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Objectives: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting., Design: A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting., Setting: Twenty Australian tertiary care hospitals in 1994., Patients: 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin., Intervention: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1., Main Outcome Measures: Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women., Results: (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response., Conclusions: Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.

A double blind comparative study comparing Mucaine, Mucaine without oxethazaine, and placebo was carried out with 50 patients with symptoms of heartburn during late pregnancy. We found that the 2 active treatments were more effective than placebo for the relief of heartburn, but there was no statistically significant difference between groups for the relief of nausea and regurgitation. There was a significant difference in the percentage of days of use of each medication, with the placebo being used least frequently. Although not statistically significant, for the 3 measures for which placebo differed from the active treatments, patients showed a better response to mucaine. This suggests that the addition of oxethazaine may be of benefit. The lack of statistical significance may be due to the relatively small number of cases, and the findings are promising. No side effects were recorded for any treatment.

Selection for ethanol tolerance was equally successful in two populations of D. melanogaster in both of which the frequency of AdhF was 0.5 at the start of the experiment. Increased tolerance to ethanol was not invariably associated with increased frequencies of AdhF. In one population alcohol dehydrogenase (ADH) activity was significantly higher in three of the four selected sublines compared with their controls but there was no difference in activity between the selected and control sublines in the second population. The level of ADH activity in the control and selected lines was significantly correlated with the frequency of AdhF, but not with ethanol tolerance. These results show that adaptation to environmental alcohols in populations of D. melanogaster can be independent of the ADH system.

A retrospective cohort study of mortality was conducted to assess whether the military service of young Australian men in Vietnam has influenced their overall death rates, or those from specific causes. The study was of all national servicemen who were conscripted during the conflict and served in the Army for at least 12 months. Of these, 19 205 served in Vietnam (veterans) while 25 677 served only in Australia (non-veterans). These men were traced from the end of their national service (between 1966 and 1973) until the beginning of 1982. For most causes of death, the observed number of deaths of veterans and of non-veterans was less than expected from Australian population death rates, and for no cause was there a statistically significant excess of deaths compared with that of the Australian population. Similarly, when veterans were compared with non-veterans, there was no statistically significant difference in deaths for all causes combined, for diseases of the circulatory system, for deaths in motor vehicle accidents, for suicide and for all external causes after adjustment for the different subsequent death rates of men who had served in different Army corps. All seven deaths from diseases of the digestive system were of veterans. There was no excess of deaths among veterans from cancer or from atypical causes of death in this group of young men. Three-quarters of deaths of both veterans and non-veterans were from external causes, often involving motor vehicle accidents.

Accuracy and consistency of death certification and coding practices in Australia were examined in relation to a defined population of 552 young men who died aged 20 to 40 years. For each death a mock death certificate was prepared by a team of physicians using all available clinical, pathological, and coronial data. These certificates, and their International Classification of Diseases (ICD 8) codes derived by an Australian Bureau of Statistics (ABS) nosologist, were compared with the actual death registration papers and their ICD 8 codes. Data for deaths from malignant neoplasms were also compared with results of histopathological review. The mock death certificates were superior to the true death certificates in both completeness of content and accuracy of the recorded cause of death. The major source of discrepancies was unsatisfactory narrative on the original death certificates, the standard of which varied with Australian state and with cause of death. The cause of death coding by ABS was of high standard, but its coding practices generally identify only death certificates where content is inadequate for specific coding. Where the narrative is sufficiently specific to be coded there is no mechanism for checking the accuracy of the cause of death recorded. Suggestions are made for improving the narrative.

From the records of an automated multi-phasic health testing centre, daily drinkers in four alcohol consumption groups were each separately matched for sex, age and obesity to a single non-drinker control. All subjects satisfied strict eligibility criteria selected to exclude the effects of other factors known to influence blood pressure or renal function or both. The 5500 pairs of subjects were compared for systolic and diastolic blood pressure and serum creatinine. After allowing for smoking, drinkers had significantly elevated blood pressure compared with their controls, and the elevation was greater the heavier the alcohol intake, except for the heaviest drinking females. This result was more pronounced in males than females, and for systolic than diastolic blood pressure. By contrast, smoking cigarettes was shown to be associated with lower blood pressure, independent of sex and drinking history. Smoking was also associated with a decreased serum creatinine concentration as was drinking three or more drinks per day. However, drinkers of two or fewer drinks daily had higher serum creatinine concentrations than their non-drinker controls.

Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.

Subjects attending a large, multiphasic health screening centre in Sydney, Australia estimated their alcohol consumption and specimens of their blood were analysed. The most useful univariate estimates of alcohol consumption were erythrocyte mean corpuscular volume and plasma aspartate-aminotransferase, gamma-glutamyl-transpeptidase, triglycerides and uric acid. The most statistically significant of these tests have been combined to form a multivariate predictor of alcohol intake which is more successful in identifying heavy-drinkers than single tests. To describe this population further, and to aid comparisons between populations, information about non-drinkers has also been provided.

Infants with anomalies diagnosed at, or shortly after, birth were individually matched to control infants born without an anomaly, in the same hospital, to a mother of similar age, and at about the same date. The fathers in 8517 such case-control pairs were identified, and compared with a list of men who served in the Australian Army between 1962 and 1972 - the period of Australian involvement in Vietnam. Fathers identified as having served in the Army during this period were then classified according to whether or not they had served in Vietnam. One hundred and twenty-seven fathers of infants who were born with anomalies and 123 fathers of control infants were Vietnam veterans. The risk of a Vietnam veteran fathering a child with an anomaly, compared with that of a non-veteran, was estimated at 1.02, with 95% confidence limits of 0.78 to 1.32. There was no evidence that Army service in Vietnam increases the risk of fathering children with anomalies diagnosed at birth.