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G Campion

Publications and source records attributed to G Campion.

14 recordsLinked to original sources
PubMed1998

Synthesis and polymerization of benzyl (3R,4R)-3-methylmalolactonate via enzymatic preparation of the chiral precursor.

beta-methylaspartate ammonia-lyase, EC 4.3.1.2, (beta-methylaspartase) from Clostridium tetanomorphum was used to produce a 40/60 molar ratio of (2S,3R) and (2S,3S)-3-methylaspartic acids, 2a and 2b, respectively, from mesaconic acid 1 as substrate, on a large scale. To prepare (3R,4R)-3-methyl-4-(benzyloxycarbonyl)-2-oxetanone (benzyl 3-methylmalolactonate) 6, 2a and 2b were transformed, in the first step, into 2-bromo-3-methylsuccinic acids 3a and 3b and separated. After three further steps, (2S,3S)-3a yielded the alpha, beta-substituted beta-lactone (3R,4R) 6 with a very high diastereoisomeric excess (> 95% by chiral gas chromatography). The corresponding crystalline polymer, poly[benzyl beta-(2R,3S)-3-methylmalate] 8, prepared by an anionic ring opening polymerization, was highly isotactic as determined by 13C NMR. Catalytic hydrogenolysis of lactone 6 yielded (3R,4R)-3-methyl-4-carboxy-2-oxetanone (3-methylmalolactonic acid) 7, to which reactive, chiral, or bioactive molecules can be attached through ester bonds leading to polymers with possible therapeutic applications. Because of the ability of beta-methylaspartase to catalyse both syn- and anti-elimination of ammonia from (2S,3RS)-3-methylaspartic acid 2ab at different rates, the (2S,3R)-stereoisomer 2a was retained and isolated for further reactions. These results permit the use of the chemoenzymatic route for the preparation of both optically active and racemic polymers of 3-methylmalic acid with well-defined enantiomeric and diastereoisomeric compositions.

Aspartate Ammonia-Lyase↗
PubMed1996

Prognostic value of contrast enhanced Gd-DTPA MRI for development of bone erosive changes in rheumatoid arthritis.

Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.

Arthritis, Rheumatoid↗
PubMed1995

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.

OBJECTIVE: To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months. METHODS: Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6-12 weeks from prior second-line therapy was required. RESULTS: Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groups; no opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients. CONCLUSION: Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.

Adult↗
PubMed1992

Metabolism and characterisation of kinins and Hoe 140 (kinin antagonist) in the synovial fluid of patients with inflammatory joint diseases.

Methods have been optimised for the collection of synovial fluid and the chromatographic separation of individual kinins (bradykinin and kallidin) in the fluid by HPLC. In addition, the stability of the kinin antagonist, Hoe 140, in synovial fluid was compared with that of synthetic bradykinin. Although bradykinin was completely degraded after incubation for only 6 h in pooled synovial fluid obtained from patients with rheumatoid arthritis, Hoe 140 was stable for as long as 2 weeks under the same conditions. These studies will provide quantitative information regarding levels of kinins in inflamed joints and an insight into the therapeutic potential of kinin antagonists.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Hip fractures in the elderly: a world-wide projection.

Hip fractures are recognized to be a major public health problem in many Western nations, most notably those in North America, Europe and Oceania. Incidence rates for hip fracture in other parts of the world are generally lower than those reported for these predominantly Caucasian populations, and this has led to the belief that osteoporosis represents less of a problem to the nations of Asia, South American and Africa. Demographic changes in the next 60 years, however, will lead to huge increases in the elderly populations of those countries. We have applied available incidence rates for hip fracture from various parts of the world to projected populations in 1990, 2025 and 2050 in order to estimate the numbers of hip fractures which might occur in each of the major continental regions. The projections indicate that the number of hip fractures occurring in the world each year will rise from 1.66 million in 1990 to 6.26 million by 2050. While Europe and North America account for about half of all hip fractures among elderly people today, this proportion will fall to around one quarter in 2050, by which time steep increases will be observed throughout Asia and Latin America. The results suggest that osteoporosis will truly become a global problem over the next half century, and that preventive strategies will be required in parts of the world where they are not currently felt to be necessary.

Adult↗
PubMed1990

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations.

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.

Adult↗
PubMed1988

Mixed crystal deposition.

Mixtures of crystals are found in joint tissues more commonly than would be expected by chance. In osteoarthritic joints, for example, mixtures of different calcium salts are more common than any one type of crystal alone. This is partly explained by the predisposing factors and mechanisms of crystal formation, many of which are not salt specific. It is suggested that rheumatic disorders should not be diagnosed or classified by crystal type.

Calcinosis↗
PubMed1987

HLA DQ alpha and DQ beta restriction fragment length polymorphisms associated with Felty's syndrome and DR4-positive rheumatoid arthritis.

HLA DQ alpha and DQ beta cDNA probes were used to study TaqI generated restriction fragment length polymorphisms (RFLPs) in DR4-positive patients with Felty's syndrome (FS), seropositive rheumatoid arthritis (RA), and in HLA-DR4 positive controls. The results of this analysis revealed two DQ beta RFLP patterns (DQ beta 3a and DQ beta 3b) associated with DR4, of which DQ beta 3b was found at significantly higher frequency in patients with FS (73%) or with RA (52%) than in DR4 controls (29%). Hind III generated RFLPs provide evidence that DQ beta 3b is in strong linkage disequilibrium with the gene encoding the serologically recognized epitope TA10. Results obtained using a DQ alpha chain probe revealed polymorphic differences between DQ alpha chain genes associated with different DR types, thereby providing a possible explanation for the lack of association between RA and other DR haplotypes in linkage disequilibrium with TA10. We conclude that both DQ alpha and DQ beta genes may be important in determining HLA-linked susceptibility to severe forms of RA.

Arthritis, Rheumatoid↗
PubMed1984

Use of anti-idiotypic antibodies to demonstrate rheumatoid factor producing bone marrow cells in essential mixed cryoglobulinaemia.

Specific cells producing rheumatoid factor (RF) were demonstrated in a bone marrow preparation of a patient with essential mixed cryoglobulinaemia. This was achieved by the use of labelled anti-idiotypic antibodies raised against purified RF from the patient's circulating cryoglobulin. This technique may be applicable to other diseases in which specific antibodies are pathogenetically implicated. The more precise demonstration of specific antibody-producing marrow cells may in addition have therapeutic implications.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Contrast enhanced Gd-DTPA magnetic resonance imaging in the evaluation of rheumatoid arthritis during a clinical trial with DMARDs. A prospective two-year follow-up study on hand joints in 31 patients.

OBJECTIVE: The aim of this prospective 24-month follow-up study was to compare clinical features with radiological and magnetic resonance imaging (MRI) findings in evaluating synovial proliferation in the hand joints of 31 patients with rheumatoid arthritis (RA). A single joint was used for the follow-up of each patient. METHODS: Thirty-one small hand joints were examined by conventional radiography and MRI before and after 24 months of treatment. MRI assessment of disease progression (volume and/or signal intensity of the synovial proliferation on T1 weighted precontrast, T1 weighted postcontrast and T2 weighted images) was compared with a clinical assessment of the chosen joints, and with a plain x-ray film evaluation (Larsen's score). RESULTS: Of 26 joints which clinically improved (14 markedly and 14 slightly) during the study, on MRI 16 showed improvement, 8 showed no change, and 2 showed deterioration. Four clinically unchanged joints appeared improved on MRI. One joint deteriorated clinically and on MRI. Overall, there was a 58% congruence between clinical and MRI findings. On x-ray 23 joints showed no change; nine of these were also unchanged on MRI, while 13 showed improvement and one deterioration. Only in 2 out of 8 joints showing deterioration on x-ray were the MRI findings in accordance. In the remaining six joints MRI showed improvement. The congruence between x-ray and MRI was therefore 36%. CONCLUSION: The long-term follow-up of rheumatoid synovial proliferation of the small joints in the hand using contrast enhanced MRI is feasible and may provide additional information regarding disease activity. Important advantages over conventional radiography methods are its ability to demonstrate qualitative differences of synovial proliferation within bone erosions, and demonstrate not only deterioration, but also the improvement of inflammatory disease.

Adult↗