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Biomedical subjects

J Melin

Publications and source records attributed to J Melin.

At least 37 records · Page 2Linked to original sources

Biological pathways of radionuclides originating from the Chernobyl fallout in a boreal forest ecosystem.

In an attempt to understand the mechanisms governing the transfer and retention of radiocaesium in the understorey vegetation, 39 macromycetes species and 33 plant species, together with humus samples, were systematically collected from the undercover vegetation in a boreal coniferous forest. The results indicate that the main factors determining interspecific differences in contamination level are the rooting depth in plants, the depth of mycelium in fungi, and the ecophysiological behaviour of fungi, mycotrophism or plant parasitism. A comparison between the investigated species and the same species growing in similar ecosystems, albeit under different climatic conditions, resulted in an almost identical ranking in terms of radiocaesium contamination levels; the contamination ratios between species were also relatively constant. From an experiment involving humus samples, it was shown that up to 40% of the radiocaesium could be retained by the microflora, particularly by mycelia.

Cesium Radioisotopes↗

Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor.

Left ventricular function and neurohormonal status in patients with heart failure remaining symptomatic during therapy with angiotensin-converting enzyme inhibitors were assessed, and the effects of dopaminergic receptor stimulation in this setting were determined. Neurohormonal and left ventricular function (radionuclide angiography) data were obtained in 19 patients with symptomatic ischemic heart failure. Measurements were repeated after 4 to 6 weeks of therapy with the dopamine agonist ibopamine (100 mg, 3 times/day) or placebo administered in a double-blind, randomized, parallel group design. At baseline, despite therapy with enalapril, the angiotensin II levels (mean 39.4 pg/ml; p < 0.01 vs controls) were significantly increased, as were plasma norepinephrine (497 +/- 240 pg/ml; p < 0.01 vs controls), endothelin-1, atrial natriuretic peptide and arginine vasopressin. Moreover, in comparison with pretreatment values, left ventricular ejection fraction had decreased substantially (-9.1%) in patients with plasma norepinephrine > or = 600 pg/ml, but not in those with lower values of norepinephrine. With ibopamine, plasma norepinephrine decreased from 516 +/- 241 to 391 +/- 208 pg/ml (n = 8; p < 0.025 vs placebo), whereas it increased with placebo. In conclusion, the neurohormonal control provided by an angiotensin-converting enzyme inhibitor is reduced in a large subset of patients during prolonged therapy; ibopamine appears to be a potentially useful drug to improve neurohormonal control in this setting.

Aged↗

Effects of nisoldipine therapy on myocardial perfusion and neuro-hormonal status in patients with severe ischaemic left ventricular dysfunction.

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

High metabolic activity demonstrated by positron emission tomography in human auditory cortex in case of deafness of early onset.

Glucose metabolism has been studied in the auditory cortex of human subjects with deafness of early onset, and compared to normal subjects with ears plugged. The metabolism in the auditory cortex and in the association auditory cortex was higher in deaf subjects than in normal subjects. This result is compared to similar observations that we made previously in the visual cortex of human subjects with blindness of early onset.

Adolescent↗

Optimal use of dobutamine stress for the detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both?

OBJECTIVES: This study was conducted to examine the efficacy of dobutamine stress two-dimensional echocardiography and perfusion scintigraphy for the detection of coronary artery disease in routine practice, to establish the causes of erroneous results and to derive appropriate criteria for the selection of either or both tests. BACKGROUND: Dobutamine stress combined with echocardiography or perfusion scintigraphy may be used to detect coronary artery disease. Although both imaging approaches have demonstrated similar levels of accuracy, it is not known whether there may be particular indications for the use of one or the other technique or a rationale for their combination. METHODS: Two hundred seventeen patients without previous infarction were studied prospectively with dobutamine stress echocardiography and technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography at the time of diagnostic coronary angiography. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or stress-induced abnormalities of perfusion and regional function. The extent of these abnormalities was correlated with an equivalent score of extent of angiographic disease. RESULTS: Significant coronary artery disease was found in 142 patients; 102 (72%) were identified by dobutamine echocardiography and 108 (76%, p = NS) by perfusion imaging. In 75 patients without significant disease, the specificity of dobutamine echocardiography was 83% compared with 67% for scintigraphy (p = 0.05). Echocardiographic sensitivity was lower in patients unable to complete the test because of side effects (n = 64) than in the remainder (59% vs. 77%, p = 0.02); this influence was less apparent with scintigraphy (71% vs. 78%, p = NS). Selective use of scintigraphy in the 31 patients with a negative submaximal stress echocardiogram led to a sensitivity of 80% for this combination. Patients with left ventricular hypertrophy accounted for most of the difference in specificity between echocardiography and scintigraphy (94% vs. 59%, p = 0.02). Their respective accuracies were 76% and 73%. CONCLUSIONS: Dobutamine stress echocardiography and perfusion scintigraphy have equivalent accuracy. In patients with left ventricular hypertrophy, echocardiography appears to be the test of choice. Selective use of sestamibi scintigraphy in patients with a negative submaximal echocardiogram enhances the accuracy of stress echocardiography alone.

Aged↗

Diagnosis of coronary artery disease in elderly patients: safety and efficacy of dobutamine echocardiography.

Coronary artery disease may be difficult to diagnose in the elderly because its clinical symptomatology is frequently atypical and because the performance of submaximal tests makes exercise stress testing sometimes unreliable. Dobutamine stress testing may be a useful alternative in such patients. This study compared the safety and accuracy of dobutamine stress echocardiography in 73 'young' (< 60 years old) and 63 'old' (> or = 60 years old) patients without previous myocardial infarction undergoing diagnostic coronary angiography. The sensitivity in young patients (79%, (67-91, 95% CI)) was similar to that in old patients (80% (69-91, 95% CI)). Similar levels of specificity (88% (75-101, 95% CI) vs 75% (54-96, 95% CI)) were found in the two groups. Both groups showed a trend to a higher sensitivity for multi-vessel disease than for single-vessel disease. No major side effect occurred during the entire study and peak dose (40 micrograms.kg-1.min-1) was attained with similar frequency in both groups (56% vs 49%). Minor side effects occurred equally in 'young' and 'old' patients and never persisted more than a few minutes after ending the first infusion of dobutamine. Dobutamine echocardiography appears to be safe and accurate for the detection of coronary artery disease regardless of age.

Adult↗

Selection of the optimal nonexercise stress for the evaluation of ischemic regional myocardial dysfunction and malperfusion. Comparison of dobutamine and adenosine using echocardiography and 99mTc-MIBI single photon emission computed tomography.

BACKGROUND: The mechanisms of action of exercise-simulating and vasodilator stressors support their combination with imaging techniques that evaluate left ventricular function and perfusion, respectively. However, reported accuracies of either pharmacological stress together with two-dimensional echocardiography (2DE) or single photon emission computed tomography (SPECT) of myocardial perfusion are similar. The purpose of this study was to establish the optimal stress for each imaging technique by comparing the results of digitized 2DE and 99mTc-methoxyisobutyl isonitrile (MIBI) SPECT using both dobutamine and adenosine stresses in the same patients and conditions. METHODS AND RESULTS: Ninety-seven consecutive patients without evidence of previous infarction undergoing coronary angiography for clinical indications were studied prospectively. Dobutamine was infused during clinical, ECG, and echocardiographic monitoring in dose increments from 5 to 40 micrograms.kg-1.min-1. Adenosine was infused under the same conditions in doses of 0.10, 0.14, and 0.18 mg.kg-1.min-1. For each protocol, the end points were achievement of peak dose, development of severe ischemia, or intolerable side effects. At peak stress, 20 mCi of MIBI was injected, and SPECT imaging was performed 2 hours later; abnormal poststress images were compared with resting SPECT: Digitized 2DE images were compared qualitatively before, during, and after stress in a cine-loop display. Significant coronary disease (n = 59 patients) was defined by the quantification of > 50% stenosis in a major epicardial vessel. The sensitivity of adenosine 2DE was 58%, less than those of adenosine MIBI (86%, p = 0.001), dobutamine 2DE (85%, p = 0.001), and dobutamine MIBI (80%, p = 0.01). Their respective specificities were 87%, 71%, 82%, and 74% (p = NS). The accuracy of adenosine 2DE was 69%, compared with 80% for adenosine MIBI (p < 0.001), 84% for dobutamine 2DE (p = 0.001), and 77% for dobutamine MIBI (p = 0.005); the latter three did not differ significantly in either sensitivity or accuracy. CONCLUSIONS: This prospective, direct comparison of alternative pharmacological stresses in patients without myocardial infarction shows vasodilator stress scintigraphy and dobutamine stress echocardiography and scintigraphy to share equivalent levels of sensitivity. All three are significantly more sensitive than adenosine stress echocardiography. Dobutamine stress may be used for wall motion or perfusion imaging, but adenosine stress is best combined with perfusion scintigraphy.

Adenosine↗

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators.

BACKGROUND: Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible. METHODS AND RESULTS: One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction < or = 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P < .05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119 +/- 28 to 124 +/- 33 mL/m2, mean +/- SD) and decreased in enalapril patients (120 +/- 25 to 113 +/- 25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P < .02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group. CONCLUSIONS: Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

Cardiac mechanics during development of heart failure. SOLVD Investigators.

BACKGROUND: The changes in myocardial performance responsible for the progression from a stage of asymptomatic left ventricular dysfunction toward overt congestive heart failure are still poorly understood. Accordingly, using invasive methods, we examined the differences in baseline left ventricular function between a subgroup of patients enrolled in the treatment arm (presence of congestive heart failure) and in the prevention arm (asymptomatic patients) of the Studies of Left Ventricular Dysfunction. METHODS AND RESULTS: High-fidelity left ventricular pressures and frame-by-frame angiographic volumes were simultaneously obtained under baseline conditions in 65 patients with left ventricular ejection fraction < or = 35%. Sixteen patients had New York Heart Association congestive heart failure (class II or III), whereas the remaining 49 patients had no clinical signs of heart failure and did not receive therapy for this syndrome. A second set of data was obtained an average of 12.4 months later in 42 patients. The group with heart failure had significantly greater end-diastolic and end-systolic volumes than the asymptomatic group (both p < 0.001), but the stroke index at rest was similar in both groups. Accordingly, ejection fraction was significantly lower in the heart failure group (19.6 +/- 7.0% versus 26.3 +/- 7.2%; p < 0.02). Left ventricular end-diastolic pressure was greater and peak +dP/dt was lower in heart failure patients, but the difference did not reach statistical significance after Bonferroni correction for multiple comparisons. Moreover, the individual end-systolic stress/end-systolic volume data of the heart failure patients fell within the 95% confidence interval of the relation observed in the patients without heart failure both at baseline and after 1 year of follow-up irrespective of their changes in functional status. It was also noted that during follow-up, the changes in end-diastolic and end-systolic volumes correlated linearly, as if both dimensions always shifted in parallel, whereas alterations in contractility primarily influence end-systolic volume. CONCLUSIONS: These observations are compatible with the hypothesis that a depression in the mechanical performance of the viable myocardial areas is not the major determinant for the progression from asymptomatic to symptomatic left ventricular dysfunction. Abnormalities in left ventricular diastolic distensibility, on the other hand, might underlie the progressive ventricular dilation and create a vicious cycle through the afterload mismatch.

Adult↗

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators.

BACKGROUND: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

Angiotensin-Converting Enzyme Inhibitors↗

Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables.

A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Thrombus imaging with an I-123-labeled F(ab')2 fragment of an anti-human fibrin monoclonal antibody in a rabbit model.

The murine monoclonal antibody MA-15C5 binds to cross-linked fibrin but not to fibrinogen. Fab or F(ab')2 fragments of MA-15C5, labeled with iodine-123, were injected intravenously into nine rabbits with a nonocclusive 0.2-mL human plasma clot in the jugular vein and into eight control rabbits. Scintigrams obtained at hourly intervals after injection of the F(ab')2 fragment revealed a significantly higher accumulation of tracer in the clot region than in the contralateral region. The relative excess of tracer in the jugular vein region was significantly greater in the study animals than in the control animals throughout the study period. Blind reading of serial scans revealed no visible tracer accumulation in seven of eight control rabbits, whereas the scans of seven of nine study rabbits showed clearly visible accumulation (sensitivity = 77%, specificity = 87%). The Fab fragment of MA-15C5 had a lower affinity and bound less avidly to the blood clot in vivo. These results suggest that the F(ab')2 fragment has better imaging properties than the Fab fragment and that it may be useful for imaging blood clots in man.

Animals↗

Electrocardiographic findings in subarachnoid hemorrhage. A population study.

The prevalence of ECG abnormalities and their prognostic value in subarachnoid hemorrhage (SAH) were analysed in patients from an epidemiological study on SAH. The analysis was based on ECGs recorded during the first 72 hours after bleeding. An ECG recording was obtained in 29% of patients dying within 7 days after SAH, and in 64% of those surviving longer. Tachycardia over 100 beats/min, P mitrale, and ST segment depression greater than 1.0 mm or elevation greater than 2.5 mm were statistically significantly more common among patients dying within 7 days after bleeding. ECG changes reflecting myocardial ischemia or a compromised hemodynamic state observed during the first 3 days after SAH seem to have an untoward effect on the prognosis.

Arrhythmias, Cardiac↗