Prevalence, risk factors and outcome of hyperlactataemia in HIV-infected patients.

OBJECTIVE: We describe the prevalence, risk factors and outcome of hyperlactataemia (HL) in a cohort of 140 HIV-infected patients. PATIENTS AND METHODS: Patients were enrolled consecutively within a 3-month period (July to September 1999) and followed until 31 October 2000. One hundred and forty HIV-infected patients had venous plasma lactate levels measured. HL was defined at baseline by two consecutive lactate levels > 2.1 mmol/L (upper limit of normal). We compared baseline demographic characteristics, immuno-virological parameters, antiretroviral therapy and outcome between patients with HL (cases) or without HL (controls). We described the clinical features of patients with HL. RESULTS: Among 129 patients included in the analysis, HL was found in 11 patients (8.5%), all of whom were receiving nucleoside reverse transcriptase inhibitors (NRTIs). Cases were more likely than controls to receive didanosine or stavudine (82% vs. 19%, P= 2.7 x 10(-6) and 82% vs. 48%, P= 0.03, respectively). Only 4/11 cases (36%) had symptoms consistent with HL. After a median follow-up of 15 months, lactate level returned to normal in all three patients who discontinued NRTIs, but in only 2/8 patients who did not (P = 0.06). Only one case experienced lactic acidosis and died during follow-up. Mortality rate was similar in cases and controls. CONCLUSION: HL is associated with NRTI use, in particular didanosine and stavudine, and discontinuation of NRTIs seems to be associated with rapid resolution of HL. Lactic acidosis remains rare and the long-term outcome of patients with HL does not seem to be poorer than controls.

Multicenter evaluation of the Elecsys CA 125 II assay.

The technical performance and clinical usefulness of the newly developed Elecsys CA 125 II assay (Boehringer Mannheim) was evaluated in a multicenter study. Imprecision studies were carried out using control sera and human pool sera with CA 125 concentrations from 11 to 1026 U/ml. Within-run CVs between 0.7 to 4.8% (median 1.7%) and between-day CVs between 2.4 to 10.9% (median 5.7%) were found. Method comparison studies with Enzymun-Test CA 125 II carried out in four laboratories yielded slopes between 0.94 to 1.07 and intercepts < 3 U/ml. A good comparability of the Elecsys CA 125 II assay was also found with one MEIA and the Centocor" IRMA. For a second MEIA and a second IRMA the slopes were 1.23 and 1.42, and the corresponding correlation coefficients were 0.987 and 0.977, respectively. The Elecys CA 125 II concentrations are clearly related to the tumor stage of ovarian carcinoma patients. The maximum of diagnostic efficiency of ovarian carcinoma patients compared with patients of benign gynecological diseases is reached at 150 U/ml with a specificity of 93% and a sensitivity of 69%. Follow-up studies of ovarian carcinoma patients reflect the status of the disease and the effect of various therapeutic applications. The technical and clinical evaluation of the Elecsys CA 125 II assay show a superior analytical performance with a broad measuring range up to 5000 U/ml and a short measuring time of 18 minutes.

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.