Plasma lipids in beta-thalassemia minor.

Because total cholesterol levels have been found to be lower in patients affected by thalassemia major and intermedia, we examined the plasma lipid pattern of 628 beta-thalassemia trait carriers and 4552 controls in order to evaluate whether the plasma lipid impairment is also present in the heterozygous state. Total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in beta-thalassemia trait carriers when compared to controls, whereas plasma triglycerides and high density lipoprotein (HDL)-cholesterol levels did not differ between the two groups. We suggest that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticuloendothelial system are the main determinants of low plasma cholesterol levels in heterozygous thalassemia.

Urinary kallikrein excretion and blood pressure response to angiotensin converting enzyme inhibitors and calcium antagonists in hypertensive patients.

OBJECTIVE: To investigate whether the hypotensive effects of angiotensin converting enzyme (ACE) inhibitors in comparison with those of calcium antagonist might be predicted by urinary kallikrein activity, a marker of the activity of the renal kallikrein-kinin system. DESIGN: Seventy-five essential hypertensive patients were randomly assigned to treatment with ACE inhibitors (enalapril or lisinopril 20 mg once a day) or with calcium antagonists (nifedipine 20 mg twice a day or lacidipine 4 mg once a day). Fifty-four had normal (NK) and 21 low (LK) kallikrein activity. Blood pressure was measured after 2 weeks, and 3 and 6 months. Patients whose diagnostic blood pressure, 2 weeks after the first dose, decreased by at least 15 mmHg or was < or = 90 mmHg were defined as responders. The others were defined as non-responders. In non-responders a second drug was added and the patients were not considered for further analysis. METHODS: Urinary kallikrein activity was determined by a spectrophotometric assay using a synthetic chromogenic substrate. RESULTS: After 2 weeks therapy with ACE inhibitors 88% of NK patients were responders, whereas in the LK subgroup 40% were responders, a significant difference between subgroups. For the patients treated with calcium antagonists, conversely, 59% of NK patients were responders in comparison with 82% of the LK subgroup, a significant difference between drug groups. After 3 and 6 months of treatment blood pressure was significantly lower in NK patients treated with ACE inhibitors and in LK patients treated with calcium antagonists. In the NK group on ACE inhibitors the mean arterial pressure after the first dose was significantly related to that observed after 6 months (n = 0.71, P < 0.01). CONCLUSIONS: Our data indicate that urinary kallikrein activity may represent an index to predict the chronic antihypertensive effect not only of ACE inhibition but also of calcium antagonism, and support the concept that the renal kallikrein-kinin system might play some contributory role in modulating the hypotensive action of ACE inhibitors.

High levels of plasma atrial natriuretic factor and impaired left ventricular diastolic function in hypertensives without left ventricular hypertrophy.

OBJECTIVE: To seek possible correlations between plasma atrial natriuretic factor (ANF) and left ventricular diastolic function (LVDF) in hypertensive patients. DESIGN: Since LVDF abnormalities can be detected in patients with normal left ventricular mass, we studied a group of hypertensive patients without left ventricular hypertrophy. METHODS: Untreated hypertensive patients (n = 23) and normotensive control subjects (n = 19) were studied. LVDF indices were obtained by M-mode and pulsed Doppler echocardiography. Blood samples for plasma ANF were taken in the recumbent position from subjects on normal-sodium intake. RESULTS: Plasma ANF levels were significantly higher in hypertensive patients than in normotensive subjects. All indices for systolic function were normal in both normotensive subjects and hypertensive patients. Left atrial diameter was significantly higher for hypertensive patients than for normotensive subjects. Considering LVDF, all indices for ventricular filling were found to be altered, on average, in hypertensive patients, the only exception being peak early velocity. In addition, significant correlations were found between plasma ANF and the pulsed Doppler parameters of left ventricular filling, peak atrial velocity and the peak early:peak atrial velocity ratio. Overall correlations between plasma ANF and left atrial diameter, and between left atrial diameter and left ventricular mass index were also observed. CONCLUSIONS: The high levels of plasma ANF observed in our hypertensive patients and their correlation with the LVDF indices (which mainly reflect the atrial contribution to ventricular filling) could be the result of an increased atrial stretch due to diastolic ventricular dysfunction. This may exist in hypertensive patients before the development of ventricular hypertrophy.

Lack of evidence for alpha-adrenergic receptor-mediated mechanisms in the genesis of ischemia in syndrome X.

Patients with syndrome X (typical angina pectoris, positive exercise tests [greater than or equal to 1 mm of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries) have a reduced coronary flow reserve due to inappropriate dilatation of small resistive vessels. To assess whether alpha-adrenergic mechanisms play a role in the genesis of ST-ischemic changes in syndrome X, 12 patients with this syndrome (2 men and 10 women, mean age 50 +/- 6 years) underwent exercise testing and 24-hour ambulatory electrocardiographic monitoring. They were done off treatment and after alpha blockade with prazosin and clonidine on 2 separate weeks. Despite treatment, all exercise tests remained positive and patients were stopped because of progressive angina pain. Compared to the off-treatment tests, exercise duration and heart rate-blood pressure product at 1 mm of ST-segment depression did not change significantly after prazosin (617 +/- 203 vs 663 +/- 203 seconds and 23,857 +/- 6,125 vs 22,098 +/- 4,816 beats/min X mm Hg, respectively) and clonidine (684 +/- 148 vs 649 +/- 80 seconds and 25,514 +/- 2,386 vs 24,567 +/- 2,001 beats/min X mm Hg, respectively). Ambulatory monitoring showed similar results regarding number of episodes of ST-segment depression greater than or equal to 0.1 mV during control and after prazosin (39 vs 38) or clonidine (26 vs 23) treatment. None of the 8 patients who also underwent provocative testing with phenylephrine had ischemic electrocardiographic changes; only 2 experienced chest pain during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term variability of angina pectoris and electrocardiographic signs of ischemia in syndrome X.

The long-term course of angina and the electrocardiographic signs of ischemia were assessed in 13 patients (10 women and 3 men, mean age 49 +/- 6 years) with typical angina pectoris, positive exercise tests, no evidence of coronary spasm and angiographically normal coronary arteries (syndrome X). Clinical and electrocardiographic parameters as well as results of exercise testing and 24-hour electrocardiographic monitoring were assessed at presentation and after a mean follow-up of 6.3 years (range 3 to 9). Mean number of anginal episodes and nitroglycerin consumption per week were similar at presentation and at the last follow-up. Furthermore, no significant difference was noted in heart rate-systolic blood pressure product at 0.1 mV of ST-segment depression (20,363 +/- 5,747 vs 21,649 +/- 5,687 beats/min x mm Hg), at angina (19,223 +/- 5,680 vs 20,126 +/- 6,023 beats/min x mm Hg) and at peak exercise (22,057 +/- 5,669 vs 22,868 +/- 6,122 beats/min x mm Hg). Time to 0.1 mV of ST-segment depression, to angina and to peak exercise was also similar (595 +/- 163 vs 631 +/- 184 s, 524 +/- 156 vs 571 +/- 168 s and 671 +/- 168 vs 718 +/- 186 s, respectively). The number of episodes of ST-segment depression greater than or equal to 0.1 mV during electrocardiographic monitoring was similar at presentation and follow-up (31 vs 25) as was the proportion of painful episodes (39 vs 36%). None of the patients developed major coronary events or cardiomyopathy during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of theophylline and isosorbide dinitrate on exercise capacity in stable angina pectoris, and their mechanisms of action.

While the role of nitrates in the prevention and treatment of myocardial ischemia is well established, the use of theophylline, proposed almost a century ago, is still controversial. Also controversial is its mechanism of action, initially thought to be coronary dilation. In this randomized, single-blind study, the acute effects on exercise capacity of sublingual isosorbide dinitrate (10 mg) and of intravenous theophylline ethylenediamine (7 mg/kg) were assessed in 10 patients with chronic stable angina and positive exercise test. After the administration of theophylline, the time to onset of angina, the heart rate-blood pressure product at 1-mm ST-segment depression and the exercise duration were similar to that after isosorbide dinitrate administration (9.8 +/- 2.3 vs 9.3 +/- 1.7 minutes, 207 +/- 41 vs 207 +/- 48 beats/min.mm Hg.10(-2) and 10.8 +/- 2 vs 10.4 +/- 2 minutes, respectively). Both drugs significantly (p less than 0.001) improved all these parameters compared to the baseline exercise test. The effect of the 2 drugs on the diameters of angiographically normal segments of large epicardial coronary arteries was then assessed using computerized quantitative angiography in 10 other patients with stable angina. Whereas theophylline failed to increase the coronary diameters compared to that in the baseline angiogram (2.9 +/- 0.6 vs 2.9 +/- 0.6 mm, respectively), the subsequent administration of isosorbide dinitrate resulted in an increase up to 3.2 +/- 0.7 mm (p less than 0.02). Thus, in patients with stable angina, theophylline delays the onset of angina, increases the ischemic threshold and prolongs the exercise duration to the same degree as isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of theophylline, atenolol and their combination on myocardial ischemia in stable angina pectoris.

The effects of theophylline (400 mg twice a day), atenolol (50 mg twice a day) and their combination on myocardial ischemia were studied in 9 patients with stable angina pectoris in a randomized, single-blind, triple crossover trial. Placebo was administered to the patients during the run-in and the run-off periods. A treadmill exercise test and 24-hour ambulatory electrocardiographic monitoring were obtained at the end of each treatment period. Compared with placebo, theophylline significantly improved the time to onset of myocardial ischemia (1 mm of ST-segment depression) from 7.8 +/- 3.7 to 9.5 +/- 3.7 minutes (p less than 0.03) and the exercise duration from 9 +/- 3.4 to 10.1 +/- 3.5 minutes (p less than 0.04). During atenolol and during combination treatment, the time to the onset of ischemia and the exercise duration were similar (10.8 +/- 4.2 and 11.2 +/- 3.2 minutes, 11.2 +/- 3.6 and 11.5 +/- 3.2 minutes, respectively) and longer than during theophylline administration (p less than 0.05). Ambulatory electrocardiographic monitoring showed that, during theophylline administration, the heart rate was higher than during placebo throughout the 24 hours (p less than 0.05). During atenolol and during combination treatment the heart rate was similar and in both cases lower than during placebo (p less than 0.05). Compared with placebo, theophylline decreased the total ischemic time from 97 +/- 110 to 70 +/- 103 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease.

Myocardial blood flow (MBF) was measured using continuous inhalation of oxygen-15-labeled carbon dioxide, and positron emission tomography before and after intravenous dipyridamole in 13 patients with syndrome X (angina pectoris, angiographically normal coronary arteries, positive exercise test and negative ergonovine test), 7 healthy subjects and 8 patients with 1-vessel coronary artery disease (CAD). In patients with syndrome X, baseline MBF was greater than in healthy subjects and patients with CAD (1.24 +/- 0.27 vs 0.87 +/- 0.07 and 1.03 +/- 0.23 ml/g/min, respectively; p < 0.05), and more heterogeneous (34 +/- 7 vs 26 +/- 5 and 25 +/- 6, respectively; p < 0.05) as assessed by the coefficient of variation among myocardial regions < or = 2.3 cm3. After dipyridamole, MBF in patients with syndrome X was similar to that in healthy subjects (2.95 +/- 0.75 vs 3.40 +/- 0.82 ml/g/min; p = NS) and greater than in patients with CAD (1.78 +/- 0.76 ml/g/min; p < 0.05). However in patients with both syndrome X and CAD, MBF was more heterogeneous than in healthy subjects (48 +/- 12 and 48 +/- 11, respectively, vs 30 +/- 7; p < 0.01). Thus, in patients with syndrome X, MBF is abnormally heterogeneous both at baseline and after dipyridamole. These findings are compatible with the presence of dynamic alterations of small coronary arteries. Because these alterations appear to be very sparse within the myocardium, they can be undetected when myocardial perfusion, function and metabolism are assessed using conventional methods that are unable to detect small myocardial regions.

Clinical pharmacology of hypertension: amelioration of left ventricular performance by treatment with labetalol.

Treatment of 23 hypertensive patients with labetalol at 200 mg twice daily for 3 months resulted in a 15-17% reduction in diastolic and systolic blood pressure, a significant amelioration in the PEP/LVET ratio expressing the haemodynamic performance of the left ventricle, and a significant reduction in its hypertrophy as expressed by the Romhilt-Estes index.

Controlled trial on three beta-blockers: antihypertensive efficacy and effect on the hypertensive heart disease.

Treatment of 66 hypertensive patients with three different beta-blockers (atenolol 100 mg once a day; oxprenolol 80 mg twice a day; nadolol 80 mg once a day) for six months resulted in a significant reduction in blood pressure and heart rate, the maximum with nadolol, a significant amelioration in pre-ejection period/left ventricular ejection time ratio expressing the haemodynamic performance of the left ventricle with atenolol and nadolol, and a significant reduction left ventricular hypertrophy as expressed by the Romhilt-Estes index with all three drugs, but especially with nadolol.

Clinical pharmacology of loop diuretics: a comparative study.

The authors performed two studies to clarify the characteristics, analogies and differences of three loop diuretics (furosemide, bumetanide and piretanide) aiming at more precise indications for their clinical use. In the first study, they compared bumetanide and piretanide by the method of compensated diuresis; in the second, they tested the three loop diuretics' efficacy in refractory ascites. The authors demonstrated that with the three substances analogous results were obtained when administered at equivalent doses and that only intensive diuresis was able to resolve refractory ascites.

Life quality in patients under hypotensive treatment.

The authors studied the life quality in a group of 74 patients--31 males and 43 females--affected with essential hypertension of World Health Organization I or II degree. All patients began treatment with frusemide at a dose of 25 mg once a day. The 35 non-responsive patients to frusemide were then treated, by random selection, with captopril at a dose of 25 mg twice a day, or nadolol at a dose of 80 mg once a day, for three months. The results show no significant differences on the hypotensive effect with either drug; in view of the incidence of side-effects of the two drugs, treatment with captopril is clearly better tolerated by the patients.

[Nonischemic changes of the ST segment in dynamic electrocardiography]. / Modificazioni non ischemiche del tratto ST in elettrocardiografia dinamica.

Ambulatory ECG monitoring has become increasingly important in the diagnostic workup of patients investigated for chest pain and in the evaluation of patients with known ischemic heart disease. Following the demonstration of ischemic episodes not associated with anginal symptoms, the diagnosis of myocardial ischemia is based solely on the detection of ST segment shifts; however several conditions associated with non-ischemic ST segment changes during ambulatory ECG monitoring might potentially be misleading. These conditions include: 1) ST segment changes in the normal population: it is a rare finding in specifically designed studies that however are probably affected by a "pretest referral bias"; caution is therefore suggested in diagnosing ischemia when episodes of ST segment depression are mild (< 2 mm) and occur at high heart rates (> 120 beats/min); 2) postural changes, usually easily recognized by the typical "square" pattern of the ST segment trend; 3) ST segment changes related to respiratory manoeuvres, quite rare and usually mild; 4) ST segment changes due to drugs; 5) ST segment changes caused by rhythm and conduction disturbances. Lastly the significance of ST segment changes in patients with angina and normal coronary arteries is discussed, following recent observations of reduced coronary flow reserve and/or abnormal myocardial metabolism in a sizable proportion of these patients.

Diuresis and intensive saluresis.

Intensive saluresis, intended as an exceptional though real and practicable therapeutic approach, has made unimaginable progress possible in different sectors of Internal Medicine relating to hydrosaline balance alterations such as chronic and acute renal failure, nephrosic syndrome, refractory heart failure, acute pulmonary edema and ascites. We are proud to be the first who followed a path that assured patients compensation beyond "classic" therapeutic possibilities, and undoubtedly better quality of life, as well.

Assessment of colour flow imaging in the grading of valvular regurgitation.

To assess the accuracy of colour flow imaging in the grading of valvular regurgitation, we studied 100 consecutive patients with angiographic mitral regurgitation (55), aortic regurgitation (35) or both (10). The etiology of valve regurgitation was rheumatic in 42 and non-rheumatic in 58 patients. For comparison, 28 subjects with no structural cardiac disease were studied. Mitral valve regurgitation was assessed with colour flow imaging by measuring the maximal regurgitant jet area and the maximal jet area normalized to left atrial area; aortic valve regurgitation was assessed from jet area and jet width normalized to ventricular outflow tract width. The best correlation between colour flow imaging and angiography was obtained with normalized measurements for both mitral (r = 0.82, P less than 0.0001) and aortic regurgitation (r = 0.94, P less than 0.0001). A proportion of patients and controls without angiographic regurgitation showed evidence of mild mitral (31% and 32%) and aortic (14% and 11%) regurgitation on colour flow imaging. There was a large overlap in the normalized colour flow measurements between angiographically mild and moderate mitral regurgitation (43%); the overlap was greater when regurgitation was rheumatic in origin (45%) rather than non-rheumatic (10%) (P less than 0.001). There was also overlap in the normalized colour flow findings in patients with angiographic aortic regurgitation, which was greater in rheumatic vs non-rheumatic disease. Knowledge of the etiology significantly improved the separation of all angiographic grades of aortic regurgitation using colour flow measurements (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Similar time course of ST depression during and after exercise in patients with coronary artery disease and syndrome X.

To assess whether the time course of ST segment depression differs in patients with coronary artery disease and patients with angina and normal coronary arteries, the exercise tests of 54 patients with documented coronary artery disease and 25 patients with syndrome X (angina, positive exercise test, no evidence of coronary artery spasm, and normal coronary arteries) were compared. All tests were performed with therapy withheld, using the modified Bruce protocol. In each test, time, heart rate and blood pressure were measured at the onset and at 1 mm of ST segment depression, and at peak exercise. Recovery (return of the ST segment to baseline +/- 0.2 mm) time was also assessed. Peak ST segment depression was similar in coronary artery disease and syndrome X patients (1.5 +/- 0.3 versus 1.6 +/- 0.4 mm). In 42 coronary artery disease patients, ST segment depression developed early (less than or equal to 6 minutes) during exercise; this was associated with a short recovery (less than or equal to 3 minutes) in 17 (40%) and with a long recovery (greater than 3 minutes) in 25 (60%) patients. In 17 patients with syndrome X, ST segment depression developed early; it was associated with a short recovery in six (35%) and with a long recovery in 11 (65%) patients. Late (greater than 6 minutes) onset of ST segment depression was observed in 12 coronary artery disease patients; of these, eight (67%) had a short recovery and 4 (33%) had a long recovery. Late onset of ST segment depression occurred in eight patients with syndrome X; six (75%) had a short recovery and two (25%) had a long recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Duration of ST segment depression after exercise-induced myocardial ischemia is influenced by body position during recovery but not by type of exercise.

To assess whether the duration of ischemic ST segment depression after exercise can be modified by changes in body position during recovery or with different types of exercise, 18 patients with chronic stable angina, positive exercise test results, and documented coronary artery disease were prospectively studied. Every patient underwent testing with three different exercise protocols: (1) Bruce (Bruce-standing recovery), (2) abrupt onset of exercise (abrupt), and (3) modified Bruce protocol preceded by a 10-minute warm-up period (warm-up). After exercise test patients recovered in a sitting position. In addition, all patients performed a fourth exercise (Bruce protocol), but this time they recovered in the supine position (Bruce-supine recovery). Time and heart rate-blood pressure product at 1 mm ST segment depression were similar for Bruce-standing recovery, abrupt, and Bruce-supine recovery protocols (5.1 +/- 2, 4.4 +/- 2, and 5.2 +/- 2 minutes and 20.8 +/- 4, 21.3 +/- 4, and 20.4 +/- 4 beats/min x mm Hg x 10(-3), respectively. Heart rate and heart rate-blood pressure product at peak exercise did not differ in Bruce-standing recovery, abrupt, and Bruce-supine recovery. Maximal ST segment depression was -2.0, -1.9, and -2.0 mm with Bruce-standing recovery, abrupt, and Bruce-supine recovery exercise, respectively, and -1.5 mm with warm-up exercise (p less than 0.05). Duration of ST segment depression into recovery was significantly prolonged after Bruce-supine recovery exercise (9.4 + 5 minutes) compared with Bruce-standing recovery, abrupt, and warm-up protocols (6.8 + 3, 5.9 + 4, and 5.0 + 3 minutes, respectively; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Massive haemorrhagic pericardial effusion in beta-thalassaemia major.

The case of a child with beta-thalassaemia major who developed a massive haemorrhagic pericardial effusion is reported and in whom the clinical picture completely resolved after pericardiocentesis. Possible causes are discussed and the role of echocardiography in the follow-up of thalassaemic patients is emphasized.