Leukocytic infiltration of the umbilical cord, particularly of the umbilical vein, is common both after normal and abnormal delivery (Tab. I).

The significance and the cause(s) of this phenomenon, however, are still highly controversed subjects (Tab. II). According to some authors (Benirschke, i960; Benirschke and Clifford 1959; Blanc 1961; and Kelsall et al, 1967), cord infiltration may be an indication of intrauterine fetal infection. As a consequence, the terms vasculitis, umbilical phlebitis and funiculitis have been introduced. Other authors (Barter, 1962, and Dominguez et al, 1960), mostly impressed by the discrepancy between the incidence of clinically evident neonatal infection and funiculitis, as well as by the significant association of cord infiltration with prolonged labor and clinical signs of fetal distress, have come to the conclusion that leukocytic infiltration of the umbilical cord must predominantly be the effect of fetal hypoxia. Dominguez et al (i960) go even further and postulate “that the examination of the umbilical cord for leukocytic infiltration affords a means for a long term study of children to determine the effect of intrauterine hypoxia on their ultimate growth and development”.

One way to check the validity of the latter hypothesis, is to investigate the umbilical cords of twins. Since our group has proven that, compared to the first-born twin, the second-born infant is as a rule significantly more hypoxic at birth (Derom and Thiery, 1969), one may expect that intragroup comparison of the incidence of leukocytic infiltration of twin cords should at least permit to disprove the validity of Dominguez assumptions.

A sample of 119 pairs of twins, together with their 87 siblings and 100 pairs of parents, were examined with respect to susceptibility to the motion sickness syndrome. Children were found to exhibit resistance to the syndrome below two years of age, and females were more susceptible than males. The incidence appeared to be highest in families with both parents affected. Concordance rates were much higher in MZ (100%) than in DZ pairs (27.6%). Genetic effects are likely, but cultural factors should not be ignored.

Nation-wide data in Japan on the 112 sets of conjoined twins from fetal deaths and from postnatal deaths during 1979-1985 were analysed. Female conjoined twins accounted for 60% of cases. The incidence rate of conjoined twins remained Constant except in 1985. Overall incidence rate was 10 per million births. Maternal age effect was found in mothers over the age of 40, where the highest incidence rate was obtained. The incidence rate of conjoined twins increased with birth order. There was no seasonal variation in the time of conception.

A radiological investigation was carried out in a group of patients with the “cri du chat” syndrome. The most striking skeletal abnormalities associated with the 5p- chromosome anomaly include microcephaly hypertelorism, narrowing of the wings of ilia, which often appear rectangular in shape. In older patients additional consistent radiological features include large frontal sinuses, malocclusions, scoliosis, shortness of some metacarpal and metatarsal bones. The radiological investigations in the “cri du chat” syndrome, although of small diagnostic aid, appear to be useful for a detailed characterization of the malformations.

The use of twins as a research tool is still proving its worth both by the number of scientists engaged in twin research and by the significance of their results. Old, familiar research designs are finding new applications, and new research designs are appearing. Of greatest current interest are the epidemiological studies made possible by the assembly and the aging of large numbers of twins in twin registries. As an outgrowth partly of the twin registries, partly of conceptual and mathematical progress, new methods have emerged for diagnosis of twin types and for analysis of twin data. One line of development started with the questionnaire method of zygosity diagnosis and has given rise most recently to zygosity diagnosis by principal component analysis. Another line started with probability calculations and has led to the use of generalized distance and noncentral chi-square. The appropriateness of these methods in different contexts needs to be critically considered. Also of importance are the psychologists' new methods of extracting genetic “factors”. The greatest weakness of twin studies, long recognized, is their dependence on the assumption that DZ pairs provide an adequate control on the environmental differences within MZ pairs. This may be valid with respect to environmental influences that are highly self-selected. It is debatable for self-selected influences that differ among families, and clearly untenable for most influences imposed by the social environment peculiar to twins.

An African woman of about 40 years old reported to the out-patients' department on 31st January 1955 because of nausea and vomiting, with amenorrhoea of three months duration. Examination revealed a 2-months' pregnancy. She had six normal deliveries of which three children were still living.

On 3rd February she reported again, complaining of stomach-ache and diarrhoea. The stool examination showed some leucocytes and erythrocytes, but no amoebae, cysts or parasitic ova. On 23rd February the woman again reported, this time with a simple pharyngitis. She came again on 29th June for pre-natal examination and treatment. She had no complaints and was seen to be about 32 weeks pregnant, with a moderate degree of hydramnios. The foetal heart was inaudible.

On 1st August she was admitted to hospital in labour. The membranes were intact, the cervix fully dilatated and presentation was occipito-anterior of the vertex. Artificial rupture of the membranes released only a small amount of amniotic fluid, but labour proceeded normally with the usual quantity of fluid accompanying the birth. Immediately this child was born another bag of waters presented, which was ruptured to release about six pints of amniotic fluid. A second baby now presented by the breech and was delivered by Bracht's method. We noticed at once that this second baby was affected by mongolism.

Several lines of evidence have accumulated in recent years indicating that nuclear cytoplasmic interactions play an important role in the formation and fate of the developing mouse embryo. Early nuclear transplantation experiments indicated that the ability of nuclei to direct cleavage after transfer into enucleated zygotes falls abruptly with nuclei from more advanced preimplantation stages [1]. Transcriptional activation of the nuclei, which occurs during the second cell cycle probably precludes the reprogramming of nuclei from later cleavage stages [2]. Thus, when an 8-cell nucleus is transferred to an enucleated zygote, such a reconstituted zygote is blocked at the 2-cell stage. However, when identical 8-cell nuclei were transferred into both blastomeres of enucleated 2-cell embryos, they were able to support development to the blastocyst stage and even gave rise to live offspring [2-4]. This indicated the importance of the cytoplasmic environment for the ability of the incoming nucleus to support development. It should be noted that in these experiments, the nuclear cytoplasmic ratio was also an important factor in determining the development of the reconstituted embryos [2]. Similar observations were also made when monitoring the development of haploid embryos [5]. In another study, Latham and Solter [6] examined the ability of androgenones, obtained by replacing the female pronucleus of a zygote by the male pronucleus, to develop to the blastocyst stage. Androgenones generated from C57B1/6 eggs were found to be much more competent to give rise to blastocysts than were DBA/2 androgenones. However, when androgenones were constructed from (DBA/2×C57B1/6)F1, zygotes (genetic constitution of the embryos will hereafter be indicated with the female parent coming first followed by the male parent), by replacing the DBA/2 female pronucleus with a C57B1/6 pronucleus, they also developed poorly. This was not simply due to the lack of some component in DBA/2 cytoplasm, since the impaired development was also observed when C57B1/6 male pronuclei from pairs of (DBA/2×C57B1/6) F1, were transferred to an enucleated C57B1/6 egg.

Despite increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, an alternative hypothesis was put forward several decades ago. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease. A critical test of this hypothesis was considered the pattern of occurrence of disease in monozygotic (MZ) twin pairs in which one is a smoker and the other never has been a smoker. Initial twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried out in 1975 permitted identification of 2488 twin pairs discordant for cigarette smoking. Analyses of total mortality and mortality due to coronary heart disease and lung cancer indicate that the smoking members of discordant MZ pairs are at higher risk than their nonsmoking cotwins; increased mortality of smoking cotwins was also found on 21-year follow-up of smoking-discordant pairs in Sweden. Incidence data and noninvasive studies of atherosclerosis in the Finnish sample provide confirmatory evidence for the causal role of smoking in the etiology of coronary heart disease and lung cancer.

The variability of magnesium and zinc concentrations in plasma and erythrocytes was investigated by twin and family studies. Twins were sampled in two distinct ways and in two different West-European regions. In one of the samples, a distinction was made between twins living together and twins living apart. Two series of families were studied, one in a homogeneous environment, the other in a more diverse environment. Samples were compared by variance analysis. The results show 1) that genetic variability is significant for red blood cell (RBC) magnesium and zinc, minor for plasma magnesium and absent for plasma zinc; 2) that the family environment affects the extent of resemblance between twins and between siblings more for plasma levels than for RBC levels of magnesium and zinc. Furthermore, the intercorrelation analysis suggests that the genetic regulation systems of RBC magnesium and zinc are different, whereas some of the environmental regulation systems of plasma magnesium and zinc are the same. Biological interpretations are brought forward and discussed.

Uchida and Rowe (1957), Lamy et al (1957), as well as Campbell (1961), were of the opinion that genetic factors do not play an important role in the genesis of congenital heart deformities. These authors could not find any concordantly affected pair among a total of 32 MZ twin pairs. Impressive family case reports and systematic investigations (Fuhrmann, 1970; Jörgensen, 1970) do not support this assumption. The results of twin investigations by Nora et al (1967) also contradict previous results. Among a total of 37 twin pairs these authors found 6/13 MZ and 1/24 DZ concordantly affected pairs.

Our own investigations began in autumn, 1966 and were recently completed. With the help of the registrar of birth offices and the cardiological team of the University of Göttingen (Prof. Dr. A. J. Beuren, Prof. Dr. H.-E. Hoffmeister, Prof. Dr. J. Koncz, Prof. Dr. J. Stoermer), we were able to find 50 index patients, each being a member of a twin pair, among 2427 propositi with different congenital heart defects.

Our own results are shown in Tab. I: 4/21 MZ (19.0 ± 8.6%) and 1/24 DZ (4.2 ± 4.1%) are concordantly affected. In five cases, the zygosity of the twins, as well as the diagnosis of respective cotwins, (stillborn or perinatal-dead) is unknown.

Studies of developmental progress in high-risk twins have disparate findings. In this study, we report the outcome of 45 twin pairs born between 26 and 37 weeks gestation, and whose birthweights ranged from 840 to 2000 g. No significant differences were found for weight, risk and birth order. However, earlier preterm infants were found to have significantly lower mental scores on the Bayley Scales of Infant Development at 24 months, and lower IQ scores on the Stanford Binet Intelligence Scale at 36 months. These findings imply that gestational age is a powerful variable in determining developmental outcome.

To evaluate the influence of rate of gestational weight gain on newborn birthweight and birthlength in twin gestations complicated by preeclampsia, 74 cases of preeclampsia in twin pregnancy were matched to 148 non-preeclamptic twin controls for maternal race, height, pregravid weight, age and length of gestation. Total weight gain was significantly higher for all cases versus controls and for mild cases versus controls. However, the rate of early weight gain was lower for severe cases and severe cases with thrombocytopenia compared to their controls. Mean birthweight and birthlength did not differ between cases and controls, although the proportion with birthlength below the 10th percentile was significantly higher among cases than controls. In addition, the proportion of birthweights and birthlengths < 10th percentile was significantly higher among cases than controls. These findings suggest that inadequate early weight gain in twin gestations complicated by preeclampsia results in retarded birthlength and birthweight. The implication of these findings are discussed.

A comparison was made of the stature of women, twinning rates, and breast cancer mortality for 32 countries. As height increased, so did twinning and breast cancer mortality (P < 0.005). Dizygotic twinning and breast cancer increased sharply with the mean height of the female population. With due caution in drawing causal inferences when uncontrolled confounding variables are present, it is suggested that these findings are an evolutionary consequence of the high mortality found in twin pregnancy.

In an earlier study of blood pressure variation in middle aged parents and their young adult twin offspring, the greater blood pressure variation observed in the parent sample was accounted for in terms of an increasing influence of individual environmental experiences with increasing age and a commensurate reduction in the impact of heredity. In the present study, the sample size was enlarged to provide a more powerful test of these effects. Maximum likelihood model-fitting techniques were applied to blood pressure covariation in balanced pedigrees, consisting of 85 families (40 MZ and 45 DZ twin pairs). As before, our analysis indicated that a developmental effect was a salient factor in the older age group.

In a family with 528 members, in 7 generations, 162 (47% of the 347 examined patients) showed a Waardenburg syndrome. The frequencies of the different signs are as follows: lateral displacement of the canthi interni and lacrimal puncta: 76%; hyperplasia of the nose root: 54%; hyperplasia of the eyebrows: 52%; deafness: 9%; heterochromia of the iris: 9%; partial albinism: 6%.

This twin register was organized as a resource for studies on the eye. It has been possible to share this resource with other disciplines through effective collaboration. Conversely, only through the assistance of other investigators who are working with twins, will it be practical to undertake certain studies which are important in ophthalmology. The purpose of this presentation is to convey a description of our register and some of its limitations, and to specify the need for collaboration with others.

The original purpose in assembling this register was to identify a group of twins readily available for multiple clinical examinations. Since the first examining facility was to be located near the National Institutes of Health, practical considerations required that twin residence be limited to the metropolitan Washington, D. C. area. Twins of all ages were included in the register, since proposed investigations pertained to different age categories. No effort was made to select twins through randomization procedures; all twins who were identified were invited to membership in the register. A variety of methods were used to locate twins, including contact with schools and clubs, but the largest proportion of registrants were recommended by other twins.

Twins were offered a thorough eye examination, along with the solicitation of their interest in participating in future research activities. The clinical examination was offered for the following reasons:

1) To encourage informed interest in proposed future investigations by acquainting the twins with our facility and purpose;

2) To perform base-line observations, so as to identify and enumerate ocular characteristics as an aid in selecting subsets of twins for future studies;

3) To obtain data for possible estimates of heritability of selected ocular characteristics.

The case of a boy is reported showing the typical symptoms of Down's syndrome, in whom the chromosome analysis revealed a mosaic karyotype: 50% 48,XYY,+21/50% 47,XY,+2l. Findings of 92 cases from the literature are summarized to show the frequencies of double gonosome-autosome aneuploidies compared with single trisomies. Referring to the different chromosomes involved, the aneuploid cell formation, the frequencies of combinations, as well as the tendency to mosaic formation are analyzed. The age of parents at the time of birth and the life expectancy are described as well as the clinical symptoms. Theories concerning the origin of double aneuploidies are discussed.

A total of 204 cases of twin pregnancy occurred between 1970 and 1972 have been compared with 102 cases occurred between 1976 and 1978. During the interval of time, specialised care was instituted for the early diagnosis and management of twins. The incidence of twin pregnancy in Singapore decreased from 1:131 to 1:141 pregnancies. With a background of improved socioeconomic conditions and obstetric care, there has been a dramatic decline in perinatal mortality from 76.4 to 29 per 1000. In undiagnosed cases, the perinatal mortality of the first vs the second twin in the earlier group was 64.4 vs 93.6 per 1000. No such difference was observed in the later period, with the average birthweights of twins being significantly higher. The principles of our antenatal supervision, antenatal tocography, and management are presented and the value of early diagnosis, bedrest, and tocolytic therapy discussed. The reduced perinatal mortality and mobidity gives evidence of an improvement in prematurity and augmented intrauterine growth.

Six new cases of monoamniotic twins are reported. All had true knots of the cord, the result being double survival in 5 cases and 11 normal children. The mechanism of twin development is described and monoamniotic twins are placed in accordance with the two theories from the literature. A short review of both the Scandinavian and the world cases is presented.