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Biomedical subjects

A Terragna

Publications and source records attributed to A Terragna.

At least 19 recordsLinked to original sources

Dose-dependent effects of deflazacort and prednisone on growth and skeletal maturation.

Deflazacort (DFZ), a new glucocorticoid which has recently become available, is expected to have less negative effects on growth and skeletal maturation than conventional steroids, in children treated long term. To verify this hypothesis, a multicentre trial was organized to evaluate the effects of DFZ vs prednisone (PDN) on statural growth and skeletal maturation in a group of prepubertal children requiring glucocorticoid therapy for at least 6 months/year. The results of an analysis of 55 children (aged 3-12 years, 24 with connective tissue disease and 31 with kidney glomerular disorders) treated randomly with either DFZ (31 patients) or PDN (24 patients) and followed for a mean period of about 22 months (16 months under steroid therapy) are presented. The observation period was split up into the following phases according to dose and administration regimen: daily, high-dose therapy; alternate-day, high-dose therapy; low-dose therapy; suspension of treatment. The height, statural age, skeletal age and body weight velocities (i.e. the increase/year) were considered. In spite of large intra-individual and inter-individual variability, the results suggest that DFZ has a lower negative impact on indicators of growth. During high-dose daily administration, the height velocity tended to be lower in the PDN group and the impairment of skeletal maturity was significantly less for DFZ than for PDN. During an alternate-day regimen, height velocity was slightly higher in the PDN group and skeletal age velocity was higher in the DFZ group. It seems that steroid effects on statural growth and bone maturation occur in parallel.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton

Zidovudine therapy of HIV-1 infection during pregnancy: assessment of the effect on the newborns.

Zidovudine (ZDV) administration during pregnancy has been suggested for the prevention of mother-to-child HIV-1 transmission. Reliable levels of the drug have been observed in the fetus and in the newborn. Seven HIV-1-infected pregnant women who declined to have abortions and whose immunological status required antiretroviral treatment were administered oral ZDV 18 mg/kg in four daily doses, the initial dose being administered anytime from the 16th to the 30th week of gestation up until the time of delivery. Follow-up of the seven infants from birth with a mean duration of 22 months (range 16-32 months) revealed mild drug-related toxicity: anemia in two infants and macrocytosis in all seven, both conditions resolved by the second month of life. All infants remained HIV-1 seronegative, according to the 1987 CDC classification, and all stayed clinically well. Other virological parameters including virus culture, in vitro antibody production, and polymerase chain reaction, repeatedly performed in the infants, remained negative. Although none of the mothers transmitted HIV-1 infection to the offspring, the size of this study and the relatively low transmission rate (13%) in Europe do not permit us to draw a definite conclusion about treatment efficacy in preventing maternal-fetal transmission. However, the drug caused only limited toxicity among the infants, and its administration to large numbers of mothers in treatment trials should be considered relatively safe for both mother and child.

Female

Cotrimoxazole therapy of Toxoplasma gondii encephalitis in AIDS patients.

Twenty-four consecutive HIV-positive patients affected by Toxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75% response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients with Toxoplasma gondii encephalitis.

Acquired Immunodeficiency Syndrome

Selective increase of a subset of T cell receptor gamma delta T lymphocytes in the peripheral blood of patients with human immunodeficiency virus type 1 infection.

Increased proportions of the small lymphoid subset expressing T cell receptor (TCR) gamma delta occur in different infectious diseases, particularly in mycobacterial infections. In this study the two main subsets of TCR gamma delta+ cells in peripheral blood mononuclear cells (PBMC) of 54 patients with human immunodeficiency virus type 1 infection were analyzed. These subsets were defined by indirect immunofluorescence techniques and FACS analysis using BB3 and A13 monoclonal antibodies, which specifically react with V delta 2- and V delta 1-encoded forms of TCR gamma delta. The proportion of BB3+(V delta 2+) and A13+(V delta 1+) cells was analyzed in purified PBMC populations. Patients were stratified according to Walter Reed (WR) clinical stage. A sharp increase in percentage of A13+(V delta 1+) cells was observed in all stages of the disease. In addition, a strict correlation was found with stage of the disease and percentage of CD8+ PBMC. An inverse correlation was found with the proportion of CD4+ PBMC. An early (WR2) inversion of the V delta 2-to-V delta 1 ratio was consistently detected even before the inversion of the CD4-to-CD8 ratio.

CD4 Antigens

Detection of HIV-1 antibodies in blood specimens spotted on filter-paper.

Described are the results of an international collaborative study to evaluate the use of whole blood samples spotted on filter-paper (BSP) for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1). BSP samples were collected from 40 patients at risk for HIV-1 infection and tested blindly using commercially available HIV antibody test kits, either specifically manufactured or modified for this purpose. Parallel serum samples were also collected, and the antibody reactivity was defined and confirmed by Western blot. The results demonstrate that recovery of antibodies from BSP samples after elution can be comparable to that from serum. Some kits can be easily adapted to test BSP samples, while others cannot. At present, detection of HIV antibodies in BSP samples should therefore be carried out using kits specifically manufactured for this purpose or by the development of a modified protocol using a panel of BSP and their corresponding serum specimens.

AIDS Serodiagnosis

Malignancies in children with human immunodeficiency virus type 1 infection. The Italian Multicenter Study on Human Immunodeficiency Virus Infection in Children.

Cancer has been closely associated with human immunodeficiency virus (HIV) infection but this is less frequent in children. Non-Hodgkin's lymphomas represent the most frequently reported single tumor. The authors report seven cases of malignant tumors resulting from the analysis of all (n = 1321) children enrolled in the Italian Register for HIV Infection in Children. Tumors were distributed as follows: non-Hodgkin's B-cell lymphoma (four cases); and Kaposi's sarcoma, hepatoblastoma, acute B-cell lymphoblastic leukemia (one case each). Hepatoblastoma had never been previously reported in HIV-infected children. Also in the current series, non-Hodgkin's B-cell lymphoma is the most frequent single tumor. Five of the seven cancers belonged to the B-cell line. All but one of the seven children have died. Specific chemotherapy was provided in three cases, with some clinical improvement. The treatment of malignancies in HIV-infected children is hampered by increased risk of opportunistic infections often fatal even in children with apparent remission from the tumor.

Burkitt Lymphoma

Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: an interim long-term analysis.

The low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) aged 3-12 yrs, after a median period of 14 mo.s is reported. Children with connective tissues (CTD) and glomerular disorders (KD) were randomly allocated to DFZ or PDN. Anthropometric measurements and maturity ratings were performed. Mean daily doses of PDN (or DFZ equivalent), from 0.57 to 0.64 mg/kg (DFZ 0.92 to 0.94 mg/kg) to induce control and from 0.19 to 0.39 mg/kg (DFZ 0.34 to 0.36 mg/kg) to maintain disease under control were given in CTD and KD, respectively. The increase in bone age delay over time was significantly greater than for PDN (-4.0 mo/yr) than DFZ (-1.8 mo/yr) in the overall group. The increases in statural age delay and loss over time were significantly greater than for PDN (-5.9 and -5.9 mo/yr) than DFZ (-2.4 and -2.4 mo/yr), only in children with "taller" midparents. Although doses of DFZ 1.1-1.8 times those of PDN were given, growth retardation in PDN-treated children was nevertheless 2.3-2.5 times that in DFZ-ones.

Age Determination by Skeleton

Listeria monocytogenes brain abscesses in a girl with acute lymphoblastic leukaemia after late central nervous system relapse.

A case of Listeria monocytogenes bacteraemia and meningitis with intracerebral abscesses in a girl with acute lymphoblastic leukaemia in relapse is reported. The clinical features included subacute onset with fever and marked irritability followed by seizures, meningism and confusion. The pathogen was isolated from blood and cerebrospinal fluid. Computerised tomography of the brain showed two intracerebral parenchymal localisations, in the left frontal lobe and in the right occipital lobe, respectively. The patient survived this severe infection without neurological sequelae. 2 months later she underwent allogeneic bone marrow transplantation without major complications. This case report should alert pediatric oncologists about the possible occurrence of severe intracerebral listerial infections in the immunocompromised child and suggests that this infection can be treated successfully and should not necessarily preclude continuation of antineoplastic treatments.

Brain

Fluconazole in the treatment of candidiasis in immunocompromised children.

Fluconazole, a new triazole derivative, was evaluated in a pilot study of 34 episodes of candidiasis in 24 children. All the patients had predisposing conditions, such as human immunodeficiency virus infection, cancer, organ or bone marrow transplantation, neonatal age and malnutrition, and obstructive uropathy. The drug was administered at 6 mg/kg (body weight) once daily either orally or intravenously. Two patients with fungemia due to Candida parapsilosis required an increased dosage of 12 mg/kg. Clinical and microbiological success was achieved in 30 of 34 cases (88%). Drug-related transaminase increases were observed in two cases (6%). Fluconazole may represent an effective alternative to amphotericin B in the treatment of candidiasis in children. Comparative trials are necessary to assess optimal dosages and efficacy.

Adolescent

Neurological complications in HIV infection. Personal experience.

The personal experience on neurological disturbances associated with early HIV infection and AIDS is reported. Central nervous system (CNS) involvement occurred during the early stages in 3 cases: 2 patients with HIV-seroconversion (CDC category III) and one patient with persistent generalized lymphadenopathy (PGL, III group CDC, 1986). The patients had HIV acute meningitis. The neurological manifestations in AIDS had high incidence (49 of 83 cases), often with multiple aetiology in single patients. We remark the necessity of an early aetiological diagnosis to address the treatment.

Acquired Immunodeficiency Syndrome

Significance of specific immunoglobulin M in the chronological diagnosis of 38 cases of toxoplasmic lymphadenopathy.

The persistence of immunoglobulin M (IgM) antibody to Toxoplasma gondii in sera from 38 patients after toxoplasmic lymphadenopathy was investigated by using an indirect immunofluorescence assay, a double-sandwich enzyme-linked immunosorbent assay, and an immunosorbent agglutination assay. Positive predictive values at 3 and 6 months after lymphadenopathy were, respectively, 45 and 73% for the indirect immunofluorescence assay, 25 and 45% for the double-sandwich enzyme-linked immunosorbent assay, and 22 and 43% for the immunosorbent agglutination assay.

Adolescent

An in vitro model for Toxoplasma infection in man. Interaction between CD4+ monoclonal T cells and macrophages results in killing of trophozoites.

The cell interactions that take place between Toxoplasma gondii trophozoites and the human immune system have been investigated by using an in vitro model of infection. PBMC were co-cultured with live, appropriately attenuated, trophozoites. When cells from immune (seropositive) donors were used, a proliferative response was observed. At the same time, the proliferating T cells proved capable of controlling the growth of live trophozoites. By contrast, cells from seronegative donors failed to mount a proliferative response and intracellular overgrowth of trophozoites with subsequent cell injury occurred. Actively proliferating T cells were expanded in continuous cell lines with IL-2 and periodical restimulation with Ag in the presence of autologous irradiated mononuclear cells. From some of the lines obtained, clones were also derived. Ten clones were selected for further studies. They proliferated in response to trophozoites but not to unrelated Ag. Their response required the presence of autologous monocytes-macrophages isolated from peripheral blood on Percoll density gradients. B cells that were obtained from the same donors and immortalized by EBV infection proved inefficient as APC. These data suggest that live trophozoites have to be processed by macrophages in order to be presented to T cells. Upon appropriate antigen stimulation, all of the clones produced IL-2 and IFN-gamma, a finding that was consistent with both their CD4+ surface phenotype and their helper capacity on B cell proliferation and differentiation in vitro. The supernatants of all of the stimulated clones released a factor that activated macrophages to kill intracellular trophozoites as well as an unrelated pathogen, Listeria monocytogenes. This factor was identified as IFN-gamma because it was neutralized by specific anti-IFN-gamma antibodies. The present in vitro model of response to live protozoa may prove suitable to assess the role of both T lymphocytes and macrophages in intracellular parasite infections in man. Furthermore, this experimental system may be applied to detect specific lesions of cell mediated immunity in a number of immunodeficiency syndromes.

Adult

Whole blood collection on filter paper is an effective means of obtaining samples for human immunodeficiency virus antibody assay.

The suitability of collecting whole blood specimens on filter paper disks for HIV antibody assay was evaluated. ELISA and Western blot assay results were in complete agreement for serum and blood spot disk samples. Sensitivity of the two methods was tested using diluted whole blood and sera from HIV-seropositive individuals. Results demonstrate that ELISA and Western blot assays performed on punched-out disks of the blood-impregnated papers had the same sensitivities as those obtained with serum samples. This study suggests that whole blood collection on filter paper can be effectively substituted for serum sampling in HIV antibody screening programs.

Antibodies, Viral

Pharmacokinetics of teicoplanin in pediatric patients.

The pharmacokinetics of teicoplanin have been studied in 13 pediatric male patients from 2 to 12 years of age. Patients were given a single 3-mg/kg intravenous dose of teicoplanin for prophylaxis. Blood and urine samples were collected for 8 days after administration, and teicoplanin levels were determined by microbiological assay. Pharmacokinetic parameters were estimated from a three-compartment open pharmacokinetic model and from a noncompartmental analysis. Levels in plasma 1 h after the administration averaged 14.8 mg/liter. The half-lives of the two distribution phases were 1.3 and 9.7 h. The half-life of the terminal phase averaged 57.9 h, with similar estimates obtained from the noncompartmental analysis and from data from urine. The volume of distribution of the central compartment was 0.15 liter/kg, whereas the volume of distribution at steady state and during the elimination phase were 0.80 and 1.25 liters/kg. The total teicoplanin clearance averaged 14.8 ml/h per kg, with renal clearance accounting for about 60% of the total. The average cumulative recovery of teicoplanin in urine over 8 days was 59% of the dose, similar to the value obtained in adult volunteers. There was no significant linear correlation between elimination half-life and age. Preliminary data after repeated administration support the reliability of the model used and the validity of the mean estimated parameters. There were no local or systemic adverse reactions to teicoplanin.

Analysis of Variance

Treatment of children with chronic hepatitis B with a combination of steroids and human lymphoblastoid interferon.

The efficacy of human lymphoblastoid interferon (Wellferon) therapy was measured in 20 children with chronic hepatitis B with or without pretreatment with prednisolone. Patients were randomised to receive 0.6 mg/kg/day prednisolone for 3 weeks, then at 0.3 mg/kg for a fourth week or placebo. All patients then received interferon 5 MU/m2 i.m. for 12 weeks; daily for 5 days then three times a week for the remaining 11 weeks. Preliminary results show that 25% of children had a permanent loss of viral markers of replication. However, response to interferon varied widely between individuals and a prolonged follow-up is required in order to determine the influence of prednisolone pretreatment on the efficacy of interferon therapy.

Adolescent