TOLERABILITY AND EFFICACY OF A SLOW-RELEASE INDOMETHACIN TABLET IN ANKYLOSING SPONDYLITIS

The efficacy and tolerability of a new formulation of slow-releaseindomethacin tablet was compared in a double-blind cross-overmanner with a conventional indomethacin capsule in 30 patientswith ankylosing spondylitis. Gastrointestinal side-effects anddizziness were less frequent during the slow-release tabletperiod than during the capsule period. KEY WORDS: Ankylosing spondylitis, Indomethacin, Tolerability, Slow-release tablet ^*This formulation of indomethacin is not available in the UK—Ed.     

Free fraction change with differing volume ratios in equilibrium dialysis: cases of non-linear drug-protein binding

When equilibrium dialysis is used to measure drug-protein binding, an increase in the volume ratio (buffer solution/protein solution) causes a decrease in the total drug concentration at equilibrium. When binding is non-linear, this decrease in total drug concentration also causes a decrease in the free fraction. By use of the same volume ratio (3:1) binding curves were obtained for the binding of prednisolone to plasma proteins, and for the binding of salicylic acid and tolmetin to human serum albumin (HSA). When the volume ratio was changed, the observed free fractions were appreciably different from those expected by taking into account only the changes in the total equilibrium drug concentration. There is evidence that this phenomenon is the result of competition for binding sites between the drug and an impurity in the HSA. The effects are not the result of the presence of free fatty acids.     

ACTH versus prednisone and placebo in herpes zoster treatment

The effect of ACTH (Synacthen-depot®) versus prednisone and placebo in the treatment of herpes zoster (HZ) was studied in a controlled clinical trial comprising 60 consecutive patients. The treatment groups were comparable regarding sex, age and pre-entry symptom duration. The skin changes, patients' pain scores and the consumption of analgesics were monitored. Regarding objective symptoms and the development of postherpetic neuralgia there was no difference between the two treatment groups and placebo, while the ACTH group showed a decrease in pain score and consumption of analgesics during the first 4 days of the trial. Whether this finding will justify the application of ACTH in early HZ is arguable. Neither ACTH nor prednisone influenced the development of postherpetic neuralgia but this negative finding may be inaccurate due to the small number of patients in the three groups. Severe side-effects did not occur.     

Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.     

Contact allergy to 8-methoxypsoralen

A 20-year-old male patient was treated topically with 8-methoxypsoralen and long-wave ultraviolet light (UV-A) for alopecia areata. He developed contact allergy to 8-methoxypsoralen after the sixth treatment (day 17), which was verified by patch testing and histopathology.