Neonatal lupus erythematosus: maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human alpha-fodrin cDNA

IgG antibodies to a cleavage product of alpha-fodrin (120 kDa alpha-fodrin) have recently been identified as organ-specific autoantibodies in primary Sj?gren's syndrome. In this study, we examined seroreactivity of mothers and infants with neonatal lupus erythematosus (NLE) to a recombinant NH2-terminal protein (120 kDa alpha-fodrin) of human alpha-fodrin. Serum samples were collected during the perinatal period in seven pregnancies of five mothers delivering offspring with NLE. Anti-120 kDa alpha-fodrin antibodies were identified by immunoblotting in six of seven perinatal maternal sera of offspring with NLE: one of two congenital heart block offspring and all five offspring with cutaneous NLE. These antibodies were placentally transmitted to infants. One of the five mothers had primary Sj?gren's syndrome, and four were asymptomatic. One asymptomatic mother did not demonstrate anti-120 kDa alpha-fodrin activity at the time of the first delivery of a congenital heart block infant, but was found to be positive at the time of subsequent delivery of a second child with cutaneous NLE. We propose that maternal antibodies to 120 kDa alpha-fodrin may be an additional serologic marker for the risk of NLE in anti-Ro/SS-A positive women.     

Oncologic surgery of the larynx after failure of radiotherapy]

An association between complete congenital heart block (CCHB) and anti-Ro/SSA antibody is well recognized but has never been reported in Thailand. We report here a 37-year-old female who was admitted because of massive epistaxis secondary to immune thrombocytopenia. She had given birth to a child with CCHB 2 years previously, when she was healthy. Antinuclear antibody and anti-Ro/SSA were positive in her sera, but were negative in her son. The relationship between anti-Ro/SSA antibody and outcome of mothers with infants with CCHB is reviewed.     

Complete congenital atrioventricular block. Prenatal diagnosis and perinatal management

OBJECTIVE: To describe our experience in prenatal diagnosis and perinatal management of congenital atrioventricular heart block, as well as pacemaker treatment in the neonate. MATERIAL AND METHODS: A total of 13 fetuses are included. The diagnosis of atrioventricular dissociation was established by Doppler heart rate sample in the right atrium to show the atrial activity while the sample in the Aorta reflected the ventricular heart rate. Gestational age at diagnosis, ventricular heart rates, autoimmune maternal pathology, maternal blood tests for autoantibodies antiRo+, congenital structural heart disease, fetal hydrops, maternal medical treatment, perinatal results and pacemaker neonatal implantation are described. RESULTS: Gestational age at diagnosis ranged between 22 and 32 (mean 27.6) weeks. Ventricular heart rates ranged between 32 to 80 (mean 54) beats/min. AntiRo+ antibodies were detected in 5 mothers, and clinical systemic lupus erythematosus was found in only one. Four had congenital heart disease (2 ventricular inversion and corrected TGA, 1 complete atrio-ventricular canal and 1 tricuspid atresia). Signs of heart failure and hydrops were detected in 9 fetuses. Treatment with beta-metasona and ritodrine was administered to 7 mothers when the ventricular heart rate dropped below 60 beats/min. Intrauterine fetal death occurred in 3 fetuses with structural congenital heart disease and hydrops. Delivery was performed by cesarean section in 8 preterm fetuses (one them a twins), 3 spontaneous deliveries at term and 3 stillbirth. Postnatal pacemaker implantation was carried out in 9 newborns (3 cases with unicameral temporal right ventricle electrode and 6 cases with permanent bicameral electrodes implanted through the subclavian vein and DDD pacemaker). Follow-up of the bicameral pacemaker group was satisfactory. CONCLUSION: Persistent fetal bradycardia is the first sign to diagnose prenatal complete atrioventricular heart block. Echocardiography asses fetal haemodynamic status and may detect signs of fetal deterioration. Hydrops and further drop in the ventricular heart rate warrant urgent cesarean section and pacemaker management of the newborn.     

A second-generation study of 427 probands with congenital heart defects and their 837 children

OBJECTIVES: This study attempted to answer the question, Do mothers with congenital cardiovascular defects have more affected children than fathers with cardiac anomalies? BACKGROUND: In the 1950s to 1960s, concern was expressed about the safety of pregnancy in women with cardiac anomalies and the possibility of inheritance. METHODS: In a prospective study over 25 years, 236 women with cardiac defects were followed through pregnancy, and their 418 offspring were examined during their 1st 3 years. A high incidence of congenital cardiac malformations was noted. Then, a retrospective study of 191 men from the same clinic group and their total family (419 children) was performed to compare the incidence of affected children between the maternal study and this subsequent paternal study. RESULTS: Of 837 live children of these 427 probands, 14.1% (118) had a congenital heart defect (13.4% in the maternal study, 14.8% in the paternal study). There was no correlation with the surgical status of the proband. Concordance was somewhat greater among the children of affected mothers compared with those of affected fathers. Included in these studies were 31 high risk probands, 10 with genetic syndromes and 21 who had an affected sibling. Respectively, 53% and 41% of their children had cardiac anomalies, with a concordance > 50%; three fourths of these children had moderate to severe anomalies. CONCLUSIONS: The incidence of congenital heart defects in the children was not statistically different between the maternal and paternal studies. With removal of the high risk probands from the total study group, the risk of one affected parent having a child with a cardiac anomaly was 10.7%. Of the entire 837 children, only 7.5% had moderate or severe defects.     

Effects of maternal physical training on the fetus

The latest results of influences of physical training during pregnancy on the foetus are presented. In humane, no pathological effects on the embryogenesis have been demonstrated. During exercise, a modest increase (5-25 bpm) in foetal heart rate is a common finding. This might be caused by reduced oxygen supply to the foetus, but could more likely be due to stimuli from vasoactive hormones or training-induced uterine contractions. Foetal growth seems to be influenced by maternal training, as moderate training has resulted in significantly bigger babies compared to both inactivity and hard training. In one study it was shown that low body weight in babies from hard-training mothers was due to reduced neonatal fat mass. Pathological sequelae due to increased maternal temperature during training have not been found in humans. The results strongly suggest that moderate training during pregnancy can be recommended if simple precautions are taken.     

Chronotropic competence of the sinus node in congenital complete heart block

Electrocardiograms taken at rest of 2 children with transplacental exposure to anti-Ro antibody but 1:1 atrioventricular conduction demonstrated sinus node disease. Treadmill exercise testing of 28 patients with congenital complete heart block found 3 patients with chronotropic incompetence of the sinus node.     

Placental and fetal cardiac laminin are targets for cross-reacting autoantibodies from mothers of children with congenital heart block

The association of congenital heart block (CHB) with maternal autoantibodies to the Ro and La ribonucleoprotein antigens may be due to cross-reactions between maternal anti-La antibodies and fetal cardiac specific antigens. One of the major components of cardiac myocytes, laminin, is accessible for binding by maternal autoantibodies and we have previously reported cross-reactivity of mouse laminin with anti-La antibodies affinity purified from the sera of patients with primary Sj?gren's syndrome. Affinity purified anti-La antibodies from ten women who had at some time given birth to a child with CHB were examined for cross-reactivity with human placental laminin, which shares structural similarities with cardiac laminin. All ten anti-La antibodies bound to the surface of cryosections of normal full term placental trophoblasts. Binding could be inhibited by pre-incubation of antibodies with either La or placental laminin. Eight anti-La antibodies also reacted with placental laminin by ELISA and La inhibited up to 82% of binding to laminin while laminin inhibited up to 85% of binding to La in a dose dependent manner. Eight anti-La antibodies also bound to the surface of fetal cardiac myocytes at 10.3 weeks of gestation and five showed lower levels of reactivity with the surface of fetal cardiac myocytes at 16.5 weeks of gestation. None showed any surface staining of normal adult heart. These data confirm the cross-reactivity of anti-La antibodies with laminin and may support a placental role in preventing the majority of potentially pathogenic antibodies from reaching the fetal circulation.     

Postterm pregnancy--importance of this problem in modern obstetrics

Postterm pregnancy remains constantly a difficult and controversial problem in modern obstetrics. The aim of this study is to discuss the definition of the postterm pregnancy, complications for both the foetus (macrosomia associated with birth trauma and shoulder dystocia, oligohydramnios, meconium aspiration, postmaturity syndrome) and mother (increase rate of caesarean births). We discussed also the antepartum surveillance and the management of the postterm gestation (time and way of delivery). The management of postterm pregnancy should be individualised and based on the above findings. Treatment includes active methods (induction of labour, elective caesarean section) or conservative way (strict foetal antenatal surveillance).     

The smoking addiction of pregnant women and the consequences on their offspring's intellectual development

Many scientists have studied the effects of smoking by pregnant women on intrauterine development. Because nicotine and other toxic substances in cigarette smoke are not stopped by the placental barrier, there is a risk that the development of the child could be hindered. It has been shown, for instance, that babies whose mothers smoked during pregnancy have lower size and weight at birth. Few authors have studied the consequences a mother's pre-natal smoking may have on the intellectual development of her child. We compared two samples of children, aged 4 to 5, and aged 6 to 7 (40 children in total), whose mothers had smoked during pregnancy, with two samples of 40 children of the same ages whose mothers had not smoked. We tested them on the Wechsler scale. The social and cultural levels were equivalent. We found a difference of more than 15 IQ points in favor of the children of nonsmoking mothers. These results permit us to suppose that smoking during pregnancy hinders the intellectual development of the child.     

Does autopsy of antenatally diagnosed malformed foetuses aid genetic counselling?

BACKGROUND: Many pregnancies are terminated because of ultrasonographic diagnosis of malformation in the foetus. A detailed foetal autopsy is needed to arrive at a definite diagnosis on the basis of which genetic counselling can be provided. METHODS: Sixty-one foetuses, terminated because of antenatal diagnosis of congenital malformations by ultrasound, were autopsied. The ultrasound diagnosis was compared with the diagnosis reached after autopsy. RESULTS: In 31 cases (51%) the autopsy provided additional findings. In 21 cases (34.4%), the autopsy changed the primary diagnosis. The revised diagnosis led to a change in the risk of recurrence in 18 cases (29.5%). CONCLUSION: Genetic counselling depending solely on ultrasonographic foetal diagnosis may be erroneous. For appropriate genetic counselling, a detailed foetal examination should be carried out after termination in cases with ultrasonographically detected congenital malformations.     

Effects of processing conditions and in vitro ageing on the physical properties of Biomer

Neonatal lupus, albeit rare, affords an excellent opportunity to examine a disease from bedside to bench. Over the past year there have been numerous publications covering clinical aspects and basic research. The timing of heart block is not random; bradycardia is most often identified between 16 and 24 weeks of gestation. Investigations have focused on this apparently vulnerable period and examined the expression of known (SSA/Ro-SSB/La), novel (p57, endogenous retrovirus-3), and cross-reactive (laminin) autoantigens in fetal hearts of varied ages and in adult hearts. Clinical studies are accumulating, but a unique maternal autoantibody profile is yet to be identified. Anti-52-kD responses, measured by enzyme-linked immunosorbent assay and immunoblot, continue to be a nearly universal finding in mothers whose children have neonatal lupus. The presence of anti-U1RNP in the absence of anti-SSA/Ro-SSB/La antibodies occurs only in cases of isolated cutaneous disease and not (to date) in mothers of infants with cardiac manifestations. Immunogenetically, mothers with affected children appear to be more closely related to Sj?gren's syndrome than systemic lupus erythematosus. Asymptomatic mothers do not invariably become ill, and if an asymptomatic mother does develop lupus it is not likely to be life threatening. Heart block is associated with substantial morbidity and mortality. Although treatment of affected fetuses with dexamethasone has successfully diminished associated effusions, this therapy has not reversed established third-degree block. Treatment with sympathomimetics may be beneficial in fetuses with hydropic changes. Prophylactic therapies, other than serial echocardiographic evaluation, are not supported by any published data. To further efforts at both the bench and bedside, research registries were recently established in the United States and Canada.     

Clinical observation of cardiac pacemaker in pregnant women

OBJECTIVE: To study the clinical results in pregnant women with bradycardia implanted with cardiac pacemakers. METHOD: Five pregnant women with bradycardia were retrospectively studied in our hospital from 1980 to 1996. RESULTS: Four of the patients had A-V block, and the other one sinus bradycardia. Classification of cardiac function, showed 1 case of class IV, 3 cases of class III, and 1 case of class II before implantation of cardiac pacemaker. One case had the pacemaker implanted before pregnancy and 4 cases during pregnancy. Cardiac function improved significantly after implantation and pregnancies went uneventfully. Three women had term living birth by cesarean section, and 2 ended by therapeutic abortions safely. CONCLUSION: Bradycardia is a rare and serious complication in pregnancy, especially due to A-V block of III degree. Cardiac pacemaker should be implanted before pregnancy or at early stage of pregnancy in order to maintain adequate heart function. These patients should receive cesarean section.     

An optimized AV delay algorithm for patients with intermittent atrioventricular conduction

Detection and promotion of an intermittent atrioventricular (AV) conduction is the objective of an AV delay hysteresis algorithm in dual chamber pacemaker (DDD) pacing. The AV delay following an atrial event is automatically extended by a programmable interval (AV hysteresis interval) if the previous cycle showed spontaneous AV conduction, i.e., a ventricular event was detected within the previous AV delay. An automatic search mode scans for spontaneous ventricular events during the hysteresis interval: a single AV delay extension (equal to the programmed AV delay hysteresis) will occur after a successive, programmable number of AV cycles with ventricular pacing. If a spontaneous AV conduction is present, the AV delay will remain extended by the hysteresis interval. Our first results in 17 patients with intermittent AV block disclosed a satisfactorily working algorithm with effective reduction of ventricular stimuli. In relation to the underlying conduction disturbance and pacemaker settings, the majority of our patients showed a reduction of ventricular pacing events up to 90% without any adverse hemodynamic or electrophysiological changes. Based on clinical (promotion of a physiological activation and contraction sequence) and technical (reduction of power consumption) advantages, the AV hysteresis principle could be of incremental value for future dual chamber pacing in patients with intermittent complete heart block.     

Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome

BACKGROUND: It has been claimed that patients with sick sinus syndrome have an increased risk of developing AV block, but this has never been assessed prospectively. The aim of the present study was to evaluate in a prospective trial AV conduction during the long-term follow-up of patients with sick sinus syndrome. METHODS: Two hundred twenty-five consecutive patients with sick sinus syndrome and intact AV conduction were randomized to undergo single-chamber atrial pacing (110 patients) or single-chamber ventricular pacing (115 patients). Follow-up after 3 months and then yearly included measurement of the PQ interval and, in patients with atrial pacemakers, determination of the atrial stimulus-Q intervals at pacing rates of 100 and 120 bpm. The occurrence of AV block in the atrial group was recorded. During follow-up (mean, 5.5+/-2.4 years), there was no change in PQ interval in either group and no change in atrial stimulus-Q intervals or Wenckebach block point in the atrial group. Four of 110 patients in the atrial group developed grade 2 to 3 AV block that required upgrading of the pacemaker (0.6% per year). Two of these 4 patients had right bundle-branch block at pacemaker implantation. CONCLUSIONS: AV conduction, estimated as PQ interval and atrial stimulus-Q interval at atrial pacing rates of 100 and 120 bpm and the Wenckebach block point, remains stable during long-term follow-up. Thus, treatment with single-chamber atrial pacing is safe and can be recommended to patients with sick sinus syndrome without bundle-branch block.     

Pacemaker therapy in premature children with high degree AV block

The smallest pacemaker pulse generator and a steroid-eluting bipolar epicardial lead were implanted in two premature children with symptomatic AV block. Stable capture threshold and high amplitude evoked response electrogram resulted in normal function of the pacemaker Autocapture algorithm, which adjusts output 0.3 V above the measured capture threshold. Autocapture had previously been used only with endocardial leads. Longer-term observation is required.     

Congenital hemangiopericytoma of the skin

The management of the preterm fetus with hydrops due to complete congenital heart block is difficult. The outcome is frequently associated with significant morbidity and mortality. Two fetuses presented at the post menstrual age of 29 and 30 weeks respectively with severe hydrops due to complete heart block. The following staged approach was adopted: (1) enhance fetal lung maturation with maternal corticosteroids and thyroid releasing hormone for 48 h; (2) elective Caesarean section; (3) classical neonatal management consisting of intubation and ventilation, drainage of all cavities with effusions; (4) increase neonatal heart rate by administration of i.v. isoprenaline, by bipolar trans-oesophageal pacing or epicutaneo-oesophageal pacing; (5) after the regression of the hydrops, start epicardial pacing after implantation of 2 or 3 temporary epicardial 3/0 pacemaker; (6) implantation of a permanent abdominal pacing system with steroid epicardial tip once the threshold exceeds 20 mA or when the baby weighs more than 1500 g. In these patients a permanent pacing system was implanted at the ages of 8 weeks (2045 g) and 4 weeks (1560 g) respectively. No major complications occurred; the cardiac outcome with 37 and 34 months of follow up is excellent. CONCLUSION: This proposed staged approach with temporary epicardial leads can improve the outcome of hydropic fetuses due to complete congenital AV block.     

Clinical observation on effect of xiaoyu zhixue tablet on 104 patients with idiopathic multifocal bleeding and platelet aggregation defect

In a group of 7,721 foetuses with a high or low risk of cardiovascular pathology of the foetus, examined by complete foetal echocardiography, the authors found hyperechogenic ventricular structures in 211 foetuses (2.73% of the group) with a dominating localization in the left ventricle (97%). These structures are in the great majority a benign development variant which involves no risk for the development of the foetus. Rare localization beyond the left ventricle were not risk for the development of the foetus. Rare localization beyond the left ventricle were not associated with cardiac or other foetal pathologies. Echogenic ventricular focuses were not visualized by transvaginal echocardiography in the 13th week of pregnancy, although they were revealed in the same patient during the 21st week. Their presence does not affect left ventricular function and the function of the mitral valve pre-or postnatally. In the differential diagnosis these structures must be always differentiated from thrombi or cardiac tumours.     

Bilateral total hip arthroplasty comparing hydroxyapatite coating to porous-coated fixation

Intraventricular together with atrial-axis and nodoventricular discontinuity, in which various parts of the conduction system are replaced by fibrous or fatty tissue, constitute the three major pathological categories of isolated congenitally complete heart block. Intraventricular discontinuity is distinctly rare, with only two previous cases reported in the literature, one of which was associated with a familial history of heart block. The cardiac conduction systems of two cases of isolated congenitally complete heart block were serially sectioned and analyzed histopathologically. The findings were correlated with the clinical features, in particular, the family histories and maternal serum anti-Ro antibodies. Both cases, a 9-day-old neonate and an 8-year-old schoolgirl, showed a combination of nodoventricular and intraventricular discontinuity, with absence of the atrioventricular penetrating bundle, the entire right, and the proximal portion of the left bundle branch. The branching bundle was absent in the first case and replaced by fatty tissue in the second. In contrast to the commoner atrial-axis discontinuity in which the atrioventricular node itself is usually replaced by fibrous or fatty tissue with variable involvement distally, the sinus node, and in particular, the atrioventricular node were normal in both of our cases. There was no family history in either case, whereas tests for the maternal serum anti-Ro antibody were positive in the first but negative in the second case. Intraventricular discontinuity as a cause of isolated congenitally complete heart block is very rare. In our cases, it co-existed with nodoventricular discontinuity. It can be sporadic, familial, or associated with positive maternal serum anti-Ro antibodies.     

Congenital varicella. Problems with prenatal diagnosis after an early, primary maternal infection

Chickenpox rarely occurs as a primary infection during pregnancy. There is a risk of foetal malformation only if the mother is infected before 20 weeks of gestation. The two main problems encountered for antenatal diagnosis of congenital varicella are the rare incidence of morphology anomalies (less than 35%) and the difficulty of establishing a functional prognosis. Echography is used to detect foetal malformations. In suspected cases the proof of viral infection can be based on results of foetal serology, viral culture or polymerase chain reactions. According to the literature, echographically detected malformations in cases with certain foetal infection have a poor outcome although conflicting cases have been reported.     

Usefulness of exercise test in programming dual chamber pacemakers

Prospectively, we studied 42 patient to evaluate the usefulness of treadmill exercise to programme pacemaker DDD in relation to the functioning upper frequency (relation between block frequency of pacemaker and the upper rate frequency). We excluded patient who had no treadmill exercise test after implant pacemaker. During stress 7 (17%) patient presented AV conduction 1:1 (group I); 16 (38%) second degree AV block type Wenckebach (group II); 14 (33%) second degree AV block 2:1 (group III); and 5 (12%) showed inhibition of the pacemaker by intrinsic activity (group IV). Block frequency of the pacemaker in group I and II was superior in regard of the upper rate frequency, 156.85 +/- 22.16 vs 141.43 +/- 20.82 and 135.25 +/- 11.54 vs 121.25 +/- 5.9, respectively. In group III and IV, it was lower, 120.36 +/- 15.31 vs 138.57 +/- 13.29 and 121.0 +/- 7.38 vs 142.0 +/- 14.39. The comparative analysis of the block frequency of the pacemaker in relation with the upper rate frequency showed statistically significant differences (p < 0.05) between groups I and II, and between the group I and III. The appearance of second degree AV block 2:1 is nonphysiologic, is rather due to an abrupt falling in the cardiac output. This phenomenon is able to be predicted and corrected by programming with the use the telemetry with parameters as the AV delay, as well as upper rate frequency and post-ventricular refractory atrial period.