The use of the Simpson Angus Scale for the assessment of movement disorder: A training guide.

The Simpson Angus Scale is commonly used for the assessment of Parkinsonian Movement Disorder related to psychiatric drug treatment. The authors present a practical guide to the use of the scale to assist both the learner and the teacher.

Azathioprine and allopurinol: a potentially dangerous combination.

We report the association of leucopenia and anaemia in five patients given a combination of azathioprine and allopurinol. Three subjects were renal transplant recipients with mild to moderate impairment of graft function. The complication appeared between 4 and 6 weeks following initiation of the combination therapy. Discontinuation of one of the two drugs resulted in full recovery within 4-8 weeks.

Pharmacokinetics of cyclosporin in man following a single oral dose: relationship to body fat content.

We have investigated the pharmacokinetics of the immunosuppressive drug cyclosporin in 11 patients receiving regular dialysis therapy. After a single oral dose of cyclosporin, whole blood concentrations were measured at regular intervals for 24 h. Body fat content was estimated in each subject from the measurement of skin-fold thickness and mid-arm circumference. In ten of the 11 patients there was a relatively uniform response in the increase of cyclosporin blood concentration to a peak within the first 6 h. Calculated area under the blood concentration curve did not correlate with total bodyweight, but correlated strongly with body fat content as well as fat-free mass. This study suggests that more predictable blood concentrations of cyclosporin might be achieved if the initial dose were calculated on the basis of fat-free mass rather than total bodyweight.

Controlled trial of calcitriol in hemodialysis patients.

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.

Azathioprine and cyclosporin: different tissue matching criteria needed?

Of 275 renal transplants performed over seven years in a single unit, azathioprine was the main immunosuppressive agent in 128 and cyclosporin in 147. With azathioprine graft survival was, as expected, negatively related to the number of HLA mismatches; with cyclosporin the reverse held true.

Bopindolol: a new long acting beta-receptor antagonist; its effects on haemodynamics, and on the renin response to tilting.

Oral administration of single doses of bopindolol (1-4mg) caused significant reductions in the rises of systolic blood pressure and heart rate produced by exercise; only the reduction in the rise of heart rate was significantly dose-related. Resting heart rate was reduced by bopindolol. There were small effects on resting blood pressure. Bopindolol caused a significant attenuation of the rise in plasma renin activity produced by passive head-up tilting to 75-85 degrees. Bopindolol produced a dose-related attenuation of the increase in pulse rate evoked by passive tilting. All effects 1-4 were maintained for at least 24 h. There was no measurable effect on plasma potassium concentration, peak flow rate or forced expiratory volume (FEV1).

Hydralazine and prazosin in the treatment of hypertension.

We report the results of an observer blind crossover trial in 31 patients with essential hypertension comparing the hypotensive effect of four doses of prazosin and of hydralazine used as the third step of triple therapy and additional data on the efficacy of low dose combinations of these two drugs. Both drugs had an appreciable antihypertensive effect, 1 mg of prazosin being equivalent to 12.5 mg of hydralazine. Increasing the dose of prazosin from 4 to 8 mg twice daily and hydralazine from 50 to 100 mg twice daily did not consistently reduce blood pressure. The combination of the two drugs at low doses resulted in the blood pressure of more patients being controlled (diastolic blood pressure 90 mm Hg or below) than when either drug was used alone at high dose. The symptoms reported by patients were similar for both drugs. The combination did not lead to an increased reporting frequency. The trial demonstrates one of the problems of a crossover study, namely a treatment/period interaction.

Controlled trial of calcitriol in the prevention of bone disease in haemodialysed patients.

Seventy-six patients receiving regular haemodialysis, without biochemical or radiological evidence of renal osteodystrophy, entered a five-year double-blind placebo-controlled trial of calcitriol (1,25-dihydroxycholecalciferol) in the prevention of bone disease. Significantly more patients on placebo developed bone disease as judged by a sustained elevation of plasma alkaline phosphatase or the development of sub-periosteal erosions on hand radiographs. Serum parathyroid hormone fell significantly in the patients receiving calcitriol and was significantly lower than in patients receiving placebo. It is concluded that calcitriol delays and may prevent the development of metabolic bone disease in patients receiving regular haemodialysis therapy.

The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension.

The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term experience of alfacalcidol in renal osteodystrophy.

Thirteen patients receiving regular haemodialysis, with biochemical or radiological evidence of renal osteodystrophy, were treated with alfacalcidol (1 alpha hydroxy vitamin D3) for four years. During the first eighteen months of treatment plasma alkaline phosphatase and serum parathyroid hormone concentrations fell and subperiosteal phalangeal erosions improved. Thereafter plasma alkaline phosphatase and serum parathyroid hormone concentrations rose and after four years' treatment only four patients had a normal plasma alkaline phosphatase, only five a normal serum parathyroid hormone level and in only six had the erosions healed completely. Hypercalcaemia occurred in twelve patients, plasma calcium exceeding 3.0 mmol/l in ten. Plasma calcium rose abruptly close to the time when plasma alkaline phosphatase became normal and often remained raised despite reduction in dosage of alfacalcidol. We have reservations about the ultimate value of long-term treatment with alfacalcidol in haemodialysed patients with renal osteodystrophy and urge caution in its use.

Azathioprine in rheumatoid arthritis: double-blind study of full versus half doses versus placebo.

To test whether azathioprine in effective in rheumatoid arthritis in doses smaller than those normally used the drug was tested at 2 dosage levels, 2.5 and 1.25 mg/kg/day (2.5 AZ and 1.25 AZ), against placebo under double-blind conditions over 24 weeks. Dropouts were 7 out of 15 in the 2.5 AZ group, 4 out of 14 in the 1.25 AZ group, and 2 out of 13 in the placebo group. Some significant improvement occurred in all 3 groups, including those on placebo. However, the 2.5 AZ group fared significantly better than the placebo group, while the 1.25 AZ group results tended to fall between the other 2 groups. We conclude that, in order to obtain the reported effectiveness of azathioprine in rheumatoid arthritis, it is necessary to start treatment with 2.5 mg/kg/day. Halving this dosage reduces the effectiveness of the drug.

Hormonal and blood pressure changes during converting enzyme inhibition by teprotide.

Changes induced by i.v. and subcutaneous teprotide in plasma renin, angiotensin I, angiotensin II, aldosterone and bradykinin were studied in a renal transplant patient with severe high renin hypertension, before and after trinephrectomy. The immediate reduction in BP produced by teprotide was not solely attributable to the inhibition of conversion of angiotensin I to angiotensin II, because there was also a transient increase in serum bradykinin; however, the prolonged antihypertensive effect of teprotide appeared independent of bradykinin. After trinephrectomy, teprotide lowered systolic BP but had no significant effect on diastolic BP or plasma bradykinin. beta-Blockade prevented the secondary increase in plasma renin which followed teprotide, thereby potentiating its anti-hypertensive effect.

Hemolytic uremic syndrome following chicken pox.

A patient with hemolytic uremic syndrome complicating chicken pox is described. At post mortem, the glomeruli showed diffuse capillary wall thickening and extensive wrinkling of the basement membrane with subendothelial deposition of granular material. Although a number of viruses and other infective agents have been implicated in its etiology, this appears to be the first report of an association between hemolytic uremic syndrome and chicken pox.

Use of 1,25(OH)2-vitamin D3 in prevention of renal osteodystrophy: preliminary observations.

Hypercalcaemia regularly occurs when "prophylactic" 1,25-dihydroxyvitamin D3 (1,25[OH)2D3) in a dose of 1.0 microgram daily is given to haemodialysis patients without clinical biochemical or radiological evidence of osteodystophy. This dose is too large for such patients. Hypercalcaemia may persist for several weeks after withdrawal of 1,25(OH)2D3, particularly when previous attempts at control by dosage reduction have failed. Hypercalcaemia is better managed by stopping 1,25(OH)2D3, albeit temporarily, than by reducing the dose.