Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood.

We reported two cases of hepatitis B virus infection-related cirrhosis developed during childhood and followed up for more than 20 years. Both the subjects remained untreated, and ultimately regression of cirrhosis was documented by clinical (including ultrasound) and histological examination. Recent studies have already suggested that hepatitis B virus-related cirrhosis may regress after treatment, but this is the first demonstration that hepatitis B virus-associated cirrhosis developed in childhood may be a spontaneously reversible process. Subsidence of virus replication and of necro-inflammatory process and the efficiency of liver regeneration and repair might contribute to this favourable outcome.

Shedding of the soluble form of the CD8 complex by CD8+/HLA-DR+ cells in HIV-1-infected patients.

High levels of the soluble form of the CD8 molecule (sCD8) are detectable in the serum of HIV-1-infected patients. To investigate the mechanisms accountable for the release of this molecule we evaluated the presence of sCD8 in the supernatants obtained from in vitro cultures of highly purified CD8 cells isolated from 20 HIV-1-infected patients. At resting conditions cultured CD8 cells from HIV-1-infected patients released low amounts of sCD8; no statistically significant differences were observed between unstimulated cultures from HIV-1-seropositive patients and from HIV-1-seronegative subjects at risk for HIV-1 infection or normal healthy controls. Following in vitro activation of highly purified CD8 cells with a series of stimulatory agents, including phorbol myristate acetate, phytohemagglutinin (PHA) and recombinant interleukin-2, CD8 cells of HIV-1-infected patients significantly increased the shedding of sCD8. By expressing the results of activation-related release index (ARRI = sCD8 levels detected in the cultures with stimulatory agent/sCD8 levels detected in the unstimulated cultures), significantly higher values were observed upon PHA stimulation in HIV-1-infected patients than in control subjects. In order to identify the cell subset responsible for the enhanced release of sCD8 by PHA-stimulated cultures, we correlated the amounts of sCD8 detected in the supernatants with the phenotypic profile of CD8+ cells recovered from the cultures. A significant relationship was demonstrated between the percentage of CD8+/HLA-DR+ lymphocytes and sCD8 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired cytokine production by neutrophils isolated from patients with AIDS.

OBJECTIVES: To determine the ability of neutrophils isolated from HIV-seropositive patients to produce proinflammatory cytokines. DESIGN: The in vitro responsiveness of polymorphonuclear neutrophils (PMN) and peripheral blood mononuclear cells (PBMC) to lipopolysaccharide (LPS), used in the presence or absence of interferon (IFN)gamma, was determined in 47 HIV-positive patients with advanced stages of virus infection. METHODS: Cytokines in cell-free supernatants were measured by enzyme-linked immunosorbent assay or radioimmunoassay. RESULTS: Cell-free supernatants from PMN isolated from the peripheral blood of HIV-positive patients and stimulated with LPS contained increased amounts of tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 with respect to supernatants obtained from PMN of normal donors. In contrast, release of IL-1beta and IL-1ra (IL-1 receptor antagonist) in response to LPS, or LPS plus IFNgamma, was found to be lower in PMN from HIV-positive patients than in PMN from controls, but was significant only in the case of IL-1ra. Furthermore, the release of IL-12 induced by LPS or LPS plus IFNgamma did not significantly differ between PMN from HIV-positive patients and healthy donors. Concerning PBMC, the production of TNF-alpha and IL-12 in response to LPS, or LPS plus IFNgamma, was found to be significantly higher in cells isolated from HIV-positive patients, whereas the release of IL-1beta was significantly lower. In the case of IL-8, no statistically significant difference was found between PBMC isolated from HIV-positive patients and healthy donors. CONCLUSIONS: Collectively, the data suggest that in HIV-positive patients with advanced stages of disease, the ability of PMN to produce specific cytokines in response to LPS is significantly altered. Alterations in this ability might contribute to the evolution of HIV disease.

The effect of a single course of alpha-2B-interferon in patients with HIV-related and chronic idiopathic immune thrombocytopenia.

13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiopathic thrombocytopenic purpura (C-ITP) were treated with a single course of alpha-2b-Interferon (IFN 3 x 10(6) IU subcutaneously for 12 d). The patients had platelet counts lower than 40 x 10(9)/L and thrombocytopenia persisting for over 1 year (range 1-22 years); 7 patients were refractory to previous conventional therapy, 5 were responsive, and 11 had not been previously treated. The response to IFN was complete in 8 patients (platelets > 100 x 10(9)/L), partial in 7 (platelets 50-100 x 10(9)/L); 8 patients showed no response. The treatment with IFN was stopped after 4 d in one patient due to a fall in platelet count. The maximal platelet count (median peak 116 +/- 55 SD x 10(9)/L platelets) was obtained after 13.7 +/- 2.98 d and the improvement in platelet count was maintained for 22.8 +/- 8.6 d. No difference in platelets response was observed between HIV-ITP and C-ITP. The response to IFN seems to be related to the one obtained with previous treatments. Indeed 80% of the patients who were responsive to previous steroids, high dose immunoglobulins or azidothymidine (HIV-ITP) showed a complete or partial response while only 43% of the refractory patients showed a partial response; the positive response rate in previously untreated patients was 73%.

Prognostic significance of the evaluation of bronchoalveolar lavage cell populations in patients with HIV-1 infection and pulmonary involvement.

To investigate the prognostic utility of the morphologic and immunologic evaluation of BAL cell populations in determining mortality risk, we analyzed BAL data obtained from 115 patients infected with HIV-1. Forty fatal outcomes occurred within 73 patients with OI. The OI patients who died showed a significant increase in neutrophils with respect to surviving patients. Furthermore, the finding of a BAL neutrophilia in HIV-1-infected patients with OI strongly correlated with a high risk of death. Among 42 cases without OI, 11 patients died. Patients without OI who had a fatal outcome showed an increase in CD3+ and CD8+ BAL lymphocytes with respect to the survivors. The presence of a lymphocytic alveolitis was associated with a significant increase in the mortality rate. Taken together our data suggest that the evaluation of the BAL cell populations might be useful in predicting the risk of fatal outcome in patients with HIV-1 infection.

Hepatitis C in childhood: epidemiological and clinical aspects.

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.

Transient tonic pupils in botulism type B.

We report a 29-year-old woman who developed unilateral unreactive mydriasis and cycloplegia after 5 days of persistent constipation. During the next hours the patient complained of dry mouth and difficulties in swallowing food; iris and ciliary muscle palsies spread over the second eye. Ocular motility was normal and there were no clinical signs of neuromuscular involvement. Conventional electromyography and evoked muscle action potentials following repetitive nerve stimulation were normal; single-fiber electromyography showed normal jitter and absence of blocking. The diagnosis of botulism was considered as most likely, and the patient was given botulinum antitoxin. The post-treatment course was characterized by bilateral tonic pupillary reaction to near, sectoral iris contractions to light and pupillary constriction to 2 mm in 40 min following topical instillation of 0.1% pilocarpine. Ocular manifestations completely disappeared within 5 weeks. Botulism type B toxin was demonstrated in the pretreatment stool of the patient but not the serum.

Mediastinitis due to cryptococcal infection: a new clinical entity in the HAART era.

OBJECTIVES: Highly active antiretroviral therapy (HAART) produces a rapid decline in plasma HIV-1 RNA levels with concomitant immune reconstitution. Probably due to the enhanced immune function, shortly after starting HAART, some latent opportunistic infections precipitated. The aim of this study was to illustrate the results of a survey on Cryptococcus associated mediastinitis occurring after HAART introduction, carried out at a referral centre of Infectious Diseases in the north-east of Italy, between October 1999 and October 2000. METHODS: All consecutive HIV-positive patients, naive to HIV-protease inhibitor therapy, and diagnosed with culture-proven cryptococcal infection were included in the study. Clinical and immuno-virological parameters before HAART and subsequently for 12 months were evaluated. RESULTS: Three of five patients were diagnosed with cryptococcal mediastinitis within a median time of 90 days (range, 60-150) after commencing HAART and fluconazole prophylaxis. Diagnosis was established by lymph node biopsy alone. Clinical improvement was documented when systemic anti-fungal therapy was combined with surgical drainage of the suppurative lesions. The role of immune restoration was confirmed by the significant increase in CD4 cell count, the reduction of HIV-RNA to undetectable levels and the prominent inflammatory reactions of lymph nodes. CONCLUSIONS: Our report suggests that HIV-positive patients with prior cryptococcal systemic infection may present a re-exacerbation of atypical cryptococcosis as a manifestation of immune restoration, even when fluconazole prophylaxis is ongoing.

Spontaneous ("erosive") cerebrospinal rhinorrhea, with pneumococcal meningitis from anterior optic glioma. Case report.

A 6-year-old girl, operated upon for an optic nerve astrocytoma (resection limited to the intraorbital portion of the nerve), developed 3 years later symptoms and signs of chiasmatic invasion. Nine years after surgery (1980), she suffered from pneumococcal meningitis, due to cerebrospinal rhinorrhea that had been present in the last few years. A repeated neuroradiological investigation showed the site of the fistula and cerebral ventricles of normal size. The case is argued for bulb-to-chiasm resection of an optic nerve glioma: a spontaneous cerebrospinal rhinorrhea with its potential dangers of meningitis seems to be one more complication of a limited resection of these tumors. It is felt that this is an unusual instance of spontaneous rhinorrhea from direct tumoral erosion. The diagnostic value of metrizamide cisternography for the assessment of presence and site of the fistulous leak is confirmed.

Chemo-immunotherapy of advanced AIDS-related Kaposi's sarcoma.

AIMS AND BACKGROUND: Kaposi's sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-alpha) in complete responders. METHODS: Twenty-five previously untreated patients with advanced KS received bleomycin (BL) 10 mg/m2 and vinblastine (VB) 6 mg/m2 on days 1 and 15 every two weeks. After six cycles, patients in complete remission received IFN-alpha (3 million U s.c. 3 times/week) combined with antiretroviral therapy. All patients were evaluated for toxicity using the World Health Organization (WHO) toxicity schedule. Both Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria were used to evaluate response and survival. RESULTS: The overall response rate was 84% (95% confidence interval, 51-117%) with six complete remissions (24%) and 15 partial remissions (60%) by ECOG criteria, and 92% (95% confidence interval: 58-128%) with 17 partial remissions (68%) by ACTG criteria. The median duration of response on IFN-alpha treatment was 4.5 months (range, 2-10). The overall median survival duration for all 25 patients was 9 months (range 2-39). Grade 3-4 anemia was observed in five patients and grade 3-4 neutropenia in two patients. No other clinically significant (> or = grade 3) toxicities were observed. CONCLUSIONS: Combination of BL and VB is effective and well tolerated, even if new therapeutic options are developing. This disease remains a challenging problem, so larger studies using the combination of chemotherapy and/or IFN-alpha with antiretroviral treatment are warranted.

Intravitreal and systemic foscarnet in the treatment of AIDS-related CMV retinitis.

Cytomegalovirus retinitis is the most frequent ocular opportunistic infection in AIDS patients. Untreated, it is always a progressive and destructive disease of the retina that results in blindness. Specific treatment is therefore mandatory to halt the progression of the retinal lesions. The authors report their experience in the treatment of CMV retinitis with foscarnet in 25 AIDS patients; the drug is an analog of pyrophosphate, virostatic against all herpes-class viruses including CMV. Foscarnet was successful in halting the progression of CMV retinitis during induction treatment (180 mg/kg/day) by either a TID (three times a day) or a BID (twice a day) regimen, and in healing retinal lesions during maintenance (90 mg/kg/day) in 14 out of 19 patients. Five patients had a relapse of retinitis during maintenance. In these patients a brief course of intravitreal foscarnet, in association with the lowest dosage of the drug administered systematically (90 mg/kg/day), was effective in healing the retinal lesions. The main systemic side effects, such as renal impairment and electrolytic disturbances, were observed only during the induction treatment, and only in one case was it necessary to stop the therapy.

[Measles encephalitis. Clinical, EEG, and psychometric aspects at follow up (author's transl)]. / L'encefalite morbillosa: aspettti clinici, elettroencefalografici e psicometrici a distanza di tempo.

A follow-up of 23 patients with measles encephalitis was carried out six months to ten years after the onset of the disease. Neurological and electroencephalographic features have been examined together with specific psychological tests. Clinical and electsroencephalographic abnormalities, frequently observed during the acute phase of the disease, were rarely detected during the follow-up. However intellectual performances with specific visuo-spatial and attentional involvement are often impaired. Specific psychological tests are required to evaluate visuo-spatial and attention performances, frequently impaired as a consequence of the disease; these are often considered minor psychological disturbances as they are limited to scholastic performances. The Authors conclude that, although measles encephalitis is a fairly serious illness during its acute phase, it tends to improve with time until recovery is complete. The psychological residual deficits, detected during the follow-up, should not be considered as minor disturbances.

Prognosis of chronic hepatitis B transmitted from HBsAg positive mothers.

Nine children born to HBsAg positive mothers, who became chronic HBsAg carriers with associated liver disease, were followed for five to 10 years. Five children with active hepatitis or active cirrhosis at presentation achieved complete remission within six years, while three HBeAg positive patients with minimal histological lesions remained unchanged.

Acute non-A, non-B hepatitis in childhood.

A prospective study of acute symptomatic viral hepatitis in childhood was started at the Department of Infectious Diseases of Padua (Italy) in 1978. During an 8-year period, 93 consecutive patients (aged 3 months to 12 years) fulfilled the diagnostic criteria, including five (5.5%) cases classified as non-A, non-B hepatitis. This figure is lower than that generally reported in adult patients, probably because of a lower exposure of children to blood and contaminated materials. Two of the five children with non-A, non-B hepatitis had received blood transfusions, while three had no history of parenteral exposure. Although the outcome of the illness was favorable in all five patients, a variety of clinical features could be observed: two children had a mild, short-lasting disease, anicteric in one case, while three had a polyphasic pattern of transaminases with delayed biochemical resolution, including one patient with deep jaundice and severe early phase features. These findings suggest that in children, as well as in adults, non-A, non-B hepatitis is probably a heterogeneous entity induced by different agents with different modes of transmission.

Detection by immunofluorescence of an antigen-antibody system in patients with acute and chronic non-A, non-B hepatitis.

An antigen-antibody system has been identified by immunofluorescence in patients with non-A, non-B hepatitis. The non-A, non-B antigen was localized in the hepatocyte nuclei of liver biopsies from patients with acute post-transfusion or sporadic non-A, non-B hepatitis and in those from patients with chronic post-transfusion non-A, non-B hepatitis, the percentage of positive cells being most prominent in patients receiving immunosuppressive treatment. Absence of the antigen in normal livers and in livers from patients with type B hepatitis infection indicated its specific association with non-A, non-B infection. Antibody reacting with the nuclear antigen became detectable in serum during post-transfusion acute non-A, non-B hepatitis in 11 out of 15 cases; it was absent before transfusion. Six out of 12 cases of sporadic acute non-A, non-B hepatitis were also found to produce the antibody, which was repeatedly found to be absent during the acute phase in five patients with type A and in eight with type B hepatitis. The non-A, non-B antibody, mainly an IgM antibody, persisted in serum for prolonged periods of time after onset, both in patients showing biochemical resolution of their illness and in those who continued to have liver damage after the acute phase. Accordingly, eight out of nine patients with chronic non-A, non-B hepatitis were found positive for the antibody in serum, seven at the time the non-A, non-B antigen was detected in their liver. Thus this non-A, non-B associated antigen-antibody system shares remarkable similarities of behaviour with the "core" system of the hepatitis B virus.

Clinical-electroencephalographic correlations in measles: a long range study of 18 subjects.

EEGs of 18 cases of measles (uncomplicated, with seizures, with encephalitides) were obtained through an underground cable connection between the Infections Diseases Department and the EEG unit. The varions EEG features of the disease have been studied during the evolution of the illness. An occasional EEG does not offer specific information on either the severity or the evolution of the disease. Marked EEG abnormalities appeared in the encephalitic group. The Authors emphasize the importance of serial prolonged EEG follow-up of measles in order to define precisely the stage and the evolution of the disease.