Lack of clinical evidence for a specific HIV-associated glomerulopathy in 203 patients with HIV infection.

Several authors described a high incidence of proteinuria with frequent progression to nephrotic syndrome and/or renal failure in patients with HIV infection. Though renal histological changes were rather non-specific, the existence of a specific, HIV-associated glomerulopathy was postulated. We repeatedly investigated proteinuria and serum creatinine in 203 HIV-infected patients. One hundred and twenty-two patients (group 1) had early stages of the disease without opportunistic infections, 81 suffered from acute opportunistic infections (group 2). In patients with a positive qualitative test (Combistix), quantitative measurement (Biuret) for proteinuria was carried out; when proteinuria was greater than 0.5 g/24 h, SDS gel electrophoresis was performed. None of the patients of group 1 had a proteinuria greater than 0.5 g/24 h or an elevated serum creatinine. Eleven of 81 patients from group 2 had a proteinuria between 0.5 and 3 g/24 h; one further patient of group 2 developed a transient proteinuria of 7.7 g/24 h. Only three of the proteinuric patients showed a glomerular pattern in SDS gel electrophoresis, all three during acute CMV or EBV infections. Fourteen of 81 group 2 patients showed a transient elevation of serum creatinine (x +/- SD of the maximum serum creatinines: 225.3 +/- 163 mumol/l), most during pentamidine therapy for Pneumocystis carinii infection; one patient treated with high-dose acyclovir had to be temporarily dialysed. In the investigated 203 HIV patients no nephrotic syndrome and no sustained elevation of serum creatinine greater than 200 mumol/l was observed. All cases of proteinuria and elevation of serum creatinine were associated with severe opportunistic infections and the administration of potentially nephrotoxic antibiotics.

Cytokine secretion by peripheral blood monocytes from human immunodeficiency virus-infected patients is normal.

We have measured the production of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor alpha (TNF alpha) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of patients infected with human immunodeficiency virus 1 (HIV-1) and healthy controls. Spontaneous and LPS-induced cytokine production were not significantly different between patients and controls. Median lipopolysaccharide-stimulated cytokine secretion for patients and controls was 1.7 and 4.3 U/ml for IL 1, 475 and 625 U/ml for IL 6, and 468 and 580 pg/ml for TNF alpha. Cytokine levels were not related to stage of disease. We conclude that in vivo HIV infection itself does not alter peripheral blood monocyte cytokine secretion.

[Fluconazole in therapy of candidiasis of the oropharyngeal space in patients with HIV infection. Results of an open multicenter study of assessing the effectiveness and tolerance of fluconazole]. / Fluconazol in der Therapie der Kandidose des Mund-Rachen-Raumes bei Patienten mit HIV-Infektion. Ergebnisse einer offenen multizentrischen Studie zum Nachweis der Wirksamkeit und Verträglichkeit von Fluconazol.

50 HIV-positive patients (CDC stage III to VI) with oral candidiasis proven by culture and typical clinical findings were treated with fluconazole (50 to 100 mg/day) over a period of eight to 22 days. After completion of treatment, clinical signs of oral candidiasis had disappeared in 45/50 patients. In 10/50 patients, however, increased concentrations of candida both in pharyngeal washes (greater than 10(2) PFU/ml) and throat swabs (greater than 20 colonies/culture) persisted. Four weeks later, clinical candidiasis had reappeared in 22/42 patients and another 14/42 patients without clinical symptoms had pathological concentrations of candida in culture. In no case did treatment with fluconazole itself have to be aborted because of adverse reactions. Most of the patients had multiple concomitant bacterial and/or viral infections requiring comprehensive medication. The side effects observed (nausea, headache, changes in the blood picture, etc.) were due to the concomitant infections and their specific therapy.

Efficacy of intravenous immunoglobulins in patients with advanced HIV-1 infection. A randomized clinical study.

40 adults with symptomatic HIV-1 infection (AIDS related complex [ARC] WR 2B-4B or AIDS WR 5-6) were randomized into two groups, receiving either 200 mg of an i.v. immunoglobulin preparation (ivIg)/kg body weight every other week or no such treatment. Medical care and antibiotic therapy were comparable in the two groups. Frequency of opportunistic infections, "B"-symptoms, number of T-helper cells, change of disease stage (Walter Reed Classification, WR), delayed cutaneous hypersensitivity, onset and clinical course of Kaposi's sarcoma, neurological manifestations and proportion of patients alive at the end of the observation period were evaluated. After an average observation period of 13.8 months, decreased mortality was observed in ivIg treated patients of WR 5-6 (p less than 0.004). Frequency and microbial spectrum of opportunistic infections, the most frequent cause of death, were not influenced significantly by ivIg treatment. No statistically relevant differences concerning the other parameters were observed. A similar beneficial effect of ivIg in WR 2B-4 patients has not become apparent so far.

Immunocytochemical demonstration of human immunodeficiency virus infected cells in the cerebrospinal fluid.

Although involvement of the central nervous system represents one of the most common manifestations of the acquired immunodeficiency syndrome (AIDS), a standard diagnostic test for this condition has not yet been established. At necropsy human immunodeficiency virus (HIV) has been demonstrated in brain macrophages in such patients. HIV antigen was detected in CSF macrophages by immunocytochemistry in six out of 11 HIV infected patients. In addition to the detection of intrathecal synthesis of anti-HIV antibodies this method may be suitable for early diagnosis of CNS involvement in AIDS patients.

Regulation of the in vitro monoclonal immunoglobulin production in cultures of peripheral blood mononuclear cells and bone marrow cells from myeloma patients mediated by T cell dependent mitogens.

In vitro monoclonal immunoglobulin (mIg) production of cultured tumour cells--prepared from the bone marrow (BM) or from the peripheral blood (PB) of 40 multiple myeloma (MM) patients, 16 patients with monoclonal gammopathy of undetermined significance and two patients with M. Waldenström--was measured with an enzyme-linked immunosorbent assay (ELISA) using anti-idiotype and anti-class specific antisera. After in vitro stimulation with pokeweed mitogen (PWM) or OKT3 antibody, mIg production was regularly suppressed in BM cell cultures, whereas enhanced, unaltered or suppressed production was observed in PB cell cultures. These observations show that the expanded clone in MM can still be regulated in vitro. Separation experiments demonstrated the involvement of T cells in this in vitro system. The results could be explained by the hypothesis that activated T cells can suppress mature cells of B cell differentiation, as found in BM of the patients, but stimulate earlier B cells from the peripheral blood towards differentiation into Ig secreting cells.

In vitro immunoglobulin production by peripheral blood mononuclear cells from multiple myeloma patients and patients with benign monoclonal gammopathy. Regulation by cell subsets.

Peripheral blood mononuclear cells (PBM) from four patients with IgG myeloma and four patients with benign monoclonal gammopathy (BMG) were stimulated with pokeweed mitogen (PWM), and the in vitro immunoglobulin production over 7 days was measured with an enzyme-linked immunosorbent assay. All myeloma patients were sufficiently treated with cytostatic drugs. Their PBM did not produce monoclonal Ig in vitro, as opposed to PBM from two patients with BMG. Unseparated PBM from myeloma patients produced smaller amounts of polyclonal Ig than unseparated cells from normal donors. However, macrophage-depleted PBM from myeloma patients produced amounts of Ig comparable to those of normal donors when autologous or allogeneic adherent cells were returned in defined numbers. T cells from three of the four myeloma patients could provide help for the Ig production by B cells from healthy donors. These results indicate that functionally normal polyclonal B cells circulate in the blood of myeloma patients. The circulating T-cell population also has no obvious defect. In contrast, blood macrophages seemed to be altered with respect to their regulating function for polyclonal Ig production. The results obtained by using cell populations from patients with BMG did not differ from those of healthy people.