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Biomedical subjects

G Guaraldi

Publications and source records attributed to G Guaraldi.

27 records · Page 2Linked to original sources

Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome.

In 8 patients with symptomatic, acute primary infection with human immunodeficiency virus (HIV), a dramatic and persistent decrease in CD4+ lymphocytes was seen, accompanied by a marked increase in activated/memory CD8+ T cells (CD38+, CD45R0+, HLA-DR+, with high amounts of cell adhesion molecules), which represented most circulating lymphocytes, but no gross alterations in V beta T cell repertoire. Extremely high plasma levels of proinflammatory cytokines were observed. Three patients were followed for 2-3 years: The number of CD4+ cells, extremely low at first, increased significantly in a few months but decreased rapidly after a short stable period. Cytotoxic T lymphocytes bearing markers of immunologic activation/memory could play an important role in the earliest phases of the disease. It remains to be established how such a dramatic onset could determine the rapid progression of the infection that seems characteristic of patients with acute HIV syndrome.

Acquired Immunodeficiency Syndrome↗

Lack of selective V beta deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T-cell repertoire during acute HIV syndrome.

OBJECTIVE: To study the V beta T-cell repertoire in peripheral blood lymphocytes (PBL) during acute HIV syndrome by using several anti-V beta monoclonal antibodies (MAb) and to analyse its functionality by stimulating PBL with superantigens (SAg) such as Staphylococcus aureus enterotoxins. METHODS: Cytofluorimetric analysis of V beta T-cell-receptor expression was performed on PBL from eight patients with symptomatic, acute HIV-1 primary infection, showing a dramatic decrease of CD4+ PBL accompanied by a marked increase in activated/memory CD8+ T cells, and on 12 age- and sex-matched healthy controls. PBL were then isolated, stimulated with different SAg, anti-CD3 MAb or phytohaemagglutinin and cultured for 3 days. PBL capability to progress through cell cycle was studied by the classic cytofluorimetric method of bromodeoxyuridine incorporation and DNA staining with propidium iodide. RESULTS: Despite the presence of a few expansions of some V beta families among CD8+ T lymphocytes, no gross alterations in T-cell repertoire were present in patients with acute HIV syndrome. Its functionality was maintained overall, as PBL responsiveness to SAg was well preserved. Interestingly, all CD8+ T cells, although bearing different V beta T-cell receptors, expressed marked signs of activation, i.e., CD45R0, CD38 and major histocompatibility complex class II molecules, and also high amounts of CD11a and CD18. CONCLUSIONS: Our data suggest, at least in the early phases and in the acute form of the infection, that HIV is not likely to act as a SAg. However, further studies are needed to analyse other sites, such as lymph nodes, where HIV could exert other, significant effects, and to study the expression of other V beta families than those investigated here.

Acquired Immunodeficiency Syndrome↗

Non-typhoid Salmonella subdural empyema in a patient with AIDS.

In AIDS patients, non-typhoid salmonella metastatic abscesses in lung and brain due to bacteremia have been described previously. Here we present a case in which a group B Salmonella, serotype Copenhagen, caused right parietal subdural empyema. The etiologic diagnosis was based on culture of pus obtained from the lesion. The patient was treated for bacterial meningitis and made a good recovery. He is at present reasonably well and is taking ciprofloxacin as prophylaxis against salmonella relapse.

AIDS-Related Opportunistic Infections↗

Mosaicism for an extra small ring chromosome.

A new case for mosaicism for an extra small ring chromosome is described in a 13-year-old girl with minimal phenotype anomalies and moderate mental retardation. The origin of the extra chromosome could not be determined either cytogenetically or clinically. The present case is compared with six similar cases in the literature.

Adolescent↗

Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

Adult↗

Rituximab as treatment of posttransplant lymphoproliferative disorder in patients who underwent small bowel/multivisceral transplantation: report of three cases.

This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.

Adolescent↗

Lipid profile during pregnancy in HIV-infected women.

PURPOSE: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. METHOD: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (PIs) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. RESULTS: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p < .001), 60.8 mg/dL for total cholesterol (p < .001), 13.7 mg/dL for HDL cholesterol (p < .001), and 17.8 mg/dL for LDL cholesterol (p = .001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on PIs. The effect of PIs on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. CONCLUSION: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV.

Adult↗

Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis.

PURPOSE: To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART). METHOD: We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation. RESULTS: 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Delta lumbar-BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p = .795]). CONCLUSION: Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis.

Administration, Oral↗