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Biomedical subjects

G Famularo

Publications and source records attributed to G Famularo.

90 records · Page 5Linked to original sources

Soluble CD8 antigen in systemic sclerosis.

In 15 patients suffering from systemic sclerosis (PSS) the function of CD8+ circulating lymphocytes was assayed by determining soluble CD8 antigen (sCD8) both in sera and in 48 hr PHA-conditioned media of peripheral blood mononuclear cells (PBMCs). Furthermore, the frequency of circulating activated CD8+ cells, which express DR antigens, interleukin-2 receptor, and transferrin-receptor, was determined by cytofluorographic analysis. The results of this preliminary study indicate that only in 6 PSS sera sCD8 was elevated as compared to healthy controls; furthermore, we found slightly increased sCD8 in culture media from PSS patients. The frequency of circulating activated CD8+ cells was similar both in PSS patients and in controls. Overall, our findings suggest that CD8+ cell activation is not a major phenomenon in PSS.

Adult↗

[Cyclosporin (CyA) and H2 antagonists].

An experimental study on rats in order to discovery any possible interaction between Ciclosporin (CyA) and H2-receptor antagonists has been carried out. The results obtained demonstrated that the serum levels of CyA were higher in rats treated with CyA and Cimetidine or Ranitidine, but not Famotidine. It is probable that the increase of ciclosporinaemia is the consequence of an increased hepatotoxicity due to administration of Cya in association with Cimetidine or Ranitidine.

Animals↗

Drug interaction between cyclosporin A and nizatidine in Sprague-Dawley rats.

The H2-receptor antagonists seem to be effective in prevention and treatment of stress ulcer in transplant recipients. In a previous study on rats, an increase was observed in cyclosporinaemia and hepatotoxicity after administration of cimetidine or ranitidine in association with cyclosporin A (CyA). On the contrary, famotidine does not influence the blood CyA levels. The aim of the study was to detect the possible synergistic nephro- and hepatotoxicity of nizatidine administered in association with CyA, assaying the serum creatinine, the ALT and AST levels, and histological features of thirty young male Sprague-Dawley rats, divided into 6 groups of five animals each. After 10 days, all the rats were sacrificed, their blood was collected to assay serum creatinine, ALT, AST and serum CyA levels: kidneys and livers were processed for light microscopy. The results obtained demonstrated that, while the level of creatinine was normal in each group, the average level of transaminase and the serum levels of CyA were significantly higher in the animals receiving the association of CyA and nizatidine. Furthermore, this group demonstrated a mild infiltrate of the liver characterized in some cases with eosinophilic polymorphonuclear cells. In light of the results obtained, it is probable that the increase of cyclosporinaemia is the consequence of an enhanced hepatotoxicity due to administration of CyA in association with nizatidine.

Animals↗

Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats.

H2-receptor antagonists, such as cimetidine (C), ranitidine (R) and famotidine (F) seem to be effective in the prevention and treatment of stress ulcer in transplant recipients receiving cyclosporin A (CyA). The aim of this study was to detect the possible synergistic nephro- and hepato-toxicity of these drugs, assaying the serum creatinine (SC), ALT, AST levels, and the histological features of 45 young male Sprague-Dawley rats, divided into nine groups of five rats each. After 10 days of treatment the results showed: (i) serum CyA levels were increased in the group receiving daily CyA (5 mg/kg) + R(5 mg/kg) (2430 +/- 403 ng/ml; p less than 0.05 vs. controls) and in the group receiving daily CyA (5 mg/kg) +/- C (10 mg/kg) (2440 +/- 265 ng/ml; p less than 0.01 vs. controls); (ii) ALT and AST levels were increased in this latter group (ALT 223 +/- 133 UL, AST 114.67 +/- 39 UL; p less than 0.01 vs. controls); (iii) SC levels were normal; and (iv) steatosis of the liver was observed in these two groups. These findings suggest that C and R, but not F, may inhibit the hepatic cytochromes P-450 which are involved in the oxidative metabolism of the drugs. Furthermore, the high serum CyA levels seem to play a major role in the appearance of biochemical and histological damage to the liver.

Alanine Transaminase↗

Polyclonal B lymphocyte activation in progressive systemic sclerosis.

In 13 women affected by progressive systemic sclerosis (PSS) the activation state of circulating B lymphocytes by use of monoclonal antibodies and the in vitro IgG, IgA, IgM synthesis by peripheral blood mononuclear cells (PBMC) cultured with or without pokeweed-mitogen (PWM) were evaluated. The total and "activated" B lymphocytes were increased. The supernatants of PBMC cultured without PWM contained increased IgG and IgA levels; only in two patients, however, were IgM levels increased. The addition of PWM augmented IgG and IgA levels only in three cases and never IgM levels. Our results indicate that the polyclonal hyperactivity of B lymphocytes is a major immunologic feature in PSS patients. The lack of increase of in vitro immunoglobulin synthesis in the presence of PWM suggests either that B lymphocytes, already maximally activated in vivo, are unresponsive to further mitogen stimulation or that a more complex imbalance of B lymphocyte responsiveness to PWM may exist.

Adult↗

Acute cholecystitis and pancreatitis in a patient with biliary sludge associated with the use of ceftriaxone: a rare but potentially severe complication.

Ceftriaxone may precipitate in the bile leading to the formation of biliary sludge. Biliary complications, even serious ones, have rarely been described in patients treated with this antibiotic. A 71-year-old woman presented to the emergency room with biliary sludge complicated by acute cholecystitis and pancreatitis after 10 days of treatment with ceftriaxone (2 g, 40 mg/kg per day). There had been no evidence of sludge or gallstones on a transabdominal ultrasonography performed 6 months earlier. The patient underwent open cholecystectomy and recovered fully. Ceftriaxone should be kept in mind as a potential cause of biliary sludge. In most cases, resolution of sludge occurs after interruption of ceftriaxone. Young subjects, patients receiving a prolonged course and a daily dose > or = 40 mg/kg, and subjects with impaired gallbladder emptying have a greater risk of ceftriaxone-associated sludge. Cholecystectomy is the definitive therapy for severe complications.

Acute Disease↗

Infections, atherosclerosis, and coronary heart disease.

There is growing evidence that the immune response is involved in atherosclerosis. Studies done over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia. Overall, these data have greatly renewed interest in the infectious theory of atherosclerosis and coronary heart disease. Search of bibliographic databases (from January 1991 through December 1999) and manual scanning of both peer-reviewed publications and other documents were used to identify pertinent literature. Infections and coronary heart disease were indexed as key words. A large number of studies have reported an association of human coronary heart disease and certain persistent bacterial and viral infections. The association between Chlamydia pneumoniae and coronary heart disease appears quite significant although the sequence of infection and disease is uncertain. The association between Helicobacter pylori and coronary heart disease may be accounted for by residual confounding from classic risk factors. Preliminary findings indicate that this association could be due to a higher prevalence of more virulent Helicobacter strains. Infection with Cytomegalovirus appears to be associated with a greater risk of restenosis after angioplasty rather than primary atherosclerosis. Early trials of appropriate antibiotic therapy in subjects with recent acute myocardial infarction have been encouraging. A causal relationship between infections and coronary heart disease is still elusive. Improved studies involving prospective collection of data are required to demonstrate such an association with potential implications for public health worldwide.

Arteriosclerosis↗

Severe thrombophilia with antiphospholipid syndrome and hyperhomocysteinemia in a patient with Schnitzler's syndrome.

Schnitzler's syndrome is a rare condition with chronic urticaria, intermittent fever, bone pain, and a monoclonal IgM gammopathy. Most patients have a chronic and indolent course, but a small number ultimately progress to a lymphoplasmacytic malignancy. We describe a patient with Schnitzler's syndrome who entered an accelerated phase of clinical deterioration with repeated thromboses of the cerebral and coronary arteries that ultimately led to a fatal outcome. We found that the he fulfilled the Sapporo criteria for definite antiphospholipid syndrome and had elevated blood levels of homocysteine during the active clotting phase of the disease. We suggest that the association with immune-mediated or metabolic disorders, such as the antiphospholipid syndrome and hyperhomocysteinemia, may unfavorably affect the otherwise chronic and stable course of patients with Schnitzler's syndrome. The systemic clotting disorder, the association with the antiphospholipid syndrome and hyperhomocysteinemia, and the biclonal rather than monoclonal IgM gammopathy were striking features of this atypical case of Schnitzler's syndrome.

Antiphospholipid Syndrome↗

[Heterogeneity of epitopes of the CD4 molecule in a female patient with idiopathic pulmonary fibrosis].

Heterogeneity of the CD4 antigen epitopes has been occasionally reported in healthy subjects, in patients affected by autoimmune diseases, such as Graves' disease and systemic lupus erythematosus (SLE), and recently also in HIV-infected subjects. A 63-year-old woman was admitted to the hospital because of dyspnea, autoimmune thrombocytopenia and serum antinuclear autoantibodies. The clinical course and X-ray films of the chest were consistent with idiopathic pulmonary fibrosis. The evaluation of peripheral blood lymphocyte subsets showed low CD4+ cells by use of OKT4 (Ortho Mune) monoclonal antibody (30%, normal range 35-45) and normal values of the same CD4+ subset by use of OKT4A (Ortho Mune) and Leu3a (Becton Dickinson) monoclonal antibodies (48%, normal range 45-55), which are specific for a different epitope of CD4 molecule. These differences indicate that the patient is heterozygous for the OKT4 epitope deficiency on CD4+ lymphocytes surface. The routine use of a panel of monoclonal antibodies, such as OKT4, OKT4A, Leu3a, which recognize different CD4 epitopes, is suggested in order to perform an accurate evaluation of CD4+ lymphocyte subset in patients affected by immune-mediated disorders other than Graves' disease and SLE.

Antibodies, Monoclonal↗

[Treatment and prevention of Mycobacterium avium complex infection in AIDS].

Since Mycobacterium avium complex (MAC) infects most, if not all, HIV-positive patients, effective regimens for its treatment and prophylaxis are a necessity. We review here the available literature in an attempt to establish clear-cut criteria for the administration of antibiotics and immunotherapy and for the prophylactic treatment of MAC infections. Several antibiotics, chiefly in combination regimens, are active against MAC. Recent data indicate rifabutin as a first-line antibiotic for the treatment of MAC infections. However, since this antibiotic accelerates hepatic metabolism of many drugs (zidovudine in particular), it has the potential to reduce their serum concentrations and hence limit their antiviral activity. Moreover, rifabutin is active against retroviruses only at extremely high concentrations which are not reached in vivo at normally-prescribed dosages. The recent demonstration that the cytokine interferon-gamma (IFN-gamma) in combination with conventional antibiotic therapy may be effective for disseminated MAC infections indicates that immunotherapy could play a pivotal role in the treatment of MAC infections. Lifetime prophylaxis with rifabutin (300 mg/die) is advised for all patients with HIV infection and fewer than 100 CD4 T lymphocytes/mm3 in the peripheral blood: this antibiotic regimen significantly reduces the frequency of disseminated MAC infections. Further studies are required to evaluate the effectiveness of other prophylactic regimens such as azithromycin and clarithromycin. We conclude that rifabutin and immunotherapy with IFN-gamma will play a key role in the treatment of MAC infections.

Acquired Immunodeficiency Syndrome↗

The syndrome of idiopathic CD4+ lymphocytopenia.

The syndrome of idiopathic CD4+ lymphocytopenia has recently been recognized and referred to as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells per cubic millimeter or less than 20% of total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. The available literature indicates that neither human retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II) nor other transmissible agents play any clear-cut role in the pathogenesis. Furthermore, the epidemiologic, immunologic and clinical features of this syndrome differ substantially from those of HIV infection. The heterogeneity of both immunologic abnormalities, in addition to CD4+ depletion, and clinical course in patients with this disorder points out no common cause although in at least a subset of patients the pathogenetic pathways could be shared with common variable immunodeficiency.

Humans↗