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Biomedical subjects

E Kelly

Publications and source records attributed to E Kelly.

At least 109 records · Page 6Linked to original sources

Hypertension: variations in prevalence in the black population.

Prevalence trends in hypertension in black men and women show an inversion at about ages 45 to 54 years. Incidence, mortality, and treatment of hypertension after age 35 can probably be related to this inversion. Incidence data are inconsistent and scanty. Morbidity data are incomplete and mostly unreliable. Mortality data partially explain the inversion. Long-term epidemiologic studies of hypertension in black elderly persons are needed to explain these variations in prevalence, which may have a beneficial impact on treatment and prognosis.

Adult↗

Selective improvement in cognitive test scores of extremely low birthweight infants aged between 2 and 5 years.

The cognitive development at 2 and 5 years of a cohort of extremely low birthweight (ELBW) children (birthweight 500-999 g) was compared with that of cohorts of larger very low birthweight (VLBW) children (birthweight 1000-1500 g) and normal birthweight (NBW) children (birthweight greater than 2500 g) to determine whether the improvements in cognitive function of ELBW infants between 2 and 5 years are apparent or real. At 2 years of age, ELBW children had a mean Mental Developmental Index (MDI) on the Bayley Scales of 90.4, significantly lower than the means of 100.3 for the larger VLBW children (P = 0.006), and 107.8 for the NBW children (P = 0.0002). However by 5 years the mean scores on the Wechsler Preschool and Primary Scales of Intelligence (WPPSI) full-scale for the ELBW and larger VLBW children were virtually identical (105.9 and 106.0 respectively)--but still lower than the mean WPPSI full-scale of 114.6 for the NBW children. After standardizing the MDI and WPPSI scores relative to the NBW children, the ELBW children improved between 2 and 5 years (paired t-test, t = 3.2, P = 0.004) whereas the larger VLBW infants did not. We postulate that ELBW children require more time than larger VLBW children after birth to compensate for perinatal and other stresses, and that developmental delay at 2 years may not always persist to 5 years.

Birth Weight↗

Ca2+-dependent facilitated shortening in isotonic contraction of trachealis muscle.

We compared isotonic shortening with isometric force generation as a function of external Ca2+ in 166 tracheal smooth muscle (TSM) strips from 27 mongrel dogs in vitro. Concentration-response curves were generated with muscarinic stimulation (acetylcholine, ACh), alpha-adrenergic receptor activation (norepinephrine after beta-adrenoceptor blockade, NE), serotonin (5-HT), and KCl-substituted Krebs-Henseleit solution. The concentrations of 5-HT causing half-maximal shortening (ECS50, 1.54 +/- 0.14 X 10(-7) M) and half-maximal active isometric tension (ECT50, 1.72 +/- 0.30 X 10(-7) M) were similar (P = NS). Likewise, ECS50 (21.9 +/- 0.7 mM) and ECT50, (22.0 +/- 0.9 mM) were similar for KCl. In contrast, facilitated isotonic shortening (i.e., greater isotonic shortening for comparable degrees of force generation) was elicited with ACh and NE for all levels of force generation between 15 and 85% of maximum and for all concentrations of ACh from 3 X 10(-8) to 3 X 10(-5) M (P less than 0.05 for all points). Facilitated isotonic shortening also was elicited for all concentrations of NE from 10(-8) to 10(-6) M (P less than 0.05 for all points). Removal of Ca2+ from the perfusate substantially reduced the potency of ACh (P less than 0.001) and abolished differences between ECS50 (2.23 +/- 0.28 X 10(-5) M) and ECT50 (2.50 +/- 0.46 X 10(-5) M, P = NS). We demonstrate that for comparable degrees of force generation, muscarinic and alpha-adrenergic receptor activation cause greater isotonic shortening than KCl or 5-HT and that this facilitated shortening is associated with the concentration of external Ca2+.

Acetylcholine↗

Evidence for platelet-activating factor secretion during immune activation in dogs.

To elucidate the potential physiological significance of platelet-activating factor (PAF) in acute bronchoconstriction, we studied the effect of Ascaris suum antigen on the tachyphylactic response to PAF in 15 natively allergic mongrel dogs in vivo. Active bronchial tension was measured isometrically, and mediator secretion was measured as the arteriovenous difference (AVd) in plasma concentration across the lungs. Administration of PAF into the bronchial artery caused dose-related contraction in five control dogs (maximal active tension = 11.8 +/- 1.68 g/cm) that paralleled the increase in the AVd for serotonin (4,188 +/- 175 pg/ml) but not histamine (maximal AVd less than 6.0 ng/ml). The response to PAF was highly tachyphylactic. In contrast to PAF, 1:10 concentration of intra-arterial antigen caused substantial release of histamine (AVd = 308 +/- 57.1 ng/ml; P less than 0.001 vs. PAF). Diminished responsiveness (2-log shift in threshold and maximal contraction; P less than 0.001) to PAF was demonstrated in five dogs after 1:10 antigen, compatible with endogenous release of PAF during prior immune challenge in the same animals. Administration of Ascaris antigen caused a leftward shift in the dose-response curve to serotonin and only mild tachyphylaxis to the maximal response to histamine. Our data are compatible with physiological participation of PAF in eliciting bronchial smooth muscle contraction during the acute phase of immune activation caused by A. suum antigen.

Animals↗

Beta-adrenergic relaxation of dog trachealis: contractile agonist-specific interaction.

The phenomenon of contractile agonist-dependent relaxation by isoproterenol (ISO) of active tension elicited by acetylcholine (ACh), histamine (HIS), serotonin (5-HT), and potassium chloride-substituted Krebs-Henseleit solution (KCl) was studied in 210 tracheal smooth muscle (TSM) strips from 28 mongrel dogs in vitro. All TSM strips were contracted to similar active tensions [target tension (TT) = 50% of the maximal active tension elicited by 127 mM KCl] with ACh, HIS, 5-HT, or KCl and relaxed with either ISO, forskolin (FSK), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP), or 3-isobutyl-1-methylxanthine (IMX). The concentrations of ISO causing 50% relaxation from TT (RC50) were ACh (2.9 +/- 1.1 x 10(-6) M) greater than 5-HT (8.4 +/- 1.5 x 10(-8) M) approximately KCl (8.1 +/- 2.1 x 10(-8) M) greater than HIS (1.6 +/- 0.2 x 10(-8) M). FSK and IMX relaxed TSM in the same rank order of potency as ISO. In contrast to the contractile agonist-dependent relaxation elicited by ISO, FSK, and IMX, db-cAMP was nearly equipotent in relaxing similarly contracted strips. These results are consistent with contractile agonist-specific interaction with cAMP production by ISO and FSK. These data demonstrate that the phenomenon of contractile agonist-dependent relaxation by ISO is not related specifically to the beta-adrenoceptor.

1-Methyl-3-isobutylxanthine↗

Out-of-hospital cardiac arrest. Use of electrophysiologic testing in the prediction of long-term outcome.

We examined the role of electrophysiologic testing in the prediction of long-term outcome in 166 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction. Ventricular arrhythmias were inducible in 131 patients (79 percent) at base line and were suppressed by antiarrhythmic drugs or surgery (or both) in 91 of 127 (72 percent). During a median follow-up period of 21 months, cardiac arrest recurred in 29 patients: 11 (12 percent) of the 91 in whom inducible arrhythmias had been suppressed (including 5 patients in whom treatment had been discontinued), 12 (33 percent) of the 36 in whom inducible arrhythmias persisted, and 6 (17 percent) of the 35 in whom arrhythmias could not be induced at the initial electrophysiologic study. Cox survival analysis identified the following three variables as significant independent predictors of recurrent cardiac arrest: persistence of inducible ventricular arrhythmias (relative risk, 3.97 [95 percent confidence interval, 1.80 to 8.75], P = 0.0006), a left ventricular ejection fraction of 30 percent or less (relative risk, 2.60 [1.21 to 5.53], P = 0.0138), and the absence of cardiac surgery (relative risk, 4.20 [0.99 to 17.77], P = 0.0512). We conclude that electrophysiologic testing is useful in quantifying the subsequent risk of cardiac arrest among survivors of out-of-hospital cardiac arrest.

Anti-Arrhythmia Agents↗

The use of calcium channel blockade for the prevention of postoperative adhesion formation.

Prevention of postoperative adhesion formation is an issue of fundamental concern to the reproductive surgeon. The disappointing results of current adjunctive regimens have prompted a search for more potent antiadhesion therapies. Administration of nifedipine hydrochloride, a prototypical calcium channel blocking agent, to hamsters receiving a standardized traumatic lesion of the left uterine horn significantly inhibited primary adhesion formation as compared to control animals. These preliminary results suggest that calcium channel blockade may have the potential to favorably influence events related to peritoneal repair; further study of these agents as surgical adjuvants in the treatment of chronic pelvic adhesive disease is indicated.

Animals↗

Dopamine receptor stimulation does not affect phosphoinositide hydrolysis in slices of rat striatum.

The effect of dopamine receptor stimulation on the accumulation of labelled inositol phosphates in rat striatal slices under basal and stimulated conditions was examined following preincubation with [3H]inositol. Incubation of striatal slices with the selective D-1 agonist SKF 38393 or the selective D-2 agonist LY 171555 for 5 or 30 min did not affect the basal accumulation of labelled inositol mono-, bis-, tris-, and tetrakisphosphate. Resolution by HPLC of inositol trisphosphate into inositol-1,3,4-tris-phosphate and inositol-1,4,5-trisphosphate isomers revealed that under basal conditions dopamine did not influence the accumulation of inositol-1,4,5-trisphosphate. Depolarisation evoked by KCl, or addition of the muscarinic receptor agonist carbachol, produced a marked increase in the accumulation of labelled inositol phosphates in both the presence and absence of lithium. Addition of dopamine did not reduce the ability of KCl or carbachol to increase inositol phospholipid hydrolysis. In the presence of lithium, dopamine (100 microM) enhanced KCl-stimulated inositol phospholipid hydrolysis, but this effect appears to be mediated by alpha 1 adrenoceptors because it was blocked by prazosin. SKF 38393 (10 microM) or LY 171555 (10 microM) also did not affect carbachol-stimulated inositol phospholipid hydrolysis. These data, in contrast to recent reports, suggest that striatal dopamine receptors do not appear to be linked to inositol phospholipid hydrolysis.

Animals↗

Identification of the C5a des Arg cochemotaxin. Homology with vitamin D-binding protein (group-specific component globulin).

The chemotactic activity of human C5a des Arg is enhanced significantly by an anionic polypeptide (cochemotaxin) in normal human serum and plasma. The cochemotaxin attaches to sialic acid residues within the oligosaccharide chain of native C5a des Arg to form a complex with potent chemotactic activity for human PMN. We investigated the nature of the cochemotaxin and found that vitamin D-binding protein is the putative cochemotaxin. Vitamin D-binding protein enhanced the chemotactic activity of native C5a des Arg, but had no effect on the chemotactic activity of either native C5a or FMLP. Sialic acid prevented both enhancement by vitamin D-binding protein of the chemotactic activity of native C5a des Arg and formation of C5a des Arg-vitamin D-binding protein complexes, detected by molecular sieve chromatography. Furthermore, vitamin D-binding protein and cochemotaxin exhibited identical molecular weights, isoelectric points, antigenic reactivity, and amino acid composition.

Amino Acids↗

Residual urine volumes in patients with spinal cord injury: measurement with a portable ultrasound instrument.

Spinal cord injured (SCI) patients are often placed on an intermittent catheterization (IC) program during their initial rehabilitation in an effort to establish a catheter-free state. A noninvasive method to quantitatively determine residual urine volumes would decrease unnecessary catheterizations and be useful in the management of an IC program. This study was undertaken to determine if bladder volumes could be accurately determined in a group of SCI patients using a portable ultrasound scanner. Fifteen SCI patients underwent a total of 224 ultrasonic bladder volume determinations and 57 urethral catheterizations. Immediately prior to catheterization, two investigators alternately performed a total of four ultrasound readings on each patient using a hand-held portable instrument, the BVI 2000. The first ultrasound volume determination was comparable to the average ultrasound volume (r2 = 0.956). For catheterized volumes versus the initial ultrasound volume determination, r2 = 0.80. The average error was 18% for catheterized volumes within the range 50-700ml. Our results compare favorably with both real-time scanning using standard equipment and other portable instruments. The noninvasive nature, negligible risks, and reasonable estimates of volume warrant consideration of portable ultrasound scanning for the determination of bladder volumes in SCI patients.

Evaluation Studies as Topic↗

Neurochemical and behavioural evidence that dopamine D-2 receptors in striatum couple to the Ni regulatory protein and inhibition of cyclic AMP accumulation.

The effects of intrastriatal pertussis toxin, which inactivates the regulatory protein Ni, were investigated in various models of striatal D-2 receptor function in the rat. Using a multiple injection technique unilateral intrastriatal injections of pertussis toxin induced, after a lag phase, ipsilateral postural asymmetries which intensified upon peripheral administration of apomorphine. Injections of pertussis toxin also partially reduced the ability of a selective D-2 agonist, RU 24926 [N-n-propyl di-beta (3-hydroxyphenyl)-ethylamine], to inhibit cyclic AMP accumulation due to a selective D-1 agonist SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine), whilst also reducing the affinity of dopamine for D-2 binding sites in striatal membranes from animals given prior intrastriatal injections of the toxin. Pertussis toxin also increased striatal dopamine metabolism, seen as a reduction in the dopamine: DOPAC (3,4-Dihydroxyphenylacetic acid) ratio, similar to that seen following intrastriatal injections of the selective D-2 antagonist (+/-)-sulpiride. These results suggest that pertussis toxin has dopamine D-2 antagonist-like properties in the rat striatum, consistent with the idea that striatal D-2 function may rely, in part at least, upon the regulatory protein Ni and adenylate cyclase inhibition.

Adenylate Cyclase Toxin↗

Dopamine D-2 receptors inhibit D-1 stimulated cyclic AMP accumulation in striatum but not limbic forebrain.

The effect of dopamine D-2 receptor activation on dopamine D-1 stimulated cyclic AMP accumulation was investigated in slices of rat striatum and limbic forebrain (nucleus accumbens and tuberculum olfactorium). In striatal slices the dose-dependent increase in cyclic AMP accumulation due to dopamine (3-100 mumol/l) was enhanced by selective D-2 receptor blockade using (-)-sulpiride (30 mumol/l). In limbic slices the increase in cyclic AMP due to dopamine (3-50 mumol/l) was unaffected by selective D-2 receptor blockade. The enhancement of cyclic AMP accumulation due to the selective D-1 agonist SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 1 mumol/l) in striatal slices was attenuated in the presence of the selective D-2 receptor agonist LY 171555 (quinpirole hydrochloride; 10 mumol/l). This attenuation was in turn blocked by (-)-sulpiride (10 mumol/l). In limbic slices LY 171555 (10 mumol/l) had no effect on SKF 38393 (1 mumol/l) stimulated cyclic AMP accumulation. Conversely muscarine receptor activation, using carbachol (10 mumol/l), attenuated D-1 stimulated cyclic AMP accumulation in both striatum and limbic forebrain. Dopamine D-2 or muscarine receptor stimulation in either striatal or limbic slices did not attenuate cyclic AMP accumulation due to VIP (vasoactive intestinal polypeptide; 0.5 mumol/l), isoprenaline (10 mumol/l) or 2-chloroadenosine (100 mumol/l). This suggests that in striatal slices, D-2 receptors mediate a selective inhibition of D-1 stimulated cyclic AMP accumulation, but that in the limbic forebrain D-2 receptors are unlikely to be coupled to D-1 receptor-linked adenylate cyclase. These data indicate a fundamental difference in the properties of D-2 receptor-effector coupling in these brain regions.

1-Methyl-3-isobutylxanthine↗

Endogenous dopamine functionally activates D-1 and D-2 receptors in striatum.

Rat striatal slices incubated with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine at 1 mM were exposed to different concentrations (1-100 microM) of the catecholamine-releasing drug amphetamine. This produced both a concentration-dependent release of endogenous dopamine and accumulation of cyclic AMP in the slices. The cyclic AMP accumulation due to amphetamine was greatly increased when slices were coincubated with the selective dopamine D-2 antagonist (-)-sulpiride (30 microM), but the amphetamine-induced release of dopamine from the slices was the same in the presence or absence of (-)-sulpiride. Pretreatment of animals with reserpine (5 mg/kg s.c., 18 h before death) and in vitro incubation with alpha-methyl-p-tyrosine (50 microM for 90 min), respectively, reduced the ability of amphetamine (1-100 microM) [in the presence of 30 microM (-)-sulpiride] to induce release of dopamine and to elevate cyclic AMP accumulation in striatal slices. A similar reduction in amphetamine-induced dopamine release and cyclic AMP accumulation in striatal slices was observed 7 days following unilateral 6-OHDA lesions of the medial forebrain bundle of rats. These results suggest that amphetamine induces release of endogenous dopamine from the terminals of nigrostriatal dopamine neurones. Released dopamine is then able functionally and concomitantly to activate D-1 and D-2 receptors, seen as stimulation and inhibition of cyclic AMP accumulation, respectively.

Amphetamine↗

Comparison of changes in locomotor activity with striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations following the bilateral intranigral injection of dopamine agonist drugs in rats.

Bilateral injection of apomorphine (2.5 micrograms) into the substantia nigra zona reticulata of rats reduced both locomotor activity and striatal HVA and DOPAC concentrations. Bilateral injection of dopamine (10 micrograms) did not affect locomotor activity whereas a higher dose of dopamine (50 micrograms) enhanced locomotor activity. Striatal HVA and DOPAC concentrations were unchanged following injection of dopamine. Bilateral injection of (+/-)-3PPP (0.1 or 2.5 micrograms) into the zona reticulata of the substantia nigra did not alter locomotor activity while a higher dose (10 micrograms) enhanced locomotion. Injection of (+/-)-3PPP (0.1-10 micrograms) into the zona reticulata was without effect on striatal HVA or DOPAC concentrations. The bilateral manipulation of nigral dopaminergic neurotransmission alters motor activity and nigrostriatal dopamine turnover in conscious rats. However, the changes in motor activity are not necessarily related to altered nigrostriatal activity, suggesting the involvement of dopamine receptors located at non-dopaminergic sites within the substantia nigra.

3,4-Dihydroxyphenylacetic Acid↗

Beyond the online catalog: developing an academic information system in the sciences.

The online public access catalog consists essentially of a machine-readable database with network capabilities. Like other computer-based information systems, it may be continuously enhanced by the addition of new capabilities and databases. It may also become a gateway to other information networks. This paper reports the evolution of the Bibliographic Access and Control System (BACS) of Washington University in end-user searching, current awareness services, information management, and administrative functions. Ongoing research and development and the future of the online catalog are also discussed.

Catalogs, Library↗

Reality perceptions of television: a comparison of emotionally disturbed, learning disabled, and nonhandicapped children.

The Stony Brook Videotest (SBV), a measure of reality perceptions of television programs and commercials, was administered to 38 emotionally disturbed (ED), 35 learning disabled (LD), and 159 nonhandicapped elementary school children. The ED and LD children scored significantly lower than the comparison group, indicating that ED and LD children are less able to distinguish between reality and fantasy on television. The clinical implications of these findings and possible remedial actions are discussed.

Affective Symptoms↗