Autoimmune T-cell response to the CD4 molecule in HIV-infected patients.

In a previous study, we demonstrated that by downregulating plasma membrane CD4 and increasing its processing, human immunodeficiency (HIV)-1-gp120 unveils hidden CD4 epitopes, inducing an in vitro anti-CD4-specific T-cell response. We report herein that this mechanism may potentially have important implications in HIV immunopathogenesis, because it could take part in the severe depletion of CD4+ cells that characterizes acquired immune deficiency syndrome (AIDS) and be related to disease progression. Freshly isolated peripheral blood lymphocytes (PBMC) from about 1/4 of a conspicuous cohort of HIV-infected patients responded to CD4 and this response was correlated with beta2-microglobulin levels, widely recognized as marker for progression of HIV infection. Moreover, we provide evidence that a CD4-specific T cell priming can occur in vivo, following a gp120 or anti-CD4 monoclonal antibody (mAb)-mediated CD4 molecule downregulation on antigen-presenting cells (APC). To our knowledge, this is the first study indicating that an autoimmune T-cell response is linked to HIV infection and that it could have an important impact on the immunopathogenesis of this disease.

Effect of risedronate in osteoporotic HIV males, according to gonadal status: a pilot study.

The aim of the study was to evaluate the effect of risedronate on bone mineral density (BMD) and bone turnover markers in HIV-infected osteoporotic males, according to their gonadal status. HIV patients were followed up for 24 months and divided into two groups: patients with osteoporosis or osteopenia with fractures (group A, n = 20) and those without (group B, n = 21). Group A and B were further divided according to the presence of reduced androgenizations. Both groups were treated with cholecalciferol 800 I.U. and calcium (Ca) 1,000 mg orally every day for the first 12 months. Risedronate 75 mg for two consecutive days a month orally was then added in group A, for another 12 months. Group B continued treatment with Ca and vitamin D. Every 6 months each patient underwent biochemical evaluation, and BMD measurement. A significant increase in lumbar BMD was observed in HIV males with adequate androgenization after 12 months of risedronate treatment in group A together with a reduction of bone turnover markers. BMD remained stable with a concomitant significant slight reduction of bone turnover markers in group B. Risedronate increased BMD and reduced bone turnover markers to a greater extent in patients with adequate androgenization compared to osteoporotic HIV males with symptomatic hypoandrogenization.

Pharmacokinetics of zidovudine and concomitant inosine-pranobex in AIDS patients.

3'-azido-3'-deoxythymidine (AZT) was administered orally to 8 AIDS patients at a dose of 100 mg every 6 hours for 14 days. On days 8 - 14 the patients were also given 1 g inosine-pranobex (INPX) every 6 hours. On day 7, while the subjects were taking AZT alone and on day 14 while they were receiving AZT + INPX, blood samples were obtained over a 6-hour dosing interval for measurement of AZT by a specific AZT radioimmunoassay. AZT levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment. INPX is an immunomodulatory drug with an inhibitory effect on HIV. The potential advantages of a combined treatment AZT + INPX are: 1) need for lower dose of AZT for maintaining a therapeutic anti-retroviral level; 2) a longer interval period between AZT treatments; 3) a potential to enhance immunological response resulting from INPX treatment; 4) reduced costs of care for patients.

[Clinical-therapeutic considerations in a case of miliary tuberculosis in an indonesian girl]. / Considerazioni clinico-terapeutiche su un caso di tubercolosi diffusa ad evoluzione grave in una bambina indonesiana.

The authors describe the case of widespread miliary tuberculosis, that arose in a ten year-old Indonesian girl of middle-class, who has been living in Italy from about three years. The girl was probably contaminated by a subject belonging to the same ethnic-social community, who was affected with tubercular disease. The diagnosis was effected on the ground of: clinical picture including continued-remitting fever, a loose cough, asthenia, anorexia, weight reduction, aching tumefaction on the left side of the neck; isolation of Mycobacterium tuberculosis from the expectoration, blood, urine, and a lymph node located on the left side of the neck; radiological picture that revealed a widespread miliary tuberculosis. In spite of polychemotherapy with isoniazid , rifampicin, pirazinamide, and streptomycin that was subsequently replaced by ethambutol, the course of the illness worsened and it was characterized with fever, cachexia, respiratory insufficiency and repeated episodes of pneumothorax. For such reasons on the ground of susceptibility to the antibiogram amikacin and ciprofloxacin, as well as glucocorticoids to limit the fibrousness, were added to the specific therapy that was already being out. For persisting of relapsing pneumothoraxes, the patient underwent a thoracoscopy and plerodesis with talcum powder. After four months of antitubercular therapy, the research of M. tuberculosis resulted negative in the expectoration, urine, bronchus-alveolar washing liquid and blood, in addition to improvement in general state of health with remission of fever was noticed.

Immunoblot analysis of Salmonella typhi lipopolysaccharide (LPS) using typhoid sera.

Lipopolysaccharide (LPS) of Salmonella typhi has been analyzed by immunoblotting with pooled sera from typhoid patients. Pooled typhoid sera have recognized all the antigenic determinants of S. typhi LPS, giving a strong reaction with the repeating units on the O-side chains as well as with the core region. Cross-reacting antigens have been observed with the LPS of S. typhimurium and S. enteritidis, while no heterologous reactions were seen with the LPS of E. coli strains.

[Acyclovir in the treatment of varicella in immunocompetent children]. / L'acyclovir nel trattamento della varicella nei bambini immunocompetenti.

We evaluated safety and tolerance of acyclovir ACV per os in immunocompetent children affected by chicken-pox admitted to our department from January 1993 to December 1994. 183 subjects (102 males and 81 females) aged between 0 and 14 years were treated by ACV (80 mg/kg/daily in 4 divided doses): 88 children were treated within 24 hours and 95 subjects within 48 hours from the onset of symptoms. The control group consisted of 83 children (52 males and 31 females) aged between 0 to 14 years. In all patients routine blood-test were performed and in those with respiratory illness Chest-Rx was also done. We evaluated clinical course, degree of eruption, the appearance and kind of complications, duration of hospitalization, the compliance and the potential consequences on specific antibody response. Our results show a faster improvement of clinical symptoms in treated patients with respect to the control group with shortening of the period of the fever, itch and appearance of new vescicles. The percentage of complications was lower in treated than in untreated patients. 16 cases tested for specific antibody response showed protective titers six months after treatment. In conclusion, ACV administered per os within 48 hours from onset of exanthema causes reduction of the period and the degree of general symptoms and exanthema, a lower incidence of complications even if non statistically significant. The drug is safe and well-tolerated.