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Biomedical subjects

P Emery

Publications and source records attributed to P Emery.

At least 253 records · Page 14Linked to original sources
PubMed1994

Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

OBJECTIVE: To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS: Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS: The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION: The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.

Acute Disease↗
PubMed1994

Early rheumatoid arthritis: therapeutic strategies.

The early stage of rheumatoid arthritis (RA) is a unique and critical phase of disease which is often characterized by profound inflammation, severe symptomatology and a high likelihood of radiological progression. Decisions on treatment strategies need to be taken before irreversible damage and functional deterioration occur. There is evidence that early intervention with disease-modifying drugs may reduce functional deterioration and improve long-term outcome. Stable genetic markers and rheumatoid factor are useful in predicting disease severity and thus in identifying those patients who require early aggressive therapy. The acute phase response (APR) is a valuable marker of disease activity and catabolism in RA, and suppression of the APR improves outcome. The use of early aggressive therapy to suppress disease efficiently in patients with a poor prognosis should improve the long-term morbidity and mortality associated with RA.

Acute-Phase Reaction↗
PubMed1994

Adverse interaction between intramuscular methylprednisolone and sulphasalazine in patients with early rheumatoid arthritis. A pilot study.

A defective hypothalamic-pituitary-adrenal axis has been associated with susceptibility to arthritis in rats and with rheumatoid arthritis in humans. The effect of corticosteroid supplementation in early RA has not been tested previously. We undertook a double-blind placebo-controlled study of sulphasalazine plus either corticosteroid or placebo. No early benefit was demonstrated as 7 of 11 of the corticosteroid supplemented group had withdrawn by 1 year. The addition of corticosteroids to sulphasalazine in patients with early disease did not appear to offer any benefit.

Adult↗
PubMed1994

Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis.

The continuing morbidity of patients with vasculitis, despite the improved prognosis with aggressive therapy, underlines the need for accurate disease assessment. We have devised a clinical index of disease activity, and evaluated its use in several forms of necrotizing vasculitis. The weighted score is based on symptoms and signs in nine separate organ systems. Disease features are only scored if they are attributable to active vasculitis. The Birmingham Vasculitis Activity Score (BVAS) was compared with two other published vasculitis activity scores, with the physician's global assessment (PGA), with outcome, and with serological markers of disease activity. In a cross-sectional study of 213 consecutive patients with different forms of vasculitis, all 107 vasculitis patients who were judged completely well on clinical assessment had a BVAS score of 0. Twenty-two patients with active vasculitis prior to treatment had a median score of 7.5 (range 4-30) and 69 with active disease on treatment had a median score of 10 (1-29). Of the 12 who died, median score immediately prior to death was 20.5 (9-30). In a serial prospective study, 30 cases had documented episodes of active disease. During periods of disease activity, the median BVAS values were significantly higher than in remission (15 [range 3-32] vs. 0 [0-2], p < 0.001); the same was true for CRP values (80 [9-361] vs. 13.5 [5-68], p < 0.001). This was not true for erythrocyte sedimentation rate (ESR), haemoglobin (Hb) or von Willebrand factor (VWF).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Assessment of rheumatoid arthritis--a clinician's viewpoint.

There are many measures that can be used for the short and longterm monitoring of patients with rheumatoid arthritis (RA). An important requirement for such assessments is the development of new pharmacologic therapies. It is important to assess the need for and the outcome of therapy. In recent years, it has been realized that subjective assessments have many advantages over objective ones. However, in the majority of cases subjective measures and objective measures parallel each other closely. The measurement of acute phase protein, in particular C-reactive protein (CRP), is helpful as an indicator of successful therapy. From data regarding axial osteoporosis, CRP has been shown to be a convenient marker indicating persistent active disease that will produce catabolic effects. Dual energy X-ray absorption scans have also been shown to be promising in objectively measuring change in the hand for patients with inflammatory arthritis. In patients presenting early with RA, it is necessary to have accurate indicators. In this respect, genetic predictors have a particular value. The most important aspect of the assessment of RA is subjective impressions. Therefore, a functional questionnaire such as the health assessment questionnaire combined with the objective measure of choice, CRP levels, are the assessments of choice.

Absorptiometry, Photon↗
PubMed1994

Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings.

OBJECTIVE: To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cysteine derivatives. METHODS: Measurement of cysteine dioxygenase substrate (cysteine) and product (sulfate) under controlled conditions, with elemental assessment by proton induced x-ray emission (PIXE). RESULTS: Plasma inorganic sulfate was significantly depressed in patients with rheumatoid arthritis (RA) compared to both controls and non-RA disease, 85 +/- 36 nm/ml vs 267 +/- 146 and 604 +/- 412 (mean +/- SD. RA patients vs non-RA disease p < 0.001). Fasting cysteine levels were significantly raised compared to controls (59 +/- 20 nm/ml vs 17 +/- 81 nm/ml p < 0.001). Synovial fluid (SF) sulfate was also significantly reduced in patients with RA compared to non-RA controls (202 +/- 117 nm vs 1041 +/- 700 p < 0.001). PIXE data confirmed the low sulfate levels in serum and SF while showing no reduction in the levels of other elements analyzed. CONCLUSIONS: These cysteine/sulfate findings confirm the validity of the previous probe drug abnormalities and the importance of defective cysteine dioxygenase activity in RA.

Adult↗
PubMed1994

Classical versus non-renal Wegener's granulomatosis.

We investigated whether 'limited' or 'non-renal' Wegener's granulomatosis (WG) differs from classical or 'renal' WG. Renal WG is characterized by necrotizing granulomatosis of the upper and or lower respiratory tract, accompanied by systemic vasculitis and focal segmental necrotizing glomerulonephritis. This last feature is absent in non-renal WG. In a prospective follow-up study of all identified cases presenting to a single teaching hospital, we reviewed 22 patients with non-renal WG, and compared their presentation and outcome with that of 28 patients with renal WG. Clinical and laboratory assessment of disease activity, frequency of death, relapse and end-stage renal disease were assessed. The two groups differed in clinical presentation, laboratory features and outcome. The group with non-renal WG had less cutaneous and pulmonary disease; the haemoglobin, white cell count and platelet count tended to be normal. Residual mortality was confined to the renal group. However, the groups shared many features, particularly their requirement for immunosuppressive therapy, since WG causes major tissue destruction regardless of whether it is a localized or widespread process. At the immunopathological level, the two groups appear to be part of a single disease spectrum. Importantly, the non-renal WG group may change the pattern of their disease to involve the kidney. Long-term follow-up of such patients is therefore essential.

Adult↗
PubMed1993

Subpopulations of primed T helper cells in rheumatoid arthritis.

OBJECTIVE: To analyze subsets of primed T helper cells, defined by expression of the CD45RB isoform of the leukocyte common antigen, in the blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA). METHODS: Three-color immunofluorescence was used to study CD45 isoform expression by peripheral blood and SF CD4+ T cells. RESULTS: CD45 isoform expression in the peripheral blood of patients with either RA or reactive arthritis did not differ from that in healthy controls. SF T cells from both RA patients and reactive arthritis patients were almost exclusively primed (CD45RO+) cells. RA SF T cells expressed very low levels of CD45RB; this is the most highly differentiated subset of primed cells. Patients with acute reactive arthritis showed higher levels of CD45RBbright cells in their synovial fluid. CONCLUSION: The highly selected cell population in SF, representing one subset of primed cells, may relate to the apparent functional abnormalities of cells from this site in patients with RA.

Adult↗
PubMed1993

The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequence.

HLA-DRB1 and -DRB3 are two genes encoding two distinct HLA-DR beta chains in the DRw52 family of haplotypes (DR3, DR5, DR13, and DR14). These beta chains determine the structural and functional identity of the two kinds of HLA-DR molecules expressed. The highly polymorphic HLA-DRB1 locus is always expressed at a higher level than the HLA-DRB3 locus, and functional assays indicate that the proximal promoter of DRB1 is indeed more active than that of DRB3. The DNA sequence of the two promoters in nine different DRw52 haplotypes has revealed a stricking allelic conservation as well as characteristic, isotype-specific, conserved-sequence motifs. These isotype-specific differences concern the functionally essential X and Y box motifs of HLA class II promoters, and they do indeed affect binding of specific nuclear factors to the X and Y boxes of DRB1 or DRB3 promoters. Finally, analysis of the activity of various normal and mutated DRB1 or DRB3 promoters indicates that the X box region of these promoters plays a dominant role in controlling the relative levels of HLA-DRB1 and -DRB3 gene expression.

Alkaline Phosphatase↗
PubMed1993

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).

Adult↗
PubMed1993

The genetic basis of responses to drugs--a rheumatological perspective.

The wide individual variations seen in all metabolic pathways which have been examined largely explain differences in drug dose response and toxicity. In some cases, distinct sub-sets occur where the enzyme activity is markedly different from that in the rest of the population (genetic polymorphism). Studies on isolated enzymes and use of restriction fragment length polymorphisms have in some cases helped to elucidate the relevant molecular biology. However, the lack of certain concordance between genotype and phenotype has shown that many questions remain unanswered. As more information becomes available at the molecular level, it may be easier to gain an understanding of the endogenous biochemistry which underlies the human condition. Either genotyping or phenotyping may then be used to predict potential drug side-effects or clinical outcomes.

Anti-Inflammatory Agents↗
PubMed1993

Pelvic insufficiency fractures in rheumatoid arthritis.

The occurrence of pelvic insufficiency fractures in patients with rheumatoid arthritis has not previously been well emphasized. These fractures are difficult to detect clinically and appropriate radiological investigation is necessary for diagnosis. We describe five patients with a spectrum of radiological features and discuss the approach to diagnosis and treatment of these lesions.

Aged↗
PubMed1993

The association of HLA DR beta alleles with self-limiting and persistent forms of early symmetrical polyarthritis.

RA is associated with a group of class II DR beta alleles, which share a conserved sequence in the third allelic hypervariable region (3AHVR). These include the DR4 subtypes Dw4, Dw14 and Dw15, and also DR1. In contrast Dw10 and Dw13 which are also DR4 subtypes show no association with RA and have a quite distinct 3AHVR. We have assessed the frequency of these alleles in 55 patients who initially presented with symmetrical peripheral polyarthritis suggestive of RA. After 4 years 27 had progressed to definite or classical RA, while 28 had never fulfilled the criteria for this disease. Dw4 was markedly elevated in the rheumatoid group (17/23) compared with either the non-rheumatoids (5/28) or healthy controls (12/100). Dw14 and non-DR4 associated DR1 were not elevated in either group of patients. This study suggests that the DR beta association with RA is likely to facilitate persistence or severity of disease rather than the initial induction of symmetrical peripheral arthritis.

Adult↗
PubMed1993

The validity of surrogate markers in rheumatic disease.

Although RA is an inflammatory disease primarily affecting the synovial joints it also has marked systemic consequences. Pro-inflammatory systemically active cytokines are produced within the joint, found in the serum and are capable of inducing the hepatic synthesis of acute-phase proteins. Initially it was believed that the acute-phase response was elicited by the cytokine, interleukin-1 alone. However, it is now clear that there is a complex interaction between the cytokines with interleukin-6 predominant, but also involving interleukin-1, tumour necrosis factor and a group of recently described cytokines including interleukin-11, leukaemia inhibitory factor and oncostatin M all of which influence the levels of acute-phase proteins. In clinical practice CRP is frequently used as a marker of the acute-phase response. It has a short half-life and consequently is a sensitive measure of cytokine-induced protein synthesis. The rate of appearance of bony erosions early in disease correlates with the mean serum concentration of CRP in some studies. It has been suggested that a weak correlation probably reflects the fact that joints in which erosions most frequently occur, namely the small joints of the hand, produce smaller amounts of cytokine than the large joints such as the knee. A recent study examining the rate of spinal trabecular bone loss in the first year of rheumatoid disease found a strong correlation between bone loss and serum CRP concentrations. It appears that CRP concentrations reflect the level of 'systemic osteoclast-activating factor' and are, therefore, a good measure of the general catabolic state of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗