severe on one side and reversal of blood flow in the proximal ipsilateral anterior cerebral artery was demonstrated, consistent with cross flow from the contralateral side via the anterior communicating artery of the Circle of Willis. In the fourth patient augmentation of posterior cerebral artery blood velocities during common carotid compression indicated the major collateral source was from the vertebrobasilar system.

Adult↗
PubMedDate not supplied

Influence of various technological parameters on the preparation of spray-dried poly(epsilon-caprolactone) microparticles containing a model antigen.

This work evaluates the efficacy of the spray-drying technique to prepare poly(epsilon-caprolactone) (PCL) microparticles containing an entrapped model antigen (bovine albumin, BSA). The presence of a stabiliser was found to be an important parameter when preparing PCL microparticles containing a hydrophilic antigen. The effect of various technological parameters (concentration of the polymer and protein solutions, organic/aqueous phases ratio, nature of solvents and emulsion parameters such as duration and speed of agitation) on microparticle morphology and size, BSA entrapment and encapsulation efficiency was studied. Microparticles were characterized by a mean size from 9.56+/-0.25 to 24.31+/-2.87 microm and a BSA entrapment from 0.80+/-0.02 to 24.21+/-0.23% (w/w). SDS-PAGE electrophoresis and isoelectric focusing (IEF) confirmed the conservation of the physicochemical characteristics of the BSA entrapped within PCL microparticles produced by spray-drying. Together, these results showed that spray-drying is an efficient technique to overcome the key obstacle that represents the scaling-up of the manufacturing process to produce sufficient quantities of vaccine for clinical trials and, ultimately, commercialization.

Animals↗
PubMedDate not supplied

Protein-loaded poly(epsilon-caprolactone) microparticles. I. Optimization of the preparation by (water-in-oil)-in water emulsion solvent evaporation.

The aim of this work was to optimize protein entrapment in pure poly(epsilon-caprolactone) (PCL) microparticles (MP) using the (water-in-oil)-in water solvent evaporation technique and bovine serum albumin (BSA) as drug model. Therefore, the preparative variables such as polymer solvent, protein/polymer ratio, polymer molecular weight, internal aqueous/organic phases ratio, organic/external aqueous phase ratio, and nature of the emulsifier were evaluated on microparticle characteristics such as BSA entrapment, entrapment efficiency, size and morphology. The in vitro release profiles of BSA from such MP in two different media with or without sodium dodecyl sulphate (SDS) were investigated. In optimum conditions, smooth and spherical pure PCL MP with high encapsulation efficiency (50.29 +/- 5.01%) were prepared. The release profiles of BSA in the release media were significantly different and faster in the presence of SDS. Moreover, they exhibited a relatively low burst effect after 24h (<30%) followed by a continuous release over 28 days. Due to PCL's numerous desirable characteristics, such MP could be an exciting alternative for the controlled release of proteinaceous compounds.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Protein-loaded poly(epsilon-caprolactone) microparticles. II. Muramyl dipeptide for oral controlled release of adjuvant.

This work investigated the means for the efficient encapsulation of muramyl dipeptide (MDP) in poly(epsilon-caprolactone) (PCL) microparticles (MP) by a solvent evaporation method in order to optimize the effect of the adjuvant for oral immunization. Therefore, the influence of MDP concentration in the inner aqueous phase was evaluated on MP characteristics such as size, morphology, drug entrapment, entrapment efficiency and the eventual interactions of MDP with co-entrapped model antigen, bovine serum albumin (BSA). The process of manufacturing produced a high entrapment efficiency of MDP (63.58 +/- 0.40%) without altering its integrity, as shown by chromatogram peaks analysis of a and beta anomers. The crystallinity of the polymer was dramatically increased (+24.6%) either with or without MDP loading but the entrapment of BSA reduced this crystallinity suggesting BSA-PCL interaction. These MP were resistant to simulated gastric fluid and exhibited a continuous BSA release. Moreover, their average diameter (<10 microm) combined with their high hydrophobicity make of this delivery system an exciting alternative for enhanced oral immunization.

Acetylmuramyl-Alanyl-Isoglutamine↗