Chronic periaortitis associated with membranous nephropathy: clues to common pathogenetic mechanisms.

Chronic periaortitis (CP) is a rare disease hallmarked by the presence of a periaortic retroperitoneal fibro-inflammatory tissue which can often cause obstructive uropathy. CP is isolated in most cases but it may also be associated with other sclerosing inflammatory and immune-mediated diseases. We here present the case of a patient who was initially diagnosed as having CP and subsequently developed membranous nephropathy and chronic sclerosing sialoadenitis of the right parotid gland. As these conditions were all characterized by either pronounced infiltration of IgG4-positive plasma cells or marked IgG4 tissue deposition, we hypothesize that they are part of the same disease spectrum, and discuss the immune-mediated pathogenetic mechanisms potentially shared by these conditions. In particular, we consider the role of Th2-mediated immune reactions and of immunogenetic factors such as HLA genotype as common determinants of these disorders.

Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-alpha in patients with renal cell carcinoma.

Very low doses of recombinant interleukin-2 (rIL-2) and interferon-alpha (rIFN-alpha) induce, in patients with advanced renal cell carcinoma (RCC) clinical response rate and median survival time comparable to other protocols, other than immunological response in terms of expansion of NK cells and cT lymphocytes. The aim of this pilot study was to verify whether very low dose immunotherapy can enhance NK cell cytotoxicity against tumoral target cells. Eight patients with advanced and 13 patients with localised disease received 4-week cycles of rIL-2 (total dose per week 7 MIU/m(2), s.c.) and rIFN-alpha (total dose per week 3.6 MUI/m(2), i.m.) according to the scheme proposed by Buzio et al. Neutrophils, monocytes, eosinophils, NK cells (CD56+bright, CD56+dimmer, CD3-CD56 +), NK-T cells (CD3+CD56+), Th-lymphocytes, cT-lymphocytes, HLA-DR+ and CD25+ lymphocytes and NK cell cytotoxicity were evaluated before and after cycle. The treatment led to the significant expansion of eosinophils (P < 0.001), NK cells (P < 0.001), CD56+bright (P < 0.001), CD56+dimmer (P < 0.001), Th-lymphocytes (P = 0.001), cT-lymphocytes (P = 0.014), HLA-DR+ (P = 0.007) and CD25+(P = 0.002) cells. Neutrophils significantly decreased (P = 0.001), whereas no significant effect was observed on monocytes (P = 0.22) or NK-T cells (P = 0.20). Patients with localised disease responded significantly better to treatment than metastatic patients in terms of the expansion of CD56+bright (P = 0.038), DR+ (P = 0.021), CD25+ (P = 0.006) and Th-lymphocytes (P = 0.014). The NK cell cytotoxicity was significantly increased by the immunotherapy in the whole population (P = 0.021) and similarly in the two groups of patients (P = 0.860); a reverse relation, even if not significant, was seen between the variation of NK-T cells and NK cells cytotoxicity (r = -0.39; P = 0.074).

Peripheral inflammatory arthritis in patients with chronic periaortitis: report of five cases and review of the literature.

OBJECTIVES: Chronic periaortitis (CP) is a rare disease with a potentially immune-mediated pathogenesis. The study aims to report the frequency and the clinical characteristics of peripheral inflammatory arthritis in a cohort of CP patients, and to review the literature regarding the association between arthritis and CP. METHODS: Forty-nine consecutive CP patients were seen at our department between 2000 and 2006; all of them underwent imaging (abdominal computed tomography and magnetic resonance imaging) and laboratory examinations, also including erythrocyte sedimentation rate, C-reactive protein and a panel of autoantibodies. The clinical history of the patients who developed peripheral inflammatory arthritis is reported in detail. A PubMed/Medline search without any date limits was performed for English-language articles reporting the association between CP and arthritis. RESULTS: Five of the 49 enrolled patients developed an inflammatory form of peripheral arthritis: three were diagnosed as having RA, one palindromic rheumatism and one acute reactive arthritis. In all but one case, arthritis became clinically overt months to years after the onset of CP, and its outcome was good, since almost all patients were asymptomatic at the end of follow-up. No patient suffered from ankylosing spondylitis. In the literature review, 20 cases of CP-associated arthritis were found, mainly in the form of case reports: 14 of them were spondyloarthropathies, whereas the remaining ones were RA, juvenile RA or undifferentiated arthritis. CONCLUSIONS: Peripheral inflammatory arthritis, particularly RA or RA-like forms, may develop in CP patients. This overlap strengthens the hypothesis of an autoimmune origin of CP.

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study.

OBJECTIVES: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. DESIGN: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count. RESULTS: After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l. CONCLUSIONS: There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.

Failure of mebendazole in the treatment of humans with Trichinella spiralis infection at the stage of encapsulating larvae.

Trichinella spiralis larvae infective for laboratory mice were collected from muscle biopsies performed at different times (from 1 day to 16 months) following the end of treatment, indicating the failure of mebendazole to kill Trichinella parasites when they are encapsulating in muscles.

Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies.

In order to establish a safe and reliable treatment for human immunodeficiency virus (HIV)-associated scabies, we have treated 60 episodes of scabies in this setting, occurring in 39 patients, with one of the following regimens: (i) topical treatment with benzyl benzoate solution; (ii) single-dose oral treatment with ivermectin alone; and (iii) combination therapy with benzyl benzoate solution and oral ivermectin, employing the same regimens as single-agent therapy. Patients were stratified according to the severity score of the disease and the outcome (eradication, relapse, failure). We found that both benzyl benzoate and ivermectin alone were quite effective in mild to moderate scabies, but they were both associated with an unacceptable rate of relapse and failure in severe or crusted scabies. In contrast, combined treatment produced an optimal rate of success, without significant treatment-related side-effects. Therefore, we consider that combination treatment with benzyl benzoate solution and oral ivermectin is preferable to single-agent therapy in crusted scabies occurring in HIV/acquired immune deficiency syndrome patients.

Antiretroviral therapy in HIV-infected individuals in clinical practice: are the criteria for initiating and choosing the type of drug regimen based only on immunologic and virologic values?

OBJECTIVES: To determine factors associated with beginning antiretroviral therapy and with the number of drugs used. METHODS: Longitudinal study of 3169 HIV-infected individuals naïve from antiretroviral drugs at enrollment in 65 infectious disease clinics in Italy. Initiation of antiretroviral therapy and number of drugs used (i.e., < 3 vs. > or = 3 drugs) were the main outcome measures. Adjusted odds ratios were calculated by logistic models to establish cofactors of these two measures. RESULTS: From January 1997 to December 1998, 1288 (40.6%) individuals started therapy, 58.0% of whom were given a triple combination regimen. This regimen became more frequent over time. By multivariate analysis, high levels of HIV-RNA and low CD4 counts were the most important independent predictors of starting any type of therapy. A significant association was also found with HIV exposure category, reason for being antiretroviral-naïve, presence/absence of liver disease, presence/absence of a new AIDS-defining disease, and clinical centre. High levels of HIV-RNA and low CD4 counts were also the most important predictors of starting with > or = 3 drugs, compared to < 3 drugs, and men had an independent higher probability of starting with > or = 3 drugs, compared to women. The probability of starting with > or = 3 drugs significantly increased with calendar time. CONCLUSIONS: CD4 and HIV-RNA were the main cofactors of initiating both any type of therapy and therapy with > or = 3 drugs. The large variability among clinical centres suggests that clinicians are uncertain as to the exact timing of beginning therapy and the specific regimen, especially among women.

Temporal changes in the rate of progression to death among Italians with known date of HIV seroconversion: estimates of the population effect of treatment. Italian HIV Seroconversion Study (ISS).

OBJECTIVE: To evaluate changes in survival among HIV-positive individuals with known date of seroconversion (SC). DESIGN: Prospective cohort study. METHODS: Follow-up lasted from SC to death or to the end of 1997. A multivariate Cox model was applied to estimate relative hazards (RH) of death. The year of SC (as a categoric fixed variable) and calendar year (as a time-dependent variable) were considered to evaluate, respectively, cohort and prevalent changes in the rate of death. A separate Cox model was used to assess the association between survival and new combination therapies, using an "intention to treat" approach. RESULTS: The study included 1535 individuals (53.9% injecting drug users, 25.3% homosexuals, 19.5% heterosexuals); 75.8% seroconverted between 1980 and 1991, and 24.2% seroconverted between 1992 and 1997. When adjusting for year of SC, the RH of death (and that of AIDS) was significantly lower in 1997, compared with before 1991 (RH = 0.54; 95% confidence interval, 0.30-0.98). Adjusted RHs of death were significantly lower for combination antiretroviral therapy, compared with no therapy. When combining the two Cox models, the 1997 reduction in risk of death was largely due to antiretroviral therapies; similar results were obtained when the endpoint was AIDS. CONCLUSIONS: A reduction in the risk of death, probably due to combination antiretroviral therapy, was observed in 1997 after having adjusted for age at SC and year of SC.

Hydroxyurea and didanosine long-term treatment prevents HIV breakthrough and normalizes immune parameters.

Hydroxyurea and didanosine treatment suppressed HIV replication for more than 2 years, in the absence of viral breakthrough, in chronically infected patients. The profile of viral load reduction was unusual for a two-drug combination, since a continuous gradual decrease in viremia persisted despite residual viral replication. The increase in CD4+ T cell counts was not robust. However, unlike those of patients treated by other therapies, CD4+ T lymphocytes were functionally competent against HIV, mediating a vigorous HIV-specific helper T cell response in half of these patients. In addition, the percentages of naive CD4+ and CD8+ T lymphocytes were not different from those in uninfected individuals. These results demonstrate that prolonged antiretroviral therapy with a simple, well-tolerated combination of two affordable drugs can lead to sustained control of HIV, normalization of immune parameters, and specific anti-HIV immune response.

Longitudinal human immunodeficiency virus type 1 load in the italian seroconversion study: correlates and temporal trends of virus load.

A prospective study of 149 human immunodeficiency virus type 1 (HIV-1) seroconverters was conducted to describe trends and correlates of HIV-1 load after seroconversion and over time. HIV-1 load was quantified from frozen sera by reverse transcriptase-polymerase chain reaction. High early virus load was associated with lower CD4 cell counts and male sex but not with age at seroconversion or injection drug use. Early virus load predicted progression to clinical AIDS and AIDS/<200 CD4 cells/microL. Virus load exhibited a decline of 52% by 18 months after seroconversion then increased 23% annually (95% confidence interval, 13%-33%). Men and those developing AIDS during follow-up had higher virus loads over the course of disease. Persons who developed AIDS had a steeper virus load slope than those who were AIDS-free (P=.01). In long-term follow-up, virus load exhibited a gradual and sustained increase over time. Virus load and annual increase are strong predictors of disease progression.

A randomized, double-blind trial on the use of a triple combination including nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Human outbreak of trichinellosis associated with the consumption of horsemeat in Italy.

Trichinellosis is endemic among sylvatic mammals in Italy, though it causes only few infections in humans, usually due to the consumption of pork from pigs grazing in wild areas or from wild boars. Most cases of human trichinellosis in Italy are due to th

[Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection]. / L'imaging diagnostico e le implicazioni terapeutiche nelle infezioni polmonari del paziente affetto da HIV1.

We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.

A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection.

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.

Clinical and pharmacokinetic evaluation of a new lipid-based delivery system of amphotericin B in AIDS patients.

To evaluate the safety, tolerance and pharmacokinetics of a new formulation of amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds of mycoses were studied: oropharingeal and/or esophageal azole-resistant candidiasis (9), CNS cryptococcosis (7) or aspergillosis (2). Amphotericin B daily dose was infused in 100 ml of a lipid emulsion. The patients aged from 26 to 54 years with body weight ranging from 42 to 89 kg. Blood samples were collected at fixed intervals and plasma stored at -20 degrees C until tested by a specific HPLC assay. The individual kinetic analysis of plasma drug levels was performed by a two-compartment open model. The data were analyzed using P-Pharm, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The effect of a variety of demographic factors on clearance and volume of distribution was investigated. The clearance and the apparent volume of distribution were, respectively, (mean +/- SD): 0.037 +/- 0.015 l/h/kg and 0.45 +/- 0.32 l/kg. The interindividual variability in AmB clearance and volume of distribution was modelled with proportional error with an estimated coefficient of variation of 40.6% and 70.9%, respectively. Clinical and biological tolerance was very good and no patient experience infusion-related adverse effects or hematologic and hepatic toxicity; a moderate renal failure occurred in only one patient.

Isolated kidney localization of invasive Aspergillosis in a patient with AIDS.

Although the importance of Aspergillus in AIDS is now increasing, extra-pulmonary disease is still an unusual event, especially when a single localization occurs. A case of isolated renal aspergilloma in an AIDS patient is described. At onset, no recognized risk factors were present in our patient. An early surgical approach combined with antifungal chemotherapy (amphotericin B, Itraconazole) led to a good control of the disease, with no evidence of recrudescence at 8 months' follow-up.

Hepatitis C virus (HCV) infection in the Piacenza dialysis center.

In a group of 110 dialysis patients, 21% had anti-HCV antibodies. Statistical differences were noted according to method and duration of dialysis as well as the presence of further risk factors.

[Multibacillary atypical mycobacteriosis]. / Micobatteriosi atipica multibacillare.

A case of atypical multibacillary mycobacteriosis is described. The differential diagnosis is discussed on the basis of clinical, microbiological and histopathological parameters.