Effects of a low-sodium high-potassium salt in hypertensive patients treated with metoprolol: a multicentre study.

A multicentre study, involving 358 subjects, was carried out to evaluate the effects of a low-Na/high-K dietary salt in hypertensive patients receiving beta-blocker monotherapy. At the end of a 4-week treatment period with 200 mg slow-release metoprolol patients were randomly divided into two groups: one group was given common salt and the other the dietary salt. Both salts were given at table, in double-blind conditions over a period of 4 weeks. The dietary salt group showed a systolic and diastolic blood pressure (BP) reduction (4.2 and 3.0 mmHg, respectively, in the supine position and 4.0 and 2.5 mmHg in the standing position), which was virtually absent in the common salt group. A statistically significant difference between the two groups was found only between the systolic values (P less than 0.05). Twenty-four-hour urinary sodium excretion did not change in either group, while the excretion of 24-h urinary potassium increased significantly in the dietary salt group. It is concluded that in mild or moderately hypertensive patients already receiving a beta-blocker, ancillary treatment with a low-Na/high-K salt can be expected to lead to a further, slight reduction in systolic BP, probably due to the daily potassium load (around 20 mmol).

Acute effects of felodipine in exertional angina pectoris.

To investigate the antianginal efficacy, duration of action and tolerability of 2 doses of the new calcium antagonist felodipine, 15 patients (14 men and 1 woman, mean age 62 years) with stable exertional angina pectoris and angiographically demonstrated coronary artery disease were randomly given felodipine, 5 and 10 mg, and placebo on 3 different days. A bicycle ergometer exercise test was performed 3 and 10 hours after dosing. In comparison with placebo, felodipine 5 and 10 mg significantly increased resting heart rate and decreased resting systolic and diastolic blood pressure 3 hours after administration (p less than 0.001). Ten hours after administration, only supine systolic blood pressure was still significantly lower (p less than 0.001). Anginal (time to mild chest pain) and ischemic (time to 1 mm ST depression) thresholds, as well as duration of exercise and total work at peak exercise, were higher in comparison with placebo at 3 and 10 hours (p less than 0.001). In comparison with the lower dose, 10 mg felodipine induced a decrease in supine (p less than 0.05) and sitting (p less than 0.01) systolic blood pressure at rest and an increase in total work to anginal threshold (p less than 0.01), as well as in total work and duration of exercise at peak exercise (p less than 0.05). These results suggest that a single administration of felodipine, 5 and 10 mg, may improve exercise capacity over a 10-hour period in patients with stable exercise-induced angina due to atherosclerotic heart disease.

Extended release felodipine in essential hypertension. Variations in blood pressure during whole-day continuous ambulatory recording.

Intraarterial blood pressure (BP) monitoring during free ambulation (Oxford technique) was carried out in 12 essential mild-to-moderate hypertensive patients undergoing 4 weeks treatment with felodipine, 10 mg given once daily in an extended release formulation. Compared to placebo, felodipine significantly reduced systolic and diastolic blood pressure throughout 24 h. The greatest reduction was observed at 10 AM, 3 h after drug administration (-32 +/- 6/-24 +/- 5 mm Hg for systolic and diastolic BP, respectively, P less than .001). Hourly BP values remained significantly lower up to and including the 24th hour during felodipine extended release treatment (-18 +/- 5/-11 +/- 3 mm Hg, P less than .001). Felodipine extended release also reduced 24 h blood pressure variability, evaluated on the standard deviation of each hourly mean (from 16.3 +/- 0.9/12.6 +/- 0.6 to 13.4 +/- 0.6/10.4 +/- 0.6 mm Hg, P less than .01). Furthermore, absolute BP values dropped significantly at the peaks of dynamic exercise (bicycle ergometer: from 248 +/- 13/123 +/- 11 to 204 +/- 24/102 +/- 13 mm Hg, P less than .001), isometric exercise (hand grip: from 232 +/- 18/133 +/- 16 to 180 +/- 20/101 +/- 16 mm Hg, P less than .001), and cold pressor test (from 229 +/- 20/127 +/- 14 to 178 +/- 22/99 +/- 15 mm Hg, P less than .001). In conclusion, felodipine extended release exerts a good antihypertensive effect which is maintained for 24 h and reduces the level of blood pressure peaks reached under different physical stresses.

Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: a multicentric study. The Collaborative Nitro Group.

Eighty-eight patients (84 men and 4 women; mean age 59.3 years) with stable exercise-induced angina pectoris were enrolled in this within-patient, placebo-controlled study aimed at comparing the efficacy of the continuous and intermittent (12 hour on, 12 hour off) application of transdermal nitroglycerin. Eighty-one patients completed the study. After a 1-week placebo run-in period, during which the stability of angina was assessed on a bicycle ergometer, the patients received continuous treatment (two 10 mg/24 hour patches twice daily, at 8 a.m. and 8 p.m.), intermittent treatment (two 10 mg/24 hour patches at 8 a.m. and two placebo patches at 8 p.m.) and placebo (two placebo patches twice daily, at 8 a.m. and 8 p.m.), each given for one week in a double-blind randomised sequence, according to a 3 x 3 latin-square design. A cycloergometric exercise test was performed at the end of each period of treatment, 4 and 10 hours after the application of the morning patch. In comparison with placebo, both schedules of the active treatment induced a significant increase in both the ischemic (duration of exercise to 1 mm ST segment depression) and the angina threshold (duration of exercise to mild angina) at the 4th and at the 10th hours after-dosing. A significant difference was also found between continuous and intermittent treatment at the same times of observation, in favour of the intermittent schedule. The limited number of anginal attacks recorded during placebo prevented any clinical evaluation of the treatments. This study shows that the efficacy of transdermal nitroglycerin is more pronounced when it is given following an intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Individual responses to transdermal nitrates after chronic administration in angina pectoris.

The aim of this study was to investigate whether, and to which extent, sustained treatment with transdermal nitroglycerin plasters may lead to the development of tolerance in patients with effort-induced angina pectoris. Ten patients, all men, mean age 62.7 years, took part in a double-blind, cross-over, acute study, comparing the transdermal therapeutic system of nitroglycerin 10 mg/24 hours with placebo. Patients were then treated for 1 month with the active drug in single-blind condition, and finally they took part in a further acute study identical to the first. Cycloergometric exercise tests were carried out 4 hours after dosing. In comparison with placebo, the active drug significantly (P less than 0.01) increased ischaemic threshold (ST depression = 1 mm) after both acute (from 299 +- 92 to 413 +- 120 sec) and chronic treatment (416 +- 107 sec). The same results were obtained for exercise duration to peak exercise (acute study: from 336 +- 65 to 482 +- 90 sec; chronic treatment: 466 +- 118 sec). The final acute study confirmed the stability of angina, showing that the improvement in exercise tolerance after chronic treatment was entirely due to the pharmacological effect of the drug. In terms of single patient response to the active treatment, 7 of the 10 patients showed an improvement in exercise tolerance after both acute and chronic treatment, while in 3 patients no antianginal effect was observed. These results suggest that nitrate tolerance cannot be considered an inevitable finding in patients chronically treated with transdermal patches.

Chlorthalidone alone or in fixed combination with slow-release metoprolol in the management of arterial hypertension: a long-term study of 545 patients.

In a double-blind trial, 545 out-patients with essential hypertension received 25 mg/day chlorthalidone alone (274 patients) or in fixed combination with 200 mg/day slow-release metoprolol (271 patients) for 8 weeks. Both treatments significantly (P less than 0.001) decreased systolic and diastolic blood pressure; 45.6% of patients receiving chlorthalidone and 82.5% receiving combined therapy had a diastolic blood pressure of less than 95 mmHg. Patients not controlled by chlorthalidone or chlorthalidone plus metoprolol subsequently received chlorthalidone plus metoprolol (137 patients) or chlorthalidone plus metoprolol plus a third drug (34 patients), respectively, for 8 weeks. A total of 79.5% of patients receiving chlorthalidone plus metoprolol and 61.8% receiving chlorthalidone plus metoprolol plus a third drug had a diastolic blood pressure of less than 95 mmHg. Only 5.9% of patients experienced mild to moderate side-effects. Plasma potassium levels significantly (P less than 0.01) decreased during the first 8 weeks only. It is concluded that a diuretic alone or in fixed combination with a beta-blocker is effective in the long-term treatment of arterial hypertension.

[Case of autochthonous subcutaneous dirofilariasis in man]. / Un caso autoctono di dirofilariasi sottocutanea nell'uomo

An autochthonous case of dirofilaria infection observed in Italy is described. The parasite was an unidentified species of dirofilaria removed from a subcutaneous nodule of a patient. The most recent data about epidemiology and geographical distribution of the parasite in Italy are briefly discussed.

Acute effects on exercise tolerance of felodipine and diltiazem, alone and in combination, in stable effort angina.

The acute effects on exercise tolerance and electrocardiographic ischaemia of felodipine and diltiazem, alone or in combination, were investigated in 12 patients with documented stable effort-induced angina pectoris. After being withdrawn from their previous antianginal treatments, patients received a single oral dose of felodipine 10 mg, diltiazem 60 mg, their combination or placebo on four different days, according to a double-blind, 4 x 4 latin-square design. Exercise time to ischaemic threshold (ST-segment depression = 1 mm) and to peak exercise was significantly prolonged by the felodipine-diltiazem combination (492 and 504 s, respectively) against placebo (301 and 370 s, both P less than 0.01), felodipine alone (381 and 428 s, both P less than 0.01) and diltiazem alone (367 and 422 s, both P less than 0.01). The effects on total work followed a similar pattern. In comparison with placebo, the administration of felodipine and diltiazem alone significantly increased exercise duration as well as total work to ischaemic threshold and to peak exercise, with no differences between the two drugs. Systolic blood pressure during exercise was not affected by any of the treatments. However, in comparison with both placebo and diltiazem, the combination induced an increase (P less than 0.01) in heart rate during exercise. One patient suffered from symptomatic hypotension with the combination, and another had sinus tachycardia after felodipine. In conclusion, the acute concomitant administration of felodipine and diltiazem in patients with stable effort angina induces a marked improvement in exercise tolerance in comparison with placebo, felodipine alone and diltiazem alone. However, the benefit/risk profile of such a combination requires further, long-term investigation.

A case of primary undifferentiated sarcoma of the liver.

The authors report a case of primary undifferentiated sarcoma of the liver, observed in a 36-year-old man. Diagnosis was established at peritoneoscopy and guided biopsy, and confirmed by autopsy two months later.

[Histochemical detection of HBsAg in liver biopsies using the orcein staining method]. / Dimostrazione istochimica di HBsAg in biopsie epatiche con il metodo di colorazione all'orceina.

Liver biopsies from 30 HBsAg seronegative and 33 HBsAg positive subjects affected by liver diseases were stained by orcein method for the histochemical detection of HBsAg. All biopsies from HBsAg negative cases were orcein negative. Staining was positive in 55% of seropositive patients. The frequency of the different patterns of the staining is analyzed and its value as a diagnostic and prognostic tool in chronic liver disease is discussed.

[Radioimmunologic determination of the Australia antigen during the course of viral hepatitis]. / Determinazione radioimmunologica dell'antigene Australia durante la evoluzione dell'epatite da virus

Australia Antigen was detected by radioimmunoassay technique in 80 cases of viral hepatitis. Incidence of the antigen was 40% in patients with epidemiologic data of infectious hepatitis, 84% in patients with epidemiologic data of serum hepatitis and 61% in a group of patients not reporting a reliable epidemiologic history. The count rate was periodically determined during the course of the illness in the attempt to evaluate, within the limits of the method, the amount of the antigen in the serum samples. Results are briefly discussed, together with the problem of the correlation between the presence of Australia Antigen and the two types of hepatitis infection.

Serum alpha-fetoprotein in viral hepatitis and its complications.

Alpha-fetoprotein levels were measured by radioimmunoassay in 40 cases of acute viral hepatitis, 5 cases of chronic persistent hepatitis, 15 cases of chronic aggressive hepatitis and 5 cases of hepatic coma from fulminant viral hepatitis. Serum concentrations were increased in 55% of patients with acute viral hepatitis and in about 33% of patients with chronic aggressive hepatitis. Levels resulted markedly raised among the patients with coma from fulminant viral hepatitis who survived. The high aplha-fetoprotein values may reflect liver cell regeneration after necrosis of a critical mass of hepatic tissue.

[Status of the "cure" of non-complicated myocardial infarct in Italy]. / Lo stato delle "cure" per l'infarto miocardico non complicato in Italia.

To analyze the state of health care for patients with myocardial infarction, questionnaires were sent to 191 Italian general hospital and university cardiological departments equipped with an intensive coronary care unit (ICCU). A total of 139 returned the questionnaire (72.7%), of which 138 were usefully completed. The mean number of beds per ICCU is 5.7 and still today 14% of the ICCU's transfer their patients to a medical department. The mean time to admission is 7 hours. In the acute phase, rehabilitation is begun in 49% of the ICCU; mobilization and hospitalization times are shorter than in 1978. The most widely employed pharmacological treatment in the acute phase is the glucose-potassium-insulin infusion (74%). Prior to discharge, 16% of the institutions obtain an exercise test, 74% an echocardiogram and 42% a dynamic ECG. Health education programs, on the other hand, are very poor: only a few Centers provide educational material. In the case of recurrent chest pain, 81% of the institutions advise the patients to take nitroglycerin, and 67% with the patients to report to the hospital. Eighty-nine percent of the Centers carry out follow-up tests on all their patients 1 month after discharge. Calcium antagonists and nitrates are prescribed on discharge by one half of the departments. In the post-infarction period an effort test is performed in 54% of Centers; coronary angiography is carried out on the youngest patients in 9% of Centers; in 30% of Centers, coronary angiography is only performed in patients with severe symptoms. Sixty-five institutions administer their own rehabilitation programs, while 35 send their patients to other institutions.(ABSTRACT TRUNCATED AT 250 WORDS)

[TTS-nitroglycerin and slow-release metoprolol: efficacy in patients with stable exercise-induced angina]. / TTS-nitroglicerina e metoprololo retard: efficacia nei pazienti con angina da sforzo stabile.

The antianginal efficacy of slow-release metoprolol (SRM) alone and associated to a transdermal therapeutic system containing nitroglycerin (TTS-TNG), was investigated in 10 patients with chronic, stable exertional angina and angiographic evidence of obstructive coronary artery disease, by means of a double blind, cross-over trial. Each patient performed a symptom-limited exercise test 4 and 24 hours after single blind placebo on day 1, and double blind SRM (200 mg) alone or SRM plus TTS-TNG, on days 3 and 5, in a randomized sequence. The protocol of Redwood was employed. Compared to the beta-blocker alone, the combined administration of SRM and TTS-TNG was associated to a significant increase in mean exercise duration 4 hours (528 +/- 180 vs 412 +/- 110 sec.; p less than 0.001) and 24 hours (432 +/- 115 vs 391 +/- 100 sec.; p less than 0.05) after drug administration. A significant increase in mean total work performance 4 hours (4626 +/- 1070 vs 3272 +/- 803 kgm; p less than 0.01) and 24 hours (3445 +/- 1045 vs 2941 +/- 773 kgm; p less than 0.01) after drug administration was observed as well. During placebo all the tests were stopped due to angina associated with ST depression greater than or equal to 1 mm. Conversely, the test was terminated due to fatigue by 8 patients at 4 hours and 5 patients at 24 hours after combined therapy, and respectively by 5 and 1 patient after SRM alone. No side effects were observed after the administration of SRM alone, whereas 5 patients complained of mild headache after SRM and TTS-TNG.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative evaluation of the effect of two doses of Nitroderm TTS on exercise-related parameters in patients with angina pectoris.

The effectiveness of Nitroderm TTS 5 and Nitroderm TTS 10 in stable effort-induced angina pectoris was assessed by measuring the tolerance of 20 selected in-patients to cycloergometric symptom-limited tests. During the week preceding the trial previous anti-anginal treatment was gradually withdrawn except for short-acting nitrates. Patients were also familiarized with ergometric laboratory environment. The trial started with a 24-h control period when placebo was given single-blind to each patient. A double-blind cross-over design was then followed, two groups of 10 patients each being subjected successively to two sequences of therapy. By means of the double-dummy technique, Nitroderm TTS 5 or Nitroderm TTS 10 and matching placebos were applied simultaneously once daily for 24 h on two different days. Resting heart rate and blood pressure were measured before starting each exercise test, which was performed 3 h after placebo as well as 3 and 24 h after Nitroderm TTS application. The results of the tests were evaluated in terms of maximum workload, duration of exercise and total work performed for each of the two doses administered and compared with the corresponding baseline values. When compared with placebo both Nitroderm TTS doses produced a significant change (P less than 0.01) in the assessment variables. After application of the active treatment, duration of exercise, total work performed and maximal workload were increased while lying and standing blood pressures were decreased. There was no significant difference between the two doses of Nitroderm TTS in the assessment variables, except for systolic blood pressure and lying heart rate 3 and 24 h, respectively, post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitroderm TTS in exercise-induced angina pectoris--a randomized double-blind study.

Nitroderm TTS is a new transdermal delivery system for nitroglycerin, consisting of a self adhesive disc from which the drug diffuses into the skin at a predetermined rate through a microporous membrane. In an acute, randomized, double-blind, within-patient study, a TTS formulation releasing 10 mg of nitroglycerin over 24 hours (TTS 10) was compared with placebo and isosorbide dinitrate (ISDN) 20 mg slow-release. TTS 10, ISDN and placebo were given on 3 successive days, according to a 3 X 3 latin square design 3 times replicated, to 9 in-patients with coronary heart disease and stable exercise-induced angina pectoris. At rest, both TTS 10 and ISDN significantly lowered lying (p less than 0.05) and standing (p less than 0.01) systolic blood pressure as compared to placebo, but there was no difference between the 2 active treatments. On the symptoms-limited cycloergometric exercise test, carried out 4 hours post-dosing, both TTS 10 and ISDN significantly (p less than 0.05) improved exercise tolerance in respect to placebo. Treatments were well tolerated. In conclusion, both TTS 10 and ISDN, 4 hours post-dosing, are superior to placebo in improving exercise tolerance in patients with coronary heart disease and exercise-induced angina pectoris. The transdermal therapeutic system, allowing constant plasma nitroglycerin levels over 24 hours, has the advantage of once daily administration.

Effect of a new transdermal therapeutic system containing nitroglycerin on exercise capacity in patients with angina pectoris.

In a double-blind, within-patient, randomized, placebo-controlled, acute study, the effects at rest and on exercise capacity of two doses of a new transdermal therapeutic system (TTS), releasing respectively 10 and 20 mg of nitroglycerin (NTG) over 24 hours, were assessed in 15 outpatients with stable exercise-induced angina pectoris. A symptom-limited exercise test was performed 4 and 24 hours after the application of each system. In comparison with placebo, both TTS-NTG doses induced a statistically significant (p less than 0.01) increase in total duration of exercise, in exercise duration to 1 mm ST segment depression, in maximal workload and in total work performed, at both 4 and 24 hours after dosing. Furthermore, both TTS-NTG doses induced a significant rise in the pressure-rate product, both 4 and 24 hours after dosing (p less than 0.01 and p less than 0.05, respectively). No statistical difference was found between the two doses of active drug in any of the above-mentioned evaluation parameters. The only unpleasant side effect was the typical nitrate headache, which occurred in 11 of 15 patients. In conclusion, a single application of TTS-NTG, 20 cm2 or 40 cm2, may improve exercise capacity over a 24-hour period in patients with stable exercise angina due to atherosclerotic heart disease.

Increased exercise tolerance and reduced electrocardiographic ischaemia 3 and 12 hours after oral felodipine in effort angina.

The antianginal properties and the duration of action of two doses of felodipine, a dihydropyridine calcium antagonist with a vascular:myocardial potency ratio approximating 100:1, were investigated in 15 patients suffering from disabling effort angina pectoris with reproducible exercise tolerance. Felodipine (5 mg, 10 mg) and placebo were administered once in the morning on three different days, with a 24 h interval between them, according to a double-blind 3 x 3 latin square design, 5 times replicated. Symptom-limited cycloergometric exercise tests were performed 3 and 12 h after administration. Duration of exercise to ST segment depression of 1 mm and to peak exercise was increased (all P less than 0.01) by both doses of felodipine in comparison with placebo. Twelve hours after administration, the 10-mg dose induced a significant improvement in the exercise time and a smaller ST segment depression (all P less than 0.01) in comparison with the 5-mg dose. The relationship between ST segment depression and the pressure-rate product during exercise was favourably influenced by the 10-mg dose at 3 and 12 h after intake, and by the 5-mg dose only at 3 h after intake. These findings suggest an increase in coronary blood flow induced by felodipine. Apart from mild headache there were no other unwanted effects. In conclusion, felodipine improves exercise tolerance and reduces electrocardiographic ischaemia for up to 12 h after single oral administration in patients with effort angina. Increasing the dose from 5 mg to 10 mg produces a more prolonged effect, with increased exercise tolerance 12 h after intake.

Intermittent transdermal nitroglycerin monotherapy in stable exercise-induced angina: a comparison with a continuous schedule.

The aim of this study was to investigate nitrate tolerance during continuous treatment with nitroglycerin patches (NTG) as monotherapy, and to assess whether tolerance might be prevented by an overnight nitrate-free interval. Ten male patients, of mean age 53.2 years (range 41-62 years), with pathological coronary angiography and stable exercise-induced angina pectoris took part in a double-blind crossover study (two 15-day periods), during which the continuous and intermittent (12-h nitrate-free interval) application of NTG 20 mg (24 h)-1 patches were compared. Single-blind placebo was given acutely before and at the end of the crossover. Exercise testing was performed on a treadmill according to the Bruce protocol 4 and 12 h after dosing, both during placebo and at the end of the two active treatment periods. In comparison with continuous treatment, the intermittent administration of 20 mg (24 h)-1 NTG patches significantly increased ischaemic threshold and total work time at the 4th and the 12th hour. Night-time withdrawal of NTG transdermal delivery systems determined during the 15-day period a total of 11 night anginal attacks in six out of 10 patients (0.07 attacks per patient per nitrate-free interval).