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Biomedical subjects

F M Sullivan

Publications and source records attributed to F M Sullivan.

At least 73 records · Page 4Linked to original sources
PubMed1983

Predicting insulin requirements for a portable insulin pump using the Biostator. Evidence for reversible insulin resistance in poorly controlled type I diabetics.

Glycemic control was achieved in 14 patients with insulin-dependent diabetes mellitus (IDDM) by 36-48-h treatment with a recently marketed clinical model, Biostator glucose controller (Life Science Instruments, Miles Laboratories, Elkhart, Indiana). Control was maintained by continuous subcutaneous insulin infusion with a portable pump, programmed using infusion profiles from the Biostator. Control of glycemic excursion with the Biostator was variable among patients. This control, reflected by the M-value or a blood glucose index (mean of pre-, peak, and 2-h postmeal levels for four meals) of each patient, correlated directly with their prior glycemic control, as assessed by hemoglobin A1c (HbA1c) level (r = 0.66, P less than 0.01 and r = 0.82, P less than 0.005, for M-value and blood glucose index, respectively). Total insulin infused by the Biostator/24 h overpredicted the subcutaneous infusion dose required on day 2 of pump treatment (183 +/- 11%, P less 0.001). Therefore, these data were not used to program the portable pump. Instead, total insulin dose was estimated using a dietary glucose/insulin (G/I) ratio. This ratio, derived from dietary total available glucose, urine glucose, and insulin dose/24 h during depot insulin treatment, accurately estimated total insulin for pump infusion (97 +/- 4%). The basal infusion rate of the Biostator between 2400 and 0600 h also exceeded the subcutaneous infusion requirement and was reduced to 40% for the initial pump basal rate. The remainder of the insulin (total minus basal) was distributed as premeal boluses according to the Biostator infusion profile for meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Studies on the teratogenic effects of different oral preparations of caffeine in mice.

Caffeine in doses up to 250 mg/kg per day in drinking water or up to 150 mg/kg per day in sustained release pellets was administered to pregnant mice. Apart from a low incidence of cleft palate, in the 50 mg/kg and 150 mg/kg caffeine pellet groups no gross abnormalities were observed which were attributable to caffeine treatment. The most important effect observed was a reduction in fetal weight. Retarded ossification particularly of the supraoccipital bones was observed in fetuses when caffeine (150 mg/kg) was administered in drinking water but not when the same dose was given as a sustained release pellet. Analysis of caffeine blood level data showed that the total exposure from the pellets was greater than from the drinking water. It would thus appear that the effect on the supraoccipital bones is an indirect one mediated through reduced food and water intake of the dams when caffeine is administered in drinking water.

Animals↗
PubMed1981

Effect of prenatal phenytoin administration on postnatal development of the rat: a behavioral teratology study.

Adult pregnant Wistar rats were treated with phenytoin (100 Mg/kg) orally from day 7 to 19 of pregnancy, and a control group was pair-fed during the whole treatment period. Within 24 hours after parturition , the offspring were culled to six to eight per litter and reared by fostering or cross-fostering. The physical and behavioral development of the offspring was observe up to 90 days of age. There was a reduced survival of the offspring and a reduction in body weight which persisted to the end of the experiment, though both of these effects could be reduced by cross-fostering. Certain neurological defects were also seen in the prenatal phenytoin group. For example, there was a delay of up to 15 days in the development of the dynamic righting reflex, a decrease in ability of offspring to stay on a rotating rod, and a decrease in ability to walk along elevated parallel rods. There seemed also to be some loss of cliff avoidance. However, there was no change in the development of crawling and walking activities at 9-21 days of age, and no important changes were observed in a head dipping test or in a conditioned avoidance test at 26-34 days. There was a significant decrease in brain weight of the treated group at age 3 days which remained significantly lower than the controls even at 90 days, but no change in the brain/body weight ratio. There was no difference in cerebellar DNA content.

Animals↗
PubMed1981

Acute studies to investigate the mechanism of action of caffeine as a teratogen in mice.

1 In Charles River CD1 mice, a single dose of 100 mg kg-1 caffeine injected intraperitoneally on day 14 of pregnancy caused a low incidence of cleft palate in the fetuses. 2 Single oral doses of caffeine of 200 and 300 mg kg-1 but not 100 mg kg-1 on day 14, caused cleft palate in some of the fetuses, but was clearly toxic to the dams. 3 Oral doses of caffeine up to 300 mg kg-1 on day 14 of pregnancy did not reduce utero-placental blood flow, placental transfer function, or amniotic fluid volume. 4 An oral dose of 100 mg kg-1 caffeine induced a marked stimulation of adrenocortical secretion producing plasma corticosterone levels of 1248 +/- 129 microgram per 100 ml by 2 h and with elevated levels persisting more than 8 h. 5 It is suggested that the elevated plasma corticosterone is the cause of the cleft palate induced in mice by caffeine. Since corticosterone is a known cleft palate inducer in mice but not in man these results do not predict a hazard from normal caffeine consumption in man.

Abnormalities, Drug-Induced↗
PubMed1980

Effect of prenatal phenytoin administration on brain tryptophan metabolism of rat offspring during the preweaning period.

Serum 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations in control rat offspring increased progressively during the preweaning period reaching adult values by day 21. It has been shown the prenatal phenytoin administration (100 mg kg-1 orally, days 7-19 of pregnancy) increased serum tryptophan and brain tryptophan, 5-HT and 5-HIAA of rat offspring at 3 days of age but not at 4, 15 or 21 days of age. The effect of prenatal phenytoin administration on the offspring at 3 days of age was not observed when these pups were cross-fostered to control mothers at 2 days of age suggesting that the alteration in rain tryptophan metabolism during the development of tryptaminergic neurons in rat offspring, as a result of prenatal phenytoin administration is mediated through changes in lactation or nursing ability of the mothers. It is important that such non-specific factors are controlled when studying the effect of prenatally administered drugs on neonatal brain transmitter concentrations.

Animals↗
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↗