From micro to mesoscale: Understanding the influence of macroalgal communities on Ostreopsis Schmidt blooms.

Harmful Algal Blooms (HABs) are increasing in temperate areas, and the growth rates of benthic harmful dinoflagellates may be favoured in the context of global climate change. Benthic dinoflagellates, including species belonging to the Ostreopsis Schmidt genus, are known to develop on the surface of macroalgae and different macroalgal morphotypes and communities could host higher or lower cell abundances. The physical structure of the macroalgal substrate at the small scale (cm, microhabitat scale) and the structural complexity of the macroalgal community at the medium scale (few m, mesohabitat scale) could play a relevant role in bloom facilitation: the hypothesis that Ostreopsis species could be associated with macroalgal turfs and shrubs, structurally less complex communities than canopy-forming macroalgae, is especially under discussion and, if confirmed, could link bloom occurrence to regime shifts in temperate ecosystems. The present study, performed in two locations of the Ligurian Sea (Rochambeau, France and Vernazzola, Italy) aimed at understanding marine vegetation's role at the micro and mesohabitat scales in controlling the distribution and abundance of Ostreopsis. The abundance of the microalgal cells was quantified at different spatial scales, from cm to a few m, on different macroalgal species and communities, including artificial substrates, to tease apart the micro and mesohabitat effects. The results obtained show a high spatio-temporal variability, potentially hiding habitat-related patterns. The substrate's preferences diminish when cell abundances are very high, as in the case of Rochambeau, while in presence of moderate cell abundances as in Vernazzola or the first phases of blooms, it is possible to appreciate differences in abundances among substrates (in our study, Dictyota fasciola (Roth) Lamouroux supporting higher abundances). Our results open new research topics such as the study of blooms at a larger scale (macrohabitat) and testing different sampling methods to standardise the cells' abundances independently on the substrate.

HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis.

BACKGROUND: We hypothesized that there may be a correlation between the interleukin-7 (IL-7)/IL-7 receptor (IL-7R) regulatory system and parameters of T-cell homeostasis in HIV-infected long-term nonprogressors (LTNPs) as compared with patients with disease progression. METHODS: The possibility of a correlation between T-cell homeostatic parameters and IL-7/IL-7R was investigated in 22 LTNPs (CD4 count > or =500 cells/microL for >10 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count > or =400 cells/microL ; 15 late (AIDS-presenters): CD4 count < or =150 cells/microL ]. RESULTS: Compared with early-stage HIV-positive patients, LTNPs displayed a higher circulating IL-7 concentration (P=0.05), which was positively associated with higher IL-7Ralpha expression and a higher T-cell receptor excision circle (TREC) content specifically within CD4 cells (P<0.05). Compared with late-stage disease patients, early-stage disease patients displayed a lower IL-7 concentration (P<0.01) and higher percentages of IL-7Ralpha+ CD4 and CD8 cells (P=0.05). IL-7 was positively correlated with the percentage of TREC+ CD4 cells (P<0.01), which translated into a higher percentage of naïve CD4 cells in early-stage disease patients than in late-stage disease patients; however, the CD4 cells in early-stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (P<0.05). In late-stage AIDS-developing patients, substantially increased IL-7 was correlated with a decreased percentage of IL-7Ralpha+ CD4 cells (P=0.01), which resulted in these patients having a significantly lower percentage of naïve T cells (P<0.01) and a significantly lower content of TREC (P<0.01) than the other patients. CONCLUSIONS: The maintenance of high CD4 cell counts in LTNPs was associated with a specific IL-7/IL-7R pattern characterized by increased IL-7 and highest IL-7Ralpha-expressing CD4 cells relative to other patients. Compared with patients with late-stage disease, LTNPs displayed a phenotypically naïve, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL-7-mediated pathway specifically sustaining peripheral CD4 counts.

Does fluvastatin favour HCV replication in vivo? A pilot study on HIV-HCV coinfected patients.

Fluvastatin showed anti-hepatitis C virus (HCV) activity in vitro, through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)-alpha. Nevertheless statins up-regulate low-density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T-cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid-lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV-RNA levels, CD36 expression and T-cell homeostasis in HCV-RNA positive patients. HCV-RNA was measured at baseline and after 4 weeks in 42 HCV/HIV-1 co-infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T-cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)-10, IFN-gamma and IL-7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group (P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV-RNA levels was seen after 4 weeks of fluvastatin (P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV-RNA replication in vivo; conversely we observed a significant increase of HCV-RNA levels. CD36 expression on monocytes were not up-regulated by statins as previously reported in vitro. The correlation between HCV infectivity, oxidized-LDL receptor and statins in HCV infection need further evaluation.

Habitat effects on Ostreopsis cf. ovata bloom dynamics.

In the last few decades, Ostreopsis spp., toxic benthic dinolagellates of tropical origin, generated large interest in the Mediterranean Sea, where several bloom events have been observed. Ecology and proliferation dynamics of O. cf. ovata are driven by complex interactions among biotic and abiotic drivers, and understanding mechanisms triggering bloom events is still far from being complete. The aim of the present study is to highlight the role of different habitat conditions, elucidating the effects of i) exposure to hydrodynamic conditions, ii) macroalgal community and iii) urbanisation level, in driving O. cf. ovata bloom dynamics. A significant effect of hydrodynamics was observed only for cells in seawater, with higher abundances in sheltered zones, irrespective of the urbanisation level. Similarly, a significant effect of the dominant macroalgal community, with higher abundances in Corallinales and turf dominated communities, and lower ones in Cystoseira amentacea canopies, has been recorded, consistently in the differently urbanised sites. Additionally, stretches of the coast suffering from a more intense anthropic exploitation are in general more prone to the proliferation of potentially toxic benthic microalgae. All these results imply a larger risk exposure to toxic effects for humans in urban beaches and sheltered areas, usually more attended by swimmers and bathers. These findings underline the need to preserve, and eventually restore, canopy dominated assemblages, which presently are under regression because of human threats, providing a straightforward example that restoration of relevant habitats implies a cascading improvement of human welfare.

Thyroid nodules in Graves disease and the risk of thyroid carcinoma.

BACKGROUND: The risk of thyroid carcinoma in patients with Graves disease has been particularly emphasized when nodules coexist with thyroid hyperplasia; a surgical approach has been suggested. OBJECTIVES: To detect thyroid nodules early in patients with Graves disease and to evaluate the risk of carcinoma. METHODS: The study group included 315 consecutive outpatients with Graves hyperthyroidism not previously treated with surgery or radioiodine therapy. Thyroid ultrasonography was performed at the time of enrollment and repeated annually in all patients; fine-needle aspiration (FNA) was carried out in those patients with nodules and repeated after 2 years or at shorter intervals. RESULTS: One hundred six of 315 patients with Graves disease had thyroid nodules 8 mm in diameter or larger detected by ultrasonography. In 49 patients, nodules were present at the time of the first examination; in 57 patients, nodules developed during follow-up. Fine-needle aspiration cytology results revealed features of carcinoma in only 1 patient; this was confirmed by histologic examination of excised thyroid tissue. The nodules with normal cytologic features at the time of the first examination did not show any clinical and/or cytologic evolution toward malignancy during follow-up. CONCLUSIONS: Ultrasonographic evidence of nodules was frequently found among our patients with Graves disease, but malignant FNA cytologic findings of the examined nodules were rare at the time of diagnosis and throughout the course of the disease. When FNA cytologic evaluation does not indicate malignancy, the presence of thyroid nodules in patients with Graves disease does not indicate an aggressive therapeutic approach.

Evidence for type 2 cytokine production and lymphocyte activation in the early phases of HIV-1 infection.

OBJECTIVE: To analyse changes in cytokine production in vitro and T-lymphocyte immunophenotype in the early phases of HIV-1 infection. DESIGN AND METHODS: Mitogen-stimulated in vitro production of interferon (IFN)-gamma, interleukin (IL)-2 (type 1 cytokines), IL-4, and IL-10 (type 2 cytokines) and surface expression of activation and non-activation markers were evaluated in 11 individuals HIV-infected for > 3 but < 12 months (seroconverters). The data were compared to those obtained in 33 asymptomatic HIV-positive individuals infected > 3 years previously and who were stratified according to CD4+ lymphocyte count (group 1: > 500 x 10(6)/l, group 2: < 500 x 10(6)/l CD4 cells) and in 12 HIV-seronegative healthy controls. RESULTS: We observed that the early phase of HIV infection is characterized by (1) reduced mitogen-stimulated IL-2 and IFN-gamma production, (2) increased mitogen-stimulated IL-4 and IL-10 production, (3) a relative decrease in CD4+ and CD4+CD7- as well as an increase in CD4+CD7-CD57+ lymphocytes, and (4) a relative increase in CD8+, CD8+CD38+ and CD8+CD57+ T lymphocytes. In addition, during a 6-month follow-up of six seroconverters we observed a dynamic pattern of changes of these parameters in most individuals, with a resulting profile similar to that observed in group 1 HIV-positive patients. CONCLUSION: The early phase of HIV infection is immunologically characterized by type 2 cytokine secretion and alterations in the expression of phenotypic markers, and closely resembles the more advanced phases of HIV infection. These immunologic alterations are temporally limited by the successive return to a more normal profile. Thus, HIV infection is an immunological complex dynamic process even in its earliest phases.

CD4 cell counts at the third month of HAART may predict clinical failure.

OBJECTIVE: To evaluate the influence of immunological and virological markers on clinical outcome in patients receiving their first highly active antiretroviral therapy (HAART) regimen. DESIGN AND METHODS: Observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of 3-month CD4 cell counts on clinical outcome. RESULTS: Clinical failure occurred in 55 patients (9.4%) during a median follow-up of 483 days (range 33-1334 days): 45 new AIDS-defining events (ADEs) in 38, ADE recurrence in six, and death in 11. Twenty-four of the 45 new ADEs (53.4%) occurred during the first 3 months of HAART, and 11 of 45 (24.4%) in the presence of CD4 cell counts > 200 x 10(6) cells/l. The mean (median, range) CD4 counts were 144 x 10(6) cells/l (128, 4-529) in patients with and 322 x 10(6) cells/l (288, 14-1162) in patients without clinical failure (P < 0.0001). Moreover, the proportion of patients with mean CD4 cell counts < 200 x 10(6) cells/l was higher in those experiencing subsequent clinical failure (X2 test: 26.75; P < 0.00001). Multivariate analysis showed that baseline CD4 cell counts < 50 x 10(6) cells/l and AIDS at enrolment predicted failure; after adjusting for 3-month CD4 cell counts, this marker was the only one independently associated with clinical failure (hazard risk, 4.79; 95% confidence interval, 1.40-16.47). CONCLUSIONS: The 3-month immunological response is a reliable predictor of long-term clinical outcome.

Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection.

Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters. Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs). Surface expression of activation and nonactivation markers was also analyzed in a group of these donors. We report that (1) IL-2 and IFN-gamma production is reduced and IL-4 and IL-10 production is increased in PI patients compared to HCs and LTNPs; (2) prevalence of HIV isolation is lower in LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of type 2 cytokines is paralleled by an increase in CD57+CD4+CD7- lymphocytes. Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL-10 cytokine production pattern is present in HC and in LTNP HIV+, progression of HIV infection is associated with a low IL-2 low IFN-gamma/high IL-4, high IL-10 cytokine profile; increased prevalence of HIV isolation; and an augmented percentage of CD57+CD4+CD7- lymphocytes. These findings further confirm that a dominant type 1 cytokine profile together with reduced prevalence of virus isolation is associated with lack of progression in HIV infection.

Frequent detection of antibodies against HTLV antigens in patients with AIDS-related non-Hodgkin lymphoma.

We studied the prevalence of anti-HTLV-I/II antibodies in 22 patients with AIDS-related non-Hodgkin lymphoma (NHL), 453 HIV-1-infected patients without lymphoma (194 of whom were diagnosed as having AIDS), and 6 HIV-1-positive and 75 HIV-1-negative patients with Hodgkin lymphoma. The frequency of serological reactivity against HTLV antigens was significantly higher in the AIDS patients with lymphoma than in those without (8 of 22, 36.4% vs. 20 of 194, 10.3%-p = 0.0027). One of the HIV-1-positive and none of the HIV-1-negative patients with Hodgkin lymphoma showed anti-HTLV-I/II reactivity. Four of the eight seropositive NHL patients showed antibodies directed against HTLV-II recombinant antigens when tested for serological discrimination in a Western blot assay. A PCR study of PBMCs from the only patient with NHL still alive at the time of the study showed HTLV-II-specific sequences in the genomic DNA. These data suggest that HTLV-II or a closely homologous retrovirus infects a high proportion of patients with AIDS-associated NHL.

Tracheoesophageal fistula in an HIV-1-positive man due to dual infection of Candida albicans and cytomegalovirus.

We report a 35-year-old HIV-1-positive man who presented with severe dyspnea and a nonproductive cough. Three fiberoptic bronchoscopic examination revealed an infiltrating and vegetating tracheal mass that was diagnosed as necrotizing candidiasis of the trachea. The lesion resulted in the formation of a tracheoesophageal fistula that eventually led to the death of the patient. Postmortem examination showed cytomegalovirus vasculitis in the esophageal wall.

Acute hepatic and renal failure caused by Pneumocystis carinii in patients with AIDS.

Clinical and pathological findings are described in two AIDS patients with Pneumocystis carinii infection who received prophylactic treatment with nebulised pentamidine and developed unusual hepatic and renal failure. Histological examination showed clumps of P carinii massively obstructing hepatic sinuses and portal vessels in the first patient, and merular and intertubular capillaries in the second. These findings could explain the unusual clinical features, characterised by acute hepatic and renal failure.

Thyroid vascularization by color doppler ultrasonography in Graves' disease. Changes related to different phases and to the long-term outcome of the disease.

To investigate possible correlations between thyroid vascularization and activity of Graves' disease, we measured blood flow (TBF) at the inferior thyroid artery and intraparenchymal vascularization (number of vessels per square centimeter) by color Doppler ultrasonography (CDU) on Graves' patients at different phases of the disease. We studied 88 patients cross sectionally: 22 untreated; 17 euthyroid after 6 months of methimazole; 49 euthyroid at drug withdrawal after 12 to 24 months of treatment. The patients of the latter group were followed up for 29.1 +/- 6.3 months after discontinuation of treatment. On the day of CDU examination, free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), antiperoxidase and anti-TSH receptor (TRAb) antibodies were measured. Vascularization indices were significantly higher in the Graves' patients than in controls. In the patients euthyroid under treatment, vascularization was not significantly lower than in the untreated group, but TBF and vessel number both appeared clearly reduced in the patients tested at drug withdrawal. The vascularization indices at drug withdrawal were significantly higher in the patients who relapsed than in those in stable remission: TBF (mL/min) 50.6 +/- 36.8 vs. 23.8 +/- 17.5, p = 0.001; vessel number/cm2 1.8 +/- 0.8 vs. 0.8 +/- 0.5, p = 0.002. A multivariate analysis, evaluating the predictive value of vascularization, hormonal and immunological parameters for relapse, demonstrated a significant predictive value for TRAb (RR 8.2; p = 0.001) and a weak predictive value for TBF (RR 1.1; p = 0.02). In conclusion, CDU examination confirms that thyroid hypervascularization in Graves' disease is not related to thyroid hormone circulating levels. The association of increased TBF and high levels of TRAb in the relapsing forms of disease suggests that thyroid hypervascularization is probably related to the activity of the underlying autoimmune processes.

Predictive role of the three-month CD4 cell count in the long-term clinical outcome of the first HAART regimen.

The aim was to evaluate whether the three-month CD4 cell counts are a reliable predictor of the long-term clinical outcome of HAART-treated patients, by an observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529) in patients with and 362/microL (326; 18--1162) in patients without clinical failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts < 200 microL was higher in those experiencing subsequent clinical failure (chi2: 41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50 microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after adjusting for three-month CD4+ counts, this marker was the only one independently associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month immunologic response is a reliable predictor of long-term clinical outcome.

Human lymphocyte antigens in Graves' disease: correlation with persistent course of disease.

Graves' disease is a thyroid autoimmune disorder associated with specific human lymphocyte antigen (HLA) alleles, characterized by an unpredictable long-term course. To investigate possible relations between HLA phenotype and outcome of the disease, the authors typed for HLA antigens in 105 patients with Graves' disease with different course of disease. All patients were treated with antithyroid drugs for at least 12 months; 29 patients had stable remission 24 or more months after withdrawal of treatment; 76 patients had persistent disease--66 unremitting/relapsing hyperthyroidism, 10 stable hypothyroidism--36 or more months after onset of disease. The following findings emerged from this study: 1) HLA B8 and DR3 were increased significantly in Graves' patients versus 6,682 control subjects from the same geographic area (23.80% vs 12.01%, odds ratio [OR] 1.98, and 31.43% vs 18.00%, OR 1.75, respectively); the antigen combinations B8-DR3, B8-Cw7-DR3, and A1-B8-Cw7-DR3 were significantly more frequent in Graves' patients vs control subjects; in addition, these combinations were present exclusively in patients with persistent disease (B8-DR3 28.95%, OR 7.14, B8-Cw7-DR3 27.63%, OR 11.24, and A1-B8-Cw7-DR3 18.42%, OR 11.29). These data provide evidence that not only susceptibility to Graves' disease, but also persistent activity of the autoimmune process, producing either hyperthyroidism or stable hypothyroidism, is associated with specific HLA antigen phenotypes.

Persistent parvovirus B19-induced anemia in an HIV-infected patient under HAART. Case report and review of literature.

Recent reports document resolution of human parvovirus B19-related pure red blood cell aplasia (PB19-PRCA) in HIV-infected patients upon commencement of highly active antiretroviral therapy (HAART). This article describes a patient with PB19-PRCA who, despite fully suppressive HAART, required cyclic administration of intravenous human immunoglobulin over a period of 17 months before PB19 seroconversion and subsequent resolution of relapsing severe anemia. All reports in the English literature describing PB19-related hematologic abnormalities in the post-HAART era are also described herein.

Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome.

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL) observed mainly in Sudan and India where it follows treated VL in 50% and 10% of cases, respectively. We report a 46-year-old patient with acquired immune deficiency syndrome who, 7 months after diagnosis of VL, developed PKDL and uveal leishmaniasis following HAART-induced immune recovery. In southern Europe PKDL seems to be an emerging clinical presentation among human immunodeficiency virus (HIV)-infected patients experiencing HAART-induced immune recovery after a previous diagnosis of VL. The best treatment among HIV-infected patients remains to be determined.