Seasonal onset of systemic-onset juvenile rheumatoid arthritis

1. To examine the effects of sustained resistive loading on the relationship between inspiratory effort sensation and respiratory drive (P0.1) and to determine if the change in CO2 responsiveness after sustained loading is accompanied by altered effort perception, hypercapnic responses were measured before, immediately after and 15 min after sustained resistive loading in seven subjects (six men, one woman). Sustained resistive loading was set to exceed a diaphragm tension-time index of 0.2. 2. Mean time to task failure during sustained loading was 17.7 min (range 12.5-22.5 min). The mean inspiratory effort sensation score rose from 3.4 (SEM 0.8) to 8.1 (0.8), whereas P0.1 fell from 29.5 (3.6) to 18.1 (3.6) cmH2O. 3. Immediately after loading the slopes of the ventilatory and sensory responses to CO2 fell (ventilatory response: before loading 16.7 (2.4) lmin-1kPa-1, immediately after loading 7.88 (2.18)lmin-1kPa-1; sensory response: before loading 1.95 (0.38) units/kPa; immediately after loading 1.12 (0.38) units/kPa; P < 0.05. Changes reverted to preloading levels by 15 min. 4. Sustained loading can lead to a dissociation between respiratory drive, as reflected by P0.1, and inspiratory effort sensation, and this disturbance can persist once the load is removed. Impaired sensory perception may be the primary determinant of the change in CO2 responsiveness seen after sustained resistive loading.     

The lag time between onset of symptoms and diagnosis of rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients.     

Treatment of rheumatoid arthritis of senile onset with methotrexate

Elderly onset rheumatoid arthritis is a not rare disease with relevant social implications. The most important question is represented by the therapeutic choice, in relation to the typical problems of the elderly patients and to the frequent coexistence of other diseases. In this work, we evaluated the practicability and the efficacy of methotrexate therapy, at the dose of 5 mg/week, in 27 patients affected by elderly onset rheumatoid arthritis (mean age 73.76 +/- 3.39 years, range 70-83). Low dose prednisone was associated in order to control painful symptoms. Also sulindac was allowed. Frequent clinical and hematochemical controls were made in order to precociously evaluate the appearance of side effects. All the 27 patients completed the first year of treatment; during this period there was no drop out. Sixteen patients finished the second year too; during this year one patient dropped out because of significant hypertransaminasemia and another patient did not respect the follow-up. Clinical and hematochemical parameters were monitored. A significant improvement of all data was observed from the third month. A further amelioration was recorded in the following months. Our data suggest the efficacy and the safety of low dose methotrexate in the treatment of elderly onset rheumatoid arthritis. A careful evaluation of side effects is obviously necessary.     

Enigmas of adrenal androgen and glucocorticoid dissociation in premenopausal onset rheumatoid arthritis

Interferon-gamma (IFN-gamma) is implicated as a participant in the immune effector and regulatory mechanisms considered to mediate the pathogenesis of multiple sclerosis (MS). We have used an intracellular cytokine staining technique to demonstrate that the proportion of ex vivo peripheral blood CD4 and CD8 T-cell subsets expressing IFN-gamma is increased in secondary progressing (SP) MS patients, whereas the values in untreated relapsing-remitting (RR) MS patients are reduced compared with those of controls. Patients treated with interferon-beta (IFN-beta) have an even more significant reduction in the percentage of IFN-gamma-secreting cells. The finding that the number of IFN-gamma-expressing CD8 cells is increased in SPMS patients, a group with reduced functional suppressor activity, and is most significantly reduced by IFN-beta therapy, which increases suppressor activity, indicates that IFN-gamma secretion by CD8 T cells and functional suppressor defects attributed to this cell subset in MS can be dissociated.     

Diminished autonomic nervous system responsiveness in rheumatoid arthritis of recent onset

OBJECTIVE: To investigate responsiveness of the autonomic nervous system in rheumatoid arthritis (RA) of recent onset. METHODS: 21 patients (17 women, mean age 55.7 years) and 20 healthy controls (16 women, mean age 52.7 years) were subjected to 4 tasks eliciting divergent autonomic reactions: film watching, mild physical exercise, cognitive discrimination, and the Stroop color-word interference test. Changes in heart rate, diastolic (DBP) and systolic (SBP) blood pressure, and skin conductance relative to pretask baseline values were computed and related to erythrocyte sedimentation rate, pain, mobility, and dexterity. RESULTS: Mean autonomic levels of patients were normal, as well as autonomic responses to film watching and mild physical exercise. Diminished autonomic responses were observed during cognitive discrimination and during the Stroop test. Blood pressure responses were negatively related to pain severity, but positively to impaired dexterity. CONCLUSION: Diminished autonomic nervous system response is observed in RA of recent onset, most clearly in patients with more severe pain. This suggests that it is associated with primary pathophysiological mechanisms.     

The prognosis of rheumatoid arthritis

Although DNA replication is a very accurate process, a small number of new mutations are generated at every cell division. The generation of a new mutation during the formation of an ovum or sperm cell can cause an early miscarriage or birth defect. The generation of new mutations during embryogenesis can cause a variety of localized birth defects. The molecular delineation of these errors in somatic and gonadal cells has clarified the basis of some birth defects, and has both refined and complicated genetic counselling for a number of paediatric conditions. The processes responsible for these new mutations are present in all cells. For this reason new mutations accumulate in all cells throughout life and contribute to the ageing process. Thus the molecular events that cause many miscarriages and birth defects are the same as those that ultimately lead to death.     

The pathogenesis of rheumatoid arthritis and the mode of action of various drugs: an hypothesis

In the region of the passage of the ulnar nerve from the anterior to the posterior compartment of the arm an arcade is formed which can be a primary or secondary factor in the production of traumatic lesions of this nerve in the arm. It is the purpose of this paper to present the details of this arcade and to note its clinical significance.     

Torticollis as the sole initial presenting sign of systemic onset juvenile rheumatoid arthritis

We describe a 6-year-old girl with acute torticollis as the initial manifestation of systemic onset juvenile rheumatoid arthritis (JRA). She presented with isolated torticollis for 2 weeks, followed by daily intermittent fever and polyarthritis. We discuss the pathogenesis of cervical spine involvement in JRA and the clues to early diagnosis.     

Pregnancy and rheumatoid arthritis

Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of pregnancies. Most women who improve experience initial relief in the first trimester. RA almost invariably recurs within 3 to 4 months of delivery. The effect of pregnancy upon the risk of first developing RA is similar in some respects but also differs from that observed in women with established disease. Analogous to women with established disease, the chance of a woman first developing RA is significantly reduced during pregnancy but increased in the first year post partum; thereafter risk is decreased. There is no indication of any adverse effects of RA on pregnancy outcome. Although limited, some medications can be used during pregnancy and during lactation without jeopardizing the well-being of the fetus.     

The use of Neoral in rheumatoid arthritis

Neoral (a microemulsion-based formulation) is an immunomodulator that possesses a more predictable and improved absorption than the conventional oral formulation (Sandimmun). The increased bioavailability of Neoral could result in improved efficacy. The pharmacokinetics of cyclosporin and efficacy of cyclosporin in rheumatoid arthritis are reviewed in this article. Current guidelines for the use of Neoral in the treatment of rheumatoid arthritis patients are outlined.     

Juvenile rheumatoid arthritis

JRA is a multisystem disease characterized by exacerbations and remissions. Recognition of the three modes of onset can important in early diagnosis, identification of extra-articular manifestations, and prognosis. This is a chronic illness that requires consideration of the whole patient, his family, and his place in society, both in the present and in the future. With a positive, comprehensive approach and an awareness of the pitfalls of seeking immediate relief, the physician can help to assure a good functional outcome.     

HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis

Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.     

Noninfectious canine arthritis: rheumatoid arthritis

Chronic unremitting, generally symmetric, erosive polyarthritis was studied in 8 dogs. The disease had clinical, serologic, radiographic, and pathologic changes similar to those of rheumatoid arthritis of man. The condition occurred mainly in smaller breeds of dogs, with time of onset from 8 months to 8 years of age, Characteristic radiographic changes were seen in the joints several weeks to several months after the appearance of the initial lameness. Synovial fluid contained an increased number of neutrophils, and synovial fluid and synovial tissues were sterile for anaerobic and aerobic bacteria, mycoplasma, chlamydia, and viruses. Corticosteroids were therapeutically ineffective in all of the cases; however, corticosteroids, cyclophosphamide, and azathioprine were effective when used in combination in several dogs.     

The supinator notch sign in rheumatoid arthritis

Unconcentrated CSF and 200 times diluted serum samples from 192 patients were examined by agar electrophoresis; their albumin and transferrin content were determined simultaneously by radial immunodiffusion. Using the data on transferrin and albumin concentrations in serum and cerebrospinal fluid, the transferrin/albumin index was calculated in a similar way to the IgG/albumin index. Normally the transferrin/albumin index is 1.68 (n = 77; S.D. = 0.22). If the permeability of the blood-CSF barrier increases, the transferrin/albumin index gradually decreases to 1. If the tau-globulin fraction is increased on the agar pherogram, the transferrin/albumin index will be greater than 2.34 (mean + 3 S.D.).     

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.