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Biomedical subjects

M H Pritchard

Publications and source records attributed to M H Pritchard.

At least 37 records · Page 2Linked to original sources

Synovial protease/inhibitor ratios in erosive and nonerosive arthropathies.

Although rheumatoid joint fluids contain numerous polymorphs capable of secreting neutral proteases known to be able to digest cartilage, the high level of inhibitors (mainly alpha 1-antitrypsin and alpha 2-macroglobulin) has always been considered to be more than sufficient to inhibit their activity completely. Consequently little interest has been paid to the potential role of these enzymes in cartilage damage. Four arthropathies of different erosive potential are here compared: spondyloarthropathies, rheumatoid arthritis with and without gold or D-penicillamine therapy, and septic arthritis. The synovial concentration of the inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin has been compared with the polymorph enzyme output, as measured by beta-glucuronidase. Total haemolytic complement, white cell count, and C-reactive protein have also been measured in the joint fluid. The range of white cell count and inhibitors was the same in all 4 groups, while the enzyme output varied substantially from low levels in the spondyloarthropathies to very high levels in the septic joints. The higher the erosive potential of the disease, therefore, the more disadvantageous is the inhibitor/enzyme ratio. It is also pointed out that cartilage has physiochemical properties which facilitate and enhance polymorph enzyme output while severely curtailing the activity of the inhibitors. The observation that synovial fluid is inhibitory in vitro may therefore bear little relationship to the situation at the cartilage surface in vivo.

Arthritis↗

Nephelometry compared with differential antibody titre in routine rheumatoid factor measurements.

The comparative merits of agglutination techniques (differential agglutination titre (DAT)/latex slide test) and nephelometry for the routine measurements of IgM rheumatoid factors have been studied in this 2-part paper. The first part investigates the errors inherent in standard DAT measurements, and the second determines the rate of false positive results in an elderly nonrheumatoid population. It was found that the errors in agglutination techniques are due to differences in setting up the tests rather than in interpreting the results, and that the coefficient of variance was consistently around 20%. Approximately 1 in 5 of DAT results have such a high error as to be clinically valueless. The false positive rate in the elderly nonrheumatoid population was only 2% with nephelometry compared with 9% on the latex slide test. A previous study had demonstrated the advantages of nephelometry over DAT in routine rheumatological use, showing not only greater reproducibility but also a more accurate positive detection rate than the DAT in rheumatoid arthritis. The results also suggest that the traditional spectrum of rheumatoid factors of low titre detectable in the general population is probably an artefact inherent in agglutination techniques and that a definitive cut-off point is more likely. As nephelometers are generally available in biochemistry laboratories there is much to recommended their routine use for the measurement of IgM rheumatoid factors.

Aged↗

Nephelometry v differential agglutination titre in the measurement of rheumatoid factors.

IgM rheumatoid factors have been measured in 92 patients by both laser nephelometry and the traditional hospital procedure of a latex slide test followed by differential agglutination titre (DAT). Of the results 86% were in accordance by both methods, but seronegative patients with a high nephelometry score all showed, after reference to their clinical state and previous investigations, that the nephelometry result more accurately represented their clinical state than the DAT, which was shown to be in error in five out of the six cases. Six seropositive patients with low nephelometry scores were also studied; three were in complete remission on gold or penicillamine therapy. Nephelometry is both technically simpler and more reliable than the traditional DAT method, and our results suggest that it has some advantages over the DAT in routine use.

Agglutination Tests↗

A study of amyloid arthropathy in multiple myeloma.

Forty-three patients with classical multiple myeloma were studied to assess the prevalence and characteristics of amyloid arthropathy using clinical, radiological, and histological methods. Two patients were found to have amyloid arthropathy, and a third case is described in detail. Complement and cryoprecipitate analysis of the synovial fluid, and electronmicroscopy of the synovium, synovial debris and cartilage were undertaken in an attempt to shed further light onto the pathogenesis of what has hitherto been regarded as a rare complication of multiple myeloma. Complement components were not depressed and no evidence of specific light chain containing immune complexes was found in synovial fluid cryoprecipitates. Histochemical and electron microscopic localization of amyloid in perichondrocytic lacunae as well as in synovial fluid debris, synovium and the articular cartilage surface suggest the possibility that chondrocytes and synovial macrophages may share a role in processing immunoglobulin components as a prelude to the formation of amyloid fibrils. Amyloid arthropathy occurs in about 5 per cent of patients with multiple myeloma. The clinical picture can resemble rheumatoid arthritis with median nerve compression in the carpal tunnel and symmetrical arthritis of the wrists and small joints of the hands. Diagnosis can be established by examination of Congo red stained synovial fluid sediments under polarized light even in the absence of other clinical features of amyloidosis and when rectal biopsy is negative.

Aged↗

Systemic lupus erythematosus, repeated abortions, and thrombocytopenia.

A case is described of severe thrombocytopenia in a pregnant patient with mild SLE. Three previous pregnancies had ended in abortion. Attempts to reverse the thrombocytopenia with steroids, plasmapheresis, and splenectomy failed, the platelet count returning to normal immediately after the death of the fetus at 20 weeks gestation.

Abortion, Habitual↗

Gold and penicillamine: a proposed mode of action in rheumatoid arthritis, based on synovial fluid analysis.

Although in common use, there is still controversy as to the way in which gold and penicillamine act in rheumatoid arthritis (RA). In this study, synovial fluids from 4 groups of patients have been compared: (1) RA patients on gold/penicillamine, (2) RA patients on non-steriodal anti-inflammatory drugs (NSAID) only, (3) osteoarthritis patients, and (4) patients with sero-negative arthropathies. The parameters measured were differential agglutination titre (DAT), total haemolytic complement (CH50), total protein, total white cell count, and immunoglobulins. RA patients on gold/penicillamine have lower synovial DAT levels and higher CH50 levels than RA patients on NSAID only, and total and cryoprecipitable IgM levels very close to those found in the sero-negative joint fluids. The non-specific inflammatory parameters, ie, white cell count and total protein are unchanged after good/penicillamine therapy. In a second study, the serum DATs of patients in total remission after gold/penicillamine were compared with similar patients on NSAID only. The DAT falls significantly in the former group (P less than 0.001), but not in the latter suggesting that fall in DAT is a consequence of therapy rather than remission. The parameters altered by gold/penicillamine in the synovial fluid are those that distinguish RA from non-rheumatoid arthropathies suggesting the drug's primary effect is to render the disease sero-negative. The results support the hypothesis that both drugs have a common mode of action based on their active thiol groups, and that the fall in DAT is due to the reduction of the antigenicity of the IgG complexes.

Anti-Inflammatory Agents, Non-Steroidal↗

Chondrocalcinosis in primary hyperparathyroidism. Influence of age, metabolic bone disease, and parathyroidectomy.

Chondrocalcinosis is known to be common in hyperparathyroidism. In order to discover the effect of parathyroidectomy on chondrocalcinosis and to investigate this association further, we studied two groups of patients. In one group were 41 postparathyroidectomy patients, and in the other 100 admissions to the acute geriatric unit. The total incidence of chondrocalcinosis in the parathyroidectomy group was 32%, and in the elderly control group 11%. There was little or no osteoarthrosis in these patients. It was found that chondrocalcinosis occurred in the normal population from the age of 75 and in the hyperparathyroid group from the age of 45. In both groups the incidence rose steadily with age. In the hyperparathyroid group alone, preoperative serum calcium levels were no different in those without chondrocalcinosis, suggesting that hypercalcaemia alone is not a sufficient stimulus for chondrocalcinosis. Those with chondrocalcinosis had higher mean preoperative alkaline phosphatase levels, nearly twice as much radiological bone disease, and were older. Parathyroidectomy had no effect on attacks of pseudogout or on preexisting cartilage calcification. A connection with high levels of circulating parathyroid hormone is suggested, and a link with physical age-related changes in cartilage postulated.

Adult↗

Two new zoogonid digenea from deep-sea fishes in the Gulf of Panama.

Panopula cavernossa gen. et. sp. n. from the intestine of the brotulid Enchelybrotula (?) paucidens differs from other members of the Steganodermatinae by having testes near the anterior of the acetabulum, a posttesticular ovary, and a postequatorial acetabulum. Two related species are transferred to the genus Brachyenteron as B. pycnorganum comb. n. and B. spinosum comb. n. Neosteganoderma gillissi sp. n. from the synaphobranchid eel Synaphobranchus bathybius differs from N. glandulosum and N. polymixiae, the most similar species, because conspicuous glandular cells envelop the esophagus and pharynx, others about the genital atrium occur in elongated sacs, epithelium is lacking at the cecal bifurcation, and the cirrus sac is straight. We establish N. infundibulum comb. n. and expand Steganodermatinae to include Brevicreadium congeri and Hudsonia agassizi.

Animals↗

A trial of micro-encapsulated and enteric-coated aspirin in rheumatoid arthritis.

In a trial of 48 patients with rheumatoid arthritis, enteric-coated aspirin (4.55 g daily( and micro-encapsulated aspirin (4.50 g daily) proved to be equally effective in reducing morning stiffness, relieving pain, increasing grip strength, reducing ESR, and reducing the need for additional analgesic tablets, compared with placebo. Reduction of joint tenderness was also found, but this was not statistically significant. Proximal interphalangeal joint circumference altered little during the trial. Tinnitus and deafness were commoner with enteric-coated aspirin, but gastric side-effects were similar. Of 39 patients completing the trial, there was an equal patient preference for enteric-coated aspirin and micro-encapsulated aspirin. Salicylate side-effects necessitated withdrawal of six patients from the trial and dose reduction in nine patients. It was concluded that the efficacy and side-effects in rheumatoid arthritis of both aspirin preparations were similar.

Administration, Oral↗