Acute effect of cigarette smoking on placental circulation - a study by carbon-monoxide measurement and Doppler assessment.

OBJECTIVE: Carbon-monoxide (CO) decreases placental vascular impedance. We assessed the consequences of smoking-induced temporary maternal CO-increase on fetal and placental circulation. STUDY DESIGN: In a prospective study twenty-nine smoking pregnant women and their fetuses were evaluated. We determined the changes in maternal blood CO levels after smoking, and the concomitant changes in maternal and fetal circulation. Changes in fetal heart rate, uterine artery (UTA), middle cerebral artery (MCA), and descending aorta (DA) flow were measured by Doppler velocimetry. Changes in maternal CO level and umbilical flow value were assessed by paired t-test. The correlation between CO level and placental flow was assessed by partial correlation test. RESULTS: CO level increased (mean +/-SD 1.7 +/- 0.065% vs. 2.36 +/- 0.89, p<0.0001). Nicotine-related maternal circulatory parameters changed significantly, but uterine flow values remained unchanged. Fetal heart rate increased, while flow in MCA and DA showed no change. CO-dependent umbilical artery impedance remained unchanged (Pulsatility Index: 0.956 +/- 0.18 vs. 0.948 +/- 0.21). Partial correlation between CO level and umbilical arterial impedance showed no significance (r:-0.324). CONCLUSION: Despite significant CO elevation, the mainly CO-regulated placental flow remained unchanged.

Breath holding test in preeclampsia: lack of evidence for altered cerebral vascular reactivity.

Twenty-five healthy and thirty-one preeclamptic pregnant women were assessed by means of transcranial Doppler sonography. Resting cerebral blood flow velocities in the middle cerebral arteries were measured followed by a repeat measurement 30 s after breath holding. Absolute blood flow velocities and per cent changes after breath holding procedure were compared between the groups. Absolute blood flow velocities were higher in preeclamptic pregnant women both at rest and after breath holding. The percent increase in cerebral blood flow velocity after breath holding (cerebral vascular reactivity) was similar in the two groups. Our data suggest that cerebral vascular reactivity is preserved in pregnant women with preeclampsia.

[Doppler evaluation of the fetal arterial circulation: reference values of the Resistance Index and Pulsatility Index between the 28th and 41st weeks of gestation]. / A magzat artériás vérkeringésének ultrahangvizsgálata: a rezisztenciaindex és a pulzatilitási index referenciaértékei a terhesség 28. és 41. hete között.

The authors established reference ranges for the Resistance Index and the Pulsatility Index of the umbilical artery, the fetal descending aorta and the middle cerebral artery in order to facilitate the uniform evaluation of the Doppler ultrasound examination in obstetrics. 164 patients with uncomplicated pregnancies between the 28th and 41st weeks of gestation were recruited for the longitudinal assessment of Doppler Resistance Indices and Pulsatility Indices in the fetal and umbilical arteries. Data were retrospectively analysed in order to establish the weekly mean values and standard deviations. The mean values of the indices in three periods (I.: 28-31, II.: 32-36, III.: 37-41 weeks) were compared. The normal haemodynamic resistance is reflected by the Doppler indices within the weekly mean +/- 2SD range. The results designate decreasing haemodynamic impedance in the umbilical and in the middle cerebral arteries while the resistance to the blood flow in the abdominal aorta is constant throughout the third trimester of gestation. The introduction and the clinical application of the reference values provides appropriate interpretation of the physiologic fetal blood flow patterns which is the prerequisite of the diagnostic accuracy of the Doppler ultrasound in obstetrics.

[Open heart surgery with extracorporeal circulation during pregnancy]. / Szívmútét extracorporalis keringéssel és terhesség.

The incidence of heart disease in pregnancy has been gradually falling during the last three decades. Cardiopathy still remains a prominent cause of maternal and fetal morbidity and mortality. Most patients know about their heart disease long before conception, even though the potential risk factors of deteriorating cardiac function during pregnancy are generally not emphasized. These women when pregnant may develop heart failure due to the increased cardiorespiratory requirements. When medical therapy proves insufficient heart surgery becomes mandatory to save the patient's life. The pregnant state is not optimal for cardiac surgery as the principle interest of the mother and the fetus is different. We report on two pregnant patients who underwent unavoidable heart surgery with cardiopulmonary bypass and review the literature regarding the optimal management of open-heart operation in pregnancy aiming to decrease the feto-maternal mortality. The successful outcome of the cardiac surgery on pregnant women is determined by the severity of the preexisting disease, the surgical techniques, and the circumstances of the cardiopulmonary bypass. The best possible results can be achieved by providing preconceptional counseling for the cardiopathic patients regarding the relation between the preexisting risk factors and the adverse maternal and neonatal outcome. When heart surgery is mandatory in pregnancy the careful technical precautions and the continuous cardiotocography help to minimize fetal complications during the cardiopulmonary bypass (CPB).

Comparison of cerebral blood flow velocity as measured in preeclamptic, healthy pregnant, and nonpregnant women by transcranial Doppler sonography.

AIM: To test the hypothesis that the middle cerebral artery blood flow velocity (MCAV) is altered in preeclamptic pregnant women as compared with healthy pregnant and nonpregnant women. METHODS: Preeclamptic (n = 21) and healthy pregnant (n = 17) as well as healthy nonpregnant (n = 29) women underwent transcranial Doppler MCAV measurements. The mean MCAV values were compared between the different groups. Anova combined with Bonferroni correction was used for statistical analysis. RESULTS: The MCAV was significantly higher in nonpregnant women (mean +/- SE 73.0 +/- 2.12 cm/s) as compared with healthy pregnant women (67.0 +/- 1.8 cm/s, p = 0.0356). Preeclamptic women showed significantly higher MCAV values (83.5 +/- 2.1 cm/s) as compared with nonpregnant females (73.0 +/- 2.12 cm/s, p = 0.0014). Similar to nonpregnant women, healthy pregnant women showed lower MCAV values (67.0 +/- 1.8 cm/s) as compared with preeclamptic women (83.5 +/- 2.1 cm/s, p = 0.001). After Bonferroni correction the MCAV values in patients suffering from preeclampsia were still statistically significantly higher as compared with the two other groups. CONCLUSIONS: We detected increased resting MCAV values in pregnant women with preeclampsia. In our opinion, this finding refers to arteriolar dilation of the resistance vessels of the brain. Further studies are needed to prove altered vasoreactivity responses of the brain resistance arterioles in preeclampsia.

[The role of uterine and umbilical artery Doppler velocimetry for the early detection of pathologic pregnancy]. / Az arteria uterina és az arteria umbilicalis Doppler-ultrahangvizsgálatának szerepe a kóros terhesség korai felismerésében.

Pregnancy induced hypertension remains the most frequent reason of maternal and fetal complications. Recent studies of the entire pathophysiology of the abnormal implantation proved association between the impaired placental performance and the reduced uteroplacental circulation. Therefore the Doppler examination of uterine and umbilical blood flow may provide the early recognition of high-risk pregnancies complicated by maternal hypertension and fetal intrauterine growth retardation. The authors endeavor to describe the details and characteristics of uteroplacental haemodynamic changes during the course of physiologic and defective implantation. On the basis of the currently available scientific publications they summarize the role of the uterine and umbilical artery Doppler velocimetry as a screening tool in the detection of the consequences of the impaired uteroplacental perfusion. They conclude that abnormal velocity waveforms obtained from the uterine and umbilical arteries may help to improve the efficacy of the prenatal care and the perinatal outcome as well. The clinical benefits of this screening method will be precisely defined on the basis of further multicenter studies in Hungary.

Effect of hyperventilation on cerebral blood flow velocity in preeclamptic pregnancies: is there evidence for an altered cerebral vasoreactivity?

The purpose of this study was to investigate cerebral arteriolar vasoreactivity function in preeclampsia. Preeclamptic (n = 26) and healthy pregnant (n = 22) women underwent transcranial Doppler sonography of the middle cerebral artery at rest and after 60 seconds of hyperventilation (HV). Systolic, diastolic, and mean blood flow velocities were recorded. The percentage change of the blood flow velocities after HV was calculated. Mean blood flow velocity of the middle cerebral artery was higher in preeclamptic women as compared with healthy pregnant women. No difference could be detected in percentage change of middle cerebral artery blood flow velocities after HV between the two groups. There is no evidence of a small-vessel vasoconstriction among preeclamptic patients. The role of vasoconstriction of the large cerebral arteries and vasodilation of the resistance arterioles, as well as a combination of these 2 pathomechanisms, in determining cerebral blood flow in preeclampsia and eclampsia should be investigated in further studies.

Assessment of cerebral hemodynamics during roll over test in healthy pregnant women and those with pre-eclampsia.

OBJECTIVE: To compare cerebral autoregulatory responses obtained during roll over tests in healthy pregnant women and those with pre-eclampsia in order to assess the middle cerebral artery velocity changes in relation to the roll over test in normotensive and pre-eclamptic women. PARTICIPANTS: Twenty-two healthy pregnant women and 26 with pre-eclampsia underwent transcranial Doppler measurements of the middle cerebral artery. METHODS: Systolic, mean and diastolic blood flow velocities and mean arterial blood pressures were recorded in the left lateral position and five minutes after turning to the supine position. Absolute values of mean blood flow velocities, mean arterial blood pressure values and calculated cerebral blood flow indices as well as cerebrovascular resistance area products were compared at different positions among the groups. RESULTS: Mean arterial blood pressure increased in both groups while turning from the left lateral to the supine position. In women with pre-eclampsia both mean arterial blood pressure and absolute values of mean blood flow velocity values were higher in both positions, compared with healthy pregnant women. In both groups, changing the position resulted in a decrease of absolute values of mean blood flow velocities. Calculated cerebral blood flow indices did not change, while cerebrovascular resistance area products increased significantly in the groups during roll over testing. In women with pre-eclampsia, the increase of cerebrovascular resistance area products was more pronounced as compared with healthy pregnant women. CONCLUSIONS: In women with pre-eclampsia roll over test results in an increase of the mean arterial blood pressure, which is accompanied by a decreased mean blood flow velocity in the middle cerebral artery. Further studies are needed to clarify the pathophysiological background of cerebral haemodynamic changes in pre-eclampsia.

[Alterations of cerebral hemodynamics in pre-eclampsia and eclampsia]. / Az agyi hemodinamika változása praeeclampsiában és eclampsiában.

Clinical and pathophysiological aspects of preeclampsia and eclampsia have been found to be responsible for the majority of maternal mortality, but the exact role of them is still unknown. It is conceivable that altered cerebral hemodynamics and autoregulation is responsible for the neurological complications. The background of the cerebral processes is still not clarified. Authors summarize the changes of cerebral circulation which develop during preeclampsia and explanations for cerebral hemodynamic alterations during normal, preeclamptic and exclamptic pregnancies are discussed. They conclude that there is no accurate method for predicting eclampsia. Cerebral hemodynamical studies are only helpful in better understanding the pathophysiological background of preeclampsia-eclampsia syndrome at present.

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

[Intrauterine fetal death in the third trimester]. / Harmadik trimeszterbeli intrauterin magzati elhalások.

Retrospective analysis of third trimester intrauterine deaths has been performed at the Department of Obstetrics and Gynecology University Medical School Debrecen, Hungary. Among 32,126 deliveries between 1988 and 1997 retrospectively 163 intrauterine deaths occurred in the third trimester. Cases were analysed on the basis of the Nordic-Baltic Perinatal Death Classification. The role of intrauterine growth retardation, cord complication and fetal malformation are discussed. An interesting finding was the high rate of intrauterine growth retardation where cord complication was supposed to be the cause of intrauterine death. Concerning both to medical and legal aspects precise and exact documentation should be needed for the correct retrospective analysis.

[Use of erythropoietin in pregnancy: review of the literature in connection with 2 cases]. / Erythropoietin alkalmazása terhességben: irodalmi áttekintés két eset kapcsán.

Recently a growing number of case reports has been published about successful pregnancy outcome of dialysed women on recombinant human erythropoietin therapy. During pregnancy the maternal demand for erythropoietin may undergo changes, with consideration of recombinant human erythropoietin therapy in the early stage of renal insufficiency, as is shown by our two reported cases. The use of recombinant human erythropoietin seems to be safe for the foetus: it does not cross the placental barrier, and therefore lacks any direct foetal effect. The treatment of anaemia with recombinant human erythropoietin carries benefits for both the mother and foetus. One of the most important preconditions for successful recombinant human erythropoietin therapy is adequate iron supplementation. Due to the increased risk of pregnancy induced hypertension or preeclampsia, there is a need for slow and gradual correction of anaemia, and an individually tailored target hematocrit. A close follow up of he patient by the obstetrical-nephrological team is essential, with the intensive monitoring of the fetuses. In some cases with normal renal function the stimulation of erythropoiesis with recombinant human erythropoietin may also be needed during the pregnancy.

Epstein-Barr virus permissively infects human syncytiotrophoblasts in vitro and induces replication of human T cell leukemia-lymphoma virus type I in dually infected cells.

Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1), as well as human T-cell leukemia-lymphoma virus type I (HTLV-I), may interact in the pathogenesis of human retroviral infections. The placental syncytiotrophoblast layer represents a barrier protecting the fetal compartment from exposure to retroviruses. We studied the interactions of EBV with HIV-1 and HTLV-I in human term syncytiotrophoblast cells to investigate the significance of double infections in transplacental transmission of human retroviruses. We found that syncytiotrophoblast cells could be productively infected with EBV. Dual infection of the cells with EBV and HTLV-I resulted in full replication cycle of otherwise latent HTLV-I. In contrast, the restricted permissiveness of syncytiotrophoblasts for HIV-1 was not influenced by coinfection of the cells with EBV. Infection of syncytiotrophoblast cells with EBV, but not HTLV-I, induced interleukin-2 and interleukin-6 secretion, and augmented secretion occurred on coinfection with both viruses. Coinfection of syncytiotrophoblast cells with EBV and HTLV-I induced tumor necrosis factor-beta and transforming growth factor-beta 1 secretion, but infection with either virus alone did not lead to secretion of these cytokines. Permissive replication cycle of HTLV-I was induced by the EBV immediate-early gene product Zta. Pseudotype formation between EBV and HTLV-I in coinfected syncytiotrophoblast cells was not found. Our data suggest that activation of HTLV-I gene expression by EBV in coinfected syncytiotrophoblast cells may be a mechanism for transplacental transmission of HTLV-I.

Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

Interactions between human immunodeficiency virus type 1 and human cytomegalovirus in human term syncytiotrophoblast cells coinfected with both viruses.

Human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. We analyzed the patterns of replication of HIV-1 and HCMV in singly an dually infected human term syncytiotrophoblast cells cultured in vitro. Syncytiotrophoblast cells exhibited restricted permissiveness for HIV-1, while HCMV replication was restricted at the level of immediate-early and early gene products in the singly infected cells. We found that the syncytiotrophoblasts as an overlapping cell population could be coinfected with HIV-1 and HCMV. HIV-1 replication was markedly upregulated by previous or simultaneous infection of the cells with HCMV, whereas prior HIV-1 infection of the cells converted HCMV infection from a nonpermissive to a permissive one. No simultaneous enhancement of HCMV and HIV-1 expression was observed in the dually infected cell cultures. Major immediate-early proteins of HCMV were necessary for enhancement of HIV-1 replication, and interleukin-6 production induced by HCMV and further increased by replicating HIV-1 synergized with these proteins to produce this effect. Permissive replication cycle of HCMV was induced by the HIV-1 tat gene product. We were unable to detect HIV-1 (HCMV) or HCMV (HIV-1) pseudotypes in supernatant fluids from dually infected cell cultures. Our results suggest that interactions between HIV-1 and HCMV in coinfected syncytiotrophoblast cells may contribute to the transplacental transmission of both viruses.

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells cultured in vitro.

We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C'-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C'-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADE of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE seems to be more efficient in enhancing HIV-1 replication than C'-ADE. While FcR-ADE leads to increased internalization of HIV-1, C'-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE are reactive with the gp120 viral envelope antigen, whereas antibodies involved in C'-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADE and C'-ADE may contribute to the spread of HIV-1 from mother to the fetus.

A simple method for intraoperative autotransfusion in cardiac surgery.

Authors present a simple, safe and inexpensive method of intraoperative autotransfusion (ATF) for open-heart surgery. A brief comparison is given with other techniques already in use.

Open mitral commissurotomy in pregnancy. A case report.

Correction of severe mitral stenosis by open commissurotomy during the second trimester of pregnancy is reported. The further course of the pregnancy was uneventful and at 34 weeks a healthy boy was vaginally delivered. Mother and child were in good health on discharge from hospital one month later.

Changes in serum cyclic nucleotide concentration during open-heart surgery.

Changes in serum cyclic AMP and GMP concentrations were studied in 14 patients undergoing open-heart surgery with cold cardioplegia. Blood samples were taken on total bypass from the radial artery and from the coronary sinus before aortic cross-clamping and 1 and 9 min after declamping. The samples were analyzed for cyclic nucleotides. The cAMP levels showed no pronounced change in the arterial samples, but were significantly increased in the coronary sinus samples after declamping of the aorta. The cGMP values showed the same trend of change in the arterial and the coronary sinus samples, viz. significant fall after aortic release, and after 9 min an increase. The cAMP/cGMP ratio after clamp removal showed pronounced increase in the first minute and some reduction at 9 min. All the changes were statistically significant. Beating recommenced spontaneously in seven hearts. The cAMP levels were lower in this group than in the patients without spontaneous recovery. The outset cGMP levels and the cAMP/cGMP ratio were higher in the latter group. Absence of increase in the cGMP level may be due to effectiveness of cardioplegia in reducing the energy requirements of the ischemic myocardium. The study indicates that hearts without spontaneous recovery of beating react more sensitively to hypoxia and have to use up more of their energy resources for restoration of function.