Identifying homologous anatomical landmarks on reconstructed magnetic resonance images of the human cerebral cortical surface

Guided by a review of the anatomical literature, 36 sulci on the human cerebral cortical surface were designated as homologous. These sulci were assessed for visibility on 3-dimensional images reconstructed from magnetic resonance imaging scans of the brains of 20 normal volunteers by 2 independent observers. Those sulci that were found to be reproducibly identifiable were used to define 24 landmarks around the cortical surface. The interobserver and intraobserver variabilities of measurement of the 24 landmarks were calculated. These reliably reproducible landmarks can be used for detailed morphometric analysis, and may prove helpful in the analysis of suspected cerebral cortical structured abnormalities in patients with such conditions as epilepsy.     

The Developmental Toxicity of Diethylene Glycol Dimethyl Ether in Mice

The Developmental Toxicity of Diethylene Glycol Dimethyl Etherin Mice. PRICE, C. J., KIMMEL, C. A., GEORGE, J. D., AND MARR,M. C. (1987). Fundam. Appl. Toxicol. 8, 115–126. Diethyleneglycol dimethyl ether (diEGdiME) is structurally related toseveral compounds which produce reproductive and developmentaltoxicity, including teratogenicity in laboratory animals. Inthe present study, diEGdiME (0, 62.5, 125, 250, or 500 mg/kg/day)was administered by gavage in distilled water to timed-pregnantCD-1 mice during major organogenesis [gestational days (gd)6–15]. Clinical status of treated females was monitoreddaily during treatment and on gd 17. At sacrifice (gd 17), pregnancywas confirmed by uterine examination for 20–24 dams pergroup; each live fetus was examined for external, visceral,and skeletal malformations. No maternal deaths, morbidity, ortreatment-related clinical signs were observed. Reduced maternalweight gain during treatment at 250 mg/kg/day was primarilyattributed to compromised pregnancy status resulting in reducedgravid uterine weight. Maternal weight gain during gestationcorrected for gravid uterine weight, and relative liver weight(% body weight) were not affected. Average fetal body weight/litterwas significantly reduced at 125 mg/kg/day. The percentageof postimplantation loss/litter (5, 8, 7, 12, and 50% for controlthrough high dose) and the percentage of malformed live fetuses/litter(0.4, 0, 2, 24, and 96%) were significantly increased at 250mg/kg/day. Developmental defects involved primarily the neuraltube, limbs and digits, craniofacial structures, abdominal wall,cardiovascular system, urogenital organs, and both the axialand appendicular skeleton. In summary, oral administration ofdiEGdiME during major organogenesis did not produce any distinctivesigns of maternal toxicity, but did produce selective and profoundadverse effects upon fetal growth, viability, and morphologicaldevelopment at 125 mg/kg/day.     

The Developmental Toxicity of Ethylene Glycol Diethyl Ether in Mice and Rabbits

Timed-pregnant CD-1 outbred Albino Swiss mice and New ZealandWhite rabbits were dosed by gavage with ethylene glycol diethylether (EGdiEE) in distilled water during major organogenesis.Mice were dosed on Gestational Days (gd) 6 through 15 (0, 50,150, 500, or 1000 mg/kg/day) and rabbits on gd 6 through 19(0, 25, 50, or 100 mg/kg/day). Maternal clinical status wasmonitored daily during treatment. At termination (gd 17, mice;gd 30, rabbits), confirmed-pregnant females (22–24 pergroup, mice; 26–32 per group, rabbits) were evaluatedfor clinical status and gestational outcome; each live fetuswas examined for external, visceral, and skeletal malformations.In mice, no maternal mortality was observed, but maternal bodyweight gain during gestation and treatment, and at terminationwas reduced at 1000 mg/kg/day. The reduction of maternal bodyweight gain during gestation was secondary to embryo/fetal toxicity,i.e., reduced gravid uterine weight as a consequence of decreasedlitter size and fetal weight. The no-observed adverse effectlevel (NOAEL) for developmental toxicity was 50 mg/kg/day. At150 mg/kg/day the number of litters of mice with malformed fetuseswas increased. At 500 mg/kg/day fetal body weight was reduced,and malformation incidence was significantly increased. Exencephalyand fused ribs were observed most often. In rabbits, maternalbody weight was unaffected by treatment even though 6% maternalmortality was observed at 100 mg/kg/day. The developmental NOAELwas 25 mg/kg/day. Malformations were increased at 50 mg/kg/day,short tail, small spleen, fused sternebrae, and fused rib cartilagewere observed most often. In summary, oral administration ofEGdiEE to mice and rabbits during organogenesis produced profoundadverse developmental effects even in the absence of significantmaternal toxicity. Developmental effects in rabbits were morevaried.     

Murine malaria: dissociation of natural killer (NK) cell activity and resistance to Plasmodium chabaudi

Striking differences in the resistance to P. chabaudi infection among different inbred mouse strains have previously been correlated with the level of both the spontaneous and the infection-induced enhanced level of NK cell activity. We have examined this putative correlation in individual animals of backcross progeny derived from A/J (malaria-susceptible, low NK cell activity) and B10.A (malaria-resistant, high NK cell activity) progenitors. We have found that NK cell activity and resistance to malaria segregated independently. Furthermore, C57BL/6-bg/bg mice which are deficient in NK cell activity were found to be as resistant to malaria as their heterozygous C57BL/6-bg/+siblings. We conclude that low NK cell activity, characteristic of A/J strain mice, is not a sufficient determinant of the exquisite susceptibility of these animals to infection with Plasmodium chabaudi.     

Factors affecting the uptake of screening for neural tube defect

Summary. A questionnaire concerning pregnant women's knowledge of, and attitudes to, serum alpha fetoprotein (AFP) screening for spina bifida was sent to all pregnant women receiving a health education leaflet on AFP screening who booked at the Birmingham Maternity Hospital in the first quarter of 1984. The majority said that they would accept the test, and subsequently did so. This suggests that low uptake of the test is not a result of patients' resistance, and the results indicated that the provision of early information about the test is likely to improve uptake and decrease anxiety. With the increasing clinical usefulness of the AFP test, routine screening of pregnant women with an 'opt-out' system is becoming clinically desirable, and the survey suggests that it would be acceptable to the patients.     

Dr J. Ayrton Paris and Cancer of the Scrotum: 'Honour the Physician with the Honour due unto Him'

Dr Paris's account of cancer of the scrotum caused by arsenicis not generally believed. From a study of the relevant litratureof the period we consider that his account is true. Dr Carole M. Bishop, Employment Medical Adviser, Health and Safety Executive, 3rd Floor Grove House, Grove Place, Swansea SA1 5DH.     

The Developmental Toxicity of Orally Administered Oxytetracycline in Rats and Mice

The Developmental Toxicity of Orally Administered Oxytetracyclinein Rats and Mice. MORRISSEY, R.E., TYL, R.W., PRICE, C.J., LEDOUX,T.A., REEL, J.R., PASCHKE, L.L., MARR, M.C, AND KJMMEL, C.A.(1986). Fundam. Appl. Toxicol. 7, 434-443. Timed-pregnant CDrats and CD-1 mice were dosed by gavage with oxytetracyclinehydrochloride (OXT) in corn oil on gestational days (gd) 6-15(0, 1200, 1350, or 1500 mg/kg/day for rats; 0, 1325, 1670, or2100 mg/kg/day for mice). Deaths among treated females occurredin a dose-related manner in all OXT dose groups (2-7%, mice;5-24%, rats), but no maternal deaths occurred in the vehiclecontrol groups. Significant dose-related decreases in maternalweight gain during treatment, as well as for corrected gestationalweight gain (i.e., maternal gestational weight gain minus graviduterine weight), were observed at all doses in rats but notin mice. Gravid uterine weight was reduced in a dose-relatedmanner only in mice, with the high-dose group significantlyreduced compared to the control group. At termination (gd 20,rats; gd 17, mice), the status of uterine implantation siteswas recorded and live fetuses were weighed. Fetuses were examinedfor external, visceral, and skeletal abnormalities. There wereno significant effects of OXT in either species on the incidenceof postimplantation loss (resorptions plus dead fetuses) ormalformations. In both species, there was a significant trendtoward reduced fetal body weight, and each group of rats receivingOXT was significantly reduced compared to the control group.Administration of OXT during organogenesis at doses exceedingthe therapeutic range for humans produced maternal and fetaltoxicity, but did not produce any treatment-related increasein malformations.     

Development of a parent-report computer-adaptive test to assess physical functioning in children with cerebral palsy I: lower-extremity and mobility skills

The objective of this project was to develop computer-adaptive tests (CATs) using parent reports of physical function in children and adolescents with cerebral palsy (CP). The specific aims of this study were to (1) examine the psychometric properties of an item bank of lower-extremity and mobility skills for children with CP; (2) evaluate a CAT using this item bank; (3) examine the concurrent validity of the CAT with the Pediatric Outcomes Data Collection Instrument (PODCI) and the Functional Assessment Questionnaire (FAQ); and (4) establish the discriminant validity of simulated CATs with Gross Motor Function Classification System (GMFCS) levels and CP type (diplegia, hemiplegia, or quadriplegia). Parents ( n =190) of children and adolescents with spastic diplegic (48%), hemiplegic (22%), or quadriplegic (30%) CP consisting of 108 males and 82 females with a mean age of 10 years 7 months (SD 4y 1mo, range 2–21y) and in GMFCS levels I to V participated in item pool calibration and completed the PODCI and FAQ. Confirmatory factor analyses supported a unidimensional model for the 45 basic lower-extremity and mobility items. Simulated CATs of 5, 10, and 15 items demonstrated excellent accuracy (intraclass correlation coefficients [ICCs] >0.91) with the full item bank and had high correlations with PODCI transfers and mobility (ICC = 0.86) and FAQ scores (ICC = 0.77). All CATs discriminated among GMFCS levels and CP type. The lower-extremity and mobility skills item bank and simulated CATs demonstrated excellent performance over a wide span of ages and severity levels.     

Psychological symptoms, psychiatric disorder and alcohol dependence amongst men and women attending a community-based voluntary agency and an Alcohol Treatment Unit

One-fifth of clients attending a community-based voluntary agency presented for treatment with an alcohol problem complicated by affective disorder, phobic anxiety or personality disorder. A matched sample of patients recruited from an Alcohol Treatment Unit, and assessed using the same stringent clinical criteria, had similar levels of formal psychiatric disorder, except for a small group of women. One quarter of women in this group were phobic with some overlap of affective disorder. Rates of psychological symptoms as opposed to psychiatric disorder were high in both samples and appeared to be associated with severity of dependence on alcohol. No sex differences were apparent in the rates of psychological symptoms. The practical as well as theoretical implications of these findings were discussed.     

HLA Sharing and Fertility in Hutterite Couples: Evidence for Prenatal Selection Against Compatible Fetuses

ABSTRACT: Antigenic differences between mother and fetus (i.e., blood group incompatibilities) were traditionally considered deleterious for viviparous reproduction. Recently, evidence has accumulated suggesting that maternal response to paternally derived fetal antigens, paradoxically, may facilitate maintenance of pregnancy. Thus, fetuses whose paternally derived antigens do not differ from maternal antigens (i.e., histocompatible pregnancies) may be at a selective disadvantage during pregnancy. Parents sharing histocompatibility antigens (i.e., HLA) may produce compatible fetuses and show overall reduced fertility. Indeed, increased HLA sharing has been reported in some couples experiencing repetitive spontaneous abortion. However, the effects of HLA sharing in couples not selected because of previous pregnancy losses have not been assessed. To elucidate the reproductive effects of maternal-fetal histocompatibility, we initiated prospective population-based studies of parental HLA sharing and reproductive outcome in the Hutterites, a population isolate that lives communally and proscribes contraception. The relationship between HLA-A, -B, and -DR sharing and reproductive outcome was examined in 111 Hutterite couples. Intervals from marriage to each birth were no longer among couples sharing antigens; differences were significant at the second birth and remained significant through the sixth birth (P < .05). When the effects of sharing at individual loci were examined, HLA-DR was the only individual locus that was a significant predictor of birth interval length (P = .025). Completed family sizes were 6.5 and 9.0 among couples sharing and not sharing HLA-DR, respectively (P = .082, 2-tailed). However, recognized fetal loss rates did not differ among couples sharing and not sharing antigens. We interpret these results as evidence for reduced fertility among some Hutterite couples sharing HLA, as a result of maternal-fetal compatibility for HLA-DR, per se, or alleles at an undefined, HLA-DR-linked locus. Our data further suggest that longer intervals associated with HLA-DR sharing may result from losses occurring early in gestation, before Hutterites would recognize pregnancy.