Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B.

Pilot studies have demonstrated that recombinant interleukin 2 (rIL-2) has an indirect antiviral activity against hepatitis B virus, but the minimal dose of rIL-2 for induction of this effect was not defined. The aim of the study was to ascertain the most efficient dose of rIL-2 for induction of the loss of detectable serum HBV-DNA or a 50% or greater decrease in its level. Thirty-one patients with chronic hepatitis B, hepatitis B e antigen and serum HBV-DNA positive were enrolled in this double-blind randomized controlled trial. Patients were divided: Group I (n = 8) placebo; Group II (n = 7) treated with 0.9 MU of rIL-2 subcutaneously administered daily for 8 weeks; Group III (n = 8) treated with 1.8 MU of rIL-2 under the same schedule; Group IV (n = 8) which received 3.6 MU of rIL-2 under the same conditions. At the end of treatment 25% of the patients in the placebo group, and 13% and 25% in rIL-2 groups III and IV, respectively, had a decrease in HBV-DNA higher than 50% of the basal value. None of the patients lost serum HBV-DNA. Only three patients (one from group II and two from group IV) normalized the ALT levels. Overall, during treatment, ALT levels decreased in the treated groups. This decrease occurred simultaneously with an increase in serum HBV-DNA concentration. Since the response rate in the treated groups was similar to that of the placebo group, rIL-2 is not useful as monotherapy for the treatment of chronic hepatitis B at the doses and schedules used in this study.

Continuous versus intermittent therapy for chronic hepatitis C with recombinant interferon alfa-2a.

BACKGROUND/AIMS: Prolonged interferon administration to patients with chronic hepatitis C, although increasing the sustained response rate, is poorly accepted and may favor drug resistance. A pulse-treatment schedule would be preferred for compliance and costs. METHODS: One hundred thirty-five patients with chronic hepatitis C received 6 MU units of interferon alfa-2a, three times weekly, continuously for 9 months (group 1: 66 patients) or for two 3-month cycles, separated by 6 months pause (group 2: 69 patients). RESULTS: At the end of therapy, 25 of 54 patients of group 1 (46.3%) and 28 of 60 of group 2 (46.7%) had normal serum aminotransferase levels. Six months after the end of treatment, sustained responders were still similar in the two groups (11 or 16.7% vs. 7 or 10.1%; NS). A loss of response before the end of therapy was seen in 10 patients of group 1 and 6 of group 2; interferon-neutralizing antibodies developed in 1 of 7 and 6 of 6 of such patients, respectively. CONCLUSIONS: The intermittent administration of interferon alfa-2a to patients with chronic hepatitis C shows a sustained response rate comparable with that achieved with continuous treatment at the same dosage. Hepatitis breakthroughs during pulse therapy appeared to be limited to interferon neutralizing antibodies, whereas a prolonged, continuous treatment is more likely to induce other forms of interferon resistance.

In vitro evaluation of a heparinized blood sampler for ionized calcium measurement.

When ionized calcium measurements are needed urgently blood has to be sampled with an anticoagulant to allow rapid specimen processing. Heparinate salts cause a decrease in ionized calcium by binding which is clinically significant when the concentration exceeds 15 IU/mL of whole blood. The use of an anticoagulant in an aqueous state induces 'solution-dilution' errors. To avoid these two types of error the use of calcium-titrated sodium heparinate in a dry state has been proposed. However, in this situation the actual calcium concentration could be modified if its value were different from the titration level. This possibility has been studied using a commercially available sampler (Radiometer B-129). When the sampler was used as recommended, errors were non-significant around 1.25 mmol/L. There was a +3% increase for low (0.75 mmol/L) values and a -2% decrease for high (2.50 mmol/L) values. Incomplete syringe filling increased these errors.

Use of calcium-titrated sodium heparinate for ionized calcium determination on plasma and whole blood (heparinized blood sampler B-129 Radiometer).

We report modifications of ionized calcium as observed on specimens collected in a commercially available sampling device (Radiometer B-129). When the sampler is used as recommended, errors are non-significant around 1.25 mmol l-1. There is a +3% increase for low (0.75 mmol l-1) values and a -2% decrease for high (2.50 mmol l-1) values. Incomplete syringe-filling increases these errors.

Preanalytical errors in ionized calcium measurements induced by the use of liquid heparin.

The use of heparin in a liquid form to measure ionized calcium (Ca++) in plasma or whole blood can induce preanalytical errors by dilution and by changing the original Ca++ value by binding or by re-equilibration with calcium in the anticoagulant solution. To quantify these errors, Ca++ was measured on serum pools under different sampling conditions. Incomplete syringe filling and specimen volume/syringe nominal volume ratio effects were tested. Syringes were rinsed with saline to yield pure dilution effects, with sodium heparinate to study binding and with calcium-titrated heparinate to evaluate 'calcium-distortion'. Detailed tables provide percentage error values for all sampling conditions. Dilution errors could reach -5% and binding was always important (-14 to -50%). Distortion was minimal around 1.25 mmol/L but could reach -4% for high and +8% for low Ca++ values. Errors increased when syringes were not filled to their nominal volume, especially with small-sized specimens.

Anomalies in pH 7.40 correction in ionised calcium analysers.

As a preliminary step in a study of the effects of calcium ligands on the pH standardisation of ionised calcium (Ca2+) measurement in blood, the change in Ca2+ induced by Pco2 variation was investigated in 12 serum pools on three different instruments. This type of study should yield a log Ca2+ = f(pH) linear relationship in a pH range around pH 7.40 with a slope characterising the pH-sensitive calcium buffer capacity of the specimen. The pH 7.40 correction line should be horizontal. This was the case for an ICA2 analyser but not for an ICA1 or a Nova 8 analyser. The difference was due to an incorrect setting of the built-in slope correction factor in the ICA2: fortuitously its value was close to the effective slopes of the serum pools used for the test. Thus the anomalous behaviour of the ICA1 and the Nova 8 was due to a discrepancy between the standard built-in algorithm and the characteristics of our serum pools. These findings led us to question the use of a constant correction factor to normalise actual ionised calcium values.

Anticoagulant-induced preanalytical errors in ionized calcium determination on blood.

When anticoagulated blood is necessary for ionized calcium (Ca2+) measurements especially in urgent circumstances, the type (sodium or 'calcium-titrated' heparinate) as well as the form (aqueous or dry) of anticoagulant induce preanalytical errors. To quantify these modifications Ca2+ was measured in three aqueous solutions and in three serum pools in different 'sampling' conditions. Incomplete syringe filling and specimen volume/syringe nominal volume ratio effects were tested. Syringes were rinsed (i) with saline to yield 'pure' dilution effect ('solution-dilution'); (ii) with sodium heparinate to study binding; (iii) with calcium-titrated heparinate to evaluate 'calcium-distortion'. All types of errors increased when syringes were not filled to their nominal volume, especially on small-sized specimens. Detailed tables provide percentage error values for all sampling conditions. Thus, 'solution-dilution' can reach -5%; binding is always important (-15 to -50%). 'Calcium-distortion' is minimal, around 1.25 mmol/l Ca2+, but can reach -7% for high Ca2+ and +10% for low Ca2+.

Inadequate algorithm: a cause for 'incorrect pH 7.40 correction' in ionized calcium analysers.

As a preliminary step in a study of the effects of calcium ligands on the pH standardization of ionized calcium (Ca2+) measurements in blood, the slope of logCa2+ = f(pH) linear relationship characterizing the pH-sensitive calcium buffer capacity of the specimen was investigated in 12 serum pools on three different instruments. The pH 7.40 correction line should be horizontal. This was the case for the ICA-2 but not for the ICA-1 and the NOVA-8. The discrepancy was caused by an incorrect setting of the built-in slope correction factor in the ICA-2; coincidentally, its value was close to the effective slopes of the serum pools used in the study. Thus, the 'abnormal' behaviour of the ICA-1 and the NOVA-8 was caused by an inadequacy of the built-in algorithm to the characteristics of our serum pools. These findings lead us to reconsider the use of a fixed and constant correction factor to normalize actual ionized calcium values.

[Early pregnancy interruption using an antiprogesterone steroid: Mifepristone (RU 486)]. / Interruption précoce de la grossesse par un stéroïde antiprogestérone: la Mifépristone (RU 486).

Mifepristone (RU 486) is a new steroid which is a progesterone antagonist and which is able to interrupt early pregnancy. The purpose of our study was to evaluate clinical efficacy and tolerance of two doses of Mifepristone (600 and 200 mg) in a single intake. The study included 205 women applying for a legal abortion with pregnancies under 7 weeks. Clinical examination was confirmed by ultrasound and plasma HCG assessment. Success was assumed by repeating these exams on 8th day. 175 patients took 600 mg of Mifepristone and 147 (84%) had a complete abortion. 30 patients took 200 mg of mifepristone and only 19 (63%) had a complete abortion. Very few side effects were observed. So, Mifepristone in able to terminate early pregnancy under medical supervision.