HIV-related Hodgkin's disease. Report of nine cases.

BACKGROUND: The association between lymphoproliferative disease and AIDS is now well known, but only non-Hodgkin's lymphomas (LNH) are surely related to HIV infection. Hodgkin's disease (HD) occurs rarely in HIV seropositives, so it is impossible to establish a connection between AIDS and this neoplasm. METHODS AND RESULT: We describe nine cases of HIV seropositive patients who developed HD in different stages of the HIV infection. We carefully examine clinical course and response to therapy in these patients, above all paying attention to opportunistic infections (OI) and progression to full-blown AIDS. CONCLUSION: Finally, we discuss the possibility of including HD among the definition criteria for AIDS.

Immunoglobulin G3-specific antibodies as a marker for early diagnosis of HIV infection in children.

Early diagnosis of HIV infection in the child of an HIV-infected mother may be difficult as HIV-specific immunoglobulin (Ig) G antibodies are transmitted to the fetus transplacentally. In an attempt to provide a new, simpler tool for early identification of HIV-infected children we analysed the HIV-specific IgG subclass pattern during the first year of life. One hundred and one samples were collected from 35 children born to HIV-seropositive mothers, among whom 18 seroreverted during follow-up and 17 were HIV-infected (two P1 and 15 P2 according to the Centers for Disease Control classification). Serum HIV-specific IgG3 was detectable at least in one sample in 26 out of 35 children. All 17 HIV-infected children showed persistently detectable specific IgG3, both with stable or progressive disease. Out of the 18 uninfected children who seroreverted during follow-up, nine were HIV-specific IgG3-negative when first tested and nine lost HIV-specific-IgG3 within 28 weeks after birth. The correlation of the serological results with clinical information and any other diagnostic tool on each child suggests that the clearance of specific-IgG3 antibodies heralds seroconversion in uninfected passive antibody-carrier children. This observation provides the basis for a new, simple and effective method for early diagnosis of HIV infection in children born to seropositive mothers.

Neurophysiological markers of central and peripheral involvement of the nervous system in HIV-infection.

Peroneal motor and sural sensory conduction velocities (MNCVs/SNCVs), somatosensory evoked potentials to median nerve stimulation (MN-SEPs) and motor evoked potentials (MEPs) to transcranial stimulation were examined in 138 HIV-infected patients (in the different stages of the disease), 20 seronegative intravenous drug abusers (IVDAs), and 20 healthy subjects. Findings of peroneal MNCV slowing in patients ranged from 16% (asymptomatic HIV patients) to 63% (AIDS) and of sural SNCV slowing from 13% to 40%. Altered MN-SEPs ranged from 10% to 30%, and MEPs ranged from 44% to 72%, mostly due to a prolongation of the central motor conduction time (CMCT). All seronegative IVDAs showed patterns within the normal range. Electrophysiological techniques were helpful in demonstrating early and subclinical alterations in HIV patients.

Chlamydia trachomatis infection in "sine causa" recurrent abortion.

One hundred and one women suffering from "sine causa" recurrent abortion were screened for Chlamydia trachomatis (C.T.) infection by using direct examination, cultural and serological procedures. In this series, C.T. infection did not appear to be related to increased risk of recurrent abortion. The culture-positive and serology-positive rates (14.85% and 34.65%, respectively) did not differ from other unselected populations. Neither time from last abortion nor type of abortion were significantly related to C.T. infection. Nonetheless, the women who underwent examination within one year from last abortion and had a culture-positive partner as well, were more likely to present with a C.T.-positive culture.

Phagocytosis of human erythrocytes by Naegleria is not related to species pathogenicity. A phase-contrast cinemicrographic study.

This phase contrast cinemicrographic study evaluated the phagocytic activity of Naegleria spp. (Naegleria fowleri, Naegleria australiensis and Naegleria lovaniensis) towards human red cells. Thus erythrophagocytosis, a marker of pathogeneicity for Entamoeba histolytica, did not correlate with virulence in either the pathogenic or non-pathogenic Naegleria spp. tested. Our study also revealed no quantitative differences in phagocytosis by Naegleria spp. of human erythrocytes.

Chlamydia trachomatis infection in primary unexplained infertility.

In recent years Chlamydia trachomatis has emerged as a significant cause of acute salpingitis and reproductory failure. In this study, 85 women suffering from primary infertility and 85 parous women as control group were screened for C. trachomatis genital infection by means of cell culture and antigen detection on genital samples as well as the detection of anti-chlamydial antibodies in blood. C. trachomatis was detected in 31.8% of infertile women and 5.8% of fertile subjects. Isolation of C. trachomatis in cell culture proved to be the most reliable diagnostic tool when compared to immunofluorescence staining on smears and serology. Although the latter may be considered of great value in epidemiological researches, culture isolation should be associated for the diagnosis of active infection.

Kinetics of p24 antigenemia, IgM, IgG antibodies to p24 and p41 and Ig virus isolation in rabbits experimentally infected with HIV-1.

In rabbits experimentally infected with 1.10(5) u.i./ml HIV, IgM antibodies were detected 10-15 days after infection, reaching peak value two weeks later and remaining stable for two weeks long. Then a the IgM serotiters progressively decreased and were negative at ten weeks. HIV p24 antigen was detected ten-fifteen days after infection, reaching peak value five-six weeks later. Antigenemia subsequently decreased and reached a second peak after nine weeks. In our experimental conditions, the antigenemia persisted throughout the observation period. The IgG antibody titer reached a maximum two weeks after infection; the time course showed a decrease after ten weeks, followed by progressively decreasing fluctuating course. After twenty four weeks of infection the serotiter values though lower were always positive. Three-four weeks after infection we detected IgG antibodies to the major core protein p24. Reactivity of IgG antibodies to gp41 was observed earlier than reactivity to p24; these antibodies were detected over six months after infection. Viruses indistinguishable from HIV were isolated from the peripheral blood mononuclear cells of infected rabbits 30, 60 and 180 days after infection. These data further confirm that the rabbit may serve as an economical and reproducible model for HIV infection in which vaccines and antiviral agents could be tested.

Bone marrow morphology and proliferative activity in acquired immunodeficiency syndrome.

Peripheral cytopenia has been reported in a number of patients with the acquired immunodeficiency syndrome (AIDS), but the mechanism of bone marrow (BM) failure is unclear. We have examined the BM morphology and cytokinetics of 16 untreated HIV-positive patients whose clinical condition ranged from asymptomatic (stage 1 WR and II CDC classifications) to overt AIDS (stage 6 WR and IV CDC classifications). BM aspirates and iliac crest threphine biopsies were obtained for myelogram and histologic examination, as well as for propidium iodide flow cytometric (FMC) DNA analysis. FCM data were compared with those from the BM of patients with solid tumors without BM involvement. Four patients had normal peripheral blood counts, 2 were anemic, 2 had granulocytopenia, 2 thrombocytopenia, 4 bicytopenia and 2 pancytopenia. BM cellularity was normal or increased, but only 2/16 patients had normal BM morphology. Ten patients had atypical lymphoid aggregates, relative plasmacytosis and eosinophilia, and 4 had typical myelodysplastic changes. There was no correlation between morphology and WR or CDC grade. The mean proliferative fraction (i.e. the percentage of cells in the S phase of the cell cycle) of the HIV-positive patients was 11% (range 5.5-18.3%). The mean value for the control patients was 15.1% (range 7.7-26.9%) (p less than 0.05). All patients had modal diploid DNA content without aneuploid clones. These data suggest that the mechanism of BM failure in HIV-positive patients lies in a reduced proliferative activity whose exact cause is still unclear.

Therapy of entamebiasis.

Therapy of entamebiasis is critical in that, if untreated, the disease can be fatal. Recently, a new method for differentiating pathogenic and non-pathogenic amebae has been standardized. This method relies upon the electrophoretic analysis of 4 isoenzymes which allow the identification of 20 different zymodemes. It is now widely accepted that non-pathogenic strains of Entamoeba histolytica are not a hazard for humans and therefore don't need therapy. As a consequence, treatment must be addressed only toward infections caused by pathogenic strains. As there are different drugs available for treating amebiasis, from a therapeutical point of view the disease must be divided into two forms: intestinal and extraintestinal. For the former, drugs which reach therapeutical levels in the gut are required. The mainstay for the treatment of asymptomatic carriage of pathogenic strains is DILOXANIDE FUROATE, a very well tolerated luminal amebicide. METRONIDAZOLE and other 5-nitroimidazole compounds such as ORNIDAZOLE are indicated for the treatment of symptomatic intestinal infections as they reach good concentrations in tissues, including the bowel where ulcerations develop. In order to ensure the clearance of amebae from the gut, a subsequent cycle with diloxanide furoate is advisable. Extraintestinal forms include amebic abscesses which can develop in many sites, but most commonly in the liver. Metronidazole and related compounds are the drugs of choice; in case of liver abscess, the addition of CHLOROQUINE is indicated because of its good concentration in tissues. A subsequent cycle with diloxanide furoate is also indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of computerized electroencephalography in diagnosing, staging and monitoring AIDS-dementia complex.

One hundred and one subjects, with various degrees of HIV infection, were enrolled in a longitudinal study aimed at evaluating the correlation between clinical and instrumental findings in the development of HIV-related subacute encephalitis. The method used was electroencephalography coupled with computerized spectral analysis (EEG-CSA) and mapping. The findings recorded by this method were compared with those obtained by computed tomography (CT) scan and neurological examination. The EEG-CSA findings were divided into four categories according to their severity. EEG-CSA was shown to be very sensitive in detecting the first signs of a forthcoming neurological disease. Following 11 months of observation, 22 out of 40 (55%) neurologically asymptomatic individuals who, at the beginning of the study showed some EEG-CSA abnormalities, had clinical evidence of a subacute encephalitis whereas only two out of 37 (5.4%) subjects who were previously free of EEG-CSA abnormalities had some signs of neurological disease (P less than 0.001) after the same period. Of those remaining who were already symptomatic when the study started, the neurological progression of HIV infection was also monitored by EEG-CSA.

Ultrasonographic and microbiological diagnosis of mycetic liver abscesses in patients with AIDS.

A rare case of multiple mycetic abscesses in a patient with AIDS is reported: the diagnosis was suspected after an ultrasound (US) examination and was obtained with US guided percutaneous puncture. The US appearance and differential diagnosis of mycetic liver abscesses are discussed and the increasing role of US and US guided percutaneous puncture in the screening of these patients is stressed.

Detection of IgG anti-HIV antibodies in mice experimentally infected with HIV-1.

In the present work we report our preliminary data demonstrating the susceptibility of mouse to HIV infection. IgG antibodies were found in mice intraperitoneally inoculated with H9/HTLV-IIIB infected cells. Infected mice showed a humoral response and the antibodies detection includes specific immunoglobulin directed against the major gene product of HIV. Two weeks after infection with HIV infected cells we detected in mice IgG antibodies to p24, and the reactivity to gp41 was observed as early as reactivity to p24 and persisted throughout observation period. The persistence of specific antibody response to HIV after one year seems to demonstrate the possibility of the use of the mouse as animal model for HIV in vivo experiments. Studies concerning the degree and kinetic of HIV infection in mouse are in progress in our laboratory.

The spectrum of chronic hepatitis in the last two decades in a university hospital for infectious diseases.

During the last eighteen years (1970-1987) at the Infectious Diseases Clinic of the University of Pavia, Ospedale Policlinico S. Matteo, IRCCS, Pavia (referral Center for hepatitis in our district: 502534 inhabitants) we observed 4238 patients (2706 M = 63.8%; 1532 F = 36.2%) admitted with presumptive diagnosis of hepatitis. The male to female sex ratio was 1.78 and average age was 38 (1-90) years. Acute viral hepatitis was diagnosed in 3238 patients (76.4%), 1960 of which were males (60.5%) and 1278 (39.5%) females, with an average age of 35 (1-88) years. The possible route of transmission was: drug addition in 487 patients (15%), blood transfusion in 464 (14.3%), other (sexual, professional, familiar) in 332 (10.3%), unknown in 1955 (60.4%). Chronic hepatitis (CH) was diagnosed according to the European Association for the Study of the Liver (EASL) and to the International Association for the Study of the Liver (IASL) in 848 patients (20%), 704 M(83%) and 144 F (17%) with an average age of 48 (2-90) years. 463 patients (54.5%) were biopsied during admission, 385 (45.5%) received definitive diagnosis by clinical and previous histologic records. CAH was found in 268 (57.9%), CPH in 161 (34.8%) and CLH in 20 (4.3%) patients. Other liver diseases (steatosis, cirrhosis, HCC) were identified in 152 subjects (3%). The prevalence of A, B, NANB and Delta hepatitis virus and HI virus in the acute disease was respectively of 5.4%, 54.8%, 33.9%, 0.28% and 0.77%. In CH the HBV aetiology accounted for 49.1%, NANB virus for 44.5%, co/super infection with HDV for 15%. Among factors involved in pathogenesis of chronic hepatitis we focused attention on drug addition which was found in 129 (28.7%) patients, blood transfusion in 70 (15.6%), HIV infection in 35 of 166 (21.1%). The data still demonstrate the high prevalence of HBV aetiology of CH and existence of co-factors in the pathogenesis of chronicity. The lack of markers for NANB infection persists as the main problem in the diagnosis of liver disease. This work was supported by grant 40% from M.P.I.: "Epatiti virali acute e croniche"....

An in vitro comparative study on the effect of amphotericin B, econazole, and 5-fluorocytosine on Naegleria fowleri, Naegleria australiensis, and Naegleria australiensis s.sp. italica.

We tested in vitro amphotericin B (AMP-B), econazole (ECO), and 5-fluorocytosine (5-FC) on pathogenic Naegleria fowleri (KUL strain), Naegleria australiensis s.sp. italica (AB-T-F3, original strain) to assess their sensitivity to chemotherapeutic compounds. Previous reports have shown the polyene antibiotic AMP-B to be the most active agent. It was, however, much more active on N. fowleri than on N. australiensis and N. australiensis s.sp italica. 5-FC and ECO gave rise to non appreciable effect at non-toxic corresponding dosages in vivo. The results of these in vitro tests are discussed.

Serial study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B.

To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibitory factor assay) and humoral (RIA) immunity to LSP (a macromolecular, liver-derived lipoprotein complex) and hepatic lectin (HL), the liver-specific receptor for desialylated glycoproteins, which appears to be a major target antigen for autoreactions in autoimmune chronic active hepatitis. Anti-LSP and anti-HL autoantibodies were found, at some stage during acute HBV infection, in 4/5 subjects, whereas cellular immunity to the same antigens was detected in only two patients. Sustained production of anti-HL antibodies was noted only in patients showing cellular immunity to this antigen and was apparently secondary to liver damage, whereas anti-LSP antibodies were first detected at the onset of liver injury when there was no evidence of T-cell immunity to the same antigenic complex. One explanation for this apparent dichotomy between cellular and humoral responses to LSP is that a helper T-cell response to the major envelope component of HBV, HBsAg, which precedes by 10-20 days the development of anti-LSP antibodies, promotes a humoral reaction to autoantigens contained in the LSP preparation, coexpressed with HBsAg, on the surface of infected hepatocytes.

Sequential studies of pre-S2 antigenemia and anti-pre-S2 antibodies in relation to viral replication in acute hepatitis B followed from the early incubation phase.

To determine the time sequence of expression of pre-S2 peptide (120-150) during the presymptomatic phase of acute hepatitis B, we used a monoclonal antibody radioimmunoassay in five subjects followed from 30 to 70 days before the onset of liver damage. Pre-S2 peptide was present in serum at low levels from the early incubation phase and started to increase immediately after the first detection of HBV-DNA in serum, in parallel with the increase in HBsAg levels. During the symptomatic phase, levels of pre-S2 peptide declined rapidly; it was no longer detectable after recovery. Anti-pre-S2 antibodies were detected, in four patients, only in the recovery phase. These results demonstrate that expression of pre-S2 peptide occurs very early in the incubation phase of acute HBV infection and is cleared in parallel with HBsAg. Anti-pre-S2 antibodies seem to play no role in viral clearance in these patients.

Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B.

Cellular immunity to hepatitis-B-virus (HBV) antigens was followed prospectively in five patients who were identified in the early incubation phase of acute HBV infection, between 30 and 70 days before the onset of liver damage. Cellular immunity to pre-S antigens was the first detectable immune response, appearing 30 days before the first rise in serum aminotransferases in every case. T-cell sensitisation to HBcAg followed, with IgM anti-HBc appearing 10 days later. A cellular immune response to HBsAg was the last to appear, 10 days before the onset of liver damage. These cellular immune responses are the earliest host responses to the virus infection and could be critical in initiating and directing the processes of liver damage and viral clearance.