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Biomedical subjects

F M Sullivan

Publications and source records attributed to F M Sullivan.

At least 19 recordsLinked to original sources
PubMed1992

The European Community classification of chemicals for reproductive toxicity.

The classification and labelling of dangerous substances was first introduced in 1967 in the European Community with Council Directive 67/548/EEC known as the Dangerous Substances Directive. The "6th Amendment" to this directive in 1979 introduced a notification procedure and a requirement for labelling chemicals for toxicity. Three special categories for labelling were for "Carcinogenicity, Mutagenicity and Teratogenicity". The teratogenicity classification was restricted to chemicals inducing "teratogenic" effects in the classical sense of the word ie. producing only gross structural malformations. Discussions by expert advisors to the European Commission over several years has lead to a widening of concern in this area of toxicology and under the forthcoming "7th Amendment" the classification of "Teratology" will be changed to "Toxic to Reproduction". This will include adverse effects on fertility, pre- and postnatal development and lactation and will encompass not only structural but also functional deficits. This will bring about a major change in the testing requirements to allow adequate classification of chemicals for these other aspects of reproductive toxicity.

Animals↗
PubMed1992

Primary medical care in Seychelles.

This paper describes some of the current health problems faced by a tropical country whose standard of living and lifestyle is approaching that of many countries in Western Europe. Long-term health problems such as cardiovascular diseases and diabetes have become at least as important as infectious diseases. A change in approach to a more proactive style of primary care is needed to allow the contribution of community doctors to be effective. The system of primary care in the Republic of Seychelles is based on the UK model of general practice where recent improvements in education and organization are raising standards. How some of these improvements might be transferred elsewhere is discussed.

Adult↗
PubMed1992

Outpatient clinic referrals and their outcome.

A cohort of 392 patients referred to six outpatient clinics by general practitioners during 1987 with diagnoses of rheumatoid arthritis, osteoarthritis, peripheral vascular disease, psoriasis or eczema, were studied from the time of their first attendance until up to two years later. Six consultant clinics were studied in the three specialties: rheumatology, vascular surgery and dermatology. For each specialty a clinic in both a teaching hospital and a district general hospital were included. The cohort members were predominantly middle-aged or elderly people, with a greater proportion of women, except at the vascular surgery clinic where 65% of patients were men. The 392 patients made a total of 936 visits (median two, range one-eight) during the study period; 91 patients were still attending up to two years after the first visit. Patients referred by their general practitioner for therapy were less likely to be discharged than those referred for other reasons. The principal reason for continuing attendance as perceived by patients, general practitioners and hospital doctors was the necessity for consultant supervision, although agreement was far from complete in individual cases. Junior staff tended to see a higher proportion of patients at follow-up visits than did consultants, and were found to have lower discharge rates than consultants. Analyses of data showed that at the first visit, diagnosis, disease severity and the grade of doctor seeing the patient in the clinic was significantly associated with patient discharge at the P < 0.05 level of significance. Patients considered that their visits had produced improvement in their condition in 38% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The 1990 contract: have patients noticed?

We carried out a questionnaire survey in a Semi-urban General Practice in Renfrewshire to evaluate patients' knowledge and understanding of changes to General Practitioner services six months after implementation of 'The 1990 Contract'. The survey assessed the point prevalence of patients' knowledge in an opportunity sample. A total of 237 patients attending morning surgery during one week in September 1990 were asked to complete a short questionnaire. Despite 38% of respondents declaring they were aware of the changes, only 10% of the respondents showed evidence of understanding of the changes. There was a lack of perceived usefulness of Well Person Checks despite a relatively good understanding of what this involves. Most of the recent changes in General Practice were perceived as being useful or extremely useful to patients after they had been explained. It is suggested that further publicity with careful targeting and explanation is required before the public can make appropriate and effective use of these changes.

Contract Services↗
PubMed1991

The consequences of iron overdose and its treatment with desferrioxamine in pregnancy.

A study was carried out to assess the effect on the outcome of pregnancy of iron overdose and its treatment with desferrioxamine. Sixty-eight cases were drawn from those reported to the United Kingdom National Poisons Information Centre and the Teratology Information Service at Guy's Hospital, London, and follow-up was obtained in 51 of these. Two were subsequently reported not to be pregnant and there were 49 records of pregnant patients who took iron overdoses and where outcome of the pregnancy was known. Twenty-five of these patients were treated with desferrioxamine. In 48 of the 49 patients the dose of iron allegedly taken was known and in 28 (60%) was over 20 mg kg-1, sufficient to put them at risk of toxicity. In the 36 whose serum iron levels were measured, 20 patients had levels in excess of 60 mumol l-1, indicating a risk of moderate or severe toxicity. Of the 49 pregnancies, 43 resulted in live babies, two had spontaneous abortions and there were four elective terminations. Of the live babies, three were premature, two of whom had problems, and there were three other babies with abnormalities. All babies with malformations were associated with overdoses after the first trimester and so the malformations cannot be directly related to the overdose. A total of 25 patients received desferrioxamine of whom two had malformed babies, but the desferrioxamine can be excluded as a cause. There was no correlation between the serum iron levels and the birthweights. In conclusion, iron overdose in pregnancy can be fatal and antidote treatment if appropriate should not be withheld.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1979

Congenital malformations and other reproductive hazards from environmental chemicals.

From a number of disasters which have already occurred throughout the world, it is known that the reproductive process in both animals and man may be severely affected by chemicals. The range of effects that might occur include not only foetal death or malformation, but also effects on the subsequent development, behaviour, intelligence and reproductive capacity of offspring which appear otherwise normal at birth. The special sensitivity of the foetus to some environmental carcinogens is also discussed. Some of the problems in screening for such effects in animals are mentioned along with the need for adequate monitoring programmes to detect reproductive toxicity both from industrial exposure to chemicals and from more general environmental exposure.

Abnormalities, Drug-Induced↗
PubMed1979

Prevention by diazepam of adverse effects of maternal restraint stress on postnatal development and learning in the rat.

Rats on days 12--14 of pregnancy were treated with restraint stress alone (9h daily), restraint stress plus diazepam (1 mg/kg, twice daily), diazepam alone, or left as untreated controls. Postnatal development and behaviour was assessed on a wide-ranging battery of tests. Offspring of mothers subjected to restraint stress alone were significantly retarded on a number of developmental measures including growth, ear-opening, cliff avoidance response, auditory startle response and mid-air righting reflex. When adult these offspring also showed significantly impaired learning ability in a swimming maze. However, the rate of development and learning ability in the restraint plus diazepam or diazepam alone groups was comparable to or slightly advanced of that in untreated controls. It is concluded that concurrent administration of a low dose of the tranquiliser diazepam during restraint stress prevents the adverse postnatal effects of maternal restraint stress.

Animals↗
PubMed1979

Plasma corticosterone responses to stress following chronic oral administration of diazepam in the rat.

The effect of daily, oral administration of diazepam on plasma corticosterone responses to stressors of varying intensity was investigated. In rats exposed to the mild stress of noise, diazepam, 10 mg kg-1 but not 1.0 or 0.1 mg kg-1, reduced plasma corticosterone concentrations by 30% in comparison with controls. However, in rats exposed to the more severe stressors, foot-shock or immobilization, none of these doses of diazepam reduced plasma corticosterone responses. In unstressed rats, diazepam 10 mg kg-1 raised plasma corticosterone concentrations. It is suggested that plasma corticosterone concentrations are not a reliable indicator of the tranquillizing effect of diazepam during stress.

Animals↗
PubMed1978

The outcome of pregnancy in women suffering from migraine.

The reproductive histories of 777 women suffering from migraine were compared with 182 non-migrainous women. The incidence of miscarriage, stillbirth and toxaemia of pregnancy was very similar in both groups and there was no increase in the number of congenital malformations in the children born to women who suffered from migraine compared with the control group or with the national average. It was concluded that women suffering from migraine did not have an increased risk of giving birth to children with deformity and it was unlikely that drugs most commonly used in the treatment of migraine were teratogenic.

Abortion, Spontaneous↗
PubMed1977

Teratogenic activity and metabolism of primidone in the mouse.

Primidone, 25, 50, 100, and 150 mg/kg, was administered orally to mice of the I.C.I. strain from days 6-16 of pregnancy. The fetuses were removed by caesarian section on day 19 and examined by dissection and alizarin staining for gross structural and skeletal defects. The most common abnormalities found were palatal defects with full-length or submucosal clefts. In the controls--25, 50, 100, and 150 mg/kg groups--the incidence of palatal defects was 0/85, 16/84, 18/117, 19/102, and 17/92 fetuses, respectively. Essentially no other major or minor drug-related abnormalities were found. The metabolism of primidone in the pregnant and nonpregnant mouse was also studied and shown to be similar to that previously reported in the rat. Peak blood levels of primidone were obtained after 1 hr; they fell to very low levels by 6 hr. and were completely cleared by 24 hr. The metabolites produced, PEMA and phenobarbital, are similar to those produced in other species including man. Blood levels following single oral doses of 5 to 150 mg/kg were dose-related so that no explanation for the lack of dose-related teratogenic effect was found.

Animals↗
PubMed1977

The metabolism of primidone in non-pregnant and 14-day pregnant mice.

1. Non-pregnant and day-14 pregnant mice treated with a single dose of primidone (5 to 150 mg/kg) by gastric intubation were bled at 1 and 4 h after dosage, and the plasma analysed for primidone, phenobarbitone and phenylethylmalondiamide (PEMA) by g.l.c. 2. Marked differences in the rate of metabolism were observed between the non-pregnant and day-14 pregnant mouse. Plasma levels of primidone and PEMA, but not phenobarbitone, were much lower in the day-14 pregnant mouse than in the non-pregnant animal.

Animals↗
PubMed1977

Plasma level studies of primidone and its metabolites in the mouse at various stages of pregnancy.

1. Mice were treated with a teratogenic dose of primidone (100 mg/kg) by gastric intubation at three different times during pregnancy, viz. days 6-14, days 12-14 on day 14 only. Blood samples were taken on day 14 at 1, 4, 8 and 24 h after dosage. Primidone and its metabolites phenylethylmalondiamide (PEMA), and phenobarbitone, were assayed by g.l.c. 2. There was no accumulation of the parent compound or the metabolites after repeated administration of primidone; each of the substances was cleared from the plasma within 24 h. 3. The rate of metabolism of primidone increased with prolonged treatment. The peak concentration of the metabolites was higher in the two multiple-dose groups than in the single dose group. 4. The concentration of PEMA exceeded that of primidone between 3-8 h and then began to decrease in the multiple-dose groups, a similar pattern was established for phenobarbitone also, although the concentrations were lower than those of PEMA.

Animals↗
PubMed1975

The relation between maternal restraint and food deprivation, plasma corticosterone, and induction of cleft palate in the offspring of mice.

The blood level of corticosterone was measured in mice following the injection on day 14 of pregnancy of a dose of corticosterone sufficient to cause a low frequency of cleft palate in the fetuses. This was compared with the blood levels present during maternal restraint and food deprivation that produced a similar frequency of cleft palate. The mean blood level over the 24 h following injection of corticosterone was 660 mug/100 ml, and during a similar period of restraint was 485 mug/100 ml. Other mice were subjected either to restraint or food deprivation for 24 h beginning day 14 of pregnancy, the plasma corticosterone levels measured during that time, and the frequency of cleft palate in late fetuses compared with the individual plasma corticosterone levels during treatment. There was a significant (P less than 0.025) correlation between high maternal corticosteroid levels and the frequency of cleft palate in the offspring of the restrained mice but not in the food-deprived animals. It is suggested that in some stressed mice endogenous plasma corticosterone can reach levels sufficient to account for the development of cleft palate.

Animals↗