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2.
Eur J Clin Invest ; 27(8): 696-702, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9279535

ABSTRACT

A high incidence of alpha 1-antitrypsin (AAT) deficiency has been reported in patients with C-ANCA systemic vasculitis in association with antibodies against proteinase-3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C-ANCA or P-ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C-ANCA vs. P-ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C-reactive protein (PCR) (P < 0.001), with a less severe renal involvement or a minor risk of death, and, in one tested patient, with a novel point mutation (TCGA-->TCAA) at the enhancer-promoter region of the AAT gene. Low AAT serum levels did not correlate with either type/titre of autoantibody or distribution/severity of the vasculitis process. In the case-control study, high AAT levels emerged as a major determinant of progression towards end-stage renal failure [odds ratio 3 (95% CI 1.1-8.4)]. These results indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency associated with the normal PiM phenotype becoming manifest only during acute illness; (c) dysregulation of the acute-phase response affecting selectively AAT or both AAT and PCR; (d) correlation between low plasma levels of AAT and less severe renal involvement or risk of death.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/immunology , Granulomatosis with Polyangiitis/immunology , Granulomatosis with Polyangiitis/metabolism , alpha 1-Antitrypsin Deficiency , alpha 1-Antitrypsin/genetics , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Female , Genotype , Granulomatosis with Polyangiitis/genetics , Humans , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Phenotype , Prognosis , Proteins/analysis , Proteins/immunology , Sequence Analysis, DNA , Serine Proteinase Inhibitors/analysis , Serine Proteinase Inhibitors/immunology
5.
Adv Exp Med Biol ; 336: 435-40, 1993.
Article in English | MEDLINE | ID: mdl-8296651

ABSTRACT

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.


Subject(s)
Autoantibodies/blood , Glomerulonephritis/chemically induced , Glomerulonephritis/immunology , Immunoglobulin G/blood , Occupational Diseases/chemically induced , Silicon Dioxide/poisoning , Antibodies, Antineutrophil Cytoplasmic , Case-Control Studies , Glomerulonephritis/epidemiology , Humans , Male , Middle Aged , Necrosis , Occupational Diseases/immunology , Peroxidase/immunology
6.
Adv Exp Med Biol ; 336: 465-8, 1993.
Article in English | MEDLINE | ID: mdl-8296658

ABSTRACT

Eight untreated patients with an apparent renal-limited disease continued to maintain high titres of ANCA long after the onset of the disease and the start of dialysis. In spite of the high ANCA titres, three of them remained for a long time free of symptoms related to the disease. Three pts developed, at various times from the beginning of the disease, fatal pulmonary hemorrhages.


Subject(s)
Autoantibodies/blood , Glomerulonephritis/therapy , Immunoglobulin G/blood , Renal Dialysis , Antibodies, Antineutrophil Cytoplasmic , Glomerulonephritis/immunology , Humans , Peroxidase/immunology
8.
Minerva Chir ; 30(6): 311-22, 1975 Mar 31.
Article in Italian | MEDLINE | ID: mdl-1226242

ABSTRACT

Personal experience with phentonium, a new synthetic synaptolytic, in the treatment of 26 patients with gastric or duodenal ulcerous conditions and of 4 other patients with gastroduodenitis is reported. Some subjective symptoms (pain, pyrosis, etc.) were taken into consideration and radiographic controls were carried out before and after treatment in order to determine the effect on the evolution of the ulcer niche. Phentonium was administered initially in all cases by the parenteral route (intravenous or intramuscular) in the dose of 10, 20 or 40 mg daily, according to the clinical picture, in one or two divided doses for varying periods (on the average 25 days) and in half the cases treatment was continued by the oral route at the dose of 60-80 mg daily (3-4 tablets) for about 20 days; in 3 cases treatment was continued by the oral route at the dose of 60-80 mg daily (3-4 tablets) for about 20 days; in 3 cases treatment was continued respectively for 5, 14 and 15 months. The therapeutic effect was evaluated as very favourable in 24 cases, discrete in 4 cases, scarce or absent in 2 cases. The time of disappearance or marked attenuation of the symptoms was very brief. The general tolerability of the preparation was excellent. On the basis of the observations made, it is concluded that phentonium represents an effective drug with a high therapeutic index in the treatment of ulcerous disease.


Subject(s)
Parasympatholytics/therapeutic use , Peptic Ulcer/drug therapy , Adult , Aged , Drug Evaluation , Female , Gastritis/drug therapy , Humans , Male , Middle Aged
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