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Biomedical subjects

M G Ross

Publications and source records attributed to M G Ross.

176 records · Page 10Linked to original sources

Mechanism of arginine vasopressin suppression of ovine fetal lung fluid secretion: lack of V2-receptor effect.

Fetal lung liquid production is essential for in utero pulmonary development, and the resorption of lung liquid at birth facilitates neonatal transition. Lung liquid also contributes importantly to amniotic fluid volume. Factors that influence lung liquid production/resorption may, therefore, impact fetal pulmonary growth and development as well as amniotic fluid homeostasis. Arginine vasopressin (AVP) inhibits fetal lung liquid production and facilitates lung liquid resorption. In view of studies administering fetal AVP or the V2 receptor agonist, 1 desamino 8-D AVP (dDAVP) for the regulation of amniotic fluid volume, we sought to determine the impact of AVP V2 receptor stimulation on fetal lung liquid production. Eight near-term ovine fetuses (130 +/- 2 d; term = 145 d) were prepared with hind limb vascular catheters, a bladder catheter, and a tracheal catheter. Each ewe received vascular and amniotic catheters. After 5 days of recovery, the animals were studied for a 2-hr control period and for 2 hr following intravenous dDAVP injection (1 ng/kg). Lung liquid and urine flow rates and plasma electrolyte and osmolality composition were determined at 30-min intervals. To confirm fetal lung liquid suppression in response to AVP, two animals received an intravenous injection of AVP (2 ng/kg) 24 hr after the first experiment. dDAVP administration had no effect on lung liquid production (3.4 +/- 0.4 ml/kg/h), electrolyte concentrations, or osmolality. Fetal urine electrolyte concentrations and osmolality (154 +/- 24-295 +/- 22 mOsm/kg H2O) increased in response to dDAVP, whereas urine flow decreased (9.4 +/- 2.5-4.2 +/- 1.5 ml/kg/h). In the fetuses exposed to AVP, lung liquid production decreased (3.3-1.6 ml/kg/h). As AVP, although not dDAVP, inhibited fetal lung liquid production, these results indicate that AVP effects on lung liquid are likely mediated via the AVP V1 receptor, not the V2 receptor. The use of fetal administration of dDAVP for the regulation of urine production and amniotic fluid volume will not adversely impact lung liquid production.

Amniotic Fluid↗

Human and ovine amniotic fluid composition differences: implications for fluid dynamics.

OBJECTIVE: The ovine model is frequently utilized to extrapolate data regarding fetal and amniotic fluid dynamics to human pregnancy. The ovine amnion is highly vascularized, facilitating intramembranous exchange of water and solutes between the amniotic fluid and fetal plasma. In comparison, the relatively avascular human amniotic membrane may have a reduced potential for intramembranous absorption. In view of these anatomical differences, we hypothesized that comparison of human and ovine amniotic fluid composition would provide insight into differences in the mechanisms of amniotic fluid exchange. METHODS: Amniotic fluid was sampled from 43 patients upon hospital admission, and from 27 ovine ewes at five days following amniotic fluid catheter placement. Both human (32 to 39 weeks' gestation) and ovine pregnancies (125 to 136 days' gestation) were sampled during the last 20% of gestation. Samples were analyzed for osmolality and sodium, potassium and chloride concentrations. The contribution of electrolytes to amniotic fluid osmolality and changes in osmolality and electrolyte composition versus gestational age were assessed by regression and covariance analysis. RESULTS: Mean (+/-SEM) amniotic fluid sodium concentration (134.6+/-1.9 vs. 127.1+/-2.0 mEq/1) was greater and potassium (4.6+/-0.1 vs. 6.1+/-0.6 mEq/l) and osmolality (263.9+/-3.7 vs. 285.1+/-1.6 mOsm/kg) less in human than sheep. The range of amniotic fluid osmolality was greater in human (223 to 336 mOsm/kg) than in sheep (274 to 298 mOsm/kg). Human amniotic fluid osmolality was highly correlated with amniotic fluid sodium (r = 0.97) and chloride (r = 0.96) while ovine amniotic fluid osmolality was only weakly correlated with amniotic fluid sodium (r = 0.75) and chloride (r = 0.51). The slope of the regression line of amniotic fluid sodium and osmolality was greater for human than for sheep amniotic fluid (P < 0.0001). The percent of amniotic fluid osmolality accounted for by sodium, chloride and potassium concentrations was greater for human (97%) than for sheep (86%; P < 0.0001). CONCLUSIONS: The results suggest that human amniotic fluid osmolality is comprised almost entirely of the major electrolytes while alternative solutes (e.g., fructose) contribute to ovine amniotic fluid osmolality. Extrapolation of fetal and amniotic fluid dynamics from ovine models to humans should incorporate differences in amniotic fluid osmolality and electrolyte composition.

Amniotic Fluid↗

Intrapartum screen for diabetes in patients without prenatal care: use of labor admission serum glucose.

OBJECTIVE: For patients presenting in labor with no prenatal care, a rapid screening test for gestational diabetes would potentially aid in decisions for tocolysis (e.g., preterm patients) and mode of delivery (e.g., large for gestational age). We sought to determine whether a labor admission serum glucose is of predictive value in the diagnosis of gestational diabetes. METHODS: We obtained labor admission glucose values for laboring patients and compared these with 1-h (50-g) postglucola (1 degree PG) screens obtained at 24 to 32 weeks' gestation. Diabetics being treated with insulin were excluded from the study. Labor admission serum glucose values were compared to 1 degrees PG values by linear regression. Sensitivity and specificity of admission glucose for identification of a positive 1 degree PG (140 mg/dl) were evaluated by a receiver operator curve (ROC). RESULTS: A total of 98 patients with both 1 degree PG screens and labor admission glucose were identified. Linear regression showed no significant correlation of labor admission glucose and 1 degree PG values (r = 0.13; P = 0.9). The ROC failed to demonstrate an optimal admission random glucose cutoff value for diagnosis of diabetes. CONCLUSIONS: In laboring patients without insulin-requiring diabetes, labor admission glucose does not predict an abnormal 1 degree PG and thus does not aid in labor management of patients with suboptimal prenatal care.

Adult↗

Ovine hourly fetal urine production: relation to fetal electrocortical activity.

OBJECTIVE: Ultrasound studies of hourly urine production rate in human fetuses have suggested that a fall in urine production occurs in state 2F (fetal quiet sleep) secondary to a state-dependent decrease in renal blood flow. We sought to ascertain the relationship between fetal hourly urine production rate and behavioral state in the near-term ovine fetus, a model in which urine production and fetal brain activity can be directly measured. METHODS: Six ewes with singleton pregnancies were prepared with vascular and amniotic fluid catheters. Fetuses were prepared with hindlimb vascular catheters, a bladder catheter, and biparietal ECoG electrodes. After at least 5 days of recovery (ga 130 +/- 2 days; term = 145-150 days), each animal was monitored for a 6-h period. Urine production was measured by draining the bladder catheter through a drop counter and fetal ECoG was continuously recorded (sampling rate of 50 Hz). ECoG activity was analyzed using power spectral analysis and periods of active and quiet sleep identified using both signal amplitude and corresponding 85% spectral edge frequency. RESULTS: Basal fetal arterial pH (7.36 +/- 0.01), pO2 (22.0 +/- 1.2 mmHg) and pCO2 (47.0 +/- 1.6 mmHg) and plasma (295 +/- 2 mOsm/kg) and urine (179 +/- 3 mOsm/kg) osmolalities were within normal ranges. Active and quiet sleep comprised 50 +/- 2 and 43 +/- 1% time, respectively. There was no difference in hourly urine production rate in active sleep (21.4 +/- 9.7 ml/h) and quiet sleep (18.8 +/- 7.7 ml/h). CONCLUSIONS: 1) Hourly fetal urine production rate is independent of ECoG activity state in the near-term ovine fetus. 2) Assuming only minor species differences, ultrasound measurement of human fetal hourly urine production rate can be performed without concern for fetal neurobehavioral state changes.

Animals↗

Novel technique for assessing amniotic fluid volume: use of a three-dimensional bladder scanner.

OBJECTIVE: Abnormalities of amniotic fluid (AF) volume are associated with significant perinatal morbidity and mortality. Although current ultrasound techniques provide a linear amniotic fluid index (AFI) or 2-D area of AF, these indices have limited correlation with actual AF volume. The bladder volume instrument (BVI) 2500 ultrasound (Diagnostic Ultrasound Corp., Redmond, WA) utilizes a rotating 2 MHz transducer, a computer-defined fluid interface, and computer integration of 12 cross-sectional images to calculate 3-D fluid volume. In term pregnancies with normal AF volume, we previously demonstrated a correlation between the AFI and the 3-D volume as determined by BVI. In the present study, we sought to establish normative gestational values for BVI-determined 3-D volume and the relation to simultaneous AFI determinations. METHODS: Following written informed consent, 73 gravidas (17-41 weeks) with uncomplicated pregnancies and normal

Adult↗

Impact of FDA advisory on reported vacuum-assisted delivery and morbidity.

OBJECTIVE: In May 1998 the US Food and Drug Administration (FDA) issued a health advisory reporting neonatal injuries/deaths following vacuum delivery and encouraged voluntary reports of future adverse events. We compared FDA reports of vacuum delivery adverse events prior to and following the advisory. METHODS: The FDA database (MAUDE) was searched for vacuum deliveries using brand name, manufacturer name, and procedure "string searches." Cases were sorted by report date, source, and manufacturer. Neonatal morbidity was quantified as deaths and life-threatening or nonlife-threatening events. RESULTS: A total of 80 reported adverse cases were identified after duplicate cases were consolidated. Twenty-five were reported to the FDA prior to the 1998 advisory and 55 in the immediate 6-month period following the advisory. There was a 22-fold increase in reported events from five events/year prior to the advisory to an estimated 110 events/year following the advisory. The distribution of reporting sources changed significantly following the advisory with increased "manufacturer" (8-43%) and decreased "voluntary" reports (56-20%). All major brand names were represented. During the 6 months following the FDA advisory there were 10 neonatal deaths, 30 life-threatening events, 12 nonlife-threatening events, and three equipment-related reports. Infant deaths were due to intracranial or subgaleal hematomas. Injuries included skull fracture, scalp abrasions, and cephalohematomas. CONCLUSIONS: The FDA advisory was associated with a 22-fold increase in the rate of reported adverse events. This increase in reporting likely represents both enhanced awareness of complications as well as an increase in vacuum-related adverse neonatal sequelae. As vacuum delivery is associated with greater neonatal morbidity/ mortality than was previously recognized, the adage that the vacuum is "designed to come off before infant damage occurs" appears unsubstantiated. It is recommended that manufacturers quantify the suction and traction capabilities of present and new proposed vacuum cup designs.

Cerebral Hemorrhage↗

Fetal lung fluid response to maternal hyperosmolality.

Lung fluid production in utero, a significant source of amniotic fluid, may be regulated by the fetus in response to environmental stress. We monitored changes of maternal and fetal plasma osmolality, plasma arginine vasopressin level, and fetal lung fluid production in response to mannitol-induced change in maternal osmolality in five chronically catheterized ovine fetuses. Four additional ewes and their fetuses did not receive mannitol and served as controls. Maternal infusion of 20% mannitol resulted in maternal and subsequent fetal hyperosmolality (changing from 303 +/- 2 to 322 +/- 2 mOsm and 300 +/- 5 to 319 +/- 8 mOsm, respectively), Mean fetal lung fluid production significantly decreased (from 2.6 +/- 0.4 to 1.6 +/- 0.4 ml/10 min), whereas lung fluid osmolality significantly increased (from 298 +/- 2 to 303 +/- 3 mOsm) in the study animals. No changes in lung fluid sodium or potassium concentrations were observed in study or control fetuses. Fetal plasma arginine vasopressin level significantly increased in the study fetuses (2.2 +/- 0.3 to 5.3 +/- 1.6 microU/ml), though not in control animals. These results indicate that the fetal lamb responds to increased osmolality by decreasing lung fluid production, and that there is a concomitant increase in lung fluid osmolality. This response appears to be mediated via increased fetal plasma vasopressin levels.

Animals↗

Fetal absorption of intra-amniotic aldosterone: effects on urine composition.

OBJECTIVES: Amniotic fluid (AF) volume and composition are maintained by a balance of fetal fluid production and resorption. Ovine fetal resorption of peptide hormones (e.g., arginine vasopressin) from the amniotic cavity has been demonstrated, with resultant effects on fetal urine production. The present study was undertaken to determine whether intra-amniotically administered steroid hormones could be absorbed from the amniotic cavity into fetal plasma and whether intra-amniotic aldosterone administration would affect fetal renal sodium and potassium excretion. METHODS: Seven singleton fetuses (132 +/- 2 days) were prepared with bladder, vascular, and amniotic cavity catheters. After a 5-day recovery period, a bolus of aldosterone was injected into the amniotic cavity. Fetuses were monitored for an additional 24 hours during which time maternal, fetal, and AF samples were collected at timed intervals. RESULTS: After intra-amniotic aldosterone injection, AF aldosterone concentrations increased at 30 minutes and remained elevated for 4 hours after the aldosterone bolus. In response to increased AF aldosterone, fetal plasma aldosterone levels significantly increased by 30 minutes, peaked at 1 hour (17 +/- 4 to 758 +/- 160 pg/mL), and remained elevated for a minimum of 4 hours. Fetal urine sodium excretion significantly decreased and potassium excretion increased. Maternal plasma aldosterone levels increased significantly (25 +/- 10 to 401 +/- 56 pg/mL) but to levels below fetal values. Amniotic fluid and fetal and maternal aldosterone concentrations and fetal urine sodium and potassium excretion returned toward basal levels by 24 hours. CONCLUSION: The steroid hormone aldosterone can be absorbed from the amniotic cavity into the fetal circulation and can alter fetal urine electrolyte excretion. These results suggest that the amniotic cavity is a potential route of in utero pharmacologic fetal therapy.

Absorption↗

Monochorionic twins and twin-twin transfusion syndrome: the protective role of arterio-arterial anastomoses.

Unidirectional arterio-venous (AV) anastomoses often result in twin-twin transfusion syndrome (TTTS). Additional oppositely directed anastomoses may compensate for the circulatory imbalance and either prevent, delay the onset, or moderate the severity of TTTS. Intuitively, higher pressure gradient, oppositely-directed AV anastomoses (indicated as VA) would be expected to compensate better for TTTS than lower pressure gradient arterio-arterial (AA) anastomoses. However, clinical evidence suggests AA anastomoses compensate more efficaciously, because virtually all non-TTTS monochorionic twin placentas have AAs (84 per cent), contrary to TTTS placentas, where only 30 per cent have an AA. We sought to explain this observation by comparing the capabilities of various size VA and AA anastomoses to compensate for the effects of the primary AV. As study design we used a previously developed mathematical computer model of TTTS to determine ranges of anastomotic vascular resistances which cause varying fetal and amniotic fluid discordances. Anastomotic resistances were related with the radii of their feeding vessels, using fractal geometry modelling to mimic the placental vascular tree, and various assumptions regarding arterial blood flow. The results were as follows. An AA anastomosis of equal size as the feeding artery of an AV or VA has a significantly smaller resistance. The primary AV anastomosis may be compensated by both VA as well as AA anastomoses. However, VA transfusion adequately compensates AV flow only for a small range of VA to AV vascular radius ratios. In contrast, AA transfusion compensates the AV flow for a much wider range of AA to AV vascular radius ratios. In conclusion, the wider range of AA than VA radii for adequate compensation of the AV explains the finding that an AA protects more frequently than a VA of similar size against the manifestations of TTTS. These results may possibly allow future risk stratification of monochorionic twins by non-invasive sonographic assessment of the size and type of anastomoses.

Adult↗

Ontogenic expression of putative feeding peptides in the rat fetal brain and placenta.

The well-demonstrated "fetal programming" paradigm is based on the observation that environmental changes can reset the developmental path and thus, gene expression during intrauterine development. As appetite-regulatory neural pathways develop in utero, we sought to determine the ontogenic expression of putative orexigenic and anorexigenic feeding-regulatory peptides in the fetal rat brain and placenta during the last third of gestation. Pregnant Sprague-Dawley rats (n = 12) at D14, D16 and D18 were sacrificed and fetal whole brain and placenta removed and examined for mRNA levels of orexigenic (neuropeptide Y (NPY), agouti-related peptide (AgRP)) and anorexigenic (cocaine and amphetamine regulated transcript (CART), pro-opiomelanocortin (POMC)) peptides and leptin receptor (OB-Rb) using real-time reverse transcription polymerase chain reactions (RT-PCR). For adult comparisons, the hypothalamus, cortex and cerebellum from male rats were also examined for feeding peptides. In the fetal brain and placenta, mRNA levels of AgRP decreased 10-fold from D14 to D16 and was undetectable at D18. Appetite inhibitory factors OB-Rb and CART mRNA levels increased from D14 to D18 in the brain and placenta. NPY and POMC expression remained unchanged from D14 to D18. The pattern of expression of feeding regulatory peptides in the fetal brain most closely resembled the expression profile of the adult cerebral cortex. The continued maturation of feeding regulatory mechanisms in late gestation indicates the potential for in utero programming of ingestive behavior.

Agouti-Related Protein↗

Assessments of fetal swallowed volume: tracer disappearance versus esophageal flow.

OBJECTIVE: We sought to compare fetal swallowed volume determinations simultaneously by two techniques--amniotic fluid (AF) tracer disappearance and esophageal flow probe measurements. METHODS: Six ovine fetuses (129 +/- 1 days) were chronically prepared with a thoracic esophageal flow probe and vascular and two AF catheters. 125I-labeled albumin was injected into the AF cavity, and samples were withdrawn at timed intervals for 8 hours. The AF volume was calculated by time-0 extrapolation of the semilog of 125I disappearance. Tracer-determined swallowed volume was calculated as the product of AF volume and the slope of isotope disappearance. Flow probe measurement of swallowed volume was determined by computer integration of calibrated flow probe velocity recordings. RESULTS: The AF volume averaged 805 +/- 168 mL. The isotope disappearance rate from the AF was 2.8 +/- 0.4%/hour. Average tracer-determined swallowed volume (547 +/- 113 mL/day) was greater than flow probe volume (366 +/- 81 mL/day), although these values were not significantly different. However, when corrected for estimated swallowed lung fluid, tracer-determined volume was significantly greater than flow probe volume (P < .05). CONCLUSION: Ovine fetal swallowed volume determinations by AF tracer techniques are greater than those determined by esophageal flow probe measurements.

Amniotic Fluid↗

Artifactually elevated basal uterine tonus resulting from measurement of hydrostatic pressure by transducer-tipped intrauterine catheters.

Accurate measurements of uterine activity are a valuable adjunct in the management of parturition. Recently transducer-tipped intrauterine pressure catheters (IUPC) have been advocated because of their accurate recording of uterine contraction pressures. We hypothesized that the transducer-tipped IUPC may record elevated basal uterine pressures because of measurement of additional hydrostatic pressures within the uterus. Eight laboring patients received intrauterine placement of a transducer-tipped IUPC. Catheters were zeroed to air pressure, electronic zero was checked, and monitors were calibrated before insertion. Catheters were not rezeroed during labor. Basal resting uterine pressures were recorded at insertion and before IUPC removal. After removal, electronic zero and catheter accuracy were tested in a specially designed pressure chamber (21 and 60 mm Hg). Electronic zero averaged -3 mm Hg before insertion and after removal. Baseline uterine resting tone averaged 15 +/- 1 mm Hg in seven patients, and one patient had a measurement of 34 mm Hg. Uterine resting tone remained stable in five patients and decreased to 20 mm Hg in the one patient with elevated basal tone. Uterine resting tone increased markedly to 36 and 41 mm Hg in two patients with normal pressures on insertion, in spite of no evidence of uterine hyperstimulation. Extrauterine pressure testing recorded pressures of 23 +/- 1 and 62 +/- 1 mm Hg, respectively. Because of the measurement of the amniotic fluid column above the catheter, transducer-tipped IUPCs may artifactually elevate uterine pressure measurements and basal levels may shift during the course of labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗