David G. Palmer

A myocardial syndrome. With particular reference to the occurrence of sudden death and of premature systoles interrupting antecedent T waves.

Abstract Eighty cases of a well defined myocardial syndrome, an important feature of which is the interruption of T waves by premature QRS complexes, are reported. Other features of the syndrome include myocardial damage and sudden death, multiform premature ventricular complexes, aberration in the form of ventricular complexes of supraventricular origin, variation in the interval between successive ectopic complexes and the preceding sinus complex and ectopic complexes in runs of two or more. Post-extrasystolic T wave changes are sometimes observed. The R on T phenomenon is by no means uncommon when looked for, and it may be seen in a wide variety of pathologic states involving the heart, such as myocardial infarction, ischemic heart disease, hypertensive heart disease and several distinct myocardiopathies. It may also be seen during cardiac surgery and during diagnostic procedures such as cardiac catheterization, angiocardiography and ventricular puncture. The phenomenon may be suspected clinically when very premature beats are noted on auscultation, and it is frequently found in electrocardiograms recording such arrhythmias as multiform ventricular systoles, ventricular tachycardia, flutter and fibrillation, auricular paroxysmal ftachycardia and auricular fibrillation. The incomplete syndrome without T wave interruption is very common and, frequently, further observation and electrocardiography will reveal the missing features. The syndrome is frequently associated with sudden death and prophylactic administration of quinidine is recommended as a therapeutic measure.

Immunohistochemical analysis of synovial membranes from inflammatory and non-inflammatory arthritides: scarcity of CD5 positive B cells and IL2 receptor bearing T cells.

Summary Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual immunohistological techniques with a number of monoclonal antibodies against lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently expressed MHC Class II antigens and were found in sublining collections in close association with activated macrophages as well as B lymphocytes. CD8 positive T cells surrounded these collections as well as being scattered throughout the membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r) expression on T cells and CD5 expression on B cells were rarely seen in these synovial membranes. Similar immunohistological architecture was found in synovial membranes from patients with psoriatic arthritis (PA) and Reiters Syndrome (RS). Normal synovium contained few T cells, with few cells expressing MHC Class II antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar immunohistological changes to those found in inflammatory arthritides, suggesting that there are only quantitative rather than qualitative differences between the synovial membrane immunohistological architecture from patients with inflammatory and noninflammatory arthritides.

Interruption of T waves by premature QRS complexes and the relationship of this phenomenon to ventricular fibrillation.

Abstract The mechanism of interruption of the T wave has been described. It has been shown that interruption may be produced if an area of repolarized myocardium is stimulated before other areas have recovered from the passage of the preceding impulse. However, the extent of interruption of the T wave may be increased by propagation of the premature impulse before local repolarization has been completed. Interruption of the T wave was produced under the following conditions: (1) by the premature stimulation of the ventricular septum after the passage of a supraventricular impulse; (2) by the premature stimulation of the site of origin of an ectopic ventricular complex; and (3) by the premature stimulation of an ischemic area of ventricular myocardium after the passage of a supraventricular complex. Ventricular fibrillation was frequently observed to be precipitated by interruption of the T wave, and evidence has been produced which suggests that such very premature impulses may meet refractory tissue which is bypassed. Re-entry into such bypassed areas might well explain the onset of ventricular fibrillation. I think that these experimental results have provided a physiologic basis for the R-on-T phenomenon as encountered clinically and have confirmed the relationship of T-wave interruption to serious ventricular arrhythmias.

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules

SummaryThe mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.

A mononuclear phagocyte subset associated with cell necrosis in rheumatoid nodules: identification with monoclonal antibody 5.5

A subset of mononuclear phagocytes identified by mAb 5.5 has been found within rheumatoid subcutaneous nodules. These cells appear to be derived directly from blood-borne monocytes. They form a variable proportion of the mononuclear phagocyte population within the nodule and are intimately associated with the tissue necrosis which characterizes these lesions. Necrosis appears within small aggregates of mAb 5.5-positive cells. Similar cells are also associated with localized extensions of necrosis through the palisade zone. Centrifugal extension of the necrotic centers through incorporation of the inner cells of the palisade layer appears to be an independent phenomenon.

The response of human peripheral blood mononuclear phagocytes to rheumatoid arthritis.

The maturity of peripheral blood mononuclear phagocytes (B‐MPs) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and reference (“normal”) subjects was compared. Mononuclear cell isolates from peripheral blood were separated on discontinuous gradients of Percoll into low density (more mature) and high density (less mature) subpopulations. Contrary to expectations, the proportion of immature B‐MPs in RA patients was found to be significantly lower than that in reference subjects. In RA patients with synovial effusions the proportion of immature B‐MPs approached but did not exceed those found in reference subjects, despite the fact that 31% of these patients displayed a peripheral blood monocytosis. It was concluded that the bone marrow precursor population had adapted to the long‐term demand for B‐MPs in the course of this chronic inflammatory disease.

Changes in Anti-DNA Antibody Affinity during Exacerbations of Systemic Lupus Erythematosus

The level and average functional affinity of anti-DNA antibody were measured retrospectively in successive serum samples from 5 patients with systemic lupus erythematosus. In 2 patients, severe flares of disease activity were associated with an increase in the level and average functional affinity of anti-DNA antibodies. Three patients who did not experience significant flares in disease activity exhibited more constant levels of antibody of lower average functional affinity. The appearance of antibody of high functional affinity during disease exacerbations suggests that such antibodies may be pathogenic.

Dispersed cell cultures of rheumatoid synovial membrane.

The morphology of cells released from synovial tissues involved by rheumatoid arthritis and grown in tissue culture has been described. Cultures were well established and differentiated by the third day. In growth medium enriched with heat-inactivated rheumatoid serum syncytial cell masses frequently formed. This change particularly, was very like the characteristic cytopathic effect of a number of viruses.

Clinical evaluation of two daily doses of naproxen and indomethacin: result of a double-blind crossover trial

SummaryA double-blind crossover clinical trial is reported on the effects of naproxen in two doses, 500 mg. and 750 mg. daily, and 100 mg. indomethacin daily in 23 patients with classical rheumatoid arthritis, each drug being given for 1 week. The results show that there was little to choose between the drugs and that there was clinical equivalence between the two doses of naproxen. Radioactive pertechnetate (99mTc) joint uptakes were depressed by both naproxen and indomethacin, indicating anti-inflammatory effect.

Development of an enzyme immunoassay for the quantitation of cellular antigen expression

An enzyme immunoassay is described which can be used to quantitate the cellular expression of antigens recognised by mouse monoclonal antibodies (mAb). To provide the sensitivity required, complexes of alkaline phosphatase and mouse monoclonal anti-alkaline phosphatase (APAAP) have been used. The speed and reproducibility of the assay was improved with the aid of immunofiltration methodology. Quantitative measurement of HLA-DR antigen expression by ELISA did not correlate directly with the number of mononuclear cells scored positive following immunohistochemical staining of cytocentrifuged preparations. In patients with rheumatoid arthritis, more HLA-DR was expressed on synovial fluid mononuclear cells than on the corresponding cells obtained from peripheral blood.