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Biomedical subjects

P Puddu

Publications and source records attributed to P Puddu.

At least 145 records · Page 8Linked to original sources

[Atrial natriuretic factor in physiological conditions and pathological states].

Having outlined the principal physiological and pathological aspects of the atrial natriuretic factor (ANF) on the basis of data found in the literature, the authors report the results of their research on variations of ANF plasma level during hyperkinetic atrial arrhythmia, acute myocardial infarction with and without complications as well as hypotensive and renal effects of synthetic ANF in congestive heart failure. Regardless of the cause of hyperkinetic atrial arrhythmia, high ANF levels were normalized or significantly reduced after the return to sinus rhythm whereas with the sole reduction of ventricular rate ANF remained raised. In uncomplicated myocardial infarction ANF level was raised to an extent inversely proportional to the ejection fraction. In cardiogenic shock, ANF values were high and correlated to the high central venous pressure and heart rate. On the contrary, in the hypotensive bradycardia syndrome ANF values were normal even when the syndrome had occurred in the acute stage of infarction. In congestive heart failure, ANF administration had contradictory effects in that diuresis was induced by lower doses, and hypotension by higher ones.

Animals↗

Correlations between serum lipids and complement components in adults without demonstrated atherosclerotic disease.

The variability due to age and sex and the reciprocal relations of serum IgG, IgA, IgM, C3, C4, total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) were studied in 87 subjects (46 men and 41 women, aged 20-75 years) selected for the absence of significant atherosclerotic lesions. Serum IgA and C3 were higher in men than in women (P less than 0.05) mainly in the age group 41-60, while IgM and HDL-C were higher in women than in men (P less than 0.05 and P less than 0.01, respectively), especially in the age group 20-40. Direct univariate correlations with age were found for serum TC (P less than 0.0001), IgA (P less than 0.001), and C4 (P less than 0.01) but the latter correlations was confirmed only in women by multivariate analysis. These 3 variables had the major increment in the age group 41-60 in men, while in women the increase associated with age was more progressive or late. Univariate analysis showed a 'ring' of highly significant correlations (P less than 0.0001) involving serum lipids and complement components (TC-C4-C3-TG-TC). The correlation between TC and C4 was present only in men in multivariate analysis and improved with increasing age. These findings might represent a clue to explain the previously reported association between serum C4 and atherosclerosis.

Adult↗

Interferon alpha-2a in cutaneous T-cell lymphoma.

23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.

Adult↗

Calcium stimulates opioid receptor agonism in rat cardiac sarcolemma.

We have found that calcium stimulates, in a dose-dependent manner, the binding of opioid to kappa and delta receptors in sarcolemma from rat's ventricles isolated by hypotonic lithium bromide shock. Opioid binding was measured using [3H]-diprenorphine as a radioligand. The delta-selective agonist [D-Ala2, D-Leu5]-enkephalin and the kappa-selective agonist U-50, 488H both inhibited control and Ca(2+)-stimulated [3H]-diprenorphine binding to the sarcolemma, whereas [D-Ala2,MePhe4,Gly-(ol)5]-enkephalin was ineffective. The stimulatory effect of calcium increased the maximal binding capacity without affecting the affinity of the receptor for the ligand.

Animals↗

Receptors for atrial natriuretic factor in cardiomyocytes and aortic smooth muscle.

The aim of this work was to investigate whether specific receptors for atrial natriuretic factor (ANF) are present in ventricular cardiomyocytes and aortic smooth muscle membranes. 125I-ANF was employed to test the binding of the radioligand to isolated rat cardiomyocytes. Calcium-tolerant ventricular cardiomyocytes were obtained by retrograde perfusion with collagenase. 125I-ANF binding to cardiomyocytes was highly specific (70-80%) with a KD value of 72.6 pM and a Bmax of 9.37 fmol/mg protein. In other studies, 125I-ANF binding was investigated with a membrane preparation obtained from calf thoracic aorta, from which the endothelium had been previously stripped off. In this preparation too the interaction of 125I-ANF (70-80%) was highly specific, with a KD value of 70.4 pM and a Bmax of 8.78 fmol/mg protein. These results suggest that specific receptors to atrial natriuretic factor are present both in isolated rat cardiomyocytes and in the smooth muscle of calf thoracic aorta. This second observation is in agreement with the hypothesis that the vasodilator effect of atrial natriuretic factor is due to a direct interaction between this peptide and vascular smooth muscle cells.

Animals↗

Antibody patterns against cytomegalovirus and Epstein-Barr virus in human atherosclerosis.

The immune response against Cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-induced antigens has been determined in teh sera of 36 patients with angiographically assessed atherosclerosis and compared with that of 36 matched control subjects. Significantly higher titres of antibody against CMV and EBV - induced antigens and a significant increase in CMV- and EBV- reactivated infections were found in atherosclerotic patients as compared to control subjects. Moreover serological signs of concomitant EBV and CMV infections occurred more frequently in atherosclerotic patients than in controls. One atherosclerotic patient, however, completely lacked antibody to CMV while CMV- and EBV- reactivated infections were also noted in control subjects, probably connected with their old age. Our data suggest that multiple reactivations of latent viruses may represent a consequence rather than a causal factor of atherosclerosis.

Antibodies, Viral↗

[Mexiletine in patients with progressive infarction and reduced ventricular function: anti-arrhythmic efficacy and hemodynamic effects].

Reduced left ventricular function and ventricular arrhythmias are the main risk factors associated with sudden death in patients with previous acute myocardial infarction. Antiarrhythmic therapy may have side-effects on myocardial contractility and sometimes makes the arrhythmia itself worse, especially when the pump function is seriously compromised. The aim of this study was to evaluate the efficacy of oral mexiletine as well as any modifications in left ventricular function by means of ambulatory ECG monitoring and angiocardiography with Tc 99m, at rest and after the handgrip test, in 20 patients with previous myocardial infarction and ventricular arrhythmias who were grouped into NYHA class II and class III. The mexiletine therapy lasted three weeks. Both classes showed a significant decrease in the number of ventricular extrasystoles/hour and in the number of couples (p less than 0.01). The decrease in the number of the ventricular runs proved to be higher in the general analysis (p less than 0.01) than in each NYHA class (p less than 0.05). At the end of the study, significant modifications were not observed either in the end-diastolic and end-systolic volumes, or in the ventricular ejection fraction.

Aged↗

[Variant angina which interacts with two phenomena: local hypersensitivity and abnormal response in the coronary tree to vasoconstrictor stimuli].

The aim of the present study was to evaluate the vasomotion of the entire coronary tree in variant angina, particularly focusing the attention on the behaviour of the "non spastic" epicardial vessels, using a quantitative coronary technique. Two different groups of patients served as controls. The first group consisted of 10 patients with accessory nodal pathway but without any sign of myocardial ischemia (Group I). The second group included 8 patients with stable exertional angina pectoris and coronary artery disease (Group II). The third group (Group III) consisted of 16 patients presenting with variant angina and spontaneous or hyperventilation-induced (HV: 30 cycles/min for 5 min) ST segment elevation. All patients underwent coronary angiography before and 2 min after HV testing; the evaluation of the coronary diameters was performed on baseline and after HV. In Group III, the HV testing caused a 26 +/- 12% reduction of the "non spastic" coronary vessels, with the mean control diameter of 2.00 +/- 0.61 mm that decreased to 1.48 +/- 0.55 mm. The patients of Group I showed only a mild degree of vasoconstriction (9 +/- 6%) of the epicardial coronary vessels; the Group II patients, also, showed a moderate response to vasoactive stimulus (11 +/- 8%), with the mean control diameter of 2.36 +/- 0.69 mm that decreased to 2.09 +/- 0.65 mm. The greater amount of vasoconstriction showed by patients with variant angina was statistically significant compared to both control groups (p less than 0.001). A further analysis of the coronary vasomotion, in Group III patients, showed that the 6 patients with normal or near normal coronary angiograms exhibited a 34% reduction in the vessel diameter. The remaining 10 patients who presented with a diffuse atherosclerotic involvement of the epicardial vessels (organic stenosis greater than or equal to 50% at the site of spasm) showed a lesser (20%) but yet significant extent of vasoconstriction compared to both control groups (p less than 0.001). In conclusion, our data indicate that: patients with variant angina exhibit a marked and diffuse coronary narrowing of the coronary vessels during vasoconstrictor stimuli; focal spasm occurs more frequently at the level of atherosclerotic coronary segments, whether they are critical or not. An interaction between these 2 phenomena, ie atherosclerosis and abnormal vasoconstriction, is supposed to be a cause of the occurrence of focal coronary spasm in variant angina.

Adult↗

Comparison of verapamil versus propranolol therapy in syndrome X.

The effects of oral verapamil, 320 mg daily, propranolol, 120 to 160 mg daily, and placebo were compared in 16 patients presenting with transient myocardial ischemia without evidence of coronary atherosclerosis or vasospasm on angiography (syndrome X). Testing was done according to a randomized double-blind crossover placebo-controlled trial consisting of 3 consecutive 7-day treatment periods with verapamil or propranolol or placebo. Patients underwent continuous 48-hour electrocardiographic monitoring before therapy (run-in phase) and during the last 2 days of each treatment period. A total of 391 episodes of diagnostic (greater than or equal to 0.15 mV) ST depression was recorded during the trial. Of these, 23 were symptomatic. None of the episodes occurred while the patients were asleep, 25% during exercise, 35% during minimal physical activity and 40% at rest. Rest included activities demanding mental arousal (conversation, reading or watching television). Heart rate at the onset of ST depression was higher (greater than or equal to 10 beats/min) than that observed in the 5 minutes preceding ischemia in 95% of the episodes. In the group as a whole, the average number of ischemic episodes per 24 hours was significantly reduced during propranolol therapy compared with placebo (0.7 +/- 0.6 vs 3.9 +/- 1.8; p less than 0.0005). No significant differences were seen during verapamil treatment (3.4 +/- 1.7 vs 3.9 +/- 1.8). It is concluded that transient myocardial ischemia in syndrome X is mostly precipitated by an increase in oxygen consumption, presumably due to a heightened sympathetic activity. Accordingly, beta blockers may represent the first line of treatment.

Adult↗

Association of serum IgA antibodies to milk antigens with severe atherosclerosis.

The presence of antibodies of the IgA class against dietary antigens (bovine IgG (BGG), beta-lactoglobulin, casein, alpha-lactalbumin and xanthine oxidase, chicken ovalbumin and crude gliadin) was checked in the sera of 23 severely atherosclerotic subjects (ATS) and 20 highly selected controls (C). In these subjects an association between serum IgA levels and atherosclerosis had previously been shown. Determinations were performed by a micro-ELISA method and results were expressed as absorbances at 405 nm x 1000. Higher levels of IgA antibodies were found in ATS with respect to C against beta-lactoglobulin (respectively, 113.4 +/- 152.4 (1 SD) vs. 40.0 +/- 34.2; P less than 0.005) and casein (69.8 +/- 35.5 vs. 52.4 +/- 27.5; P less than 0.05). There was no difference in IgG and IgM against these 2 proteins between the 2 groups. Significant differences of prevalence of IgA antibodies were found for the following antigens: beta-lactoglobulin (4 C and 16 ATS over the limit value of 51; P less than 0.002), xanthine oxidase (1 C and 9 ATS over 289; P less than 0.01), BGG (7 C and 17 ATS over 87; P less than 0.02) and casein (5 C and 14 ATS over 60; P less than 0.02). These data suggest an association between anti-milk IgA antibodies and atherosclerosis. Its relevance and significance deserves further investigation.

Aged↗

ST/HR slope during prostacyclin treatment: an improved method to identify patients with advanced coronary artery disease.

Constriction of atherosclerotic coronary segments during exercise may further reduce coronary flow reserve in patients with coronary artery disease. This could influence the linear regression analysis of the heart rate-related changes in ST-segment depression (ST/HR slope) thereby limiting the accuracy of this method in identifying the severity of the disease. To test this hypothesis, the exercise related ST/HR slopes on placebo were compared with those obtained during coronary vasodilation induced by a prostacyclin analogue (iloprost 6 ng kg-1 min-1) in 42 anginal patients with documented coronary artery disease. In seven of these, the same protocol was repeated during right heart catheterization. The overall diagnostic accuracy of the ST/HR slope on iloprost was better than on placebo in patients with advanced coronary artery disease. This was due mainly to a consistent rightward shift of the ST/HR slope in patients with one- and two-vessel, but not three-vessel disease or left main stem disease. The reason for the greater effects of iloprost on ST/HR slopes in patients with a lesser degree of atherosclerosis remains unclear. However, coronary blood flow was higher during drug infusion, which suggests that iloprost may prevent the occurrence of dynamic coronary events able to reduce the maximum coronary flow reserve during exertion. This mechanism may be predominant in patients with minor coronary artery disease.

Adult↗

Bacterial lipopolysaccharide and gamma interferon induce transcription of beta interferon mRNA and interferon secretion in murine macrophages.

Bacterial lipopolysaccharide (LPS) induces interferon (IFN) secretion and an antiviral state in murine peritoneal macrophages (PM). These cells secrete predominantly IFN-beta, as shown by neutralization assays with monoclonal antibodies. Secretion of IFN-beta is also induced in PM by IFN-gamma. LPS and IFN-gamma synergistically stimulated PM to produce IFN in amounts almost comparable to those induced by infection with Newcastle disease virus. Low levels of IFN-beta mRNA can be detected in freshly harvested PM by hybridization assays. The accumulation of this mRNA is markedly increased in PM treated with LPS or IFN-gamma, and it is further enhanced in the presence of the inhibitor of protein synthesis, cycloheximide. Similar studies were carried out on the RAW 264.7 line of transformed macrophages. These cells are induced to secrete IFN-beta by LPS but not by IFN-gamma, suggesting that this cytokine may elicit such specific response only in PM. IFN-beta mRNA is undetectable in untreated RAW 264.7 cells, and accumulation of this mRNA is induced by LPS but not by IFN-gamma. The secretion of IFN induced by these agents in PM and by LPS in RAW 264.7 cells and the corresponding accumulation of IFN-beta mRNA are blocked by an inhibitor of protein kinase C, staurosporine. The activity of this kinase is apparently necessary to stimulate accumulation of IFN-beta mRNA. The induction of IFN-beta by IFN-gamma appears to be a characteristic response of PM and may be at least in part responsible for the resistance of these cells to viral infections.

Animals↗

[Abnormal coronary response to vasomotor stimuli: analogies between variant angina and X syndrome].

The aim of this study was to evaluate the effects of hyperventilation (HV) and of ic nitroglycerin (NTG) on coronary diameters and hemodynamics in 32 patients with angina pectoris. Of these, 10 patients had stable angina and critical coronary artery disease (CAD, Group I), 12 patients with variant angina (VA) and no or minor coronary atherosclerosis (Group II), and 10 patients with angina and normal coronary arteries (syndrome X (SX), Group III). All patients underwent coronary angiography as well as right heart catheterization; measurements of left anterior descending coronary diameters (mid segment), great cardiac vein blood flow, aortic pressure and coronary resistance were performed on baseline, after HV and following NTG. HV caused coronary spasm in 4 patients with VA and significantly (p less than 0.001) reduced coronary diameters and regional blood flow both in Groups II and III, but not in Group I. NTG resulted in increased coronary diameters in all patients, however variations were greater in VA and SX (44 and 39%, respectively) than in Group I (18%; p less than 0.025). NTG induced an increase of coronary blood flow only in patients with CAD. We conclude that patients with VA and SX present a similar coronary response to vasomotor stimuli, either after HV or following NTG. Response is abnormal if compared to that of patients of group I, and it involves both epicardial and intramural coronary vessels. Thus, we suggest that SX and VA belong to a single pathogenetic entity with a spectrum of clinical manifestations.

Adult↗

Association of serum IgA and C4 with severe atherosclerosis.

To assess the possible involvement of humoral immunity in diffuse atherosclerosis, IgG, IgA, IgM, C3 and C4 were measured in the sera of 23 atherosclerotic subjects (at least 3 stenoses greater than 75% in the arteries of the limbs and neck, as assessed by panangiography) and of 20 controls (possible stenoses less than 40% documented by arteriography of the aortic arch and epi-aortic branches and "normal" response to exercise stress testing and Doppler ultrasonography of the arteries of the lower limbs). Age (59-69) and sex distribution did not differ significantly in the 2 groups. The following serum concentrations were higher in the atherosclerotic subjects than in the controls: C4 (28.7 +/- 6.5 (1 SD) vs. 23.4 +/- 3.8 mg/dl; P = 0.0013); IgA (323.3 +/- 155.0 vs. 210.3 +/- 87.9 mg/dl; P = 0.0020); and C3 (126.3 +/- 16.9 vs. 111.0 +/- 18.9 mg/dl; P = 0.0109). To assess whether these parameters were independently associated with atherosclerosis, a multiple logistic regression was performed, also including other variables which differed between the atherosclerotic group and the control group with P values less than 0.20 (cigarette smoking, arterial hypertension, body mass index, serum HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, serum triglycerides, IgG and IgM). In multivariate analysis only IgA (P = 0.0012), C4 (P = 0.0072), cigarette smoking (P = 0.0141) and serum triglycerides (P = 0.0177) were independently associated with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Angina of effort with a variable threshold: a unique entity due to different mechanisms?].

Variable threshold during exertion is a common feature in patients with chronic exertional angina. Changes in coronary vasomotor tone, when occurring at sites of critical narrowings, are a plausible explanation for variability of symptoms in these patients. However, the evidence supporting this hypothesis is still uncertain. Accordingly, we performed four computer assisted, multistage bicycle ergometer tests, without drugs, in 30 patients with chronic exertional angina, exercise induced ST depression, and a history of variable anginal threshold during exertion. Significant coronary artery disease was documented in each case by coronary arteriography. Patients were tested at the same time of day within a two week period. Comparison was made between each single test and the average of the remaining three. Time to 0.1 mV ST depression showed significant (+/- 20%) changes in 27 (90%) patients. Variability was shown in two out of four tests in 25 patients (83%), in three tests in 10 (33%), and in four tests in 2 (7%). Rate pressure product at 0.1 mV ST depression was concurrently changed (+/- 20%) in 20 patients (67%). Variability in two, three and four tests was observed in 7 (22%), 2 (7%) and 2 (7%) patients, respectively. Changes in time to 0.1 mV ST depression paralleled those in rate-pressure product at the onset of ischemia in 6 patients (22%) (dynamic ischemic threshold). Rate pressure product at 0.1 mV ST depression was unchanged despite variations in time to 0.1 mV ST depression in 10 patients (37%) (fixed ischemic threshold). The remaining 11 patients (41%) showed variable exercise tolerance associated with fixed (13 tests) and dynamic (13 tests) ischemic threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗