(111)Indium-transferrin for localization and quantification of gastrointestinal protein loss.

OBJECTIVE: To evaluate the indium-111 ((111)In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. METHODS: Fourteen patients and 15 healthy subjects underwent an (111)In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of (111)In during the course of 5 days. Two of the patients went through a subsequent chromium-51-trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. RESULTS: The patients had a mean +/-SEM whole-body loss of (111)In of 10.9+/-2.9% for 96 h, while the healthy controls lost 1.8+/-1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0+/-1.0 h in patients and 12.1+/-1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the (51)CrCl(3) test, the loss of radio-labelled protein appeared to be in the same order of magnitude. CONCLUSIONS: Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the (111)In-transferrin method comparable with the former standard using (51)CrCl(3). Plasma measurements of (111)In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality.

Continuous methimazole therapy and its effect on the cure rate of hyperthyroidism using radioactive iodine: an evaluation by a randomized trial.

BACKGROUND: A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine ((131)I) therapy influences the final outcome of this therapy. DESIGN: Consecutive patients with Graves' disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before (131)I (-MTZ; n = 36) or to continue MTZ until 4 wk after (131)I (+MTZ; n = 39). Calculation of the (131)I activity included an assessment of the (131)I half-life and the thyroid volume. RESULTS: The 24-h thyroid (131)I uptake was lower in the +MTZ group than in the -MTZ group (44.8 +/- 15.6% vs. 62.1 +/- 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T(4) index was observed in the +MTZ group (109 +/- 106 vs. 83 +/- 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the -MTZ group (180 +/- 110 vs. 82 +/- 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and -MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid (131)I uptake (50.1 +/- 13.8% vs. 56.4 +/- 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid (131)I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid (131)I uptake predicted a better outcome (P = 0.006). CONCLUSION: Continuous use of MTZ hinders an excessive increase of the thyroid hormones during (131)I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid (131)I uptake.

[The value of myocardial perfusion scintigraphy as a "gatekeeper" for coronary angiography and revascularisation in patients with stable angina pectoris--a secondary publication]. / Vaerdien af myokardieskintigrafi som gatekeeper for koronararteriografi og revaskularisering hos patienter med stabil angina pectoris--sekundaerpublikation.

In 507 out of a series of 972 patients referred consecutively to coronary angiography (CA) for stable angina pectoris, preceding "blinded" myocardial perfusion scintigraphy (MPS) demonstrated normal perfusion in 51%, reversible defects in 40%, and fixed defects in 9% of patients. CA showed insignificant findings in 49% and in 41% of the entire series. Of 168 revascularised patients, no more than 74% had reversible perfusion defects with MPS. On this basis it could be estimated that almost half of catheterizations and nearly one fifth of revascularisations were "superfluous".

Potential impact of myocardial perfusion scintigraphy as gatekeeper for invasive examination and treatment in patients with stable angina pectoris: observational study without post-test referral bias.

AIMS: To evaluate the impact of using myocardial perfusion scintigraphy (MPS) as gatekeeper for coronary angiography and revascularization in stable angina pectoris. METHODS AND RESULTS: A prospective series of 507 out of 972 adult patients referred to coronary angiography for known or suspected stable angina pectoris underwent clinical examination followed immediately by MPS, the result of which was not communicated. MPS showed normal perfusion in 258/507 (51%) patients, reversible defects in 201/507 (40%), and fixed defects in 48/507 (9%). Of 168 revascularized patients, 27 (16%) had normal perfusion and 13 (8%) had fixed defects. Coronary angiography was undertaken in 476 patients of whom 252 (53%) had normal findings or insignificant stenoses. The same was the case in 361 (41%) out of the 883 of the 972 consecutive patients, who had this examination. Assuming that the true rate of normal perfusion in the entire series was correspondingly lower, 48% of catheterizations and 19% of revascularizations were superfluous. CONCLUSION: The use of MPS as gatekeeper appears to make about half of catheterizations and almost one-fifth of revascularizations redundant. Even in high-risk groups, substantial savings are possible, and the risk of overlooking patients with severe disease seems negligible.

Diagnostic accuracy of myocardial perfusion imaging in a study population without post-test referral bias.

BACKGROUND: Most previous studies on the accuracy of myocardial perfusion imaging (MPI) are hampered by post-test referral bias, in that referral for coronary angiography was influenced by the MPI result. In this way, patients with a normal MPI result less frequently underwent catheterization, a tendency supposed to cause an underestimation of test specificity and an overestimation of test sensitivity. METHODS AND RESULTS: MPI by use of a gated dual-isotope protocol was undertaken before angiography in 357 patients referred for angiography for suspected stable angina pectoris. The MPI reports were kept secret to prevent post-test referral bias. The MPI study was normal in 215 patients (60%) and showed reversible perfusion abnormalities in 118 (33%) and fixed defects in 24 (7%). Angiography was normal in 231 patients (65%) and revealed 1 or more significant stenoses in 126 (35%). With angiography as the reference, the sensitivity and specificity of MPI for detecting significant coronary artery stenosis were 75% and 79%, respectively. CONCLUSIONS: In this prospective study without post-test referral bias, we found a lower sensitivity and slightly higher specificity than in studies with post-test referral bias. The imperfect accuracy may reflect differences between anatomic and physiologic imaging.

Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites.

In the present study, we tested the hypothesis that inhibition of renal phosphodiesterase type 5 (PDE5) in patients with liver cirrhosis and ascites increases sodium excretion. The effect of sildenafil citrate was studied in a randomized double-blind. placebo-controlled crossover study. Diuretics were withdrawn, and a fixed sodium diet (100 mmol/day) was given to the patients for 5 days before both study days. After a 60-min basal period, eight patients received either oral sildenafil (50 mg) or placebo. Glomerular filtration rate (GFR) and renal blood flow (RBF) were determined by 99mTc-diethylenetriamine-pentaacetate and (131)I-hippuran clearances. In human nephrectomy specimens, PDE5 mRNA was expressed at similar levels in the cortex (n = 6) and inner medulla (n = 4). Histochemical staining showed PDE5 immunoreactivity in collecting ducts and vascular smooth muscle. At baseline, cirrhotic patients exhibited elevated plasma concentrations of ANP, renin, ANG II, and aldosterone that did not differ on the 2 study days. Basal sodium excretion was similar at the 2 study days (median 17 and 18 mmol, respectively), and patients were in positive sodium balance. Sildenafil increased heart rate, plasma renin activity, plasma ANG II, and aldosterone concentrations significantly after 60 min. Plasma cGMP concentration was increased after 120 and 180 min, and urinary sodium excretion and mean arterial blood pressure were decreased significantly at 120 and 180 min. Plasma ANP concentration, GFR, and RBF did not change after sildenafil. In patients with ascites and cirrhosis, inhibition of PDE5 did not promote natriuresis but led to increased plasma levels of the renin-angiotensin-aldosterone system.

Recombinant human thyrotropin markedly changes the 131I kinetics during 131I therapy of patients with nodular goiter: an evaluation by a randomized double-blinded trial.

The present study compares, in a randomized double-blinded design, the expected and the actual absorbed thyroid radioactive dose in response to 0.3 mg recombinant human (rh)TSH (n = 35) or placebo (n = 28) given 24 h before (131)I therapy in patients with nodular goiter (median volume, 69 ml; range, 20-440 ml). The (131)I activity calculation was based on thyroid (131)I uptake (RAIU) at 24 and 96 h after a tracer dose of 0.5 MBq (131)I. After (131)I therapy, 24- and 96-h RAIU were repeated allowing a more exact assessment of the actual absorbed thyroid dose. The median (131)I activity was 617 and 632 MBq, respectively, in the rhTSH and the placebo group. At baseline, the 24- and 96-h RAIU and the expected thyroid dose were 32.8 +/- 9.1%, 32.1 +/- 8.2%, and 96.3 +/- 16.3 Gy, respectively, in the rhTSH group and 35.7 +/- 11.8%, 35.2 +/- 11.3%, and 94.1 +/- 18.5 Gy, respectively, in the placebo group (P value not significant between groups). After (131)I therapy, the 24- and 96-h RAIU and the actual absorbed thyroid dose were 46.9 +/- 11.7%, 45.0 +/- 12.1%, and 136.7 +/- 47.9 Gy, respectively, in the rhTSH group and 33.0 +/- 11.4%, 31.0 +/- 11.3%, and 76.9 +/- 27.5 Gy, respectively, in the placebo group (P < 0.001 between groups). Comparing the expected with the actual absorbed thyroid dose, this corresponds to a mean increase of 36.4% (95% confidence interval, 21.3-53.4) in the rhTSH group and a decrease of 21.5% (95% confidence interval, -33.9 to -6.6) in the placebo group (P < 0.001), equivalent to an increase of 73.8% in the absorbed thyroid dose in the rhTSH-treated group. We have thus for the first time shown that stimulation with rhTSH before (131)I therapy not only hinders the decrease in the thyroid RAIU observed with conventional (131)I therapy but in fact also significantly enhances the absorbed thyroid dose. Whether this also leads to a significant increase in goiter size reduction needs additional study.

Observer variability in the evaluation of dual-isotope Tl-201/Tc-99m sestamibi rest/stress myocardial perfusion SPECT in men and women with known or suspected stable angina pectoris.

BACKGROUND: Observer variability of dual-isotope myocardial perfusion imaging (MPI) with single photon emission computed tomography has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. METHODS AND RESULTS: We report on 507 patients with known or suspected stable angina who were studied before coronary angiography. A 1-day thallium 201/technetium 99m sestamibi rest/stress MPI protocol was used. MPI was interpreted by 2 independent observers without knowledge of clinical data, using a 20-segment scoring model. By consensus, the overall rate of abnormal MPI was 49% (59% in men and 34% in women). The interobserver agreement for the whole group (kappa = 0.85) and for men and women separately (kappa = 0.86 and 0.82, respectively) was excellent with regard to the overall diagnosis (normal, reversible, or fixed defects) as well as left anterior descending and left circumflex artery vascular territories (kappa = 0.85 and 0.82, respectively). However, in the right coronary artery territory, agreement was excellent in men (kappa = 0.83) but moderate in women (kappa = 0.57). CONCLUSIONS: In a relatively large group of men and women with stable angina pectoris, interpretive reproducibility (overall and individual vessel diagnosis) was excellent, except in the right coronary artery territory of women, in which it was moderate.

Scatter and attenuation correction changes interpretation of gated myocardial perfusion imaging.

Attenuation correction may improve the diagnostic accuracy of myocardial perfusion imaging (MPI). However, few studies have dealt with the clinical consequences for reporting. We compared routine reports based on scatter-corrected MPI (MPI-routine) with consensus readings of scatter-corrected (MPI-scatter) and scatter plus attenuation-corrected studies (MPI-attenuation) to investigate the impact of attenuation correction on reporting. One hundred consecutive stable angina patients (including 55 men) were investigated in a 99mTc-sestamibi 2-day gated protocol with scatter and attenuation correction. With MPI-routine, 53 patients had normal perfusion and 47 abnormal perfusion, compared to 62 and 38 with MPI-attenuation, and 54 and 46, respectively, with MPI-scatter. Agreement between MPI-routine and MPI-attenuation with respect to overall diagnosis (normal/abnormal perfusion) was 89% (kappa=0.78) compared to 95% (kappa=0.90) between MPI-routine and MPI-scatter. With MPI-attenuation, the overall routine diagnosis changed in 11 patients, of which ten cases were judged normal after scatter plus attenuation correction. The majority of the "normalised" studies were among patients with apparently single-vessel RCA disease as judged from MPI. Agreement rates with regard to normal, reversible or irreversible defects between MPI-attenuation and MPI-routine for the LAD, LCX and RCA territories were 88%, 97% and 85%, respectively, without significant sex differences. In conclusion, attenuation correction caused a change in diagnosis in approximately 10% of the patients, corresponding to one-fifth of the abnormal studies. In all but one case, the shift was from abnormal to normal, mostly because of a different interpretation in the RCA territory.

Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial.

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.