No abstract

On two occasions at least 1 week apart, nine healthy male volunteers were administered in random order either 2 x 200 mg (1.8 mmol) acyclovir tablets or 400 mg of acyclovir in 500 ml of 5% dextrose solution which was infused at constant rate into the duodenum over 4 h. Six of the subjects subsequently sipped the same solution at the rate of 10.4 ml in each 5 min period for 4 h. Blood and urine were sampled over 24 h for each mode of administration. Acyclovir was assayed by radioimmunoassay. Mean areas under the plasma concentrationtime curves (AUCs) + s.d. for tablet (T), intraduodenal infusion (I) and sipping (S) were, respectively: T = 14.7 + 5.1; I = 24.6 + 5.1; S = 28.4 + 9.5 (n = 6) ,umol 1-1 h. AUCs for I and S were significantly greater than that for T (2P < 0.05). Mean apparent maximum plasma concentrations (Cmax) + s.d. were T = 3.8 + 1.5; I = 4.8 + 0.9; S = 5.1 + 1.5 ,umol 1-1. This trend to higher values for I and S was not significant. Mean apparent plasma disappearance half-lives (ttl2) + s.d. were respectively T = 2.3 + 0.4; I = 2.7 + 0.5; S = 3.0 ± 0.2 h, I being significantly greater than T (2P < 0.05), as was S greater than T (2P < 0.01). The mean 24 h urinary recovery + s.d. of acyclovir (n = 8) was T = 309 + 119 ,umol (17% of dose); I = 471 + 83 ,imol (26% of dose); S = 507 ± 180 ,umol (28% of dose). I > T (P < 0.01), S > T (P < 0.05). Acyclovir absorption is increased when contact time of a solution with the absorptive area of the human gut is increased as compared with absorption available from the tablet. This suggests capacity limited absorption.

1 The influence of vagal and sympathetic efferent activity on sinus arrhythmia in man has been studied in six healthy subjects by administration of hyoscine butylbromide and/ or various 3-adrenoceptor blocking drugs using a microcomputer-linked electrocardiogram system. Sinus arrhythmia was quantitated as the s.d. of the R-R interval.2 Sinus arrhythmia was almost abolished by hyoscine butylbromide irrespective of the absence or presence and nature of the ,-adrenoceptor blocking drug. 3 Atenolol and metoprolol alone prolonged the mean R-R interval and increased sinus arrhythmia. Oxprenolol, a drug with modest partial agonist or intrinsic sympathomimetic activity (ISA), prolonged the mean R-R interval to a lesser extent but had no effect on sinus arrhythmia. Xamoterol, which has high ISA, shortened the mean R-R interval but had no effect on sinus arrhythmia. These data yielded a non-linear relationship between sinus arrhythmia and mean R-R interval. 4 Exaggerated sinus arrhythmia appears to accompany 3-adrenoceptor blockade only in the absence of ISA when bradycardia ensues. These findings are consistent with the hypothesis that the exaggeration in sinus arrhythmia is due to a central vagotonic effect secondary to the action of the drugs in the periphery. 5 Changes in R-R interval induced by the adrenoceptor blocking drugs were altered to some extent by vagal blockade. This observation is consistent with the hypothesis that changes in heart rate induced by such drugs are determined in part by a change in vagal tone.

Recent uncontrolled work has suggested that dietary supplementation with fish oils high in eicosapentaenoic acid may improve psoriasis.1 We have investigated this in a double‐blind, placebo‐controlled trial. Twenty‐nine patients (12 male, 17 female) with stable chronic plaque psoriasis, using only topical medicaments, were recruited into the trial. Patients were randomly allocated to receive either 10 capsules ‘MaxEPA’ daily, containing 1·8 g eicosapentaenoic acid (treatment group), or 10 identical capsules containing vegetable oil daily (control group), for a period of 12 weeks. Patients were allowed to continue their previous topical treatments, the quantity used being recorded at each visit. The percentage surface area affected, itching, erythema and scaling were assessed at 0, 4, 8 and 12 weeks. Tablet counts and erythrocyte membrane lipid measurements were performed to assess compliance. Twenty‐five patients completed the trial, 12 in the treatment group and 13 in the control group. Two patients defaulted from each group. After 8 weeks, 11 out of 12 patients in the treatment group had a reduction in surface area affected, compared with seven of 13 controls (P < 0·05; x2 test). The mean surface area affected (± SEM) at 0 and 8 weeks was 11·3 ± 1·7% and 7·6 ± 1·4% in the treatment group, and 11·8 ± 1·6% and 10·3 ± 1·5% in the control group, respectively. Itching improved at 8 weeks in 10 of the treatment group compared with four of the control group (P < 0·01;x2 test). Erythema improved in 10 of the treatment group compared with four of the controls, but this was not statistically significant (P < 0·01;x2 test). There was no improvement in scaling in either group. This study confirms that dietary supplementation with fish oil is a useful adjunctive therapy in patients with psoriasis, particularly when itching is a prominent symptom.

female, aged 54 years. History. The patient has a 2-year history of blood blisters and erosions forming on the hands, following slight trauma. The lesions heal quickly leaving little scarring. She has also noticed a tendancy to bruise easily on the hands, and to a lesser extent on the arms, legs and faee. She has occasionally developed erosions on her lower limbs after trauma. Her general health is good, and she feels well. She has had no serious illnesses.Examination. There is purpura on the palmar and dorsal surface of the hands. The dorsal surfaces of both hands (Fig. i) have erosions intermittently. Intaet blisters have not been observed by medical staff. The nails are ridged longitudinally and there is oncholysis. Milia are present on the finger webs. Small areas of purpura are usually present on the legs, and sometimes on the trunk, face and buccal mucosa. The tongue is normal in size.