Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis.

One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids (30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study (not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive either 1 microgram/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed by dual-photon absorptiometry on entry and after 3, 6 and 12 months' treatment. Safety was monitored by the recording of all adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the 145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6 and 12 months. The percentage change in BMD after 6 months' treatment was -2.11% in the alfacalcidol group and -4.00% in the placebo group (p = 0.39). After 12 months the percentage change in BMD was +0.39% (CI: -4.28 to 4.81) in the alfacalcidol group and -5.67% (CI: -8.13 to -3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p = 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol's favor (3.81%, p = 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose at any time point during the study. Serum calcium was measured throughout and there were no significant differences between the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse group of patients.

Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men.

We prospectively studied adrenal function in 51 human immunodeficiency virus-positive male patients, including heterosexuals, homosexuals, and iv drug users, classified according to 1987 CDC criteria as belonging to stages II/III or IVC. Basal serum concentrations of cortisol (F), progesterone (P4) and 17 alpha-hydroxyprogesterone (17 alpha-OHP4) were determined during the two stages. In stage IVC patients, the circadian rhythms of ACTH and F were assessed, and ovine CRH (oCRH) and immediate cosyntropin-stimulating tests were evaluated. Serum concentrations of hormones were analyzed in relationship to the absolute CD4 cell count in all subjects. The mean serum F concentration in stage IVC patients, the mean P4 concentration in stage II/III and IVC patients, and the mean 17 alpha-OHP4 level in stage II/III patients were significantly increased compared to control values (P < 0.0001, P < 0.0001, and P < 0.002, respectively). The mean serum F concentration in stage IVC patients was significantly increased compared to that in stage II/III patients (P < 0.004), and the mean serum 17 alpha-OHP4 concentration in stage II/III patients was significantly increased compared to that in stage IVC patients (P < 0.02). In the 22 stage IVC patients, the circadian rhythms of ACTH and F were normal in all but 7 for ACTH and 5 for F, whereas oCRH test results indicated that 14 of them had reduced or blunted responses. By contrast, cosyntropin stimulation results were normal. CD4 cell counts were significantly negatively correlated with the serum F concentration (P < 0.02). In conclusion, during human immunodeficiency virus infection, the serum F concentration was negatively correlated with CD4 cell counts. Cosyntropin test results were normal, but 63% of the stage IVC men had abnormal responses to oCRH.

Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients.

Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.5 +/- 14.6 mg of Hx-Ara were removed by one PE during the first week of treatment (15 mg kg-1 d-1, continuous infusion) and 7.8 +/- 10.2 mg were eliminated by one PE during the second week of treatment (7.5 mg kg-1 d-1, continuous infusion). Based on the vidarabine intake per hour and the resulting quantity of Hx-Ara removed per hour, PE recovery was quite important (ca. 30 per cent), during both the first and second weeks of continuous infusion. Data were subject to large interindividual variability. However, these results do not favor vidarabine dosage supplementation in this indication because the duration of PE is less than 8 per cent of a daily administration period. For paracetamol (1 g, single oral dose) and diclofenac (100 mg, single oral dose), the fractions of drug removed during PE effected within 2 h of drug intake, were respectively 5.0 +/- 3.1 per cent and 13.6 +/- 9.5 per cent, while plasmapheretic clearance reached, respectively, 13.0 +/- 10.7 per cent of the systemic clearance for paracetamol and 23.0 +/- 1.0 per cent for diclofenac.