A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.

Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K(d)=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.

Sulphur leaching from headwater catchments in an eroded peatland, South Pennines, U.K.

A detailed investigation into sulphur leaching in peatland headwater catchments in the South Pennines, UK shows that, despite significant reductions in sulphur emissions, sulphur remains a key acidifier. This sulphur can be considered as legacy atmospheric pollution, stored within the peat by processes of dissimilatory sulphate reduction and now being leached into the region's surface waters. Persistently lower water tables at gully edge locations define a thick erosional acrotelm that is vulnerable to aeration, oxidation and flushing throughout the year, and not solely confined to periods of drought. Stream discharge behaves as a two-end member system, whereby pre-event water, rich in DOC and sulphate, is diluted by event water as a result of event water flowing through fast flow pathways such as macropores and overland flow. A rapid increase in water table elevation during the storm and a decrease in elevation after the storm indicate that event water has infiltrated the peat and has then been released into the stream. Streamwaters in peat dominated upland catchments with high densities of gullying have high concentrations of sulphate and low concentrations of DOC, whereas the reverse is true for those catchments with low densities of gullying. This is consistent with the concept that high concentrations of sulphate can suppress the solubility of DOC. A significant store of sulphate exists within South Pennine peats, and continued gully erosion will enhance sulphur leaching meaning that the timescale involved for any depletion is uncertain. It is therefore important that models predicting recovery from acidification in these upland systems include an understanding of how this stored sulphur is being leached, especially with respect to gully erosion, climate change and reduced precipitation.

Time-resolved dosimetric verification of respiratory-gated radiotherapy exposures using a high-resolution 2D ionisation chamber array.

The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS(®) SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of <0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0 ± 0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates >90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam.

Commitment, pro-relationship behavior, and trust in close relationships.

The present work advances and tests an interdependence-based model of the associations among commitment, pro-relationship behavior, and trust. Findings from two longitudinal studies revealed good support for model predictions. Commitment-inspired acts such as accommodation and willingness to sacrifice provide diagnostic information regarding a partner's pro-relationship motives. Individuals come to trust their partners when they perceive that their partners have enacted pro-relationship behaviors, departing from their direct self-interest for the good of the relationship. The results of mediation analyses are consistent with a model of mutual cyclical growth in which (a) dependence promotes strong commitment, (b) commitment promotes pro-relationship acts, (c) pro-relationship acts are perceived by the partner, (d) the perception of pro-relationship acts enhances the partner's trust, and (e) trust increases the partner's willingness to become dependent on the relationship. Auxiliary analyses revealed that self-reported attachment style does not account for substantial variance beyond the features of interdependence that form the basis for the present model.

Substituting the forest for the trees: social networks and the prediction of romantic relationship state and fate.

This research focused on perceptions held by heterosexual couples' friendship network concerning the couple's relationship. In a three-wave longitudinal study, we examined (a) whether these perceptions were similar to the couple's views of the relationship, (b) whether they predicted current relationship state and future fate, and (c) how they compared with the couple's perceptions in predicting fate. Consistent with within-dyad idealization, results from a North American sample indicated that network perceptions of relationship state were significantly more negative than those held by a couple. Although both the couples' and the total networks' perceptions predicted fate, friends of the female couple member were particularly successful at predicting relationship dissolution. An examination of possible mechanisms whereby friends may come to possess particularly predictive perceptions supported the role of couple-disclosure in this process.

Studying the retention of rural physicians.

Rural communities and policy-makers struggle with efforts to enhance the retention of rural physicians. Research available to guide these efforts is often weak methodologically and thus may be pointing retention efforts in nonproductive directions. This article discusses a range of methodologic issues encountered in rural physician retention studies for the purpose of strengthening future studies. Ideal study approaches to answer causal questions, including questions about the "causes" of rural physician retention, must demonstrate good internal validity, for which chance, bias, and confounding are accounted. Retention studies that rely simply on asking physicians why they stay or leave rural areas can be useful at times, but are too prone to bias and their findings difficult to verify. Simply identifying what physicians find satisfying or dissatisfying about rural work also will not reliably reveal why they stay or leave, a related but still distinct question. Stronger approaches to studying retention include the traditional quantitative study--in which retention factors are identified when they are statistically related to physicians' retention, and the increasingly popular qualitative study--in which retention issues are revealed through prolonged, in-depth interactions with physicians. This article also discusses various definitions of retention, the use of survival curves to present retention findings, and the importance of studying retention in inception cohorts. The benefits and downside of studying retention with prospective and retrospective study designs are described.

Querying physicians' beliefs in career choice studies: the limitations of introspective causal reports.

Numerous studies in family medicine literature explore the determinants of physicians' specialty and practice location choices. A research approach frequently used in these studies has been to ask study physicians what led them to make specific career choices, labeled here as the introspective causal reports study design. This paper explores the validity of introspective causal reports and their usefulness in making health manpower policy recommendations. The accuracy of people's beliefs about the causes of their own behaviors is examined, and social psychology literature is drawn upon in this examination. Data are presented characterizing the use of introspective causal reports in recent family medicine literature. Recommendations are made for stronger research designs in future physician career choice determinant studies.

Reliability of ultrasound in predicting uterine leiomyoma volume.

Recently ultrasound has been used to size and track individual myoma volumes for patients undergoing medical therapy. However, little is known about the specific performance characteristics and limitations of this technique with respect to volume measurements. We performed and prospectively interpreted serial ultrasound examinations on myoma patients and confirmed the location, size and number of myomas in the surgical specimens. The smallest detectable tumor was 2.7 cm in diameter. The specificity was 94%; reproducibility had a 14% coefficient of variation for tumors with diameters greater than 6 cm. We conclude that ultrasound is suitable for imaging and sizing myomas provided that the diagnosis is otherwise certain and the tumors tracked are large.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system.

PURPOSE: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac. METHODS AND MATERIALS: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan. RESULTS: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam. CONCLUSIONS: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac.

Monitoring daily MLC positional errors using trajectory log files and EPID measurements for IMRT and VMAT deliveries.

This work investigated the differences between multileaf collimator (MLC) positioning accuracy determined using either log files or electronic portal imaging devices (EPID) and then assessed the possibility of reducing patient specific quality control (QC) via phantom-less methodologies. In-house software was developed, and validated, to track MLC positional accuracy with the rotational and static gantry picket fence tests using an integrated electronic portal image. This software was used to monitor MLC daily performance over a 1 year period for two Varian TrueBeam linear accelerators, with the results directly compared with MLC positions determined using leaf trajectory log files. This software was validated by introducing known shifts and collimator errors. Skewness of the MLCs was found to be 0.03 ± 0.06° (mean ±1 standard deviation (SD)) and was dependent on whether the collimator was rotated manually or automatically. Trajectory log files, analysed using in-house software, showed average MLC positioning errors with a magnitude of 0.004 ± 0.003 mm (rotational) and 0.004 ± 0.011 mm (static) across two TrueBeam units over 1 year (mean ±1 SD). These ranges, as indicated by the SD, were lower than the related average MLC positioning errors of 0.000 ± 0.025 mm (rotational) and 0.000 ± 0.039 mm (static) that were obtained using the in-house EPID based software. The range of EPID measured MLC positional errors was larger due to the inherent uncertainties of the procedure. Over the duration of the study, multiple MLC positional errors were detected using the EPID based software but these same errors were not detected using the trajectory log files. This work shows the importance of increasing linac specific QC when phantom-less methodologies, such as the use of log files, are used to reduce patient specific QC. Tolerances of 0.25 mm have been created for the MLC positional errors using the EPID-based automated picket fence test. The software allows diagnosis of any specific leaf that needs repair and gives an indication as to the course of action that is required.

Ammonium release from a blanket peatland into headwater stream systems.

Hydrochemical sampling of South Pennine (UK) headwater streams draining eroded upland peatlands demonstrates these systems are nitrogen saturated, with significant leaching of dissolved inorganic nitrogen (DIN), particularly ammonium, during both stormflow and baseflow conditions. DIN leaching at sub-catchment scale is controlled by geomorphological context; in catchments with low gully densities ammonium leaching dominates whereas highly gullied catchments leach ammonium and nitrate since lower water tables and increased aeration encourages nitrification. Stormflow flux calculations indicate that: approximately equivalent amounts of nitrate are deposited and exported; ammonium export significantly exceeds atmospheric inputs. This suggests two ammonium sources: high atmospheric loadings; and mineralisation of organic nitrogen stored in peat. Downstream trends indicate rapid transformation of leached ammonium into nitrate. It is important that low-order headwater streams are adequately considered when assessing impacts of atmospheric loads on the hydrochemistry of stream networks, especially with respect to erosion, climate change and reduced precipitation.

Implementation of phantom-less IMRT delivery verification using Varian DynaLog files and R/V output.

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at -0.03-0.12 mm for prostate and -0.02-0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus.

BACKGROUND: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. AIM: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. DESIGN: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. METHODS: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. RESULTS: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study. CONCLUSION: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms.

Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p<0.00001) and between GTN and non-GTN test states (p=0.0002).

Ovine fetal swallowing and behavioral state responses to sublingual water.

Ovine fetal swallowing primarily occurs in bouts of activity associated with low voltage electrocorticogram activity and breathing movements. Despite similar rates of electromyographic swallowing activity, there are significant differences in the net esophageal fluid flow among fetuses. To determine if variations in the volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary secretions) affect fetal swallowing, we studied the effects of sublingual distilled water infusions on ovine fetal swallowing rates and esophageal flow. Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular and electromyograph electrodes, an esophageal flow probe and a sublingual infusion catheter. Following a 2-hour control period, consecutive sublingual infusions of room temperature distilled water (10 and 20 ml/kg/h) were administered for 2 h each. In response to sublingual infusions, fetal plasma sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/- 0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg) decreased significantly. Swallowing activity and esophageal flow did not change significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during the sublingual infusions. However, fetal low-voltage electrocortical activity increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%). Sublingual distilled water infusion decreases fetal plasma osmolality and alters fetal behavioral state without affecting swallowing frequency or esophageal flow.

Concentration thresholds for fetal swallowing and vasopressin secretion.

In adults, plasma osmolality thresholds for hypernatremia-induced arginine vasopressin (AVP) secretion are similar or less than thresholds for stimulation of thirst. In the fetus, the thresholds for swallowing stimulation and AVP secretion have not been defined. Fetal swallowing and AVP secretory responses to hypertonic NaCl and urea were determined in six fetuses (130 +/- 1 1 days) chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyograms (EMG), an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15, 0.30, 0.45, 0.60, 0.75, and 0.90 M), administered at 2-min intervals. A swallow was defined as a coordinated time-sequence of fetal thyrohyoid, nuchal esophagus, and thoracic esophagus EMG activity. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) after four of five injections at each dose. During a 2-h control period swallowing averaged 25.0 +/- 10.1 ml/h and 39.4 +/- 14.6 swallows/h. The mean NaCl threshold concentration for swallowing stimulation was 0.56 +/- 0.06 M. Fetal plasma AVP (2.6 +/- 0.9 pg/ml) increased significantly at the maximum subthreshold (7.6 +/- 4.0 pg/ml) and the threshold NaCl concentration (8.2 +/- 4.0 pg/ml) that stimulated swallowing. On a subsequent day, equiosmolar urea injections increased plasma AVP (from 2.2 +/- 0.7 to 7.6 +/- 2.6 pg/ml) but had no effect on swallowing activity. Fetal mean arterial blood pressure increased after injections of threshold saline and urea concentrations. Fetal arterial blood osmolality and sodium concentration did not change during any study.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovine fetal swallowing and renal responses to oligohydramnios.

Amniotic fluid (AF) volume regulation is dependent on a balance between fluid production and fluid resorption. We examined the effects of reduced AF volume on AF production by fetal urine and resorption by fetal swallowing and the response of these parameters to AF volume replacement. Eight time-dated pregnant ewes (125 +/- 1 days gestation) were studied before (day 1) and after (day 3) AF and fetal urine drainage. Drainage resulted in a significant decrease in AF volume (415 +/- 89 to 157 +/- 36 ml). Fetal urine osmolality increased (139 +/- 10 to 286 +/- 33 mosmol/kgH2O), while urine flow did not change significantly (0.31 +/- 0.04 to 0.23 +/- 0.06 ml/min), resulting in nonsignificant increases in osmolar, sodium, and chloride excretions. Fetal electromyographic swallowing activity decreased 30% (1.0 +/- 0.1 to 0.7 +/- 0.1 swallows/min; P < 0.05), while net esophageal flow decreased 74% (0.31 +/- 0.12 to 0.07 +/- 0.04 ml/min; P < 0.05). On day 4, 0.15 M NaCl (500 ml; 37 degrees C) was administered into the AF over 30 min. During the 2 h after reinfusion, urine flow (0.29 +/- 0.07 to 0.40 +/- 0.09 ml/min) and osmolar sodium and chloride excretion significantly increased, though fetal swallowing activity and esophageal flow did not change. Thus the ovine fetus responded to reduced AF volume by maintaining AF production and decreasing AF resorption. In response to AF replacement, urine flow increased while fetal swallowing activity did not change, consistent with an intramembranous pathway for fetal AF resorption.

Maternal/fetal dehydration: prolonged effects and responses to oral rehydration.

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.

Amniotic fluid volume response to esophageal occlusion in fetal sheep.

Although ovine and human fetuses swallow considerable volumes of fluid, the impact of absence of fetal swallowing on amniotic fluid volume regulation is unclear. To study the role of fetal swallowing on urine production and amniotic fluid, seven ovine fetuses (126 +/- 1 days) were chronically prepared with fetal bladder and vascular catheters, an esophageal flow probe, an inflatable esophageal cuff, and amniotic fluid catheters. In the five fetuses that underwent esophageal ligation after the control period, fetal swallowing averaged 0.27 ml/min before occlusion. In response to esophageal occlusion, significant increases were noted in fetal plasma arginine vasopressin (6.9 +/- 2.6 to 16.6 +/- 4.4 pg/ml) and urine osmolality (159 +/- 1 to 324 +/- 30 mOsm/kg), whereas urine volume (0.25 ml/min) did not change. Amniotic fluid volume increased nearly threefold after 3 days of esophageal occlusion (582 +/- 180 to 1530 +/- 271 ml). Amniotic fluid volume remained normal (334 to 419 ml) in the one fetus in which the occluder did not inflate. In the one fetus in which the esophagus was occluded at surgery, amniotic fluid volume was increased after the surgical recovery period (1489 ml). These data indicate an important role of fetal swallowing in amniotic fluid homeostasis and the potential interaction of swallowing with fetal urine production.