Biomedical subjects
Publications and source records attributed to A C Kennedy.
1. Foetal rat hemi-calvaria were incubated in organ culture with sera from patients with active rheumatoid arthritis. 2. Increased 45Ca resorption was produced by sera from patients who were hypercalcaemic. 3. This bone-resorbing effect could be inhibited by calcitonin.
A study was made of the plasma and synovial-fluid levels of ketoprofen after single oral doses of 50 mg and 100 mg given to patients with rheumatoid arthritis. The drug was rapidly absorbed and plasma levels were similar to those seen in healthy volunteers. The mean early plasma half-life of ketoprofen in both volunteers and patients with rheumatoid arthritis was 1.5 to 2 hours. A cumulative effect of ketoprofen was evident in the synovial-fluid of the patients studied.
A double-blind cross-over trial of ketoprofen (200 mg daily) compared with placebo and aspirin (4 g daily) was carried out in 24 patients with rheumatoid arthritis. Ketoprofen was shown to be significantly more effective than placebo in terms of pain relief, degree and duration of morning stiffness, articular index and patients' assessment of improvement. No significant differences were noted between ketoprofen and aspirin, although side-effects were less with ketoprofen.
Ten patients not maximally controlled on an oxprenolo/cyclopenthiazide regimen for moderately severe hypertension were treated in a double blind crossover trial with either hydrallazine (75-150 mg/day) or phentolamine (60-120 mg/day) or placebo in addition to their other therapy. Additional phentolamine therapy did not lower blood pressure significantly when compared with placebo. Additional hydrallazine (75-150 mg/day) produced an approximate 10 mm, Hg fall in diastolic blood pressure, but no significant fall in systolic blood pressure. Pulse rates did not alter with the addition of hydrallazine or phentolamine. In patients who fail to attain optimal blood pressure response to beta-adrenoceptor blocking drugs it is suggested that the addition of hydrallazine is a useful measure.
Serum immunoreactive gastrin is raised in some patients with rheumatoid arthritis (RA). In this paper paired samples taken within 30 minutes of each other show that this phenomenon is reproducible. Dilution curves show identity between gastrin from RA patients and from patients with no RA, and the raised immunoreactive gastrin concentration is demonstrable in patients who do not have chronic atrophic gastritis and in whom both basal and stimulated acid output concentrations are normal. Samples of gastric mucous membrane obtained from the body of the stomach and gastroscopy under direct vision in 18 patients with raised serum immunoreactive gastrin concentrations were normal.
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1 The pharmacokinetics of frusemide have been studied in thirteen patients with severe chronic renal failure by using 35 S-frusemide. 2 The abosrption of aqueous frusemide was 57 +/- 20 percent (SD) and the bioavailability of 500 mg tablets was 42 +/- 12 percent, this differnece not assuming significance. 3 The renal clearance of frusemide was negligible (1.45 +/- 1.7 ml/min).
An activated charcoal haemoperfusion device containing 300 g acrylic hydrogel coated activated charcoal, was combined with haemodialysis, on six occasions in each of two patients, for a 2-hour portion of a routine 5-hour dialysis schedule. Blood pressure changes with combined treatment were minimised by using a low priming volume dialysis filter. Plasma clearance of both creatinine and urate were increased during the combined haemodialysis-haemoperfusion period. During the two hours of the combined treatment period in one patient creatinine removal amounted to 70% and urate removal to 50% of that obtained during a 5-hour haemodialysis. No significant additional urea or phosphate removal occurred. Changes in middle molecular weight substances with combined treatment were slightly greater than changes occurring with dialysis alone. Haemodialysis alone did not result in a terminal platelet fall, but combined treatment resulted in a terminal 20-30% platelet reduction, despite unchanged platelet counts at the end of the 2-hour haemoperfusion period. This preliminary study suggests that combined haemodialysis-haemoperfusion, is worthy of further scrutiny.
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(1) Plasma and urine electrolytes and whole body potassium have measured before and after a 2-week administration of depot tetracosactrin 0.5 mg on alternate days to eight patients with rheumatoid arthritis (RA.) The effects of adding supplements of potassium chloride (48 mmol/d) and spironolactone 200 mg daily have been investigated. (2) Acute changes in red blood cell water and potassium content, plasma electrolyte concentration, and plasma 11-hydroxycorticosteroid levels were measured for 48 hours after a single intramuscular injection of 0.5 mg depot tetracosactrin in six patients with RA. (3) The measured total body potassium was significantly less than that predicted from the height, weight, and age formula in patients with RA. (4) Treatment with depot tetracosactrin resulted in an acute fall in plasma and red cell potassium independent of external potassium loss. (5) Two weeks of treatment with depot tetracosactrin resulted in hypokalaemia and a rise in plasma sodium and bicarbonate. There was no associated electrocardiogram changes or a rise in blood pressure. (6) Neither oral potassium supplements nor spironolactone altered total body potassium. (7) The significance of the findings and the physiological mechanisms underlying them are discussed.
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A retrospective study is reported of 160 patients with definite or classical rheumatoid arthritis, in which changes in haemoglobin concentration were analysed against changes in various routine clinical and laboratory indices of disease activity over a period of time. Although statistically significant correlations were found between haemoglobin concentrations and the articular index of joint tenderness, serum albumin concentration, and erythrocyte sedimentation rate at one point in time, significant relationships in changes in haemoglobin concentration were only found with changes in the latter two laboratory indices. The significant correlations were weak and less important than the cumulative effect of unknown variables in determining haemoglobin level. The study shows that the routine clinical and laboratory parameters of disease activity in rheumatoid arthritis are of no value in predicting the haemoglobin concentration.
A three-part study on mineral metabolism in patients with classical rheumatoid arthritis is described. In the first two parts, biochemical abnormalities were revealed suggestive of parathyroid over-activity, and in the third part, observation on calcium absorption provides a hyperparathyroid pattern. The importance of these findings in relation to demineralisation of bone in rheumatoid arthritis is discussed.
Both male and female patients with rheumatoid arthritis show a significant bone loss in the femur, compared with the loss of bone seen in normal subjects with increasing age. A very similar pattern is seen in corticosteroid treated patients with rheumatoid arthritis. There is no evidence to suggest that the corticosteroid therapy has caused a greater loss of bone from the femur than would have occurred as a result of the rheumatoid arthritis alone. There was a statistically significant relation between the duration of the rheumatoid arthritis and femoral bone lo-s in women over the age of 45 years, whether or not they had been given steroid therapy in both male and female patients over 45 years of age, but again it appears unlikely that corticosteroid therapy had contributed significantly to the femoral bone loss. The Metacarpal and Femoral Indices of the patients were significantly related in both male and female groups.
Osteoporosis was studied in 307 patients with "definite" or "classical" rheumatoid arthritis by measurement of the clavicular cortical thickness (C.C.T.). Bone loss, as measured by this index, fell with advancing age, and was significantly greater than in non-rheumatoid control subjects matched for age and sex. Bone loss from the clavicles was not greater in patients treated with corticosteroid drugs. Loss of bone from the clavicle correlated with osteoporosis in other parts of the skeleton, as determined by the femoral and metacarpal indices. This suggests that osteoporosis in rheumatoid arthritis is a generalised phenomenon rather than a localised process secondary to adjacent joint inflammation.