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Biomedical subjects

R Underwood

Publications and source records attributed to R Underwood.

At least 37 records · Page 2Linked to original sources
PubMed1996

Potentiation of the immune response in HIV-1+ individuals.

T cells from HIV-1+ individuals have a defect in mounting an antigen specific response. HIV-1 Tat has been implicated as the causative agent of this immunosuppression. We have previously shown that HIV-1 Tat inhibits antigen specific proliferation of normal T cells in vitro by binding to the accessory molecule CD26, a dipeptidase expressed on the surface of activated T cells. We now demonstrate that the defective in vitro recall antigen response in HIV-1 infected individuals can be restored by the addition of soluble CD26, probably by serving as a decoy receptor for HIV-1 Tat. The restored response is comparable to that of an HIV-1- individual, suggesting that early in HIV infection there is a block in the memory cell response, rather than deletion of these cells.

Dipeptidyl Peptidase 4↗
PubMed1996

Antitumor activity of the R- and S-enantiomers of RS-2-[[hydroxy[[2-[ (octadecyloxy)methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N, N,N,-trimethylethylaminium hydroxide inner salt.

The R- and S-enantiomers of 2-[[hydroxyl[[2-[(octadecyloxy) methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N,N,N,- trimethylethylaminium hydroxide salt (SRI 62-834) have been evaluated in several assays to determine potential antitumor activity. The S-enantiomer showed slightly greater cytotoxic activity than the R- or RS-forms against several murine tumor cell lines. In the mouse Meth A fibrosarcoma model, the S-enantiomer was ca. 4 times more effective than the R-isomer in controlling size of tumor growth and increasing the number of survivors.

Animals↗
PubMed1996

Electron-beam CT scanning for detection of coronary calcification and prediction of coronary heart disease.

Electron-beam or ultrafast computerized tomographic (CT) scanning provides a convenient and sensitive means of detecting coronary calcification, which is an early index of atherosclerosis. The procedure has strong negative predictive power for the presence of coronary artery disease, but a limited ability to predict disease severity. However, preliminary indications are that it is as good or better than conventional risk factors in this respect. Although further validation is needed before electron-beam CT can be regarded as an established method of detecting presymptomatic coronary atherosclerosis, the procedure has potential in this context.

Adult↗
PubMed1996

Echocardiography overestimates left ventricular mass: a comparative study with magnetic resonance imaging in patients with hypertension.

OBJECTIVE: To compare measurement of left ventricular mass (LVM) by M-mode echocardiography and magnetic resonance imaging (MRI) in hypertensive subjects. DESIGN: A prospective study. SUBJECTS: Twenty-four untreated hypertensive patients [19 men and five women, aged 51 +/- 2 (mean +/- SEM) years, supine blood pressure 159/101 +/- 3/1 mmHg]. SETTING: The Blood Pressure Unit, St Georges Hospital Medical School and Magnetic Resonance Unit, Royal Brompton National Heart and Lung Hospital, London. MAIN OUTCOME MEASURES: LVM estimated both by M-mode echocardiography and by MRI. RESULTS: Using three standard M-mode formulae, widely different values of LVM were obtained with echocardiography [American Society of Echocardiography (ASE) 319 +/- 21 g, Penn 273 +/- 19 g. Teichholz 191 +/- 11 g]. By MRI, the LVM was 232 +/- 11 g. The differences between MRI and echocardiography could not be explained in terms of the timing of measurements in the cardiac cycle. When single-slice MRI measurements at the appropriate level were applied to the ASE and Penn formulae, the LVM was again overestimated. CONCLUSION: Our study has shown major differences in LVM estimated using methods based on one-dimensional (echocardiography) compared with three-dimensional (MRI) data. These differences seem to be largely the result of the geometrical assumptions on which M-mode measurements are based. Our findings have important clinical implications for the assessment of the severity and response to treatment of left ventricular hypertrophy in hypertensive patients.

Echocardiography↗
PubMed1995

Dobutamine stress: effects on regional myocardial blood flow and wall motion.

OBJECTIVES: This investigation studied the relation between regional myocardial blood flow and left ventricular function during dobutamine stress in patients with coronary artery disease. BACKGROUND: Dobutamine stress is becoming more frequently used as an alternative to dynamic exercise in patients with ischemic heart disease. METHODS: We studied 12 patients with coronary artery disease. Dobutamine was infused from 5 micrograms/kg body weight per min up to 40 micrograms/kg per min or until chest pain or other intolerable side effects. Regional myocardial blood flow was measured with positron emission tomography and oxygen-15-labeled water. Regional wall motion was assessed in three short-axis slices by magnetic resonance imaging. Each slice was subdivided into four regions: septal, anterior, lateral and inferior. A total of 140 regions were suitable for comparison. RESULTS: During stress, new wall motion abnormalities developed in 27 regions. Myocardial blood flow (mean +/- SD) increased in 113 regions that did not develop wall motion abnormalities (0.98 +/- 0.26 [baseline] vs. 1.98 +/- 0.87 [dobutamine] ml/min per g, p < 0.001), whereas it did not change significantly in regions with stress-induced wall motion abnormalities (1.00 +/- 0.28 [baseline] vs. 1.30 +/- 0.62 [dobutamine] ml/min per g, p = NS). An absolute decrease in myocardial blood flow below the value at rest was observed in seven segments that developed wall motion abnormalities during stress. CONCLUSIONS: The normal functional response to dobutamine stress is paralleled by an increase in coronary flow, whereas mechanical dysfunction is accompanied by a blunted increase, or even a paradoxic decrease, in regional coronary flow.

Adult↗
PubMed1995

Localization of a misplaced coronary artery stent by magnetic resonance imaging.

Coronary artery stents have been developed to overcome arterial abrupt closure and restenosis following balloon angioplasty. Complications of stent insertion include loss of the device from its delivery system into the peripheral circulation. Certain types of stents are almost radiolucent, making localization of the lost devices difficult. Nonferromagnetic metallic biomedical implants induce alteration of the local magnetic field and this leads to loss of signal from the surrounding tissues. We have used this property to localize a misplaced coronary artery stent in a 53-year-old man who underwent unsuccessful stent insertion. A 0.5 Tesla magnetic resonance scanner was used to acquire gradient-echo and spin-echo images. An in vitro experiment was first carried out on a stent similar to that used in our patient to establish that it was nonferromagnetic and to determine the optimum imaging technique. Gradient-echo images with a relatively long echo time (22 ms) gave the largest area of signal loss around the stent, and this sequence was used for localization of the stent found in the patient's left profunda femoris artery. This was subsequently confirmed by digital radiography. We have demonstrated the convenience and practicality of using magnetic resonance imaging for the localization of a misplaced coronary artery stent in a patient. The technique is safe, noninvasive, and uses no ionizing radiation.

Angioplasty, Balloon, Coronary↗
PubMed1995

A comparison of resting images from two myocardial perfusion tracers.

We have compared stress-redistribution and delayed rest thallium-201 with rest technetium-99m methoxyisobutylisonitrile (MIBI) tomograms in order to compare the tracers for the assessment of myocardial viability and to validate a rapid protocol combining the two tracers. We studied 30 consecutive patients with known or suspected coronary artery disease [group 1: 16 with normal left ventricular function, mean left ventricular ejection fraction (LVEF) 55%, SD 6%; group 2: 14 with abnormal function, mean LVEF 28%, SD 8%]. 201Tl was injected during infusion of adenosine followed by acquisition of conventional stress and redistribution tomograms. On a separate day, 201Tl was injected at rest with imaging 4 h later. 99mTc-MIBI was then given at rest and imaging was performed. Three images were compared: redistribution 201Tl, rest 201Tl, and rest 99mTc-MIBI. Tracer activity was classified visually and quantitatively in nine segments and segments with > 50% activity were defined as containing clinically significant viable myocardium. Mean (+/- SD) global tracer uptake as a percentage of maximum was similar in group 1 (rest 201Tl 69% +/- 12%, redistribution 201Tl 69% +/- 15%, rest 99mTc-MIBI 70% +/- 13%, ANOVA P > 0.05), but in group 2 mean tracer uptake was significantly greater in the rest 201Tl images (59% +/- 16%) than in redistribution 201Tl images (53% +/- 17%) or rest 99mTc-MIBI images (53% +/- 19%) (ANOVA P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

The application of a non-imaging nuclear probe system to the critically ill: laboratory validation and a clinical trial.

Non-imaging nuclear probe systems have been available for bedside monitoring of left ventricular function since the early 1970s. The purpose of this study was to evaluate a recently developed system, the Cardioscint (Oakfield Instruments, Oxford, UK), both in the laboratory and clinically prior to its application in the critically ill on the intensive care unit. The probe system was stable at body temperature for prolonged periods and its count rate capability was adequate for those encountered clinically. An adequate period of data acquisition was shown to be important because random isotope decay produces a significant noise at these count rates. Left ventricular ejection fraction in patients with symmetrical ventricular contraction agree closely with the results obtained with radionuclide ventriculography (mean difference = 0.98%, S.D. = 2.8%, n = 30). However, in patients with asymmetrical ventricular contraction the agreement is poor (mean difference = -3.0%, S.D. = 6.2%, n = 10).

Adolescent↗
PubMed1994

Relations between resting ventricular long axis function, the electrocardiogram, and myocardial perfusion imaging in syndrome X.

OBJECTIVE: To investigate interrelations between ventricular long axis function, resting electrocardiogram, and myocardial perfusion imaging in a group of patients with syndrome X in order to define possible underlying mechanisms. DESIGN: Prospective echocardiographic, electrocardiographic, and myocardial perfusion imaging. SETTING: A tertiary referral centre for cardiac diseases with invasive and non-invasive facilities. PATIENTS: 50 consecutive patients with syndrome X selected on the basis of a history of angina, ST segment depression on exercise, and normal coronary arteriograms and 21 controls of similar age. RESULTS: Long axis motion of one or both ventricles assessed by echocardiography was abnormal in 37 patients. The onset of systolic shortening was delayed by > 130 ms (upper limit of normal 95% confidence interval) in eight patients, and was associated with prolonged shortening during the isovolumic relaxation period in seven (p < 0.01) (systolic abnormalities). The onset of diastolic lengthening was delayed by > 80 ms in 20. Early diastolic peak lengthening rate was < 4.5 cm.s-1 in 13 patients, and the relative amplitude of lengthening during atrial systole was > 45% in 18. On the resting electrocardiogram septal q waves were absent in 12 patients. This was associated with long axis systolic disturbances in seven patients (p < 0.05). T waves were abnormal in 10 and associated with delayed onset of early diastolic lengthening in all (p < 0.001). Late diastolic long axis disturbances were not associated with any consistent electrocardiographic abnormality. Myocardial perfusion imaging was abnormal in six of 33 patients, four of whom had systolic abnormalities (p < 0.03). Imaging was normal in the rest, but in 13 of them long axis function was abnormal in the left side and in four it was abnormal on the right ventricle. Both electrocardiography and imaging were normal in 10 patients. No patient with an abnormal electrocardiogram or myocardial perfusion had normal long axis motion on echocardiography. CONCLUSION: The function of the left and right ventricular long axes was abnormal in about 70% of a sample of patients with syndrome X. Systolic disturbances were consistently associated with absent septal q wave and abnormal myocardial perfusion imaging, while early diastolic disturbances correlated with T wave abnormalities. These associations suggest that the three different investigations detect related objective abnormalities in one or more subgroups of patients with syndrome X.

Echocardiography↗
PubMed1993

Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages.

Because fibroblast growth factors (FGFs) modulate important functions of endothelial cells (EC) and smooth muscle cells (SMC), we studied FGF expression in human vascular cells and control or atherosclerotic arteries. All cells and arteries contained acidic (a) FGF and basic (b) FGF mRNA. Northern analysis detected aFGF mRNA only in one of five control arteries but in all five atheroma tested, while levels of bFGF mRNA did not differ among control (n = 3) vs. plaque specimens (n = 6). Immunolocalization revealed abundant bFGF protein in control vessels (n = 10), but little in plaques (n = 14). In contrast, atheroma (n = 14), but not control arteries (n = 10), consistently exhibited immunoreactive aFGF, notably in neovascularized and macrophage-rich regions of plaque. Because macrophages colocalized with aFGF, we tested human monocytoid THP-1 cells and demonstrated accumulation of aFGF mRNA during PMA-induced differentiation. We also examined the expression of mRNA encoding FGF receptors (FGFRs). All cells and arteries contained FGFR-1 mRNA. Only SMC and control vessels had FGFR-2 mRNA, while EC and some arteries contained FGFR-4 mRNA. The relative lack of bFGF in plaques vs. normal arteries suggests that this growth factor may not contribute to cell proliferation in advanced atherosclerosis. However, aFGF produced by plaque macrophages may stimulate the growth of microvessels during human atherogenesis.

Arteries↗