Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women.

Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.

Management of chronic ventilatory insufficiency with electrical diaphragm pacing.

We have had experience with diaphragm pacing in 24 patients at the Toronto Western Hospital. Fourteen patients have undergone bilateral implants to treat chronic ventilatory insufficiency (CVI) caused by traumatic tetraplegia at the C1/2 level (eight patients), neurogenic apnea (five) and one case of neonatal apnea. Unilateral stimulators for nocturnal pacing have been implanted in five patients with central alveolar hypoventilation (sleep apnea) and five patients who suffered CVI resulting from various etiologies. Of the patients who were ventilatory dependent, 80% were successfully weaned and in the entire series, 58% of the patients are living. Diaphragm pacing was successful in 67%, partially successful in 8% and ineffective in 25%. The major complications were: death by pneumonia, failure of the radio receivers, and infection. Diaphragm pacing is the treatment of choice for patients who are ventilator dependent and tetraplegic from upper cervical trauma or in some cases of neurogenic apnea; it may be life saving for patients who suffer central alveolar hypoventilation.

Ferrozine iron and total iron-binding capacity method adapted to the ABA-100 Bichromatic Analyzer.

A sensitive method (Clin. Chem. 26: 327--331, 1980) for serum iron, in which the color reagent Ferrozine is used, is modified and adapted to the Abbott ABA-100 discrete analyzer. The standard curve is linear to at least 10 mg/L and the method showed day-to-day precision (CV) of 2.4% for a 1.03 mg/L sample (n = 63) and 1.9% for a 2.13 mg/L sample (n = 63). Lower values were obtained than with the modified continuous-flow technique of Giovanniello et al., but the correlation was good (r = 0.98). Bilirubin and copper do not interfere; hemoglobin and gross lipemia interfere only slightly. The total iron-binding capacity, based on Ramsay's method, was evaluated with regard to the effect of adding various amounts of magnesium carbonate. Results led us to use a ratio of approximately 180 mg of magnesium carbonate to each 5 micrograms of excess iron added. Day-to-day, the method for total iron-binding capacity gave a CV of 3.1% for a 2.55 mg/L sample, 2.8% for a 3.63 mg/L sample.

[Pathogenesis of endemic goiter: evidence of a dietary factor different from iodine deficiency (author's transl)]. / Mise en évidence d'un facteur alimentaire distinct de la carence iodée dans la pathogénie du goitre.

The role of cassava was investigated in particularly severe endemic goiter area (Ubangi). Dietary intake of cassava induces an increase of plasma thiocyanate concentration and an increase of urinary excretion of stable iodine. Generalized iodine deficiency induces very high thyroid uptakes; the other parameters of thyroid function are more or less affected according to the dietary intake of thiocyanate. When thiocyanate intake is high an adaptation is obtained only at the expense of a drop of plasma T4 level and very high increase of plasma TSH.