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Biomedical subjects

T Reynolds

Publications and source records attributed to T Reynolds.

At least 109 records · Page 6Linked to original sources
PubMed1997

Detection rates and false positive rates for Down's syndrome screening: how precisely can they be estimated and what factors influence their value?

Down's syndrome screening is currently carried out using a combination of biochemical markers measured in maternal serum samples; these include MSAFP, Total hCG, uE3 and Free beta-hCG. Recently a number of papers have compared the effectiveness of different combinations of these markers. Some recommend MSAFP, Total hCG and uE3 (triple test) while others advocate MSAFP and Free beta-hCG (double test). The cases put forward to support these tests rely on estimated detection and false positive rates for the proposed test. A recent paper by Wright used simulation techniques to estimate the effects of sampling error on such error rates. In prospective studies there are two methods commonly used for estimating these rates. We obtain formulae for the standard deviations of these estimates and show that one of them always gives a smaller standard error than the other. We also show that in such studies the accuracy of estimating detection rates and false positive rates depends not only upon the method of calculation but also on the age distribution of pregnant women and the parameters used to calculate patient specific risk. We show that these effects can result in estimation errors of such magnitude that many observed differences in detection rates could be of questionable significance, a conclusion also reached by Wright.

Adult↗
PubMed1997

Neuromedin C decreases potassium conductance and increases a non-specific conductance in rat suprachiasmatic neurones in brain slices in vitro.

Whole-cell recordings were made, in both current and voltage clamp, from suprachiasmatic neurones maintained in coronal rat brain slices. In current clamp doses of 10 and 100 nM neuromedin C (NMC) were shown to increase basal firing rate in 9 out of 32 neurones. The excitatory responses to 100 nM NMC were accompanied by small increases in neuronal input resistance (25.0 +/- 9.9% in 4 out of 7 neurones tested) and depolarisations of membrane potential (9.8 +/- 3.4 mV in 4 out of 7 neurones tested). However, 10 nM NMC caused no changes in either neuronal input resistance or membrane potential despite the clear increases in neuronal firing rate. When voltage-clamped at -60 mV, 100 nM NMC induced an inward current of 14.8 +/- 1.2 pA in 46 of 210 neurones. The NMC-induced inward current was shown to be unaffected by perfusion with 1 microM tetrodotoxin (TTX). The inward current recorded at -60 mV was typically associated with a decrease in membrane conductance. Construction of current-voltage relationships in the absence and presence of 100 nM NMC showed that with the majority of the NMC-sensitive neurones the inward current either reversed polarity close to the potassium reversal potential or decreased at hyperpolarised potentials. This reversal potential was shifted to more depolarised potentials when the extracellular concentration of potassium was increased. The NMC-induced inward current was unaffected by reduction of the extracellular concentration of sodium or by addition of 0.2 mM cadmium. In potassium-free conditions, in both the dialysing pipette solution and perfusing saline, NMC was still able to induce an inward current. The additional reduction of the extracellular concentration of sodium, whilst recording in potassium-free conditions, was also unable to abolish the inward current. Recordings made with an electrode containing the non-hydrolysable guanosine triphosphate analogue, guanosine 5'-thio-triphosphate, resulted in NMC-induced inward currents which failed to recover to baseline. It is concluded that NMC excites a subpopulation of suprachiasmatic neurones by decreasing a resting potassium conductance and increasing a non-specific conductance, via a G-protein link.

Animals↗
PubMed1997

Measure the gap! A proposed simplified approach for measuring the descent of the base of the left ventricle.

The evaluation of left ventricular systolic function represents a common request for an echocardiographic examination. Several parameters have been proposed to quantitate left ventricular systolic function. The descent of the base of the left ventricle is founded on sound principle but currently requires multiple, time-consuming steps to derive during an echocardiographic examination. This article has reviewed the basic tenet of the descent of the base, reviewed the current required echocardiographic measurements needed to obtain a descent of the base value and has proposed a simplified approach by measuring the gap seen during the routine calculation of left ventricular end-systolic volume, end-diastolic volume, and ejection fraction by the recommended method of discs.

Echocardiography↗
PubMed1997

Comparison of Wallgraft and Wallstent for treatment of complex iliac artery stenosis and occlusion. Preliminary results of a prospective randomized study.

We performed a prospective randomized study to compare the use of a bare metal stent (WALLSTENT Endoprosthesis) with use of a covered stent (WALLGRAFT Endoprosthesis)-both made by Schneider, Inc.; Minneapolis, Minn-for the treatment of complex iliac artery stenosis and occlusion. We report the preliminary results of a study performed at our institution from 1 February 1997 through 31 April 1997. The patient group was composed of 6 women and 4 men, with a mean age of 61.8 years (range, 47 to 73 years). Six WALLGRAFT endoprostheses (4 in the left iliac artery and 2 in the right) and 9 WALLSTENT endoprostheses (5 in the left iliac artery and 4 in the right) were implanted. The mean percent stenosis before treatment was similar in both groups (84.17% in the WALLGRAFT group and 82.14% in the WALLSTENT group). The post-treatment stenosis and peak systolic gradients were negligible or zero in both groups. The devices were safely deployed and technical success (< 30% residual stenosis) was achieved in both groups. The mean thigh-brachial index was similar in the 2 groups, both before treatment (0.65 in the WALLGRAFT group and 0.64 in the WALLSTENT group) and after treatment (1.12 in the WALLGRAFT group and 1.12 in the WALLSTENT group). Evaluation of clinical success revealed that symptoms of intermittent claudication improved markedly in 4 of 5 patients who received the WALLGRAFT Endoprosthesis. In the WALLSTENT group, 1 patient had symptomatic improvement, another had 1 limb improve and the other worsen, and the rest had no improvement. Clinical complications were observed in only 1 patient in the WALLGRAFT group and in 2 patients in the WALLSTENT group. These preliminary results indicate very good technical and early success at the 1-month follow-up with the use of the WALLGRAFT Endoprosthesis in complex iliac artery stenosis and occlusion. Despite these promising preliminary results, a longer follow-up study with a larger number of patients is needed to determine the benefits of the WALLGRAFT Endoprosthesis in patients with complex iliac artery stenosis or occlusion.

Adult↗
PubMed1996

Bombesin receptors in the brain.

We have shown that in the central nervous system BN receptors are closely associated with 5-HT systems. On a subpopulation of dorsal raphe neurons, NMB receptors are able to depolarize cells by reducing gK+. In one of the target regions of the dorsal raphe 5-HT neurons, the SCN, we have also shown that neurons are excited by BN-related peptides. In the SCN, the GRP receptors excite neurons by two different mechanisms: closure of gK+ and opening of an unidentified cation conductance. Expression of human BN receptors from the brain in CHO cells or Xenopus oocytes shows a very similar pharmacological profile to that seen in the rat brain slice preparations. In the CHO cell line, following BN receptor activation, a major second-messenger path involves hydrolysis of PIP2 by phospholipases to yield IP3, which releases Ca2+ from intracellular stores. In the oocyte expression system, a similar second messenger pathway is clearly apparent, and Ca2+-sensitive gCl- represents the last phase in a cascade of events. The final phase of the mechanism of action in the artificial systems does not involve gK+, suggesting a different second messenger cascade to that in neurons. However, the involvement of phospholipases and their phospholipid products have not been excluded in neurons.

Amino Acid Sequence↗
PubMed1996

A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis.

A novel gene, designated byr4, was identified in Schizosaccharomyces pombe that affects the mitotic cell cycle and shows genetic interactions with the ras1 signaling pathways. Null alleles of byr4 cause cell cycle arrest in late mitosis and permit multiple rounds of septation. The multiple septa typically divide two nuclei, but the nuclei frequently do not stain equally with 4',6-diamidino-2-phenylindole (DAPI), suggesting that byr4 is required for proper karyokinesis. Overexpression of byr4 inhibits cytokinesis, but cell cycle progression continues leading to multinucleate cells. When byr4 is overexpressed, the early steps in the cytokinesis pathway, including formation of the medial F-actin ring, occur normally; however, the later steps in the pathway, including contraction of the F-actin ring, septation, and rearrangement of the medial F-actin following mitosis, rarely occur, byr4 shows two genetic interactions with ras1. The inhibition of cytokinesis by byr4 overexpression was exacerbated by null alleles of ras1 and scd1, suggesting a link between pathways needed for cell polarity and cytokinesis. Overexpression of byr4 also partially bypasses the need for ras1 for sporulation. The electrophoretic mobility of the byr4 protein varied in response to mutants that perturb cytokinesis and karyokinesis, suggesting interactions between byr4 and these gene products. A more rapidly migrating byr4 protein was found in cells with mutations in cdc16, which undergo repeated septation, and in cdc15, which fail to form a medial F-actin ring in mitosis. A slower migrating byr4 protein was found in cells with a mutation in the beta-tubulin gene, which arrests cells at the metaphase-anaphase transition.

Actins↗
PubMed1996

Pharmacokinetics and pharmacodynamics of TP-9201, a gpIIbIIIa antagonist, administered in combination with recombinant tissue-type plasminogen activator, heparin, and aspirin in beagles.

The effect of heparin, aspirin, and recombinat tissue-type plasminogen activator (rt-PA) on TP-9201 pharmacokinetics and pharmacodynamics was investigated in beagles. Animals received TP-9201, an Arginine-Glycine-Aspartic acid (RGD)-containing synthetic peptide glycoprotein (gp)IIbIIIa antagonist as a bolus of 0.31 mg/kg, followed by a 4-h infusion of 0.5 mg/kg/h. rt-PA was administered as a modification of the weight-adjusted standard regimen. Heparin was administered as a bolus followed by an infusion producing a 1.5- to 2-fold increase in the activated prothromboplastin time (aPTT) above baseline values. Aspirin was administered orally, approximately 24 and 2 h before TP-9201. TP-9201 had a plasma clearance of 9.9 +/- 2 ml/min/kg and a volume of distribution that was larger than plasma volume. Administration of heparin and aspirin with TP-9201 did not affect the clearance of TP-9201, whereas rt-PA resulted in a faster clearance (p = 0.05). Whether the faster clearance is physiologic or a result of rt-PA interference in the TP-9201 assay is unclear. TP-9201 completely inhibited ADP-mediated platelet aggregation. After discontinuation of TP-9201, recovery of platelet aggregation had a half life (t1/2) of 2-3 h and was complete < or = 24 h. Coadministration of heparin did not interfere with TP-9201 pharmacodynamics, whereas aspirin and rt-PA slowed the recovery of platelet aggregation. The template bleeding time profile for the TP-9201-treated animals was similar to that of the aspirin-treated animals.

Animals↗