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Christopher R Newton

Publications and source records attributed to Christopher R Newton.

16 recordsLinked to original sources
PubMed2006

Factors affecting patients' attitudes toward single- and multiple-embryo transfer.

OBJECTIVE: To identify factors that influence patient decision making concerning embryo transfer. DESIGN: Prospective analysis. SETTING: In vitro fertilization unit at a tertiary-care, university-affiliated teaching hospital. PATIENT(S): Seventy-nine women and 53 men who were referred consecutively for IVF treatment. INTERVENTION(S): Provision of risk information about complications of twin pregnancy. MAIN OUTCOME MEASURE(S): Rated desirability of different transfer options and twin pregnancy, together with standardized measures of depression and infertility stress. RESULT(S): Women's initial preference for two-embryo transfer (2ET) was related to beliefs that the chance of pregnancy was higher with 2ET vs. elective single-embryo transfer and that the personal chance of twins was relatively likely with 2ET but was not related to a specific desire for twins. Providing risk information increased the desirability of elective single-embryo transfer and decreased the desirability of twin pregnancy among both men and women. CONCLUSION(S): Cautious patients, preferring transfer of fewer embryos, balance desires to maximize the chance of pregnancy with acceptance of risks associated with twins. Less-cautious patients may be motivated by beliefs about the influence of age, desires for, and likelihood of twin pregnancy. Information about risks may affect these groups differently and diverse patient motivations may require tailored information to ensure informed consent.

Adult↗
PubMed2005

Angiotensin II type 1 receptor activation increases microvascular permeability via a calcium dependent process.

BACKGROUND: Elevated serum angiotensin II (Ang II) has been implicated in the endothelial barrier dysfunction associated with shock. We hypothesized that the increase in microvascular permeability seen with activation of the type 1 (AT1) receptor is a calcium dependent process. MATERIALS AND METHODS: Microvascular hydraulic permeability (Lp) was measured in rat mesenteric venules using the Landis micro-occlusion model. A 100 mm KCl (HK) solution was used to negate the electrochemical potential of calcium influx, and measures of Lp were obtained before and after 20 ng/ml Ang II plus HK solution (n = 5). Intracellular calcium dependence on AT1 activation was evaluated two ways: 1) Lp changes were measured in response to 10 microm of the type 1 receptor agonist [SAR] [1]-angiotensin II in HK solution (n = 6), and 2) Lp changes were measured in response to 25 microg/ml of the type 2 (AT2) receptor blocker PD-123319 (PD) plus 20 ng/ml Ang II in HK solution (n = 6). RESULTS: As expected, HK perfusion (P < 0.08) and Ang II plus HK solution (P < 0.42) did not affect Lp. Although perfusion of [SAR] [1]-angiotensin II in HK solution (P < 0.001) and PD plus Ang II in HK solution (P < 0.003) both significantly increased Lp, the magnitude of this response was less than that observed with Ang II alone. CONCLUSIONS: Abrogation of intracellular calcium influx during AT1 activation blunted the known Ang II induced increase in microvascular permeability. Although the effect observed during AT1 activation was blunted by the HK solution, a significant elevation of Lp was still observed. This suggests that Ang II activation of the AT1 receptor increases microvascular permeability primarily, but not exclusively, via modulation of endothelial intracellular calcium ion levels.

Angiotensin II↗
PubMed2004

Angiotensin II type 2 receptor effect on microvascular hydraulic permeability.

BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor that modulates microvascular permeability. Angiotensin II type 1 (AT1) and type 2 (AT2) receptors have been described with subsequent development of their respective antagonists. We hypothesized that the AT2 receptor modulates microvascular permeability. MATERIALS AND METHODS: Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Following baseline L(p) measurements, paired measures of microvessel L(p) were obtained after perfusion with a test solution. The test solutions consisted of the AT2 receptor agonist CGP42112A at 10 microm (n = 6), 100 microm (n = 6), and 200 microm (n = 6), as well as the AT2 receptor antagonist PD-123319 at 3 microm (n = 6), 30 microm (n = 6), 300 microm (n = 6), and 600 microm (n = 6). RESULTS: From mean baseline L(p) of 0.99 +/- 0.03, 100 microm CGP42112A decreased L(p) to 0.76 +/- 0.02 (P = 0.005), and 200 microm CGP42112A decreased L(p) to 0.61 +/- 0.02 (P < 0.001). From mean baseline L(p) of 0.90 +/- 0.05, PD-123319 increased L(p) at 30 microm to 1.60 +/- 0.2 (P = 0.003), at 300 microm to 2.28 +/- 0.3 (P = 0.008), and at 600 microm to 4.30 +/- 0.9 (P = 0.03). Units for L(p) are mean +/- SEM x 10(-7) cm s(-1) cmH(2)O(-1). CONCLUSION: AT2 activation decreased L(p), while AT2 blockade increased L(p). These changes in L(p) may be explained by (1). a permeability-decreasing effect of the AT2 receptor that is induced by AT2 activation and inhibited by AT2 blockade; and/or (2). a permeability-increasing effect of the AT1 receptor observed during AT2 blockade and selective AT1 activation by endogenous locally released Ang II. These mechanisms would support the theories that the AT1 receptor increases microvascular permeability, while the AT2 receptor decreases microvascular permeability.

Angiotensin II Type 2 Receptor Blockers↗
PubMed2004

Angiotensin II type 1 receptor activation increases microvascular hydraulic permeability.

BACKGROUND: In addition to its vasoconstricting effects, angiotensin II (Ang II) has also demonstrated the ability to modulate microvessel permeability. We hypothesized that activation of the angiotensin II type 1 receptor (AT1) would increase hydraulic permeability. METHODS: Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Paired measures of L(p) were obtained at baseline and after perfusion with the AT1 agonist, [Sar(1)]-angiotensin II, at 10 micromol/L (n=6) and 100 micromol/L (n=6). Activation of the AT1 receptor was also achieved by perfusion with 20 nmol/L Ang II plus the angiotensin II type 2 receptor (AT2) antagonist, PD123319. In these studies, 30 micromol/L (n=6) and 300 micromol/L (n=6) of PD123319 were used. RESULTS: [Sar(1)]-angiotensin II increased L(p) 2-fold with the 10 micromol/L dose (P=.04) and 4-fold with the 100 micromol/L dose (P < .001). The L(p) peak due to [Sar(1)]-angiotensin II occurred sooner than the peak observed with Ang II. PD123319 (30 micromol/L) plus 20 nmol/L Ang II increased L(p) 5-fold (P=.003), while PD123319 (300 micromol/L) plus 20 nmol/L Ang II increased L(p) 20-fold (P < .0001). The magnitude of the effect due to PD123319 (300 micromol/L) plus Ang II (20 nmol/L) was approximately twice the summation of effects due to PD123319 (300 micromol/L) alone and Ang II (20 nmol/L) alone. CONCLUSIONS: We conclude that endothelial cell Ang II receptors play an important role in modulating transendothelial fluid flux. Activating the AT1 receptor increases L(p); the AT2 receptor may operate to oppose this action. Pharmacologic manipulation of Ang II receptors may be beneficial during shock states to limit intravascular fluid loss.

Analysis of Variance↗
PubMed2004

Modulation of microvascular hydraulic permeability by platelet-activating factor.

BACKGROUND: Platelet-activating factor (PAF) is a modulator of the inflammatory response to shock. Edema formation and intravascular fluid loss have been associated with PAF. The increase in microvessel permeability caused by PAF may be related to direct endothelial cell activation and leukocyte activation. We hypothesized that PAF increases hydraulic permeability by means of the direct activation of endothelial cells. METHODS: Hydraulic permeability (Lp) was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. After baseline Lp measurements, paired measures of Lp were obtained during PAF perfusion at doses of 0.1 nmol/L (n = 6), 1.0 nmol/L (n = 6), 10 nmol/L (n = 6), and 50 nmol/L (n = 6). The temporal effects of pulse administration of PAF and repeated exposures to PAF were also assessed. RESULTS: Compared with baseline values (Lp = 1.16 +/- 0.11), the Lp of the microvessels significantly increased at PAF doses of 0.1 nmol/L (Lp = 1.46 +/- 0.1) (p < 0.002), 1 nmol/L (Lp = 2.0 +/- 0.11) (p < 0.004), 10 nmol/L (Lp = 4.09 +/- 0.09) (p < 0.005), and 50 nmol/L (Lp = 5.13 +/- 0.07) (p < 0.0001). All units for Lp are given as +/- SE x 10 -7 cm s-1. cm H2O-1. CONCLUSION: PAF increased microvessel permeability in a dose-dependent manner. The permeability-increasing effect of PAF was transient even with continuous endothelial exposure to PAF. This study emphasizes the ability of PAF to directly modulate microvascular permeability and increase venular permeability.

Animals↗
PubMed2004

Endothelin-1 decreases microvessel permeability after endothelial activation.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor that is released during shock and sepsis. We hypothesized that ET-1 plays a role in the modulation of the elevated microvascular permeability state of the activated endothelium. METHODS: Hydraulic permeability (Lp) was measured using the modified Landis micro-occlusion technique. The effect of different ET-1 doses on Lp was determined by obtaining paired measures of Lp at baseline and after the vessels were perfused with ET-1 at doses of 2.0 pg/mL (n = 6), 20 pg/mL (n = 6), 200 pg/mL (n = 6), or 2,000 pg/mL (n = 6). To evaluate the effects of ET-1 in the activated endothelium, additional vessels were perfused with either 10 micromol/L adenosine triphosphate (ATP) (n = 6) or 1 nmol/L bradykinin (n = 6). The vessels were then perfused with 200 pg/mL ET-1 followed by the final L determination. RESULTS: ET-1 significantly decreased Lp at doses of 20 pg/mL (p = 0.03), 200 pg/mL (p = 0.03), and 2,000 pg/mL (p = 0.01). Endothelial activation with ATP and bradykinin increased Lp to 4.21 +/- 0.39 (p < 0.0001) and 2.72 +/- 0.24 (p = 0.001), respectively. ET-1 significantly decreased the Lp to 1.99 +/- 0.48 after activation with ATP (p = 0.004). ET-1 also decreased the Lp to 1.10 +/- 0.19 after activation with bradykinin (p = 0.001). Units for Lp are x10(-7) cm x s(-1) x cm H2O(-1). CONCLUSION: In this model, ET-1 attenuated the increase in microvascular permeability that can be seen in inflamed vessels. In addition to its vasopressor function, ET-1 may be of benefit in pathophysiologic states by decreasing third-space fluid loss. This receptor-mediated function of ET-1 may be amenable to pharmacologic manipulation.

Adenosine Diphosphate↗
PubMed2003

Effect of hypertonic saline on microvascular permeability in the activated endothelium.

INTRODUCTION: The effect of hypertonic saline (HTS) on microvascular permeability in microvessels with activated endothelial cells is unclear. We hypothesized that HTS and HTS with dextran would decrease hydraulic permeability after activation of the endothelium. METHODS: Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. The effects of 185 mM HTS and HTS plus 2% dextran (HSD) were tested in the activated endothelium by measuring L(p) at baseline, after perfusion with ATP, and again after HTS (n = 6) or HSD (n = 6). ATP (10 microM) activated endothelial cells and increased L(p) 4-fold. Additional venules were used to test the effects of 135 mM NaCl (n = 6) and 235 mM (n = 6) NaCl after endothelial activation with ATP. RESULTS: After endothelial activation with ATP, L(p) values were 6.05 +/- 1.63. Subsequent perfusion with HTS decreased L(p) to 2.05 +/- 0.52 (P = 0.01). In the HSD trails, L(p) values after ATP were 6.17 +/- 1.38. Perfusion with HSD decreased L(p) to 1.65 +/- 0.30 (P = 0.001). After endothelial activation, 135 mM NaCl had no effect on L(p); however, 185 mM NaCl decreased L(p) 3-fold and 235 mM NaCl decreased L(p) 6-fold. Units for L(p) are x10(-7) cm - s(-1). cmH(2)O(-1). CONCLUSIONS: Both HTS and HSD decreased hydraulic permeability after endothelial activation. These findings suggest that HTS may decrease microvascular fluid loss during states of elevated microvascular leak. In addition to the ability of hypertonic solutions to withdraw intracellular water to increase plasma volume, these findings propose an endothelial barrier mechanism whereby HTS and HSD act to maintain intravascular volume.

Animals↗
PubMed2003

Embryo donation: attitudes toward donation procedures and factors predicting willingness to donate.

BACKGROUND: The aim of the study was to assess infertile couples' attitudes toward the procedures of embryo donation (ED) and to identify factors predicting interest in donation. METHODS: Fifty-one couples who had received IVF treatment and had subsequently had embryos cryopreserved for >3 years were located and sent written information about the procedures for ED and possible implications of donation. A total of 49 couples agreed to participate in the study with 36 women and 31 men subsequently returning questionnaires describing their reasons for not claiming unused embryos and attitudes towards ED. RESULTS: Patients were supportive of donor screening procedures, but less comfortable sharing non-identifying information. Comfort levels declined as information became increasingly personal. Support for unconditional (i.e. the donation of embryos without conditions attached) and conditional (i.e. where couples could limit the donation of their embryos to persons/couples according to their preferences) models of donation was highly polarized and a substantial minority expressed strong opposition to each model. Willingness to donate was associated with greater comfort about disclosing personal information, a desire to know the outcome of donation and willingness to have future contact with a child, but not with current family size. CONCLUSIONS: Comfort in sharing information with a recipient couple is more important than acceptance of screening procedures, or attainment of family size goals in predicting willingness to donate embryos. Offering the option of conditional donation could increase the acceptability of ED for some patients.

Attitude↗
PubMed2003

Dextran modulates microvascular permeability: effect in isotonic and hypertonic solutions.

Hypertonic saline solutions with Dextran (HSD) have been advocated for rapid restoration of intravascular volume. Dextran is thought to increase the duration of action of hypertonic saline (HS) by selectively partitioning the water in the vascular space that has been drawn out of cells by HS. The goal of this study was to define the microvascular permeability modulating activity of Dextran in both isotonic and hypertonic solutions. We hypothesized that Dextran would decrease hydraulic permeability (Lp). Using the modified Landis micro-occlusion technique, single rat mesenteric venules were perfused with either normal Ringers (NR) with 135 mM NaCl or HS with 185 mM NaCl. In sequential cannulations of the venules, 1%, 2%, and 3% of Dextran was added to the NR perfusion (n = 6) and the HS perfusion (n = 6). The Lp was measured at baseline and after perfusion with each Dextran concentration. Baseline Lp measurements for NR and HS solutions were 1.01 +/- 0.034 and 5.14 +/- 1.02, respectively. In the NR group, the 2% and 3% Dextran decreased permeability below baseline levels to 0.79 +/- 0.028 (P < 0.0001) and 0.66 +/- 0.028 (P < 0.0001), respectively. In the HS group, the 2% and 3% Dextran decreased permeability to 1.65 +/- 0.53 (P < 0.0001) and 0.99 +/- 0.2 (P < 0.0001), respectively. All values for Lp are x10(-7) cm s(-1) x cm H2O(-1). The addition of Dextran to isotonic and hypertonic solutions results in a decrease in microvessel permeability. This effect is more pronounced with the perfusion of hypertonic solutions. The results demonstrate the oncotic potential of Dextran and its ability to hold water in the vascular space. Dextran may have a beneficial effect when used for resuscitation with HS by decreasing microvascular permeability and augmenting intravascular volume.

Animals↗
PubMed2003

The impact of albumin on hydraulic permeability: comparison of isotonic and hypertonic solutions.

Hypertonic saline, Dextran, and albumin have been advocated for rapid restoration of intravascular volume. The goal of this study was to define how albumin impacts the effects of hypertonic saline and Dextran on hydraulic permeability. We hypothesized that albumin would decrease the hydraulic permeability (L(p)) of isotonic and hypertonic solutions containing Dextran. Using the modified Landis micro-occlusion technique, single rat mesenteric venules were perfused with either Ringer's + 1% albumin (RA) or hypertonic saline + 1% albumin (HSA). In sequential cannulations of the venules, 1%, 2%, and 3% Dextran was added to the RA perfusion (n = 6) and the HSA perfusion (n = 6). These results were compared with similar studies completed without albumin. Albumin significantly decreased L(p) with all HS solutions studied compared with HS without albumin. Baseline L(p) measurements for RA and HSA solutions were 1.08 +/- 0.07 and 0.51 +/- 0.03, respectively. In the RA group, 2% and 3% Dextran was associated with a lower L(p) of 0.83 +/- 0.04 (P = 0.002) and 0.67 +/- 0.05 (P = 0.002), respectively. In the HSA group, 2% and 3% Dextran was associated with a lower L(p) of 0.37 +/- 0.02 (P = 0.001) and 0.32 +/- 0.02 (P < 0.0001), respectively. All values for L(p) are x 10(-7) cm x s(-1) x cmH2O(-1). Albumin maintains low hydraulic permeability levels during perfusion with hypertonic saline. In the setting of sufficient of endothelial albumin levels, hypertonic saline and Dextran may be advantageous when used for resuscitation by decreasing trans-endothelial fluid flux and augmenting intravascular volume.

Albumins↗
PubMed2003

Dose-dependent actions and temporal effects of angiotensin II on microvascular permeability.

BACKGROUND: Angiotensin II is a potent vasoconstrictor that is elevated after shock. Previous studies suggest that angiotensin II may directly modulate the endothelial barrier. Our hypothesis was that angiotensin II would increase microvascular hydraulic permeability in a dose-dependent fashion. METHODS: Hydraulic permeability (Lp) is a measure of water flow across the endothelial barrier. Lp was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. Venules were first perfused with Ringer's solution and baseline measurements of Lp were obtained. The venules were then recannulated and perfused with angiotensin II at 0.2 ng/mL (n = 5), 2.0 ng/mL (n = 5), 20 ng/mL (n = 8), and 200 ng/mL (n = 5), before final Lp measurements. RESULTS: Baseline values for Lp averaged 1.35 +/- 0.12. The 20-ng/mL and 200-ng/mL concentrations of angiotensin II significantly increased Lp to 3.86 +/- 0.4 (p < 0.0008) and 7.94 +/- 1.1 (p < 0.005), respectively. The maximal effect of angiotensin II was seen at 15 minutes of perfusion. Units for Lp are x 10(-7) cm.s-1.cm H2O-1. CONCLUSION: Angiotensin II affects a dose-dependent increase in microvascular permeability. This suggests that angiotensin II is involved in modulating intravascular fluid flux across the vessel wall. This effect is opposite to that observed in other vasoconstrictors that are up-regulated after trauma.

Angiotensin II↗
PubMed2003

Examining congruence between partners' perceived infertility-related stress and its relationship to marital adjustment and depression in infertile couples.

Because studies examining the emotional impact of infertility-related stress generally focus on individuals, there has been little research examining how relationship and individual variables are linked. The purpose of this study was to explore the impact of congruence (e.g., agreement) between partner's perceived infertility-related stress and its effects on depression and marital adjustment in infertile men and women. Couples referred for infertility treatments at a University-affiliated teaching hospital completed the Fertility Problem Inventory (FPI), the Beck Depression Inventory (BDI), and the Dyadic Adjustment Scale (DAS) 3 months prior to their first treatment cycle. Study findings show that men and women in couples who perceived equal levels of social infertility stress reported higher levels of marital adjustment when compared to men and women in couples who perceived the stress differently. In addition, women in couples who felt a similar need for parenthood reported significantly higher levels of marital satisfaction when compared to women in couples where the males reported a greater need for parenthood. While couple incongruence was unrelated to depression in males, incongruence over relationship concerns and the need for parenthood was related to female depression. These findings provide initial support for the theory that high levels of agreement between partners related to the stresses they experience help them successfully manage the impact of these stressful life events. Possibilities for future research examining the construct of couple congruence are discussed.

Adult↗
PubMed2002

Effect of angiotensin II on microvascular permeability.

BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor that is released during shock and sepsis. It is known to have activity on vascular endothelial cells. We hypothesized that Ang II plays a role in the modulation of fluid flux across the microvascular endothelium. MATERIALS AND METHODS: Hydraulic permeability (L(p)) is a measure of water flow across the endothelial barrier. L(p) was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. To determine the effect of Ang II in basal states, venules were perfused with control Ringer's and measures of L(p) obtained before and after a subsequent perfusion with 20 ng/ml Ang II (n = 5). In additional studies 10 microM ATP was used to activate the endothelium, thereby increasing the L(p) approximately 3-fold. Measures of L(p) were then obtained before and after a subsequent perfusion with 20 ng/ml Ang II (n = 6). RESULTS: In the basal state, Ang II significantly increased L(p) from 1.45 +/- 0.29 to 3.45 +/- 0.28 (P = 0.013). Following activation by ATP, Ang II decreased L(p) from 4.51 +/- 0.45 to 3.05 +/- 0.28 (P = 0.02). Units for L(p) are x10(-7) cm s(-1) x cm H(2)O(-1). CONCLUSIONS: Ang II increased microvascular permeability under basal conditions while in the activated state it decreased microvascular permeability. In addition to its vasopressor function this differential action of Ang II in modulating fluid flux across the fsendothelium in basal versus activated states may be of benefit under pathophysiological conditions and may be amenable to pharmacologic manipulation.

Adenosine Triphosphate↗
PubMed2002

The effect of tonicity and hypertonic solutions on microvascular permeability.

BACKGROUND: The effect of hypertonic saline (HS) on microvascular permeability is unclear. We hypothesized that varying degrees of tonicity and HS solutions alter microvascular fluid flux across the endothelium. METHODS: Hydraulic permeability (L(p)) is a measure of water flow across the endothelial barrier. L(p) was measured in cannulated rat mesenteric venules using the modified Landis micro-occlusion technique. The effect of tonicity was tested by measuring L(p) after successive perfusions with Ringers' solutions of varying sodium chloride (NaCl) concentrations (85, 135, 185, and 235 mM) (n = 6). Additional venules were perfused with control Ringers' ([NaCl] = 135 mM) and measures of L(p) were obtained after subsequent perfusions with 7% NaCl followed by 7% NaCl with 6% dextran (n = 6). RESULTS: Tonicity had a significant dose-dependent effect on L(p) (P < 0.0001). Perfusion with 7% NaCl significantly increased L(p) (P < 0.0001). The addition of 6% dextran to 7% NaCl significantly decreased L(p) compared with perfusion with 7% NaCl alone (P = 0.002). CONCLUSIONS: We conclude that (1) tonicity influences microvascular permeability, (2) HS increases microvascular permeability, and (3) the addition of dextran to HS greatly attenuates this response. These findings suggest an important role for tonicity and a possible deleterious effect of HS in modulating microvascular permeability as well as the benefit of dextran with HS for maintaining intravascular volume.

Animals↗