Antibiotic regimen including linezolid for treating prosthetic valve endocarditis with cerebral embolism due to methicillin-susceptible Staphylococcus aureus after failure with oxacillin and teicoplanin.

A case of prosthetic valve endocarditis due to methicillin susceptible Staphylococcus aureus (MSSA) with cerebral metastatic seeding is described. The patient is a 61 year old man with diabetes mellitus, chronic renal failure and previous bacterial endocarditis. Despite appropriate MSSA therapy, the patient was eventually cured with the introduction of linezolid, without needing surgical intervention.

Serum non-organ specific autoantibodies in human immunodeficiency virus 1 infection.

Serum samples from 66 seropositive subjects (56 with a history of intravenous drug abuse), including asymptomatic carriers and patients with persistent generalised lymphadenopathy (PGL), AIDS related complex (ARC), and AIDS, were tested by indirect immunofluorescence on rat tissue sections and HEp-2 cells for the presence of antibodies to nuclei, smooth muscle, intermediate filaments (anti-IMF) and microfilaments (anti-MF). Counterimmunoelectrophoresis was also used to detect antibodies to extractable nuclear antigens. Smooth muscle antibodies with the V pattern or antinuclear antibodies, mainly of the speckled type, or anti-IMF, occurred in 35 cases, being widely distributed in all groups. Such an autoantibody response resembles the "viral" autoimmunity described in various infectious diseases and in particular that of non-A, non-B post-transfusion hepatitis. Autoantibodies may be of some prognostic relevance, as the prevalence of smooth muscle antibodies V increased as the disease progressed (asymptomatic carriers 20%, those with PGL 29%, those with ARC 47%, and those with AIDS 63%. In the PGL group autoantibody positivity correlated with the presence of skin anergy. The fact that autoantibodies were more frequently detected in patients with circulating immune complexes suggests that these can contain autoantibodies and the corresponding autoantigens.

Hodgkin's Disease in 50 Intravenous Drug Users with HIV-Infection.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients. In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

Serum thymidine kinase (TK) evaluation in HIV infection.

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 of patients 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.

[Considerations on a series of malaria cases]. / Considerazioni su una casistica di malaria.

Stress is laid on the seriousness of malaria and the causes of its unusual clinical pictures. Results obtained in the evaluation of G-6-PD, PK, intracellular K and globular resistance, in addition to other parameters, suggest (as pointed out in the literature) that altered cell metabolism may be the primary cause of haemolysis. Attention is also drawn to the lengthy persistance of gametes after gametocidal management in some patients, and the risks that this involves.

[Notes on immunology in a series of cases of chronic hepatitis. Cellular immunity and stimulation with PPD]. / Note di immunologia in una casistica di epatiti croniche. Immunità cellulare e stimolazione con P.P.D.

The authors estimated E, E.A.C., and E-active rosette in 13 chronic active hepatitis (C.A.H.), 5 chronic persistent hepatitis and 4 cirrhosis. The results showed a significant decrease of the concentration of peripheral blood T-lymphocytes in patients with C.A.H., C.P.H., cirrhosis. E.A.C. rosette forming cells were not significantly different from the control population in all groups studied. E-active rosette were decrease in patients with C.A.H. and C.P.H. and were increased after stimulation by P.P.D. (5 U.V.I.) in C.A.H. and C.P.H. and in control group studied.

[Meaning and development of markers of acute hepatitis]. / Osservazioni sul significato e la evolutività dei markers delle epatiti acute.

The Authors analyse the results of their tryls about the markers of HBV and HAV acute hepatitis (HBsAg, anti-HAVAb) by R.I.Z. method. HAVAb was in 75% of the cases, its meaning was of post-contact with HAV. The title of HAVAb was effected in 18 patients with viral acute hepatitis; the results were 3 cases of HAV acute hepatitis and in other 7 cases no Ano B viral acute hepatitis. The 58.3% of acute viral hepatitis was HBsAg positive, the study of other markers of HBV and the title of HAVAb showed a viral acute hepatitis caused by HBV. We were not able to demonstrate the viruses which caused 7 HBsAg negative acute virale hepatitis, anti-HBcAg was in 97.8% of HBV acute hepatitis; its the most sensitive of HAV past-infection. The system c-anti-e was in 78.2% of HBsAg viral acute hepatitis. The persistence after 7th week of illness of HBeAg coincided with the hepatitis cronicity. On the contrary anti-HBeAg has not always a protective meaning.

[Hepatitis B and hepatitis A markers in 33 cases of acute hepatitis B surface antigen-negative, hepatitis A virus antibody-positive viral hepatitis. Importance of immune complexes]. / Studio dei markers dell'HBV, dell'HAV in 33 casi di epatiti virali acute HBsAg negativi, HAVab positivi. Importanza degli immunocomplessi.

The authors have looked for the markers of HBV by R.I.A. method (HBsAg, anti HBsAg, HBeAg, anti HBeAg, anti HBcAg), of HAV (by measurement on two samples of HAVab or by measurement of HAVab IgM), the immune-complexes (I.C.C.) by C1q solid-phase binding assay method with E.L.I.S.A. with determination after division I.C.C. of HBsAg by R.I.A. method in 33 cases of HBsAg negative acute viral hepatitis. The 9% (3 cases) were HAV acute hepatitis, the 42,4% (14 cases) no A no B acute hepatitis, the 36,3% (12 case) were HBV acute hepatitis, in 9 anti HBcAg positive cases the I.C.C. with HBsAg positive after division resulted positive, the 12,3% (4 cases) had a positivity for HAVab by stereoconversion (2 cases) or HAVab IgM (2 cases) with HBsAg positivity after division I.C.C. This result puts a nosologic problem about the 4 cases of acute viral hepatitis, which, from epidemiological and clinical point of the view are HAV acute hepatitis.

[Zinc and lymphocyte subsets in patients with HIV infection]. / Zinco e assetto linfocitario in pazienti con infezione da HIV.

Serum zinc levels were assayed in patients with AIDS and related syndromes, using spectrophotometry and atomic absorption. Statistical data have shown that serum zinc levels, in addition to being significantly lower (p less than 0.001) among different groups and controls, decrease progressively with the worsening of the clinical and immunological picture from LAS to AIDS. Serum zinc levels in patients with AIDS and ARC have, moreover, been demonstrated to be related (r = 0.8240; p less than 0.001) to the lymphocyte subset CD4 helper-induced. These results suggest that serum zinc determination and possibly zinc therapy might be reasonably considered in the management of patients with symptoms of HIV infection.

[Pneumocystosis]. / Pneumocistosi.

On the basis of personal experience, the microbiological, epidemiological, clinical and therapeutic features of Pneumocystis carinii pneumonia are analysed.

Invasive Aspergillosis in Italian AIDS patients.

BACKGROUND: We studied the prevalence, epidemiological features, symptoms, diagnosis, treatment and outcome of invasive aspergillosis in AIDS patients in Italy. PATIENTS AND METHODS: All patients affected by both aspergillosis and AIDS hospitalized between January 1986 and April 1997 (before highly-active antiretroviral therapy, HAART) in four Italian Department of Infectious Disease. Patients were included in the study only if culture, cytology or histology showed firm evidence of Aspergillus infection. Invasive aspergillosis was defined as the presence of characteristic, closely septate hyphae with repeated acute angle branching in either biopsy materials or percutaneous aspirates from tissues other than the lung. Hyphae were identified using hematoxylin-eosin and methenamine silver stain. RESULTS: During the study, 54 out of 2,614 patients admitted with AIDS showed aspergillosis (2.1%). The disease usually occurred in patients with < 50 CD4 cells/mm(3). Aspergillosis was associated with neutropenia and steroid treatment. Nonspecific symptoms were frequently encountered. Fever and cough were both present in > 70% of the cases of pulmonary aspergillosis. Biopsy specimens were analyzed for definitive diagnosis. Invasive aspergillosis is usually treated with amphotericin B, but in 90% of the cases this did not prevent death. CONCLUSION: In AIDS patients with neutropenia and long-term steroid therapy, it is important to consider invasive aspergillosis in the differential diagnosis of opportunistic infections.

Preliminary observations using HIV-specific transfer factor in AIDS.

Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV) were treated orally with HIV-1-specific transfer factor (TF) for periods varying from 60 to 1870 days. All patients were receiving antiviral treatments in association with TF. The number of lymphocytes, CD4 and CD8 subsets were followed and showed no statistically significant variations. In 11/25 patients the number of lymphocytes increased, whilst in 11/25 decreased; similarly an increase of the CD4 lymphocytes was observed in 11/25 patients and of the CD8 lymphocytes in 15/25. Clinical improvement or a stabilized clinical condition was noticed in 20/25 patients, whilst a deterioration was seen in 5/25. In 12/14 anergic patients, daily TF administration restored delayed type hypersensitivity to recall antigens within 60 days. These preliminary observations suggest that oral HIV-specific TF administration, in association with antiviral drugs, is well tolerated and seems beneficial to AIDS patients, thus warranting further investigation.

[Diagnosis of major depression in HIV-infected patients]. / Diagnosi psichiatrica di depressione maggiore in soggetti con infezione HIV.

A survey of current mood disorders (and especially major depression) is performed after considering quoted literature over the last five years. The sample includes all the HIV-infected-patients continuously referred to the Outpatient Service of the Infectious Diseases dept. of Bologna's "Ospedale Maggiore" General Hospital during some five days (19-23rd, July 1993). Each of the 53 recruited subjects was seen by a psychiatrist in the same morning of his/her medical visit; then also BPRS, STAI, CGI, BDI and MADRS were administered. A psychiatric diagnosis has been found in the 45% of the sample. The results being discriminated on the basis of absence-presence and diagnostic category, they point out a significant prevalence of ARC among subjects with psychiatric diagnosis and prevalence of asymptomatic HIV-infection among those ones with absent psychiatric diagnosis. Drug dependence (72%) and personality disorder are markedly prominent among ARC patients. But the surprising outcome (lower than references data) is that the diagnosis of current major depression is found only in 1.9% of cases (mood disorder in 9.4%).

The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases.

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.

Alveolar macrophages from patients with AIDS and AIDS-related complex constitutively synthesize and release tumor necrosis factor alpha.

To verify the hypothesis that alveolar macrophages (AMs) from patients infected with HIV-1 could synthesize and release TNF alpha, AMs recovered from the BAL fluid of 11 patients with seropositive HIV-1 (six with AIDS and five with ARC) were tested in vitro for their ability to destroy TNF alpha-susceptible targets. Furthermore, the presence of TNF alpha was assessed in AM-conditioned supernatants on the basis of their cytotoxic activity and by using an immunoenzymatic test and immunoblotting. Transcription of the TNF alpha gene in AMs was also studied by means of the Northern blot analysis. AMs freshly recovered from patients infected with HIV-1 exhibited high levels of cell-mediated cytotoxicity against U937 targets, and the addition of a polyclonal anti-TNF alpha antibody resulted in a significant inhibition of the target lysis. Cell-free supernatants conditioned by unstimulated AMs exerted high levels of cytotoxic activity against TNF alpha-sensitive targets, whereas duplicate, neutralization experiments performed in the presence of an anti-TNF alpha antibody proved that the observed cytotoxic activity was mostly mediated by TNF alpha. The presence of high amounts of TNF alpha in the conditioned media was confirmed by the immunoenzymatic test. In addition, the immunoblot analysis showed that the TNF alpha released by AMs has a Mr 17,000 band, identical to a standard preparation of recombinant TNF alpha. The Northern blot demonstrated that unstimulated AMs express detectable levels of mRNA transcripts for TNF alpha. Taken together, our data support the concept that AMs from patients with HIV-1 infection constitutively release TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant interleukin-2 (rIL-2) in acquired immune deficiency syndrome (AIDS): preliminary report in patients with lymphoma associated with HIV infection.

In an ongoing phase II study, 12 patients with lymphoma and HIV infection were treated with zidovudine (ZDV) and recombinant interleukin-2 (rIL-2) to evaluate if this association may produce beneficial effect on the immunologic status and the outcome of lymphoma. The protocol included daily doses of rIL-2 at 6 MIU/m2 over 5 days in c.i. per week for a total 4 courses; ZDV was associated at 600 mg/d in the period under study. An improved CD4 count, exceeding 2- to 4-fold the basal count, was obtained in patients with a basal CD4 number greater than 100/microliters accompanied by a significant increase of NK and LAK activity (p less than 0.001). From the clinical point of view the reduction of tumor manifestation was proportional to CD4 basal number; 2 patients from those with CD4 greater than 100/microliters obtained a complete remission after rIL-2 and ZVD. The p24 antigen, taken as parameter of viral replication, remained invariably negative after rIL-2 and ZDV in patients already negative and became negative in 1 patient previously positive. Our conclusion is that the association of rIL-2 and AZT is safe and useful in patients with lymphoma and HIV infection.

Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV).

The efficiency of HIV-1 specific transfer factor (TF) administration, combined with Zidovudine (ZDV), in asymptomatic persistent generalised lymphadenopaty, or AIDS related complex (ARC) patients was evaluated. Twenty patients were randomly assigned to receive only ZDV (1st group) or ZDV together with HIV-1-specific TF (2nd group). HIV-1-specific TF was administered orally at 2 x 10(7) cell equivalent daily for 15 days, and thereafter once a week for up to 6 months. There were no significant differences between the two groups in clinical evolution, red blood cells, haemoglobin, lymphocytes, CD20 subset, transaminases, beta-2-microglobulin, p24 antigen. White blood cells, CD8 lymphocytes as well as IL-2 levels increased in the second group, while the CD4 subset increased in the first group. The combination treatment with ZDV and TF appeared to be safe and well tolerated. Furthermore, levels of serum cytokines were investigated in 10 patients (8 asymptomatic and 2 ARC) treated with ZDV, and compared with 5 patients of the 2nd group (3 asymptomatic and 2 ARC) treated with ZDV plus HIV-1-specific TF. Peripheral lymphocytes, CD4, CD8 subsets, IL-2, TNF alpha, IL-6, p24 antigen, IL-2 soluble lymphocyte receptors (sR), CD4sR, CD8sR and beta-2-microglobulin were evaluated at the baseline and at the 3rd month. The CD4 subset was not significantly different in the two groups, whilst IL-2 increased in the 2nd group receiving ZDV plus TF, suggesting an activation of the Th1 secretion pattern.

3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic combination in the treatment of human immunodeficiency virus-related non-Hodgkin's lymphomas.

We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can possess a significant antineoplastic activity when combined with drugs that disrupt de novo thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of the present study was to evaluate the efficacy and the tolerance of the combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed or pretreated, have been enrolled in the trial; the median age was 34 years, 45% had acquired immunodeficiency syndrome before lymphoma and 19 patients had less than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20 patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh patient on, in case of complete or partial remission, the treatment was continued with three additional courses, using AZT at the maximum dose. In 26 evaluable patients, the total (complete + partial) response rate was 77% (95% confidence interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95% confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52% and 31% of the courses, respectively. There was one therapy-related death due to bacteremia followed by septic shock; the only other recorded infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen in HIV-related NHL.