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Biomedical subjects

G Armstrong

Publications and source records attributed to G Armstrong.

At least 37 records · Page 2Linked to original sources
PubMed2000

Use of peak systolic strain as an index of regional left ventricular function: comparison with tissue Doppler velocity during dobutamine stress and myocardial ischemia.

OBJECTIVES: The goals of this study were to examine peak systolic strain as an index of regional function in an animal model of inotropic stress and ischemia, and to compare these results with peak systolic myocardial tissue Doppler velocity (MDV). BACKGROUND: Myocardial tissue Doppler velocity is an objective measure of regional left ventricular responses to inotropic stimulation and ischemia, but it is affected by tethering from adjacent segments and translational movement. Myocardial Doppler strain (epsilon, relative change in length) is a more local measure of contractility, which can now be derived noninvasively from MDV. METHODS: Eight dogs underwent graded dobutamine infusion followed by coronary occlusion. Epicardial 2-dimensional echocardiography and color MDV of the left ventricle were obtained and digitized from the short-axis view at baseline and with dobutamine doses of 2, 4, and 8 microg/kg per minute. These were repeated 0, 10, 20, 45, and 90 seconds after occlusion of the left anterior descending artery (LAD) (n = 3) or circumflex coronary artery (n = 5). Dobutamine was continued at 8 microg/kg per minute during coronary occlusion. The peak systolic radial MDV (cm/s) and systolic strain (epsilon(s), percent thickening) in the anterior and posterior walls were measured off-line at each stage. RESULTS: Dobutamine caused an increase in MDV (P =.0001) and epsilon(s) (P =.09) above baseline values. Coronary occlusion caused a reduction in wall motion; after 45 seconds, all nonperfused segments were hypokinetic. There was a corresponding decrease in MDV and epsilon(s), but this occurred earlier for epsilon(s), and the difference between ischemic and nonischemic segments was greater for epsilon(s) than for MDV (P <. 03). Nonischemic regions trended to an increase in epsilon(s) (compensatory hyperkinesis), whereas MDV trended downward, probably reflecting the global decrease in left ventricular function. CONCLUSION: Both MDV and epsilon(s) increase with dobutamine and decrease during ischemia. epsilon(s) appears to respond to local ischemia earlier than MDV, perhaps because it is a more local measure. Thus epsilon(s) may prove to be an accurate parameter for the clinical recognition of regional ischemia.

Animals↗
PubMed1999

Influence of dobutamine or exercise stress on the results of pulsed-wave Doppler assessment of myocardial velocity.

BACKGROUND: Pulsed-wave Doppler assessment of myocardial velocity (MDV) may permit a more quantitative interpretation of stress echocardiography. This technique has been used with dobutamine echo (DbE), but exercise echo (ExE) may be preferred in patients who are able to exercise maximally. The influence of these stressors on the results of MDV are undefined. PURPOSE: This study sought to determine whether differences between the physiology of DbE and ExE could influence the MDV responses to stress and whether interpretative criteria should be different with exercise or dobutamine stress. METHODS: DbE or ExE was performed in 105 patients tested for known or suspected coronary artery disease. Pulsed-wave MDV was obtained in basal segments of anteroseptal, septal, anterior, posterior, lateral, and inferior walls in the apical views at rest and at peak doses of dobutamine or immediately after exercise. Segments were classified as normal or abnormal (ischemia or scar) according to results of 2-dimensional echocardiography, and MDV obtained at rest and stress was compared by using analysis of variance. RESULTS: Resting heart rate was similar before both dobutamine and exercise, but heart rate at peak dobutamine exceeded that after exercise (137 +/- 10 vs 115 +/- 22, P <.01). For both ExE and DbE, MDV was significantly greater at rest and stress in normal than in abnormal segments. Stress MDV in both normal and abnormal segments was greater with DbE than with ExE (17.0 +/- 4.8 cm/s vs 10. 3 +/- 3.4 cm/s, P <.001 for normal segments and 10.7 +/- 4.4 cm/s vs 7.9 +/- 3.3 cm/s, P <.001 for abnormal segments. Increase in MDV/Deltaheart rate induced by DbE was greater than by ExE in normal (0.14 +/- 0.07 cm/s. beat for DbE and 0.09 +/- 0.08 cm/s. beat for ExE; P <.05) but similar in abnormal segments (0.06 +/- 0.07 cm/s. beat for DbE and 0.05 +/- 0.09 cm/s. beat for ExE). MDV correlated better with peak heart rate at ExE (r = 0.56, P <.01) than at DbE (r = 0.28, P <.01). CONCLUSIONS: MDV responses to exercise and pharmacologic stress appear to be different, reflecting differences in inotropy, loading, and the timing of imaging. These findings may influence the ability of MDV to differentiate normal from abnormal stress echocardiography responses.

Aged↗
PubMed1999

Latent left ventricular dysfunction in patients with mitral regurgitation: feasibility of measuring diminished contractile reserve from a simplified model of noninvasively derived left ventricular pressure-volume loops.

BACKGROUND: Assessment of left ventricular (LV) contractility in mitral regurgitation is difficult, and latent systolic dysfunction may be present despite conventional indexes being in the "normal" range. We sought to demonstrate the presence of latent LV dysfunction in mitral regurgitation by showing diminished contractile reserve with the use of simplified pressure-volume loops from noninvasively derived parameters. METHODS AND RESULTS: We performed exercise echocardiography in 72 patients with isolated mitral regurgitation, minimal or no symptoms, normal resting LV function, and no coronary disease who subsequently underwent uncomplicated valve repair and in 15 healthy subjects. Simplified pressure-volume loops were constructed and LV stroke work was estimated at rest and immediately after exercise. As pressures were estimated, the findings were confirmed with a validated numerical model to estimate stroke work in patients and control subjects. Patients had a higher stroke work than did control subjects at rest (1.45 +/- 0.39 vs 0.92 +/- 0.21 J, P <.001). Eighteen patients had LV dysfunction develop after surgery. Patients with postrepair dysfunction had a significantly lower exercise stroke work (1.79 +/- 0.69) than did patients without (2.28 +/- 0.84 J, P =.02), but there was no difference in resting stroke work (1.48 +/- 0.39 vs 1.44 +/- 0.4, P = not significant). Change in stroke work with exercise was higher in patients with normal postoperative function (0.84 +/- 0.59 J) and control subjects (0.59 +/- 0.36 J) than patients with postoperative dysfunction (0.31 +/- 0.55 J, P =.001). The numerical model confirmed the lower exercise stroke work and change in stroke work in patients with postoperative dysfunction. CONCLUSIONS: The clinical study and numerical model confirmed diminished contractile reserve in patients who had LV dysfunction develop after uncomplicated mitral valve repair. Diminished contractile reserve may be a preoperative marker of latent contractile dysfunction.

Cardiac Volume↗
PubMed1999

Reflex testing II: evaluation of an algorithm for use of cardiac markers in the assessment of emergency department patients with chest pain.

A reflex algorithm was developed and evaluated for the use of serum cardiac markers for the diagnosis and rule out of acute myocardial infarction (AMI), and risk stratification of unstable angina patients for those who present to emergency departments (ED) with chest pain. The process begins with testing of total CK and myoglobin at admission. Based on these results, the algorithm determines the need for subsequent testing for the CK-MB isoenzyme and cardiac troponin I (cTnI). The algorithm also directs the need for further blood collection and cardiac marker testing at 4, 8, and 12 h after presentation. A total of eleven stopping points were identified. For some of these stopping points, the algorithm concluded that further blood collections and testing was unnecessary and redundant. The algorithm was retrospectively evaluated on 101 non-consecutive chest pain patients who presented to the EDs at three hospitals. For the AMI group (n=34), six of nine possible different stopping points were reached: 64.7% of cases were diagnosed with the first sample at admission, an additional 32.3% after 4 h, and 2.9% at 8 h. The 12-h sample was not necessary for any of the AMI patients. For the non-AMI group (n=67), most reached the stopping point of no cardiac injury or risk. There were five unstable angina patients who had minor myocardial damage on the basis of a marginally increased cTnI. Of these, one patient subsequently suffered AMI, and three others required angioplasty or bypass surgery. Compared to performing four tests on all patient samples, the reflex algorithm would have reduced the number of necessary tests from 442 to 130 (71% reduction) for AMI patients, and 871 to 469 (46% reduction) for non-AMI patients, if prospectively implemented.

Algorithms↗
PubMed1999

Use of segmental tissue Doppler velocity to quantitate exercise echocardiography.

BACKGROUND: A quantitative technique is required to reduce the subjectivity and improve the reproducibility of stress echocardiography. Tissue Doppler imaging may offer these benefits, but its feasibility with exercise echocardiography (ExE) is undefined. This study sought the determinants of the exercise tissue Doppler velocity (TDV) response and the feasibility and accuracy of color TDV during ExE. METHODS AND RESULTS: Fifteen volunteers and 85 patients (age 60 +/- 10 years, 19 women) with known or suspected coronary artery disease were studied with standard 2-dimensional (2D) echocardiography and pulsed wave (PW) and color TDV before and after they underwent exercise treadmill testing. After the study PW TDV was measured in 6 basal segments, and off-line software was used to display color TDV data from all myocardial segments. Color TDV was compared with PW TDV in the basal segments at rest and stress with the use of linear regression. Color TDV in mid and basal segments was compared with wall motion on 2D echocardiography. The predictors of the TDV response to exercise were defined in a multiple linear regression. A logistic regression model was used to integrate clinical, exercise, and TDV variables for prediction of abnormal regional left ventricular function. Color and PW correlated well at rest (r = 0.81) and stress (r = 0.84), but PW was greater than color velocities at rest and stress. On the basis of 2D echocardiography, 752 myocardial segments were classified as normal in patients without evidence of coronary disease, 309 were normal in patients with abnormal wall motion in another territory, and 128 showed ischemia or scar. Segmental comparison of velocities assessed by color TDV showed that scar segments had a lower velocity than normal segments at rest and stress (P <.001). Ischemic segments had a lower peak TDV and less increment in velocity than normal segments. Heart rate, functional capacity, and regional dysfunction (scar or ischemia) were independent predictors of TDV at peak exercise. With the use of receiver operating characteristic analysis, the "correction" of TDV by these other variables increased the accuracy of the technique for the detection of regional left ventricular dysfunction. CONCLUSION: Color TDV is feasible during ExE. The correlation found between TDV and wall motion analysis of experienced observers indicates that TDV may be useful as a quantitative tool for interpretation of ExE.

Blood Flow Velocity↗
PubMed1998

Octreotide suppression test predicts beneficial outcome from antrectomy in a patient with gastric carcinoid tumor.

Multiple gastric carcinoids are a well-recognized complication of hypergastrinemia associated with chronic atrophic gastritis. However, the management of large tumors (>2 cm in diameter) remains uncertain, with the decision between antrectomy or total gastrectomy being empirical. This report describes the investigation of a patient with chronic atrophic gastritis and multiple large gastric carcinoid tumors. Before surgery, octreotide was infused for 72 hours to suppress enterochromaffin-like (ECL) cell and gastrin cell function. The infusion decreased plasma gastrin and gastrin synthesis; moreover, there were marked reductions in markers of ECL cell function, e.g., histidine decarboxylase and chromogranin A messenger RNA abundance, in carcinoid tumor tissue and macroscopically normal corpus mucosa. An antrectomy was performed, after which the patient made an uneventful recovery. Six months after surgery, a single residual polyp, enriched with smooth muscle cells but not ECL cells, was removed. One year after antrectomy, the remaining stomach was normal. The response of ECL cell markers in carcinoid tissue to octreotide suggested that these cells were under neuroendocrine control and, therefore, predicted a beneficial outcome for antrectomy. It is suggested that an octreotide supression test coupled with assay of histidine decarboxylase or chromogranin A gene expression is useful in the assessment of gastric carcinoid tumors.

Adult↗
PubMed1998

Gastrointestinal tolerability of meloxicam and piroxicam: a double-blind placebo-controlled study.

AIMS: The aim of the study was to compare the effects of meloxicam and piroxicam on the gastroduodenal mucosa in healthy adults. METHODS: Forty-four healthy volunteers were given a 28 day course of either meloxicam 15 mg, piroxicam 20 mg or placebo. Damage to the oesophageal, gastric and duodenal mucosa was assessed, mucosal blood flow (MBF) measured at endoscopy and biopsies taken for prostaglandin content and microscopic assessment of damage before NSAID administration and during days 1, 7 and 28 of continued intake. RESULTS: Maximal macroscopic gastric mucosal damage (median grade+IQR) occurred within 24 h of piroxicam administration, the damage score increasing from 0 to 2.5 (0-3) (P=0.02) at day 1 before falling to 2.0 (0-2) at day 7 and 0 (0-1) at day 28 with resolution of damage observed in six out of the seven subjects who sustained acute injury. No significant macroscopic gastric damage occurred in either of the two other groups although some minor damage was observed in seven subjects taking placebo and five taking meloxicam. There was a trend towards piroxicam causing more acute gastric damage than meloxicam (P=0.06). Baseline antral, body and duodenal MBF were similar in all three groups. No significant changes occurred in any of the groups on any of the visits. There were also no changes in gastric mucosal prostaglandin content in any group. CONCLUSIONS: These observations suggest that meloxicam causes little acute damage to the upper gastrointestinal tract and piroxicam causes some acute gastric injury but such damage resolves in most subjects by 28 days.

Adult↗
PubMed1997

Nutrient uptake into undifferentiated and differentiated HT-29 cells in culture.

HT-29 human colon carcinoma cells in culture have many characteristics of enterocytes, and these cells have been used by others to study intestinal drug and nutrient transport and metabolism. When grown in glucose-containing medium, HT-29 cells are largely undifferentiated (HT-29glu), but when grown in the absence of glucose but in the presence of galactose (HT-29gal), the population of cells is mostly differentiated. This study was undertaken with HT-29glu and HT-29gal cells to study the uptake of palmitic acid (16:0), linoleic acid (18:2), and cholesterol. The relationship between concentration and uptake of 16:0, 18:2, and cholesterol was linear in HT-29glu and HT-29gal cells, with the relative values of the slopes of this relationship being 18:2 > > 16:0 > > cholesterol. The rates of uptake of these lipids were at least three times higher in HT-29gal than in HT-29glu cells. In HT-29glu cells, the relative rates of uptake of the sugars at 32 mM were D-glucose = galactose > fructose > > alpha-methylglucose. Uptake of these sugars was much greater in HT-29gal than in HT-29glu cells. When 100 microM forskolin was added to the incubation medium for 7 days post-confluency, which stimulates the activity of adenylate cyclase and thereby increases the intracellular synthesis of cAMP, there was no effect on the uptake of the lipids or the sugars in either HT-29glu or HT-29gal cells. Thus, (i) differentiated HT-29gal cells transport larger amounts of lipids and sugars than do undifferentiated HT-29glu cells; (ii) forskolin has no effect on the uptake of lipids or sugars in these cells. This human cell culture system may be useful to study the in vitro transport of lipids, to establish the role of cell differentiation on these uptake processes, and to determine the potential role of selected intracellular signals.

Absorption↗
PubMed1996

Influence of Helicobacter pylori on gastric mucosal adaptation to naproxen in man.

Our objective was to determine whether H. pylori influences gastric mucosal injury and adaptation caused by naproxen. Twenty-four healthy volunteers, 12 H. pylori-positive and 12 H. pylori-negative, were given a 28-day course of naproxen 500 mg twice a day. They were each gastroscoped to assess gastric mucosal damage and mucosal blood flow before and at 1, 7, and 28 days during treatment. Maximal gastric mucosal damage (median grade + IQR) occurred during the first 24 hr in both groups and was of similar magnitude (H. pylori-positive: 2.5, 2.0-3.0 P < 0.01; H. pylori-negative: 2.0, 1.0-3.0 P < 0.01). This damage was associated with a fall in antral but not corpus mucosal blood flow. With continued NSAID administration, gastric damage resolved confirming adaptation (H. pylori-positive 1.0, 0-2.0, H. pylori-negative: 1.0, 0-1.0) and antral mucosal blood flow returned to baseline in both groups by day 28. These observations suggest that initial gastric mucosal injury is not influenced by H. pylori colonization and adaptation occurs regardless of its presence.

Adaptation, Physiological↗
PubMed1995

Isolation and classification of chlorophyll-deficient xantha mutants of Arabidopsis thaliana.

Mutant lines of Arabidopsis thaliana that are either blocked at various steps of the biosynthetic pathway of chlorophyll (Chl) or that are disturbed in one of the subsequent steps leading to the assembly of an active photosynthetic membrane were isolated by screening for Chl-deficient xantha (xan) mutants. Only mutants that segregated in a 3:1 ratio, that contained the same carotenoid spectrum as etiolated wild-type seedlings and less than 2% of the Chl of wild-type control seedlings, and whose Chl content was not affected by the addition of sucrose to the growth medium were selected for a more detailed analysis. As a final test for the classification of the selected mutants, light-grown xan mutants were vacuum-infiltrated and incubated with the common precursor of tetrapyrroles, delta-aminolevulinic acid (ALA), in the dark. Two major groups of mutants could be distinguished. Some of the mutants were blocked at various steps of the Chl pathway between ALA and protochlorophyllide (Pchlide) and did not accumulate the latter in the dark. The other mutants accumulated Pchlide in the dark regardless of whether exogenous ALA was added. This latter group could be subdivided into mutants with a biochemical lesion in a recently discovered second light-dependent Pchlide reduction step that occurs in green plants and mutants that have blocks in the assembly of Chl protein complexes. In the present work a total of seven different loci could be defined genetically in Arabidopsis that affect the synthesis of Chl and its integration into the growing photosynthetic membrane.

Arabidopsis↗
PubMed1995

Gastric mucosal adaptation to etodolac and naproxen.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently cause damage to the gastroduodenal mucosa, principally by suppressing mucosal prostaglandin synthesis. However, such acute mucosal injury usually resolves, despite continued NSAID administration, by a process known as adaptation. Newer NSAIDs, such as etodolac, have been developed to minimize effects on prostaglandin synthesis. AIM: To determine whether etodolac causes less acute damage than naproxen, and whether the damage produced resolves with continued NSAID administration. METHODS: Twenty-four healthy volunteers were given a 28-day course of either etodolac 300 mg b.d. or naproxen 500 mg b.d. Gastroduodenal damage was assessed using a modified Lanza scoring system and mucosal blood flow with laser doppler flowmetry at endoscopy before NSAID administration and during days 1, 7 and 28 of continued intake. RESULTS: Maximum gastric damage (median grade and interquartile range, IQR) occurred during the first 24 h of administration, being greater with naproxen (2.0, IQR 1.0-3.0) than etodolac (1.0, IQR 1.0-1.5; P = 0.03). Such damage was associated with a fall in antral blood flow in the naproxen group (mean +/- S.E.M.) from 54.5 +/- 3.4 to 43.8 +/- 3.4 arbitrary units (P = 0.07) and a slight increase in mucosal blood flow in the etodolac group from 43.5 +/- 2.24 to 49.5 +/- 3.6 arbitrary units. With continued intake this damage resolved in all subjects taking etodolac and in eight of 14 subjects on naproxen. Resolution in the naproxen group was associated with a return to normal of antral blood flow. CONCLUSIONS: These observations suggest that etodolac causes less mucosal damage than naproxen and that adaptation occurs to both.

Adolescent↗
PubMed1995

D-cycloserine transport in human intestinal epithelial (Caco-2) cells: mediation by a H(+)-coupled amino acid transporter.

1. The ability of D-cycloserine to act as a substrate for H+/amino acid symport has been tested in epithelial layers of Caco-2 human intestinal cells. 2. In Na(+)-free media with the apical bathing media held at pH 6.0, D-cycloserine (20 mM) is an effective inhibitor of net transepithelial transport (Jnet) of L-alanine (100 microM) and its accumulation (across the apical membrane) in a similar manner to amino acid substrates (L-alanine, beta-alanine, L-proline and glycine). In contrast L-valine was ineffective as an inhibitor for H+/amino acid symport. Both inhibition of L-alanine Jnet and its accumulation by D-cycloserine were dose-dependent, maximal inhibition being achieved by 5-10 mM. 3. Both D-cycloserine and known substrates for H+/amino acid symport stimulated an inward short circuit current (Isc) when voltage-clamped monolayers of Caco-2 epithelia, mounted in Ussing chambers, were exposed to apical substrate in Na(+)-free media, with apical pH held at 6.0. The D-cycloserine dependent increase in Isc was dose-dependent with an apparent Km = 15.8 +/- 2.0 (mean +/- s.e. mean) mM, and Vmax = 373 +/- 21 nmol cm-2h-1. 4. D-Cycloserine (20 mM) induced a prompt acidification of Caco-2 cell cytosol when superfused at the apical surface in both Na+ and Na(+)-free conditions. Cytosolic acidification in response to D-cycloserine was dependent upon superfusate pH, being attenuated at pH 8 and enhanced in acidic media. 5. The increment in Isc with 20 mM D-cycloserine was non-additive with other amino acid substrates for H+/amino acid symport.

Amino Acid Transport Systems↗
PubMed1994

X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene.

X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.

Aphasia↗
PubMed1993

Physiological and psychological responses to a university fitness session.

The purpose of this study was to examine the physiological and psychological responses to a university fitness session entitled 'popmobility'. A popmobility session consists of 20 min of aerobic activities, 5 min of local muscular endurance exercises and 5 min of flexibility exercises. Ten regular participants of these sessions, women of mean(s.d.) age 21.2(1.5) years, took part in the study. A maximal oxygen uptake (VO2max) treadmill test was performed by each subject to obtain VO2max and maximum heart rate values. In a laboratory, heart rate and VO2 were measured throughout a popmobility session for each subject. Rate of perceived exertion (RPE) was measured every 5 min throughout the session. The mean intensity of the aerobic part of the session ranged from 67.7-82.6% of the subject's VO2max (mean of 76.4% VO2max). The mean heart rate reserve for the aerobic section was 75.6%. While the relative oxygen consumption remained fairly static during the aerobic section, the RPE score rose. The mean(s.d.) total energy expenditure was 236.6(28.4) kcal (range 203-288). The popmobility session is of adequate intensity to improve the aerobic fitness of its participants. Heart rate, as used as a measure of intensity during a popmobility session, would appear to be a fairly accurate indicator of intensity. However, the use of RPE for exercise prescription in popmobility sessions is inappropriate. Popmobility could also be useful in a weight-reduction programme.

Adult↗