PubMed Health⌕ Search

Biomedical subjects

G Comolli

Publications and source records attributed to G Comolli.

At least 19 recordsLinked to original sources
PubMed2007

Control of human cytomegalovirus infection in patients infected with human immunodeficiency virus by high levels of specific CD8+ T-cells.

A new technique was used to simultaneously determine human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells in highly active anti-retroviral therapy (HAART)-naive and HAART-treated patients infected with human immunodeficiency virus (HIV). HIV-infected patients with HCMV infection, but without HCMV disease, showed low numbers of HCMV-specific CD4(+) cells and high numbers of CD8(+) T-cells, both before and during HAART. HIV-infected patients with HCMV disease had no HCMV-specific CD4(+) T-cells and extremely low levels of CD8(+) T-cells. Resolution of disease during HAART was associated with rescue of specific CD4(+) T-cells and a large increase in the specific CD8(+) T-cell count. Thus, HAART does not completely restore the normal immune function. In HIV-infected patients, sustained control of HCMV infection requires high frequencies of specific CD8(+) T-cells.

Adult↗
PubMed2006

Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation.

Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection.

Adult↗
PubMed2004

Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation.

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.

Adult↗
PubMed2001

Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART.

OBJECTIVE: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 ( n = 22) with nadir CD4(+) cell count <50/microl and no HCMV disease; group 2 ( n = 16) with <50/microl CD4(+) T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. STUDY DESIGN AND METHODS: The two groups of patients were tested prospectively for CD4(+) T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4(+) T-cell counts <100/microl was also investigated. RESULTS: No LPR to HCMV was found in any of the treatment-naive patients nor in any patient of the two groups examined at baseline, when HCMV viremia was 13.6% in the patient group without disease and 87.5% in the group with disease ( p <.0001). After 3 years of HAART, the frequency of patients who recovered an LPR to HCMV was not significantly different (81.8% in the group without HCMV disease, and 68.7% in the group with HCMV disease), whereas, compared with baseline, the HIV load decreased and the CD4(+) T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3%, respectively) in association with high median CD4(+) T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4(+) T-cell counts >150/microl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4(+) T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4(+) T-cell counts >150/microl, recovery of HCMV LPR, and no HCMV viremia. CONCLUSIONS: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.

AIDS-Related Opportunistic Infections↗
PubMed2001

Higher levels of HIV DNA in memory and naive CD4(+) T cell subsets of viremic compared to non-viremic patients after 18 and 24 months of HAART.

The degree of infection of memory and naive CD4(+) T cells in patients treated with HAART and with durable undetectable or detectable viral load in plasma was evaluated. The following two groups of patients were analyzed cross-sectionally: (i) patients with undetectable HIV RNA plasma levels during follow-up (responders); (ii) patients with no reduction or with rebound in HIV RNA levels during treatment (non-responders). Patients were examined following 6, 12, 18 and 24 months of HAART, respectively, by quantifying: (i) plasma HIV RNA load; (ii) CD4(+) T cells; (iii) memory and naive CD4(+) T cells; (iv) HIV DNA levels in memory and naive CD4(+) T cells. HIV RNA plasma levels were significantly higher in non-responders vs responders at each time point (P<0.02), while CD4(+) T cell counts as well as memory and naive CD4(+) T cell levels were comparable in both viremic and non-viremic patients. However, higher HIV DNA values were observed in both memory and naive CD4(+) T cells of non-responders vs responders after 18 and 24 months of HAART (P<0.02), suggesting an increased amount of HIV-infected naive CD4(+) T cells and a sustained high degree of infection of memory CD4(+) T cells. Immunological reconstitution following HAART might potentially be hampered in viremic patients despite the absolute increase in CD4(+) T cell counts.

Anti-HIV Agents↗
PubMed2001

Comparative analysis of human cytomegalovirus-specific CD4(+) T-cell frequency and lymphoproliferative response in human immunodeficiency virus-positive patients.

Evaluation of human cytomegalovirus (HCMV)-specific T-helper immunity could contribute in optimizing anti-HCMV therapy in human immunodeficiency virus (HIV)-infected patients. Testin the lymphoproliferative response (LPR) is the standard technique used to evaluate T-helper response, but its use in the routine diagnostic laboratory setting can be problematic. The most promising new alternative technique is the determination of HCMV-specific CD4(+) T-cell frequency by flow cytometry detection of intracellular cytokine production after short-term antigen-specific activation of peripheral blood mononuclear cells. HCMV-specific LPR and CD4(+) T-cell frequency were compared in a group of 78 blood samples from 65 HIV-infected patients. The results showed concordance in 80.7% of samples. In addition, comparative analysis of sequential blood samples from 13 HIV-infected patients showed that while in about half of patients the T-helper HCMV-specific immune response remained stable during highly active antiretroviral therapy (HAART), in the other half declining levels of the HCMV-specific CD4(+)-mediated immune response were determined by either one or both assays. In conclusion, our data suggest that the determination of HCMV-specific CD4(+) T-cell frequency can be considered a valuable alternative to the LPR test for the detection of HCMV-specific T-helper response in HIV-infected patients. It could facilitate wider screening of anti-HCMV T-helper activity in HIV-infected patients, with potential benefits for clinicians in deciding strategies of discontinuation or maintenance of anti-HCMV therapy.

Adult↗
PubMed2000

Early immunisation with hepatitis B vaccine: a five-year study.

We evaluated the response to the recombinant Hepatitis B vaccine using an accelerated schedule versus the traditional schedule by studying the immunologic memory induced in 200 children with HBs-Ag negative mothers. At seroconversion, the traditional schedule presented a higher percentage of children with serum HBs-Ag concentrations over 100 mIU/ml than the accelerated schedule. After five years this difference was no longer statistically significant and children who presented anti-HBsAg concentrations below 10 mUI/ml received an additional booster dose which stimulated the antibody concentration to exceed 100 mIU/ml in all cases. Recombinant HBV vaccine induced better long term immunologic memory when it was administered earlier.

Antibodies↗
PubMed2000

Higher short-term virologic efficacy of three-class versus two-class highly active antiretroviral salvage therapy in HIV-infected patients.

The efficacy of two-class versus three-class antiretroviral salvage treatment was analyzed retrospectively in 63 HIV-infected patients in whom highly active antiretroviral therapy failed. Twenty-eight patients (group A) received two-class therapy, and 35 patients (group B) received three-class therapy. After 3 months of treatment, a significantly greater proportion of patients in group B (23/35, 65.7%) than in group A (8/28, 28.5%) showed a > or = 1 log10 decrease in the plasma HIV RNA level (P = 0.0034). However, after 9-12 months, 12 of 23 (52.1%) group B responders showed viral load rebound. The results were partially explained by the finding that, at baseline, the great majority (21/27, 77.7%) of group A patients showed mutations conferring resistance to all drugs administered, whereas in group B patients' susceptibility to at least two drug classes was retained. However, after 9-12 months of therapy, most (18/20, 90%) of the short-term responders in group B showed emergence of additional mutations that hampered long-term response.

Anti-HIV Agents↗
PubMed1999

Circulating progenitor cell release and functional characterization after topotecan plus G-CSF and erythropoietin in small cell lung cancer patients.

Topotecan is a new antineoplastic agent active in ovarian cancer, with promising activity in small cell lung cancer and predictable toxicity. As a part of our ongoing attempt to optimize the use of disease-specific drugs as circulating progenitor cell (CPC) priming in solid tumors, we have evaluated the effects on CPC release of single-agent Topotecan followed by granulocyte colony-stimulating factor (G-CSF) + human recombinant erythropoietin (rhEPO), together with the cell cycle status of the collected CD34+ cells. Ten pretreated patients with small cell lung cancer received Topotecan (1 mg/m2, i.v. for 5 consecutive days) followed by G-CSF (5 microg/kg/day, s.c.) + rhEPO (10,000 I.U. daily, s.c.), starting 24 h after Topotecan. The combination was well tolerated and no relevant side-effects were recorded. On day +10 (range +9 to +11) after the last dose of Topotecan, the median WBC count and the CD34+ cell peak were 8.2 x 10(3) microl (range 4.9-13.9) and 55 microl (range 28-75), respectively. Using flow cytometry, a detailed cell cycle analysis was performed on these CD34+ cells. The cell cycle distribution was determined by DNA content coupled with bromodeoxyuridine incorporation analysis. Apoptosis was evaluated by quantitating DNA strand breaks. The percentage of CD34+ cells in active S-phase was 10.2+/-5%, while early apoptotic CD34+ cells were detected in a low percentage (5.5+/-3%). Topotecan followed by G-CSF + rhEPO mobilizes CPCs effectively. This sequence exerts a stimulation on CD34+ cell cycle with a protective effect from chemotherapy-induced apoptosis. Taken together, these data could be of value for the incorporation of Topotecan, as well as of the combination of G-CSF and rhEPO, into high-dose chemotherapy programs with CPC support.

Adult↗
PubMed1998

Coinfection of the immunocompromised but not the immunocompetent host by multiple human cytomegalovirus strains.

Coinfection by multiple human cytomegalovirus (HCMV) strains was investigated in immunocompetent individuals and AIDS patients. Thirty HCMV maternal and fetal or newborn isolate pairs from 9 cases of congenital HCMV infection as well as 36 HCMV isolates and 2 PCR-HCMV-positive CSF samples from 13 AIDS patients were tested by restriction fragment length polymorphism analysis of multiple genome regions. Results from the group of congenital infections showed that: i) all the 9 women with primary HCMV infection presumably harboured a single HCMV strain; ii) all strains were genetically unrelated; iii) isolates from infected fetuses or newborns consisted of a single strain apparently indistinguishable from the maternal strain; iv) no strain variations were observed in isolates from different body sites or in sequential isolates from newborns up to 8 months after birth. Results from the AIDS patient group demonstrated that; i) all patients were infected by unrelated strains; ii) 6/13 (46.1%) patients were coinfected by 2 or more HCMV strains; iii) in a single patient two different HCMV strains were detected in blood and urine, respectively, whereas a mixture of the two was found in the pharynx; iv) 4 patients showed the sequential appearance of a mixed virus population or different strains suggesting sequential reinfections.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Expression of dipeptidylaminopeptidase IV/CD26 in peripheral blood lymphocytes of hemophilic subjects.

CD26 antigen, a 110 kDa membrane glycoprotein with exopeptidase activity (DAP IV), is an activation marker of T lymphocytes preferentially expressed on CD4+ memory cells and involved in T cell proliferation and IL-2 production after antigenic stimulation. We employed cytochemical and immunocytochemical techniques to study DAP IV/CD26 expression in circulating lymphocytes from 40 hemophilic patients, chronically treated with coagulation factors, in order to verify the possible involvement of this molecule in the immunological alterations of hemophilia. In all the hemophiliacs DAP IV activity was significantly lower than in the controls, independently of the quantity of blood transfused and previous exposure to viruses. This reduction may be responsible for the impaired proliferative response of lymphocytes to antigens and mitogens, notoriously observed in hemophilia. Whereas in the group of HIV- patients CD26 expression was similar to that of normal controls, in the 8 HIV+ hemophilic patients both percentages of positive lymphocytes and intensity of staining were significantly lower. In only 4 of the 8 cases was this deficit associated with CD4+ cell depletion. The significant selective loss of CD26 expression observed in HIV+ patients is probably an early event after HIV infection and seems to occur even before CD4 cell depletion. In conclusion, evaluation of DAP IV/CD26 might be a useful option for monitoring the immunological alterations of all hemophilic patients, HIV positive or not, chronically treated with coagulation factors.

Adolescent↗
PubMed1996

Successful immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus.

The study aimed to evaluate the immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus (IDDM), in view of reports of reduced efficacy in adults with IDDM. Sixty-five young people with IDDM, age 4.5 to 27.5 and diabetes duration 0.3 to 19 years and 174 age- and sex-matched healthy subjects were injected with a recombinant hepatitis B vaccine at 0, 1 and 6 months intramuscularly in the deltoid region. Three (4.6%) IDDM patients and 2 (1.1%) controls were non-responders (HBsAb titre, < 2 IU l-1) and 1 control was a low responder (HBsAb titre = 10 IU l-1). Among the 3 non-responder IDDM subjects, 2 had other autoimmune disease. Median HBsAb titre was similar in responding patients (120 IU l-1 and controls (125 IU l-1). There were no significant correlations between antibody titre and age, diabetes duration, HbA1c or insulin requirement. No association was found between HBsAb titre and any HLA genotype or the presence of microangiopathy. IDDM does not adversely affect the immune response to a recombinant hepatitis B vaccine in children, adolescents, and young adults, who can thus expect to benefit from its use in situations of risk of contracting hepatitis.

Adolescent↗
PubMed1993

HIV-1 and parasitic infections in rural Tanzania.

A sample of 300 sexually-active adults was selected at random from patients, from the rural area of Malenga Makali, Tanzania, who were attending a dispensary because they had diarrhoea of at least 2 weeks' duration. The potential associations between the patient's health (in terms of the World Health Organization's clinical definition of AIDS), HIV-1 seroprevalence and malaria and other parasitic infections were then investigated. Although, HIV-1 seroprevalence was 20.6% overall, the level of seroprevalence was directly correlated with the distance between the patients' home villages and the nearest main road. Strict application of the clinical definition of AIDS gave 98.7% specificity, 46% sensitivity and a predictive value of 90.6% when validated by HIV-1 seropositivity. Although malaria infection was more common in HIV-1 seropositives than in the seronegatives, the intensity of the Plasmodium falciparum infections, intestinal amoebiasis and giardiasis did not appear to be correlated with HIV-1 infection. In contrast, intestinal infections with Cryptosporidium parvum and Isospora belli were virtually restricted to HIV-1 seropositive individuals who had had diarrhoea for a relatively long time.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Control of hepatitis B: evaluation of two different vaccinal schedules in newborns from HBsAg negative mothers.

504 healthy infants, born to HBsAg negative mothers from May 1st to December 31st 1991, were randomly allocated to an accelerated (group A) or traditional (group B) immunization schedule. The group A infants were immunized at 4 days, 1 month and 3 months of life with 10 micrograms of recombinant HBV vaccine (Engerix B, SKF) while the group B infants were immunized at 4 days, 1 month and 6 months of life with the same dose of vaccine. One month after the first dose of vaccine, 9.2% of the infants in both groups had an HBsAb serum level > 10 mIU/ml. One month after the booster dose, at 4 months of life for group A and at 7 months for group B, 97.40% and 98.53% of the infants presented a serum level > 10 mIU/ml respectively. None in group A and only 2 patients in group B could be considered non-responders (serum concentration below 2 mIU/ml) and 4 infants in group A and 4 in group B were considered hypo-responders (serum level between 2.1 and 9.9 mIU/ml). Immunogenetic study performed on the 2 non-responders and 6 of the hypo-responders, revealed the presence in all but two of the HLA haplotypes, classically involved in the lack of hyporesponsiveness to foreign peptides, namely: HLA-DR7; DQ2, DR4; DQ3, DR15; DQ6 and DR3; DQ2. Surprisingly, 2 hypo-responders carried the HLA haplotypes (DR11, DQ7 and DR13, DQ6), usually associated with hyperresponsiveness. Both vaccinal cycles provided evidence that infants respond well to vaccination, started at birth, against hepatitis B virus with a high degree of protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗
PubMed1990

Effect of teicoplanin and vancomycin on Staphylococcus aureus ultrastructure.

Morphological changes induced by teicoplanin and vancomycin on Staphylococcus aureus have been comparatively evaluated. The most pronounced structural damages were found on the cell wall which was uniformly thickened on bacteria exposed to teicoplanin while it was of irregular thickness and often absent around the cells in those exposed to vancomycin. The inhibitory action of teicoplanin on proteoglycan polymerization but not on nucleic acid and protein synthesis indicates that the effect in the wall is due to the accumulation at this level of proteoglycan soluble precursors continuously produced by the cell. The different effects induced by vancomycin on cell wall morphology can also be related to the compatibility of this antibiotic in altering cytoplasmatic membrane function and ribonucleic acid synthesis.

Anti-Bacterial Agents↗