James Willocks and the innovation of fetal cephalometry.

James Willocks (1928-2004), a Glasgow obstetrician, was an important pioneer of obstetric ultrasound and the originator of the first clinically useful technique of fetal cephalometry. He collaborated with Tom Duggan, an engineer, who designed and built an electronic cephalometer to be used in conjunction with a Kelvin Hughes industrial flaw detector. Working in the Royal Maternity Hospital, Willocks was able to measure the biparietal diameter to an accuracy of better than 2mm. This major innovation enabled fetal growth in the third trimester to be accurately charted and thus greatly improved the detection of placental insufficiency, as well as the management of antepartum haemorrhage, hypertension and other complications of late pregnancy.

Childhood abuse and lifetime psychopathology in a community sample.

OBJECTIVE: The authors assessed lifetime psychopathology in a general population sample and compared the rates of five psychiatric disorder categories between those who reported a childhood history of either physical or sexual abuse and those who did not. METHOD: A modified version of the Composite International Diagnostic Interview and a self-completed questionnaire on child abuse were administered to a probability sample (N=7,016) of Ontario residents 15 to 64 years of age. RESULTS: Those reporting a history of childhood physical abuse had significantly higher lifetime rates of anxiety disorders, alcohol abuse/dependence, and antisocial behavior and were more likely to have one or more disorders than were those without such a history. Women, but not men, with a history of physical abuse had significantly higher lifetime rates of major depression and illicit drug abuse/dependence than did women with no such history. A history of childhood sexual abuse was also associated with higher rates of all disorders considered in women. In men, the prevalence of disorders tended to be higher among those who reported exposure to sexual abuse, but only the associations with alcohol abuse/dependence and the category of one or more disorders reached statistical significance. The relationship between a childhood history of physical abuse and lifetime psychopathology varied significantly by gender for all categories except for anxiety disorders. Although not statistically significant, a similar relationship was seen between childhood history of sexual abuse and lifetime psychopathology. CONCLUSIONS: A history of abuse in childhood increases the likelihood of lifetime psychopathology; this association appears stronger for women than men.

Bone cells and matrices in orthopedic tissue engineering.

The ability to harvest and manipulate osteogenic cells gives clinicians the opportunity to harness capacity of these cells for targeted regeneration and repair of skeletal tissues. Further opportunities to optimize use of cells exist in the ability to design specialized matrices that act as conductive scaffolds. Realization of the full potential of engineered matrix materials and cell-matrix composites can provide new solutions to many clinical problems in skeletal reconstruction.

Slapping and spanking in childhood and its association with lifetime prevalence of psychiatric disorders in a general population sample.

BACKGROUND: Little information is available in Canada about the prevalence of and outcomes associated with a history of slapping and spanking in childhood. The objectives of this study were to estimate the prevalence of a history of slapping or spanking in a general population sample and to assess the relation between such a history and the lifetime prevalence of psychiatric disorders. METHODS: In this general population survey, a probability sample of 9953 residents of Ontario aged 15 years and older who participated in the Ontario Health Supplement was used to examine the prevalence of a history of slapping and spanking. A subgroup of this sample (n = 4888), which comprised people aged 15 to 64 years who did not report a history of physical or sexual abuse during childhood, was used to assess the relation between a history of slapping or spanking and the lifetime prevalence of 4 categories of psychiatric disorder. The measures included a self-administered questionnaire with a question about frequency of slapping and spanking during childhood, as well as an interviewer-administered questionnaire to measure psychiatric disorder. RESULTS: The majority of respondents indicated that they had been slapped or spanked, or both, by an adult during childhood "sometimes" (33.4%) or "rarely" (40.9%); 5.5% reported that this occurred "often." The remainder (20.2%) reported "never" experiencing these behaviours. Among the respondents without a history of physical or sexual abuse during childhood, those who reported being slapped or spanked "often" or "sometimes" had significantly higher lifetime rates of anxiety disorders (adjusted odds ratio [OR] 1.43, 95% confidence interval [CI] 1.04-1.96), alcohol abuse or dependence (adjusted OR 2.02, 95% CI 1.27-3.21) and one or more externalizing problems (adjusted OR 2.08, 95% CI 1.36-3.16), compared with those who reported "never" being slapped or spanked. There was also an association between a history of slapping or spanking and major depression, but it was not statistically significant (adjusted OR 1.64, 95% CI 0.96-2.80). INTERPRETATION: There appears to be a linear association between the frequency of slapping and spanking during childhood and a lifetime prevalence of anxiety disorder, alcohol abuse or dependence and externalizing problems.

Forty years of obstetric ultrasound 1957-1997: from A-scope to three dimensions.

In this article, we record the history of obstetric ultrasound as it developed worldwide in the second half of the twentieth century. The technological advances during this period saw the evolution of equipment from the original adapted metal flaw detectors producing a simple A-scan to the modern, purpose built, real-time colour flow machines with three-dimensional capability (Fig. 1). Clinically, ultrasound began as a research tool, but the poor quality of the images led to the ridicule of many of the early investigators. However, because of their perseverance, ultrasound developed into an imaging modality providing immense diagnostic capabilities and facilitating with precision many invasive procedures, diagnostic and therapeutic, both of which have made significant contributions to patient care. In this history, we recall the people, the personalities, and the problems they encountered during the development of ultrasound and how these problems were resolved, so that ultrasound now is available for use in the care of pregnant women throughout the developed world.

First-trimester growth and the risk of low birth weight.

BACKGROUND: Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS: From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS: A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS: Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.

Age-dependent accumulation of advanced glycation end-products in adult Drosophila melanogaster.

Advanced glycation end-product(s) (AGE) are formed in biological systems when reducing sugars react with amino groups on proteins. Long-lived proteins such as collagen and lens crystallins are known to be susceptible to AGE modification and may play a major role in the development of diabetes and other age-related pathologies. It has been previously suggested that AGE formation might affect the lifespan of experimental animals. Our study is the first to examine the effect of AGE accumulation on the life span of an organism, Drosophila melanogaster. We found that Drosophila melanogaster maintained at 24 degrees C accumulate significant AGE over their lifespan. Young flies (10 days old) had 44% less AGE than senescent flies (75 days old). We were able to reduce AGE accumulation in Drosophila melanogaster by raising the flies on a medium containing a known AGE inhibitor, aminoguanidine HCl. Reduction of AGE in flies failed to increase their mean lifespan, and high concentrations (40 mM) reduced the mean life span, which suggests that aminoguanidine is toxic at levels near those required for inhibition of AGE formation. However, the common fruit fly, Drosophila melanogaster, provides a simple model system to study the age-dependent accumulation of glycated proteins and their inhibition by novel compounds.

Monoclonal antibody against adult marrow-derived mesenchymal stem cells recognizes developing vasculature in embryonic human skin.

We have described previously a monoclonal antibody (SH2) that specifically recognizes undifferentiated mesenchymal progenitor cells isolated from adult human bone marrow. These cells, which we operationally refer to as mesenchymal stem cells, have the capacity to differentiate and form distinct mesenchymal tissues such as bone and cartilage when the isolated cells are placed in the appropriate in vivo or in vitro environment. We report here the partial biochemical characterization of the antigen recognized by the SH2 antibody. Metabolically radiolabelled adult marrow-derived mesenchymal stem cells in culture were extracted and immunoprecipitated with the SH2 antibody. The purified antigen migrated as a single band of 90 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed under reducing conditions. The SH2-immunoprecipitated protein exhibited a molecular weight band shift after removal of N-linked oligosaccharides. We investigated the expression of the SH2 antigen, along with the endothelial markers factor VIII-related antigen and Ulex europaeus I (UEA-I) lectin during specific developmental periods in human dermal embryogenesis and in the postnatal period through aged adults. Frozen sections of human embryonic, fetal, or postnatal skin ranging from 8 weeks estimated gestational age (EGA) through 84 years of age were immunostained or double immunolabelled with antibodies SH2, UEA-I, or factor VIII-related antigen followed by second antibodies with fluorescent markers. Positive cell surface reactivity with the SH2 antibody was seen in cells in the vascular plane in the earliest specimens (day 55 EGA) corresponding to the late cellular dermis period. During the period of the cellular to fibrous transition, in which the initiation of appendage development occurs, most SH2-reactive cells colocalized with vasculature markers UEA-I and factor VIII-related antigen, although there was a subset of cells recognized by SH2 antibody that did not colocalize with the endothelial markers. In contrast to the endothelial markers UEA-I and factor VIII-related antigen, in which the number of immunopositive cells became more prominent with age and maturation of the dermis, the frequency of cells that contained the SH2-reactive antigen diminished with age. The SH2 reactivity evident in embryonic, fetal, and early postnatal periods was not observed in human skin specimens taken from adults greater than 30 years old. These observations support the hypothesis that the SH2 antigen is a cell surface marker of developing microvasculature and may play a role in dermal embryogenesis and angiogenesis.

Coculture of human sperm with bovine oviduct epithelial cells decreases sperm chromatin structural changes seen during culture in media alone.

OBJECTIVE: To compare sperm chromatin structural changes seen in media only culture or in coculture with bovine oviduct epithelial cells. DESIGN: Three freshly ejaculated and three cryopreserved sperm samples in media culture or in oviduct epithelial cell coculture. Sperm in each treatment were evaluated by the sperm chromatin structure assay during a 72-hour time course. SETTING: An academic research laboratory. PATIENT(S): Normospermic donors with children. INTERVENTION(S): Semen collection through masturbation after 48 hours of abstinence. MAIN OUTCOME MEASURE(S): The sperm chromatin structure assay using flow cytometry to detect the susceptibility of sperm in either treatment to denaturation of DNA in situ. RESULT(S): The sperm chromatin structure assay data differed for sperm type (fresh or cryopreserved), over time, and between treatments within 6 hours of culture. In oviduct epithelial cell coculture, fresh sperm chromatin structure assay values for fresh sperm were stable, whereas in control medium higher chromatin degeneration levels were seen by 10 hours. For cryopreserved sperm, chromatin degeneration had increased by 1 hour postthaw in both treatments, although levels were higher in the control treatment thereafter. CONCLUSION(S): Sperm chromatin structural changes occur over time in culture. Such changes were observed within 2 hours for cryopreserved sperm. Coculture of sperm with oviduct epithelial cells results in a stabilizing effect for sperm against chromatin changes.

Adequacy of interviews vs checklists for classifying childhood psychiatric disorder based on parent reports.

BACKGROUND: The advantages and disadvantages of lay-administered structured interviews and self-administered problem checklists for estimating prevalence and associated features of childhood psychiatric disorder have attracted little comment. This article compares the scientific adequacy of these 2 instruments for classifying DSM-III-R categories of childhood psychiatric disorder in general population samples. METHODS: Study data are from parental assessments of 251 children aged 6 to 16 years participating in a 2-stage measurement evaluation study. Reliability and validity were compared between the Diagnostic Interview for Children and Adolescents (the structured interview in the study) and the revised Ontario Child Health Study scales (the self-administered problem checklist used in the study). RESULTS: Reliability estimates based on the kappa statistic were comparable for the 2 instruments and ranged from 0.21 (conduct disorder) to 0.70 (depression) on the lay interview and from 0.17 (depression) to 0.61 (oppositional defiant disorder) on the self-administered checklist. Validity coefficients tended to favor the checklist categories, but only marginally. CONCLUSIONS: On balance, differences in reliability and validity were small between the 2 instruments. These differences would appear to have no discernible impact on the knowledge about prevalence and associated features of disorder generated by use of such instruments in general population surveys.

Prevalence of child physical and sexual abuse in the community. Results from the Ontario Health Supplement.

CONTEXT: Although child maltreatment is considered common, few community surveys have examined the prevalence of more than 1 type of maltreatment among both males and females. OBJECTIVE: To determine the prevalence of a history of physical and sexual abuse during childhood among the general population. DESIGN: General population survey. SETTING: Household dwellings in the province of Ontario, Canada. PARTICIPANTS: A random sample (N=9953) of residents aged 15 years and older participated in the Ontario Health Supplement. MAIN OUTCOME MEASURE: Self-administered questionnaire about a history of physical and sexual abuse in childhood. RESULTS: A history of child physical abuse was reported more often by males (31.2%) than females (21.1%), while sexual abuse during childhood was more commonly reported by females (12.8%) than males (4.3%). Severe physical abuse was reported by similar proportions of males (10.7%) and females (9.2%). A greater percentage of females reported a history of severe sexual abuse (11.1%) compared with males (3.9%). Age of the respondent was not significantly associated with childhood abuse within any category for males. However, for females, the reported prevalence in childhood of sexual abuse, co-occurrence of physical and sexual abuse, and both categories of severe abuse decreased with increasing age of the respondent. CONCLUSIONS: A history of childhood maltreatment among Ontario residents is common. Child abuse may be more prevalent in younger women compared with older women, or there may be a greater willingness among younger women to report abuse.

The relation between fetal abdominal circumference and birthweight: findings in 3512 pregnancies.

OBJECTIVES: To establish the relation between fetal abdominal circumference and birthweight in a large population of fetuses; to identify whether the error in estimating birthweight by abdominal circumference varied with the magnitude of abdominal circumference; and to establish whether adding femur length to abdominal circumference caused a clinically important reduction of error in predicting birthweight. DESIGN: A retrospective study. SETTING: The ultrasound department of a teaching maternity hospital offering a tertiary referral service. SAMPLE: From 3512 nondiabetic women with a normally formed singleton fetus, an abdominal circumference measurement of the infant was made within seven days of delivery; of these, 1213 had a femur length measurement performed at the same time. RESULTS: There was a linear relation between abdominal circumference and birthweight. There was a strong inverse correlation between the proportional error in predicting birthweight from the abdominal circumference and the magnitude of the abdominal circumference. Both the Campbell and Wilkin equation (abdominal circumference alone) and the Hadlock equation (abdominal circumference and femur length) were associated with systematic errors, especially with larger birthweight infants. The median absolute errors for the two equations were not significantly different overall (6.98% and 6.86% respectively), although the Hadlock equation was significantly more accurate in predicting birthweight in infants weighing greater than 4500 g. However, no threshold value of abdominal circumference or of estimated fetal weight using the Hadlock equation had a positive predictive value in estimating infants of > 4500 g of greater than 35%. CONCLUSIONS: Prediction of birthweight should be by abdominal circumference alone. Table 1 presents robust estimates of the error of predicting birthweight using fetal abdominal circumference.

Prolonged fetal pre-ejection period corrected for PR interval associated with cerebral palsy.

OBJECTIVE: To identify whether the correction of human fetal pre-ejection period (PEP) for the effect of catecholamines, as estimated by the PR interval (the interval of time measured between the P and R waves of the electrocardiogram (ECG)), might improve PEP as a measure of fetal cardiac contractility. METHODS: A retrospective analysis of PEP and PR intervals was carried out, using tape recordings of fetal ECG and Doppler ultrasound recordings of cardiac valve movements, from 43 human fetuses in the first stage of labour. RESULTS: There was a strong positive correlation between PEP and PR intervals in the population studied: r = 0.641, P < 0.0001, indicating that about 40% of the inter-patient variation in PEP could be corrected for by concomitant measurement of the PR interval. Only one fetus had markedly prolonged PEP when corrected for PR interval. This individual developed cerebral palsy over the first year of life. CONCLUSION: Correction of PEP for the effects of catecholamines may greatly improve its usefulness in detecting fetal compromise. Combined measurement of the PEP and PR interval needs to be evaluated as a technique of fetal monitoring.

Identifying thresholds for classifying childhood psychiatric disorder: issues and prospects.

OBJECTIVE: To evaluate empirically the implications of choosing different thresholds to classify conduct disorder and attention-deficit hyperactivity disorder for estimating prevalence, test-retest reliability of measurement, and informant (parent/teacher) agreement and for evaluating comorbidity and associated features of disorder. METHOD: Data for the study came from problem checklist assessments done by parents and teachers of children aged 6 to 16 years (N = 1,229) selected with known probability from a general population sample and from structured interviews obtained in a stratified, random subsample (n = 251). RESULTS: Estimates varied widely depending on the rationale used to set thresholds. Percent prevalence went from 0.1 to 39.2; kappa estimates of test-retest reliability went from .19 to .82. Parent-teacher agreement based on kappa went from .0 to .38. Relative odds between disorder and associated features varied twofold. CONCLUSION: Use of different rationales to set thresholds for classifying childhood psychiatric disorder in the general population has profound implications for what we learn about the epidemiology of childhood disorder.

Integrating assessment data from multiple informants.

OBJECTIVE: To examine the consequences for measurement of child psychiatric disorder (conduct and oppositional disorders) of not integrating the data on the same individual from different informants compared with integrating the information from parents and teachers, using three different strategies. METHOD: Data for the study came from problem checklist assessments done by parents and teachers of children aged 6 to 16 years (N = 1,134) selected with known probability from a general population sample and from structured interviews obtained in a stratified random subsample (n = 251). RESULTS: As expected, parent-teacher agreement was low. The pattern of associated features of disorder was found to vary markedly in parent-identified compared with teacher-identified disorder. Furthermore, combining informants had the disadvantage of masking the distinctive patterns of associated features noted in informant-specific disorders. Finally, by treating disorder as informant-specific, the internal properties of the measure are not generally inferior to those obtained by combining informants in various ways. CONCLUSION: Child psychiatric disorders should be conceptualized as informant-specific phenomena.

Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null mutant of Drosophila melanogaster.

Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster are male sterile, have a greatly reduced adult life span, and are hypersensitive to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD+ recipient strain followed by genetic crossing of the transgene into a strain carrying the CuZnSOD-null mutation, cSODn108. The resulting transformants express bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant rescues male fertility and resistance to paraquat to apparently normal levels. However, adult life span is restored to only 30% of normal, and resistance to hyperoxia is 90% of that found in control flies. This striking differential restoration of pleiotropic phenotypes could be the result of a threshhold of CuZnSOD expression necessary for normal male fertility and resistance to the toxicity of paraquat or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fertility, resistance to active oxygen, and life span might indicate different cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZnSOD gene but are only partly compensated for by the transcriptional control elements of the actin 5C promoter.

Evaluation of the Diagnostic Interview for Children and Adolescents for use in general population samples.

This article presents evaluative data on the use of the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) to classify DSM-III-R disorders in the general population. Data for the analyses came from a probability sample (N = 251) of parent-child/adolescent dyads aged 6 to 16 separately administered the DICA-R on two occasions, 10- to 20 days apart, by trained lay interviewers and child psychiatrists. Data are presented on prevalence, test-retest reliability, parent-child/adolescent agreement, and trained lay interviewer-child psychiatrist agreement. High prevalences of oppositional defiant disorder derived from parent assessments and overanxious disorder and dysthymia derived from adolescent assessments suggest that these disorders may be overidentified. Interview data provided by 6- to 11-year olds to classify the internalizing disorders were too unreliable to be useful. Agreement between parent-child/adolescent dyads was generally low while agreement between trained lay interviewers-child psychiatrists was generally high.