Immunosuppressive and Monooxygenase Induction Activities of Highly Chlorinated Diphenyl Ether Congeners in C57BL/6 and DBA/2 Mice

The dose-response effects of 2,2',3,3',4,5,5',6,6'–,2,2',3,3',4,4',5,6,6'-and2,2',3,3',4,4',5,5',6-nonachlorodiphenyl ether (non-aCDE) anddecachlorodiphenyl ether (decaCDE) on the splenic plaque-formingcell (PFC) response to sheep red blood cells (SRBCs) and theinduction of hepatic microsomal ethoxyresorufin O-deethylase(EROD) activity was determined in aryl hydrocarbon (Ah)-responsiveC57BL/6 and less Ah-responsive DBA/2 mice. All the congenersexhibited immunotoxicity at doses between 2.5 and 10 µmol/kgin C57BL/6 mice whereas in DBA/2 mice doses25 µmol/kgwere required to cause inhibition of the PFC response to SRBCs.The results also showed that the nonaCDE isomers and decaCDEwere more active as inducers of hepatic EROD activity in C57BL/6than DBA/2 mice; however, there was not a correlation betweenthe induced EROD activity and the CYP1A1 and CYP1A2 mRNA levelsin the C57BL/6 mice. These data suggested that the immunotoxicityof these compounds was mediated through the Ah receptor. However,the results showed that the immunotoxicity of the nonaCDE isomersand decaCDE was unexpectedly high compared to that of lowerchlorinated diphenyl ethers and there were no apparent structure-activityrelationships among the higher chlorinated congeners. This suggeststhat some of the immunosuppressive effects observed for thenonaCDE isomers and decaCDE may be Ah receptor-independent.     

FERTILITY AFTER CHILDBIRTH: CHANGES IN SERUM GONADOTROPHIN LEVELS IN BOTTLE AND BREAST FEEDING WOMEN

Changes in basal serum gonadotrophin levels during the resumption of ovarian activity post partum have been studied longitudinally in breast and bottle feeding mothers. On the basis of urinary steroid levels, ovarian activity was classified as showing complete suppression, follicular activity only, deficient luteal phases or normal menstrual cycles. Complete suppression of ovarian activity during lactation was associated with normal levels of FSH but low levels of LH. The resumption of follicular development was not accompanied by any increase in levels of either LH or FSH when compared with the phase of complete suppression and this pattern persisted during menstrual cycles characterized by deficient luteal phase progesterone secretion. Basal LH levels did not rise to normal levels during lactation until the resumption of normal ovulatory cycles. FSH secretion remained at a level comparable with the follicular phase of normal ovulatory cycles throughout the post partum period. In mothers who did not breast feed, LH levels rose more rapidly than in breast feeding mothers and had returned to within normal limits by three weeks post partum. At 4 weeks post partum FSH levels were lower in bottle feeding mothers than in breast feeders probably in response to the early rise in oestrogen levels among bottle feeders. These results suggest that decreased LH but not FSH secretion may be important in maintaining infertility associated with breast feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

PREOPERATIVE CIMETIDINE DOES NOT PREVENT SUBCLINICAL HALOTHANE HEPATOTOXICITY IN MAN

To assess the influence of pretreatment with cimetidine on changesin hepatocellular integrity after halothane anaesthesia, 53patients were allocated randomly to receive either cimetidine1600 mg orally or placebo tablets before anaesthesia. Plasmaconcentrations of glutathione S-transferase (GST) were measuredas an index of hepatic damage. Data from 45 patients were availablefor analysis. Plasma GST concentration increased significantly3 h after induction of anaesthesia in both groups (P < 0.01,both groups) and at 6 h in the cimetidine groups (P < 0.05).Pretreatment with cimetidine did not influence the magnitudeof increase in GST concentration. There was no difference betweenthe groups in the frequency of abnormal GST concentrations atany time. Cimetidine does not appear to prevent release of GSTfrom the liver by halothane anaesthesia in man.     

RETURN OF OVARIAN FUNCTION FOLLOWING SPONTANEOUS ABORTION

Assays of first morning urine samples for oestrone-3-glucuronide, LH and pregnanediol-3-glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post-partum (range 13-103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P less than 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68.8 IU/g C; P less than 0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P less than 0.02). The mean luteal phase length of 12.9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P less than 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.     

Fetal growth achievement and neurodevelopmental disability

Summary. To investigate the role played by chronic intrauterine insult in the genesis of neurodevelopmental disability (NDD), three analyses have been applied to a case-controlled study which compared a population of children with NDD with a control group of normally developed children. In the first analysis, average birthweight in children with NDD was 3138 g (SD 592) which was significantly less than in normally developed children, 3280 g (SD 491) ( P <0·0005). After correction for confounding factors, birthweight-for-gestation (Z score) remained lower in children with NDD (-0·42) than normal children (-0·21) ( P <0·0025). In the second analysis the fetal growth achievement of children, who had NDD after the prenatal complications, severe hypertension, unclassified antepartum haemorrhage and preterm uterine activity, was significantly less ( Z score, -0·76) than children who were normally developed after the same maternal prenatal complications ( Z score, -0·37) ( P <0·03). In the third analysis, a risk analysis to assess the relative importance of fetal growth achievement and prenatal complications in the genesis of NDD suggested that the latter was the dominant factor. These data are consistent with the hypothesis that prenatal complications, severe enough to retard fetal growth, can compromise fetal brain development and make an important contribution to NDD.     

Measurement of Stress as it Affects the Work of the General Practitioner

Porter A M D (Department of General Practice, University ofEdinburgh, 20 West Richmond Street, Edinburgh EH8 9DX, Scotland),Howie J G R and Levinson A. Measurement of stress as it affectsthe work of the general practitioner.Family Practice 1985; 2:136–146. This paper describes a preliminary study which collected informationon the work of 18 general practitioners during a total of 52days, and also recorded their feelings of pressure and stressfrom hour to hour throughout each day. The instruments usedto record information on day-to-day activities and to measureself-perceived pressure, stress and arousal are described. Thereliability and validity of the methods used are discussed,and some suggestions made for future development. A few preliminaryfindings are presented.