Biomedical subjects
Publications and source records attributed to B Donovan.
A case of transmission of the acquired immune deficiency syndrome (AIDS) associated retrovirus (ARV) by brachioproctic eroticism is described.
A short-term double-blind controlled trial has been performed comparing a slow-release 5'-aminosalicylic acid (5-ASA) tablet (Pentasa) with placebo in the outpatient treatment of mild and moderate active Crohn's colitis. The disease activity was measured objectively by quantitation of the faecal excretion of 111In-labelled autologous granulocytes, which directly reflects gut inflammation. Twelve patients were randomized to receive either Pentasa or placebo. After 10 days of treatment faecal granulocyte excretion fell in all patients receiving 5-ASA, while no consistent change was found in the placebo group. These results suggest that this slow-release preparation of 5-ASA should be tested in larger controlled therapeutic trials over a longer period of time.
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In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.
H.261, a new transition state inhibitor of human renin with an IC50 of 6.9 X 10(-10) M, was given by intravenous infusion to six anaesthetized baboons. The inhibitor was infused first at 0.1 mumol/kg/h for 15 min, then at 1.0 mumol/kg/h for a further 15 min. After a recovery period of 2 h in which the animals received 5% dextrose, they were infused with captopril, 25 mumol/kg/h for 15 min. At both rates of infusion H.261 markedly and significantly reduced the enzymatic action of renin in plasma, the blood concentration of angiotensin I, the plasma concentration of angiotensin II and mean arterial pressure. All changes reverted towards or to control values in the subsequent control period. Captopril also lowered plasma angiotensin II concentration and mean arterial pressure markedly and significantly but, as expected for an inhibitor of the angiotensin I-converting enzyme, plasma active renin concentration and blood angiotensin I concentration increased. The changes of angiotensin II and arterial pressure were similar with captopril and H.261.
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Infusion of H.261, the inhibitor of human renin in the baboon, lowered blood angiotensin I, plasma angiotensin II, and arterial pressure suggesting that in the sodium-depleted state angiotensin II contributes to the maintenance of arterial pressure. In a second experiment dose-response infusions of angiotensin II were given in conscious sodium-depleted dogs before and during infusion of the renin inhibitor H.77. These suggested that the contribution of angiotensin II to the maintenance of arterial pressure in this state was made mainly by a circulating peptide. Preliminary results in normal humans show that infusion of H.142 intravenously lowered angiotensin I, angiotensin II, and arterial pressure.
Seventy prostitutes were screened at their place of work, a Sydney house of prostitution, on a weekly basis over one year. Of these, 10% acquired new infections with gonorrhoea each week (53 episodes). Clinical guidelines (symptoms, contact history, physical signs) were found to be unreliable, in this context, for predicting the isolation of Neisseria gonorrhoeae. Of the 39 women observed over one month or more, 17 (44%) acquired gonorrhoea within the first month. Stability of the place of work appeared to be associated with a lower isolation rate (5.5%). Five asymptomatic, urethrally infected men (two clients, three boyfriends/husbands) were detected, and appeared to have an important role in the hyperendemicity of gonorrhoea in this environment.
All the women working in a Sydney house of prostitution were surveyed for one year for the presence of sexually transmitted diseases (STDs) and other medical problems, and for the contraceptive methods they used. Considerable potential morbidity from STD was noted, particularly pelvic inflammatory disease (23 episodes). Contraception was an area of unsatisfactory practice. Suggestions are made for the clinical management of these women, with the intention of diminishing the impact of STDs on them and, as a direct result, rendering them less infectious, to the benefit of the community. It is hoped that greater knowledge will improve the standard of current debate about prostitution.
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A new inhibitor of human renin (H. 189) is described. It is a decapeptide analogue of human renin substrate with the amino acid, statine, substituted for leucine in the scissile bond. Its inhibitory potency as shown by IC50 is 1.0 X 10(-8) M with human plasma renin and 1.5 X 10(-8) M with baboon plasma renin. It is less effective with dog and rat renin, but its inhibitory potency with human renin is similar to that of another inhibitor of ours (H. 142) having a reduced isostere in the scissile bond. H. 189 has some inhibitory effect on cathepsin D (IC50 6.5 X 10(-5) M) but H. 142 has no discernible effect. Pepstatin, on the other hand, was highly effective against cathepsin D (IC50 1.2 X 10(-8) M). H. 142 and H. 189 were infused intravenously at 10 mg/kg/h in four anaesthetized salt-deplete baboons (Papio hamadryas). The activity of renin in plasma decreased markedly as did the circulating concentration of its products, angiotensin I and angiotensin II.
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The concentrations in plasma of triglycl-8-lysine-vasopressin (TGLVP), determined by radioimmunoassay, and lysine-vasopressin, determined by bioassay, have been monitored in five subjects after intravenous (7.5 micron/kg) or intranasal (5 mg) administration of TGLVP. The level of excretion in urine was also measured. The TGLVP concentration in plasma fell rapidly after the intravenous injection, the mean half-time of disappearance being 24.2 +/- 1.9 (S.E.M.) min (d.f. 4). Biologically active lysine-vasopressin reached a peak between 60 and 120 min. A similar pattern was seen following intranasal instillation but only a small proportion of the administered dose appeared in the plasma and the concentration of lysine-vasopressin was relatively higher. Less than 1% of the TGLVP injected appeared in the urine. Intravenous TGLVP had no effect on systolic blood pressure but produced an increase in diastolic blood pressure of 1.7 +/- 0.19 kPa (d.f. 4) and a fall in heart rate of 9 +/- 2.3 beats/min. Creatinine clearance and sodium excretion remained relatively constant in all subjects throughout the study but intravenous injection of TGLVP resulted in an antidiuresis which was evident within the first hour of observation and was maintained for a further 4 h. It was concluded that TGLVP is converted to lysine-vasopressin in man and after an intravenous injection of 7.5 micron/kg sufficiently high concentrations of lysine-vasopressin may be maintained for 2 h to produce sustained vasoconstriction. Tryglycylvasopressin may therefore be of value in controlling haemorrhage.
Feprazone, 200 mg t.d.s., was compared with indomethacin, 25 mg t.d.s. rising to 50 mg t.d.s., in an eight-week double-blind cross-over study in twenty-three patients with active rheumatoid arthritis. Both therapies proved equally efficacious and acceptable. Measurement of the plasma levels of the two drugs showed no consistent correlation between efficacy and plasma concentrations.
The blood levels and excretion of radioactivity administered as 14C- or 3H-4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) have been studied after oral administration to dogs and man. After a single dose of 14C- or 3H-DA 2370 (10 mg/kg) to dogs the daily loss of radioactivity in urine and faeces fell to less than 1% of the dose in 4 days and the plasma levels showed a biexponential decay with mean half-lives of 3.7 and 62 h. When a single 200 mg dose of 3H-DA 2370 was administered to human subjects maximum urinary excretion of radioactivity occurred during day 2 with 4% of the total during day 5. Maximum faecal excretion was on day 2-3 with 0.5% of the dose on day 7. The plasma half-life was 32.5 h. A similar dose three times a day for 3 days had a half-life of 39 h when dosing ceased; radioactivity in the urine and faeces was 2% and 2.5% of the dose, respectively, 4 days later.