Histocompatibility antigens in multiple sclerosis in children

A phenotyping was done in respect of HLA system in 14 children with documented multiple sclerosis (MS), 20 children with potential MS, and 42 their near relations. HLA-B12 antigen was recordable with high frequency (RR = 6.29; P < 0.025) while HLA-B18 with low one (P < 0.01) as compared to normal subjects both among patients in the general group and in those with proved MS. The latter showed a tendency toward increase in frequency HLA-B7. Children with significant MS where there was an association in the phenotype of HLA-B12 or HLA-B7 with HLA-A3 ran predominantly an aggravating course while their association with HLA-A2 resulted in a more benign course. The results obtained in respect of HLA antigens in MS in children differ from those of other authors on MS in adults.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Histocompatibility (HL-A) antigens and primary open-angle glaucoma

For the diagnosis of lumbar P.I.D. discography is much superior to myelography. The risks of both techniques are the same, but the side-effects of discography are clearly less. Higher lesions remain a problem if they do not show up neurologically (s. the prolapsed disc at L 2/3). Here segmental blocking, posterior gaping of the intervertebral space and displacement of the dural sac show clearly the posterior prolapse. In the standard discogram of the lower 3 discs it would have been missed. In spite of this our present experience with lumbar discography is so positive, that we are about to test a long term series, whether and to which extend discography could replace myelography in cases where there is no hint at a space-occupying lesion, other than a disc or whether the order of these investigations should be reversed.     

A simple index to assess disease activity in rheumatoid arthritis

Changes in clinical and laboratory measures of disease activity were studied prospectively in 12 European centers. Altogether 282 rheumatoid patients were evaluated during 6 months of therapy with slow-acting drugs. Patients' global assessment was taken to indicate overall response. The number of swollen joints and number of tender joints correlated highly with this. The erythrocyte sedimentation rate (ESR) correlated less well but was more uniform across centers. Grip strength, C-reactive protein and hemoglobin performed poorly between centers. There were cultural and linguistic difficulties using the Health Assessment Questionnaire in a European setting. Physician's global assessments were similar to the patient's global assessments and provided redundant information. The best measures are: the number of swollen joints, the number of tender joints, the ESR, and the patient's global assessment. It may also help to measure articular pain.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Embryos from certain mouse strains are arrested at the 2-cell stage in cell culture ('2-cell block'), whereas those from other strains develop to the blastocyst stage under the same conditions. It was previously shown that blocking embryos can be rescued in culture by aggregation with an excess of 2-cell stages of a non-blocking strain such as CBA x C57BL/6 F2. Here we have employed a LacZ transgene in a blocking strain (NMRI) to follow the fate of rescued blastomeres up to the blastocyst stage. We found that rescued blastomeres can participate in both inner cell mass and trophoblast formation, thus completely overcoming the 2-cell block.     

Tumors in rheumatoid arthritis

Benign (bTu) and malignant tumours (mTu) were studied in a randomised autopsy material of 161 patients with rheumatoid arthritis (RA). The tissue specimens were fixed in 8% formaldehyde solution at pH 7.6 and embedded in paraffin. The tumours were diagnosed histologically and confirmed by immunohistochemical methods. Five benign (3.1%), and thirteen malignant tumours (8.1%) found observed in 18 (11.2%) of 161 cases. There was no significant difference between laboratory parameters of patients with malignant tumours and without tumours. One benign (0.62%) and seven malignant (4.35%) tumours led to death in 8 (4.97%) of 18 cases altogether. Neoplasms were detected clinically in 8 of 18 cases (44.4 rel%). None of tumorous patients received immunosuppressive treatment and only five had gold (Tauredon) therapy. Paraneoplastic syndromes with rheumatoid complaints may be excluded by the onset and duration of RA and tumours. Benign neurogenic tumours and malignant bronchioloalveolar carcinoma were frequently associated with RA not treated by immunosuppressive drugs. Our data do not support the assumption of a high risk of malignant lymphomas associated with RA treated with immunosuppressive therapy.     

Osteoporosis in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) develop both periarticular and generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs early in the course of RA and is one of the earliest radiological signs of RA. An uncoupled state in bone resorption-formation linkage, contributes to the development of periarticular osteopenia and it might be mediated through an increased productions of cytokines and prostaglandins by synovium and bone marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for the prevention of periarticular osteopenia. Generalized osteoporosis is also common in RA and leads to increased risk of fractures. Generalized osteoporosis considered to be multifactorial and factors contributing to lumbar osteoporosis might be different from those to loss of appendicular bones, such as femur and radius. Corticosteroids and menopausal state are important risk factors for lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also important determinants. According to the previous studies, however, the influence of functional impairment is more prominent in the femoral BMD compared to spinal BMD. In addition to control of RA and maintenance of physical activity, hormone replacement therapy (HRT) and bisphosphonate are possible agents for the treatment of osteoporosis in RA patients, especially postmenopausal women.     

Infection in rheumatoid arthritis

Sepsis is an unusually common cause of illness and death in RA. All sorts of infections occur, but pyarthrosis produces exceptional problems. Clinically, pyarthrosis, empyema, and purulent pericarditis mimic bland rheumatoid effusions. Aspiration of the attendant effusions is the only reliable diagnostic procedure. Subcutaneous nodules on the sacrum and back are easily overlooked. Necrosis and ulceration of these nodules may provoke septicemia. Those with Felty's syndrome do not uniformly have problems with recurrent infection. Splenectomy may not benefit such patients. The belief that corticosteroids cause increased infections in rheumatoid patients is not totally justifiable at present. Steroids can, however, disguise underlying sepsis and hamper proper diagnosis.     

Osteoporosis in rheumatoid arthritis

In cases of rheumatoid arthritis, osteoporosis may be local or general. The aetiology is multifactorial. Reduced bodily function, synovial inflammation, steroids and menopause are important risk factors. Studies have shown that, in cases of primary osteoporosis, bone mineral density measurements in the distal radius may predict risk of fracture at other sites, such as the neck of the femur and the dorsal vertebrae. Such a connection is not found for rheumatoid arthritis. Bone density measurements in the distal radius may overestimate the risk of fractures due to localised periarticular osteoporosis. Overall bone quality is assumed to be poorer, however, in patients with rheumatoid arthritis, leading to higher risk of fracture than the bone mineral density measurements seem to show. Data are lacking on the effect of antiresorptive drugs on this condition. Treatment with oestrogen and the bisphosphonate pamidronate has been shown to increase bone mineral density. Data are lacking on fractures. As shown in the case of primary osteoporosis, decreased risk of fracture is to be expected also in patients with secondary osteoporosis.