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Biomedical subjects

M De Roo

Publications and source records attributed to M De Roo.

At least 37 records · Page 2Linked to original sources

Labelling of poly-L-lysine with 99mTc and evaluation as a possible tracer agent for ventriculography.

A stable 99mTc-labelled compound that is easy to prepare and that is retained for a long period of time in the blood would constitute an ideal replacement for 99mTc-HSA (limited by its rapid diffusion) and 99mTc-erythrocytes (lengthy and risky in vitro labelling) as tracer agent for ventriculography. We investigated whether 99mTc-labelled polymers would be suitable for this purpose. Four types of poly-L-lysine (PL) (Mw 41,000 to 377,000) were used either in underivatized form labelled at pH 12, or derivatized with a varying number of mercaptoacetyl (MA) substituents by reaction with N-hydroxysuccinimidyl-S-acetylmercaptoacetate followed by deprotection with hydroxylamine and labelling at pH 7.5. A high labelling yield was obtained in all cases. HPLC-purified 99mTc-PLs and 99mTc-MA-PLs were evaluated in mice, with 125I-HSA as an internal biological standard. The retention in the blood at 10 minutes and 60 minutes p.i. was not higher than about 30% for any of the tested compounds versus 84% for 125I-HSA, and was only 10% for the smallest 99mTc-labelled PL and MA-PL. Liver uptake was high for the 99mTc-PLs, whereas the 99mTc-MA-PL's were excreted in significant amounts to the urine. It is concluded that 99mTc-labelled poly-L-lysines or polymercaptoacetyl-poly-L-lysines are not suitable as blood pool tracer agents.

Animals↗

Different perceptual tasks performed with the same visual stimulus attribute activate different regions of the human brain: a positron emission tomography study.

To investigate the processing of visual form in human cerebral cortex, we used the PET (positron emission tomography) activation technique to compare the human brain regions that are involved in a visual detection task and two orientation discrimination tasks: the temporal same-different (TSD) task, which includes a short-term memory component, and the identification (ID) task, which is without this component. As a control task we used passive viewing. Stimuli were identical in all four tasks. Subtraction of passive viewing from detection showed that the detection task activates early visual cortical regions (areas 17/18) as well as several motor brain regions, while decreasing activity in several higher order frontal, temporal, and parietal regions. Comparing the ID task to the detection task revealed no further visual cortical activation, while comparison of the TSD task to the detection task revealed an activation of several right visual cortical regions, one of which remained significant after the subtraction of ID from TSD (right area 19). These experiments demonstrate the task dependence of visual processing, even for very closely related tasks, and the localization of the temporal comparison component involved in orientation discrimination in human area 19.

Adult↗

A new quantitative method for the analysis of cardiac perfusion tomography (SPET): validation in post-infarct patients treated with thrombolytic therapy.

In this study a new method for assessment of perfusion defects (PDs) derived from myocardial perfusion tomograms was evaluated in patients treated with thrombolytic therapy. Using global constraints and dynamic programming, a model-based delineation algorithm defined myocardial borders, the basal plane and absolute and relative PD size in 49 thallium-201 chloride (201TL CL) and 60 technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) tomograms. Tomographic (single-photon emission tomography: SPET) and planar quantification of PDs was compared to enzymatic infarct size as well as to global (LVEF) and regional ventricular function (RWM) obtained by contrast angiography. The algorithm delineated the myocardium and the valve plane in most cases, even when large PDs were present. Manual correction of the automatic delineation of the basal plane was necessary in less than 20% of the studies. Using 201Tl Cl, LVEF correlated better with tomographic PD (r = -0.67) than with planar PD (r = -0.54). Comparing planar to tomographic imaging using 99mTc-MIBI, a higher correlation with enzymatic infarct size (r = 0.73 vs 0.57) and with global ventricular function (r = 0.64 vs -0.52) was found when tomographic techniques were used. No close correlation between PD and RWM was found. The beneficial effect of thrombolysis was shown by a significant difference of PD in patients with open versus occluded infarct-related vessels. It can be concluded that this new automated algorithm for quantification of SPET perfusion defect size provides a useful tool in evaluating thrombolytic therapy.

Algorithms↗

Experimental validation of a new quantitative method for the analysis of infarct size by cardiac perfusion tomography (SPECT).

Using global constraints and dynamic programming, a new model-based segmentation algorithm was developed to determine myocardial borders and basal plane. The segmented image is transformed to a countrate polar map and the infarct size (I.S.) is determined by comparison with a reference polar map. In order to evaluate our method the algorithm was applied to heart phantoms, to software simulations and to animal studies. In the last experiments, Tc-99m Sestamibi was used as a perfusion agent. The total myocardial volume and infarct size of a Jasczack phantom were overestimated, especially when I.S. was expressed in absolute rather than relative values. It was proven by software simulations of cardiac Spect studies that those errors were mainly due to finite resolution effects causing a clear overestimation of myocardial thickness. Implementation of a constant thickness in the algorithm resulted in a much better correlation with actual values. In a dog experiment the size of total myocardial volume of the area at risk during occlusion and of the final infarct size after thrombolysis was correlated with the histologic values obtained by planimetry after TTC staining. In 8 studies, an excellent correlation between the histologic area at risk versus the estimated perfusion defects was obtained (r = 0.97). The automatic delineation of myocardial borders and valve plane was excellent even when perfusion defects were present. Manual intervention was only necessary in certain slices where a clear overlap between liver and myocardium was present in the dog studies. Segmental polar maps expressing count rate and volume information provided a visual and quantitative tool to evaluate the influence of thrombolysis in acute ligation experiments. It is concluded that the new algorithm is ready to be used in a clinical environment for the quantitative evaluation of perfusion defects after acute myocardial infarction and for the follow-up of the therapeutic strategy.

Animals↗

The measurement of fecal thyroxine in the diagnosis of thyrotoxicosis factitia.

Two patients with prolonged thyrotoxicosis are presented with low radioiodide uptake, low-normal serum thyroglobulin concentrations, and low iodide content of the neck on x-ray fluorescence studies. The surreptitious intake of thyroid hormone was directly proven by a high fecal concentration of T4 (12.38 and 23.99 nmol/g) compared with low concentrations in healthy subjects (1.03 +/- 0.64 nmol/g; mean +/- SD, n = 6) and in patients with hyperthyroidism due to Graves' disease (1.93 +/- 1.86; n = 8). Fecal thyroid hormone measurement may help to provide formal proof of factitious thyrotoxicosis.

Adult↗

A rare case of sebaceous carcinoma with very malignant characteristics.

A case of a sebaceous carcinoma is presented. This carcinoma of the skin appendages requires diagnosis by histopathology because the clinical appearance is often atypical. Because of the frequency of metastases to local lymph nodes and bone, a careful physical examination and appropriate radiologic/scintigraphic examinations of these organs should be performed routinely. The case presented illustrates the very malignant character of this tumor.

Adenocarcinoma↗

Limitations of quantitative radionuclide bone scanning in the evaluation of total knee replacement.

To establish the value of quantitative radionuclide bone scanning after total knee replacement, 21 patients were scheduled for examination. Eight patients were scanned more than 1 year after surgery (group 1), and 13 within the first postsurgical year (group 2). Ratios were calculated for three regions of interest. The ratio was defined as the counts per pixel for each region of interest, normalized by dividing them by the counts per pixel of the ipsilateral femoral shaft. There was no significant difference in uptake between control subjects and patients in group 2, indicating that the test was not reliable within this time period. No statistical difference was found between the uptake scores in groups 1 and 2, demonstrating that an uninterpretable period of 1 year is perhaps too short. Using a ratio of more than three, seen more than 1 year after surgery as pathologic, a sensitivity of 100%, a specificity of 33%, and an accuracy of 75% was found. Quantitative bone scanning is a very sensitive test for detecting complications, but it is nonspecific in diagnosing loosening of total knee arthroplasties. The value of quantitative scanning presumably lies in the follow-up of patients as an objective method for the evaluation of sequential scanning. Nevertheless, radionuclide data need to be interpreted in correlation with clinical and radiologic findings.

Evaluation Studies as Topic↗

Early and late effects of rt-PA vs placebo on left ventricular function measured by nuclear ventriculography.

The aim of the study was the functional re-evaluation of 296 patients 12 to 18 months after a double-blind trial evaluating the effect of tissue plasminogen activator (rt-PA) versus placebo given within 5 h of onset of symptoms caused by an acute myocardial infarction. All patients underwent rest-stress radionuclide angiography (Egna). For each exercise level the global left ventricular ejection fraction (LVEF) was calculated together with an estimate of regional wall motion abnormalities (RWMA). A clear difference of the total workload and the peak workload was found between both therapeutic groups. Discriminant analysis evaluating four parameters (LVEF at peak exercise and at the endpoint and the workload at those levels) revealed a beneficial therapeutic effect. The RWM at rest showed only a difference in the apico-inferior region. There were less wall motion abnormalities in the treated group. Radionuclide analysis demonstrated a larger functional capacity and a better coordination of myocardial contractility during stress RNA one year after thrombolytic therapy. At rest, no major differences were found between the hospital stage and the follow-up in both therapeutic groups one year later.

Adult↗

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.

Diabetic Neuropathies↗

Clinical usefulness of Tc-99m HMPAO labeled white blood cell imaging in prosthetic vascular graft infections.

The reported frequency of prosthetic vascular graft infections after reconstructive vascular surgery is low. However, it is a serious and potentially catastrophic complication of this treatment, with high morbidity and mortality rates. Effective therapy involves graft excision and replacement. Tc-99m HMPAO labeled leukocyte scintigraphy appears to be an accurate method of detecting prosthetic vascular graft infections. The value of leukocyte scanning is illustrated by two case reports.

Aged↗

Seasonal variation in bone metabolism in young healthy subjects.

Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD3 but also for 1,25(OH)2D3, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)2D3 for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes.

Adult↗

Evaluation of a multicentre study with Iomazenil--a benzodiazepine receptor ligand.

After showing in an earlier publication that Iomazenil is a potent benzodiazepine receptor antagonist, the substance has been distributed to 11 clinical centres in Europe for further tests. The protocol asked for volunteers, epileptic cases and patients with Alzheimer's disease. Prior to the Iomazenil examination, flow images by perfusamine or HMPAO were required, and as comparative methods EEG, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. The results allowed first the determination of the normal distribution of the benzodiazepine receptors in the human brain. The highest uptake was found in medial occipital cortex. Second, the evaluation of the epileptic cases shows a 100% positive prediction value for Iomazenil compared to 92% for flow images. Negative prediction values were calculated as 81% for Iomazenil and 54% for flow images. Furthermore, one group reported the successful diagnosis of Alzheimer's disease at an early stage. The visual image examination was tentatively compared to a more objective semiquantitative one based on quotients of corresponding left/right regions of interest. This semiquantitative method has not proved successful yet, but the problems have been identified. A more precise protocol for further studies is therefore proposed.

Adult↗

Clinical significance of squamous cell carcinoma antigen in cancer of the human uterine cervix. Comparison with CEA and CA-125.

Serum squamous cell carcinoma antigen (SCCa) concentrations were determined by a radioimmunoassay kit before and during the treatment of 50 patients with cervical carcinoma: 44 with squamous cell carcinoma (SCC) and 6 with adenocarcinoma. The positivity rate of SCCa was 50% (52% for SCC and 33% for adenocarcinoma). The sensitivity of SCCa for SCC was twice as high as that of CEA and CA-125. Low serum concentrations were observed in early-stage carcinoma, indicating that SCCa is not useful for diagnosis. In advanced cases, serum levels were directly and significantly correlated with the stage of the disease.

Adenocarcinoma↗

Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies.

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

Adult↗