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Biomedical subjects

M Carlesimo

Publications and source records attributed to M Carlesimo.

At least 19 recordsLinked to original sources

Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease.

OBJECTIVES: Evaluation of immunological reconstitution after 2 years of highly active antiretroviral therapy (HAART) in AIDS patients. DESIGN: Previous data showed the effectiveness of HAART but conflicting evidence of immune reconstitution has been found in severely immunocompromised patients. Therefore, T-cell subsets and functions were analysed during 24 months of HAART in 21 AIDS patients (mean baseline CD4 cell count, 20 x 10(6)/l). METHODS: Subjects were tested at baseline and after 4, 12 and 24 months of therapy for clinical symptoms and the following investigations were carried out: plasma HIV RNA, T-cell subsets and lymphoproliferative responses to mitogens (phytohaemagglutinin, anti-CD3), and recall antigens (Candida mannoprotein, tetanus toxoid and recombinant glycoprotein 160). RESULTS: Increase in body weight, improvement of Karnofsky's score and reduction of opportunistic infections were observed. All patients showed an initial increase in the CD4 memory subset, whereas naive CD4 cells consistently increased only after 1 year. The magnitude of immune recovery was stronger in patients showing a significant reduction in viral load. However seven out of 21 patients who did not reach a sustained suppression of viral load showed also an increase in T-cell subsets. The majority of patients recovered lymphoproliferative responses to mitogens, whereas only four subjects showed a functional response to Candida mannoprotein. No patients showed a response to HIV recombinant glycoprotein 160 or tetanus toxoid. CONCLUSIONS: The immune recovery observed is slower and not complete in severely immunocompromised patients. Our data suggest that HAART may be continued also in the absence of a significant HIV RNA decrease if alternative drugs are not available.

Adult↗

Clinical and immunologic response without decrease in virus load in patients with AIDS after 24 months of highly active antiretroviral therapy.

This study reports an analysis of clinical, virological, and immunologic outcomes in a cohort of 77 multidrug-experienced AIDS patients during 24 months of highly active antiretroviral therapy (HAART). Our results have shown a reduced risk of AIDS complications, prolonged survival, and immunologic benefit even in the absence of sustained virus suppression. The degree of immunodepression, the risk factors for HIV-1 infection, the use of 2 drugs instead of 3, and a change in protease inhibitor were independently correlated with virological failure. In the majority of studied patients, an increase in CD4+ T cells was observed after HAART. However, the increase was more pronounced in patients who showed a decrease in virus load than in those who did not. Moreover, we observed an absence of relapses among patients who permanently discontinued prophylaxis for Cytomegalovirus retinitis and atypical mycobacterial infections. Peripheral lipodystrophy developed in the majority of patients, regardless of treatment used and virological outcome.

AIDS-Related Opportunistic Infections↗

Alkaptonuria.

Explore the source record for details and available documents.

Aged↗

Phase II controlled trial of post-exposure immunization with recombinant gp160 versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn Protocol Team.

OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN: Multicentre, double-blind, three-arm, placebo-controlled study. SETTING: Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). RESULTS: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

AIDS Vaccines↗

Skin diseases in immigrants seen as out-patients in the Institute of Dermatology of the University of Rome 'La Sapienza' from 1989 to 1994.

In the Institute of Dermatology of the University of Rome 'La Sapienza' (IDURLS) from 1989 to 1994, 2198 immigrants from countries outside the European Community were seen as out-patients. Their personal and pathological data were collected by a particular software 'Questio', set up together with colleagues of the Interdepartimental Center for Scientific Calculous (ICSC) of the University of Rome 'La Sapienza'. The number of patients has been increasing from 326 in 1989 to 436 in 1994. Most of the people were coming from Africa, but from 1989 to 1994 the number of patients from the regions of ex-Yugoslavia has been increasing. About one third of the immigrants were unemployed, whereas 40% of them had a job (worker or employee), and the remaining 20% was composed by students and housewives. Most immigrants (1474 patients) were 20-39-year-old. Their data were compared with those of a control group composed by 2100 Italian people of the same age and sex, seen as out-patients in IDURLS in the same period. The most frequent skin disorders observed in immigrants were skin infectious or parasitic diseases, above all scabies. Excluding people with scabies, both immigrants and Italian patients shared the same skin diseases typical of young adult people: many fungal infections, many contact dermatitis and very few skin malignant tumors.

Adolescent↗

CD28 costimulation and T lymphocyte proliferative responses in HIV-1 infection.

To investigate whether defective costimulatory signals could be involved in the loss of T lymphocyte functions during HIV-1 infection, we tested the effect of CD28 costimulation on both T cell receptor/CD3 and HIV-1 antigen-induced proliferative responses. Although CD3-mediated responses significantly decreased with more advanced stages of HIV-1 infection, the ability of potentiating the responses through CD28 costimulation was maintained at all stages and did not differ from that of HIV-1- subjects. When CD28 costimulation was studied in lymphocyte cultures stimulated with HIV-1 gp160 or p24, potentiation was seen only when a significant response was present without additional CD28 triggering, namely in subjects receiving active immunization with recombinant gp160. These results confirm the integrity of the CD28 pathway of costimulation during HIV-1 infection, and suggest that lymphocytes responding to soluble HIV-1 antigen are not deleted in HIV-1-infected patients, but do not receive significant priming during the natural course of the infection.

CD28 Antigens↗

Long-term evaluation of cellular immunity during antiretroviral therapy and immunization with human immunodeficiency virus type 1 (HIV-1) Env glycoprotein in HIV-1-infected persons.

Cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens, microbial recall antigens, and CD3 monoclonal antibody were studied in HIV-1-infected asymptomatic patients in a phase II, double-blind trial of immunization with recombinant HIV-1 gp160 in or not in association with zidovudine. A vigorous and persistent lymphoproliferative response (LPR) to HIV-1 Env antigens was observed in vaccinated patients. Neither Env-specific lymphocyte cytotoxicity nor LPR to recall antigens was significantly influenced by gp160 administration. The induction of LPRs to HIV-1 envelope proteins did not show positive effects on the course of HIV-1 infection. Patients treated with zidovudine alone or in combination with the immunogen showed improvement of T lymphocyte responses and transient reduction of viremia. These results suggest that antiretroviral therapy is more beneficial than immunization with gp160 and should always be considered in association with future vaccination and immunotherapeutic interventions in HIV-1-infected subjects.

Adolescent↗

Alterations of microsatellites in neurofibromas of von Recklinghausen's disease.

von Recklinghausen's disease, or type I neurofibromatosis, a common familial tumor syndrome, is characterized by the occurrence of multiple benign neoplasms of nerve sheath cells. The disease is caused by germ-line mutations of the NF1 gene, which encodes a member of the GTPase-activating superfamily of Ras regulatory proteins. We analyzed 5 dinucleotide repeat loci in DNAs from neurofibromas and matched normal skin from 16 NF1 patients. Eight cases (50%) manifested microsatellite alterations. Expansions or compressions of dinucleotide repeats were observed at one locus in four cases and at two loci in one case. Banding patterns compatible with the loss of a microsatellite allele were observed in four cases, including one that also presented microsatellite instability. The surprisingly high frequency of microsatellite alterations suggests that the NF1 gene or another gene(s) contributing to the pathogenesis of neurofibromas might be directly or indirectly implicated in the control of genomic integrity.

Adult↗

Treatment of cutaneous and pulmonary sarcoidosis with thalidomide.

Many therapeutic agents have been proposed for treatment of steroid-resistant sarcoidosis. Because administration of low doses of thalidomide has been successful in treating other inflammatory diseases, it was used in a patient with systemic sarcoidosis who was unresponsive to corticosteroids and in a patient with pulmonary sarcoidosis, in whom Kaposi's sarcoma developed after a course of corticosteroid therapy. Thalidomide, 200 mg/day for 2 weeks followed by 100 mg/day for 11 weeks, was given. This treatment was effective in both patients. No adverse reactions were observed. Thalidomide, 100 mg on alternate days, is still being administered. No relapse has occurred. Thalidomide, particularly because of its inhibition of the macrophage function, may be a useful alternative therapy in steroid-resistant cases. In addition, the correlation between the angiotensin-converting enzyme level and the clinical improvement observed in our patients suggests a direct parallel between angiotensin-converting enzyme and the activity of the granulomatous process.

Aged↗

HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals.

In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens.

Adolescent↗

Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.

OBJECTIVES: To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS: Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 women, three men; mean age 45.0 (10.1) years). RESULTS: Plasma ET-1 levels were significantly greater in patients affected by systemic sclerosis (1.65 (0.29) pg/ml) than in controls (0.63 (0.19) pg/ml) (p < 0.0001). Pulmonary artery systolic hypertension alone was present in 14 patients with systemic sclerosis (50.5 (8.49) mm Hg, range 37-67 mm Hg), and systemic hypertension alone (160.7 (5.9)/100.6 (3.2) mm Hg) was present in 11 patients. Both conditions were present in 12 patients, while 11 patients had systemic hypertension. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension alone (1.62 (0.21) pg/ml) and those with systemic hypertension alone (1.65 (0.43) pg/ml). In particular, patients with normal pulmonary artery and systemic pressures (n = 11) had plasma ET-1 concentrations identical to those found in patients (n = 12) with both pulmonary and systemic hypertension (1.70 (0.15) v 1.64 (0.35) pg/ml, respectively). No correlations were observed between plasma ET-1 and either pulmonary or systemic pressures. CONCLUSION: Systemic sclerosis is characterised by increased plasma ET-1 levels, but neither pulmonary nor systemic hypertension are accompanied by further increase in plasma peptide levels.

Endothelins↗

Late infantile ceroid-lipofuscinoses. An ultrastructural study.

The aim of the present study is to investigate further the ultrastructural skin patterns in five cases of late infantile ceroid-lipofuscinosis: two of these were classic forms, the others were variants. Ultrastructural examinations of skin biopsies revealed the presence of characteristic cytosomes; typical lipofuscin, consisting of osmiophilic granular materials, curvilinear bodies, and fingerprint bodies. Different ultrastructural profiles were found simultaneously in each case, without a significant prevalence of any specific one, and were often associated with lipid droplets. These inclusions were found in several epidermal and dermal cells. A different degree of involvement of the myelinated sheaths in the five cases was observed. This difference could be genetically determined or perhaps related to different stages of the disease. The findings demonstrate the involvement of clinically unaffected skin and confirm the relevance of electron microscopic studies in diagnosing these disorders. In fact, recognition of typical ultrastructural changes is a valuable diagnostic tool that can be used in supplementing clinical and electrophysiological examinations, especially when the metabolic error is unknown and no diagnostic biochemical assay is available.

Child↗

Cyclosporin A: preliminary results in the treatment of psoriasis.

Cyclosporin A (CYA) has recently attracted the attention of the dermatologists with regard to its use in the treatment of severe psoriasis. We report four cases of psoriasis resistant to conventional therapy. Three patients were affected by chronic plaque psoriasis and one by erythrodermic psoriasis. The initial dosage of CYA was 5 mg/kg/day per os, and was gradually reduced according to the course of the disease. The drug was administered for a period of 6 weeks. All patients showed a significant improvement of the clinical picture. No remarkable clinical side effects were observed. During the trial we took skin biopsies on which we conducted histological and immunohistochemical studies. The efficacy of CYA in the treatment of psoriasis demonstrates the important role of the cell mediated immunity in the pathogenesis of psoriasis.

Adult↗