Application of phosphorus loading models to understand drivers of eutrophication in a complex rural lake-watershed system.

Several lakes in southwestern Nova Scotia, Canada have experienced reoccurring algal blooms and possess concentrations of phosphorus (P) that are in the eutrophic to hypereutrophic range (>35 µg/L). In this study a mass balance modeling approach was used to evaluate the relative contribution of P sources within these watersheds and lakes. Primary sources of P included land runoff, septic systems, agricultural activities including mink fur farming, aquaculture, as well as internal loading. These sources were assessed for three different study years (1983, 2008, and 2017), based on availability of water quality data, and to quantify the relative impact of the mink farming industry as it rapidly expanded during this time period. A novel method to estimate P loads from intensive fur farming operations was developed, using agricultural census, remote sensing, and publicly available spatial data. A suite of simulations were generated, using a steady state mass balance model, to examine lake P concentrations and sources for baseline conditions (no anthropogenic sources), no mink farming, and varying levels of P retention on mink farms (25%, 50%, 75%) scenarios. An additional scenario was also constructed which involved calibrating mink farm P retention coefficients using available water quality data. In the baseline scenario it was predicted that all study lakes would be oligotrophic, indicating that cultural eutrophication of these lakes has occurred. In the no mink farming scenario, it was predicted that all study lakes would be oligotrophic except for Hourglass Lake, which was predicted to be mesotrophic due to inputs from an aquaculture facility. Internal loading of P from lake sediments was also identified as an important potential P loading mechanism, which will likely be exacerbated by climate change. These findings indicate that the P from mink farms is the primary driver of cultural eutrophication in the study lakes, and highlights the need to consider these nutrient sources within watershed management plans. It is recommended that lake remediation efforts continue to focus on reducing P inputs from mink farms, and on controlling P loading from any new anthropogenic development in these watersheds.

Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays.

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

The influence of ductal left-to-right shunting during extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: The aim of this study was to analyze whether a ductal left-to-right (L-R) shunt will prolong extracorporeal membrane oxygenation (ECMO) in neonates with severe pulmonary hypertension. This report discusses the onset and termination of a ductal L-R shunt and its potential influences on ECMO when pulmonary hypertension decreases during venoarterial bypass. METHODS: Twenty-nine neonates were monitored during veno-arterial ECMO, using bedside echocardiography with 12-hour interval observations. RESULTS: Up to 43% of the patients showed this type of shunt already after 12 hours on bypass. In total, this type of ductal shunt was found between 12 and 72 hours on ECMO in 62% of the patients. After 72 hours, the ductal L-R shunt no longer was detected. In 38% of the patients, no ductal L-R shunt was found during ECMO. Comparisons between these 2 patient groups showed a significantly longer ECMO duration in patients with ductal L-R shunt (P <.007). The mean prolongation time was 46 hours. Also, a significant decrease of left atrium to aorta ratio (P <.01) was observed during ECMO in the ductus group after closure of the duct, illustrating the decrease in volume load for the left heart and lungs. CONCLUSIONS: Ductal L-R shunting is related with a substantial prolongation of the ECMO course (mean prolongation of almost 2 days). The authors suggest that on one side, the ductal L-R shunt will lead to pulmonary hypercirculation and on the other side, postductal stealing from the descending aortic circulation will lead to prerenal failure. Possibly because of interactions with pulmonary and renal function, a ductal L-R shunt will, among other factors, interfere with weaning from ECMO, resulting in a prolonged bypass time.

Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome (SLOS) is caused by deficient Delta(7)-dehydrocholesterol reductase, which catalyzes the final step of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursors 7-dehydrocholesterol (7DHC) and 8DHC. We hypothesized that i) 7DHC and 8DHC accumulation contributes to the poor outcome of SLOS patients and ii) blood exchange transfusions with hydroxymethylglutaryl (HMG)-CoA reductase inhibition would improve the precursor-to-cholesterol ratio and may improve the clinical outcome of SLO patients. First, an in vitro study was performed to study sterol exchange between plasma and erythrocyte membranes. Second, several exchange transfusions were carried out in vivo in two SLOS patients. Third, simvastatin was given for 23 and 14 months to two patients. The in vitro results illustrated rapid sterol exchange between plasma and erythrocyte membranes. The effect of exchange transfusion was impressive and prompt but the effect on plasma sterol levels lasted only for 3 days. In contrast, simvastatin treatment for several months demonstrated a lasting improvement of the precursor-to-cholesterol ratio in plasma, erythrocyte membranes, and cerebrospinal fluid (CSF). Plasma precursor concentrations decreased to 28 and 33% of the initial level, respectively, whereas the cholesterol concentration normalized by a more than twofold increase. During the follow-up period all morphometric parameters improved. The therapy was well tolerated and no unwanted clinical side effects occurred. This is the first study in which the blood cholesterol level in SLOS patients is normalized with a simultaneous significant decrease in precursor levels. There was a lasting biochemical improvement with encouraging clinical improvement. Statin therapy is a promising novel approach in SLOS that deserves further studies in larger series of patients.

Neonatal pulmonary hypertension during extracorporeal membrane oxygenation.

OBJECTIVES: This prospective study was designed to monitor severe pulmonary hypertension during extra corporeal membrane oxygenation using echo Doppler variables. BACKGROUND: All neonates treated with extracorporeal membrane oxygenation also have severe pulmonary hypertension. A study which monitors the reaction of the pre-existing pulmonary hypertension during extracorporeal oxygenation by frequent sampling of those variables related to pulmonary pressure is still lacking. Such a study is necessary to analyze the complex haemodynamic changes in patients undergoing extracorporeal membrane oxygenation. METHOD: In 29 neonates, we estimated pulmonary arterial pressure using peakflow velocity of regurgitation across the tricuspid- and pulmonary valve, peakflow velocity of shunting across persistent arterial ductus, and systolic time intervals of the right ventricle. Correlation between the several estimations of pulmonary arterial pressure were analysed with the Spearman correlation coefficient. RESULTS: Systolic pulmonary arterial pressure measured by the velocity of tricuspid regurgitation illustrated severe pulmonary hypertension prior to extra corporeal membrane oxygenation (mean 63 mmHg, sd 20). Similar levels for the systolic pulmonary arterial pressure could be derived (mean 73 mmHg, sd 17) from ductal shunting. A fair correlation of 0.76 (p< 0.002) could be demonstrated. Pulmonary hypertension responded well and quickly to treatment by extra corporeal membrane oxygenation, with reductions within 24 hours to mean systolic levels of 35 mmHg, sd 23. This very early reaction has not previously been demonstrated and could be of importance in defining parameters for weaning from cardiopulmonary bypass. Diastolic pulmonary arterial pressure was investigated because of its relation to vascular resistance. It proved more difficult to measure because of the low incidence of pulmonary regurgitation. Derived diastolic pressures did not show any good correlations. CONCLUSION: Pulmonary hypertension is well documented prior to extra corporeal membrane oxygenation and response very quickly to the institution of treatment. Ultra sound techniques are indicated at the bedside, and prove useful in monitoring pulmonary blood pressure during the procedure.

Misinterpretation of trisomy 18 as a pseudomosaicism at third-trimester amniocentesis of a child with a mosaic 46,XY/47,XY, +3/48,XXY, +18 karyotype.

False-negative trisomy 18 has been reported after chorionic villus sampling, but not after amniocentesis. We describe a double aneuploidy in cultured amniocytes that was initially misinterpreted as a pseudomosaicism. A patient was referred at 31 weeks of gestation because of fetal anomalies at ultrasound examination. Karyotyping of amniocytes showed a 47,XY, +3 karyotype in 61 clones and a 48,XXY, +18 karyotype in one clone. The latter was interpreted as a pseudomosaicism, the more since a second amniocentesis revealed only cells with a 47,XY, +3 karyotype. At 36 weeks gestational age, a boy was born with congenital anomalies suggestive of trisomy 18. A blood culture showed a 48,XXY, +18 karyotype, while in fibroblasts a 47,XY, + 3/48,XXY, +18 mosaicism was found. Umbilical cord and bladder epithelial tissue also revealed normal 46,XY cells, besides the aneuploid cells. Therefore, the child proper had a 46,XY/47,XY, +3/48,XXY, +18 mosaicism with the clinical symptoms of trisomy 18. To the best of our knowledge, this is the first report of a false-negative result of trisomy 18 together with three sex chromosomes after amniocentesis.

[The Coffin-Siris syndrome. Description of 4 patients and a literature review]. / Het syndroom van Coffin-Siris. Beschrijving van vier patiënten en een literatuuroverzicht.

Four patients with Coffin-Siris syndrome are described. In addition a 30 cases are reviewed. The most frequent symptoms are dysmorphic features of the facies with sparse scalp hair, nail hypoplasia and mental retardation.

The effect of maternal hyperoxia on breathing movements, body movements and rest-activity cycles of low-risk human fetuses.

The effects of maternal hyperoxia on fetal breathing and body movements, and on fetal activity state as reflected in the fetal heart rate pattern, were studied in 20 healthy gravida. Fetal breathing and trunk movements were observed by means of real-time ultrasound scanning, and the fetal heart rate was recorded continuously before, during and after 30 min of maternal oxygen inhalation by mask. Maternal transcutaneous oxygen tension (TcPO2) was measured in 9 subjects. The protocol was also carried out in ten of the gravidas with substitution of compressed air for oxygen. Maternal TcPO2 nearly doubled during oxygen breathing in the subjects in whom this was measured. There were no significant changes in the incidence of fetal breathing or trunk movements, or in the distribution of heart rate patterns, during maternal oxygen breathing. Also, no differences were observed in these variables between the oxygen and compressed-air experiments. We conclude that the normal level of fetal oxygenation does not limit fetal activity in uncomplicated pregnancies.

Prochlorperazine in childhood: side-effects.

The side-effects of prochlorperazine (CompazineR StemetilR) were traced in thirty-six children up to the age of sixteen years and compared with those collected from literature. These side-effects appeared to be predominantly neurological and were independent of the dosage. Impaired consciousness, dyskinesia, pyramidal signs and hypertonus were the main neurological manifestations. Dyskinesia was the most frequent sign. These side-effects disappear spontaneously after discontinuation of the drug. Instant cure can be acquired by intra-muscular administration of orphenadrine (DisipalR).

Paraquat poisoning in man.

In three cases of intoxication by Gramoxone¿, the concentration of paraquat dichloride in blood, dialysate, feces, and urine was determined spectrophotometrically after a clean-up of the biological material by means of ion exchange chromatography (with Dowex 50W-X12 or Zeo-Karb 225). Although good results were obtained after clean-up with Dowex 50W-X12, Zeo-Karb was preferred as ion exchange resin, especially when large sample volumes were needed for the determination. The reported findings indicate that: only 5 to 10% of an ingested dose of paraquat dichloride is absorbed in man, Fullers' earth is very useful, and that primary, e.g. immediate, hemodialysis is necessary.