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Biomedical subjects

A Agostoni

Publications and source records attributed to A Agostoni.

At least 19 recordsLinked to original sources
PubMed1992

Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease.

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.

Adult↗
PubMed1992

Peripheral edema due to increased vascular permeability: a clinical appraisal.

The release of vasoactive substances produces reversible changes of endothelial permeability with consequent edematous syndromes. We present 899 patients referred to our clinic for "non-hydrostatic non-hyponcotic" recurrent edema problems. Personal and family histories were recorded and a complete physical examination was carried out for each patient. In chronic situations laboratory tests [blood cell count, cryoglobulins, thyroid hormones, complement components (C3, C4, C1 inhibitor), total IgE, skin testing] were performed. Four subgroups of angioedema are identified for relevant clinical and etiopathogenetic differences. Seventy-three percent of patients had an urticaria-angioedema syndrome responding to antihistamine and/or corticosteroid treatment (histamine-dependent angioedema). Twenty-three percent had an angioedema related to a deficiency in C1 esterase inhibitor (complement-dependent angioedema). In a minority of patients, angioedema was due to the pharmacological effect of a drug (pharmacological angioedema) or was of a totally unknown origin (idiopathic angioedema). A generalized increase in vascular permeability was reported in 3 patients (systemic capillary leak syndrome). A brief survey of the literature is given with the review of our patients.

Adolescent↗
PubMed1992

Erythrocyte antioxidant activity, serum ceruloplasmin, and trace element levels in subjects with alcoholic liver disease.

Erythrocyte antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and reduced glutathione, serum ceruloplasmin, and serum trace elements (copper, zinc, iron, and selenium) related to antioxidant enzymes were assayed in subjects with alcoholic liver disease of different degrees of severity. The erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis had an unbalanced antioxidant system (normal superoxide dismutase, low catalase and glutathione peroxidase activities, and low glutathione content). Serum ceruloplasmin levels were in the normal range. Levels of the serum trace elements zinc and selenium were significantly low in subjects with moderate and severe cirrhosis, whose red cell half-life was also significantly short, as measured by radioactive chromium. These data suggest that the erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis are less protected against oxidant stress. The particular erythrocyte antioxidant system and serum trace element pattern may play a role in the genesis of hemolytic disorders and of alcoholic hepatic damage.

Adult↗
PubMed1992

Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients.

Two hundred and twenty-six patients with inherited C1 inhibitor (C1-INH) deficiency, also known as hereditary angioedema (HAE), have been studied. They belonged to 80 unrelated families, and in 11 of them C1-INH was functionally deficient but antigenically normal (type II HAE). Genetic analysis of type 1 families demonstrated restriction fragment length polymorphisms in 11% and abnormal mRNAs in 25%. In type II families, the site of the mutation appeared to determine the rate of catabolism of the dysfunctional C1-INH and its antigenic plasma levels. Clinical symptoms (subcutaneous and mucous swellings) generally first appeared within the second decade of life. The frequency of symptoms was highly variable from patient to patient, but a few patients remained asymptomatic throughout their lives. Prophylactic treatment with attenuated androgens was administered to 59 patients and was totally effective in 57, without significant side effects. Sixty-seven laryngeal and 15 abdominal attacks were treated with C1-INH plasma concentrate, yielding initial regression of symptoms in 30 to 90 minutes. The acquired deficiency of C1-INH, also known as acquired angioedema, was diagnosed in 9 patients. Eight of them had an autoantibody against C1-INH; the only patient without the autoantibody had associated chronic lymphocytic leukemia. Prophylactic treatment with attenuated androgens was effective in this last patient, while those with the autoantibody against C1-INH benefited from prophylaxis with antifibrinolytic agents. Replacement therapy with C1-INH concentrate was necessary only for patients with autoantibodies and required doses 3 or 4 times higher than those used in HAE.

Adolescent↗
PubMed1992

Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy.

A collaborative survey was carried out in Italy on a group of 59 subjects with a past history of meningococcal meningitis. The aim was to evaluate the prevalence of complement deficiencies, the serogroup of meningococci responsible for the disease and other possible immune abnormalities associated with the infection. Complement analysis allowed the detection of 10 cases (17%) with deficiencies of the terminal components, and in particular six cases of C8 beta, three of C7 and one of C6 defect. Half of the subjects with complement deficiencies had recurrences of meningitis and developed the infection at an older age in comparison with the control group with normal complement activity. The meningococcal C strain was the most diffuse (68%) and infected all the complement-deficient subjects. Evaluation of the antibody response to meningococcal capsular polysaccharides (PS) showed that only 42.5% of the individuals with group C had antibodies as opposed to 83% and 100% of the patients with meningitis due to group A and B, respectively. In all 59 subjects serum Ig as well as IgG subclasses were present, at normal levels for the age. Vaccination of seven out of the 24 subjects without detectable anti-meningococcal PS antibodies with the sole PS A+C induced a normal response in six of them, including a subject with complement defect. In the subject who did not respond to the antigen, the antibodies against the ubiquitous pneumococcal PS type 14 were also lacking, whereas anti-tetanus toxoid (TT) antibodies were normally present. From these data we may conclude the following: (1) the high prevalence (17%) of late complement components defect among survivors of meningococcal meningitis is also confirmed in the Italian population; (2) the serogroup C, responsible for the infections in all the cases with late complement components defect, is highly recirculating in Italy and apparently less immunogenic; (3) specific vaccination with meningococcal PS is a valid prophylaxis in subjects with lack of specific antibodies as well as in subjects with complement defect.

Adolescent↗
PubMed1992

Leukotriene B4 and peptido-leukotriene levels during radiographic contrast media infusion.

The pathogenic mechanisms of radiographic contrast media (CM) reactions are still not well understood. Recently it has been proposed that leukotrienes (LT) may be involved in CM reactions. We measured plasma LTB4 and peptido-LT levels in 20 subjects undergoing urography with 2 low osmolality CM (ioxaglate and iopamidol) in order to elucidate if CM infusion determines LT release in plasma. LTB4 and peptido-LT did not change significantly during infusion of the 2 CM. Blood pressure, heart rate, and the number of circulating granulocytes were not affected by CM infusions, further evidence that LT release did not occur. We conclude therefore that LT are not released during infusion with the CM studied.

Adult↗
PubMed1992

Tissue-type plasminogen activator and von Willebrand factor plasma levels as markers of endothelial involvement in patients with Raynaud's phenomenon.

In order to investigate the significance of high circulating levels of von Willebrand factor (vWF), recently observed in patients with vascular diseases, we compared the plasma levels of vWF with those of tissue-type plasminogen activator (t-PA) and the platelet content of serotonin (5-HT) in 40 patients with Raynaud's phenomenon (RP), primary or associated to systemic sclerosis (SSc), and in 14 patients with chronic peripheral obstructive disease due to arteriosclerosis (PAOD). VWF and t-PA plasma levels were significantly increased (p < 0.001) in SSc (vWF: 158.2, range 116.3-305.0%; t-PA: 10.2, range 6.4-17.8 ng/ml). By contrast, normal plasma levels of both vWF (85.3, range 53.5-157.0%) and t-PA (6.5, range 2.7-9.3 ng/ml) were observed in primary RP. VWF and t-PA were normal in PAOD patients, compared with age-matched healthy controls (vWF: 143.0, range 57.0-204.0%; t-PA: 7.5, range 3.4-13.6, ng/ml). The platelet content of 5-HT was within the normal range (37.3-99.7 ng/10(8) platelets) in RP patients, but significantly reduced (P < 0.05) in PAOD patients (39.0, range 14.7-91.4). Our data suggest that the different pattern of circulating vWF and t-PA between SSc and arteriosclerotic patients may be related to a different endothelial cell involvement. Whether this increase may reflect active attempts of regeneration and repair, indicating endothelial cell viability rather than damage is a matter of speculation.

Adult↗
PubMed1991

L-arginine therapy in Raynaud's phenomenon?

Since L-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects of L-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynaud's phenomenon. After therapy, patients with Raynaud's phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.

Adolescent↗
PubMed1991

Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience.

Fifty-six patients affected with hereditary angioedema have been followed during long-term prophylaxis with attenuated androgens. The treatment was started in patients who had one or more severe attacks per month. In 24 patients, the therapy lasted for more than 5 years. The minimal effective dose usually did not exceed 2 mg/day of stanozolol or 200 mg/day of danazol. Only in two patients were these doses not sufficient to achieve the complete disappearance of symptoms. Irregular menstruation, but rarely amenorrhea, was the only significant side effect. One patient had to stop the therapy because of laboratory signs of hepatic cell necrosis. In one patient, danazol was administered during the last 8 weeks of pregnancy without side effects for the mother but with transient signs of virilization for the female baby. To find a biochemical marker for the minimal effective dose of androgen derivatives, we measured the plasma levels of C1 C1 INH complexes at different doses of stanozolol in four patients with hereditary angioedema. We found that these complexes, elevated before treatment, promptly reverted to normal values during androgen therapy and remained normal with any reduction of the dose of the drug as long as the patient remained symptom free. Therefore, the measurement of C1 C1 INH complexes appears to reflect the activity of the disease and not the amount of androgen that is administered.

Adolescent↗
PubMed1991

Nonsense mutations affect C1 inhibitor messenger RNA levels in patients with type I hereditary angioneurotic edema.

Members of two unrelated families with type I hereditary angioneurotic edema (HANE) were found to have elevated levels of C1 inhibitor (C1INH) mRNA. DNA sequence analysis of PCR-amplified monocyte C1INH mRNA revealed normal and mutant transcripts, as expected in this disorder that occurs in heterozygous individuals. Single base mutations near the 3' end of the coding sequence were identified in affected members of each family. One mutation consisted of insertion of an adenosine at position 1304 which created a premature termination codon (TAA), whereas the second consisted of deletion of the thymidine at position 1298 which created a premature termination codon (TGA) 23 nucleotides downstream. These mutations are approximately 250 nucleotides upstream of the natural termination codon. Nuclear run-off experiments in one kindred revealed no difference in transcription rates of the C1INH gene between the patients and normals. C1INH mRNA half-life experiments were not technically feasible because of the prolonged half-life of the normal transcript. Dideoxynucleotide primer extension experiments allowed the differentiation of the normal and mutant transcripts. These studies showed that the mutant transcript was not decreased relative to the normal, and this therefore was at least partially responsible for the C1INH mRNA elevation. This elevation may be due to the decreased catabolism of the mutant transcript.

Angioedema↗
PubMed1991

Cold-induced changes in plasma norepinephrine, epinephrine and dopamine concentrations in patients with Raynaud's phenomenon.

To investigate the role of the sympathetic system in Raynaud's phenomenon, which has not yet been elucidated, we measured the levels of norepinephrine, epinephrine and dopamine before, immediately and 30 min after the cold pressor test in plasma from 17 patients with primary, 6 with secondary Raynaud's phenomenon and 19 volunteers, matched for age and sex. Patients had significantly low baseline epinephrine (0.13 +/- 0.02 vs 0.37 +/- 0.04, nmol/l, p less than 0.001, mean +/- S.E.), but normal norepinephrine and dopamine (norepinephrine: 1.77 +/- 0.16 and 2.06 +/- 0.18; dopamine: 0.10 +/- 0.01 and 0.11 +/- 0.02, patients and controls). Immediately after the cold test norepinephrine significantly increased (p less than 0.001) in patients (2.42 +/- 0.22) and controls (3.24 +/- 0.28); epinephrine increased in patients (0.18 +/- 0.02, p less than 0.02); dopamine did not show any significant change (0.13 +/- 0.01 and 0.13 +/- 0.02, patients and controls). In the recovery period, while norepinephrine and epinephrine returned to baseline in both groups, dopamine increased in controls (0.21 +/- 0.04, p less than 0.005) but remained unchanged in patients (0.11 +/- 0.01). We conclude that there is no sympathetic overactivity in Raynaud's phenomenon and propose a role for circulating dopamine in post-ischaemic vasodilatation as an explanation for the particular behaviour of dopamine.

Adult↗
PubMed1991

Complement activation in diabetes mellitus.

To see whether or not there is complement activation in patients with diabetes mellitus, we investigated the plasma concentrations of C4, C3, C4a, C3a and SC5b-9 in either juvenile or adult onset insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients at least 2 years after diagnosis. C4, C3, SC5b-9 plasma levels were not significantly different in IDDM and NIDDM patients than in age-matched controls. Anaphylatoxin peptide conversion product C4a, but not C3a, was found significantly higher in adult-onset IDDM patients than in patients with juvenile onset IDDM, NIDDM patients and age-matched controls. Complement activation did not appear to be correlated with the metabolic control, nor the duration of disease nor the presence of circulating antibodies (including islet cells (ICA), insulin (IA), thyroid microsomal (TMA), and thyroglobulin (TGA)). Although there are many factors that may trigger complement activation, we found the highest levels of C4a in elderly subjects (both diabetics and control subjects) and particularly in those who had clinically detectable vascular complications.

Adolescent↗