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Biomedical subjects

A Agostoni

Publications and source records attributed to A Agostoni.

At least 91 records · Page 5Linked to original sources

Inherited C1 inhibitor deficiency.

The paper reports our experience of a 15-year follow-up of 179 patients with hereditary angioedema (HAE). The disease is transmitted as an autosomal dominant trait and two variants have been described: type I characterized by functional and antigenic C1-inhibitor (C1-INH) deficiency and type II with normal or upper normal C1-INH antigenic levels but no functional activity. The clinical picture is characterized by self-limiting bouts of swelling in the subcutaneous and/or mucous tissues. Data about frequency, localization and possible triggering factors of HAE attacks are reported. Analysis of genomic DNA from our patients using a C1-INH cDNA probe demonstrated the presence of restriction fragment length polymorphisms tightly linked with the disease in a minority of them. Data concerning prophylaxis and treatment of HAE attacks are also shown.

Angioedema↗

Complement activation during hemodialysis.

Hemodialysis, as other extracorporeal circulation treatments, determines activation of the complement system. In this paper molecular mechanism of complement activation by different hemodialysis membranes are reviewed as well as the biological consequences and clinical relevance of the activation.

Anaphylatoxins↗

Platelet and plasma serotonin in patients with liver cirrhosis.

To evaluate the role of serotonin in liver cirrhosis, serotonin was determined by high-performance liquid chromatography in plasma, platelets and ascitic fluids from 14 cirrhotic patients. Plasma-free serotonin was within the normal range, but intraplatelet serotonin was significantly low in cirrhosis (p less than 0.001) and this decrease paralleled the severity of the disease. The concentration of serotonin in ascitic fluids was 12% of the corresponding plasma concentrations. Our data indicate that serotonin levels are influenced by hepatic injury, but the reasons for these changes are still unclear.

Ascitic Fluid↗

Ketanserin treatment and serotonin in patients with primary and secondary Raynaud's phenomenon.

In a double-blind, placebo cross-over study in 14 patients with Raynaud's disease, oral ketanserin 40 mg b.d. for two months reduced the number of digital ischaemic attacks in 36% of the patients, with no difference between primary or secondary cases. Intraplatelet and circulating serotonin concentrations were significantly higher in patients than in controls. During treatment there was a significant decrease in intraplatelet serotonin, but no change in circulating serotonin or in the amount of serotonin released by platelets in vitro. The results suggest that oral ketanserin is of minor help in Raynaud's phenomenon and they support a role for serotonin in the disorder.

Adolescent↗

Plasma free and intraplatelet serotonin in patients with Raynaud's phenomenon.

Plasma free and intraplatelet serotonin concentrations were measured by high-performance liquid chromatography coupled with electrochemical detection, in 30 patients with Raynaud's phenomenon of various etiologies. Serotonin was significantly higher in plasma (P less than 0.005) and in platelets (P less than 0.005) from Raynaud's patients than from normal controls. Moreover, plasma circulating serotonin could differentiate primary from secondary Raynaud's phenomenon, with significantly higher levels (P less than 0.05) for patients with an underlying connective tissue disease. Our data indicate a role for serotonin in Raynaud's phenomenon.

Adolescent↗

The proposal of the Italian Committee on Occupational Cardiology.

This paper describes a protocol of assessing specific working fitness of post-myocardial infarction patients proposed by the Italian Committee on Occupational Cardiology. After cardiovascular (cross-sectional echocardiography, Holter monitoring and maximal symptom-limited ergometric test) and psychological evaluation (CBA-2.0), two ambulatory ECGs were used during work to confirm the first judgement of specific work fitness expressed by occupational specialists. The preliminary results obtained in 106 uncomplicated male patients (mean age 49 +/- 8 years) show that: (i) return to work (89.6%) at 117 +/- 51 days after the acute event is mainly related to socio-occupational variables rather than to cardiovascular status; (ii) the results of the ambulatory monitoring usually confirm the first judgment of specific work fitness; (iii) heart rate responses recorded during work are unrelated to the judgment of fitness; and (iv) the repeatability of the results observed during the two ambulatory ECGs at work is good.

Adult↗

CO binding to hemoglobin and myoglobin in equilibrium with a gas phase of low PO2 value.

The aim of this paper was to measure the binding of CO to myoglobin and hemoglobin at various PO2 values. For this purpose we have studied an "in vitro" system made up of solutions of hemoglobin and myoglobin equilibrated in two connected tonometers with the same gas phase of various PO2 and PCO. The results indicate that a significant proportion of CO is released by hemoglobin and binds myoglobin at low PO2 values (approximately 2-3 Torr), in qualitative agreement with the predictions of a previous computer simulation of the "in vivo" system.

Carbon Monoxide↗

Haemostasis contact system and fibrinolysis in hereditary angioedema (C1-inhibitor deficiency).

Factors of the classical complement pathway, the contact system and fibrinolysis were evaluated both with functional and immunochemical methods, in patients with inherited deficiency of C1-inhibitor. Evaluations were performed under basal conditions, during acute attacks and during prophylaxis with low doses of anabolic steroids. Patients in the basal state showed no significant abnormalities of any of the parameters that we investigated. During acute attacks a slightly reduced prekallikrein concentration was registered. During treatment with low doses of danazol and stanozolol, protein C and plasminogen were found to be increased. Our data suggest that C1-inhibitor deficiency per se does not lead to a derangement of the fibrinolysis and coagulation contact system, and that the kinin system may be involved during acute attacks of angioedema.

Adolescent↗

Antioxidant system and serum trace elements in alpha-thalassaemia and Hb Lepore trait.

Erythrocyte antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase were found to be significantly high in subjects with alpha-thalassaemia and Hb Lepore trait, as a consequence of the increased oxidant stress which is known to exist in these conditions. Among the serum trace elements present in these enzymes, selenium was increased in subjects with Hb Lepore trait and significantly low in those with alpha-thalassaemia trait, while selenium erythrocyte content was significantly increased in alpha-thalassaemic subjects.

Adult↗

Restriction fragment length polymorphism of the C1 inhibitor gene in hereditary angioneurotic edema.

Hereditary angioneurotic edema (HANE) results from the deficiency of the inhibitor of the first component of human complement (C1-INH). It is inherited as an autosomal dominant trait. Heterogeneity of this defect has been shown at the protein and mRNA level. Southern blot analysis of genomic DNA was performed after digestion with six different restriction endonucleases in 24 families affected with type 1 HANE (low antigenic and functional C1-INH levels) and five with type 2 (low functional C1-INH levels and normal or elevated levels of dysmorphic C1-INH). Blots were hybridized with a C1-INH cDNA probe of 1,227 bp. With one enzyme (Pst I), two different patterns of restriction fragment length polymorphism (RFLP) were detected. One was present in one kindred with type 1 HANE and the other appeared the same in one type 1 and in one type 2 family, thus indicating that each RFLP resulted from a different mutation. Analysis of a total of 34 members of these three families suggested that the polymorphisms are tightly linked to the mutation responsible for the disease. Using a 170-bp probe we showed that the three different mutations leading to these polymorphisms are located in the same region of the C1-INH gene. These data suggest that different mutations in the same region of the C1-INH gene are responsible for C1-INH deficiency in these families. Most of these mutations are probably point mutations or other "minor" defects and do not appear to be due to major deletions or rearrangements.

Angioedema↗

Circulating dopamine in Raynaud's phenomenon.

Plasma free and conjugated and intraplatelet free dopamine, norepinephrine, and epinephrine levels were determined by high-performance liquid chromatography coupled with electrochemical detection for 20 subjects with Raynaud's phenomenon of various etiologies. Circulating free dopamine and epinephrine were significantly lower in Raynaud's patients than in controls (dopamine 26.0 +/- 13.6 vs 56.3 +/- 39.6 pg/ml, p less than 0.005; epinephrine 25.8 +/- 16.9 vs 56.9 +/- 40.9 pg/ml, p less than 0.005), while the corresponding conjugated forms in plasma and the intraplatelet contents were within normal limits. There were no abnormalities in plasma free, conjugated, or intraplatelet free norepinephrine. All of the levels were independent of the etiology, the duration, and the severity of the disease. The reduced plasma levels of free dopamine and epinephrine might be due to impaired adrenal release in response to some kinds of sympathetic stimulation or to rapid tissue uptake and peripheral metabolism. A possible role for a postischemic dopaminergic vasodilating system is discussed.

Adolescent↗

Cigarette smoking and platelet function.

To assess the influence of cigarette smoking on platelet activation, we studied the changes in intraplatelet and platelet-released serotonin (5-HT) and plasma levels and platelet-associated production of thromboxane B2 (TXB2), in 6 non smokers and 6 habitual smokers, before and after acute exposure to smoke. Before smoking, habitual smokers showed slightly higher, albeit not significantly, 5-HT platelet concentrations and TXB2 plasma levels, as well as lower TXB2 platelet production after collagen and even more after ADP stimulation (0.59 +/- 0.27 vs 1.35 +/- 0.46 and 0.99 +/- 0.47 vs 2.08 +/- 0.51 ng/10(8) platelets for habitual smokers vs controls, 4 and 10 min after ADP, p less than 0.02). No significant differences in platelet 5-HT release were observed. Acute smoking did not induce any significant change from baseline in either 5-HT or TXB2 for controls, while significantly reduced TXB2 production from ADP-challenged platelets from habitual smokers (0.30 +/- 0.15 vs 0.59 +/- 0.27 ng/10(8) platelets, immediately after smoking vs baseline, p less than 0.01). Ninety min after the completion of the smoking, the values had returned to baseline. Immediately after smoking, significant differences were found between habitual smokers and controls for TXB2 platelet production (2.76 +/- 1.78 vs 6.42 +/- 1.60, p less than 0.025 and 3.01 +/- 1.90 vs 6.44 +/- 2.26 ng/10(8) platelets, p less than 0.05, for habitual smokers vs controls, 4 and 10 min after the addition of collagen; 0.30 +/- 0.15 vs 1.20 +/- 0.84 and 0.79 +/- 0.50 vs 1.70 +/- 0.74 ng/10(8) platelets, p less than 0.05, after ADP stimulation). Differences were no longer significant 90 min after smoking. Our data indicate that cigarette smoking is associated with platelet dysfunction, which seems due to impairment of metabolic platelet capacity rather than increased platelet activation in vivo.

Adenosine Diphosphate↗

Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure.

Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means.

Acute Disease↗

In vivo study of the complement system during infusion of radiographic contrast media.

It has been claimed that activation of the complement system may play a role in reaction to radiographic contrast media (RCM) infusion. In order to clarify the effects of RCM on the complement system, three different parameters (CH50, C3a, and C1 inhibitor) were measured in 20 patients undergoing intravenous pyelography for diagnostic purposes. We found no significant changes in C3a levels, but CH50 and C1 inhibitor fell significantly at the different sampling times; however, the decreases lost significance when the data were corrected for hemodilution with the total protein content of each sample as a reference. We conclude that RCM infusion does not activate the complement system.

Complement Activation↗

Immunoreactive precipitation of C1 inhibitor protein from plasma of normal subjects and of patients with hereditary angioedema after isoelectric focusing.

C1-inhibitor is an acid glycoprotein, isoelectric point 3.5-3.6. Plasma of some patients with a variant form of hereditary angioedema contains high levels of functionless C1-inhibitor-albumin complex with an isoelectric point at 4.5-4.6. Therapy with Danazol, which increases C1-inhibitor levels, does not modify the isoelectric focusing pattern of such protein in patients with hereditary angioedema.

Adult↗

Serotonin levels in hypertension.

The present study examines the putative role of serotonin (5-hydroxytryptamine) in the pathogenesis of essential hypertension. Intraplatelet and plasma free serotonin levels, as well as the amounts released from aggregating platelets, were measured in six patients with untreated essential hypertension, using high performance liquid chromatography with electrochemical detection. Platelet serotonin contents were similar to those in age-matched controls. However, hypertensive patients showed significantly higher levels of plasma free serotonin as well as a significantly higher release from aggregating platelets, stimulated by collagen or adenosine diphosphate (ADP). These data suggest that serotonin may be involved in the pathogenesis of essential hypertension.

Adult↗