Incidence Of Structural Abnormalities Research Articles

Clinical profile and cytogenetic correlations in females with primary amenorrhea.

This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.

Essential and non-essential heavy metal levels in key organs of winter flounder (Pseudopleuronectes americanus) and their potential impact on body condition

This study explored whether winter flounder, a benthic species, are potentially exposed to contaminants such as heavy metals released from the sediment of the Bay of Fundy/Gulf of Maine, both critical habitats identified to have increases in heavy metal levels. Experimentally in fish, exposure to certain heavy metals resulted in reduced weight for length and structural abnormalities, but it is unknown if this occurs in wild fish. Winter flounder (n = 72), harvested between 2015 and 2018 from the aforementioned western Atlantic region of Canada/USA, had detectable levels of most heavy metals, with some exhibiting levels of concern (arsenic, cadmium, lead, selenium, zinc) in muscle, liver, and kidney. A 1.4% incidence of structural abnormalities was noted. When compared to 1980 regionally matched flounder data, the 2018 flounder had significantly reduced weight for length, exacerbated with age. Clearly winter flounder are affected by worsening heavy metal contaminant levels in this geographic area.

Impact of estrogen replacement on letrozole-induced embryopathic effects

The aromatase inhibitor, letrozole, exerts embryo toxic effects in rats, causing increased embryo lethality and anomalies of the axial skeleton at pharmacologically relevant doses. Letrozole acts by inhibiting estrogen biosynthesis. It may thus be feasible that estrogen deprivation is a crucial determinant of the elicited developmental toxic effects. In order to gain insight on this hypothesis, the present study tested the capacity of estrogen replacement in preventing letrozole-mediated embryopathy. Pregnant Sprague Dawley rats were exposed to letrozole alone (0.04 mg/kg), or in combination with estradiol cyclopentylpropionate (ECP) at 0.5, 1 or 2 microg/rat. A control group receiving only the vehicles was also included. Animals were exposed during gestation Days 6-16 (corresponding approximately to 3-10 weeks of gestation in the human). Developmental end-points, including intrauterine mortality, fetal growth, placental weight and incidence of structural abnormalities, were evaluated near term gestation. Exposure to letrozole alone was lethal for 41% of conceptuses, and caused minor axial skeletal anomalies in 51% of live fetuses. ECP co-administration effectively prevented letrozole-induced embryolethality, but failed to reduce the incidence of axial skeletal alterations. The obtained results support the concept that inhibition of estrogen biosynthesis represents a critical determinant of letrozole-induced embryonic mortality. A mechanism other than estrogen deprivation appears to underlie the initiation of skeletal anomalies.

Anomalias e prognóstico fetal associados à translucência nucal aumentada e cariótipo anormal

This study aimed to evaluate the incidence of chromosomal abnormalities in fetuses with increased nuchal translucency (NT) measurement. Incidence of structural abnormalities and pregnancy outcome was also described in fetuses with increased NT and abnormal karyotype.This was a retrospective study involving 246 fetuses with increased NT and known karyotype followed at the Fetal Medicine Unit, Hospital das Clínicas, São Paulo University Medical School.Fetal karyotype was abnormal in 14.2% of the cases. Ultrasound anomaly scan and specialized echocardiographic studies in these cases showed fetal structural abnormalities in 80.8% and cardiac defects were found in 61.5% of the fetuses. Pregnancy outcome was abnormal in 76.5% of these women.Increased NT measurement at 11 to 13 weeks and 6 days is an important marker for fetal chromosomal and structural abnormalities, mainly fetal cardiac defects. This finding also indicates increased risk of spontaneous fetal and neonatal death.

Multicenter clinical study on birth weight and associated anomalies of single umbilical artery

normal infants serving as the control group. Results: A statistical difference was observed between the groups in birth weight and in vitro fertilization. The incidence of infants with SUA was 0.37%. Congenital malformations were observed in 21 infants with cardiovascular (n=15, 25.4%), gastrointestinal (n=2, 3.4%), genitourinary (n=9, 15.3%), neuromusculoskeletal (n=6, 10.2%), central nervous system (n=1, 1.7%), chromosomal (n=1, 1.7%), and other (n=3, 5.1%) abnormalities. There were 49 (83.1%) infants with isolated SUA in this study population; among them, the associated congenital malformations were cardiovascular (n=6, 12.2%) and genitourinary (n=6, 12.2%) abnormalities. Two infants with cyanotic heart disease were operated and four infants with acyanotic heart disease showed improvements without any treatment. Six infants with genitourinary abnormalities on renal ultrasound had mild hydronephrosis without further consequences. Conclusion: The incidence of structural abnormalities in the cardiovascular and genitourinary systems is high and the genitourinary anomalies associated with isolated SUA have relatively good prognosis. (Korean J Pediatr 2009;52:655-660)

Effects of the aromatase inhibitor letrozole on in utero development in rats

The aromatase inhibitor letrozole has recently been identified as a promising ovulation-inducing agent. As information regarding possible adverse effects on gestation outcome is limited, the present study was undertaken to evaluate the developmental toxicity potential of letrozole in the rat. Pregnant Sprague-Dawley rats were exposed via drinking water to letrozole at 0 (control group), 0.01, 0.02, or 0.04 mg/kg during the period of organogenesis. Developmental endpoints, including intrauterine mortality, fetal growth and incidence of structural abnormalities, were evaluated near the end of gestation. Major treatment-related effects included: (i) a dose-dependent increase in post-implantation loss, which reached 47.2% following exposure to 0.04 mg/kg letrozole; (ii) minor vertebral anomalies affecting 32.2, 29.3 and 42.2% of fetuses exposed to 0.01, 0.02 and 0.04 mg/kg, respectively. Gestational exposure to doses of letrozole that are equal to or lower than the daily recommended human dose has toxic effects on prenatal development in rats.

The expansion of 300 CTG repeats in myotonic dystrophy transgenic mice does not induce sensory or motor neuropathy

Although many studies have been carried out to verify the involvement of the peripheral nervous system (PNS) in dystrophia myotonica (DM1) patients, the results remain controversial. The generation of DM1 transgenic mice displaying the human DM1 phenotype provides a useful tool to investigate the type and incidence of structural abnormalities in the PNS. In the present study, the morphological and morphometric analysis of semi-thin sections of sciatic and sural nerves, lumbar dorsal root ganglia (DRG) and lumbar spinal cords revealed that in DM1 transgenic mice carrying 300 CTG repeats, there is no change in the number and diameter of myelinated axons compared to wild type. Only a non-significant reduction in the percentage of thin myelinated axons was detected in electron micrographs of ultra-thin sciatic nerve sections. Analysis of the number of neurons did not reveal a loss in number of either sensory neurons in the lumbar DRG or motor neurons in the lumbar spinal cord in these DM1 mice. Furthermore, in hind limb muscle sections, stained with a neurofilament antibody and alpha-bungarotoxin, the intramuscular axon arborization appeared normal in DM1 mice and undistinguishable from that in wild-type mice. Moreover, in DM1 mice, there was no irregularity in the structure or an increase in the endplate area. Also statistical analysis did not show an increase in endplate density or in the concentration of acetylcholine receptors. Altogether, these results suggest that 300 CTG repeats are not sufficient to induce axonopathy, demyelination or neuronopathies in this transgenic mouse model.

Cytogenetic toxicity of leaf extract of Putranjiva roxburghii, a medicinal plant.

Young weaning Swiss albino mice were orally administered leaf extract of Putranjiva roxburghii at 0.5, 1.0 or 2.0 g/kg body weight/day for seven consecutive days. The results showed that the leaf extract significantly induced mitosis-disruptive chromosomal changes in bone marrow cells. No change in the incidence of structural abnormalities was, however, noticed among the metaphase chromosomes. It is proposed that the extract might have interfered with the spindle and other proteins causing polyploidy, aneuploidy, c-mitosis, etc.

A critical review of the developmental toxicity and teratogenicity of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin: Recent advances toward understanding the mechanism

A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. These three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity and are thus among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity but does not induce a significant increase in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species; however, mice are particularly susceptible to development of TCDD-induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves examined in this in vitro system were found to approximate the rat in terms of sensitivity for induction of cleft palate. Investigators have suggested that altered regulation of growth factors and their receptors may involve inappropriate proliferation and differentiation of target cells, ultimately producing TCDD-induced terata. Why the teratogenic effects of TCDD are so highly species and tissue specific, and which animal species most accurately predicts the response of the human embryo/fetus, at the levels of exposure experienced by humans, still remains to be clarified.

Epilepsy in children with attention deficit disorder: Cognitive, behavioral, and neuroanatomic indices

Our study examined the hypothesis that if epilepsy adversely influences the cognitive and behavioral performance of children, then children with both attention deficit-hyperactivity disorder and epilepsy (ADHD-Sz) should exhibit more severe cognitive and behavioral difficulties and be more likely to demonstrate abnormalities on cranial computed tomography than ADHD children without epilepsy. We compared ADHD-Sz and ADHD patients using a variety of psychologic, behavioral, and educational measures, as well as cranial computed tomography. ADHD-Sz children scored significantly below the ADHD group on the Wechsler Intelligence Scale for Children-Revised (performance and full scale scores). In both ADHD-Sz and ADHD groups, the prevalence of learning disabilities (LD) and a variety of behavioral features were similar. Neither seizure disorder nor ADHD was associated with an increased incidence of structural abnormalities or asymmetries of the brain. These findings support the belief that epilepsy adversely affects IQ but does not appear to affect the prevalence of LD or behavioral abnormalities in ADHD children. They further support the accumulating body of data demonstrating normal brain anatomy in ADHD by computed tomography.

Causes of late onset epilepsy in Saudi Arabia: the role of cerebral granuloma.

Cerebral granulomas, due to infections, have been rarely reported as a cause of late onset epilepsy. The incidence of cerebral granulomas was 7% in this prospective study of 56 consecutive patients with onset of seizures after the age of 20 years. Other main causes included cerebral tumours (20%), arteriovenous malformations (5%) and cerebrovascular disease (15% amongst patients with onset of seizures above the age of 40 years). The incidence of structural abnormalities was higher with increasing age at the onset of seizures and declined with long duration of history of epilepsy. Simple partial seizures were strongly associated with structural abnormalities (86%) as opposed to complex partial (33%) and generalised tonic-clonic seizures (33%).

Bone marrow chromosomes in acute lymphoblastic leukaemia: A long‐term study

The bone marrow chromosomes of 25 children with acute lymphoblastic leukaemia (ALL) were examined at diagnosis before treatment, during remission, and in 12 cases, also during relapse. Follow-up was for at least six years. At diagnosis, 17 patients had a major population of chromosomally abnormal cells and of these 11 had identifiable clones. The commonest abnormality was hyperdiploidy. Eight patients had predominantly normal cells, but four of these had a minor abnormal clone. In remission, some samples were completely normal but, when pooled, remission samples had a minor population of chromosomally aberrant cells which were rarely clonal. The incidence of structural abnormalities was the same in patients who ultimately relapsed and those who remained in first remission at the end of the study, but the presence of hyperdiploid cells and/or clones in remission was more frequently associated with subsequent relapse. Relapse patterns were of two kinds: in three patients there was a return of the chromosomal abnormalities seen at diagnosis; in six others, chromosomal features in relapse were distinct from those at diagnosis. It is suggested that relapse associated with distinct chromosomal features may represent malignant transformation of a previously unaffected cell line. While chromosomal abnormalities seen prior to treatment can be related to the leukaemic event alone, abnormalities seen in remission and in relapse may result partly from drug and X-ray treatment. The relative importance of treatment and other factors to chromosomal change in ALL is discussed.