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Cystic echinococcosis (CE) is increasingly seen in immigrants from endemic areas to Western countries; however, it is rarely reported in short-term travels to endemic areas. This is partly because the echinococcal cyst typically grows slowly and may long remain clinically silent. We describe a case of cystic echinococcosis in a man born and living in a nonendemic urban area in North Italy that was acquired during a period of frequent travels in highly endemic countries. [ABSTRACT FROM AUTHOR]

Objectives: Splenic abscess is an uncommon disease, with a reported incidence of 0.14-0.7% in autoptic series. The best treatment option remains unclear. We report our experience of percutaneous drainage of splenic abscess under ultrasound (US) guidance., Methods: From 1979 to 2005, 16 consecutive patients (12 male and four female; mean age 39.9 years, range 16-72 years) were diagnosed with splenic abscess by means of US, and were treated with medical therapy alone or combined with US-guided percutaneous aspiration or catheter drainage., Results: Ten of 16 patients had bacterial abscesses (including one case of tubercular abscess), two had an amebic abscess, and four had fungal abscesses. Seven of ten patients with bacterial abscesses were successfully treated with fine needle aspiration alone, one patient was successfully treated with fine needle aspiration for one abscess and catheter drainage for another, and one patient, who subsequently required a splenectomy for an abdominal trauma, successfully underwent percutaneous catheter drainage alone. Four patients with fungal lesions were treated with medical therapy alone, and two patients later required a splenectomy. One patient with a bacterial abscess due to endocarditis was treated with medical therapy alone, and his recovery was uneventful., Conclusions: US-guided percutaneous aspiration of splenic abscesses is a safe and effective procedure. It can be used as a bridge to surgery in patients who are critically ill or have several comorbidities. Percutaneous aspiration may allow complete non-operative healing of splenic abscesses or temporize patients at risk for surgery.

To assess the comparability of ultrasonographic (US) subcutaneous fat thickness (SFT) measurements in comparison with computed tomography (CT) at reference points (RPs) representative of HIV related adipose redistribution syndrome (HARS) in patients treated with antiretrovirals. US and CT measurements were compared in nine patients with clinical reports of HARS. We obtained the best resolution of facial (at deepest point of Bichat pad), brachial (in the dorsal face of arm) and crural SFT (at mid thigh) by means of minimal transducer pressures avoiding potential biases such as stand off pads pressure on the skin and artefacts due to too abundant quantity of gel. CT scans were obtained in the same RP where US measurements were performed such as identified by means of metallic skin markers. Median US measurement of facial SFT was 8.8 mm (95% CI: 3.1 to 13.4), 3.95 mm (95% CI: 2.62 to 5.84) for brachial SFT and 4 mm (95% CI: 3.4 to 9.4) for crural SFT. Median CT assessments of facial SFT was 8.7 mm (95% CI: 3.5 to 13.5), 4.2 mm (95% CI: 2.6 to 5.88) for brachial SFT and 5 mm (95% CI: 3.9 to 10.3) for crural SFT, with no significant difference at each RP. A linear regression showed good CT/US comparability at each RP, with no significant deviation from linearity (p > 0.10). US shows to be highly comparable with CT, excluding invaliding biases as the transducer pressure on the skin. Given the proven efficacy on the HARS assessments, if well standardized, US could be a reliable method, simpler than CT in the management of body fat changes related to HARS.

Objective: To prove intra- and inter-observer's reliability of ultrasound (US) in the assessment of lipoatrophic findings related to the HIV associated Adipose Redistribution Syndrome (HARS)., Patients and Methods: In two separated sessions, 2 consecutive measurements of subcutaneous fat thickness (SFT) were performed by each observer at the deepest point of Bichat pad, the dorsal face of arm and the mid thigh for the assessment of facial, brachial and crural lipoatrophy, respectively. We enrolled 20 HIV patients, rotating an experienced and untrained sonologist. The assessments were performed avoiding any stand off pads in the skin and excluding artefacts due to the too abundant quantity of gel to obtaining, with minimal transducer pressure, the best resolution of the reference points., Results: Means of facial, brachial and crural SFT showed no significant differences between the workers. Coefficients of variability (SD/mean x100) were similar for facial (ranges: 4.7-5.2% vs 4.9-5.6%, respectively), brachial (ranges: 5.8-8.4% vs 9.7-11.2%) and crural SFTs (ranges: 5.9-6% vs 6.2-8.7%). There was greater consistency in the measurements performed by the experienced vs the untrained worker. Inter-observer agreement, assessed through kappa statistic (k) analysis, confirmed increased measurement's agreement in the facial (k ranged from 0.40 to 0.60), brachial (k: 0.23-0.63) and crural SFT assessments (k: 0.58-0.70) from the 1(st) to 2(nd) session., Conclusions: US shows low intra observer variability and good inter observer reliability in the assessment of body fat changes related to the HARS. The different degree of consistency by the workers and the improvement of interobserver agreement, suggest to stating a well defined period of training to obtain better US reliability.

Image-guided percutaneous treatments for echinococcal cysts were introduced in the mid-eighties. Today they represent a third therapeutic option, after surgery and benzimidazole derivatives. Two types of percutaneous treatments are available, based on the destruction of the germinal layer or the evacuation of the endocyst. To assess the extent of their use and their safety, a Medline search of the literature on this subject was performed. The number of cysts treated, their anatomical sites, the complications and, length of follow-up (when available), were all examined. The results show that percutaneous treatments for cystic echinococcosis are safe and efficacious in selected anatomical sites, provided basic safety issues are correctly addressed. However, before drawing final conclusions, a more detailed analysis of the literature is needed. Percutaneous treatments could be simplified and made more effective if a scolecidal agent could be found that melts the entire endocyst without causing harm to the biliary epithelium.

Surgical excision of echinococcal cyst has long been considered the only effective treatment for echinococcosis. However, the remarkable advances in imaging techniques, particularly ultrasound, made during the past 25 years have greatly facilitated diagnosis, treatment and follow-up. Today, chemotherapy and percutaneous treatments have become widely available. A major step forward in management of the disease came in 2001, when the WHO International Working Group on Echinococcosis (WHO-IWGE) came to a consensus by developing a standardized classification of ultrasound images in cystic echinococcosis. Thus, the most appropriate treatment for patients affected by this serious and sometimes life-threatening disease may now be chosen. An overview of the three main therapeutic options for abdominal- and particularly hepatic-cystic echinococcosis is presented, with focus on the indications and contraindications of each one. Data from long-term follow-up studies are also discussed, with emphasis on the resulting stage-specific criteria for treatment.

Virus-specific activation of the CD8+ cytotoxic T lymphocytes, which may affect the extension of histopathological damage in chronic hepatitis C, is closely related to the role of the so called "costimulatory antigens", particularly CD28, allocated on the surface of the T lymphocytes. This study evaluated the display of CD28 antigen on circulating T lymphocytes CD8+ in patients with chronic hepatitis C. The eventual correlation between CD28 expression, viral load, aminotransferase levels and degree of histological damage was also studied. According to our data, the prevalence of circulating TCD8+ CD28+ cells didn't differ among anti-HCV positive, HBV positive subjects and healthy controls. In HCV-positive subjects, prevalence of TCD8+ CD28+ cells was higher in patients with chronic persistent hepatitis than in chronic active cases with a significant negative correlation with the Knodell histological "score". Further studies are required to ascertain the role of CD28+ expression in those subjects with severe hepatic histological damage due to chronic hepatitis C.

The natural ligands for the CCR5 chemokine receptor, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES (regulated on T-cell activation, normal T-cell expressed and secreted), are known to inhibit human immunodeficiency virus (HIV) entry, and N-terminally modified RANTES analogues are more potent than native RANTES in blocking infection. However, potent CCR5 blocking agents may select for HIV-1 variants that use alternative coreceptors at less than fully inhibitory concentrations. In this study, two N-terminal chemical modifications of RANTES produced by total synthesis, aminooxypentane (AOP)-RANTES[2-68] and N-nonanoyl (NNY)-RANTES[2-68], were tested for their ability to prevent HIV-1 infection and to select for coreceptor switch variants in the human peripheral blood lymphocyte-SCID mouse model. Mice were infected with a CCR5-using HIV-1 isolate that requires only one or two amino acid substitutions to use CXCR4 as a coreceptor. Even though it achieved lower circulating concentrations than AOP-RANTES (75 to 96 pM as opposed to 460 pM under our experimental conditions), NNY-RANTES was more effective in preventing HIV-1 infection. However, in a subset of treated mice, these levels of NNY-RANTES rapidly selected viruses with mutations in the V3 loop of envelope that altered coreceptor usage. These results reinforce the case for using agents that block all significant HIV-1 coreceptors for effective therapy.

Neutralizing antibodies can protect against challenge with HIV-1 in vivo if present at appropriate concentrations at the time of viral challenge, but any role in the control of established infection is unclear. Here, we show that high serum concentrations of neutralizing monoclonal antibodies, either singly or as a cocktail, have little sustained effect on viral load in established HIV-1 infection in hu-PBL-SCID mice. In some instances, virus replication of neutralization-sensitive virus continues even in the presence of high levels of neutralizing antibody. In most instances, neutralization escape occurs in a few days, even from a cocktail of three antibodies that recognize distinct epitopes. The results imply that humoral immunity is unlikely to play a significant role in the control of established HIV-1 infection in humans.

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.

Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium-inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of M-tropic, NSI viruses and the slow evolution ofT-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry. We have examined plasma viral RNA levels and the extent of CD4+ T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with M-tropic, dual-tropic, or T-tropic HIV-1 isolates. The cell tropism was found to determine the course of viremia, with M-tropic viruses producing sustained high viral RNA levels and sparing some CD4+ T cells, dual-tropic viruses producing a transient and lower viral RNA spike and extremely rapid depletion of CD4+ T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid-intermediate rates of CD4+ T-cell depletion. A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to switch from M-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4+ T cells.

The body-cavity-based lymphoma cell line BCBL-1, which is infected with Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, was injected alone or with human peripheral blood mononuclear cells into SCID mice. Immunoblastic lymphomas developed at or near the site of injection. The lymphomas appeared to derive exclusively from the injected BCBL-1 cells and not from the injected human PBMC. The tumors elicited a marked murine angiogenic response, but known angiogenic cytokines were not detected in BCBL-1 cells. Transfer of BCBL-1 cells to SCID mice may represent an in vivo model for the study of KSHV/HHV8-stimulated angiogenesis.

Objective: Mice with severe combined immunodeficiency (SCID) transplanted with human peripheral blood lymphocytes (hu-PBL) have been shown to be useful as an animal model for HIV-1 infection. This model was used to assess the ability of a human anti-gp120 antibody to protect against HIV-1 infection., Design and Methods: hu-PBL-SCID mice were injected with an HIV-1 broadly neutralizing human monoclonal antibody against the gp120 CD4-binding site prior to challenge with HIV-1SF2. The antibody b12, employed for these studies, was isolated from an antibody phage-display library prepared from bone-marrow of a long-term asymptomatic HIV-1-seropositive donor. Both Fab fragments and whole immunoglobulin (Ig) G1 b12 antibody were assessed for protection., Results: Fab b12, tested at a dose approximately 1.9 mg/kg, was able to protect 25% of hu-PBL-SCID mice from HIV-1 infection. IgG1 b12, which displayed favorable pharmacokinetic properties, showed a dose-dependent protection that was complete with a regimen of two injections of 100 micrograms per mouse. The in vivo protective dose of antibody at the time of virus challenge was estimated to be 4.5-7 mg/kg from antibody clearance data., Conclusions: This study demonstrates for the first time that complete protection against HIV-1 infection can be achieved in the hu-PBL-SCID model by passive immunization with physiologically relevant doses of a human gp120 CD4-binding site antibody derived from natural infection.

In these studies, neonatal C.B-17 severe combined immunodeficient (nSCID) mice were reconstituted with human cord blood leukocytes (hu-CBLs). The resulting hu-CBL-nSCID mice contained readily detectable human CD3+ T lymphocytes and CD20+ human B cells, and produced substantial levels of human IgM and IgG (including all subclasses). Human cells persisted in lymphoid organs and peripheral blood for at least 8 weeks, and CD4+ T cells outnumbered CD8+ T cells. Engraftment of human cells in peripheral lymphoid organs and blood was much greater than that seen in adult SCID mice grafted with adult peripheral blood leukocytes (PBLs). Hu-CBL-nSCID mice were susceptible to infection with laboratory-adapted and fresh clinical human immunodeficiency virus type 1 (HIV-1) isolates. Following infection with HIV-1, virus could be recovered by the coculture of spleen, lymph node, peritoneal cavity, liver, and plasma samples from hu-CBL-nSCID mice with fresh human peripheral blood mononuclear cells, and proviral copies were detectable following amplification using the polymerase chain reaction (PCR). HIV p24 core antigen levels in hu-CBL-nSCID mouse plasma were consistent with ongoing viral replication and high viral burdens. Rapid CD4+ T cell depletion occurred following infection with laboratory isolates of HIV-1 or a syncytium-inducing clinical isolate, but a non-syncytium-inducing clinical isolate caused expansion of CD8+ T cells, leading to an inversion of the CD4:CD8 ratio with only a transient decrease in CD4+ T cells. These results suggest that the hu-CBL-nSCID mouse system has unique features that mimic certain aspects of pediatric HIV infection, and distinguish it from other animal models of HIV infection, including the related hu-PBL-SCID model.

Human immunodeficiency virus (HIV) isolates differ in cell tropism, replication, pathogenicity, and syncytial induction in vitro. CD4+ T cells were enumerated in severe combined immunodeficient mice transplanted with human peripheral blood leukocytes (hu-PBL-SCID mice) and infected with HIV isolates with different in vitro cytopathicity. Two noncytopathic, macrophage-tropic strains, HIV-1SF162 and HIV-2UC1, induced extensive CD4+ T cell depletion, whereas HIV-1SF33, which is highly cytopathic for T cells in vitro, caused little CD4+ T cell depletion at equivalent virus burden. In vitro cytopathicity assays therefore do not predict CD4 depletion in the hu-PBL-SCID model.

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.

In an attempt to characterize the heterogeneity of the human autoantibody response, mice with severe combined immunodeficiency were reconstituted with synovial or blood lymphocytes from patients with rheumatoid arthritis (RA). Mononuclear cells extracted from synovial fluid or tissue (SMC) were a greatly enriched source of IgM rheumatoid factor (RF)-producing cells compared to the peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis patients or normal donors. Six to nine weeks after reconstitution of mice with synovial mononuclear cells, 0%-39.3% (mean = 11.4%) of total IgM consisted of IgM RF compared to 0%-0.15% (mean = 0.02%) in mice given RA PBMC and 0%-1.2% (mean = 0.34%) in mice given normal PBMC. Detectable levels of IgM RF were maintained in some mice for as long as 20 weeks after transfer. Mice reconstituted with synovial membrane or synovial fluid lymphocytes produced a heterogeneous mixture of immunoglobulins. These included other autoantibodies, such as anti-nuclear and anti-cytoplasmic antibodies, and antibodies to exogenous antigens such as the Epstein-Barr virus nuclear antigen-1 (EBNA-1). This heterogeneity is further illustrated by the demonstration that the sera from mice given synovial cells also contained IgG antibodies possessing all three major VH families (VH1, VH3 and VH4) and the four major V kappa families (V kappa 1 to V kappa 4). Autoantibody production gradually decreased with time even under circumstances where total immunoglobulin levels increased, and elevated production could not be induced by antigenic stimulation. These findings describe a new model for the analysis of human autoantibody production.

The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans. Current studies of the human immune responses are limited to relatively restrictive in vivo experiments and several in vitro systems that, although useful, allow only short-term studies and support responses to a few antigens. Neither model is particularly amenable to studies of the pathogenesis of diseases of the immune system. We report here that injection of human peripheral blood leukocytes (PBL) can result in the stable long-term reconstitution of a functional human immune system in mice with severe combined immunodeficiency (SCID). Human PBL transplanted to SCID mice increase in number and survive for at least six months; reconstituted mice show spontaneous secretion of human immunoglobulin and a specific human antibody response is induced following immunization with tetanus toxoid. All of the major cell populations present in PBL are found in the lymphoid tissue and blood of SCID recipients, although the relative proportions of B cells, T-cell subsets and monocytes/macrophages in long-term recipients differ from those found in normal PBL and, in mice transplanted with 50 x 10(6) or more PBL from Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest that xenogeneic transplantation of human lymphoid cells into SCID mice may provide a useful model for the study of normal human immune function, the response of the immune system to pathogenic agents and early events in lymphomagensis.

Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 x 10(6) or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8-16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from "normal" donors to SCID mice. SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells.(ABSTRACT TRUNCATED AT 250 WORDS)