Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization

The development and application of fluorescence in-situ hybridization (FISH) has opened the way for comprehensive studies on numerical chromosome abnormalities in human spermatozoa. FISH can be rapidly applied to large numbers of spermatozoa and thus overcomes the major limitation of karyotyping spermatozoa after penetration of zona-free hamster oocytes. The simultaneous hybridization of two or more chromosome-specific probes to spermatozoa and subsequent detection of the bound probes using different fluorescent detection systems enables two or more chromosomes to be localized simultaneously in the same spermatozoon and provides a technique for undertaking reasonable estimates of aneuploidy. The most commonly used probes are those which bind to the centromeric region of specific chromosomes. Most studies to date have concentrated on estimating aneuploidy in spermatozoa from normospermic men, although reports are beginning to appear on aneuploidy in spermatozoa from subfertile and infertile men. Multi- probe FISH studies have generally reported disomy (hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary evidence that some chromosomes such as X, Y and 21 are predisposed towards higher rates of non-disjunction during spermatogenesis. There are also suggestions of inter-donor variability in aneuploidy frequencies for specific chromosomes, although this requires confirmation in larger studies. While FISH is clearly a powerful technique that has many applications in reproductive medicine, it must also be realized that it does have limitations and the technology itself is still evolving and has yet to be fully validated on spermatozoa.      

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Accuracy of fetal echocardiography

The reliability of prenatal ultrasound (US) for the detection of structural heart defects was investigated in a consecutive population of patients referred for prenatal US. Twenty-eight of 49 fetuses (57%) shown to have one or more heart defects with physical examination or autopsy were found to have congenital heart disease with prenatal US. There were 66 cardiac defects in 49 fetuses, 33 of which were entirely or partly identified (50%). Defects correctly diagnosed included hypoplasia of either ventricle, common atrioventricular canal, tetralogy of Fallot, transposition of the great vessels, and Ebstein anomaly. Defects rarely diagnosed correctly included semilunar valve stenosis, total anomalous pulmonary venous drainage, coarctation of the aorta, pulmonic atresia, atrioseptal defect, and ventricular septal defect. Many types of heart defects can be diagnosed accurately with prenatal US in a general population of patients not at high risk for congenital heart disease. Some lesions, however, were difficult to detect.     

The Alabama Preterm Birth Study: Diffuse decidual leukocytoclastic necrosis of the decidua basalis,a placental lesion associated with preeclampsia,indicated preterm birth and decreased fetal growth

Objective. Laminar necrosis, a band-like distribution of coagulative necrosis, has been reported at the choriodecidual interface of the free membranes of placentas of women with various adverse neonatal outcomes. Our goal in this study was to evaluate the frequency of an equivalent feature in the decidua basalis, diffuse decidual leukocytoclastic necrosis (DDLN), a diffuse coagulative necrosis admixed with karyorrhectic debris, in preterm births <32 weeks, and to determine its association with various obstetric conditions, markers of placental inflammation, and newborn outcome.

Study design. Four hundred and forty-six mother/infant dyads who delivered between 23 and 32 weeks gestational age (GA) had their medical records abstracted, a variety of placental and cord blood cultures performed, cord interleukin-6 (IL-6) levels determined, and the placentas evaluated histologically by a single pathologist (OFP).

Results. Women with DDLN (27%) were significantly more likely than other women to have preeclampsia (57.6 vs. 24.8%, p < 0.0001), an indicated preterm birth in this pregnancy (61.9 vs. 26.4%, p < 0.0001), and a prior indicated preterm birth (12.7 vs. 4.1%, p = 0.001), but were not more likely to have an abruption, diabetes, to smoke or be Black. Among DDLN-positive vs. DDLN-negative women, birth weight was significantly lower (1069 ± 373 vs. 1171 ± 389 g, p = 0.014), despite the GAs being similar (28.6 ± 2.2 vs. 28.6 ± 2.3 weeks, p = NS). Women with DDLN were less likely to have a positive placental culture for any organism (50.0 vs. 61.3%p = 0.03), Ureaplasma urealyticum and Mycoplasma hominis in either the placenta or cord blood (29.7 vs. 42.1%, p = 0.02), or an elevated cord blood IL-6 (21.5 vs. 32.9%, p = 0.059). They also were less likely to have acute inflammation of the membranes (27.4 vs. 56.4%, p < 0.0001), chorionic plate (17.0 vs. 48.6%, p < 0.0001) or cord (15.7 vs. 36.6%, p < 0.0001). Decidual necrosis in the free membranes also occurred more frequently in the presence vs. absence of DDLN (25.2 vs. 9.2%, p < 0.0001). Infants whose placentas had DDLN were significantly less likely to have neonatal systemic inflammatory response syndrome (20.7 vs. 35.2%, p = 0.004), but were not significantly different for other neonatal outcomes including respiratory distress syndrome, intraventricular hemorrhage or death.

Conclusion. DDLN of the decidua basalis is relatively common in placentas of 23–32 week newborns, and, when present, is inversely associated with inflammatory maternal and newborn conditions and positively associated with preeclampsia, indicated preterm birth, and lower birth weight. The positive correlation of DDLN with obstetrical and neonatal conditions associated with underperfusion of the placental bed, suggests that DDLN may be a marker of vascular compromise.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。