Evidence for less marked potential signs of T-cell immunosenescence in centenarian offspring than in the general age-matched population

People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4(+) and CD8(+) early- and late-differentiated T cells, as well as potentially senescent CD8(+) T cells, suggesting that the adaptive T-cell arm of the immune system is more "youthful" in centenarian offspring than controls. This might reflect a superior ability to mount effective responses against newly encountered antigens and thus contribute to better protection against infection and to greater longevity

Percutaneous ethanol injection of hepatic tumors : single-session therapy with general anesthesia

OBJECTIVE: We studied the feasibility and the effectiveness of percutaneous ethanol injection, performed with general anesthesia in a single session, for treating malignant hepatic lesions. SUBJECTS AND METHODS: We treated 30 patients with sonographically guided percutaneous injection of ethanol. Twenty had hepatocellular carcinoma and cirrhosis, and 10 had hepatic metastases, principally from colon cancer. The mean volume of ethanol injected was 57 ml (range, 6-165 ml). RESULTS: CT showed complete necrosis (up to 8.2 cm) in seven of 10 patients with encapsulated hepatocellular carcinoma and about 90% necrosis in the remaining three patients. In four of these patients, the alpha-fetoprotein level fell from more than 200 ng/ml to less than 20 ng/ml during treatment. In 10 patients with infiltrating hepatocellular carcinoma, about 70-90% necrosis was achieved; in six of these patients, the alpha-fetoprotein level, which had been more than 200 ng/ml, decreased during treatment. In the 10 patients with metastases, more than 50% necrosis was always achieved. Levels of carcinoembryonic antigen decreased after treatment in all patients. In three patients who had cirrhosis with superficial hepatocellular carcinoma, peritoneal hemorrhage occurred but did not require transfusion. CONCLUSION: Our results show that percutaneous injection of ethanol in a single session with general anesthesia is feasible and effective and has several advantages over multisession therapy. These include shorter treatment time and the ability to treat larger and more numerous lesions

Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome? Need for a long-term follow-up.

PURPOSE: Ectopia lentis (EL) and Marfan syndrome (MFS) are considered two distinct clinical entities. We performed genetic and clinical studies to investigate whether EL is actually distinct from MFS or if it is a mild phenotypic expression of it. METHODS: Seven patients with EL were followed for 5-10 years. Mutation screening analysis of the 65 exons of FBN1 was performed by polymerase chain reaction (PCR) amplification of genomic DNA, denaturing high pressure liquid chromatography analysis, and direct sequencing of heteroduplexes. RESULTS: Yearly examinations during the 10 years of follow-up allowed the detection of a late onset of dural ectasia in six out of seven patients (age range: 32-64 years versus 8-55 years in MFS previously reported). We also detected the onset of mild thoracic aortic dilatation in a sporadic case (age 45). Six out of seven index cases of EL turned out to be mild forms of Marfan syndrome with possible late cardiovascular involvement as detected in one case. Four novel missense mutations and one known splicing mutation were detected in five out of seven (71%) patients. Their localization confirmed the presence of a first hot spot within exons 1-15 and suggested the presence of a second one between exons 31-39. CONCLUSIONS: The presence of a second major criterion in six EL patients shifted the clinical diagnosis from EL to MFS. These data demonstrate that some cases, which are initially diagnosed as EL, turn out to be mild Marfan patients. A clinical cardiovascular follow-up is therefore highly recommended for all EL patients since they may develop thoracic aortic aneurysm (TAA) or dissection later in life. Also magnetic resonance imaging (MRI) for dural ectasia (DE) should be performed in a complete follow up for a MFS diagnosis

Kaposi's sarcoma in HIV-infected patients in the era of new antiretrovirals

Kaposi's Sarcoma (KS) is a multicentric angioproliferative cancer of endothelial cells (ECs) caused by Human Herpesvirus 8 (HHV8) characterized by clinical heterogeneity depending on the host immune conditions. Despite its incidence has dramatically decreased in developed countries after the introduction of Highly Active Antiretroviral Therapy (HAART), KS remains the most frequent tumor in HIV-infected patients worldwide. Clinical presentation varies from an indolent slowly progressive behavior, generally limited to the skin, to an aggressive and rapidly progressing disease. In more than 50% of cases, the skin lesions are often associated with a more or less important visceral involvement, particularly to the oral cavity and the gastrointestinal tract that are involved in 35% and 40% of cases respectively. A large number of treatments can be used both as local and as systemic therapy. Particularly, HAART represents the first treatment in patients with moderate lesions limited to skin, and it can be sufficient to reduce significantly the size of lesions and, often, the complete disappear in 35% of cases after 3-9 months of treatment. In case of a rapidly progressive disease with extensive cutaneous and/or visceral involvement systemic drugs are used such as the liposomal anthracyclines pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX), the combined treatment adriamycin-bleomycin-vincristine (ABV) and bleomycin-vincristine (BV), Paclitaxel and Interferon-alfa. In patients with limited skin localization, the local treatment can play an important role. Local medical therapy is based on the use of alitretinoin, antineoplastic drugs vincristine, vinblastine and bleomycin and Sodium Tetradecyl Sulfate (STS). In addition to medical therapy, physical treatment, such as cryotherapy and radiotherapy, are also commonly used

Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline VIRO-immunological status and outcome in patients under first-line ART

Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to VIRO-immunoclinical events. Results Pre-ART HIV DNA [median (IQR): 10 \u20ac 702 (3397-36 \u20ac 632) copies/10 6 CD4+ T cells] was correlated with pre-ART HIV RNA [R 2 = +0.44, (P 10 \u20ac 000, 81.1% for 1000-10 \u20ac 000 and 86.4% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of VIROlogical rebound (defined as HIV RNA >50 copies/mL) by 24 months (17.2% for >10 \u20ac 000, 7.4% for 1000-10 \u20ac 000 and 4.3% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0048). Adjusted HRs of all VIROlogical rebound definitions confirmed these findings (P 64 0.02). Conclusions Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of VIROlogical suppression ( 6450 copies/mL)