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An infrequent thoracic and abdominal aortic aneurism occurred in a patient with a human immunodeficiency virus (HIV) infection well controlled by an effective combination antiretroviral therapy, already modified to minimize dysmetabolic abnormalities. No adjunctive risk factors for an accelerated atherogenesis were present (ie, cigarette smoking, arterial hypertension, metabolic syndrome, diabetes mellitus), the personal and family cardiovascular history were mute, and no infectious foci supported a mycotic aneurism. Moreover, alternative statin-fibrate therapy was administered since 18 months, and a diet-exercise program and a polyunsaturated fatty acids supplementation were recommended. Despite surgical positioning of an aortic endoprosthesis immediately after diagnosing the aortic aneurism, 11 months later an imminent aneurism rupture was avoided by the introduction of another endoprosthesis between the older thoracic graft and the suprarenal prosthetic device, although a revascularization of renal and mesenteric arteries became needed. The subsequent, 7-month-long follow-up did not disclose complications or sequelae, whereas HIV infection remained under control with a simplified, effective, and well-tolerated antiretroviral regimen. Unfortunately, a fatal relapse of ruptured aortic aneurism led rapidly our patient to death. Caregivers following HIV-infected patients should be aware of the increased risk of complicated, accelerated atherogenesis in these subjects, even when combination antiretroviral therapy is sufficiently well tolerated, and the great majority of known risk factors has been assessed and eventually treated. Severe gross vessel abnormalities deserve major attention and eventual specialistic surgery treatment, which may play an effective role in life-threatening conditions.

A rare case report of serious, relapsing, and difficult-to-treat Strongyloides stercoralisenteric infestation that occurred in a patient affected by the autoimmune Sjögren disease (a pathologic association never reported before), chronically treated with corticosteroids, has been presented and evaluated on the ground of the available literature evidences in this field. In particular, the role of underlying (and iatrogenic) immunodeficiency in the pathogenesis of S. stercoralispersisting infection and the unresolved diagnostic and therapeutic issues in the setting of strongyloidiasis are discussed. Particular attention is focused on the need to maintain clinical suspicion for this nematode worm infestation in patients suffering from a large spectrum of collagen vascular diseases, and the need for randomized clinical trials to determine suitable first-line and subsequent lines of treatment, especially when immunodeficiency and a relapsing Strongyloidesdisease are suspected.

Enfuvirtide (Fuzeon®, Roche), is the first member of a novel class of antiretroviral agents, the socalled fusion inhibitors, which act against HIV with a completely novel (extra cellular) mechanism of action, and can therefore be easily added to all anti-HIV association therapies including all other antiretroviral agents belonging to nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, since no interactions of any type are expected with enfuvirtide. Despite the need of a twice-daily parenteral (subcutaneous) delivery due to the polypeptide structure of the drug, and its proportionally short elimination lifetime, two extensive multicentre randomized clinical trials and a huge amount of other clinical and laboratory experiences confirmed the elevated potency and the safety profile of enfuvirtide in appropriate samples of HIV-infected patients (both adults and children), who failed and/or became intolerant to all previously available anti-HIV regimens, and had a very restricted choice of antiviral compounds showing residual activity. As a consequence, enfuvirtide is recommended as an adjunct to an "optimized background" containing at least one or two antiretroviral drugs, which are still active against the isolated viral strain, as assessed by resistance testing. The extremely promising profile of this novel anti-HIV drug and the reduced potential for the development of viral resistance (with no possibility of cross-resistance with the other anti-HIV classes) however warrant further pharmacokinetic, pharmacodynamic, pharmacogenomic, and pharmacoeconomic investigation. Also more extensive and prolonged clinical and quality of life studies are strongly needed to establish the best positioning of enfuvirtide in the current therapeutic guidelines of HIV disease and its future role, besides its current approval for salvage therapy of adult and pediatric HIV-infected patients with limited therapeutic options.

A case of nephrotic syndrome treated with associated cyclophosphamide and corticosteroids came to our attention after over 2 years of self-administered immunosuppressive therapy which remained unchanged and uncontrolled during this period. The self-administered therapy resulted in a severe cell-mediated immunodeficiency (as expressed by a nadir CD4lymphocyte count of 2 cellsμL). This led to a rapid unfavorable progression of hepatitis B, which was recently acquired and subsequently evolved into a severe cholestatic and fibrosing chronic hepatitis, causing multiple end-organ failure, and ultimately, death. This process was not reversed by lamivudine therapy, hemodialysis, and the use of a Molecular Adsorbent Recirculating System. The role played by repeated drug prescriptions from general practitioners without appropriate clinical and laboratory controls, and that of our patient's depression are discussed. Current literature related to the presented case and the ongoing debate regarding repeated prescriptions are considered in this study.

An exceptional case report of community-acquired, disseminated infection caused by a methicillin-resistant Staphylococcus aureusstrain, responsible for pneumonia, sepsis, and scattered septic embolism, and accompanied by diffuse polyvisceritis and thrombophlebitis as signs of an overwhelming extensive activation of the immune system, is reported and discussed on the grounds of the most recent evidence in literature. The striking features of a severe, multiresistant S. aureuspolyvisceral disease associated with multiple immune-mediated focal manifestations are in contrast with the community-acquired origin of infection and the apparent absence of supporting factors for both antimicrobial resistance and the unexpected, exaggerated immune activation occurred in an otherwise healthy man. The extensive immune activation status (as demonstrated by a proportionally maintained absolute lymphocyte cont and a T-cell subset study pointing out an increased quote of CD4+, CD34+, and CD4-CD8- cells, compared with a proportional decrease of CD8+ T-lymphocytes) probably had a prominent role in prompting several focal clinical features of our patient, which apparently were not directly related to bacterial invasion, such as the polyvisceritis, the massive pleuric and pericardial effusion, the myocarditis-pericarditis, and the thrombophlebitis occurring in multiple and remote body sites, as compared with to the initial respiratory localization. This case report raises multiple questions regarding the epidemiology, pathogenesis, clinical manifestations, and management of complicated S. aureusinfection, including the role of novel antimicrobial agents and corticosteroids.

The tissue polypeptide antigen, TPA, is a tumour-associated antigen which is synthesized during the S phase of cellular division and released later by the tissues when rapid growth takes place. For this reason, the TPA is considered to be a specific phase tumour-associated antigen [1].

Tissue polypeptide antigen (TPA) and carcino embryonic antigen (CEA) were measured in 55 patients with cancer in different locations (21 lung cancer, 133 breast cancer, 9 stomach cancer, 5 colorectal cancer, 7 cancer of unknown origin). TPA gives elevated values in all types of cancer. The statistical analysis shows that TPA is about equally sensitive for all cancer types, while CEA has a particularly high sensitivity for colorectal carcinoma. The TPA values in the group of cancer patients is significantly different from those in a group of healthy controls. TPA gives higher sensitivity than CEA in all tumour locations. By the use of combined determination of TPA and CEA the sensitivity can be further increased, to 64 for the whole patient population and 89 for the gastric tumour patients, even when the cut-off values are chosen so high that no false positives are obtained in either reference group (150 Ul-1for TPA, 10 ng ml-1for CEA). A limited correlation exists between the markers in tumour patients.

The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cysteines of the V3 regions, but its functional similarity with the HIV-1 principal neutralizing epitope is uncertain. We studied the degree of genetic variation of the HIV-2 V3 region in fresh blood samples from 12 HIV-2-seropositive individuals from Guinea-Bissau. Polymerase chain reaction was used to amplify viral fragments of 465 bp containing the V3 region from cellular DNA. Nucleotide sequence analysis of the entire envelope fragment from each patient revealed that the degree of variation among field isolates of HIV-2 is comparable to that observed in the analogous region of HIV-1. Most of the HIV-2 isolates studied were highly related, suggesting the existence of a limited number of different viral strains in the cohort studied. Thus, the HIV-2 and HIV-1 V3 regions vary to a similar degree and may also have analogous functions.

Serum thymidine kinase (TK), measured using Prolifigen TK-REA, from AB Sangtec Medical, was investigated in 24 HIV seropositive patients without immunological alterations, 26 seropositives with immunological alterations, 125 LAS, 25 ARC, and 20 AIDS. Subjects with serological markers of prior EBV, HBV, and CMV infection were included but none with acute infectious mononucleosis or acute viral hepatitis. Serum TK was elevated from the beginning of the HIV infection, the seropositive stage, and more markedly afterwards during the course of the infection, with a close correlation with the stage.TK also increased during AZT treatment, due to bone-marrow toxicity. On lowering the dosage or discontinuing the drug TK returned to basal levels.Although the rise in serum may well not be correlated only with the HIV infection, it does add to the picture given by other clinical and/or laboratory methods. Serum TK can be a helpful laboratory test in the follow-up ofpatients with HIV infection, especially when serum levels are disproportionate to the stage, opportunistic infections, lymphoproliferative malignancies. In such cases bone-marrow toxicity due to treatment can be suspected.

A reversal of key HIV protease mutations against tipranavir has been observed in a patient undergoing a late salvage antiretroviral therapy. Our patient initially introduced tipranavir/ritonavir in absence of an optimized background and novel drug classes, and nevertheless he experienced a virological-immunological benefit. Our report is a contribution to the present debate around the role of each single HIV protease mutation, and the validation of mutational “scores” (like the so-called tipranavir weighted score), to be applied to last-generation protease inhibitor compounds initially targeted on patients with limited, residual therapeutic options.

A HIV-infected patient treated since eight years with all antiretroviral classes save boosted protease inhibitors, at the time of changing therapy due to an emerging genotyping resistance to non-nucleoside reverse transcriptase inhibitors, experienced repeated episodes of hypersensitivity reactions to all available boosted protease inhibitors. After documenting a combined ritonavir and lopinavir hypersensitivity by means of a specific in vitro cellular antigen stimulation test (CAST), antiretroviral therapy was safely continued with unboosted atazanavir. According to our knowledge, we report the first case of application of the in vitro CAST assay to antiretroviral intolerance, and the subsequent, specific regimen selection in a HIV-infected subject who showed multiple allergy to all boosted protease inhibitors. Further, controlled investigation is strongly needed to implement in vitro allergometric testing in patients with HIV infection and related diseases, who are prone to show unpredictable drug intolerance reactions. In fact, HIV-infected patients may suffer from frequent allergic drug reactions which may be difficult to be systematically recognized (due to the frequent, multiple concurrent pharmacotherapy), while eventual drug rechallenges are expected to be potentially dangerous.