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Biomedical subjects

Antonella Esposito

Publications and source records attributed to Antonella Esposito.

11 recordsLinked to original sources
PubMed2006

T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART.

OBJECTIVE: To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART. DESIGN: Thirty-five HIV-positive subjects on HAART for at least 1 year, all with undetectable HIV-1 RNA, were studied. Patients were defined as InR according to a CD4 cell increase < 20% from CD4 cell baseline or CD4 cell count < 200/microl; subjects with a CD4 T-cell increase > 20% from baseline and a CD4 cell count > 200/microl were defined as immunological responders (IR). We performed a comprehensive study to characterize the immune response of InR. METHODS: The immunological phenotype of peripheral blood mononuclear cells, thymic naive T cells, T-cell receptor Vbeta repertoire, serum concentration of interleukin (IL)-7, the expression of IL-7Ralpha on naive and memory CD4 and CD8 T cells, and regulatory T cells (Treg) were studied. RESULTS: In InR a significant reduction (P < 0.0001) of naive and thymic naive CD4 T cells was associated with a reduced expression of IL-7Ralpha in both cell subsets, with an increased serum concentration of IL-7 was observed. Furthermore, an increased immune activation with a reduced Treg frequency and increased number of expansions of Vbeta families was observed. CONCLUSIONS: The reduced expression of IL-7Ralpha associated with the persistent immune activation and the alteration of Treg frequencies in part explains the low level of CD4 T cells observed in InR.

Adult↗
PubMed2006

A case of Pneumocystis jiroveci pneumonia in X-linked agammaglobulinaemia treated with immunosuppressive therapy: a lesson for immunologists.

The case of a 20-year-old patient, affected by X-linked agammaglobulinaemia (XLA), who developed severe pneumonia from Pneumocystis jiroveci (formerly Pneumocystis carinii) (PCP), is reported. This infection usually affects patients with AIDS, children affected by severe combined immunodeficiency or hypogammaglobulinaemia with hyperimmunoglobulin M, or patients undergoing severe immunosuppression. The XLA patient developed PCP during therapy with steroids and cyclosporine A, carried out for several months, due to an extended skin vasculitis, accompanied by general symptoms. The pneumonia had a severe clinical course, requiring a long hospitalization. At the diagnosis of PCP, immunosuppressive therapy was suspended and the patient recovered after a long-term trimethoprim/sulfamethoxazole therapy. Immunological studies revealed an unexpected normal number of CD4+ and CD8+ T cells. The two subsets had an exclusive naïve phenotype (95% CD4+CD45RA+CD62L+ and 89% CD8+CD45RA+CD62L+ cells), with an absence of primed cells. Lymphoproliferative responses to P. carinii and recall antigens as well as to mitogens were extremely deficient. During the follow-up, memory cells appeared with recovery of the lymphoproliferative response to mitogens and maintained defective responses to antigens. This is one of the few reported XLA cases experiencing severe PCP. In this patient, the infection became clinically evident during immunosuppressive therapy. We believe that the absence of functional activities, despite a normal level of T lymphocyte counts, sustained this long-lasting infection. Thus, the CD4+ and CD8+ T cell count evaluation, without functional studies, may not be per se sufficient for predicting the risk of a severe clinical course of PCP in patients undergoing immunosuppression.

Adult↗
PubMed2005

Immunodysregulation of HIV disease at bone marrow level.

Hematological abnormalities frequently occur in patients infected with HIV-1. Increasing evidence indicates that bone marrow (BM) suppression results from viral infection of accessory cells, with impaired stromal function and alteration of hematopoietic growth factor network. We investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells, in a group of HIV-1-infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells has been observed before treatment, characterised by decreased IL-2 and elevated TNF-alpha, MIP-1alpha, MIP-1beta, and RANTES levels, along with a defective BM clonogenic activity. Antiretroviral therapy determined an amelioration of stem cell activity, a restoration of stromal cell pattern and functions, and an increased IL-2 production at BM level and a decrease of Fas expression on progenitor cells, in parallel with the diminution of TNF-alpha levels. HIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on the BM progenitor cells. Ritonavir and indinavir increased the colony growth of BM obtained either from HIV-1-infected patients or from normal individuals, in parallel with the normalization of functional and morphologic characteristics of stromal cells.

Bone Marrow Cells↗
PubMed2004

Quantitative ultrasound of proximal phalanxes in patients with type 1 diabetes mellitus.

The influence of duration of diabetes and metabolic control on phalangeal quantitative ultrasound (QUS) was evaluated in a group of children and adolescents with type 1 diabetes. Eighty-six patients (mean age 11.9 years; mean duration 4.3 years) were studied. Daily calcium intake was assessed by means of a questionnaire. Amplitude-dependent speed of sound (AD-SoS) was measured at the phalanxes of the non-dominant hand and expressed as a z-score. Linear and multivariate correlations with duration of diabetes and, short term and long term metabolic control were sought. AD-SoS z-score was -0.43+/-1.4 (95% CI, -0.73; -0.13). Nine subjects had values below -2S.D. Daily calcium intake was 1042+/-456 mg/day; 47 subjects (54.6%) were below the recommended levels. A negative correlation was found between AD-SoS z-score and duration (r, -0.33, P=0.002) or metabolic control (HbA1c-last year r, -0.32, P=0.002; HbA1c-whole duration, r, -0.40; P=0.003). Negative AD-SoS z-scores depended significantly and directly on duration and quality of metabolic control, even when controlled for calcium intake. In conclusion, the architectural organization of bone was impaired in 10.5% patients. Duration of diabetes and poor metabolic control were the main determinants affecting AD-SoS. QUS may be a useful tool in the screening of bone disturbance in young patients with diabetes. Optimization of metabolic control is required to prevent osteoporosis.

Adolescent↗
PubMed2002

Dietary calcium intake and serum vitamin D are major determinants of bone mass variations in women. A longitudinal study.

BACKGROUND AND AIMS: Bone mineral density (BMD) is one of the main determinants in the pathogenesis of fractures. However, data on factors predicting longitudinal variations in BMD are still limited and incomplete. Such data would be of great importance in order to better focus prevention strategies in both the clinical setting and at the population level. The aim of the study was to investigate the predictive value of both serological and questionnaire variables for bone mass variations in healthy women participating in a population-based longitudinal study carried out in Napoli, Italy. METHODS: High completion rate (85.2%) and adequate sample size were obtained: 139 women (45 to 79 years of age) were examined at study entry and then again after two years (24 +/- 2 months) following the same protocol. They underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Data analysis included calculation of the percent variation in BMD in the 2-year period. Longitudinal data underwent stepwise analysis for a global evaluation of mutual interactions between independent variables. RESULTS AND CONCLUSIONS: Our findings indicate that dietary and serum calcium, and serum 25(OH)vitamin D are the only independent determinants of BMD variations at the lumbar and femoral level, respectively. While the pharmacological significance of calcium and vitamin D in the therapy of established osteoporosis is still controversial, the present longitudinal data evidence their role as essential nutrients in determining the natural history of BMD variations.

Aged↗
PubMed2002

Long-lasting bone damage detected by dual-energy x-ray absorptiometry, phalangeal osteosonogrammetry, and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation.

Bone complications after allogeneic stem cell transplant (allo-SCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1-10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a T-score less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass.

Absorptiometry, Photon↗
PubMedDate not supplied

[Osteoarticular scintigraphy in comparison with clinical evidence].

Bone scintigraphy is a technique which is often resorted to in diagnostic rheumatology. There are few data on the effective relevance of bone scintigraphy in the evaluation of chronic inflammatory diseases of the joints. The aim of this study was to compare the results of bone scintigraphy with clinical evidence in patients with rheumatoid arthritis or osteoarthritis. Seventy-five patients were submitted to total body bone scintigraphy (44 rheumatoid arthritis, 31 osteoarthritis). The nuclear medicine specialist indicated the list of joints showing uptake. For the same patients a rheumatologist indicated the number of affected joints. The laboratory and clinical data were recorded. The patients were first stratified according to the prevalence of the clinical evidence and scintigraphic uptake. The distribution was found to be not significant. Only 5.3% of patients showed no uptake. Thirty-three patients had no clinical evidence of disease; among these, 30 showed joint uptake. Considering only the patients with clinical evidence, 97.6% showed joint uptake. These results were confirmed even when the data were analyzed by sex, disease and therapy. Considering the patients with clinical evidence, the uptake/clinical ratio did not show any significant correlation. The number of joints with clinical evidence correlated with the erythrocyte sedimentation rate. The number of joints showing uptake correlated only with age. In conclusion, on average, scintigraphy, performed in patients with rheumatoid arthritis and osteoarthritis, highlights a significantly higher number of joints involved as compared to what would be expected on the basis of clinical evaluation. It remains to be defined whether this is an overestimation related to the characteristics of the scan or whether it is sign of a higher sensitivity in highlighting the site of inflammation. Against the latter hypothesis is the absence of correlation with the inflammatory indexes.

Adult↗
PubMedDate not supplied

Microalbuminuria and uric acid in healthy subjects.

BACKGROUND: Microalbuminuria has been linked to cardiovascular (CV) risk in patients with diabetes or hypertension, and in an unselected general population; serum uric acid (UA) is emerging as a novel risk factor for CV disease. The aim of our study was to evaluate the prevalence of excess microalbuminuria and its relation to established CV risk factors and serum UA in healthy subjects. METHODS: We screened 900 healthy blood donors (age range, 20-65 years; 747 men, 153 women), and measured total, HDL and LDL cholesterol, blood glucose, serum and urinary creatinine, serum UA, blood pressure (BP) and microalbuminuria (urinary albumin/creatinine ratio, ACR). The Framingham risk score was also calculated. RESULTS: After excluding 52 participants, we found that in 848 participants (702 men, 146 women) the overall prevalence of excess ACR, using a 30 mg/g creatinine cutoff, was 9.3% (9.7% of men, 7.5% of women, p=0.16); adopting a gender-dependent cutoff, we found that the overall prevalence was 13.6% (15.1% of men, 6.2% of women, p<0.01). ACR was highly correlated to diastolic (r=0.88, p<0.001) and systolic (r=0.74, p<0.001) BP, and also--though not as strongly--to serum UA (r=0.38, p<0.001). In a stepwise multiple regression model, systolic and diastolic BP, total cholesterol, serum creatinine and UA were segregated as independent predictors of microalbuminuria (model R=0.91, R square=0.83). Correlation of serum UA to ACR remained significant, albeit attenuated (r=0.09, p=0.02), after adjustment for serum creatinine, total cholesterol, systolic and diastolic BP. CONCLUSIONS: The results of our study show ACR to be abnormal in a significant proportion of seemingly healthy subjects, and serum UA to be an independent predictor of microalbuminuria.

Adult↗