Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists.

The Placental Pathology Practice Guideline Development Task Force, a multidisciplinary group, has prepared this guideline to assist those involved with placental examination. It provides recommendations related to indications and methods for placental examination as well as sample worksheets. An algorithm for the handling of placentas summarizes the recommendations of the guideline. A summary of specific findings of placental examination together with their pathogenesis and clinical associations is also provided. Recommendations related to reporting with sample reporting formats are included. The guideline is intended as an educational tool, and its use should be guided by the individual circumstances and care setting of specific cases.

The effects of antenatal steroid use in premature rupture of membranes.

We sought to determine if antepartum steroid treatment offers any clinical benefits to patients with premature rupture of membranes. One hundred and forty-five maternal-neonatal pairs were studied. Forty-five maternal-neonatal pairs with premature, preterm rupture of membranes received steroids during 24-35 weeks' gestation. One hundred maternal-neonatal pairs received no antenatal steroids. The 2 groups were identical with regard to gestational age at rupture of membranes, gravity, parity, race, fetal gender, socioeconomic status, smoking, and preterm labour risk factors. Study of the data revealed that maternal chorioamnionitis was less frequent in the steroid group (p < 0.001). Bronchopulmonary dysplasia (oxygen dependent at discharge at term gestational age) was less frequent in the steroid group (p < 0.05). The remainder of the data revealed no statistically significant differences in preterm delivery rate, necrotizing enterocolitis, respiratory distress syndrome, intraventricular haemorrhage rate or severity of haemorrhage, hospital days, latency to delivery, or ventilator days. Antepartum steroid use in preterm rupture of membranes appears to offer clinical benefit in premature infants by lessening the rate of bronchopulmonary dysplasia in those infants receiving antepartum steroids.

Hypoglycemia in normal neonates appropriate for gestational age.

A prospective study was performed to compare the frequency of hypoglycemia in normal neonates appropriate for gestational age delivered by cesarean section and neonates delivered by normal vaginal deliveries (n = 60). Intrapartal and prenatal risk factors were recorded. A cord glucose reading and a glucose reading within the first 2 hours of age were analyzed. Hypoglycemia was defined as a blood glucose level of < 40 mg/dl in a neonate. The study disclosed a 43% incidence of hypoglycemia in neonates delivered by cesarean section and a 37% incidence in neonates delivered vaginally. Neonates who were black, male, or both had a higher incidence of hypoglycemia. Other prenatal or intrapartal factors were not significantly associated with the development of hypoglycemia. The incidence of hypoglycemia in this study was much higher than in previous studies of neonates appropriate for gestational age that were performed before conduction anesthesia was widely used. Further studies should evaluate the possible impact of perinatal anesthesia on the development of transient neonatal hypoglycemia.

Association between maternal-fetal HLA-DR relationships and fetal growth.

PROBLEM: To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight. METHOD: A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal). RESULTS: After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate. CONCLUSION: Our findings supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.

Mechanisms of ventilator-induced lung injury.

OBJECTIVES: To describe the physiologic mechanisms of ventilator-induced lung injury and to define the major ventilator and host-dependent risk factors that contribute to such injury. DATA SOURCE: Basic science and clinical studies related to ventilator-induced barotrauma and lung pathophysiology. STUDY SELECTION: Emphasis on controlled, experimental studies and clinical studies related to specific mechanisms. DATA EXTRACTION: Preference given to studies with quantitative end-points to assess damage and causal relationships. DATA SYNTHESIS: Related studies are integrated to obtain basic mechanisms of damage where possible. CONCLUSIONS: Ventilation with high tidal volumes can increase vascular filtration pressures; produce stress fractures of capillary endothelium, epithelium, and basement membrane; and cause lung rupture. Mechanical damage leads to leakage of fluid, protein, and blood into tissue and air spaces or leakage of air into tissue spaces. This process is followed by an inflammatory response and possibly a reduced defense against infection. Predisposing factors for lung injury are high peak inspiratory volumes and pressures, a high mean airway pressure, structural immaturity of lung and chest wall, surfactant insufficiency or inactivation, and preexisting lung disease. Damage can be minimized by preventing overdistention of functional lung units during therapeutic ventilation.

Maternal-fetal HLA-DR relationships and pregnancy-induced hypertension.

OBJECTIVE: Some studies have found an increased prevalence of pregnancy-induced hypertension among women sharing HLA antigens with their spouses or fetuses, thus supporting the hypothesis that maternal sensitization to fetal HLA alloantigens reduces the risk for pregnancy-induced hypertension. However, not all studies have confirmed these findings. No investigators have examined the four different types of maternal-fetal HLA relationships in their studies of pregnancy-induced hypertension. Our goal was to examine such associations to test further the HLA-allosensitization hypothesis. METHODS: We conducted a cohort study of pregnancy-induced hypertension among 683 nulliparous women. Women and their neonates were typed for HLA-A, -B, -DR, and -DQ antigens using serologic techniques to establish maternal-fetal relationships. RESULTS: We found an increased prevalence of pregnancy-induced hypertension when the fetus, but not the mother, was potentially exposed to HLA-DR alloantigens (maternal allogenicity) compared with the other three conditions combined (P < .003). Controlling for confounding factors, the increased prevalence of pregnancy-induced hypertension persisted in situations of maternal HLA-DR allogenicity (P < .007). CONCLUSIONS: Based upon our observations and other immunologic studies of pregnancy-induced hypertensive and uncomplicated pregnancies, we conclude that a maternal humoral response against fetal anti-HLA-DR immunoglobulin (IgG) antibody may influence the development of pregnancy-induced hypertension. This could occur when an immunocompetent fetus is exposed to maternal HLA-DR alloantigens, maternal exposure to fetal HLA-DR alloantigens alloantigens, maternal exposure to fetal HLA-DR alloantigens is not possible, and fetal IgG antibody bears paternally inherited markers allogeneic to the mother.

Increased sensitivity to mechanical ventilation after surfactant inactivation in young rabbit lungs.

OBJECTIVES: To study the individual and combined effects of surfactant inactivation and mechanical ventilation on pulmonary microvascular permeability and lung compliance. DESIGN: Prospective, controlled trial. An isolated, perfused, lung model of surfactant inactivation and mechanical ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks) New Zealand white rabbits. SETTING: Laboratory of a university-affiliated medical school. MEASUREMENTS AND MAIN RESULTS: Isolated, perfused lungs were prepared for measurement of the capillary filtration coefficient before and after one of four interventions: instillation of dioctyl succinate, a surfactant inactivator, without ventilation (group 1); ventilation without dioctyl succinate at 15, 30, or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group 3); and control lungs without dioctyl succinate or ventilation (group 4). A significant increase in the capillary filtration coefficient was noted after dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced a significantly greater increase in the capillary filtration coefficient than ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. CONCLUSIONS: These data suggest that ventilation after surfactant inactivation is more injurious to the pulmonary microvasculature than ventilation alone, and that generalized lung overdistention is not the primary mechanism for microvascular injury in the diseased, noncompliant lung. The increases seen in the capillary filtration coefficient in postventilated surfactant inactivated lungs, even at low-ventilation pressures, suggest that low peak inspiratory pressures do not overdistend the dioctyl succinate-treated lung.

Endothelium-derived and intraneuronal nitric oxide-dependent inhibition of norepinephrine efflux from sympathetic nerves by bradykinin.

Evidence is presented that bradykinin inhibits norepinephrine efflux from sympathetic nerves innervating canine mesenteric and pulmonary arteries, in part, by releasing endothelium-derived relaxing factor (EDRF) from the vascular endothelium. Moreover, in the absence of vascular endothelium, bradykinin also inhibits norepinephrine efflux from the sympathetic nerve terminals innervating these blood vessels. This inhibition is attenuated by canavanine and LNMMA, which inhibit the conversion of arginine to nitric oxide, and is enhanced after overnight incubation of blood vessels with arginine. In endothelium-rubbed blood vessels the inhibitory effect of bradykinin on norepinephrine efflux is enhanced by increasing extracellular calcium ion ([Ca2+]o) and attenuated by nitrendipine. We propose that bradykinin inhibits norepinephrine efflux by stimulating intraneuronal nitric oxide from arginine.

Cyclic GMP modulates release of norepinephrine from adrenergic nerves innervating canine arteries.

Evidence is presented that compounds which stimulate the soluble form of the enzyme guanylate cyclase or which inhibit the enzyme cGMP phosphodiesterase (PDE), responsible for the degradation of cGMP (including endothelium-derived relaxing factor) are inhibitors of sympathetic neurotransmission to vascular smooth muscle and inhibit the efflux of norepinephrine from sympathetic nerves. Moreover, prostacyclin, papaverine, iloprost, and forskolin, compounds which stimulate the enzyme adenylate cyclase, and rolipram (neural specific) and milrinone, enoximone, and piroximone (muscle specific) inhibitors of Type III cAMP PDE and degradation of cAMP, do not inhibit nerve stimulation to most blood vessels. The data support the concept that cGMP may act as a negative feedback modulator of physiologic frequencies of sympathetic nerve activity to blood vessels. cAMP does not appear to modulate adrenergic neurotransmission to vascular smooth muscle at physiologic frequencies of neural stimulation.

Inhibition of sympathetic neurotransmitter release by modulators of cyclic GMP in canine vascular smooth muscle.

The contractile response to neurally released norepinephrine (NE) from sympathetic nerve endings innervating vascular smooth muscle are inhibited by substances which raise either cyclic AMP and cyclic GMP concentrations in smooth muscle. However, cyclic AMP is believed to facilitate NE release from sympathetic nerves whereas the role of cyclic GMP in this process is undefined. We examined the effects of presumed modulation of the intraneuronal concentration of cyclic AMP and cyclic GMP on sympathetic neurotransmission to isolated canine mesenteric artery by measurement of the efflux of [2-14C]NE during transmural nerve stimulation (calcium dependent release of NE) and administration of tyramine (calcium independent release of NE) and measurement of the contractions to exogenous NE and tyramine. Stimulation of adenylate cyclase with forskolin, prostacyclin and iloprost, a stable prostacyclin analog, and inhibition of Type III cyclic AMP phosphodiesterase with neural specific rolipram, 'non-specific pelrinone and milrinone and isobutylmethylxanthine did not enhance the efflux of [2-14C]NE from sympathetic nerves innervating the blood vessels. Isoproterenol enhanced the efflux of [2-14C]NE. The effect was inhibited by propranolol but not affected by milrinone, amrinone or rolipram. Activators of guanylate cyclase (SIN-1a an active metabolic of molsidomine, nitroglycerin and sodium nitroprusside) and inhibitors of Type II cyclic GMP phosphodiesterase (M&B-22948 and verofyllin) inhibited the efflux of NE released by transmural nerve stimulation but not by tyramine. These data support the conclusion that cyclic GMP may be an inhibitory modulator of calcium and depolarization dependent NE release from sympathetic nerves, whereas neuronal cyclic AMP may not be a primary modulator of neurotransmission to vascular smooth muscle.

Lung edema caused by high peak inspiratory pressures in dogs. Role of increased microvascular filtration pressure and permeability.

Mechanical ventilation with high peak airway pressures (Paw) has been shown to induce pulmonary edema in animal experiments, but the relative contributions of transvascular filtration pressure and microvascular permeability are unclear. Therefore, we examined the effects of positive-pressure ventilation on two groups of open-chest dogs ventilated for 30 min with a peak Paw of 21.8 +/- 2.3 cm H2O (Low Paw) or 64.3 +/- 3.5 cm H2O (High Paw). No hemodynamic changes were observed in the Low Paw group during ventilation, but mean pulmonary artery pressure (Ppa) increased by 9.9 cm H2O, peak inspiratory Ppa by 24.6 cm H2O, and estimated mean microvascular pressure by 12.5 cm H2O during High Paw ventilation. During the same period, lung lymph flow increased by 435% in the High Paw and 35% in the Low Paw groups, and the terminal extravascular lung water/blood-free dry weight ratios were 5.65 +/- 0.27 and 4.43 +/- 0.13 g/g, respectively, for the two groups. Lung lymph protein clearances and minimal lymph/plasma ratios of total protein were significantly higher (p less than 0.05) after 2 h of increased left atrial pressure (PLA) in the High Paw group versus the Low Paw group, which indicates a significant increase in microvascular permeability. Lymph prostacyclin concentration in pulmonary lymph, measured as the stable metabolite 6-0-PGF1 alpha, was increased significantly by 70 to 150% from baseline (p less than 0.05) in both groups during the periods of increased Paw and increased PLA, but it was not significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern.

To study the pulmonary microvascular injury produced by ventilation barotrauma, the isolated perfused lungs of 4 to 6-wk-old New Zealand white rabbits were ventilated by one of the following methods: peak inspiratory pressure (PIP) 23 cm H2O, gas flow rate 1.1 L/min (group 1); PIP 27 cm H2O, gas flow rate 6.9 L/min (group 2); PIP 50 cm H2O, gas flow rate 1.9 L/min (group 3); or PIP 53 cm H2O, gas flow rate 8.3 L/min (group 4). Microvascular permeability was assessed using the capillary filtration coefficient (Kfc) before and 5, 30, and 60 min after a 15-min period of ventilation. Baseline Kfc was not significantly different between groups. A significant increase over the baseline Kfc was noted at 60 min in group 2 and in all postventilation Kfc values in groups 3 and 4 (p less than .05). Group 1 Kfc values did not change significantly after ventilation. At all post-ventilation times, values for Kfc were significantly greater in groups 3 and 4 than in group 1 (p less than .05). Group 4 Kfc values were significantly greater than those in group 2 at 5 and 30 min postventilation. These data indicate that high PIP, and to a lesser extent, high gas flow rates cause microvascular injury in the compliant nonadult lung and suggest that the combination of high PIP and high gas flow rates are the most threatening to microvascular integrity.

Release of norepinephrine from adrenergic nerve endings of blood vessels is modulated by endothelium-derived relaxing factor.

The release of norepinephrine from adrenergic nerve endings is inhibited by substances which raise cyclic 3',5'-guanosine monophosphate (cGMP) in neural tissue. Endothelium-derived relaxing factor (EDRF) elevates cGMP in vascular smooth muscle. Thus, EDRF may also modulate the release of norepinephrine (NE) from adrenergic nerves. We tested this postulate in isolated canine pulmonary arteries and veins using the technique of superfusion and measurement of the efflux of radiolabeled NE during transmural nerve stimulation at 1, 2, 4, 8, 16 and 32 Hz for 10 min. In segments of artery and vein with intact endothelium the contractile responses to low frequency nerve stimulation were decreased when compared to endothelium rubbed blood vessels. Electrical stimulation of arteries and veins with intact endothelium for 10 min released less 2-[14C]-NE than rubbed blood vessels, especially at the lower frequencies of 1, 2 and 4 Hz, with lesser effects at frequencies of 16 and 32 Hz. Using the technique of bioassay, EDRF from porcine thoracic aorta inhibited the efflux of 2-[14C]-NE from the pulmonary artery and vein. The findings support the conclusion that the endothelium can inhibit release of NE from sympathetic nerve innervating canine pulmonary artery and vein. The endothelium, in part through EDRF, can act as an endogenous inhibitor or sympathetic neurotransmitter release.

Chest wall restriction limits high airway pressure-induced lung injury in young rabbits.

High peak inspiratory pressures (PIP) during mechanical ventilation can induce lung injury. In the present study we compare the respective roles of high tidal volume with high PIP in intact immature rabbits to determine whether the increase in capillary permeability is the result of overdistension of the lung or direct pressure effects. New Zealand White rabbits were assigned to one of three protocols, which produced different degrees of inspiratory volume limitation: intact closed-chest animals (CC), closed-chest animals with a full-body plaster cast (C), and isolated excised lungs (IL). The intact animals were ventilated at 15, 30, or 45 cmH2O PIP for 1 h, and the lungs of the CC and C groups were placed in an isolated lung perfusion system. Microvascular permeability was evaluated using the capillary filtration coefficient (Kfc). Base-line Kfc for isolated lungs before ventilation was 0.33 +/- 0.31 ml.min-1.cmH2O-1.100g-1 and was not different from the Kfc in the CC group ventilated with 15 cmH2O PIP. Kfc increased by 850% after ventilation with only 15 cmH2O PIP in the unrestricted IL group, and in the CC group Kfc increased by 31% after 30 cmH2O PIP and 430% after 45 cmH2O PIP. Inspiratory volume limitation by the plaster cast in the C group prevented any significant increase in Kfc at the PIP values used. These data indicate that volume distension of the lung rather than high PIP per se produces microvascular damage in the immature rabbit lung.

The endothelium modulates adrenergic neurotransmission to canine pulmonary arteries and veins.

We tested the postulate that endothelium-derived relaxing factor (EDRF) modulates adrenergic neuroeffector transmission in isolated canine pulmonary arteries and veins, using the technique of superfusion and measurement of the efflux of [2-14C]NE during transmural nerve stimulation at 1, 2, 4, 8, 16 and 32 Hz for 10 and 30 min. In endothelium-rubbed artery and vein the contractile responses to low frequency nerve stimulation were enhanced, when compared to those from endothelium rubbed blood vessels. Transmural nerve stimulation of endothelium competent arteries and veins for 10 min released less [2-14C]NE than denuded arteries and veins, especially at 1, 2 and 4 Hz, with smaller differences evident at higher frequencies (16 and 32 Hz) of stimulation. Superfusion of endothelium rubbed blood vessels with effluent from canine thoracic aorta decreased the release of [2-14C]NE during nerve stimulation. These findings suggest that the endothelium and EDRF can inhibit release of adrenergic neurotransmitter from canine pulmonary arteries and veins. The endothelium may act as an endogenous modulator of adrenergic neurotransmission to canine vascular smooth muscle.