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Biomedical subjects

M E Shipley

Publications and source records attributed to M E Shipley.

8 recordsLinked to original sources

Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.

Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in subjects without AS than in the group with AS, but these results were confined to the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from a patient with AS was examined, and no significant differences were found compared with the sequence isolated from a healthy subject. There do not seem to be significant genetic differences in the coding or in the regulatory region in HLA-B27 alleles, in subjects with or without AS.

Alleles↗

What do rheumatologists do? A pilot audit study.

Four consultant rheumatologists from different health districts compared their out-patient and in-patient workloads for 3 months. Data collection proved simple and valuable to each local unit. Inflammatory joint disease (particularly severe rheumatoid arthritis) dominated the workload in all centres. Large differences in the number of new referrals with osteoarthritis, soft tissue diseases and polymyalgia rheumatica were observed. Differences were also apparent in the organization of clinics, provision of follow-up appointments for different diagnostic groups, and usage of steroid injections. Although there may be a variety of explanations for these similarities and differences, the data emphasize the need for further audit of rheumatology practice in the UK.

Ambulatory Care Facilities↗

Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis.

Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions.

Animals↗

Pulsed methylprednisolone in active early rheumatoid disease: a dose-ranging study.

A dose-ranging, double-blind study of pulsed methylprednisolone in 71 patients with active classical or definite RA is reported. Single pulses of 40 mg, 500 mg or 1 g were administered during a 24-h admission. All patients benefited transiently, but only in those who received 1 g was this prolonged beyond 3 weeks. Laboratory measurements showed no significant change in any group. Significantly more patients in the 1 g group felt the treatment worthwhile than in the other groups. The drop-out rates in the 40 mg and 500 mg groups differed significantly from that seen in the 1 g group and were such that statistical analysis beyond 3 weeks was difficult to interpret. Side-effects were mild. Three patients subsequently developed avascular necrosis, one in the 1 g and two in the 40 mg groups. The study suggests that single doses of MP below 1 g are not helpful in the management of acute RA.

Adult↗

A double-blind placebo-controlled trial of methylprednisolone pulse therapy in active rheumatoid disease.

To confirm the findings of uncontrolled trials that methylprednisolone pulse therapy (MPPT) is a safe treatment for active rheumatoid disease, a double-blind trial was conducted in which 20 patients with active rheumatoid disease were randomly allocated to receive an infusion of either 1 g methylprednisolone or placebo. Methylprednisolone produced significant improvement in all clinical variables measured, a benefit which was sustained for at least 6 weeks. The placebo produced only transient improvement in some of the clinical variables measured. when the 10 placebo groups patients were later given an infusion of 1 g methylprednisolone, they too showed significant clinical benefit. The methylprednisolone also gave rise to improvements in some haematological and biochemical variables.

Adult↗

Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes.

Arachidonic acid is metabolised either by cyclooxygenases to produce prostaglandins and thromboxanes or by lipoxygenases to produce mono-, di- and trihydroxyeicosatetraenoic acids (HETEs). Polymorphonuclear leukocytes (PMNs) release HETEs, including mono- and dihydroxy fatty acids, when exposed to stimuli such as the calcium ionophore A23187 (refs 1, 2). The mono-HETEs are assumed to be of particular importance with respect to effects on leukocyte function because they have been shown to possess both chemotactic and chemokinetic activities towards PMNs and eosinophils. However, we have now shown that the chemokinetic and aggregating activities released from rat and human PMNs exposed to ionophore A23187 (ref. 5) are not due to the release of mono-HETEs but to that of 5, 12-di-HETE (leukotriene B). This compound is active over the concentration range 10 pg ml-1 to 5 ng ml-1.

Animals↗

Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

1. Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 microM release products which cause aggregation of rat PMNs and chemokinesis of human PMNs. 2. Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000. 3. Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10(-4) to 10(0-7) M, 5,8,11,14-eicosatetraynoic acid 10(-4) and 10(-5) M, BW 755C 10(-4) M and benoxaprofen 10(-4) M, all compounds known to inhibit lipoxygenase pathways of arachidonic acid (AA) metabolism. 4. Conventional non-steroidal anti-inflammatory agents, such as aspirin and indomethacin, inhibited little or not at all the generation of these activities. 5. We conclude that the aggregating and chemokinetic activities induced by A23187 represent generation of biologically active products of lipoxygenase pathways of AA metabolism.

Anti-Bacterial Agents↗