Interaction-Induced Shubnikov-de Haas Oscillations in Optical Conductivity of Monolayer MoSe_{2}.

We report polarization-resolved resonant reflection spectroscopy of a charge-tunable atomically thin valley semiconductor hosting tightly bound excitons coupled to a dilute system of fully spin- and valley-polarized holes in the presence of a strong magnetic field. We find that exciton-hole interactions manifest themselves in hole-density dependent, Shubnikov-de Haas-like oscillations in the energy and line broadening of the excitonic resonances. These oscillations are evidenced to be precisely correlated with the occupation of Landau levels, thus demonstrating that strong interactions between the excitons and Landau-quantized itinerant carriers enable optical investigation of quantum-Hall physics in transition metal dichalcogenides.

Nitrogen mustard in severe rheumatoid arthritis.

The value of intravenous bolus therapy was investigated in patients with severe active rheumatoid arthritis. Nitrogen mustard was given in 3 intravenous bolus injections (0.1 mg/kg body weight) over 3-5 weeks. In a controlled study of 11 patients the actively treated ones (7 cases) showed greater improvement in all the clinical and laboratory variables measured than did the controls (4 cases). A prospective evaluation of this treatment in 22 patients over 6-18 months showed it had a persistent effect and was associated with clinically significant improvements in the assessments of disease activity. We consider bolus therapy with intravenous nitrogen mustard to be of value, but its use should be restricted to patients with severe rheumatoid arthritis during hospital admission, and it should be combined with other therapy.

Outcome in patients hospitalised for psoriatic arthritis.

Forty patients hospitalised for treatment of psoriatic arthritis (PsA) were followed for a mean of 8.0 years. At the end of this time none had died and only 8% were in functional class IV. 90% received second-line therapy. There was a high incidence of skin rashes on gold but hydroxychloroquine was well tolerated. Patients with psoriatic arthritis had a better outcome than patients with rheumatoid arthritis treated with the same regime.

Long term progression of joint damage in rheumatoid arthritis.

Joint damage in rheumatoid arthritis is assessed radiologically. Previous studies have not examined in detail its long term progression. We evaluated the overall changes of peripheral joint damage radiologically in 50 rheumatoid patients followed up at one rheumatology centre for 10 years. All peripheral joints were scored in 12 groups with Larsen's standard films at 0 and 10 years. In 48 cases the total scored deteriorated (mean increase 13% maximum damage). There was no different pattern of progression in any of the patients, though seropositive patients had more initial damage and a greater rate of progress. The wrist and small joints of the feet were most affected initially. During the 10 years most progression occurred in the wrist, knee, and metacarpophalangeal joints. Progression occurred in both initially normal and abnormal joints. By 10 years only 16.5% joint groups showed no damage. Complete destruction was most common in the wrist, knee, and small joints of the feet. Damage to the hands and wrists have a god indication of overall changes at 0 and 10 years and also the increase in damage (correlation coefficients were from r = 0.74 to r = 0.85). These results show that specific joints are involved in different stages of the disease. Some joints are frequently involved and some less often. The hands and the wrists give a reasonable picture of the overall progression of damage.

Long-term outcome of treating rheumatoid arthritis: results after 20 years.

Outcome of therapy, in terms of functional capacity, radiological measures of joint damage, erythrocyte sedimentation rate (ESR), rheumatoid factor, and mortality, was determined prospectively in 112 consecutive rheumatoid arthritis (RA) patients treated for 20 years at one centre, where a policy of active treatment was pursued with the use of gold, chloroquine, steroids, and, in resistant cases, penicillamine or cytotoxic drugs. By 20 years 35% were dead. Mortality was often attributable to RA. Function improved in the early years of treatment but declined considerably between 10 and 20 years. At 20 years 19% were severely disabled. Radiographs showed related evidence of increasing joint destruction. The ESR and rheumatoid factor levels changed little. Age, late presentation, and rheumatoid factor seropositivity at presentation were poor prognostic factors. The concept of "remission-inducing" drugs is fallacious. Early treatment may be advantageous, but the prognosis of RA is not good.

Methods of X-ray assessment in rheumatoid arthritis: a re-evaluation.

We have re-examined the value of hand radiographs in the assessment of joint damage in rheumatoid arthritis in a series of related studies. Our objectives were: to assess the reproducibility of scoring hand radiographs and the relationships between different types of changes; to analyse the correlations between radiographic changes and hand function; and to assess the inter-relation between hand changes and overall joint damage. We confirmed the reproducibility of radiological assessments and showed that two observers can reproducibly score hand radiographs separately for joint space loss and erosions; both of these correlated with the Larsen score derived from standard radiographs. However, hand radiographic changes were not closely related to hand function; nor did they predict damage to large joints. Finally, examination of changes in 13 joint groups showed that there is a weak relationship between damage and disease duration, and the rate of damage is greatest in the initial years. We conclude that the status of hand radiography as a measure of overall outcome in rheumatoid arthritis remains an open question.

Rheumatoid arthritis and IgA nephropathy.

We describe four patients with seropositive rheumatoid arthritis who developed proteinuria and microscopic haematuria. Renal biopsy demonstrated a mesangial proliferative glomerulonephritis with mesangial deposits of IgA. These data suggest a possible causal relationship between rheumatoid arthritis and IgA nephropathy.

Frequency of occurrence, mode of development, and significance or rice bodies in rheumatoid joints.

The incidence of rice bodies (RB) in synovial effusions has been studied in 36 patients with rheumatoid arthritis (RA) and in 12 patients with seronegative inflammatory arthritis (7 cases of Still's disease, 3 of psoriatic arthritis, and 2 of ankylosing spondylitis). In the RA group 50 joints were aspirated before and after saline lavage with a specially designed wide-bore needle. RB were found in 72% overall of the joints studied in this group, 14% on initial simple aspiration and an additional 58% after lavage. In contrast no rice bodies were found in 31 aspirations with lavage by an identical technique in the 12 patients with seronegative synovitis. The RB in RA synovitis occurred both early and late in the course of the disease and were not related to the severity of clinical or radiological changes. However, removal of rice bodies was accompanied by clinical improvement and reduction of synovitis. Macroscopically RB varied in shape and size, some being so large as to preclude effective removal by needles of the gauge customarily employed for joint aspirations. Microscopically the majority of RB were composed of coarsely reticular material reacting immunologically with antifibrinogen and antifibronectin and containing mononuclear cells. Some showed vacuolation suggestive of fibrinolysis, but many showed organisation like that seen in established connective tissues, with the formation of mature collagen, reticulin, and elastin. These findings are discussed in relation to the origin, development, and significance of rice bodies in rheumatoid synovitis.

Progression of radiological changes in rheumatoid arthritis.

A prospective study over one year of patients who had active rheumatoid arthritis discovered 64 who had received treatment for an adequate time with second-line drugs. In these patients there was evidence of continuing joint destruction as shown by radiological progression. During the year there were highly significant correlations between improvements in clinical and laboratory measurements, but neither group of tests was related to the degree of radiological change. However, in the second 6 months of treatment there was evidence that radiological progression was reduced. In a second prospective study of 88 patients with rheumatoid arthritis given prolonged, intensive therapy with second-line drugs and followed up for 10 years two-thirds showed radiological progression. However, the number of joints damaged per year fell significantly during the study period. There was a divergence between deterioration in radiological features and improvements in the ESR and functional capacity, though patients with a persistently low ESR had less radiological progression. These studies provide evidence that treatment may be associated with a reduced rate of radiological progression but suggest that changes in radiological progression and clinical and laboratory measurements may result from different mechanisms.

Glomerulonephritis in rheumatoid arthritis.

We present data on 10 patients with RA who developed glomerulonephritis which was not related to gold or penicillamine therapy. Although two of these patients had received gold this had been discontinued 13 and 18 yr before the diagnosis of glomerulonephritis. Seven patients presented with nephrotic syndrome and three with proteinuria and microscopic haematuria. Renal histology showed a membranous nephropathy (five patients), mesangial IgA nephropathy (two patients), focal segmental necrotizing glomerulonephritis (two patients) and focal segmental glomerulosclerosis (one patient).

Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study.

We studied combination therapy with two slow-acting antirheumatic drugs given concurrently in active rheumatoid arthritis (RA). A 12-month prospective randomized controlled trial compared gold and hydroxychloroquine in 52 patients to gold and placebo in 49. The patients continued to receive non-steroidal anti-inflammatory drugs and analgesics. They were selected from three rheumatology centres in the West Midlands. Combination therapy led to a greater number of withdrawals due to adverse reactions (18 cases compared to 10 receiving gold/placebo). Patients completing 12 months' therapy (27 taking gold/hydroxychloroquine and 32 on gold/placebo) were compared using five clinical, seven laboratory, and one radiological measure. All 13 variables favoured gold/hydroxychloroquine with an overall advantage of 20-25% for the combination. This only reached statistical significance (at the 1% level) for C-reactive protein. An overall disease activity index was better at 12 months (at the 5% level) and showed a more rapid response with gold/hydroxychloroquine. This is the first randomized prospective placebo-controlled trial to show a significant advantage from a combination of two slow-acting drugs. There are many different ways of giving such combinations and we consider these should be explored to maximize the effectiveness of treatment for RA.

The influence of thyroid activity on the treatment of rheumatoid arthritis with cortisone

The effects of cortisone on thyroid radio-iodine metabolism has been demonstrated in a patient. Two other patients, one euthroid and the other hyperthyroid who were receiving long term treatment with cortisone for rheumatoid arthritis, showed evidence of an enhanced response to cortisone after commencing anti-thyroid therapy with carbimazole