Prenatal examination of the area and morphology of the atrioventricular valves using four-dimensional ultrasound in normal and abnormal hearts.

OBJECTIVE: Our aim is to evaluate the feasibility to examine the morphology and area of the atrioventricular (AV) valves in normal fetuses and fetuses with cardiac defects using spatiotemporal image correlation (STIC). METHODS: Atrioventricular valves were analyzed longitudinally in STIC volumes of 74 normal fetuses between the 15th and 36th week of pregnancy. The valve area was measured in a rendered view in diastole, the number of valve leaflets in systole. Longitudinal data analysis was performed using linear mixed models. Fifty fetuses with cardiac defects were examined. RESULTS: Examination of 355 STIC volumes of normal fetuses showed in 82.5% sufficient quality. The tricuspid valve leaflets were seen in 200 (68.3%) volumes and the mitral valve leaflets in 219 (74.7%) volumes. The tricuspid valve showed in 61.1% a round, 29.0% rectangle, and 8.9% elliptical shape and the mitral valve in 60.1% round, 28.0% rectangle, and 10.9% elliptical. Regression analysis revealed a positive relationship of the valve area with gestational age (p < 0.0001). Most heart defects with stenosis showed an area below the 5th percentile. CONCLUSION: Prenatal examination of the morphology and area of the AV valves using four-dimensional ultrasound is feasible. A rectangular valve opening is normal, which was visualized in about one third of the normal fetuses.

Differential insertion of the atrioventricular valves: measurement protocol to detect various congenital heart defects.

OBJECTIVES: The objectives of this study were to develop reference values for the distance between the atrioventricular valves, called differential insertion of the atrioventricular valves (DIAVV), in normal fetuses using four-dimensional ultrasound with spatio-temporal image correlation and to explore if DIAVV measurement can differentiate between normal hearts and hearts with cardiac defects. METHODS: The DIAVV was analysed longitudinally following a measurement protocol in 74 fetuses between 15 and 36 weeks gestational age. The DIAVV was measured in an apical four-chamber view of the heart in end-diastole. Furthermore, the DIAVV was measured in 70 fetuses with cardiac defects. RESULTS: In total, 337 normal and 70 abnormal spatio-temporal image correlation volumes were examined. Longitudinal regression analysis revealed a positive relationship of the DIAVV with gestational age and fetal biometry (p < 0.0001). The DIAVV of fetuses with double outlet right ventricle, truncus arteriosus, atrioventricular septal defects, Ebstein and tetralogy of Fallot all differed from normal fetuses (p < 0.05). CONCLUSION: Measurement of the DIAVV is a promising tool; however, a well-defined measurement protocol should be followed to accomplish the correct plane and exact moment in the cardiac cycle. This study presents new nomograms following this measurement protocol and reports an abnormal DIAVV in a wide spectrum of congenital heart disease.

Interobserver agreement in detailed prenatal diagnosis of congenital heart disease by telemedicine using four-dimensional ultrasound with spatiotemporal image correlation.

OBJECTIVE: To evaluate the clinical accuracy of four-dimensional (4D) echocardiography in the detailed prenatal diagnosis of congenital heart disease (CHD) in a telemedicine setting. METHODS: Ten second-trimester spatiotemporal image correlation (STIC) volumes were sent to three observers in different tertiary care centers with expertise in 4D echocardiography. The 10 volumes were selected based on the type of diagnosis to cover a wide spectrum of CHD anomalies, and also included one normal fetal heart. Observers were asked to provide the diagnosis, the postprocessing modalities used and the time spent on examination, and to give a rating of the confidence for the diagnosis on a 5-point Likert scale. They were free to consult other colleagues, including pediatric cardiologists, but were blinded to the prenatal diagnosis and the neonatal outcome. A diagnostic scoring system was used to evaluate different aspects of the heart defects. The results were compared with neonatal echocardiography or postmortem findings ('gold standard'). RESULTS: In two cases all observers correctly diagnosed all details of the volume datasets. The observer with the best performance reached perfect agreement in six cases and nearly perfect agreement in three. The volumes were most frequently studied by sectional planes and were analyzed in a median time of 11.0 (range, 2.5-30.0) min. The median confidence score was 4.0 (range, 1.0-5.0). CONCLUSIONS: In a telemedicine setting using STIC volumes, fetal cardiac anomalies can be diagnosed correctly by an expert. However, details required for adequate counseling and planning of postnatal care may be missed. STIC by telemedicine is a promising modality, although not accurate enough for exclusive use in clinical decision making regarding treatment, prognosis or termination of pregnancy.

Electrical cardioversion during pregnancy: safe or not?

Two pregnant patients with a sustained symptomatic maternal supraventricular arrhythmia are presented. Both patients were treated with direct-current cardioversion. Electrical cardioversion during pregnancy is a rarely applied but highly effective procedure in the treatment of maternal cardiac arrhythmias and is assumed safe for both mother and child. However, once foetal viability is reached, monitoring of the foetal heart rate is advised and facilities for immediate caesarean section should be available.

Reliability of fetal cardiac volumetry using spatiotemporal image correlation: assessment of in-vivo and in-vitro measurements.

OBJECTIVE: To assess the reliability of measurement of fetal cardiac ventricular volume, stroke volume, and ejection fraction with four-dimensional ultrasound using spatiotemporal image correlation (STIC). METHODS: Volume datasets were collected from two sources: 24 from fetuses over a range of gestational ages and 12 from a miniature balloon model. Datasets were analyzed by three observers, repeatedly in 12 fetal datasets and all balloon datasets. Volume calculations were obtained by manually tracing multiple parallel slices (three-dimensional (3D) slice method). Measurement error was assessed by calculating standard errors of measurement (SEM) and coefficients of variation (CV). Reliability was assessed by calculating interobserver and intraobserver intraclass correlation coefficients (ICC). RESULTS: Measurement errors of balloon volumes were small and reliability was good (SEM

Synthesis of heparin-like antithrombotics having perphosphorylated thrombin binding domains.

The synthesis of three heparin analogues (i.e. compounds VI-VIII) having perphosphorylated thrombin binding domains (TBDs) is reported. These compounds were tested in vitro for their antithrombin III (ATIII)-mediated anti-Xa and antithrombin activities. Conjugates VI and VIII show a remarkable increase in antithrombin activity compared to the structurally related conjugates with persulfated TBDs (i.e. compounds IV and V), whereas compound VII displays a diminished activity.

In vitro evaluation of synthetic heparin-like conjugates comprising different thrombin binding domains.

The syntheses of several heparin-like glycoconjugates (i.e., 16a-f) containing identical AT III binding domains (ABD) and spacers but different thrombin binding domains (TBDs) are described. Biological activities of conjugates 16a-f indicate that the thrombin inhibitory activity is mainly determined by the charge density of the TBD moiety.

Biological properties of synthetic glycoconjugate mimics of heparin comprising different molecular spacers.

The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin.

Conformational aspects of an uncharged phosphate analogon built in at the branch-point of a DNA four-way junction.

Electrostatic interactions appear to be important in the conformation and dynamics of DNA four-way junctions. Particularly, the Coulomb repulsion between two approaching phosphate groups at the site of strand exchange is commonly supposed to have a negative influence on the thermodynamic stability of the fully stacked conformation. We synthesized a unimolecular DNA four-way junction containing an uncharged methylene-acetal linkage, -O3'-CH2-O5'-, instead of a regular phosphodiester linkage, -O3'-PO2-O5'-, between two specific residues at the branch-point to examine the effect of charge removal. Complete sequential 1H-NMR assignments of the non-exchangeable base protons and H1'/H2'/H2" sugar protons were obtained with the aid of NOESY and TOCSY experiments. On the basis of the NMR data it is concluded that the stacking arrangement at the branch-point of the modified oligonucleotide is similar to that of the previously studied parent four-way junction. Surprisingly, this is not the stacking arrangement in which the close phosphate-phosphate contact at the site of strand exchange would be absent. Some implications of this novel information regarding the role of the phosphate-phosphate repulsion in four-way junctions are discussed.

Obesity after successful treatment of acute lymphoblastic leukemia in childhood.

Early and late effects of treatment for acute lymphoblastic leukemia (ALL) on weight was retrospectively investigated in 113 children in continuous first remission. Weight was examined at diagnosis up to 10 y after cessation of treatment. There was an increased prevalence of overweight after treatment for ALL which persisted over time. All treatment regimens included corticosteroid therapy, and 52 patients received additional cranial irradiation. Patients treated with and without cranial irradiation did not differ in weight gain, indicating that not cranial irradiation but corticosteroid therapy might explain weight gain in children treated for ALL. Dexamethasone was associated with a significant increase of weight at cessation of treatment. Patients treated with a combination of prednisone and dexamethasone had as a late effect the highest prevalence of obesity (44%). Gender or age at diagnosis were not related to weight gain.

Solid-phase synthesis of the nucleopeptide fragment H-Asp-Ser[pAAAGTAAGCC]-Glu-OH from the nucleoprotein of Bacillus subtilis phage phi 29.

The naturally occurring DNA-nucleopeptide H-Asp-Ser[5'-pAAAGTAAGCC-3']-Glu-OH was prepared via a solid-phase phosphite triester approach using N-2-(tert-butyldiphenylsilyloxymethyl)benzoyl protected nucleosides. The oligonucleotide was linked via the extremely base-labile oxalyl ester anchor to the solid support.

Solid-phase synthesis of an RNA nucleopeptide fragment from the nucleoprotein of poliovirus.

The naturally occurring RNA-nucleopeptide H-Ala-Tyr[5'-pUUAAAAC-3']-NH2 is prepared via a solid-phase phosphite triester approach using N-SiOMB/O-TBDMS-protected nucleosides. Preliminary 1H-NMR studies show that the peptidyl unit has a remarkable effect on the conformational behaviour of the RNA moiety in the nucleopeptide.

Solid-phase synthesis of H-Phe-Tyr-(pATAT)-NH2: a nucleopeptide fragment from the nucleoprotein of bacteriophage phi X174.

The preparation of the nucleopeptide H-Phe-Tyr-(pATAT)-NH2 could be realized via a solid phase phosphitetriester approach and by using the protected protecting group 2-(tert-butyldiphenylsilyoxymethyl)-benzoyl for the masking of the N6-amino function of deoxyadenosine. The latter protecting group can be removed under mild conditions with fluoride ion.

Effects of ventricular shunt treatment of normal pressure hydrocephalus on psychological functions.

A prospective trial for diagnosis, treatment and evaluation of normal pressure hydrocephalus (NPH) was carried out in 30 consecutive patients (12 women, 18 men, mean age: 61 years, range 21-80). The clinical diagnosis was based on the presence of one or more of the three clinical elements of NPH: gait disturbance, incontinence and mental deterioration as well as radiological criteria of ventricular enlargement. Preoperatively, physical and radiological investigations and psychological tests were routinely performed. Cognitive functions such as fluency, selective attention and motor speed were re-examined within 24 hours after spinal tap of 40-50 cc. of CSF. Results of shunting were confirmed by CT scans and evaluated by means of psychological tests at least 3 months postoperatively. Psychological tests included IQ tests and tests for memory, selective attention and motor speed. Results indicate that spinal tap had no predictive value for the results after shunting as far as psychological functions are concerned. Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.

Synthesis of the nucleopeptides H-Phe-Tyr(pGC)-NH2 and H-Phe-Ser(pGC)-Ala-OH via a phosphotriester approach.

Use of the protecting groups di-n-butylaminomethylene,2-nitrophenylsulfenyl and the ester of 2-(hydroxymethyl)-9,10-anthraquinone, enabled us for the first time to prepare nucleopeptide fragments containing 2'-deoxyguanosine and a free carboxylic acid group.

A model study directed towards the preparation of nucleopeptides via H-phosphonate intermediates.

The monofunctional phosphitylating reagents bis-(N,N-diethylamino)chlorophosphine and salicylchlorophosphine have been applied for the preparation of H-phosphonates of the amino acids serine, threonine and tyrosine. Experimental evidence showed that the latter reagent was less effective for the synthesis of a tyrosine H-phosphonate. The amino acids (peptide) H-phosphonates of serine or threonine proved to be suitable starting compounds for the formation of a phosphate diester bond with the 5'-OH of a d-nucleoside derivative using pivaloyl chloride as the activating reagent.

Nine days post-thawing red cell conservation in a synthetic medium. Biochemical studies.

The expiration of thawed red cells (RBC) currently is 24 hours. This leads to problems in current transfusion practice, and often wastes rare and costly products. To remedy this situation, we developed a synthetic medium containing 0.085 g per l adenine, 5 g per l glucose, 48.0 g per l sucrose, 0.75 g per l NaH2PO4.H2O, 4 g per l Na2HPO4.2H2O, and 2.5 g per l NaCl, with a pH of 7.40, and an osmolarity of 320 mOsm. After 15 days post-thawing storage at 4 degrees C in our medium, the viability and function of RBC were maintained. We propose the storage of thawed RBC at 4 degrees C in our medium for up to 9 days: sterility was maintained, pH was 6.80, and 2,3-diphosphate glycerate was 50 percent, and adenosine triphosphate 100 percent of the original values. Free hemoglobin was 122 mg per unit, adenylate energy charge was 0.90, and RBC labeled 7 days after thawing showed 89 percent survival 24 hours after transfusion and a one-half disappearance of 22 days.

[The delay of a time-limitation for thawed blood. New perspectives]. / Le délai de péremption du sang décongelé. Nouvelles perspectives.

In order to comply with the needs for delayed transfusion in current practice (rare blood types dispatched to other centers, thawed blood not finally transfused to a patient, blood bank supply of Rh negative blood), we have investigated preservative media for thawed blood. We have previously shown that thawed RBC concentrates resuspended in isologous or autologous plasma remain viable and functional for 72 hours. We have extended these investigations by resuspending thawed RBC concentrates in an original synthetic preservative medium designed in our laboratory, containing: (table; see text) The following parameters have been investigated before freezing and during 15 days following thawing and washing: sterility, pH and 2,3-DPG, ATP and energy charge, free Hb levels in the supernatant, 24 h post-transfusion life and half-life of 51Cr-labeled RBC. This preservative allows the conservation of thawed RBC for up to nine days at +4 degrees C. During that time, sterility is maintained, pH is 6.80, 2,-3-DPG levels are 50% of the original values, ATP levels are 100% of the original values, free Hb is 122 mg per blood unit, energy charge is 0.90; RBC labeled 7 days after thawing showed a 89% survival rate 24 h after transfusion and a half-life of 19 days.

Embryonal rhabdomyosarcoma of the urogenital tract in childhood.

18 children, 12 boys and 6 girls, were treated in our hospital for rhabdomyosarcoma of the urogenital tract between 1970 and 1980. This period saw a gradual change in the therapeutic approach to this disease as new therapeutic modalities became available. 7 of the patients (39%) died of the disease which, in 5 of them, arose from the prostate. The surviving children have no evidence of recurrent disease, although 1 is still undergoing chemotherapy. Surgical intervention was always required. To date, chemotherapy alone, or in combination with radiation, has not sufficed in our management of rhabdomyosarcoma of the urogenital tract.