HIV prevalence among IDUs in Australia: a methodological review

A review was carried out of Australian studies which have measured the prevalence of HIV infection among injecting drug users (IDUs). The review considered published studies which had reported on serologically-determined HIV prevalence. There were five studies reported from specialized sexually-transmissible disease of HIV clinics, five studies reported from health services aimed at IDUs, three studies reported from other health services and one multi-centre behavioural study. The main findings from the studies were that HIV prevalence in IDUs has been low in Australia, apart from in male IDUs who also had homosexual contact. HIV prevalence ranged from 20 to 24% in male IDUs reporting homosexual contact and from 0 to 5% in other IDUs.

The studies, while reflecting a range of research methodologies, are subject to a number of limitations. Most of the studies did not provide detailed analyses of HIV prevalence by age and sex or behavioural factors, and several studies used sampling frames which were not clearly defined. There is little available information on temporal trends in seroprevalence and geographical comparisons are rendered difficult by differences in the study methodology. Adoption of standardized, continuing seroprevalence surveys on IDUs would provide a better means of monitoring the occurrence of HIV infection in this group, which has been a key determinant of the course of the HIV epidemic in a number of Western countries.     

Anti-inflammatory activity of hamamelis distillate applied topically to the skin

Summary The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle.UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry.The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.     

Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts

Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4°C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511±216 vs 417±333 g/dl and 114.1±12.2 vs 91.4±12.2 mg/dl, respectively; P<0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.     

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).     

Effect of erythromycin on the oro-caecal transit time in man

Summary Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility, 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA, 2-acetyl erythromycin stearate) 800 mg in a double-blind trial. The orocaecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H₂-peak (ppm) in end-expiratory breath by two methods, t₁ representing the front and t₂ the bulk of lactulose reaching the colon.t₁ was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p < 0.05, ES vs placebo). t₂ was 74 min, 64 min, and 46 min, respectively (p < 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication.It was concluded that erythromycin shortens the orocaecal transit time in man and that EA affects the transit time slightly less than ES.     

Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 μG

Summary In a Phase I study, the tolerability, pharmacodynamics and pharmacokinetics of cicaprost have been investigated in 6 male volunteers given 5, 10, 15 and 20 g as tablets of the -cyclodextrin clathrate.Individual inhibition of platelet aggregation and changes in facial colour (measured by chromametry) were dose-dependent and reached a maximum 30 to 60 min post-dose. The maximum inhibition of platelet aggregation was about 40%. After 3 to 4 h pre-treatment values had returned. Blood pressure remained within the normal range. The peak plasma level of cicaprost was reached within 15 to 90 min after drug intake. Both C_max-and AUC were individually dose-dependent. The terminal half-life in plasma of cicaprost was approx. 1 h, and its total clearance amounted to 4–7 ml·min^–1·kg^–1. The time courses of the plasma levels and of the pharmacodynamic actions were in agreement. Interindividual differences were observed in the occurrence of unwanted effects (e.g. headache).Thus, cicaprost is an orally available PGI₂-mimetic, for which effects on platelet aggregation and vascular perfusion have been demonstrated in healthy volunteers after doses of 5 to 15 g.The results will form part of the M.D. thesis of T.Staks. Some of the findings were presented at the CPT meeting, Mannheim/Heidelberg, 1989     

Drug use in pregnancy: an overview of epidemiological (drug utilization) studies

Summary The need for further information on drug utilization patterns during pregnancy in different countries was assessed by reviewing literature obtained by hand and computer searches for the years 1960–1988.The 13 identified studies showed that pregnant women used an average of 4.7 drugs. The most commonly ingested medications were vitamins and iron preparations (almost all women), analgesics, antiemetics and antacids.However, the important variables taken into account differently in each study, such as date of surveillance, country, size of population, personal habits, and physiopathological and demographic characteristics, may it impossible to construct a comprehensive, detailed, up-to-date picture of drug utilization during pregnancy.The evaluation confirmed the need for systematic permanent surveillance of drug utilization in pregnancy, so as to avoid the use of data based on widely differing contexts, times and methods, in a field where knowledge is often derived from scanty information.This study was supported in part by the National Research Council (CNR, Rome, Italy), Convenzione Farmacologia Clinica     

Comparison of the diuretic effect and absorption of a single dose of furosemide and free and the fixed combinations of furosemide and triamterene in healthy male adults

Summary The absorption and diuretic effect of furosemide 40 mg alone (F), and of the free (F+T) and the fixed (FT) combinations of furosemide 40 mg and triamterene 50 mg have been compared in 12 healthy young men.A slight reduction in the area under the concentration-time curve (AUC) of plasma furosemide was found for the fixed combination (AUC₄₈₀) F 2.58 g · h · ml^–1; F+T 2.46 g · h · ml^–1; FT 1.97 g · h · ml^–1. There was a significant reduction in the AUC₄₈₀ of plasma triameterene (F+T 204.9 g · h · l^–1; FT 130.2 g · h · l^–1). Sodium excretion after F+T and FT was more pronounced than after F (F+T 302 mmol; FT 311 mmol; F 259 mmol). When compared to F alone, there was a reduction in the 24-hour potassium excretion after F+T as well as after FT (F 121 mmol; F+T 104 mmol; FT 107 mmol).It is concluded that the absorption of triamterene was significantly reduced after ingestion of the fixed combination tablet. However, in healthy male adults this had no influence on its natriuretic and potassium-sparing effect as compared to the free combination.     

Depression of drug metabolizing activity in the human liver by interferon-α

Summary The depressant effect of interferon- on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol·g^–1 liver·min^–1, and from 3.22 to 2.16 nmol·g^–1 liver·min^–1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon- can impair the activity of drug metabolizing enzymes in the human liver.