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From day 6 to day 20 of pregnancy, rats were treated with caffeine in a total daily dose of 10 or 100 mg/kg by gavage, either as a single bolus dose or as four divided doses given at 3-hr intervals throughout the day. Controls were given distilled water at the same times. Maternal body weight and food and water consumption were reduced in the two groups receiving a total of 100 mg caffeine/kg/day and in the group given 2.5 mg/kg four times daily. Dose-related decreases in foetal weight, placental weight and crown-rump length and dose-related retardation of skeletal ossification were observed. Major foetal abnormalities, mainly ectrodactyly, were seen only in the group given 100 mg caffeine/kg in a single daily dose.

Progestogens and oestrogens used to maintain pregnancy in cases of threatened abortion could have side-effects on the mother or fetus. The difficulties in interpreting epidemiological studies on the effects of sex hormones on pregnancy are discussed in relation to the combination of hormones employed, their purpose, time of usage and dosage.

The multiplication of M. tuberculosis, var. bovis inoculated into the cornea of mice was studied by staining the whole cornea at various stages after inoculation. Four groups of animals were studied: untreated animals, animals treated with cortisone, animals previously immunized with the same bovine strain, and immunized animals treated with cortisone.In the untreated immunized group little or no multiplication occurred. In the other three groups multiplication did occur and was about the same for the first week after inoculation. After this stage, cortisone-treated animals, whether previously immunized or not, showed increased multiplication and massive cord formation, as compared with untreated animals in which little further multiplication was seen. The cortisone treatment had thus completely suppressed immunity. The significance of these results is discussed.

1. When 5-hydroxytryptamine creatinine sulphate is injected subcutaneously in a dose of 2 mg into mice during the second half of pregnancy, the foetuses die within 1 hr. The mode of action of 5-hydroxytryptamine (5-HT) in producing this effect has been studied.2. It has been demonstrated that this is not a direct toxic effect of 5-HT. Very little passes through the placenta into the foetus, and after the injection of much larger amounts directly into the foetus no lethal effect was observed.3. It was shown that 5-HT had little effect on uterine motility in vivo, and that the much larger contractions produced by oxytocin did not produce any effect on the foetus.4. No constriction of the umbilical vessels was produced by 5-HT injected into the mother, nor did the local application of 5-HT to the cord produce any effect.5. The administration of 5-HT to the mother markedly reduced the passage of (22)Na from the maternal circulation into the placenta and foetus. This was accompanied by a reduction in the blood supply to the placenta from a normal value of 87 mul./min/g to 4 mug/min/g.6. It is suggested that the effect of 5-HT in producing foetal death is a consequence of the reduction in the transfer function of the placenta.

The subcutaneous injection of a single dose of 5-hydroxytryptamine into pregnant mice produced a large number of fetal abnormalities, mostly of the eyes, limbs, and tail; the skull and central nervous system were also sometimes affected. These effects could result from the action of the drug on placental function and blood supply.

Mice were infected intracorneally with Mycobacterium tuberculosis var. bovis and the infection allowed to develop for a period of 2 weeks. At this stage the animals were divided into two main groups; one received no treatment, the other was treated with large doses of isoniazid (3.0 mg./mouse/day). The effect of treatment on the primary lesion, the viability of the bacilli, the systemic spread of infection, and the production of immunity were observed. Treatment was continued for 11 months, after which the animals were observed for another 8 months. Within a few days of starting isoniazid treatment the primary lesion stopped increasing in size, regressed slightly and stabilized at a size of about one-third of that of the controls. There was little evidence of any clearing of the bacilli from the lesions; they remained strongly acid-fast and morphologically normal for many months after infection, although by 13 months about half of the organisms in both groups had become very granular. The evidence suggests that in control and treated animals the bacilli in the cornea had usually all died within 8 months after infection. In two treated corneas, living virulent bacilli were demonstrated 15 months after inoculation. In the untreated animals, the disease spread systemically to involve the lungs, liver, and spleen, and by one year after inoculation the systemic tuberculous infection was very heavy, though not enough to kill the animals. The lesions in these animals contained many acid-fast bacilli. In the treated group, systemic spread of infection as judged by the development of small macroscopic lung foci was slight; acid-fast bacilli were found in only one animal. In the treated animals, practically no immunity could be detected 5 months after inoculation and had not reappeared 2 months after cessation of treatment; in the untreated animals immunity was present.