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Biomedical subjects

D A Parker

Publications and source records attributed to D A Parker.

At least 19 recordsLinked to original sources
PubMed2001

Comparative activities of the enantiomeric GABA(B) receptor agonists CGP 44532 and 44533 in central and peripheral tissues.

In neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonists baclofen, (3-amino-2(S)-hydroxypropyl)methylphosphinic acid (CGP 44532), and its (R)-enantiomer CGP 44533 depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50)=10, 6.5, and 50 microM, respectively). These effects were reversibly antagonised by the GABA(B) receptor antagonist (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) (3, 10, and 30 microM) (average pA(2) value=6.0+/-0.2). In neocortical wedges, baclofen, CGP 44532 and CGP 44533 elicited concentration-dependent hyperpolarisations (the EC(50)s were 14, 7.5 and 16 microM, respectively) sensitive to Sch 50911 (1, 5, 10 microM) (average pA(2) value=6.0+/-0.1), whilst they also depressed ileal electrically elicited cholinergic twitch contractions (EC(50)=11, 7, and 50 microM) that were antagonised by Sch 50911 (average pA(2) value=6.0+/-0.1). In electrically stimulated brain slices preloaded with [3H]GABA, baclofen, CGP 44532 and CGP 44533 decreased [3H]GABA release (IC(50)=5, 0.45, and 10 microM); this effect was reversed by Sch 50911 (50 microM). It is concluded that CGP 44532 is a far more potent agonist at GABA(B) autoreceptors than at central or peripheral heteroreceptors.

Animals↗
PubMed2001

CGP 36216 is a selective antagonist at GABA(B) presynaptic receptors in rat brain.

In rat neocortical preparations maintained in Mg(2+)-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50) = 6 microM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 microM) (pA(2) = 3.9 +/- 0.1). By contrast, CGP 36216, up to 1 mM, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through gamma-aminobutyric acid(B) (GABA(B)) postsynaptic receptors. In electrically stimulated brain slices preloaded with [3H]GABA, CGP 36216 increased [3H]GABA release (IC(50) = 43 microM), which was reversed by baclofen (20 microM). While CGP 36216 is ineffective at GABA(B) postsynaptic receptors, it is appreciably more active at presynaptic receptors.

Animals↗
PubMed2001

Long-term followup of cementless versus hybrid fixation for total knee arthroplasty.

In a prospective trial, 99 patients (100 knees) with osteoarthritis were randomized to either cementless or hybrid fixation of cruciate-retaining Miller-Galante-I total knee arthroplasties between January 1987 and December 1988. Thirty-one patients died during the study period and two additional patients were lost to followup, leaving 67 total knee arthroplasties for analysis. Thirty-nine patients underwent revision surgery at an average of 6.9 years postoperatively. The main reason for revision surgery was failure of metal-backed patellas with 25 knees revised at an average of 7.4 years, and the second most common reason was tibial polyethylene failure. Survival curves showed 60% survival at 14 years for all knees, and 85% survival at 14 years when failures for metal-backed patellas and infection were excluded, with no significant difference between the two groups. Failure of metal-backed patellas was significantly higher in the cementless group. Tibial polyethylene failure occurred in five of the hybrid group and none of the cementless group, but this was not a significant difference. Surviving prostheses were assessed at an average of 12.8 years (range, 11.5-13.5 years). Average clinical scores were 94.8 points preoperatively, and 143 points at the latest followup, with significantly higher scores in the hybrid group. Differences in outcome between the two groups were not sufficiently significant to recommend one method of fixation over another. With elimination of poor design features related to the patellofemoral articulation and thin tibial polyethylene, cruciate-retaining total knee arthroplasties can yield good durable results, whether cementless or hybrid fixation is used.

Aged↗
PubMed2001

The John Charnley Award: Three-dimensional analysis of the cement mantle in total hip arthroplasty.

Cemented fixation of the femoral stem is the gold standard for patients older than 60 years. The importance of reliably achieving an adequate cement mantle has been shown in many studies. Currently, inspection and grading of plain radiographs is the accepted method for study of the cement mantle. However, the reliability of plain radiographs for this purpose has been questioned. In addition, the interobserver agreement of current grading systems has been shown to be limited. A new in vitro method of cement mantle analysis is described. Plastic replicas of six contemporary stems were implanted into femurs from cadavers. The specimens were imaged with a computed tomography scanner. Detailed, computer-assisted analysis of mantle thickness was done. Comparisons were made between designs. A subset was compared with standard radiographs. Plain radiographs overestimated thickness and underestimated the deficiencies. There was significant variability in the mantle produced by the different designs. Commonly used designs had deficiencies in their mantles by standard criteria despite proper surgical technique. The importance of being fully acquainted with the particular implant one uses is emphasized by these results. This is a valuable technique for investigation of the effects on the cement mantle of implant design, surgical technique, and patient anatomy.

Arthroplasty, Replacement, Hip↗
PubMed2000

Failure of presynaptic purinoceptors to modulate noradrenaline release from sympathetic nerves in human dental pulp.

The effects of putative presynaptic P1- and/or P2-purinoceptors on the release of noradrenaline from sympathetic nerves in human dental pulp were examined by testing the effects of agonists and an antagonist of these receptors on the stimulation-induced overflow of [(3)H]noradrenaline from tissue treated with desipramine (0.3 micromol/l) and preincubated with [(3)H]noradrenaline (0.6 micromol/l). The P1-purinoceptor agonists adenosine (1.0 mmol/l) and 2-chloroadenosine (0.01-1.0 mmol/l) and the antagonist 8-cyclopentyl-1,3-dipropyl xanthine (1.0 micromol/l), and the P2-purinoceptor agonists ATP (0.1 mmol/l) and beta, gamma-methylene-ATP (0.01 mmol/l), did not modulate the release of noradrenaline. Adenosine was also without effect in dental pulp treated with the alpha(2)-adrenoceptor antagonist rauwolscine. It is concluded that presynaptic P1-purinoceptors and those P2-purinoceptors activated by adenine nucleotides are either not present on sympathetic nerves in human dental pulp or that they exert little or no effect on the release of noradrenaline.

2-Chloroadenosine↗
PubMed2000

Effect of different types of Medicaid managed care on childhood immunization rates.

Medicaid managed care can improve access to prevention services, such as immunization, for low-income children. The authors studied immunization rates for 7,356 children on Medicaid in three managed care programs: primary care case management (PCCM; n = 4,605), a voluntary HMO program (n = 851), and a mandatory HMO program (n = 1,900). Immunization rates (3:3:1 series) in PCCM (78%) exceeded rates in the voluntary HMO program (71%), which in turn exceeded those in the mandatory HMO program (67%). Adjusting for race, urban residence, and gender, compared to children in PCCM, children in the voluntary HMO program were less likely to complete the 3:3:1 series (OR = 0.75, CI = 0.63, 0.90), and children in the mandatory HMO program were even less likely to complete the series (OR = 0.59, CI = 0.51, 0.68). Results differed by individual HMOs. Monitoring of outcomes for all types of managed care by Medicaid agencies is imperative to assure better disease prevention for low-income children.

Child, Preschool↗
PubMed1999

Pharmacological re-evaluation of a GABA(B) receptor antagonist CGP 47332A in rat brain.

In rat neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonist baclofen concentration-dependently depressed the frequency of spontaneous discharges (EC(50)=12 microM). This was reversibly antagonised by (R, S)-3-amino-2-hydroxy-propyl-P-n-butyl-phosphinic acid (CGP 47332A) (25, 100, 300 microM) which produced rightwards shifts of the baclofen concentration-response curves (pA(2) value=4.8+/-0.1). In electrically stimulated slices preloaded with [3H]GABA, CGP 47332A increased its release (EC(150)=100 microM) through antagonism of GABA(B) autoreceptors. Although CGP 47332A was some six times weaker on GABA(B) auto- than on heteroreceptors, yet its congener lacking the beta-hydroxy substituent displays equal potency in both binding (IC(50)=38 microM) and GABA(B) autoreceptor functional studies (EC(150)=38 microM) as previously reported [Froestl, W., Mickel, S.J. , Von Sprecher, G., Diel, P.J., Hall, R.G., Maier, L., Strub, D., Melillo, V., Baumann, P.A., Bernasconi, R., Gentsch, C., Hauser, K., Jaekel, J., Karlsson, G., Klebs, K., Maitre, L., Marescaux, C., Pozza, M.F., Schmutz, M., Steinmann, M.W., Van Riezen, H., Vassout, A., Mondadori, C., Olpe, H.R., Waldmeier, P.C., Bittiger, H., Phosphinic acid analogues of GABA: 2. Selective, orally active GABA(B) antagonists. J. Med. Chem. 38 (1995) 3313-3331.].

Animals↗
PubMed1999

Antagonism of GABA(B) receptors by morpholino-2-acetic acid derivatives Sch 54679 and Sch 51324 in rat brain.

In rat neocortical slices maintained in Mg2+-free Krebs medium, baclofen depressed the rate of spontaneous discharges in a concentration-dependent manner (EC50 = 4.5 microM). This depression was reversibly antagonised by 5-(S,R)-hydroxymethyl-5-methylmorpholinyl-2-(R,S)-acetic acid (Sch 54679) and 2-(R,S)-5-[spirocyclopentyl]-morpholinyl-acetic acid (Sch 51324) (respective pA2 values of 5.8+/-0.15 and 5.4+/-0.2). In electrically-stimulated slices preloaded with [3H]gamma-aminobutyric acid (GABA), Sch 54679 (EC50 = 3 microM) was 2.3 times more potent than Sch 51324 (EC50 = 7 microM) in increasing [3H]GABA release through antagonism of GABA(B) autoreceptors. These structurally novel analogues may be pharmacologically useful for elucidating GABA(B) receptor functions.

Animals↗
PubMed1999

Inhibitory effects of adrenaline on the release of noradrenaline from sympathetic nerves in human dental pulp.

The effects of adrenaline on the release of noradrenaline from sympathetic nerves in human dental pulp in vitro were examined. Sympathetic nerves were stimulated at 5 Hz for 100 sec following incubation of pulp with [3H]noradrenaline (0.6 micromol/l). In the presence of desipramine (DMI, 0.3 micromol/l), adrenaline (0.1 and 1.0 micromol/l) inhibited the release of [3H]noradrenaline, an effect which was inhibited by the alpha2-adrenoceptor antagonist rauwolscine (0.1 micromol/l) and by the alpha2-adrenoceptor agonist UK 14,304 (0.1 micromol/l). The release of [3H]noradrenaline was unaffected by adrenaline (0.001 and 0.01 micromol/l) in the presence of DMI and DMI plus rauwolscine. Although presynaptic inhibitory alpha2- and facilitatory beta-adrenoceptors are present on sympathetic nerves in human dental pulp, these results imply that adrenaline activates only the inhibitory alpha2-receptors.

Adolescent↗
PubMed1998

The morpholino-acetic acid analogue Sch 50911 is a selective GABA(B) receptor antagonist in rat neocortical slices.

The pharmacological properties of (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911) were evaluated on GABA(B) receptors in rat neocortical slices. The GABA(B) receptor agonist, baclofen, produced a concentration-dependent depression of the frequency of spontaneous discharges in slices maintained in Mg2+-free Krebs medium with an EC50 of 6 microM, reversibly antagonised by Sch 50911 (5, 10 and 25 microM) with an apparent pA2 of 6.0 +/- 0.1. The (-) enantiomer Sch 50910 (500 microM) and the racemic des-methyl analogue Sch 48588 (500 microM) were inactive. In slices preloaded with [3H]GABA, Sch 50911 antagonised GABA(B) autoreceptors, increasing the electrically-stimulated 3H overflow in a concentration-dependent manner, with an IC50 of 3 microM. The maximal effect (148 +/- 10.5%) was found at 10 microM, but at 50 microM the response was reduced to 67 +/- 19%. In contrast, evoked release was unaffected by Sch 50910 (100 microM) whilst Sch 48588 at 100 microM increased the overflow by 51.3 +/- 11.6%. In summary, Sch 50911 is a relatively potent antagonist of considerable potential in studies of GABA(B) receptor function.

Animals↗
PubMed1998

Differential effects of phosphonic analogues of GABA on GABA(B) autoreceptors in rat neocortical slices.

The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3 mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration tested (3 mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABA(B) autoreceptors may be pharmacologically distinct from the heteroreceptors.

Animals↗
PubMed1998

Evidence for presynaptic cholinergic receptors in sympathetic nerves in human dental pulp.

The purpose of this study was to determine whether presynaptic cholinergic receptors are present in sympathetic nerves in human dental pulp. Pulp was incubated with [3H]noradrenaline (0.6 mumol/l) for 30 min and then superfused with Krebs' solution at 1.0 ml/min. Electrical stimulation (100 sec, 5 Hz) increased the overflow of [3H]noradrenaline into the superfusate. Carbachol (10 and 100 mumol/l), an agonist of muscarinic receptors, decreased the stimulation-induced (SI) overflow of 3H, an effect blocked by atropine but not hexamethonium. Carbachol, atropine and hexamethonium had no effect on the resting overflow. Nicotine (10 mumol/l) increased the resting overflow and inhibited the SI overflow, although the inhibition was variable. Cytisine, another agonist of nicotinic receptors, also increased the resting overflow, but did not affect the SI overflow. To ascertain whether the actions of nicotine and electrical stimulation were influenced by the release of nitric oxide (NO), the effects of an NO donor and two NO-synthase inhibitors were examined. With the exception of one of the NO-synthase inhibitors (L-NAME), the agents were without effect on the overflow of 3H in the absence or presence of nicotine. It was concluded that sympathetic nerves in human dental pulp possess (a) presynaptic muscarinic receptors that inhibit the SI release of noradrenaline, and (b) nicotinic receptors that evoke the release of noradrenaline and that inhibit the SI release of the transmitter. The results do not point to a significant role for NO in the effects of stimulation or nicotine on the overflow of 3H.

Adolescent↗
PubMed1998

Modulation by presynaptic beta-adrenoceptors of noradrenaline release from sympathetic nerves in human dental pulp.

This study was undertaken to test for the presence of presynaptic beta-adrenoceptors on sympathetic nerves in human dental pulp and, if present, to investigate the subtype. Pulp was excised from freshly extracted teeth, incubated with [3H]-noradrenaline (0.6 micromol/l) and subsequently superfused with Krebs solution. Sympathetic nerves were stimulated at 5 Hz for 100 sec. The non-specific beta-adrenoceptor agonist isoprenaline (1.0 micromol/l), and the selective beta2-agonist salbutamol (10 micromol/l) facilitated the release of [3H]-noradrenaline; isoprenaline, but not salbutamol, also facilitated this release in the presence of desipramine (DMI, 0.3 micromol/l), corticosterone (10 micromol/l) and rauwolscine (0.1 micromol/l). BRL 37344 (1.0 micromol/l), a beta3-agonist, had no effect on [3H]-noradrenaline release. The facilitatory effects of isoprenaline and salbutamol were inhibited by the non-specific beta-antagonist propranolol (1.0 micromol/l), while that of salbutamol was inhibited in the presence of ICI-188,551 (1.0 micromol/l), a selective beta2-antagonist, as well. The beta1-antagonist atenolol (1.0 micromol/l) potentiated the facilitatory effects of isoprenaline in the presence of DMI and corticosterone. Neither propranolol nor ICI-188,551 alone affected the release of [3H]-noradrenaline. These results establish the presence of presynaptic beta-adrenoceptors on sympathetic nerves in human dental pulp. It is suggested that they are of the beta2-subtype, although a greater range of agonists and antagonists needs to be used to clarify the nature of the the beta-adrenoceptors.

Adolescent↗
PubMed1998

Management of postkeratoplasty astigmatism.

Many factors have led to the improved success rate for clear corneal grafts after penetrating keratoplasty. Unfortunately, postoperative corneal astigmatism commonly occurs and can produce significant visual impairment. Astigmatic correction may include spectacle correction or contact lenses, but if this fails, then surgical options are considered. Refractive surgical techniques such as suture removal or adjustment, relaxing incisions, wedge resections, and photorefractive keratectomy or laser in situ keratomileusis can dramatically reduce postoperative astigmatism after penetrating keratoplasty and lead to improved, functional vision. However, significant variability between results in individual patients can occur. So although general guidelines are useful, it is important to individualize and modify the planned surgery based on qualitative keratoscopy and corneal topography for the initial and subsequent astigmatic corrections.

Astigmatism↗
PubMed1996

Effects of early drinking and an antisocial orientation on the alcohol use of young Russians.

Drawing upon data from the Survey of Deviant Behavior Among Youth in the Moscow Region of Russia, this paper examines the effects of early drinking behavior and an antisocial orientation on the use of alcohol by young Russians. Using available data from the U.S. National Household Survey of Drug Abuse, the use of alcohol and the effects of early drinking among youth in the Moscow Region and the United States are compared. The analysis of the data from the two surveys indicates that a greater proportion of Russian youth began drinking by the age of 12 but that early drinking is associated with subsequent alcohol use among both Russian and American youth. Although there are no data on an antisocial orientation from the U.S. survey, there are such data from the Russian survey and an analysis of this data indicates that the greatest alcohol use is found among young Russians who began drinking by the age of 12 and who have an antisocial orientation.

Adolescent↗
PubMed1995

Effects of endolymphatic duct occlusion on the structure and function of the endolymphatic sac in the adult guinea pig.

The endolymphatic sac (ELS) has been shown to respond rapidly to sudden disruptions in fluid balance such as labyrinthectomy or systemic administration of hyperosmolar agents. The present study was designed to determine the ELS response to slower changes in fluid dynamics by occluding the endolymphatic duct (ELD), thereby interrupting the longitudinal flow of endolymph to the ELS. Morphologic studies and autoradiographic techniques were used to evaluate the effects of ELD obstruction on the structure and function of the ELS after 48 hours. There were no significant changes in cellular morphology and a slight decrease in the incorporation of radiolabeled glucose when compared with normal ELS cells. We conclude that it is rapid change in fluid balance that triggers the ELS response, which is not seen with disruption of longitudinal flow.

Animals↗