Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma.

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.

Left ventricular function in insulin-dependent and in non-insulin-dependent diabetic patients: radionuclide assessment.

The aim of this study was to compare, by gated radionuclide angiography, systolic and diastolic ventricular function in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients without overt cardiovascular disease. The study population consisted of 20 IDDM patients (15 male, 5 female; 40.7 +/- 10.3 years), 14 NIDDM patients (9 male, 5 female; 47.0 +/- 7.5 years) and 12 healthy subjects (7 male, 5 female; 41.5 +/- 6.3 years) as a control (C) group. The duration of diabetes (DD) and glycosylated hemoglobin (HbA1C) levels were significantly higher in the IDDM patients. The ventricular ejection fraction and peak ejection rate (PER) were assessed by gated radionuclide left ventriculography and were similar in three groups, while the peak filling rate (PFR) was lower in the NIDDM patients compared to the IDDM patients (p < 0.05) and controlled healthy subjects (p < 0.01, IDDM = 3.39 +/- 1.14; NIDDM = 2.65 +/- 0.83; C = 3.55 +/- 0.73), the time to PFR was significantly more prolonged in the NIDDM group than in the IDDM (p < 0.05) and C groups (p < 0.05, NIDDM = 162 +/- 26; IDDM = 140 +/- 28; C = 142 +/- 23). The PFR/PER ratio was near the normal value (approximately equal to 1) in the IDDM patients and controlled subjects, while in the NIDDM patients it was reduced (approximately equal to 0.84 +/- 0.18). Seven IDDM and 4 NIDDM patients had borderline signs of cardiovascular autonomic neuropathy, unrelated to DD, HbA1C and scintigraphic parameters. Left ventricular systolic performance was substantially normal and similar in both the IDDM and NIDDM patients. Ventricular diastolic filling was impaired in the NIDDM patients, as shown by the decrease in PFR and in particular in the PFR/PER ratio. Our radionuclide data suggest that the NIDDM patients had a prevalent abnormality of ventricular diastolic performance, with respect to the IDDM patients, although the latter patients had higher DD and HbA1C values.

Myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass surgery.

The prevalence of myocardial damage after coronary artery bypass grafting is related to the criteria of its evaluation. Indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly sensitive and specific for even small areas of myocardial necrosis or injury like those of myocarditis or transplant rejection. Our purpose was to evaluate, by using this method, myocardial damage after uncomplicated coronary artery bypass grafting. Uptake of this radio tracer was evaluated after coronary artery bypass grafting in 14 informed and consenting consecutive patients without previous myocardial infarction, with no post-surgical complications and a favorable postoperative course, following coronary artery bypass grafting for stable angina pectoris. Monoclonal antimyosin antibody indium-111 74 MBq (Myoscint Centocor) was injected on the third postoperative day; planar images in the anterior, left anterior oblique 45 degrees and 70 degrees projections were obtained 24 and 48 h later and analyzed for myocardial uptake. Indium-111 antimyosin uptake was present in 10 out of 14 patients (71.4%); it was diffuse in 6 and localized in 4. The ratio of the maximal counts in the myocardium to the counts in the adjacent lung background was measured and found elevated: 1.94 +/- 0.23, higher than the normal values reported in the literature. Indium-111 antimyosin uptake was clear in a group of patients after uncomplicated coronary artery bypass grafting. No correlation was observed between indium-111 antimyosin uptake or heart to lung ratio and creatine kinase, creatine kinase isoenzyme MB, glutamic oxalacetic transferase levels, duration of cardiopulmonary bypass or aortic cross-clamp time, while elevated serum beta myosin heavy chain fragments (IRMA Pasteur) were observed (1378 +/- 238 microU/l). This study suggests that some degree of myocardial damage, though silent, is common after coronary artery bypass grafting.

Perioperative myocardial cell damage assessed by immunoradiometric assay of beta-myosin heavy chain serum levels in patients undergoing coronary bypass surgery.

In order to investigate myocardial cell damage in patients undergoing coronary bypass surgery, serum levels of cardiac myosin fragments, using monoclonal antibodies to myosin beta heavy chains, were measured in serial blood samples of 85 patients, 79 male and 6 female, 43-66 years old, after a total of 86 internal mammary artery and 137 saphenous vein graft implants. Eight patients had perioperative acute myocardial infarction (MI), detected by abnormal Q waves and a rise of CK-MB levels. After surgery, beta-myosin levels increased from post-operative day 3 and reached peak values on day 5 in patients without and in day 7 in patients with perioperative MI, in these 8 patients, myosin peak levels were greater as compared to 77 patients without perioperative MI (3452 +/- 1596 vs. 761 +/- 494; P < 0.01). There was a correlation between myosin peak levels and creatine kinase (CK) (r = 0.71; P < 0.05) and CK-MB peak levels (r = 0.74; P < 0.05) only in the patients with perioperative MI, but not in the patients without MI. There was no correlation between myosin peak levels and the times of aortic cross clamping or cardiopulmonary bypass. Peak myosin levels over 75% confidence limits of the mean were found in 23 patients; post-operative low output syndrome occurred in 10 of these 23 patients and in 7 out of 62 patients with peak myosin levels within 75% of the mean (P < 0.005). The increase in beta-myosin heavy chain serum levels observed in almost all patients undergoing coronary surgery suggests lesser perioperative damage of the contractile apparatus, which could be detected by the usual enzyme and ECG criteria. The higher prevalence of low output syndrome in patients with higher increases in myosin levels suggests more pronounced damage to the contractile apparatus in these patients. The higher myosin levels clearly indicate the presence of perioperative MI.

Thallium 201 for detection of viable myocardium: comparison of different reinjection protocols.

BACKGROUND: The finding fo false fixed 201Tl defects by the conventional stress-redistribution protocol is a well-known phenomenon. The aim of this study was to compare two different 201Tl reinjection protocols to identify viable myocardium in the same group of patients. METHODS AND RESULTS: Twenty-seven patients with ischemic heart disease and at least one persistent defect on 201Tl uptake redistribution images 3 hours after stress were investigated. In the same-day protocol (R1) patients were reinjected with 1 mCi 201Tl immediately after redistribution images, with imaging starting 15 minutes later; in the different-day protocol the patients were reinjected with 2 mCi 48 to 96 hours later. Two sets of images were obtained, 30 (R2) and 180 (R3) minutes after reinjection. The comparison of redistribution and reinjection versus stress images showed a significant (p < 0.01) frequency distribution. The uptake of 201Tl of the 111 irreversible segments at redistribution was enhanced in 35.1% with R1, 43.2% with R2, and 49.5% with R3. The agreement among the three procedures in classifying the segmental defects was high between R2 and R3 (r = 0.81) and lower between the same- and different-day protocols. Of the 19 patients with a dominant scar pattern demonstrated by the conventional stress-redistribution study, 37%, 47%, and 53% were judged mainly ischemic after R1, R2, and R3, respectively. All but three of the 55 segments-showing an increased 201Tl uptake by R3 had an echocardiographic score of 2 or greater. CONCLUSION: The best technique to differentiate scarred from viable myocardium seems to be the reinjection of a second dose of 201Tl on a different day followed by imaging 3 hours later.

[Critical myocardial ischemia in systemic lupus erythematosus. Case report]. / Ischemia miocardica critica in corso di lupus eritematoso sistemico. Descrizione di un caso clinico.

We present the clinical case of a 26-year-old woman, suffering systemic lupus erythematosus for 15 years, who suddenly had coronary heart disease with angina pectoris on mild effort. Thallium 201 exercise test demonstrated clearcut anteroseptal and apical perfusion defects, whereas repeated echocardiography showed a hypokinetic anteroseptal segment; ECG also reported new Q wave in lead V4. After stronger corticosteroid and immunosuppressive treatment, angina pectoris attenuated and perfusion defects disappeared within few months. We hypothesize a coronary artery vasculitis in the course of systemic lupus erythematosus, probably associated with early coronary artery atherosclerosis.

[Radioisotope angiography in the differential diagnosis between aneurysm and pseudoaneurysm of left ventricle. Report of a case]. / L'angiografia radioisotopica nello studio discriminante tra aneurisma e pseudoaneurisma ventricolare sinistro. Descrizione di un caso.

We describe the case of a patient with large posteroinferior left ventricular aneurysm following myocardial infarction. Contrast ventriculography, Doppler echocardiography, as well as radionuclide angiography indicated a small orifice that was in communication with the ventricular cavity. These data suggested the presence of left ventricular pseudoaneurysm. Thus a short-term surgical intervention was performed, but the diagnosis was not confirmed by surgical observation; indeed the presence of a true aneurysm was demonstrated. Our study confirms the diagnostic difficulties by invasive and non invasive techniques in the precise identification of postinfarct pseudoaneurysm. This observation suggests the remarkable interest of our radionuclide ventriculographic results, not usually observed. Thus, we point out the possibilities of several nuclear cardiology imaging in the study of diagnostic problems concerning the analysis of these conditions of myocardial pathology.

The iodine perchlorate discharge test before and after one year of methimazole treatment of hyperthyroid Graves' disease.

We have recently reported that many euthyroid patients with a history of Graves' disease treated years earlier with methimazole (MMI) have a positive iodide (500 micrograms)-perchlorate discharge test (I-ClO4 test), suggesting a permanent thyroid iodide organification defect. We now report the results of the I-ClO4 test in patients with hyperthyroid Graves' disease before beginning a 1-yr course of MMI therapy and 40 days after MMI was discontinued. Twenty-nine patients (25 women and 4 men; mean age, 38 +/- 1.7 yr) with their first episode of hyperthyroid Graves' disease were studied. Before MMI therapy, I-ClO4 tests were carried out, and serum T4, T3, and TSH were measured to confirm the diagnosis of hyperthyroidism. A positive I-ClO4 test is defined as more than 15% 131I discharged from the thyroid 1 h after the administration of 1 g KClO4. Patients were then treated with 20 mg MMI for the first 2 months and variable doses thereafter for the next 10 months to maintain euthyroidism. Serum T4, T3, and TSH were measured monthly. Forty days after MMI was discontinued, I-ClO4 tests were repeated, and serum T4, T3, and TSH were measured every 2 months thereafter. Before MMI treatment, the I-ClO4 test was positive in 20 of 29 patients (69%) and negative in 9. The favorable responses (normal serum T4 and T3 values) to MMI therapy were similar in both groups. We have thus far studied 16 patients after MMI was discontinued and 9 of 12 patients (75%) with a negative I-ClO4 test after MMI therapy, and 1 of 4 patients (25%) with a positive test remained in remission for a mean of 7 months. We conclude that the I-ClO4 test is frequently positive in patients with untreated hyperthyroid Graves' disease, suggesting either an inability to organify the increased iodide concentrated by the hyperfunctioning gland or the concomitant presence of Hashimoto's thyroiditis, which almost always is associated with a positive I-ClO4 test. The former hypothesis is more likely, because many patients with a positive I-ClO4 test before MMI therapy had a negative test after MMI was discontinued.

Effects of chronic iodine administration on thyroid status in euthyroid subjects previously treated with antithyroid drugs for Graves' hyperthyroidism.

In view of the adverse effects of the administration of pharmacological quantities of iodine to euthyroid patients with a history of a wide variety of thyroid disorders, it has been suggested that iodine-containing medications and radioopaque dyes containing iodine should be avoided, if possible, in patients with underlying thyroid disease. We have now prospectively studied the effects of pharmacological doses of a saturated solution of potassium iodide (SSKI) on thyroid function in euthyroid patients with a previous history of hyperthyroid Graves' disease successfully treated with antithyroid drugs. Ten euthyroid women (mean age, 56 yr) who had hyperthyroid Graves' disease successfully treated with methimazole 36.4 +/- 4.7 months earlier were evaluated before, during, and after the administration of 10 drops SSKI daily for 90 days. The following thyroid function tests were obtained: serum T4, T3, TSH, TSH receptor antibody (TSH-RAb), and antithyroid peroxidase antibody (AbTPO) concentrations; TRH tests; and iodine perchlorate discharge tests. Serum T4, T3, basal and TRH-stimulated TSH, and TSH-RAb values were normal before SSKI administration, but serum AbTPO levels were markedly positive in 7 and iodine perchlorate discharge tests were positive in 4 of these 10 women. During SSKI administration, basal and TRH-stimulated serum TSH values increased above normal in 2 women with normal serum T4 and T3 concentrations; thyroid hormone values and TRH tests were normal in the other 8 patients and similar to values observed in 4 euthyroid women without a history of thyroid disease given SSKI. Serum AbTPO increased slightly, but significantly, during SSKI administration in the 7 women with positive values at baseline (P < 0.05). TSH-RAb remained undetectable. After SSKI withdrawal, the 10 women were reevaluated 60 and 120 days later. Two women developed a blunted TSH response to TRH, but normal serum T4 and T3 concentrations, and 2 women developed overt hyperthyroidism, with undetectable basal and TRH-stimulated serum TSH and elevated serum T4 and T3 concentrations, requiring methimazole therapy. All values in the remaining 6 women were similar to those present before SSKI administration. These results suggest that some euthyroid patients with a history of antithyroid drug therapy for Graves' disease may develop thyroid dysfunction during and after excess iodine administration. The development of subclinical hypothyroidism during SSKI administration was not clinically important, but the occurrence of overt hyperthyroidism after SSKI was discontinued did require antithyroid drug therapy. It is advisable, therefore, to avoid iodine-containing substances in euthyroid patients with a history of antithyroid drug therapy for Graves' disease.

[Assessment of perioperative myocardial damage based on circulating heavy chain myosin fragments]. / Valutazione del danno citomiocardico perioperatorio mediante dosaggio dei frammenti circolanti delle catene pesanti di miosina.

To evaluate myocardial damage induced by coronary bypass surgery, to construct a reference data set in postoperative patients and to ascertain the impact of perioperative myocardial infarction on myosin release from sarcolemmal membrane we serially measured levels of serum fragments of myosin heavy chains by means of monoclonal antibody immunoradiometric assay (MYOSIN IRMA ERIA Pasteur). After surgery serum levels of myosin increased from third postoperative day and peaked on seventh day. Peak myosin levels did correlate with enzymatic activities of CPK (r = 0.69; p < 0.001) and of CPK-MB (r = 0.75; p < 0.001). Six patients suffered postoperative myocardial infarction: in these patients myosin levels were significantly different from those without infarctions (3651 +/- 1569 versus 699 +/- 206 ng/ml; p < 0.01). No correlation could be demonstrated between cardiopulmonary bypass time or aortic cross clamp duration. The rise of myosin levels observed in nearly all patients suggests a minor intraoperative damage to the contractile apparatus that sometimes is diagnosed as myocardial infarction and often does not meet clinical diagnostic criteria.

Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AIT) occurs most frequently in patients with underlying thyroid disease and is generally believed to be due to the iodine contamination of amiodarone and iodine released by the metabolism of the drug. We and others have suggested that the thyrotoxicosis may also be secondary to amiodarone-induced thyroiditis. To further determine the etiology of AIT, we administered large doses of iodides [10 drops saturated solution of potassium iodide (SSKI) daily] to 10 euthyroid patients long after an episode of AIT believed to be due at least in part to amiodarone-induced thyroiditis. Six of these 10 patients had an abnormal iodide-perchlorate discharge test before SSKI administration, indicating a subtle defect in the thyroidal organification of iodide. During SSKI administration, 6 patients developed marked iodine-induced basal and/or TRH-stimulated serum TSH elevations, 2 had suppressed basal and TRH-stimulated TSH values, and 2 had normal TSH responses compared to SSKI-treated euthyroid subjects with no history of amiodarone ingestion or thyroid disease. Serum T4 and T3 concentrations remained normal and unchanged during SSKI administration in both the AIT patients and control subjects. These results strongly suggest that excess iodine may not be the cause of the hyperthyroidism associated with amiodarone therapy, especially in those patients with probable amiodarone-induced thyroiditis. Furthermore, like patients with a previous history of subacute thyroiditis and postpartum thyroiditis, the present results suggest that some patients with a previous history of AIT may be at risk to develop hypothyroidism when given excess iodine.

Impaired intrathyroidal iodine organification and iodine-induced hypothyroidism in euthyroid women with a previous episode of postpartum thyroiditis.

Postpartum thyroiditis (PPT) is common and occurs in 1.7 to 16.7% of pregnant women, depending upon the study population. Most of these women develop transient hypothyroidism and thyroid function usually returns to normal. We have studied 11 euthyroid women with a previous history of PPT to determine the incidence of subtle defects in thyroid function measured by iodide-perchlorate (I-ClO4) discharge tests and TRH tests and to determine whether these women would develop iodide-induced hypothyroidism. Seven (64%) had positive I-ClO4 discharge tests and 5 (46%) had an abnormally high TSH response to TRH. Thyroid antimicrosomal and antithyroid peroxidase were positive in 8 women (73%) with a previous episode of PPT. The administration of pharmacological amounts of iodide (10 drops of saturated solution of potassium iodide daily) for 90 days to these 11 women resulted in elevated basal and TRH stimulated serum TSH concentrations in 8 (72.7%) compared to TSH values during iodide administration to women who had never been pregnant. Antimicrosomal and antithyroid peroxidase concentrations did not change during iodide administration. These findings strongly suggest that euthyroid women with a previous episode of PPT have permanent subtle defects in thyroid hormone synthesis and are inordinately prone to develop iodide-induced hypothyroidism, similar to findings previously reported in euthyroid subjects with Hashimoto's thyroiditis, with a previous episode of painful subacute thyroiditis, or previously treated with radioactive iodine or surgery for Graves' disease.

[Right ventricular function before and 6 months after aortocoronary bypass. A radioisotope angiographic study]. / La funzione ventricolare destra prima e sei mesi dopo bypass aorto-coronarico. Studio angiografico radioisotopico.

The aim of the present paper is the study of the changes induced on right ventricular function after myocardial revascularization with aortocoronary bypass graft. Two-three days before and 6 months after operation gated radionuclide ventriculography has been performed in 25 patients with previous myocardial infarction (MI), anterior in 16 patients and inferior in 9. At postoperative examination, right ventricular ejection fraction (EF) was slightly but significantly reduced (p less than 0.01), while peak ejection and filling rates were unchanged. Symmetric parameters of left ventricular function did not show changes at post-operative control, except a clear-cut rise of left ventricular peak filling rate (p less than 0.05). Before operation, in patients with previous anterior MI, left ventricular EF was slightly less and right ventricular EF slightly more than in patients with previous inferior MI; after operation right ventricular EF significantly decreased (p less than 0.01) only in patients with previous anterior MI. No correlation has been demonstrated in pre- postoperative changes of the observed parameters, neither between the two groups of previous MI nor between right and left ventricular cavity. Six months after myocardial revascularization, left ventricular performance, as examined with radionuclide angiography, was practically unchanged except for improvement of diastolic function, while right ventricular performance was moderately impaired, more in patients with previous anterior MI than in those with previous inferior MI.

[Myocardial perfusion in coronary disease: thallium-201 planar scintigraphy]. / La perfusione miocardica nella cardiopatia coronarica: scintigrafia planare con tallio-201.

This research evaluated the diagnostic and analytic effectiveness of 201-thallium imaging in a group of patients with coronary artery disease, each one of them with different localization, extent and number of coronary vessel obstructions. The thallium-201 imaging was performed immediately after ergometric test and repeated 4 hours later. In a large percentage of patients thallium-201 imaging of reversible and irreversible perfusion defects have been found; thallium-201 scintigraphy showed a greater sensitivity than exercise ECG. With particular evidence 201-Tl imaging showed perfusion defects in a high percentage of patients with obstruction of one and two coronary vessels; in these patients, in the former especially, the results of exercise ECGs showed a lower sensitivity. Both thallium-201 and exercise ECG had a similar sensitivity in patients with obstruction of three coronary vessels. In patients with obstruction of one or two vessels, thallium-201 imaging clearly showed a regional hypoperfusion corresponding to the specific perfusion coronary vessels, while exercise ECG gave aspecific topographic results. Irreversible perfusion defects resulted corresponding to the myocardial segments that were infarcted, but were also observed in patients without previous myocardial infarction.

Impressive lung uptake during exercise thallium imaging with decrease of systolic blood pressure.

A case of very high thallium lung activity during exercise myocardial imaging in a patient with an old myocardial infarction but free from typical angina or heart failure symptoms is reported. The impressively abnormal lung uptake occurred in connection with a stress-induced fall in the systolic blood pressure, pointing out a causal rôle of a transient left ventricular dysfunction and interstitial pulmonary oedema in the genesis of the scintigraphic picture. Three weeks after the test, the patient suddenly died at home.

Left ventricular diastolic filling rate assessed by gated radionuclide angiography in patients with coronary artery disease.

This study was undertaken to determine the significance of diastolic left ventricular function in 26 normal subjects and in 74 patients with coronary artery disease (CAD). Gated radionuclide left ventriculography in supine position and left anterior oblique projection was performed at rest in both groups considered and during exercise in 11 normal subjects and in 35 patients with CAD. Compared with the normal subjects, the group of patients with CAD showed lower values of global and regional ejection fraction as well as of peak ejection and filling rates. 33 patients with CAD, presenting an ejection fraction greater than 54%, showed similar values of global and regional ejection fraction, compared with the group of normal subjects, while peak filling rate was significantly lower. During exercise peak filling rate significantly increased in normal subjects and in patients with CAD; this increase was constant and similar in the various subgroups considered among patients with CAD. We conclude that peak filling rate represents a more sensitive index than ejection fraction in evaluating left ventricular function in patients with CAD, as shown by the comparison between normal subjects and patients with CAD, who had an ejection fraction greater than 54%.