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Biomedical subjects

K Marshall

Publications and source records attributed to K Marshall.

At least 55 records · Page 3Linked to original sources
PubMed1996

Investigation into the role of cyclooxygenase products in the bradykinin response on isolated human myometrium and umbilical artery.

The aim of this study was to investigate the response to bradykinin (BK) on human myometrium and umbilical artery with respect to cyclo-oxygenase (CO) products. Dose/concentration response curves to BK were performed +/-2.79 microM indomethacin. On human myometrium the response to BK (0.001-50 nmol) was biphasic and consisted of a dose-related increase in myometrial tension which was followed by a period of inhibition of myogenic activity. In tissues from P donors the presence of indomethacin had no significant effect on the excitatory response, but the inhibitory component of the response was reduced. In tissues from NP donors indomethacin significantly enhanced the BK effect at higher doses and the inhibitory component of the response was reduced. On the HUA cumulative addition of BK (1-1000 nM) resulted in dose dependent constriction with desensitisation at the highest dose (EC50 = 38 nM). The presence of indomethacin had no significant effect on BK response on HUA. These findings suggest that CO products contribute significantly to response to BK on the human myometrium but not on HUA and that different CO products are produced by P and NP tissue.

Bradykinin↗
PubMed1996

Comparison of the effects of bradykinin and related compounds on isolated mouse and human uterus.

The purpose of this study was to investigate and compare the response of the isolated human myometrium (non-pregnant donors) and mouse uterus to bradykinin (BK), Lys-BK and des-Arg9-BK (+/-2.79 microM indomethacin). The uterine strips were set up for superfusion using Kerbs' solution. On the human myometrium the responses to BK and Lys-BK were biphasic and consisted of an increase in myometrial tension which was followed by a period of inhibition of myogenic activity. Des-Arg9-BK evoked a monophasic contractile response. On the mouse uterus the responses to BK, Lys-BK and des-Arg9-BK were monophasic and contractile only. On both of the tissues the contractile responses to BK and Lys-BK were bell shaped and indomethacin abolished the bell-shaped part of the dose response curves. The response to des-Arg9-BK and the inhibitory response to BK and Lys-BK, on the human tissue, was also significantly reduced in the presence of indomethacin. The results of this study suggest that the human and mouse uterus do posses kinin receptors of the B2 type but on human myometrium these are biphasic responses.

Animals↗
PubMed1996

A preliminary study of prostaglandin release by bradykinin (BK) on isolated human myometrium.

The aim of this study was to investigate whether the response to BK on isolated human myometrium from non-pregnant (NP) and pregnant (P) donors involves the release of prostaglandin I2 (PGI2) and/or of PGE2. BK was injected as a bolus dose into the flow of the superfusate. The perfusate was collected during a response to BK and PG concentration measured by enzymoimmunoassay for PGE2 or PGI2. The BK response was biphasic, consisting of contraction followed by inhibition of myogenic activity. In tissues from both NP and P donors BK was found to cause a dose related release of PGE2 and PGI2. BK evoked PGE2 release which was greater during the contractile response than in the inhibitory response. Following the same dose of BK, PGI2 release was found to be greater in the inhibitory response than in the contractile phase. The findings indicate that in isolated human myometrium the response to BK does involve the release of PGE2 and PGI2 and in both NP and P tissue PGE2 release is greater in the contractile response phase whilst PGI2 predominates the inhibitory phase.

Bradykinin↗
PubMed1996

Evidence for human thromboxane receptor heterogeneity using a novel series of 9,11-cyclic carbonate derivatives of prostaglandin F2 alpha.

1. The pharmacological activity of a novel series of 9,11-cyclic carbonate derivatives of prostaglandin F2 alpha (PGF2 alpha) was investigated in various isolated smooth muscle preparations possessing different prostanoid receptor subtypes as well as in human platelets. Since subdivision of thromboxane (TP-) receptors into vascular/smooth muscle and platelet subtypes is a controversial subject, our studies included a human smooth muscle preparation (myometrium) in addition to the widely used rat aorta and human platelets as TP-receptor preparations. 2. Two members of that series, AGN191976 and AGN192093 were found to be highly potent and selective thromboxane-mimetics. AGN191976 and AGN192093 contracted isolated tissues of the rat thoracic aorta with EC50 values of 0.32 +/- 0.08 and 1.30 +/- 0.53 nM, respectively. Both agonists were at least 10 times more potent than the benchmark TP-agonist, U-46619, in this preparation, whilst being at least 500 times less potent at other prostanoid receptors (DP, EP1, EP3, FP, IP) in vitro. 3. In human myometrial strips from pregnant and non-pregnant donors, both AGN191976 and AGN192093 were potent contractile agonists. The rank order of potency in myometrium of AGN191976 > AGN192093 > U-46619 correlated well with that in the rat aorta. In human platelet-rich plasma (PRP), however, AGN191976 had potent proaggregatory activity (EC50 = 16.3 +/- 1.4 nM), which is a TP-receptor-mediated event, whereas AGN192093 was a much weaker agonist (EC50 = 37.9 +/- 2.0 microM). AGN192093 did not behave as an antagonist in the platelets, since it did not antagonize platelet aggregation induced by ADP, arachidonic acid, U-46619 or AGN191976. In human washed platelets, the activity profile of AGN191976 (EC50 = 4.15 +/- 0.52 nM) and AGN192093 (no aggregation up to 10 microM) was similar to that obtained in PRP. 4. The involvement of TP-receptors was verified with the potent TP-antagonist, SQ29548. SQ29548 (0.1 microM in myometrium; 1 microM in aorta; 1 microM and 10 microM in platelets) antagonized responses to U-46619, AGN191976 and AGN192093 as expected. 5. In conclusion, AGN191976 and AGN192093, both 9,11-cyclic carbonate derivatives of PGF2 alpha, were found to be highly potent and selective thromboxane-mimetics in rat vascular and human myometrial smooth muscle. However, only AGN 191976 was a potent agonist at TP-receptors in human platelets. The differential activity of AGN192093 on TP-receptor-mediated events in platelets and smooth muscle provides further evidence for a subdivision of TP-receptors. AGN192093 appears to be a useful tool for the pharmacological distinction of TP-receptor subtypes.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Introduction of laparoscopic cholecystectomy in a large teaching hospital: independent audit of the first 3 years.

Commencing with the introduction of laparoscopic cholecystectomy, a detailed independent prospective audit of all cholecystectomies attributable to 12 general consultant surgeons has been carried out over a period of 3 years. Of 650 operations 502 were intended laparoscopic cholecystectomies. In the first year 58 per cent were intended laparoscopic cholecystectomies; this rose to 80 per cent in the second year and to 90 per cent in the third. The conversion rate was 21 per cent in the first year, 21 per cent in the second and 15 per cent in the third. The mean operating time for laparoscopic cholecystectomy was 133 min for year 1, 123 min for year 2 and 115 min for year 3, compared with 92, 101 and 95 min respectively for open cholecystectomy. The overall complication rate was 10 per cent for laparoscopic and 21 per cent for open cholecystectomy. This included six bile duct injuries (1.2 per cent) in the patients undergoing the laparoscopic procedure and one (0.7 per cent) in those having open cholecystectomy. This unselected audit of a group of general surgeons introducing laparoscopic cholecystectomy into their practice has revealed complication and conversion rates that are higher than those reported in most of the published literature, but may be representative of practice throughout the UK.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1995

Multiskilling--re-engineering work process.

Many North American companies have recognized the need to re-engineer their core processes to achieve breakthrough improvements in cost, service and efficiency. In fact, it is estimated that U.S. companies alone will spend millions on business re-engineering projects this year. But change experts say that most re-engineering is in name only, cautiously tackling only one process or department at a time. Even fewer hospitals have attempted this magnitude of change. Toronto's Sunnybrook Health Science Centre is the first institution of its size in Canada to embark on a multifaceted re-engineering strategy toward a model of patient focused care. The following is an overview of Sunnybrook's experience with the first of these strategies: multiskilling service workers. The concept of multiskilling provides for a focus on redesigning job classifications to broaden the scope of responsibility. For Sunnybrook, this entailed the amalgamation of six service positions--unit aide, health care aide, dietary aide, orderly, porter, housekeeper and attendant into one service assistant position.

Clinical Competence↗
PubMed1995

Characterization of the prostanoid receptors mediating constriction and relaxation of human isolated uterine artery.

1. This study was undertaken to characterize pharmacologically the prostanoid receptor subtypes mediating constriction and relaxation of human isolated uterine artery. 2. U-46619 was a potent constrictor agonist on human uterine artery (EC50 [95% CL] = 3.5 [1.8-6.7] nM). Prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2 only weakly constricted the uterine artery, being at least 100 times less potent than U-46619. The PGE2 and PGI2 constrictor effects may be modified by the potent dilator effects of these compounds. A number of agonists which show selectivity for FP-, DP- and EP-receptors including ICI 81008, BW 245C, sulprostone, rioprostil and butaprost, failed to cause any constriction at concentrations up to 30 microM. 3. Constrictor responses induced by all agonists tested were reduced or abolished by the TP-receptor blocking drugs, GR 32191 and EP 092. pA2 estimates for both antagonists versus U-46619 were 8.50, values which are consistent with their affinities at TP-receptors. 4. In preparations pre-constricted with phenylephrine (1 microM) both PGI2 and PGE2 were potent relaxant agonists. The selective IP-receptor agonists, cicaprost and iloprost, also dilated human uterine artery and were approximately 10 fold more potent than PGI2. The EP2-receptor agonists, butaprost and rioprostil and the selective DP-agonist, BW 245C, were at least 100 fold weaker than PGI2 and PGE2 suggesting that neither DP- nor EP2 receptors were involved. 5. We conclude that TP-receptors mediate constriction, whereas IP- and possibly EP4-receptors mediate relaxation of human uterine artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Development and evaluation of an inventory for rating client satisfaction with outcome in HIV counseling: the Albion Center scale.

We developed an inventory for rating client satisfaction with outcome in HIV counseling, based on interview responses with clients. The resulting 19-item scale was subject to factor analysis and four factors, accounting for 56% of the variance, emerged. The factors described dimensions of Perception of progress and improved mood; Recognition of a specific need for counseling; Behavior change from counseling; and Counseling climate. Factor-scored scales were significantly associated with time in counseling and for the Specific need for counseling scale, HIV-seropositive respondents had a significantly higher score. Scale reliabilities (Cronbach's alpha) were between 0.85 and 0.50. Concurrent administration with the Counseling Evaluation Inventory indicated that there were significant correlations between the two scales.

Adult↗
PubMed1994

Prediction of peptide affinity to HLA DRB1*0401.

Hydrogen bonding between conserved amino acids in the HLA DR and the peptide backbone of the ligand both provide the majority of free energy of binding and force the peptide ligands to adopt a similar extended conformation. Consequently the corresponding side chains of all peptides interact with similar pockets in the binding site. For peptides of a common length the contribution of the peptide backbone can be treated as a constant and the differential affinity can be viewed as a simple sum of the side chain interactions. These can be quantified by measuring the effects of each of the naturally occurring amino acids in the context of a simplified polyalanine backbone containing an aromatic amino acid to orient the peptide unequivocally in the binding site. The dataset of the relative contributions can be used to predict quantitatively the affinity of any peptide sequence.

Amino Acid Sequence↗
PubMed1993

Panorama.

Explore the source record for details and available documents.

Cross Infection↗
PubMed1993

Comparison of three different forms of HLA-DR4Dw4 proteins.

The biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI-DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected chinese hamster ovary cells. Recombinant and B cell-derived DR4Dw4 molecules bound monoclonal anti-DR4Dw4 antibodies with different affinities and varied in their stability in the presence of sodium dodecyl sulfate. The three forms of DR4Dw4 bound peptides with a similar apparent affinity constant, but soluble class II molecules bound up to ten times more peptide than DR4Dw4 containing a transmembrane region. Peptide binding kinetics for soluble DR4Dw4 molecules were 10-20 times faster than for the other two forms of DR4Dw4 molecules. Finally, soluble PI-DR4Dw4/peptide complexes were shown to stimulate T cell proliferation.

Amino Acid Sequence↗
PubMed1993

Calibration of a compaction simulator for the measurement of tablet thickness during compression.

For the calibration of a compaction simulator for punch displacement measurements, the displacement of the punch must be related to the voltage output of a linear variable displacement transducer (LVDT) which is attached to the punch via its movable core, with correction for any deformation of the machine parts which are inherently incorporated in the LVDT readings. Contrary to common assumptions the relationship between the displacement of the movable core and the voltage output of the LVDTs used is not linear. Similarly, the deformation of the machine parts did not follow Hooke's law of linear elasticity but exhibited characteristics of nonlinear elasticity. The data demonstrate the need for careful validation of the calibration of a compaction simulator when accurate punch displacements are required.

Calibration↗
PubMed1993

In vitro characterization of prostanoid receptors on human myometrium at term pregnancy.

1. Prostanoid receptors present on the pregnant human myometrium in vitro have been characterized according to the receptor classification proposed by Coleman et al. (1984) using natural prostanoids and synthetic, selective analogues and antagonists where available. 2. Prostaglandin E2 (PGE2) produced a biphasic effect consisting of an initial excitation followed by a dose-related inhibition. The EP2/EP3-receptor agonists, rioprostil and misoprostol, produced similar effects to PGE2, however, the excitatory event of the misoprostol response was related to dose. The EP1/EP3-receptor agonist, sulprostone, evoked a purely excitatory response which was unaffected by AH6809. The selective EP2-receptor agonist butaprost produced a long-lasting dose-dependent inhibition of activity. The results from these prostanoids indicated that inhibitory EP2- and excitatory EP3-receptors are present on myometrium from pregnant donors at term. 3. PGF2 alpha and the synthetic FP-receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP-receptors. 4. PGD2 produced a biphasic effect of which the inhibition appeared dose-related and was antagonized by the selective DP-receptor antagonist BW A868C. The selective DP-receptor agonist, BW245C, produced a potent inhibitory effect that was competitively antagonized by BW A868C (pA2 = 8.6). 5. PGI2 produced a biphasic response qualitatively similar to PGE2. The EP1/IP-receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose-related inhibition. The selective IP-receptor prostanoid, cicaprost, evoked only an inhibitory response. 6. The stable thromboxane A2 (TXA2)-mimetic, U46619, produced potent excitation which was competitively antagonized by the TP-receptor antagonist, GR32191 (pA2 = 7.2). 7. The prostanoids tested indicate that a heterogeneous population of prostanoid receptors are presen ton human myometrium from pregnant donors. It may be concluded that excitation is EP3-, FP- and TP-receptor-mediated and inhibition is EP2-, DP- and IP-receptor-mediated. Comparison of data obtained from non-pregnant specimens indicates that the lower segment tissue from pregnant donors demonstrated more pronounced responses to EP2 and IP-receptor activation.

Female↗