Absorption of iron in rats with experimental enteritis.

Inflammatory conditions of the gastrointestinal tract and iron-deficiency anemia are very common in humans. Acute intestinal inflammation was pathologically established in rats by intraluminal administration of acetic acid into the duodenum and the proximal jejunum. The study included two control groups of intact (untreated) rats and sham-operated (saline-treated) rats for each intestinal segment. A third group of rats received acetic acid. The acetic acid-induced inflammatory process was established histopathologically and biochemically. Two days after treatment, iron absorption was measured using ligated 10-cm loops of proximal jejunum or ligated duodenum in which 59Fe was injected intraluminally (n = 6 in each group). In another four control groups (intact and sham-operated for each intestinal segment) and two acetic acid-treated groups, serosal-luminal secretion of 59Fe was measured after intravenous injection (n = 5 in each group). 59Fe transfer from the lumens of the duodenum and jejunum to the portal system was significantly lower in those rats in whom inflammation was induced by acetic acid. There was no apparent serosal-luminal secretion of intravenously injected 59Fe in any of the studied groups. We conclude that acetic acid-induced intestinal inflammation significantly reduces iron absorption by the duodenum and the proximal jejunum.

Paraquat-induced formation of leukotriene B4 in rat lungs: modulation by N-acetylcysteine.

The present work is focused on the formation of the inflammatory mediator leukotriene B4 (LTB4) in the lungs of paraquat (PQ)-intoxicated rats. The levels of LTB4 and the number of neutrophils in lung lavages of PQ-intoxicated rats, measured 12 h after 30 mg/kg PQ, increased significantly compared with those of control animals; administration of 50 mg/kg IP N-acetylcysteine (NAC), 8 h after PQ, inhibited this effect. The release of LTB4 from alveolar macrophages (AM) or alveolar epithelial type II cells from healthy animals incubated with PQ and/or NAC did not offer' an explanation for the effect of these chemicals on LTB4 in the bronchoalveolar lavage fluid (BALF). The PQ-enhanced, NAC-inhibited release of arachidonic acid (AA) by alveolar epithelial type II cells did, however, explain our in vivo results, when one assumes that the AM synthesize their 5-lipoxygenase products from alveolar epithelial cell-derived AA, an hypothesis demonstrated already by other researchers.

N-acetylcysteine delays the infiltration of inflammatory cells into the lungs of paraquat-intoxicated rats.

We investigated a possible role for N-acetylcysteine (NAC), a well-known antioxidant and free radical scavenger, against oxidative lung damage as observed in the in vivo model of paraquat-intoxicated rats. The administration of two ip doses of 50 mg/kg NAC to paraquat-intoxicated animals did not change the glutathione status of the lungs, as determined by the measurement of nonprotein sulfhydryl (NP-SH) groups. The administration of NAC did however suppress the paraquat-induced release of chemoattractants for neutrophils in the bronchoalveolar fluid when the lavage was carried out 12 hr after the administration of 30 mg/kg paraquat. Also, in the intoxicated NAC-treated animals, the infiltration of inflammatory cells was significantly reduced, as demonstrated by the examination of the cell composition of the bronchoalveolar lavage (BAL), 24 hr after paraquat. Phorbol myristate acetate-stimulated superoxide anion production from the AM isolated from the BAL of paraquat-intoxicated nontreated animals was lower than that of controls, whereas in the NAC-treated animals, it was close to that of the controls. The obtained results indicate that NAC has a protective effect against oxidative lung damage by delaying inflammation. It also prevents the paraquat-induced reduction of superoxide anion production by stimulated AM. In the present model, however, the NAC administration regimen did not affect the survival rate of paraquat-intoxicated rats.

Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes.

Successful implementation of bone marrow transplantation for hematopoietic reconstitution is limited by the lack of suitably HLA-matched donors and by the occurrence of graft-versus-host disease that frequently accompanies this procedure. Recent clinical reports have implied that the use of umbilical cord blood as a source of transplantable stem cells may solve these problems. To date, definitive experiments have not been performed to assess the immunological potential of T cells found in umbilical cord blood, which could mediate graft-versus-host disease. In the present study we have observed that umbilical cord blood contains T lymphocytes that appear to be phenotypically immature. In addition, umbilical cord blood lymphocytes appeared to be functionally immature as shown by minimal responses to stimulation with interleukin 2, phytohemagglutinin, or alloantigens. Thus, umbilical cord blood may be more suitable for allogeneic transplantation than bone marrow in that these cord blood cells may not be as capable of mediating graft-versus-host disease.

Doppler flow velocities in single umbilical arteries.

Fetal compromise has been associated with an umbilical artery waveform pattern of low or absent diastolic velocity relative to systolic velocity. Fetuses with single umbilical arteries have an increased risk of major malformations, mortality, retarded fetal growth, and prematurity. In this study Doppler flow velocities were obtained in 13 fetuses (four twin fetuses and nine singletons) with a single umbilical artery. Five (38%) fetuses, consisting of four singletons and one twin, had anomalies. Six (46%) fetuses were small for gestational age, including two twin fetuses and three singleton fetuses with anomalies. Three (23%) of the 13 systolic-to-diastolic velocity ratios were abnormally high. Whereas this is a higher rate of abnormal ratios than the reported 2% to 3% in control populations, it is interesting to note that 77% of fetuses with single umbilical arteries had normal systolic-to-diastolic ratios.

Significance of oligohydramnios complicating pregnancy.

Oligohydramnios is a serious complication of pregnancy that is associated with a poor perinatal outcome. Eighty pregnancies complicated by oligohydramnios constitute the basis for this retrospective study. Forty patients had premature rupture of the membranes; of these, outcomes were good in 25. Twelve of 14 fetuses with oligohydramnios and intrauterine growth retardation survived. None of the nine fetuses with severe renal anomalies lived. None of the twins with twin-twin transfusion and oligohydramnios survived. Six pregnancies with oligohydramnios and premature separation of the placenta were identified; all of these resulted in fetal or neonatal death during the second trimester.

Doppler studies of vena cava flows in human fetuses. Insights into normal and abnormal cardiac physiology.

We examined vena cava Doppler flow velocity tracings from 69 fetuses between 22 and 40 weeks' gestation. Twenty-three fetuses had arrhythmias. Fifteen fetuses had absent end-diastolic Doppler velocities in the umbilical artery, a condition associated with intrauterine growth retardation, and 15 normal fetuses with normal umbilical artery Doppler velocity ratios were matched by gestational age. In studies in 16 additional fetuses, inferior vena cava Doppler velocity waveforms were compared with superior vena cava Doppler velocity waveforms. Peak velocities and time-velocity integrals of forward or reverse flow during systole, early diastole, and atrial contraction were measured. In addition, the time-velocity integral during flow coincident with atrial contraction (a wave) was expressed as a percent of the time-velocity integral of total forward flow during both systole and early diastole. Systolic-to-diastolic ratios of inferior vena cava forward time-velocity integrals were not significantly different from systolic-to-diastolic ratios of superior vena cava forward time-velocity integrals (p = 0.86), but the percent of blood moving in a reverse direction during atrial contraction in the inferior vena cava was greater than the percent of blood moving in a reverse direction in the superior vena cava (p less than 0.05). Relative forward flow in early diastole in the group of normal fetuses increased with advancing gestational age (r = 0.60, p less than 0.05). During premature atrial contractions flow in the inferior vena cava was reversed, and the percent of reverse flow during atrial systole increased significantly from 4.5 +/- 0.3% to 28.3 +/- 3.7% (mean +/- SEM, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal pericardial effusion.

Forty-four fetuses with pericardial effusions have been identified by ultrasonographic examinations. The clinical histories and courses of these patients were reviewed. At least eight different clinical features accompanied and were probably responsible for the pericardial effusions. The most common cause of a fetal pericardial effusion was heart failure (13 fetuses). Fetal renal cystic dysplasia with oligohydramnios and other anomalies was present in six fetuses. Four of this group had microscopic evidence of pericarditis on postmortem examination. Fetal pericardial effusions are always a manifestation of another disease process often presenting as fetal hydrops. Some pericardial effusions are transient. The etiologic origin of fetal pericardial effusions differs from that in the child or adult.

Prenatal diagnosis of congestive heart failure in a fetus with a sacrococcygeal teratoma.

Two-dimensional Doppler echocardiography was used to diagnose congestive heart failure in a fetus with a large sacrococcygeal teratoma. Ultrasound performed for size-date inconsistency revealed a 27.5-week fetus with hydrops and a large solid and cystic mass in the sacral region. Fetal echocardiography showed dilated ventricles and a pericardial effusion; Doppler ultrasound demonstrated increased velocities and volume flows, along with tricuspid and mitral regurgitation. At delivery, the mass was bleeding actively, the amniotic fluid was markedly bloody, and the neonatal hematocrit was 10%. We postulate that intrauterine hemorrhage from the teratoma led to anemia and high-output cardiac failure confirmed by Doppler echocardiography, and suggest that all fetuses with sacrococcygeal teratomas be evaluated by two-dimensional Doppler echocardiography to detect the presence of congestive heart failure, in order to allow well-timed therapeutic interventions.

Fetal cardiac Doppler flow studies in prenatal diagnosis of heart disease.

The prenatal diagnosis of fetal cardiac disease has become increasingly accurate as the technology of ultrasound has improved. Although two-dimensional real-time ultrasound remains the primary method of diagnosis, Doppler blood flow velocity estimates can provide valuable pathophysiologic information to support the anatomic diagnosis. We present six cases in which Doppler studies contributed to the accuracy of the diagnosis of fetal heart disease, including tetralogy of Fallot, right and left ventricular hypoplasia, atrioventricular canal defect, double-outlet right ventricle, and pulmonic stenosis. Velocities in these cases are compared with those in normal fetuses. If Doppler flow velocities are not consistent with the observed morphologic changes, further observations are indicated. Inasmuch as most anatomical heart lesions result in altered flow patterns, Doppler investigations of intracardiac and extracardiac flow should be a routine component of the fetal echocardiogram when structural abnormalities are found.

Changes in intracardiac Doppler blood flow velocities in fetuses with absent umbilical artery diastolic flow.

Umbilical artery Doppler blood flow velocity studies were used to identify 14 fetuses with absent flow during diastole to determine the significance of absent umbilical artery diastolic flow. Outcomes of these fetuses were recorded, and the associated intracardiac Doppler changes were identified in 12 of them. Maximal and mean intracardiac flow velocities were measured, and volume flows through the right (tricuspid valve, pulmonary valve) and left (mitral valve, aortic valve) sides of the heart were compared. Ratios of intracardiac peak flow velocity in late diastole to peak flow velocity in early diastole were calculated. Eleven fetuses had intrauterine growth retardation, and four had multiple congenital anomalies. Fetuses with no diastolic flow in the umbilical artery had increased volume flow across the tricuspid and pulmonary valves compared with normal fetuses of similar weights. The ratio of right-sided to left-sided volume flow in the heart (2.15:1) was increased compared with values in normal fetuses (1.33:1, p less than 0.01). The ratio of late diastolic to early diastolic peak flow velocities across the mitral valve was decreased (p less than 0.01). Absent umbilical artery diastolic flow is associated with increased tricuspid and pulmonary valve volume flow and changes in mitral flow velocity patterns, which suggests that there are alterations in left ventricular function.

Congenital heart block and cardiac anomalies in the absence of maternal connective tissue disease.

The association of congenital heart block with maternal connective tissue disease and autoimmunity has been recently reported. Two cases of heart block were diagnosed in utero at 23 and 24 weeks' gestation. Both mothers had extensive workups for connective tissue disease that were negative. Two-dimensional and Doppler echocardiography were performed in utero and both infants had left atrial isomerism, atrioventricular canal defects, and severe hydrops in addition to heart block. Review of the recent literature identifies a subset of congenital heart block in which the mothers have no evidence for connective tissue disease, and the fetus or neonate has complex cardiac malformations and hydrops. The common features in these babies are atrioventricular canal defects and isomerism. No reports of congenital heart disease among the children of mothers with connective tissue disease fit this description. Our recent experience and literature review emphasize the previously known association between congenital heart block and congenital heart disease. This association is especially important in light of the poor prognosis for this group of fetuses and neonates.

Cardiac Doppler flows during fetal arrhythmias: physiologic consequences.

Eighty-six fetuses of 21-41 weeks' gestation with arrhythmias were studied with ultrasound and heart rate monitoring. The type of arrhythmia was identified by M-mode studies and was confirmed by postnatal electrocardiogram in 70 infants. The most common arrhythmia was premature atrial contractions (76), followed by premature ventricular contractions (five), paroxysmal supraventricular tachycardia (four), and atrial fibrillation/flutter (one). Doppler echocardiography was performed in 54 fetuses to measure flow velocities across the atrioventricular and semilunar valves. After isolated premature atrial and ventricular contractions, post-extrasystolic potentiation was demonstrated by an increase in fractional shortening (N = 32) of 49 +/- 6% in the right ventricle and 64 +/- 7% in the left ventricle. When post-extrasystolic beats were compared with normal beats, Doppler-determined time-velocity integrals increased 43% across the tricuspid valve, 41% across the mitral valve, 34% across the pulmonary valve, and 38% across the aortic valve. Mean velocity increased significantly after conversion to normal sinus rhythm in the five fetuses with supraventricular tachycardia (P less than .05). By studying the physiologic consequences of fetal arrhythmias using two-dimensional Doppler and M-mode ultrasound, we have documented the presence of post-extrasystolic potentiation after premature contractions, the existence of the Frank-Starling mechanism, and an increase in mean velocity (and therefore in cardiac output) after conversion of fetal tachyarrhythmias to normal sinus rhythm.

Effect of maternal magnesium sulfate treatment on fetal heart rate variability.

The effect of maternal magnesium sulfate treatment on fetal heart rate variability (FHRV) was evaluated by comparing the maternal serum magnesium level drawn during labor to the degree of FHRV seen concurrently on fetal rate heart monitor strips. The records of 57 patients treated with intravenous magnesium sulfate for hypertensive disorders of pregnancy were studied. Fetal heart rate variability was measured by both subjective assessment and objective measurement. The difference in beats/min between the average high and low fetal heart rates, at the time the magnesium level obtained, was used as the objective measurement. Labor records were reviewed and neonatal outcome recorded. Data from individual patients not treated with analgesics were analyzed separately in addition. Statistical methods used included analysis of variance, Student's t-test, and Chi square analysis. The range of magnesium levels was 2.3-7.4 mEq/L. Thirty-four women had single determinations of magnesium levels and 23 had multiple determinations. Statistical analysis showed no significant change in FHRV with increasing maternal magnesium levels. In addition, no significant effect of maternal magnesium level on FHRV was noted in the group that did not receive meperidine, morphine, or epidural anesthesia. Neonatal outcome, assessed by Apgar scores, did not vary with maternal magnesium level. We conclude that maternal magnesium sulfate treatment, in the therapeutic ranges normally obtained, does not significantly affect fetal heart rate variability.

Fetal pulmonary artery and aorta: two-dimensional Doppler echocardiography.

Two-dimensional and pulsed Doppler ultrasound techniques were used to examine 87 fetuses between 17 and 41 weeks' gestation in order to compare pulmonary artery and aortic outflow diameters, mean and maximal flow velocities, and transvalve flows. For purposes of analysis, fetuses were divided into two groups: those less than 31 weeks, and those of 31 weeks or more. Diameters of the pulmonary artery and aortic outflow region increased with advancing gestational age (P less than .001), while mean and maximal Doppler flow velocities did not change. Transvalve volume flow increased across both regions (pulmonary artery from 381 +/- 12 mL/minute to 530 +/- 13 mL/minute and aortic outflow from 286 +/- 10 mL/minute to 410 +/- 13 mL/minute, P less than .001) with advancing gestation. Pulmonary artery diameters were larger than aortic outflow diameters in both groups (P less than .01), while mean Doppler flow velocities were not significantly different. Maximal Doppler flow velocities were greater in the aorta than in the pulmonary artery (P less than .001), and transvalve flow was greater across the pulmonary artery than the aorta in both groups (P less than .05, ratio 1.3:1). This work demonstrates differences in fetal pulmonary artery and aortic outflow anatomy and physiology that must be considered in evaluating studies of fetal cardiac physiology.

Effect of long-term oral contraceptive therapy before pregnancy on maternal and fetal zinc and copper status.

Thirteen pregnant women who conceived within six months after terminating oral contraceptive agent therapy of at least three years' duration participated in this study. Nine pregnant women with no history of oral contraceptive agent use served as controls. At delivery, erythrocyte counts were reduced, and during the first trimester and at delivery mean corpuscular hemoglobin and volume values were increased and erythrocyte zinc values were reduced in the oral contraceptive agent group as compared with controls. These changes appeared to be subclinical in magnitude and oral contraceptive agents may have induced a macrocytic erythrocyte population. Because no changes in maternal plasma zinc and copper levels were observed and no hematologic, biochemical, or anthropometric differences were observed in neonates, long-term oral contraceptive agent usage appeared to have little or no effect on zinc and copper metabolism in a subsequent pregnancy.

Doppler echocardiographic studies of diastolic function in the human fetal heart: changes during gestation.

With the combined use of two-dimensional ultrasound and Doppler echocardiography, noninvasive examination of the human fetal heart and circulation has recently become possible. These techniques were employed to investigate diastolic atrioventricular valve flow in the fetal heart in 120 fetuses studied between 17 and 42 weeks of gestation. Two-dimensional ultrasound was used to examine fetal and intrauterine anatomy, and estimates of gestational age were made based on biparietal diameters and femur lengths. Doppler echocardiography was performed with a 3.5 or 5 MHz Doppler sector scanner. Flow velocity patterns were obtained through the tricuspid and mitral valves during diastole. Peak flow velocity during late diastole or atrial contraction (A) was compared with peak flow velocity during early diastole (E) in four groups of fetuses: Group 1, 17 to 24 weeks of gestation; Group 2, 25 to 30 weeks; Group 3, 31 to 36 weeks; and Group 4, 37 to 42 weeks. The ratio of A to E decreased significantly as gestational age advanced, from 1.56 +/- 0.06 (+/- SE) to 1.22 +/- 0.03 across the tricuspid valve (p less than 0.001) and from 1.55 +/- 0.04 to 1.22 +/- 0.06 across the mitral valve (p less than 0.001). In tricuspid valve measurements, peak flow velocity during early diastole increased from 26.3 +/- 2.0 cm/s in Group 1 to 36.5 +/- 1.7 cm/s in Group 4 (p less than 0.001), whereas peak flow velocity during atrial contraction did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryonic heart rates before the seventh week of pregnancy.

Previous studies of normal human embryonic heart rates showed an increase in the rates between the 7th and 9th gestational weeks; the rates gradually declined thereafter until the 15th week. The present study added new information about embryonic heart rates before the seventh week. The heart rates are slower than those reported to occur after the seventh week. These observations are connected with morphologic and physiologic changes during this period of embryonic life.