Search PubMed⌕ Search

Biomedical subjects

Michael G Ross

Publications and source records attributed to Michael G Ross.

At least 55 records · Page 3Linked to original sources
PubMed2004

Modelling the influence of amnionicity on the severity of twin-twin transfusion syndrome in monochorionic twin pregnancies.

Clinical treatment for diamniotic-monochorionic twin-twin transfusion syndrome (TTTS) may include conversion of diamniotic pregnancies to a monoamniotic-monochorionic state by disrupting the amnion septum. We sought to test the underlying hypothesis, i.e. that a monoamniotic state reduces the severity of TTTS. With use of our previously developed mathematical model of two equal fetoplacental circulatory units connected by various sizes and types of placental anastomoses, we compared the haemodynamic and amniotic fluid dynamics of monoamniotic and diamniotic twins that develop TTTS. We used three anastomotic patterns that produce severe, moderate or mild forms of TTTS, respectively, in our diamniotic-monochorionic twin model. Monoamnionicity was modelled by adding the two amniotic fluid volumes and using the volume-averaged amniotic fluid osmolality. The results were as follows: for severe TTTS, small differences develop between diamniotic and monoamniotic donor twins in fetal urine production, swallowed volume, blood volume, blood pressures, net fetofetal transfusion, and blood and amniotic fluid osmolality. However, the circulatory imbalance between the monoamniotic twins deteriorates similar to that of diamniotic twins. The pathophysiological differences tend to disappear for milder TTTS. In conclusion, our model suggests that the uncommon finding of TTTS in monoamniotic twins is not due to the presence of a single amniotic sac. Rather, clinically significant differences in anastomotic patterns and the delayed or lack of identification of manifestations in monoamniotic twins account for the reduced rate of TTTS diagnosis. Based on these results we expect the clinical disruption of the amnion septum in diamniotic-monochorionic TTTS pregnancies to have only minimal benefits.

Amnion↗
PubMed2004

Maternal LPS induces cytokines in the amniotic fluid and corticotropin releasing hormone in the fetal rat brain.

Perinatal infections are a risk factor for fetal neurological pathologies, including cerebral palsy and schizophrenia. Cytokines that are produced as part of the inflammatory response are proposed to partially mediate the neurological injury. This study investigated the effects of intraperitoneal injections of lipopolysaccharide (LPS) to pregnant rats on the production of cytokines and stress markers in the fetal environment. Gestation day 18 pregnant rats were treated with LPS (100 microg/kg body wt i.p.), and maternal serum, amniotic fluid, placenta, chorioamnion, and fetal brain were harvested at 1, 6, 12, and 24 h posttreatment to assay for LPS-induced changes in cytokine protein (ELISA) and mRNA (real-time RT-PCR) levels. We observed induction of proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) as well as the anti-inflammatory cytokine IL-10 in the maternal serum within 6 h of LPS exposure. Similarly, proinflammatory cytokines were induced in the amniotic fluid in response to LPS; however, no significant induction of IL-10 was observed in the amniotic fluid. LPS-induced mRNA changes included upregulation of the stress-related peptide corticotropin-releasing factor in the fetal whole brain, TNF-alpha, IL-6, and IL-10 in the chorioamnion, and TNF-alpha, IL-1 beta, and IL-6 in the placenta. These findings suggest that maternal infections may lead to an unbalanced inflammatory reaction in the fetal environment that activates the fetal stress axis.

Amniotic Fluid↗
PubMed2004

Expression of aquaporin 9 in human chorioamniotic membranes and placenta.

OBJECTIVE: Aquaporin 9 (AQP9) is one of the recently identified water channels that is also permeable to neutral solutes including urea. To investigate the molecular mechanism of intramembranous pathway of amniotic fluid regulation, we sought to determine whether AQP9 is expressed, and the cellular localization of AQP9 expression in human fetal membranes. STUDY DESIGN: Fetal membranes from 5 normal term human pregnancies were studied. Northern analysis was used to determine the tissue AQP9 messenger RNA (mRNA) expression. In situ hybridization and immunohistochemical staining with specific anti-AQP9 antibody was used for cellular AQP9 localization in the human fetal membranes. RESULTS: Northern analysis detected AQP9 mRNA expression in human amnion, chorion, and placenta. In situ hybridization revealed AQP9 mRNA expression in epithelial cells of the amnion, chorion cytotrophoblasts, and syncytiotrophoblasts and cytotrophoblasts of placenta. Further immunohistochemical study confirmed the AQP9 protein expression in these cell types of fetal membranes. CONCLUSION: This study demonstrated the expression of AQP9 mRNA and protein in human chorioamniotic membranes and placenta. The AQP9 expression in fetal membranes suggests that AQP9 may be an important water channel in intramembranous amniotic fluid water regulation.

Adult↗
PubMed2004

Fetal gastrointestinal motility in a rabbit model of gastroschisis.

PURPOSE: Gastrointestinal (GI) dysmotility occurs frequently in full-term infants with gastroschisis (GS). Although controversial, preterm delivery of infants with GS has been advocated to prevent the development of GI dysmotility, and understanding the etiology of gestational-related bowel injury may lead to prenatal therapies. Using a fetal rabbit model, the authors assessed in vivo and in vitro GI motility in preterm GS fetuses. METHODS: On gestation day 24 (term, 31), surgery was performed in maternal rabbits and GS induced in fetuses, whereas control fetuses underwent sham procedures. On gestation day 29, both groups of fetuses received ultrasound-guided intragastric injection of fluorescein and colored microspheres. Two hours after injection, fetuses were delivered by cesarean section and stomach and small intestine harvested intact. "GI motility" was calculated as the distance traveled by fluorescein divided by total length. In vitro studies of fetal gastric muscle strips contractility responses to bethanechol, a cholinergic agonist, were assessed in an organ bath system. Data were analyzed as paired and unpaired t tests and expressed as means +/- SEM. RESULTS: GS reduced fetal body weight and intestinal length compared with controls (28.4 +/- 1.4 v. 33.5 +/- 1.5 g, 36.9 +/- 1.8 v. 25.9 +/- 1.2 cm; P <.05, respectively). Fetuses with GS showed markedly reduced in vivo GI motility (51.4 +/- 2.9 v 24.8 +/- 2.7%; P <.05) and in vitro gastric contractile tension (769 +/- 53 v 396 +/- 26 mNcm2; P <.05). CONCLUSIONS: GI exposure to amniotic fluid reduces intestinal motility and gastric contractility functions in the preterm rabbit fetus. The results suggest that GS-associated impairment of GI neuromuscular functions occurs in utero, before term, and may be responsive to manipulation of amniotic fluid content or other therapeutic interventions.

Amniotic Fluid↗
PubMed2003

Programming of hypertonicity in neonatal lambs: resetting of the threshold for vasopressin secretion.

Lambs exposed in utero to maternal hypertonicity demonstrate plasma hypertonicity and arterial hypertension. To determine whether hypertonicity is due to an altered osmoregulatory set point, we examined arginine-vasopressin and cardiovascular responses to hypertonic saline infusion in these offspring. Study lambs [dehydrated (Dehy)] were exposed to maternal hypernatremia (8-10 mEq/liter increase; 110-150 d gestation) induced by water restriction. Control singleton and Control twins were born to ewes provided ad libitum water. We anticipated reduced birth weight due to maternal dehydration-induced anorexia and therefore included a Control group of twin gestations to approach a similar birth weight near term. After delivery, ewes from all three groups were provided ad libitum water, and their newborns were allowed ad libitum nursing. At 15 +/- 2 d of age, lambs were prepared with bladder and vascular catheters. At 23 +/- 2 d, after a 2-h basal period, neonatal lambs were iv infused with hypertonic 0.83 m NaCl (0.075 ml/kg x h) for 2 h, followed by a 2-h recovery. Neonatal mean arterial pressure and urine flow were continuously monitored, and blood samples were obtained before, during, and after infusion. During the basal period, Dehy neonates and Control twins demonstrated significantly increased plasma sodium levels and mean arterial pressure than Control singletons. In addition, the Dehy neonates had significantly increased plasma osmolality compared with Control singletons and twins. In response to hypertonic infusion, the Dehy offspring continued to exhibit hypertonicity and hypertension. Importantly, plasma tonicity and blood pressure were greatest in Dehy singletons, lowest in singleton controls, and intermediate in twin controls. Furthermore, the plasma osmolality threshold for AVP secretion was significantly higher in Dehy singletons (290 +/- 2 mOsm/kg) than Control twins (285 +/- 1 mOsm/kg) and Control singletons (280 +/- 2 mOsm/kg), indicating in utero programming of an altered set point for systemic osmolality and blood pressure regulation. Because both twin gestation and dehydration-anorexia incur potential fetal nutritional stress, the results suggest that both in utero hypertonicity and nutrition reduction contribute to offspring programming. We postulate that the nutritional stress associated with twins (as well as dehydration-induced anorexia) contributes to increased plasma sodium levels, whereas the increased plasma osmolality is due to in utero hypertonicity.

Animals↗
PubMed2003

Maternal DDAVP-induced hyponatremia preserves fetal urine flow during acute fetal hemorrhage.

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/- 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 microg bolus, 4 microg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10-12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.

Acute Disease↗
PubMed2003

A randomized controlled trial of prophylactic maneuvers to reduce head-to-body delivery time in patients at risk for shoulder dystocia.

OBJECTIVE: To assess whether prophylactic use of the McRoberts maneuver and suprapubic pressure decreased the head-to-body time, as a proxy for shoulder dystocia, in at-risk patients. METHODS: Patients with estimated fetal weights over 3800 g were randomized to undergo the McRoberts maneuver and suprapubic pressure before delivery of the fetal head (prophylactic maneuvers) or to undergo maneuvers only after delivery of the head, if necessary (controls). A total of 185 patients were enrolled in the study. After exclusions (eg, abdominal delivery), there were 128 evaluable vaginal deliveries. The study had the power to detect a 30% difference in head-to-body time between groups. RESULTS: Head-to-body delivery times did not differ between the prophylactic and control patients (24 +/- 18 seconds versus 27 +/- 20 seconds, P =.38). In addition, the two groups did not differ in rates of admission of the infant to the special care nursery or in birth injuries. There was a significant increase in the risk of delivering by cesarean for patients randomized to the use of prophylactic maneuvers. CONCLUSION: This study does not support the hypothesis that prophylactic use of the McRoberts maneuver and suprapubic pressure speeds delivery in a population of patients at increased risk for shoulder dystocia.

Adult↗
PubMed2003

Unopposed orexic pathways in the developing fetus.

Fetal swallowing has important roles in fetal gastrointestinal development, and perhaps fetal somatic growth and maturation. Ingestive behavioral responses must develop in utero to provide for acquisition of water and food intake during the neonatal period. At birth, the rat, ovine and human fetus have developed mechanisms to acquire food via intact mechanisms of taste, suckling and swallowing. Our preliminary studies suggest that in sheep and likely in human fetuses, putative orexic-mediated ingestive responses are present near term gestation. We hypothesize that both orexic (appetite) and satiety mechanisms develop during the last third of gestation and the related neurotransmitters involved in this process are functional. The potential in utero imprinting of orexic mechanisms may influence infant, childhood and ultimately adult appetite "set-points". Thus, dysfunctional appetite, and perhaps obesity, may result from maternal environmental influences during critical stages of development.

Animals↗
PubMed2003

Expression of aquaporin 8 and its up-regulation by cyclic adenosine monophosphate in human WISH cells.

OBJECTIVE: Water absorption across the fetal chorioamniotic membranes is a critical regulatory pathway for amniotic fluid volume homeostasis. Aquaporins are cell membrane proteins that significantly enhance membrane permeability to water by acting as water channels. We recently demonstrated that aquaporin 8 is expressed in human amnion, chorion, and placenta. Thus, aquaporin 8 expression represents a molecular mechanism of amniotic water absorption through intramembranous pathways. The current study sought to determine whether aquaporin 8 is expressed in human amnion-derived cell culture and to explore its regulation by second messenger cyclic adenosine monophosphate. STUDY DESIGN: Human amnion-derived WISH cells were cultured. Total RNA was isolated and reverse transcriptase-polymerase chain reaction was used to determine aquaporin 8 gene expression. To determine the effect of cyclic adenosine monophosphate on aquaporin 8 expression, WISH cells were cultured in the presence of either monobutyryl cyclic adenosine monophosphate or the cyclic adenosine monophosphate-elevating agent forskolin. Multiplex semiquantitative reverse transcriptase-polymerase chain reaction was carried out to quantify aquaporin 8 messenger RNA levels. RESULTS: Reverse transcriptase-polymerase chain reaction detected aquaporin 8 expression in WISH cells. After forskolin treatment for 2 hours, aquaporin 8 messenger RNA expression in WISH cells increased 4-fold (P <.001). Stimulation of aquaporin 8 gene expression by colforsin was observed throughout the study period of 20 hours. Incubation of WISH cells with monobutyryl cyclic adenosine monophosphate resulted in a 2-fold increase in aquaporin 8 messenger RNA level (P <.001). However, stimulation of aquaporin 8 gene expression by monobutyryl cyclic adenosine monophosphate attenuated to baseline level after 20 hours of monobutyryl cyclic adenosine monophosphate treatment. CONCLUSION: The current study demonstrates the expression of aquaporin 8 water channel in human amnion-derived WISH cells and aquaporin 8 expression up-regulation by second messenger cyclic adenosine monophosphate. Aquaporin 8 messenger RNA demonstrates a relatively short biologic half-life in vitro, which renders its rapid responsiveness to regulation

Amnion↗
PubMed2003

Maternal plasma hypertonicity is accentuated in the postterm rat.

OBJECTIVE: In humans and rats, pregnancy-associated maternal plasma volume expansion and plasma hypotonicity may facilitate maternal-to-fetal water transfer. Although reduced amniotic fluid volume occurs commonly in postterm pregnancy, the mechanisms are unknown. We previously demonstrated a reversal of pregnancy-induced maternal plasma hypotonicity that occurs in the near term (20 days) pregnant rats. We sought to determine whether the relative maternal plasma hypertonicity continues in the postterm period. STUDY DESIGN: Rat gestation (normal, 21 days) was prolonged with subcutaneous progesterone injection. Pregnant rats at gestation, 18 days, 21 days, and 24 days and nonpregnant rats were studied. Maternal and fetal hematocrit levels, plasma osmolality, electrolyte levels, and amniotic fluid volume were determined. In addition, maternal and fetal tissues were analyzed for water and electrolyte content. RESULTS: Compared with term (21days), postterm pregnant rats (24 days) had a significant increase in maternal and fetal plasma osmolality (293.7+/-1.4 mOsm/kg vs 302.8+/-3.7 mOsm/kg and 301.0+/-2.0 mOsm/kg vs 310.3+/-3.2 mOsm/kg, respectively; P<.01) and sodium and chloride concentrations. Conversely, both maternal and fetal hematocrit levels decreased significantly in the postterm period. Postterm rats demonstrated an increased fetal mortality rate (24%) and a significantly reduced amniotic fluid volume (4.2+/-0.6 mL vs 6.6+/-0.6 mL, P<.01). CONCLUSION: These results indicate that the near-term reversal of maternal plasma hypotonicity that has been observed previously is further accentuated in the postterm pregnancy. This continued hypertonicity may induce a fetal-to-maternal water flow and contribute to postterm oligohydramnios and increased fetal morbidity and mortality rates.

Amniotic Fluid↗
PubMed2003

Development of ovine fetal ileal motility: role of muscarinic receptor subtypes.

OBJECTIVE: In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility. STUDY DESIGN: Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses. RESULTS: Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC(50)) was similar at all ages. Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age. CONCLUSION: These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.

Animals↗
PubMed2003

Neuropeptide Y administered into cerebral ventricles stimulates sucrose ingestion in the near-term ovine fetus.

OBJECTIVE: In adults, nutrient intake is controlled by opposing actions of appetite stimulants (eg, neuropeptide Y [NPY]) and suppressors (eg, leptin). Because NPY may exert a preferential role in mediating adult carbohydrate intake, we sought to determine the effect of central NPY on near-term fetal carbohydrate ingestion. STUDY DESIGN: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual, and intracerebroventricular catheters, electrocorticogram, and esophageal electromyogram electrodes and studied at 131+/-2 days' gestation. After a 2-hour baseline period, 10% sucrose was infused sublingually for the duration of the study. At 4 hours' time, NPY was injected into the fetal cerebral ventricles and fetal swallowing monitored for an additional 6 hours. RESULTS: During the basal period, mean (+/-SEM) swallowing averaged 0.8+/-0.1 swallows per minute. Fetal swallowing increased significantly in response to sublingual sucrose (1.3+/-0.1 swallows/min, P=.001), and further significantly increased at 4 to 6 hours after NPY injection into the cerebral ventricles (1.8+/-0.3, P=.001). CONCLUSION: These results indicate central NPY stimulation of fetal ingestion beyond that resulting from sublingual 10% sucrose. The in utero development of NPY-induced ingestive behavior may be in preparation for high neonatal caloric intake.

Animals↗
PubMed2003

Prenatal nicotine increases testosterone levels in the fetus and female offspring.

Epidemiological studies have shown that smoking during pregnancy markedly increases the risk for future tobacco use by adolescent female offspring. It has been hypothesized that the increased smoking risk in females is secondary to a nicotine-induced increase in fetal plasma testosterone levels that persist to adult life. To test this hypothesis, we randomized pregnant Sprague-Dawley rats to receive either saline or nicotine from Day 4 until the end of gestation. Blood samples for testosterone levels were obtained from 30- and 120-day-old offspring. In addition, blood samples for testosterone levels were obtained prior to and following a 2-day infusion of nicotine to chronically catheterized ovine fetuses. Maternal nicotine exposure resulted in increased plasma testosterone in 30-day-old female rat offspring, with no differences found in nicotine-exposed males. In addition, plasma testosterone levels increased in ovine fetuses in response to the nicotine infusion. We conclude that prenatal nicotine exposure increases plasma testosterone levels chronically in adolescent female rat offspring and acutely in both male and female ovine fetuses. Although our findings lack correlative behavioral information on the female offspring, these data are consistent with human epidemiological data suggesting that prenatal environmental influences may have marked effects on the subsequent smoking behaviors of offspring.

Animals↗