Christian Beckers

Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and efficiency of probability analysis.

Alternative strategies using conditional probability analysis for the diagnosis of coronary artery disease (CAD) were examined in 93 infarct-free women presenting with chest pain. Another group of 42 consecutive female patients was prospectively analyzed. For this latter group, the physician had access to the pretest and posttest probability of CAD before coronary angiography. These 135 women all underwent stress electrocardiographic, thallium scintigraphic, and coronary angiographic examination. The pretest and posttest probabilities of coronary disease were derived from a computerized Bayesian algorithm. Probability estimates were calculated by the four following hypothetical strategies: SO, in which history, including risk factors, was considered; S1, in which history and stress electrocardiographic results were considered; S2, in which history and stress electrocardiographic and stress thallium scintigraphic results were considered; and S3, in which history and stress electrocardiographic results were used, but in which stress scintigraphic results were considered only if the poststress probability of CAD was between 10% and 90%, i.e., if a sufficient level of diagnostic certainty could not be obtained with the electrocardiographic results alone. The strategies were compared with respect to accuracy with the coronary angiogram as the standard. For both groups of women, S2 and S3 were found to be the most accurate in predicting the presence or absence of coronary disease (p less than .05). However, it was found with use of S3 that more than one-third of the thallium scintigrams could have been avoided without loss of accuracy. It was also found that diagnostic catheterization performed to exclude CAD as a diagnosis could have been avoided in half of the patients without loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Variations of Iodine Nutrition and Thyroid-function During the Neonatal-period in Europe

In order to evaluate further the possibility that transient hypothyroidism and hyperthyrotropinemia in newborn infants could result from a state of relative iodine deficiency, the urinary concentration of iodine, used as an index of the dietary intake of iodine was determined in casual urine samples collected in 1,076 full-term infants aged 3-6 days in 16 cities in 10 different European countries and in Toronto, Canada. In addition, the results obtained by programs of systematic neonatal screening for congenital hypothyroidism in the same areas were compared. There were marked regional differences in iodine nutrition during the neonatal period in Europe (median urinary iodine: 16.2 micrograms/dl in Rotterdam, the Netherlands, and 1.1 micrograms/dl in Freiburg, FRG. A low iodine supply in newborn populations was accompanied by, and probably explained, an elevated frequency of transient disorders of thyroid function in young infants. Iodine prophylaxis is urgently needed in some European countries not only for the prevention of goiter, but mostly for the prevention of impairment of thyroid function during the critical period of brain development.

Area-at-risk determination by technetium-99m-hexakis-2-methoxyisobutyl isonitrile in experimental reperfused myocardial infarction.

In a canine model of reperfused myocardial infarction, we tested the hypothesis that after reperfusion, technetium-99m-hexakis-2-methoxyisobutyl isonitrile (Tc-MIBI) tomographic imaging still reflects occlusion blood flow when the tracer is injected before reperfusion. Nine anesthetized dogs underwent 2 hours of coronary occlusion followed by 3 hours of reperfusion ending by being killed. Reference coronary blood flow was determined by radioactive microspheres injected during occlusion and after reperfusion. Biopsies in normal and ischemic myocardium and single photon emission computed tomography were obtained during occlusion and after reperfusion. Circumferential profiles were applied to axial slices divided into 5-degree sectors. The sectors were divided into 3 groups selected on the occlusion acquisition (normal, mildly reduced, and severely reduced) and compared with the postreperfusion acquisition. Tissular Tc-MIBI kinetics was assessed both by Tc-MIBI time-activity curves of normal and ischemic tissue obtained by biopsy and by the relative gradient between normal, ischemic, and necrotic postmortem tissue samples. In biopsy samples, Tc-MIBI content remained unchanged during occlusion and after reperfusion in normal as well as in ischemic tissue (4,662 +/- 2,237 counts/min/mg vs. 4,599 +/- 1,577 counts/min/mg in normal tissue, NS; 941 +/- 903 counts/min/mg vs. 1,087 +/- 721 counts/min/mg in ischemic tissue, NS). In postmortem tissue samples, there was a good correlation between occlusion microsphere blood flow and Tc-MIBI activity (r = 0.91). In the necrotic samples, mean normalized Tc-MIBI activity (10 +/- 17%) was slightly higher than the normalized microsphere blood flow (3 +/- 3%, p less than 0.001) but markedly lower than the normalized microsphere reperfusion blood flow (63 +/- 31%, p less than 0.001). Comparing the single photon emission computed tomographic acquisitions before and after reperfusion, Tc-MIBI activity remained unchanged in normal as well as in mildly reduced or severely reduced segments. Thus, our data are consistent with the hypothesis that Tc-MIBI traces blood flow, does not redistribute significantly despite reperfusion, and can be used for imaging the area at risk.

‘LOW T3 SYNDROME’ IN PATIENTS CHRONICALLY TREATED WITH AN IODINE‐CONTAINING DRUG, AMIODARONE

Cardiac patients treated with the iodinecontaining drug ‘amiodarone’ undergo a significant iodine overload whch can last for months after the drug has been withdrawn. Some patients develop hyperthyroidism and others hypothyroidism. In the hyper‐ or hypothyroid patients, the indices of thyroid function are modified as usually observed in these situations. In the patients remaining euthyroid while taking amiodarone or after its withdrawal, but still under its influence as shown by the iodine overload, a ‘low‐T3 syndrome’ is observed, this state being characterized by a high total T4, a low free T4, a normal T3 resin uptake, a low total T3, a normal free T3, a high r‐T3 and a relative TSH‐unresponsiveness to TRH.

Coronary artery reperfusion in acute myocardial infarction: assessment by pre- and postintervention thallium-201 myocardial perfusion imaging.

In a randomized trial of intracoronary streptokinase (STK) therapy in acute myocardial infarction, 44 patients (21 control subjects and 23 patients treated with STK) underwent sequential thallium-201 planar imaging before angiography and after 4 hours (redistribution), 4 days and 6 weeks. Patients were classified according to the presence or absence of angiographic reperfusion of the infarct-related artery. The semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Both in control and in STK-treated groups, thallium defect scores decreased over time, but this decrease was smaller in the control group (before angiography, 33 +/- 4%; redistribution, 29 +/- 4%; 4 days, 25 +/- 4%; and 6 weeks, 22 +/- 4%) than in the STK group (44 +/- 4%, 38 +/- 4%, 26 +/- 4% and 21 +/- 3%, respectively). In patients in whom reperfusion was achieved (20 STK-treated, 6 control subjects), a marked decrease in thallium score was observed (before angiography, 40 +/- 4%; redistribution, 32 +/- 4%; 4 days, 20 +/- 5%; and 6 weeks, 14 +/- 22%) compared with patients in whom reperfusion was not achieved (37 +/- 4%, 36 +/- 5%, 33 +/- 5% and 33 +/- 4%, respectively). These results indicate that serial thallium imaging is an accurate method of assessing changes in myocardial perfusion after acute myocardial infarction. Restoration of thallium uptake was observed after reperfusion of the infarct-related artery whether this recanalization was seen spontaneously or after successful thrombolysis.

Breath 14CO2 after intravenous administration of [14C]aminopyrine in liver diseases.

The determination of14CO2 in breath after oral administration of [14C]aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the [14C]aminopyrine breath test (ABT) was performed after intravenous administration of [14C]aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86±0.1% (mean±sd) in controls and significantly less in patients (0.46 ±0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16±0.13%), alcoholic cirrhosis (0.2±0.15%), and untreated postnecrotic cirrhosis (0.47±0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86±0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83±0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test.

The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer

A strict and careful strategy has to be adopted to cure thyroid cancer. Diagnostic iodine-131 whole-body scan (WBS) and serum thyroglobulin (Tg) are important tools to detect thyroid remnants after thyroidectomy and radioiodine therapy. The aim of this retrospective study was to compare the relative sensitivity of WBS and Tg in the detection of thyroid remnants or metastases and to evaluate the predictive value of Tg in the clinical and scintigraphic course of the disease. Ninety-three patients were followed up after total thyroidectomy and the administration 4–6 weeks later of an ablative dose of 100 or 150 mCi131I. Eighty-five percent of the patients were free of regional or distant metastases. The follow-up scheme included clinical examination of the patient followed by WBS, Tg, thyroid-stimulating hormone and free thyroxine measurements performed 4 weeks after thyroxine withdrawal and the observance of a low-iodine diet for at least 1 week. WBS (+) patients received a 100- or 150-mCi therapeutic dose of131I. All patients were further followed up in the same way every 6 months until both WBS and Tg became negative, and thereafter at 1-, 2- and 4-year intervals. Six months after the postoperative radioiodine treatment (first visit), the sensitivity of WBS and Tg was 87% and 26% respectively. Among patients who were WBS(+) at the first visit, 95% of those who were Tg(-) and 47% of those who were Tg(+) had become disease-free at a median of 4 years after surgery (χ2=13.6;P<0.05). Patients whose tests were both positive required more radioiodine to be cured (335±90 vs 250±95 mCi;P<0.05). Our data indicate that in early diagnosed thyroid cancer, serum Tg measured 6 months after the postoperative131I ablative dose is less sensitive than WBS for the demonstration of persistence of residual thyroid tissue but provides predictive information on the disease course. WBS(+) and Tg(-) patients are cured earlier and with less radioiodine than those who remain Tg(+).

Recommended restrictions after 131I therapy : measured doses in family members

Absorbed doses to family members of patients treated with (131)I were measured using thermoluminescent dosimeters worn on the chest. Twenty-two patients with thyroid cancer were hospitalized for 2 d for treatment with 3,700-7,400 MBq, and 18 hyperthyroid patients were treated on an outpatient basis with 200-600 MBq. Doses were measured over periods of 15-21 d following the administration of radioiodine in 35 partners and 38 children, aged 4 mo to 25 y. These results were correlated with dose rate measurements performed with an ionization chamber, and residual thyroid uptake was assessed by scintigraphy over the same period. In the cancer group, the residual activity in thyroid remnants was less than 50 MBq in all cases at day 4 following treatment and decayed with a mean half-life of 2.2 (SD: 0.8) d. The dose measured with thermoluminescent dosimeters was lower than 0.5 mSv in all partners and children. In the hyperthyroid group, the effective half-life averaged 6.2 (SD: 1.2) d. The median of the doses measured in partners and children were 1.04 mSv (range: 0.05-5.2) and 0.13 mSv (range: 0.04-3.1), respectively. Fifteen children (88%) received less than the dose constraint of 0.5 mSv. The ICRP recommend an annual limit of 1 mSv for the members of the public. In addition, dose constraints (for example: 0.5 mSv) should be complied with whenever possible. The recommended dose limits are generally well met among family members of patients treated with 1311 for cancer. The higher doses measured in hyperthyroid patients, compared to thyroid cancer patients, relate to a higher (131)I retention by the gland and justify more extended and stringent restriction periods, based on residual thyroid activity.

Noninvasive measurement of liver regeneration with positron emission tomography and (2-11C)thymidine

The feasibility of liver regeneration determination with [2-11C]thymidine and positron emission tomography was investigated in partially hepatectomized rats. Serial tomographic scans were performed over a 120-minute period after injection of [2-11C]thymidine together with tritium-labeled thymidine. Within 10 minutes after injection, positron emission tomography scans showed a twofold higher hepatic uptake in regenerating than in nonregenerating livers. Time-activity curves over the liver area indicated that the maximal uptake was followed by a faster decrease of 11C radioactivity in controls than in regenerating animals, so that total 11C activity remaining in the liver at 120 minutes accounted for 68% of maximum in regenerating and only 38% in controls. Tissue distribution studies performed at 120 minutes showed that total 11C radioactivity, expressed in percent injected dose per gram, was six times higher in regenerating livers than in controls (0.62% +/- 0.07% in regenerating livers and 0.10% +/- 0.03% in nonregenerating livers; P less than 0.001) and correlated with 3H radioactivity measured in the nuclear fraction (r = 0.92; P less than 0.001). When the hepatic uptake was expressed in percent of dose per organ, the difference between both groups increased (2.31% +/- 0.23% in regenerating livers and 0.29% +/- 0.02% in nonregenerating livers; P less than 0.001) because of higher weight of regenerating livers than of nonregenerating livers (3.83 +/- 0.11 g in regenerating livers and 2.96 +/- 0.16 g in nonregenerating livers; P less than 0.001). In other organs examined, no difference in 11C radioactivity was found between the two groups of rats. These results indicated the potential usefulness of [2-11C]thymidine and positron emission tomography for noninvasive measurement of liver regeneration.

Thyrotropin Response to Synthetic Thyrotropin‐Releasing Hormone in Normal Subjects and in Patients with Nontoxic Goiter

Abstract. 400 μg TRH given intravenously to normal subjects produced a peak serum TSH within 20 or 30 min. TSH levels were significantly increased as early as 10 min. after the injection. An oral dose of 10 mg of TRH gave a slower and more sustained response in normal subjects. The magnitude of the TSH response was directly related to the basal serum TSH level and inversely proportional to the basal concentration of blood thyroxine. No alteration in the normal pattern of TSH response was observed in patients with euthyroid nontoxic goiters. The data obtained from the normal subjects indicate that the magnitude of the pituitary response to TRH is closely related to the level of the circulating thyroid hormones. Thus, in patients with thyroid pathology the significance of the TSH response curve to TRH must be interpreted after taking into account the level of circulating thyroid hormones. This is particulary important before drawing conclusions concerning any primary defect of the hypothalamo‐pituitary system in thyroid pathology.