Biomedical subjects
Publications and source records attributed to W H Thomson.
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Data are presented which suggest that Duchenne muscular dystrophy (DMD) may have some origin in a severe deficiency of total muscle adenine nucleotides. Using double-blind techniques, this possibility was tested in 16 DMD patients by giving oral allopurinol, a synthetic inhibitor of the purine catabolic enzyme xanthine oxidase. Sublingual procaine adenylate was also briefly tested. Instances of clinical improvement quickly occurred which were statistically significant; they were accompanied by a significant increase in physical strength. These improvements have been maintained for more than 6 mo by administration of a small amount of allopurinol daily. Procaine adenylate had little effect. These results support the above view of DMD and seem to indicate that existing purines, retained and recycled after allopurinol, can sustain such improvement, and that additional adenylate is unnecessary.
The red cell mass was measured in 44 normal subjects and showed a closer correlation with total body water or surface area than with body weight. The results obtained in a group of patients with polycythaemia, however, still overlap with the normal range. When the total number of circulating red cells is measured these patients form a group quite separate from the normals. The diagnostic value of this measurement is therefore considerably greater than results obtained with the red cell mass.
Allosterism allows individual assay of both isoenzymes, one abundant in muscle, of pyruvate kinase (PK), recently reported superior to serum creatine phosphokinase (CPK) in detecting patients with and female carriers of X-linked recessive (Duchenne) muscular dystrophy (DMD). Extensive comparative studies did not support these findings and confirmed the marked superiority of CPK over rariants of PK or other enzymes in sensitivity, stability and convenience. Deducting the adenylate kinase increment (AKI) further refined the CPK assay, eliminating the effect of haemolysis in diagnosis and enabling studies of blood cell content. Both leucocytes and erythrocytes liberated PK and lactate dehydrogenase (LDH) after brief chilling or disruption. Only erythrocytes showed a CPK content, however, constantly adjusted to match that of serum as if by free cell membrane passage, but less accomodating to a sudden large influx of CPK than of LDH, where an apparent buffering effect could account for differences in clinical response.
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Observations in 12 normal women and 12 female carriers of X-linked recessive Duchenne muscular dystrophy (DMD), of whom 4 had symptoms and 8 had none, were compared between all 4 groups and with those in 2 DMD boys, one active and one crippled. Carrier symptoms were readily ascertained by systematic examination. Measurement of both lower legs in all 24 women showed neither calf enlargement nor asymmetry in carriers beyond normal variation. Two DMD carrier daughters were noted of the same DMD carrier mother but by different fathers. Whole body counting showed the biological half-life of previously administered 86Rb to be much reduced in DMD, but no differences were found between normal women and any group of carriers. The test is thus valueless for carrier detection, and reasons are given why it should be so. Simultaneous measurement of total body K+, with subsequent determination by isotope dilution of total body water as 3H2O space and extracellular water as NH4 82Br space, showed increased intracellular water and reduced intracellular K+ concentration in all carriers, as if due to osmotic causes, with actual loss of muscle mass and slight diminution of serum K+ in the 4 symptomatic carriers only. Because of diurnal and other variations, the means and standard deviations for six serum enzymes from six fortnightly assays in all subjects were used to measure precise individual status. Their coefficients of variation were abnormal only in symptomatic carriers and ambulant DMD, easily overtexed by even accustomed exertion. This is shown to support previous propositions on the pathogenesis of DMD and the escape of muscle cell content into the circulation.
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