Clinical analysis by 1H spin-echo NMR. 2. Oxidation of intracellular glutathione as a consequence of penicillamine therapy in rheumatoid arthritis.

Spin echo NMR analysis is used to monitor the effect of penicillamine on intact erythrocytes obtained from patients suffering from rheumatoid arthritis during a 12-week period of therapy. The results are compared to the previously reported in vitro effects of the compound (McKay, C. N. N.; et al. Biochim. Biophys. Acta 1986, 888, 30-35). At clinical assessment at week 12, the 20 patients were divided into responder and nonresponder groups. The intracellular glutathione in the responder group is more oxidized (P less than 0.01) than in the nonresponder group. A retrospective analysis of the two patient groups at the initial assessment following the commencement of therapy indicated that in the nonresponder group intracellular glutathione was significantly more reduced (P less than 0.02) than in the responder group. It is postulated that penicillamine stimulates cellular defense against the oxidation of the cell membrane at the expense of cytosolic glutathione. This initial study suggests that spin-echo NMR analysis of erythrocyte glutathione can act as an early indicator of a clinical response to penicillamine therapy.

Clinical analysis in intact erythrocytes using 1H spin echo NMR.

A new method of clinical analysis based on 1H spin echo NMR spectroscopy is presented. It is capable of providing information on six metabolites within viable erythrocytes, directly and without any preparative procedures prior to analysis except for cell separation and washing. Erythrocytes from patients with rheumatoid arthritis and Graves' disease are compared with cells obtained from healthy volunteers. The NMR detectable species in the cytosol of the cells are glutathione, ergothioneine, choline, creatine, glycine, lactate and to a lesser extent alanine and valine. Significant differences are observed between the ergothioneine pools in the rheumatoid group (P less than 0.01) compared to the control group. The glutathione: di-glutathione ratio can be assessed from the ratio, g2 to g4, taken from different signals in the glutathione molecule. The total concentration of glutathione present is easily assessed qualitatively but is more difficult to quantitate.

Resonance Raman spectroscopy of hemoglobin in intact cells: a probe of oxygen uptake by erythrocytes in rheumatoid arthritis.

Resonance Raman spectra from intact viable erythrocytes can be used to study oxygen uptake in solution. In addition to changes in the oxidation state marker (nu 4), other bands due to the porphyrin ring (nu 3) and vinyl modes indicate subtle changes at oxygen pressures close to where the T/R change occurs. A comparison of whole cell and lysate spectra indicates a partial denaturation of hemoglobin on lysis. A simple smear technique is used to measure spectra from rheumatoid and normal blood. Results indicate a faster but less complete uptake of oxygen in cells from patients with rheumatoid arthritis than is the case in normal cell populations.

Transverse myelitis occurring during pregnancy in a patient with systemic lupus erythematosus.

Myelopathy is a well recognised but infrequent neurological manifestation of systemic lupus erythematosus (SLE). The case of a 27 year old woman with SLE of seven years' duration who developed a spastic paraparesis during her second pregnancy is reported. Magnetic resonance imaging did not show any intrinsic abnormality of the spinal cord. Anticardiolipin antibody was weakly positive and C4 was low. The patient responded dramatically to steroids.

Urinary excretion of the hydroxypyridinium cross links of collagen in patients with rheumatoid arthritis.

Values for urinary hydroxypyridinium cross links of collagen measured by high performance liquid chromatography in a group of 19 seropositive patients with rheumatoid arthritis (RA) were compared with 19 controls matched for age and sex. The amounts of pyridinoline, expressed relative to creatinine, were significantly higher in the RA group, but there was no significant increase in a bone specific analogue, deoxypyridinoline. There were significant positive correlations between pyridinoline excretion and both C reactive protein and erythrocyte sedimentation rate, whereas there was an inverse relation with grip strength. The data indicated that pyridinoline concentrations in urine are strongly associated with disease activity in patients with RA.

Leucopenia during sulphasalazine treatment for rheumatoid arthritis.

Leucopenia appears to be a more frequent complication of sulphasalazine treatment in rheumatoid arthritis than in inflammatory bowel disease and poses a management problem. In this study leucopenia was found in 20 patients, 14 of whom were participating in prospective studies (252 patients), giving an incidence of 5.6%. Treatment had to be discontinued in half of these patients. Most (14) episodes of leucopenia occurred early in treatment (less than 24 weeks) but some occurred late and sustained monitoring seems necessary. No predictive factors for leucopenia were elucidated. All patients recovered fully with dose adjustment or, in more severe cases, after withdrawal of sulphasalazine and appropriate supportive therapy. The incidence of leucopenia may be higher in Glasgow than in other units in Britain.

Degree and extent of response to sulphasalazine or penicillamine therapy for rheumatoid arthritis: results from a routine clinical environment over a two-year period.

An attempt was made to audit the clinical usefulness of sulphasalazine and penicillamine in patients with rheumatoid arthritis (RA) managed in a routine out-patient setting with assistance from general practitioners and to ascertain whether clinically significant differences can be shown between these two 'second-line' agents. The degree and extent of change in, and the usefulness of, various parameters of disease activity were also evaluated. Two hundred patients with active rheumatoid arthritis were randomly allocated to either sulphasalazine or penicillamine and monitored for a minimum of two years. Fifty-one percent of the 102 patients who received sulphasalazine continued treatment for two years, compared with 40 per cent of the 98 patients allocated to penicillamine. The proportion of patients stopping therapy because of adverse reactions or due to lack or loss of effect was similar in the two groups. There was no difference between the two groups in the extent of improvement in clinical and laboratory variables at one and two years. The majority of patients showed improvement in most measured parameters; very few showed global improvement. The degree of improvement varied with the parameter assessed, being greatest in relatively easily measured variables such as duration of morning stiffness and ESR, and least for functional index. The effect and toxicity of these two agents in this setting was as anticipated. No clinically relevant difference could be demonstrated between the two drugs.