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PubMed1982

Reproductive behavior in Varecia variegata.

Testicle size during the breeding season is related to age and previous social environment of the male. The size of testicles in adult males exceeds that of young males. Adult males' testicles are much larger than the testicles of young males; enlargement starts 2-3 months prior to the breeding season, peaking around copulation day. Subadult males (3-year-olds) are able to develop full-sized testicles and sire offspring, but did so only when housed with adult females and not with their family group. Although females may reach sexual maturity in their second breeding season after birth, they do not necessarily breed successfully. Vaginal estrus lasts considerably longer (2-3 days) than behavioral estrus (6-12 h). Different stages of vaginal estrus can visually be determined by the development of the vaginal region (swelling; appearance of pink point; long, pink slash; opening to round pink circle, and in the latter stage, by smears, confirming the different physiological stages, proestrus, estrus, metestrus). Behavioral estrus appears in the last hours of vaginal estrus. Captive adult females show increasingly hostile behavior to their maturing daughters. These have to be removed from the group when they are sexually mature. The same degree of hostility can be found between fathers and subadult sons during the breeding season. Dominant males show a typical 'guarding behavior' over the entire period of behavioral estrus of the female. They remain close to the female, vigorously preventing other males from approaching or mating with the female. At the beginning and the end of copulations, the female shows a sequence of aggressive behaviors towards the dominant male. Successful copulations can be determined by their duration (1-2 min), and a head-twisting movement of the male during ejaculation. Normally 16-25 copulations occur on copulation day, usually all with the same partners. The average gestation length is 102.5 days. Adult females normally give multiple births, whereas primiparous females tend to have single infants.

Age Factors↗
PubMed1985

Estimation of highly increased concentrations of fetal hemoglobin in Fanconi's anemia.

We report a case of Fanconi's anemia with an extremely high proportion of fetal hemoglobin (Hb F). A three-year-old girl with multiple birth defects, mental retardation, and aplastic anemia consistent with Fanconi's anemia showed Hb AF by electrophoresis; the Kleihauer smear showed Hb F in 70% of her erythrocytes. Total Hb concentration was 34 g/L, mean corpuscular volume 119 fL. The proportion of Hb F was 45% by densitometry, 36% by radial immunodiffusion, and 30% by cation-exchange microchromatography. The Hb A2 was 0.5%; glycated Hb was 7.8% by affinity chromatography. Sample volume was insufficient for alkali denaturation. As exemplified with this patient, we recommend microchromatographic cation-exchange assay when Hb F exceeds 30% by densitometry. Here the effect of contamination by Hb A1 was lessened by the high proportion of Hb F. Cation-exchange microchromatography provides clinically relevant Hb F values more quickly than radial immunodiffusion and more conveniently than alkali denaturation.

Abnormalities, Multiple↗
PubMed1994

Multifetal pregnancy reduction in Sweden. Utilization rate and pregnancy outcome (1986-1992)

All departments of Obstetrics and Gynecology, as well as all private clinics in Sweden offering assisted conception, were surveyed by means of a questionnaire to determine the utilization rate and outcome of multifetal pregnancy reduction (MFR) for the period 1 January 1986 to 30 June 1992. The response rae was 100%. Multifetal reduction was performed in 26 women, giving an average utilization rate of 1/7 multiple births of three or more for the entire period. Of the various techniques used, intracardiac or intrathoracic injection of a potassium chloride solution was predominant. The experience of each center with multifetal reductions varied between one and six procedures. In this series, the overall complete pregnancy loss was 27% (n = 7). In 73% (n = 19) of women the pregnancy continued to delivery. One fetus died in utero in the second trimester, one child died from a subtentorial hemorrhage perinatally, and one child had a malformation of the right foot and hand. It seems necessary to limit MFR to a few centers in Sweden in order to maintain and increase the experience of the operators involved, and to decrease the fetal loss rate associated with the procedure. However, the ultimate goal is to make these procedures unnecessary when methods of avoiding excessive ovulation are refined and by limiting the number of replaced embryos in IVF-treatment.

Abortion, Therapeutic↗
PubMed1995

Ileal pouch-anal anastomosis function following childbirth. An extended evaluation.

PURPOSE: Women undergoing ileal pouch-anal anastomosis (IPAA) are frequently within reproductive years and eager to bear children. Management issues have been raised regarding the effects of pregnancy and delivery on the pouch, particularly with respect to obstetric care. Our experience is updated to search for delayed sequelae of pregnancy and delivery and to establish whether other factors have an adverse effect on pouch function. These results are also compared with the outcome of pregnancy and delivery in patients with ileostomy or Kock pouch. METHODS: Records of 43 women who had a successful pregnancy and delivery following IPAA were reviewed, including 8 women who had more than 1 pregnancy. RESULTS: Pregnancy was generally well tolerated, with complications being managed nonoperatively. Stool frequency (P < 0.01), incontinence (P < 0.01), and pad usage (P < 0.05; sign rank test) were significantly increased during pregnancy, but prepregnancy function was restored following delivery. Vaginal delivery, multiple births, length of labor, and birth weight had no adverse permanent effect on subsequent pouch function. Longer follow-up after vaginal delivery (mean, 2.4 years) demonstrated no compromise of pouch function. CONCLUSIONS: Incidence of pouch-related complications in patients with IPAA compares favorably with incidence in patients with ileostomy or Kock pouch. Operative rate for complications was 0 percent in IPAA patients compared with 9 percent in patients with ileostomy and 19 percent in patients with Kock pouch. The cesarean section rate was higher in patients with IPAA than in those with ileostomy or Kock pouch, and this may be caused by uncertainty about how to manage delivery in patients with IPAA. Pregnancy and childbirth are well tolerated in women with IPAA, with a lower complication rate and a higher cesarean section rate than women with ileostomy or Kock pouch. Type of delivery should be influenced by obstetric considerations, with vaginal delivery avoided in patients with a noncompliant, rigid perineum.

Adult↗
PubMed2004

Can obstetric care provide further improvement in the outcome of preterm infants?

Reducing the incidence of cerebral damage in preterm infants has become a major objective of perinatal medicine. Recent studies have shown that intrapartum hypoxia is implicated in only 10% of cases, whereas prenatal factors are significantly linked with such damage. The main risk factors associated with cerebral palsy are preterm birth, multiple pregnancy, intrauterine infection, serious hypoxaemic and haemodynamic disorders and, possibly, thrombophilic disorders. Recent progress in recognition of the pathogenesis of cerebral white matter damage has underlined the roles of cytokines, including interleukins 1 and 6 and tumour necrosis factor alpha (TNFalpha), and of a massive release of glutamate, which leads to the excitotoxic cascade. Three measures have had demonstrable benefits in improving neonatal outcome in preterm infants: a policy of prenatal transfers to tertiary level care units, antenatal corticosteroid therapy, and administration of antibiotics to women with preterm premature rupture of membranes. The influence of tocolysis is usually considered to be relatively minor, but further studies in very preterm pregnancies may be required. The recent development of tocolytics without major adverse effects will probably facilitate such studies. The mode of delivery of early preterm infants is another important area of controversy. Recent studies have suggested that a policy of elective caesarean section in PPROM and in the case of breech presentation of fetuses weighing less than 1000-1500 g would be beneficial. Lastly, in vitro and animal studies have shown that several pharmacological agents can prevent white matter disease by interacting with cytokine and the excitotoxic cascade. This will probably constitute an important area of research in the future.

Birth Injuries↗
PubMed2001

How to avoid multiple pregnancies in assistive reproductive technologies.

Since 1980, there has been a worldwide dramatic increase in multiple births. This seems to be due to an increase in the age of reproduction, the use of ovulation induction, and the use of in vitro fertilization. Scarce data suggest that each of these causes is responsible for about one-third of the problem, although quintuplets and more are almost invariably due to ovulation induction. There has been little or no effort to issue guidelines or regulations with respect to ovulation induction, but there has been much advice as to how to control the problem in in vitro fertilization by limiting the number of embryos to be transferred. In sum, a good selection of high-quality embryos on day 3 would allow a high rate of pregnancy with the transfer of one or two blastocysts. Good results of cryopreservation must be part of an agreement in an in vitro fertilization program. If singleton live birthrates were considered to be the principal outcome of assisted reproductive technologies reported by centers and registry, twin and triplet rates should also be reported separately. And finally, if financial considerations would not limit the cost of reimbursement to in vitro fertilization procedures, the number of procedures could be increased with fewer embryos transferred.

Adult↗
PubMed2004

Genetics and imaging to assess oocyte and preimplantation embryo health.

Two major criteria are currently used in human assisted reproductive technologies (ART) to evaluate oocyte and preimplantation embryo health: (1) rate of preimplantation embryonic development; and (2) overall morphology. A major gene that regulates the rate of preimplantation development is the preimplantation embryo development (Ped) gene, discovered in our laboratory. In mice, presence of the Ped gene product, Qa-2 protein, results in a fast rate of preimplantation embryonic development, compared with a slow rate of preimplantation embryonic development for embryos that are lacking Qa-2 protein. Moreover, mice that express Qa-2 protein have an overall reproductive advantage that extends beyond the preimplantation period, including higher survival to birth, higher birthweight, and higher survival to weaning. Data are presented that suggest that Qa-2 increases the rate of development of early embryos by acting as a cell-signalling molecule and that phosphatidylinositol-32 kinase is involved in the cell-signalling pathway. The most likely human homologue of Qa-2 has recently been identified as human leukocyte antigen (HLA)-G. Data are presented which show that HLA-G, like Qa-2, is located in lipid rafts, implying that HLA-G also acts as a signalling molecule. In order to better evaluate the second criterion used in ART (i.e. overall morphology), a unique and innovative imaging microscope has been constructed, the Keck 3-D fusion microscope (Keck 3DFM). The Keck 3DFM combines five different microscopic modes into a single platform, allowing multi-modal imaging of the specimen. One of the modes, the quadrature tomographic microscope (QTM), creates digital images of non-stained transparent cells by measuring changes in the index of refraction. Quadrature tomographic microscope images of oocytes and preimplantation mouse embryos are presented for the first time. The digital information from the QTM images should allow the number of cells in a preimplantation embryo to be counted non-invasively. The Keck 3DFM is also being used to assess mitochondrial distribution in mouse oocytes and embryos by using the k-means clustering algorithm. Both the number of cells in preimplantation embryos and mitochondrial distribution are related to oocyte and embryo health. New imaging data obtained from the Keck 3DFM, combined with genetic and biochemical approaches, have the promise of being able to distinguish healthy from unhealthy oocytes and embryos in a non-invasive manner. The goal is to apply the information from our mouse model system to the clinic in order to identify one and only one healthy embryo for transfer back to the mother undergoing an ART procedure. This approach has the potential to increase the success rate of ART and to decrease the high, and undesirable, multiple birth rate presently associated with ART.

Animals↗
PubMed2005

SALL1 mutation analysis in Townes-Brocks syndrome: twelve novel mutations and expansion of the phenotype.

Townes-Brocks syndrome is an autosomal dominantly inherited disorder, which comprises multiple birth defects including renal, ear, anal, and limb malformations. TBS has been shown to result from mutations in SALL1, a human gene related to the developmental regulator SAL of Drosophila melanogaster. The SALL1 gene product is a zinc finger protein thought to act as a transcription factor. It contains four highly conserved, evenly distributed C2H2 double zinc finger domains. A single C2H2 motif is attached to the second domain, and at the amino terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in the N-terminal third of the SALL1 coding region and result in the production of truncated proteins containing only one or none of the C2H2 domains and the N-terminal transcriptional repressor domain of SALL1. Twenty-three SALL1 mutations were reported prior to this work, 22 of which are located in exon 2, 5' of the second double zinc finger-encoding region. Here we present 12 novel mutations in SALL1 associated with Townes-Brocks syndrome in 13 unrelated families. These include three nonsense mutations, three short insertions and six short deletions. Thus the number of SALL1 mutations increases to 35. Rare phenotypical features among mutation positive patients include hypothyroidism, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the corpus callosum, and umbilical hernia.

Abnormalities, Multiple↗
PubMed1987

Antenatal hypoxia and low IQ values.

We undertook analyses to determine if fetal, intrapartum, and neonatal hypoxia are important causes of low IQ values. We analyzed prospectively collected pregnancy, perinatal, and subsequent developmental data for 19,117 children. As expected, sociohereditary and demographic factors had a large influence on IQ scores. Taking these latter influences into consideration, nothing that happened during labor, delivery, or the neonatal period affected subsequent IQ values. The same was true for early pregnancy disorders that can produce acute fetal hypoxia. By contrast, antenatal disorders and conditions that can produce subacute or chronic fetal hypoxia correlated with low IQ values. These antenatal disorders and conditions were maternal gestational anemia, relative gestational hypotension, hypertension, multiple births, and fetal growth retardation. All of these findings were the same whether neurologic abnormalities were absent or present, suggesting that the same factors were sometimes involved in the genesis of cognitive impairments and neurologic abnormalities.

Child↗
PubMed1989

Congenital cardiovascular malformations in twins and triplets from a population-based study.

Data from the Baltimore-Washington Infant Study of congenital cardiovascular malformations permitted detailed analysis of congenital cardiovascular malformations in 62 twins and 3 triplets and 2303 singleton cases. A probability sample of controls (n = 2793) included 43 twins. The case prevalence of multiple births was 28 of 1000, compared with a 15 of 1000 prevalence among controls (chi 2 = 5.7). There were more girls among case twins than among case singletons and controls (chi 2 = 9.0). Monozygosity was no more frequent in case twins than in controls. Looping defects occurred in 4 monozygotic twin pairs compared with only 1 dizygotic twin pair. The twinning process itself may be implicated in the development of congenital cardiovascular malformations in some of these infants, especially those with looping defects, but concordance of types of defects in 4 of 65 pairs implicates genetic factors in the determination of some forms of congenital cardiovascular malformations.

Diseases in Twins↗
PubMed1998

Severe viral respiratory infections in infants with cystic fibrosis.

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991-1996 were recruited into a prospective, multiple-birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL-8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls. During infancy, 31 children (39%) were hospitalized for respiratory disease and 20 (65%) cases had an etiologic agent identified. Respiratory viruses were detected in 16/31 (52%) cases, including four with simultaneous bacterial infection. Another four were infected with Staphylococcus aureus. Respiratory syncytial virus predominated and was found in seven infants. In the absence of bacteria, those with viral infections had acute onset of respiratory distress, were not treated with antibiotics, and had an uncomplicated hospital course. Compared to noninfected CF subjects and controls, infected infants had elevated BAL inflammatory indices (P < 0.01). Eleven of 31 (35%) hospitalized infants followed for 12-60 months acquired Pseudomonas aeruginosa, compared with only three of 49 (6%) subjects not hospitalized for respiratory symptoms during infancy (risk ratio 5.8, CI 1.9, 24). We conclude that respiratory viruses are important causes of hospitalization in CF infants. While viral infections were self-limited, they were accompanied by airway inflammatory changes, and admission to hospital was associated with early acquisition of Pseudomonas aeruginosa and persistent respiratory symptoms.

Bronchoalveolar Lavage↗
PubMed1995

Some perinatal characteristics of monozygotic twins who are dichorionic.

Zygosity testing of all multiple births allowed the identification of a subgroup of 42 monozygotic twin pairs who have dichorionic placentas, fused and separate. Perinatal outcomes of this group were compared with 110 pairs of monochorionic monozygotic twins and 148 pairs of dizygotic twins. Dichorionic monozygotic twins had the lowest incidence of preterm birth, perinatal mortality, and birth weight discordance. There was an excess of like-sexed over unlike-sexed pairs among the dizygotic twins.

Birth Weight↗
PubMed2003

Polysyndactyly, complex heart malformations cardiopathy, and hepatic ductal plate anomalies: an autosomal recessive syndrome diagnosed antenatally.

A distinct syndrome was ascertained in a 3-year-old girl and her brother. The proband was the first child of first cousin parents. She was born after an uneventful pregnancy. At birth, multiple congenital anomalies were noted: ptosis of the left eyelid, hypertelorism, anteverted nares, large fontanel, long philtrum, ungueal hypoplasia, polysyndactyly, single transverse crease, complex cardiopathy, and hepatic cysts. During another pregnancy of the mother, fetal ultrasonographic examination showed an hypertrophy of the right ventricle and atria, a dextroposition of the aorta, a bilateral renal pelvis dilatation, and a club foot. After termination of the pregnancy, necropsy showed facial anomalies, a small penis, a polysyndactyly, a ventricular septum defect, and a malformation of the ductal plate. Bonneau et al. [1983: J Genet Hum 2:93-105] described a family in which three sibs had a complex cardiac malformation, hexadactyly of the first toe, and syndactyly of the third and fourth fingers. Rajab [1997: Clin Dysmorphol 6:85-88] described two sibs with similar features in an Omani family. The sibs described in this report had anomalies of the ductal plate which were not reported in the two other families. These new findings are in favor of autosomal inheritance of this condition which is amenable to antenatal diagnosis.

Child, Preschool↗
PubMed1988

Prenatal diagnosis, fetal pathology, and cytogenetic analysis of mosaic trisomy 14.

While true mosaicism occurs in only 0.25 per cent of genetic amniocenteses, nearly 2.5 per cent of amniotic fluid cell cultures contain a second cell line. In the common practice of prenatal diagnosis, an aberrant cell line confined to a single colony is usually disregarded. We present a case of mosaic trisomy 14 which was not detected on initial chromosome analysis. At birth, multiple malformations were apparent. Newborn cytogenetic studies revealed mosaicism [46,XX/46,XX,-14, +i(14q)] with an isochromosome 14 in 37 per cent of lymphocytes. Additional cells from the initial amniotic fluid culture were analysed post-delivery and the isochromosome 14 identified in only one of 12 total colonies. This case illustrates two important lessons in prenatal diagnosis. First, amniotic fluid cell cultures may not accurately reflect the relative distribution of the normal and abnormal cell lines within a mosaic fetus. Second, while it is generally reasonable to disregard mosaicism confined to a single colony, this policy will, on rare occasion, result in diagnostic error. This should be taken into consideration, particularly when dealing with autosomal trisomies potentially compatible with livebirth.

Abnormalities, Multiple↗
PubMed1977

A note on the epidemiology of acardiac monsters.

The literature on acardiac monsters has been reviewed. The following conclusions were drawn: 1. The probability of their appearance seems considerably higher among monoamniotic than diamniotic monochorionic twin pairs. 2. They seem more likely to occur within monozygotic (MZ) pairs in higher multiple births than in MZ twins. 3. The data are consistent with the suggestion that there is a slight female excess among them.

Abnormalities, Severe Teratoid↗
PubMed1993

Risk factors for cervical cancer by histology.

A case-control study in four Latin American countries enabled assessment of risk factors for different histologic types of invasive cervical cancers, with the main analyses focusing on 667 patients with squamous cell cancers and 43 with adenocarcinomas. The epidemiology of the squamous cell tumors resembled that found in other studies, namely a high risk associated with multiple sexual partners (RR = 1.5 for > or = 2 vs 1), early ages at first intercourse (RR = 2.3 for < 16 vs > or = 20), history of a sexually transmitted disease (RR = 1.8), multiple births (RR = 2.2 for > or = 7 vs 1-3), absence of prior Pap smear screening (RR = 3.0 vs Pap within 24 months), detection of HPV DNA (RR = 3.6), and limited years of schooling (RR = 1.9 for < 4 vs > or = 7). The adenocarcinomas appeared less affected by sexual, reproductive, or socioeconomic factors. There was no relationship with age at first intercourse, history of a sexually transmitted disease or education, and only marginal associations with number of sexual partners or parity. Absence of prior Pap smear screening as well as detection of HPV DNA, however, were associated with relationships equally strong as those for the squamous cell tumors. Oral contraceptive use distinctly affected risk of the adenocarcinomas, increasing risk by approximately two-fold. Analyses of the 18 subjects with adenosquamous cancer suggested some resemblance to the squamous cell tumors, especially with respect to the role of sexual and sociodemographic variables. These findings support the need for detailed studies of etiologic differences between the different histologic types of cervical cancers, with an emphasis on careful pathologic review and precise measurement of HPV.

Adenocarcinoma↗
PubMed1994

The cohort mortality perspective: the emperor's new clothes of epidemiology, an illustration using cancer mortality.

Cohort analysis of cancer mortality in industrialized countries has led to the generally accepted conclusion that these populations have been exposed to increasing levels of carcinogenic influences. Age-specific cancer mortality rates in the United States from 1962 to 1988 were portrayed in both cross-sectional and cohort manners. Both representations are consistent with the Strehler-Mildvan modification of the Gompertz relationship between aging and mortality. These observations suggest that environmental cohort effects are not responsible for rising cancer mortality. The cohort mortality perspective in epidemiology is inherently biased due to the effects of competing mortality. Competing mortality, like environmental exposures, is applied in a cross-sectional manner across multiple birth cohorts. Competing mortality produces selective mortality, or differential survival, within a birth cohort. Differential survival, an underappreciated form of selection bias, alters the gene pool of surviving birth cohort members. Since cross-sectional competing mortality risks vary with age, the gene pool of different birth cohorts is not uniformly altered. Consequently, differences between birth cohorts in age-specific mortality rates with respect to a particular disorder, for example, cancer, do not specifically imply differences in environmental exposures.

Adult↗