Microemulsion formulation of cyclosporin (Sandimmun Neoral) vs Sandimmun: comparative safety, tolerability and efficacy in severe active rheumatoid arthritis. On behalf of the OLR 302 Study Group.

OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

Blood dehydroepiandrosterone sulphate (DHEAS) levels in polymyalgia rheumatica/giant cell arteritis and primary fibromyalgia.

Blood levels of dehydroepiandrosterone sulphate (DHEAS) were measured by radioimmunoassay (RIA) in patients with: a) polymyalgia rheumatica/giant cell arteritis (PMR:TA; N = 25), with and without cortisone derivative treatment (N = 10 and N = 15, respectively); and b) primary fibromyalgia (PF; N = 15). The mean DHEAS levels were found to be significantly reduced in PMR:TA, compared to those in PF (Geom. mean 820 vs. 2300 nmol/l, respectively; p < 0.001), and the reduction was more marked in patients on cortisone derivative treatment. The DHEAS levels found in PF were found to be normal and consistent with those previously reported in non-immune mediated rheumatological diseases such as osteoarthritis, and in healthy subjects, using the same method of analysis. The low levels found in patients with PM:TA are in accordance with those previously reported in immune-mediated diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, suggesting that diminution of DHEAS is a constant endocrinologic feature in these categories of patients. The pathophysiological significance of these low DHEAS levels needs to be investigated.

Disease-modifying anti-rheumatic drug therapy. An expensive therapy despite inexpensive drugs.

In a study of the costs for drug therapy, 81 patients with rheumatoid arthritis taking parenteral gold, penicillamine or chloroquine were included. The patients were assessed for costs, directly and indirectly caused by the therapy, during a 12-week period. The three therapy groups were comparable in terms of number of patients, sex, age and duration of disease. There were substantial differences in costs for therapy between the three disease-modifying anti-rheumatic drugs. Treatment with parenteral gold gave the highest cost, 2.2 times that of chloroquine and 1.4 times the cost of penicillamine. The cost for the antirheumatic drug constituted a minor part of the total cost (4.4-15.4%). The need for patient visits for treatment and safety controls was a major factor in the overall cost.

Traction osteophytes of the lumbar spine: radiographic-pathologic correlation.

Previous reports have emphasized two types of osteophytes on the anterior aspects of the lumbar vertebral bodies: the common claw osteophyte and the less common but more significant traction osteophyte, which is indicative of spinal instability. To delineate the importance of the traction osteophyte, a radiographic-pathologic study was conducted. The results indicate that claw osteophytes are more frequent than traction osteophytes, that both may coexist in a single vertebral body, and that, in most cases, these osteophytes appear to represent different stages of the same pathologic process.

Radiography of the hyperextended lumbar spine: an effective technique for the demonstration of discal vacuum phenomena.

A prospective evaluation of dynamic lateral lumbar spine radiographs in the erect position in 52 symptomatic patients over the age of 50 years revealed vacuum phenomena in intervertebral discs in 46%. Their frequency was greatest at the L5-S1 spinal level and decreased progressively at higher lumbar levels. Analysis of the dependency of discal vacuum phenomena on spinal position during radiography revealed that hyperextension detected all such phenomena; radiography in the neutral position detected 73% of vacuum phenomena, whereas that obtained with the spine flexed revealed 20% of vacuum phenomena. Our results indicate that lateral radiographs of the hyperextended lumbar spine are useful in the differential diagnosis of intervertebral osteochondrosis (degenerative disease of the nucleus pulposus) and infection.

Magnetic resonance imaging of the lumbar spinous processes and adjacent soft tissues: normal and pathologic appearances.

The spinous processes and intervening soft tissues of the lumbar region may be involved by degenerative, inflammatory, neoplastic, and traumatic processes resulting in low back pain. While conventional radiography and computed tomography have proven useful in the demonstration of abnormalities affecting the spinous processes, they are of limited utility in the evaluation of the intervening soft tissues, which are the predominant site of initial pathologic involvement. To explore the potential role of magnetic resonance imaging (MRI) in the assessment of the spinous processes and adjacent ligaments, a retrospective review of 55 consecutive examinations of the lumbar spine was performed. The normal and pathologic appearances of the region on both T1 and T2 weighted images were characterized, and the optimal imaging variables for demonstration of the spinous processes and adjacent soft tissues were determined with subsequent prospective application to new cases. Correlative examination of cadaveric sections and dried specimens was also performed to facilitate understanding of anatomical relationships visualized by MRI. Based upon the results of this investigation, MRI is the procedure of choice in the evaluation of disease processes affecting the spinous processes and intervening ligaments, primarily owing to the ability to image directly in the sagittal plane and its superior soft tissue contrast discrimination capability.

Periostitis in hypertrophic osteoarthropathy: relationship to disease duration.

The relationship of periostitis to disease duration in primary hypertrophic osteoarthropathy and the association of periostitis with cardiopulmonary disorders (secondary type) were studied in order to define distinguishing features between the two. Radiographic skeletal surveys were performed in 24 patients with hypertrophic osteoarthropathy to analyze pattern (single layer, multilayered, irregular) and site of involvement (diaphysis, metaphysis, epiphysis). The six patients with primary hypertrophic osteoarthropathy and the 11 patients with cyanotic congenital heart disease had thicker, more widespread periostitis involving the diaphysis, metaphysis, and epiphysis, in contrast to abnormalities in the seven patients with hypertrophic osteoarthropathy secondary to carcinoma of the lung. Average cortical bone widths as determined by radiogrammetric measurement of the second metacarpals were significantly greater for the patients with primary hypertrophic osteoarthropathy (8.9 +/- 6.0 mm) and cyanotic congenital heart disease (8.5 +/- 6.4 mm) as compared with the patients with bronchogenic carcinoma (6.0 +/- 3.9 mm). Correlation of radiographic patterns with duration of disease confirms that thicker, more extensive alterations are indicative of long-standing disease. The periostitis of hypertrophic osteoarthropathy is therefore not dependent on the primary or secondary nature of the disease but principally on its duration.

Focal fat deposition in axial bone marrow: MR characteristics.

One hundred fifty-eight magnetic resonance (MR) imaging studies of the spine were reviewed to assess the frequency and distribution of focal deposits with signal behavior typical of fat in the axial bone marrow. In addition, three fresh cadaveric spines were evaluated with MR imaging and subsequently sectioned for anatomic and histologic correlation. Macroscopic evaluation of the sectioned cadaveric specimens revealed well-defined, yellow areas within the bone marrow that correlated precisely with localized zones of signal intensity characteristic of fat on MR images. Histologic evaluation of these regions demonstrated typical focal fatty replacement of hematopoietic bone marrow. Their appearance was related to age and the presence of pathologic changes such as spondylitis, kyphoscoliosis, and spondylosis. Based upon these observations, focal fatty replacement of hematopoietic bone marrow appears to be a common phenomenon that should not be confused with localized disease processes.

Langerhans cells in connective tissue diseases.

We have conducted a quantitative analysis of Langerhans cells (LC) in skin biopsies of 20 patients with various connective tissue diseases. Clinically normal skin of SLE patients as well as lesional skin of DLE showed consistently normal LC densities as assessed using ATPase staining, anti-DR and anti-OKT6. Examination of LC in clinically involved skin of patients with scleroderma revealed an absolute or relative decrease in ATPase and OKT6 expression, while staining with anti-DR gave inconclusive results. Clinically normal skin of the same individuals showed basically normal LC density. These findings suggest that the perturbation of the LC population is probably an expression of a secondary local phenomenon, and does not reflect a more widespread derangement of the accessory cells in the skin.

HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. An unusual association observed in two patients.

Two patients are described who suffered from both HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. The diagnosis of liver disease was made prior to the diagnosis of collagenosis in one of the patients, whereas the opposite was the case in the other. In spite of the fact that symptoms and laboratory data suggesting both diagnoses were present from the moment of presentation, there was a considerable delay in establishing the second diagnosis in both patients. To our knowledge, this is the first report on an association between chronic active hepatitis and mixed connective tissue disease syndrome. It illustrates the difficulties when diagnosing overlap conditions.