[The role of anti-nucleosome antibodies in systemic lupus erythematosus. Results of a study of patients with systemic lupus erythematosus and other connective tissue diseases]. / Ruolo degli anticorpi anti-nucleosomi nel lupus eritematoso sistemico. Risultati di uno studio condotto in pazienti con lupus eritematoso sistemico ed altre connettiviti sistemiche.

OBJECTIVE: The aim of our study was to investigate the prevalence and the disease specificity of anti-nucleosome antibodies in systemic lupus erythematosus and their association with disease activity and renal involvement. METHODS: Anti-nucleosome antibodies were measured by ELISA in the sera of patients with systemic lupus erythematosus (SLE) (47), rheumatoid arthritis (RA) (22), mixed connective tissue disease (MCTD) (19), systemic sclerosis (SSc) (11) and Sjögren's syndrome (SS) (10). Anti-dsDNA antibodies were measured by IIF on Crithidia luciliae. In the patients with SLE serum levels of C3 and C4 complement components were also measured. Sera of 22 healthy individuals were assayed as controls. SLE activity was evaluated by the ECLAM score. RESULTS: Anti-nucleosome antibodies were found in 40 patients with SLE (85.1%), in 10 with RA (45.4%), in 8 with MCTD (42.1%), in 4 with SSc (36.3%), in 1 with SS (10%) and in none of the healthy controls. Anti-dsDNA antibodies were found in 23 patients with SLE and were absent in the patients with other CTD and in controls. All the patients with SLE and renal involvement were positive both for anti-dsDNA antibodies and anti-nucleosome antibodies. No significant correlation was observed between anti-nucleosome antibodies and disease activity and renal involvement. CONCLUSION: Anti-nucleosome antibodies are present in a high percentage of the patients with SLE but they don't seem to be specific markers of the disease. Our data don't support a clear correlation between anti-nucleosome antibodies and disease activity and renal involvement.

Cerebral vasculitis in a patient with HCV-related type II mixed cryoglobulinemia.

The peripheral nervous system is often involved in patients with mixed cryoglobulinemia (MC), while there are few reports of central nervous system involvement. We describe a case of HCV-related type II MC with peripheral and central nervous system involvement. A 61-year-old woman, suffering from flaccid tetraparesis, was referred to our department because of an increasing disability. The presence of delirium prompted us to also investigate the central nervous system. MMSE, EEG, EMG, brain CT-scan, color-Doppler of neck vessels, retinal fluorangiography and brain MRI were performed. These investigations suggested a cerebral vasculitis. The finding of very low C4 serum levels, together with high rheumatoid factor serum levels, suggested the search for cryoglobulins. The laboratory findings showed a HCV-related type II (IgMk) MC. A marked improvement of symptoms and of laboratory data was obtained by treatment with methylprednisolone + cyclophosphamide.

[Idiopathic hypereosinophilic syndrome associated with rheumatoid arthritis. A case report]. / Sindrome ipereosinofila idiopatica ed artrite reumatoide. Descrizione di un caso.

The idiopathic hypereosinophilic sindrome (HES) is a disease characterized by persistent blood eosinophilia (> 1500 eosinophils/mm3 > 6 months) -in absence of other ethiologies for eosinophilia (parasitic, allergic, immunological or malignant diseases)- associated with multiple organ involvement (heart, lung, central nervous system, skin, bone marrow, gastrointestinal tract). Reports on rheumatologic manifestations in patients with HES are very rare. In the case we report a typical rheumatoid arthritis developed in a 58-year-old woman with HES treated with glucocorticoids. Because of the marked glucocorticoids side effects shown by the patient (cushingoid habitus, hyperglycemia), we stopped this treatment and replaced it at first by methotrexate and later by cyclosporin, both of them associated with sulfasalazine. These drugs revealed very efficacious both on articular pathology and on the clinical and laboratory manifestations of HES. These data suggest that common pathogenetic mechanisms are likely acting in rheumatoid arthritis and idiopathic hypereosinophilic syndrome.

Influence of 5-fluorouracil and folinic acid on interleukin-18 production in colorectal cancer patients.

AIMS AND BACKGROUND: This study was carried out to evaluate the IL-18 blood concentrations of operated colorectal cancer patients and their possible variation in response to combination chemotherapy with 5-fluorouracil (5-FU) and folinic acid. METHODS: IL-18 levels were assayed in sera of 18 healthy donors and 18 surgical colorectal cancer patients before and after adjuvant chemotherapy with 5-fluorouracil and folinic acid. An ELISA kit for human IL-18 was used for the assay. RESULTS: Colorectal cancer patients showed significantly higher baseline levels of IL-18 than healthy donors (p<0.005). Furthermore, serum IL-18 levels increased significantly with respect to baseline in patients receiving adjuvant chemotherapy (p<0.005). CONCLUSIONS: This study suggests that treatment with 5-fluorouracil and folinic acid may provoke an increase in IL-18 serum levels in colorectal cancer patients. This increase may help to explain the efficacy of adjuvant chemotherapy with 5-FU in colorectal cancer.

Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

[Anticardiolipin antibodies in hemodialysis patients and in renal transplant recipients: prevalence and significance]. / Anticorpi anticardiolipina in pazienti in emodialisi e con trapianto renale: prevalenza e significato.

Increased anticardiolipin antibodies (aCL) serum levels have been recently described in haemodialysis patients and in renal transplant recipients, with a prevalence ranging from 4.8 to 46.4%. The causes and the clinical significance of aCL positivity in these patients are uncertain. We measured IgG- and IgM-aCL serum levels in 61 haemodialysis patients, in 14 renal transplant recipients and in 38 healthy controls. Increased levels of IgG-aCL were found in 4 haemodialysis patients (6.55%), in 2 transplant patients (14%) and in 2 of the healthy controls (5.26%). IgM-aCL serum levels were normal in all the patients. After one year of follow-up, no vascular events have been observed in aCL positive patients. It is probable that the presence of aCL in the serum of patients with end-stage renal disease is only an epiphenomenon and does not play a pathogenetic role.

Population distribution of alcohol dehydrogenase class I in France: comparison with other populations, and distribution with respect to gender and age. The French Group for Research on Alcohol and Liver.

In Caucasians, a genetic polymorphism is known for some alcohol dehydrogenase (ADH) systems (beta and gamma). Knowledge of population frequencies of the beta and gamma hepatic isozyme variants in France is a prerequisite to understanding any role this genetic variation might play in determining the risk of alcohol-related diseases. For the present study, the ADH phenotypes of 115 French Caucasian control subjects, consisting of 64 men and 51 women, were studied. The beta2 subunit was found to have a very low frequency. The relative frequencies of ADH gamma subunits observed in French Caucasians were found to be in good agreement with those already observed in other Caucasian populations. When gender and age were taken into account, a particular group corresponding to young men (age <50 years) was characterized by a manifest discordance with the comparable female population.

[High levels of blood IgA in patients with rheumatoid arthritis]. / Alti livelli di IgA seriche in pazienti con artrite reumatoide.

MATERIALS AND METHODS: Serum levels of IgA, IgG and IgM were measured in 46 patients (34 women, 12 men) with rheumatoid arthritis. The duration of the disease ranged from 6 months to 30 years; the patients follow-up ranged from 6 months to 12 years. RESULTS: Serum IgA levels higher than the normal (> 450 mg/dl) were found in 20 patients (43.4%). These patients had mean levels of IgG, C3c and erythrocyte sedimentation rate significantly higher than the patients with normal IgA levels. CONCLUSIONS: A significant relationship between the IgA levels and the activity of the disease or its clinical and radiological features was not observed. On the other hand, a relationship was observed between IgA levels and the mean duration of the disease which was significantly more prolonged in patients with high IgA serum levels.

Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms.

In this study the GSTmu phenotype and ADH genotype at the ADH3 locus were investigated in a group of 39 alcoholic men with upper respiratory/digestive tract cancer: 21 with oropharyngeal cancer and 18 with laryngeal cancer. The results are compared with those of a control group of 37 alcoholic men without alcohol-related medical complications. Of the control subjects, 48% were found to be GSTmu deficient [GSTmu(-)] and 19% carried the ADH(3)1/ADH(3)1 genotype. In the laryngeal cancer patients, a significantly elevated frequency of both the GSTmu(-) (78%) and ADH(3)1/ADH(3)1 genotype (56%) was observed, relative to the control group. On the basis of this result, the risk of laryngeal cancer associated with the GSTmu(-) and ADH(3)1/ADH(3)1 genotypic combination within the population of alcoholics was estimated to be 12.9 with a 95% confidence interval of 1.8-92 (P < 0.01) relative to alcoholic individuals who have GSTmu [GSTmu(+)] and are not ADH(3)1/ADH(3)1. Thus, alcoholics who are GSTmu(-) and ADH(3)1/ADH(3)1 have at least an 80% greater risk of developing laryngeal cancer than alcoholics who are GSTmu(+) and who are not ADH(3)1/ADH(3)1. In addition, the oropharyngeal cancer patients had excess frequencies of both GSTmu(-) (62%) and ADH(3)1/ADH(3)1 (43%) relative to the control group, but these excess frequencies were not statistically significant. The GSTmu(-) and ADH(3)1/ADH(3)1 genotypic combination may be a constitutional risk factor for laryngeal cancer among alcoholics.

Eosinophilic fasciitis: report of a case diagnosed 14 years after its onset.

The authors describe a case of eosinophilic fasciitis diagnosed 14 years after the onset of the clinical and laboratory manifestations of the disease. Failure to carry out an adeguate histopathological examination during this period played a role in delaying diagnosis.

[Connections between ischemic heart disease and anti-cardiolipin antibody positivity]. / Sui rapporti tra cardiopatia ischemica e positività per anticorpi anti-cardiolipina.

IgG and IgM anti-cardiolipin antibodies (aCL) were measured in 60 patients with ischaemic heart disease by an immunoenzymatic assay. aCL levels higher than normal were detected in 12 of 40 patients (30%) with acute myocardial infarction (AMI) and in 7 of 20 patients (35%) with angina pectoris (AP). These values were significantly higher (p < 0.05) than those detected in the control group (3/40; 7.5%). As regards the clinical picture, the complications and the outcome of the disease, no difference was observed between aCL-positive and negative patients with AMI. 9 of 12 aCL-positive patients with AMI showed increased levels of aCL in a blood sample obtained in day 1 after admission. Therefore, we must admit such positivity as preexistent to the myocardial infarction. These data together with the high prevalence of aCL in patients with AP suggest that an association should exist between raised levels of aCL and increased risk for AMI in patients with coronary artery disease.

Abdominal attack of hereditary angioedema associated with marked leucocytosis. A case report.

Hereditary angioedema (HAE) attacks are not usually associated with an increase of peripheral blood leucocytes. In a 25-year-old woman suffering from HAE a marked leucocytosis (31,000/mm3) with polynucleosis was observed during a severe attack of the disease. Awareness of the underlying disease, physical examination and the results of instrumental investigations allowed for appropriate treatment avoiding invasive procedures. A leucocytosis of the severity observed in our patient suggests that the abdominal attack of HAE can involve the peritoneum as well as the intestinal mucosa. Thus, in a patient with an attack of abdominal pain the presence of leucocytosis does not exclude the diagnosis of HAE.

[Presence and significance of anticardiolipin antibodies in infectious diseases]. / Sulla presenza e sul significato degli anticorpi anti-cardiolipina nelle malattie infettive.

IgG and IgM anti-cardiolipin antibodies were measured, by an ELISA technique, in the sera of patients with B hepatitis (28), infectious mononucleosis (10), chicken pox (12), HIV infection (20), acquired toxoplasmosis (41) and other infectious diseases [HBsAg+ chronic hepatitis (5), brucellosis (6), herpes zoster (4), boutonneuse fever (3), viral pneumonitis (4), rheumatic fever (2)]. Increased levels of anti-cardiolipin antibodies (aCL), at least in one immunoglobulin class, were detected in 37 out of 135 patients [27.4%; range: 7.3% (in the patients with toxoplasmosis) -80% (in the patients with HIV infection)]. Low or medium titer aCL were present in 28 patients, high titer in 9 (6 with HIV infection, 2 with chicken pox and I with lymphoadenopathic toxoplasmosis). None of the manifestations associated with aCL was present in the aCL-positive patients. Finally, positivity for aCL didn't seem to modify the clinical picture and the prognosis of the infectious disease.

[Alcohol and idiopathic dilatated cardiomyopathy: a pathogenetic hypothesis]. / Alcool e cardiomiopatia dilatativa idiopatica: una ipotesi patogenetica.

In a group of 120 chronic alcoholics, we observed two cases of severe dilated cardiomyopathy, fatal within a year, similar to the so called "idiopathic" form, among cases of cardiovascular involvement related to alcohol abuse (63.5%) but susceptible of improvement following abstention. On the basis of their observation we believe that alcohol itself, as has already been demonstrated for certain viruses, in the presence of particular genetic factors can cause the onset of an immune reaction able to impart an autonomous course which cannot be checked even after abstention from alcohol.

[Clinical contribution to the problem of correlations between hereditary angioneurotic edema and pregnancy]. / Contributo clinico al problema dei rapporti tra edema angioneurotico ereditario e gravidanza.

Hereditary angioneurotic edema (HAE) is an autosomal dominant disease caused by a deficiency of a complement regulatory protein, the C1INH.HAE is clinically characterized by recurrent, self-limited attacks of edema involving the extremities, face, upper respiratory tract or gastrointestinal tract. Pregnancy in a woman affected by HAE poses therapeutical problems. In fact, prophylactic treatment with danazole or tranexamic acid is control indicated in a pregnant woman. However HAE shows a favourable course in most cases and the delivery, despite the local trauma, is not usually associated with complications. But the occasional occurrence of local edema and the literature report of a death in postpartum, suggest the administration of purified C1INH prophylactically before the delivery. HAE, per sé, neither alters the evolution of pregnancy nor does foetus harm. The A. report on a 22-years old primigravida affected by HAE. She had no attack during the whole gestation, the delivery and the postpartum. She was given 1000 units of purified C1INH concentrate both four hours before the delivery and 24 hours after it.

[Antithrombin activity in chronic obstructive bronchopneumopathy]. / Attività antitrombinica nelle broncopneumopatie croniche ostruttive.

In a group of 22 patients affected by chronic obstructive bronchopathies (COBP) with respiratory insufficiency and at the same time in a group of 12 controls, were determined plasma Antithrombin (AT) III concentrations. The mean of AT III level in patients with COBP was 40.5% and was 96.8% in the controls. On the basis of these data, the authors think that in patients with COBP decrease AT III can cause the rising of bleeding complications.