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Biomedical subjects

M Marziali

Publications and source records attributed to M Marziali.

14 recordsLinked to original sources
PubMed2003

Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.

Adolescent↗
PubMed2002

Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles.

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by repeated infections and hypogammaglobulinaemia. Additionally, T-cell abnormalities including lymphopenia, decreased proliferation to mitogens and antigens, and the reduced production and expression of cytokines, have also been observed. In this study we have investigated the expression of naive, memory and activation markers in T-cell subpopulations in 17 CVID patients in comparison to age-matched normal controls. The numbers of CD4+ T cells, including CD45RA+CD62L+ and, to a lesser extent, CD45RA-CD62L+/RA+CD62L- were significantly reduced in patients, whereas CD8+ T cells were within normal range. In contrast, HLA-DR+ cells were increased both in CD4+ and CD8+ T cells. To assess the thymic output, we analysed the presence of T-cell receptor excision circles (TRECs) in CD4+ and CD8+ T cells by quantitative PCR. TRECs were decreased significantly in patients and the rate of TREC loss was higher with increasing age. TRECs correlated with naive CD4+ T cells, whereas there was an inverse relationship between TRECs and CD8+HLA-DR+ and CD8+CD45RA-CD62L+/RA+CD62L- T cells. Our results suggest the presence of a defect in the naive T cell compartment with origin at the thymic level in CVID, and indicate that TREC may be a useful marker to monitor thymic function in this primary immunodeficiency.

Adult↗
PubMed2002

Skin diseases as extrahepatic manifestations of HCV. Review of some clinical cases.

Among extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis. Aim of this paper is to analyze these typical dermatoses in a population of patients with HCV infection and describe the characteristic clinical pictures. These clinical pictures confirm the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

Journal Article↗
PubMed2001

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity.

The immunological correlates of highly active antiretroviral therapy (HAART)-induced suppression of human immunodeficiency virus type 1 (HIV-1) replication have been investigated. 20 HIV-1-infected patients with mean CD4+ T cell count of 298/microl, plasma viral load of 4.7 log10 copies/ml and naive for protease inhibitors (PI) were studied during12 months of HAART. An increased number of both CD4+ and CD8+ naive T cells and a normalization of the frequency of CCR5- and CXCR4-expressing CD4+ T cells were readily observed after starting therapy. Single cell analysis of cytokine production after 12 months of HAART showed an increased number of interleukin (IL)-2-, but not IL-4- and (IFN)-gamma-, producing T cells and a decreased percentage of CD8+ IFN-gamma + cells. A correlation between the frequency of IFN-gamma-producing T cells and that of memory, CCR5+ and CD95+ T cells was demonstrated in both CD4+ and CD8+ subsets. The diversity of T cell receptor (TCR) variable beta (BV) chain repertoire significantly increased after 12 months of HAART within the CD4+ but not the CD8+ T cell subset. However, the level of perturbation of the third complementarity-determining region (CDR3), was not significantly modified by effective therapy. The number of anti-HIV Gag and Pol cytotoxic T lymphocytes precursors (CTLp) decreased during HAART and highly correlated with the CD8 IFN-gamma response. Ameliorated clinical conditions were observed in all patients in absence of any opportunistic infections during all the study period. These observations indicate that a better restoration of immunity may be obtained in patients starting HAART at less advanced stages of the disease.

Adult↗
PubMed2001

T-Cell immune activation in children with vertically transmitted hepatitis C virus infection.

Little is known concerning the clinical features, the histological outcome, and the effects on the maturation of immune system of children with vertically-transmitted hepatitis C virus (HCV) infection. Specifically, no data are available on the peripheral distribution of T-cell subsets. The frequency of naive and memory cells, activated T cells, and cytokine-producing T cells was analyzed in nine HCV-infected children born to HCV-positive mothers. In HCV-infected children, the distribution of naive and memory cells was not significantly altered in the CD4 subset whereas within the CD8 subset, an increase of memory and a decrease of naive cells was observed. The frequency of HLA-DR-positive and Fas-positive T cells was increased in HCV-infected children in both CD4 and CD8 subsets. The distribution of Fas-expressing T cells was directly related to that of HLA-DR cells and inversely related to the frequency of naive T cells. In regard with cytokine production we found increased levels of both CD4 and CD8 interferon-gamma (IFN-gamma)-producing cells whereas no difference in the percentage of interleukin-2 (IL-2)-producing T cells was observed. No meaningful correlation was observed between individual T cell subsets and ALT levels or HCV viral load. In conclusion, our results indicate an increased T-cell activation and a shift to a T(H)1 pattern of cytokine production in children with vertically transmitted HCV infection. The cause of this kind of immune response could reside in the persistent antigenic stimulation by chronic HCV infection.

Adolescent↗
PubMed2000

Low-dose IL-2 reduces lymphocyte apoptosis and increases naive CD4 cells in HIV-1 patients treated with HAART.

During HIV disease an increased in vitro apoptosis of peripheral blood mononuclear cells has been demonstrated. This can be reversed in vitro by interleukin (IL)-2. Recent trials with highly active antiretroviral therapy (HAART) and IL-2 in HIV-1-infected patients showed promising immunological and clinical results. Here we investigated the effects of subcutaneous low-dose IL-2 administration in combination with HAART on in vitro apoptosis and the relationship between apoptosis, CD4(+) counts, and HIV replication. Twenty-two asymptomatic HIV patients were randomized for HAART (arm I) and HAART plus IL-2 (arm II). Spontaneous apoptosis was decreased in both arms after 28 weeks of therapy but the reduction was highly significant only in arm II (P = 0.05 vs P = 0.001). As the percentage of apoptosis decreased, there was a significantly higher increase of both CD4(+) and CD4(+) naive T cells in arm II vs arm I. HIV plasma viremia was reduced in all patients after therapy. Our data suggest that intermittent therapy with low-dose subcutaneous IL-2 in addition to HAART induces a positive immunomodulation in asymptomatic HIV-infected patients.

Adult↗
PubMed2000

Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Irhan Study Group.

The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P < 0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Another effect induced by HAART was a significant increase in IL-2Ralpha expression on total PBMC (P < 0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

Adult↗
PubMed2000

T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome.

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Abnormalities, Multiple↗
PubMed1998

[Modifications to the technic of cesarean section after Stark].

BACKGROUND: As the operating births (caesarean section) increase, many surgical equipes have been compelled to revise operating techniques in order to reduce fetus extraction times and the whole expense of operation without renouncing, at the same time to beauty advantages. With Stark technique, that we have modified, we have obtained all these aims, improving at the same time patients' postoperative course as well succeeding to extract the fetus in about five minutes. In the '70 Cohen explained the utility of a transiliac incision allowing the access to abdominal cavity with rectus muscles unsticking in an area in which these muscles should present a less adhesiveness. METHODS: Since 1988 Stark has used Cohen's technique changing however uterus closing times, peritoneal membranes and abdominal walls. Our technique is different since we performed the incision according to Pfannestiel. RESULTS: The times are considerably reduced to 4.8 minutes for fetus extraction and in postoperative time the complications are drastically reduced too (infection, pain, hematoma, adhesions). CONCLUSIONS: Therefore we can surely say that this kind of technique can be used with success in all gynaecological surgery, in extrauterine pregnancies and adnexial tumefactions (not malignant). Personal opinion is that spinal anesthesia is the best analgesic technique.

Antibiotic Prophylaxis↗
PubMed1998

Flumazenil for hepatic coma in patients with liver cirrhosis: an Italian multicentre double-blind, placebo-controlled, crossover study.

Several factors suggest that endogenous benzodiazepines and gamma-amino-butyric acid may be involved in pathophysiology of hepatic encephalopathy (HE). Contrasting opinions exist on the therapeutic efficacy of flumazenil in the treatment of HE. This study was planned to assess the efficacy of flumazenil by a double-blind, placebo-controlled, crossover design in a large and selected population of cirrhotic patients in stage 4a HE admitted to intensive care units over a 4-year period. Out of 236 patients selected for the study, 132 received flumazenil, whereas 131 patients received placebo. Improvement of the neurological score was documented in 31 patients (23%) of flumazenil group and in two patients (1.5%) of placebo group (p < 0.001) during the first study period, whereas during the crossover period, improvement of the neurological score was documented in seven patients (5.3%) of the flumazenil group and in none of the placebo group (p = 0.022). Improvements in EEG tracings were observed in 44 patients (33.3%) of flumazenil group and in five patients (3.8%) of placebo group (p < 0.001) during the first study period; during the crossover period, improvements in EEG tracings were observed in 10 patients (7.5%) of the flumazenil group and in two patients (1.5%) of the placebo group (p = 0.040). The presence of benzodiazepines was detected in the serum of three responders and in two non-responders. The presence of diazepam and NN-desmethyl diazepam was documented in two responders; prior intake of synthetic diazepam was later confirmed in these patients. The results of our study suggest that flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with hepatic coma or to cirrhotic patients with less severe HE still remains to be determined.

Adult↗
PubMed1997

[From atopic dermatitis to asthma].

Atopic dermatitis (AD) is the most common chronic skin disorder in infancy and childhood and is the main hallmark of atopic constitution. The disease is multifactorial, and although genetic predisposition is certainly a prerequisite, a number of environmental factors modulate the phenotypic expression of AD. The majority of affected children shows IgE sensitisation towards a large variety of foods and aeroallergens. Since at least 1600, it has been recognized that patients with AD have a high predisposition to develop asthma. Recent epidemiological studies show that AD is commonly seen in individuals from families with a history of asthma. In addition, in population where asthma is uncommon, AD is also uncommon. The sex distribution of AD and asthma is the same, with boys affected significantly more often by these two atopic diseases and in similar proportions. The ETAC project (Early Treatment of the Atopic Child) is a large multicenter, multi-national, double blind, placebo controlled, randomised trial. The main objective of the study is to stop the progression from AD to asthma in young children with AD using early therapeutic intervention with Cetirizine and the second objective is to investigate the main risk factors for the onset of asthma. The results of this study indicate that exposure to potent allergens such as cat or mite significantly increased the risk of sensitisation to these allergens. Prolonged breast feeding was associated with a lowest sensitisation rate to cow milk proteins and to egg. Therefore environmental factors seem to play a crucial role in IgE sensitisation in children with AD.

Asthma↗
PubMedDate not supplied

[Food allergy: recent findings].

Food allergy induces in infancy and childhood a large variety of symptoms which may be trivial in many children, chronic and severe in others and even fatal in rare cases. According to double-blind placebo controlled oral food challenges, cow's milk, egg, wheat and fish are the most common offending foods. Elimination of the offending food(s) is imperative for the management of children with food allergy. An appropriate formula without cow's milk proteins and allergenic epitopes should be given to infants with cow's milk allergy. Breast feeding and selected weaning after the sixth month of life are recommended for the prevention of food allergy in atopic prone babies.

Child↗
PubMedDate not supplied

[Antiphospholipid syndrome in obstetrics].

BACKGROUND: The purpose of this study was to verify the frequency of antiphospholipid syndrome in pregnancy associated with fetal wastage and maternal hypertension. The antiphospholipid antibody syndrome is a clinical syndrome of venous and arterial thrombotic events, recurrent pregnancy loss, and thrombocytopenia associated with two autoantibodies: the lupus anticoagulant (LAC) and anticardiolipin antibody (ACA). METHODS: A group of 83 pregnant patients with recurrent fetal loss or with maternal hypertension for the presence of autoantibodies has been studied. None of the patients had systemic lupus erythematosus or any other autoimmune disease such as sclerodermia, myasthenia, autoimmune thrombocytopenic purpura. The patients have been divided into two groups: a) 45 women with fetal wastage history; b) 38 women with maternal hypertension. RESULTS: The prevalence of autoantibodies in the first group reaches 31.1% (14/45 patients). Two of these 14 patients (14.3%) had fetal loss (one with treatment and one without). 12 of this 14 patients (85.7%) had a normal delivery and all with treatment. Two treatment scheme were used in this study: one with aspirin and another with aspirin and prednisone. In the group of 45 patients there were 34 normal deliveries: 27 (79.5%) pregnancies were treated with aspirin and 7 (20.6%) were treated with aspirin and prednisone. There were 11 fetal loss and 9 (81.1%) in patients without treatment and 2 (18.2%) in treated pregnancies. The prevalence of autoantibodies in the second group reaches 21%. CONCLUSIONS: In conclusions, it can be suggested that treatment strategies for the prevention of fetal loss in the antiphospholipid syndrome are warranted because treatment appears to alter fetal outcome favorably.

Abortion, Habitual↗