Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial.

OBJECTIVE: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. METHODS: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. RESULTS: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. CONCLUSION: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

Minimally invasive esophagectomy. An update on the options available.

Minimally invasive techniques have been successfully applied to esophageal surgery. Initially, they were used for benign disease, but as experience has increased, so have the indications for minimally invasive esophageal surgery. Today, minimally invasive esophagectomy has been reported in all types of patients with a variety of esophageal diseases and different stages of esophageal cancer. Currently, the biggest limitation for proceeding with minimally invasive esophagectomy is experience in performing the procedure. This article provides an update on the myriad of options for performing minimally invasive esophagectomy including advantages and disadvantages of each option and outlines the surgical technique for each. It highlights the current debate on open versus minimally invasive esophagectomy. Since there is no consensus on the operative approach to open esophagectomy, it is not surprising that a number of debates over the best operative approach to minimally invasive esophagectomy exist today.

First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study.

OBJECTIVE: To determine whether first- and second-trimester Down syndrome screening markers and screen-positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs). METHODS: ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), and intrauterine insemination with OI (IUI-OI) or without OI (IUI). Each group was compared to non-ART controls using Mann-Whitney U analysis. RESULTS: First-trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP-A levels in the IUI-OI group. In contrast, second-trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha-fetoprotein (AFP) was increased in ED pregnancies. Second-trimester screen-positive rates were significantly higher than expected for ART pregnancies, except when ED was used. CONCLUSIONS: These data show that ART significantly impacts second-, but not first-, trimester markers and screen-positive rates. The type of adjustment needed in second-trimester screening depends on the particular type of ART used.

Minimal-access fetal surgery for twin-to-twin transfusion syndrome.

BACKGROUND: Laser ablation of placental vessels effectively halts severe twin-to-twin transfusion syndrome (TTTS), but fetal surgery remains a dangerous approach. The authors present the technical aspects of endoscopic fetal surgery in their initial clinical experience. METHODS: Altogether, 11 women underwent endoscopic fetal surgery for severe TTTS. Access to the recipient's sac was obtained by the Seldinger technique via minilaparotomy. A 12-Fr peel-away introducer was used as a cannula to accommodate a custom-curved 9-Fr sheath containing a 1.9-mm semirigid fiber endoscope. Laser ablation was performed on all unpaired vessels crossing the intertwin membrane using a 400- micro m neodymium: yttrium-aluminum-garnet (Nd: YAG) fiber. The cannula was removed over a gelatin sponge plug. RESULTS: The median operating time was 65 min (range, 45-105 min). No patient experienced amniotic leak postoperatively. The length of hospital stay was 2.8 +/- 1.6 days. Immediate improvement of the TTTS was noted in all but two patients. Pneumonia developed, in one mother leading to premature labor. There were no other major surgical complications. Fetal survival at 2 weeks was 73%. CONCLUSIONS: The safety and efficacy of endoscopic fetal surgery for severe TTTS can be optimized with the application of current minimal-access techniques. The superiority of this approach over less invasive means is still being evaluated through prospective studies.

Experience with a multidisciplinary antenatal diagnosis and management model in fetal medicine.

BACKGROUND: Fetal medicine is a new and evolving specialty. Complex fetal conditions may require the multidisciplinary input of clinicians from many different specialties. METHODS: Referral of fetal patients was made to a multidisciplinary antenatal diagnosis and management (MADAM) board if more than one specialty (in addition to maternal-fetal medicine) needed to be intimately involved in the evaluation or care of the fetus; consultation would probably lead to alterations in fetal or perinatal management; or development or revision of management guidelines was anticipated. The case log of the MADAM conferences was reviewed retrospectively for number and type of fetal anomalies, and outcome of the presentation to the MADAM board. RESULTS: During a 5-year period, 1% of 25654 pregnant women who were evaluated required consultations with individual pediatric and pediatric surgical specialists. Of these, 114 patients were referred to one of 77 MADAM conferences for consensus recommendation. Of these 77 discussions, 32 (42%) led to an alteration in prenatal management, 14 (18%) led to co-ordination of postnatal management and 12 (16%) led to the establishment of a new treatment guideline, or the modification of an existing one. In all, perinatal management was altered in 75% of cases. CONCLUSION: The MADAM model functions as a forum for exchange of up-to-date scientific information, development of evidence-based treatment protocols and continuity of care through the pre-, peri- and postnatal periods.

Preoperative planning with magnetic resonance imaging and computerized volume rendering in twin-to-twin transfusion syndrome.

Our purpose was to illustrate the feasibility of preoperative planning with magnetic resonance imaging, 3-dimensional reconstruction, and volume-rendering techniques in twin-to-twin transfusion syndrome treated by endoscopic laser ablation of communicating vessels. After ultrasonographic determination of the syndrome and the indications for intervention, 2 patients with an anterior placenta underwent magnetic resonance imaging without the need for maternal or fetal sedation. Raw image data were downloaded into a desktop computer and manipulated with 3-dimensional reconstruction, volume rendering, and surgical navigation software. In both patients a virtual rendering of the fetuses, placenta, and uterus could be manipulated to expose all sides, demonstrate the location of the intertwin membrane, and plan the point of entry and curve of the endoscopic instruments. Preoperative planning and virtual surgical navigation in fetal surgery are now possible, as a result of shorter magnetic resonance imaging acquisition times and volume-rendering software. In this manner an entire virtual endoscopic fetal operation can be performed and fine-tuned before the actual procedure is to take place.

Rhesus isoimmunization.

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Disease severity may be assessed using the modalities described above and frequently, invasive techniques are required to determine the risk of severe disease. Doppler flow studies appear to offer accurate, noninvasive means of evaluating fetal risk, which may allow for a decrease in invasive diagnostic procedures. The Rh isoimmunized patient, managed by an experienced team, can anticipate a favorable pregnancy outcome.

Idiopathic spontaneous intraperitoneal hemorrhage: a clinical update on abdominal apoplexy in the year 2001.

Idiopathic spontaneous intraperitoneal hemorrhage is a rare and often fatal condition that has been historically referred to as abdominal apoplexy. The presentation varies widely, and preoperative diagnosis is seldom obtained. Immediate surgical exploration remains the treatment of choice. At the time of exploration a through examination of the visceral arteries and solid organs should be done, as these are common sites for intra-abdominal bleeding. Often the site of hemorrhage cannot be localized at time of surgery despite thorough exploration. Today a postoperative diagnosis can often be confirmed and treated with interventional radiology. In rare cases the site of bleeding remains unknown despite intraoperative exploration and radiographic studies.

The unpredictable character of congenital cystic lung lesions.

BACKGROUND: The spectrum of congenital cystic disease of the lung ranges from hydrops and neonatal respiratory distress to asymptomatic lesions. Surgical management is dictated by the presence of symptoms, recurrent infection, and the potential risk of malignant transformation. METHODS: Since 1995, all consecutive patients with congenital cystic lung lesions underwent follow-up for symptoms, treatment, and correlation of presumptive with pathological diagnosis. RESULTS: Twelve cystic lung lesions were identified. Seven were diagnosed with mediastinal shift in utero; in 6 of 7, the shift subsequently resolved. Overall, 6 of 7 lesions that were followed up serially decreased in size. Two patients were symptomatic in utero; 1 underwent thoracoamniotic shunting, 1 pleurocentesis for impending hydrops. Postnatally, these 2, and 2 other newborns required urgent surgery. Five of 8 asymptomatic patients had elective resection by 16 months, and 4 await operation. In 6 of the 9 surgical cases (67%), there was a discrepancy between preoperative and pathological diagnosis. There were 4 hybrid congenital cystic adenomatoid malformation (CCAM)/sequestrations. CONCLUSIONS: At least 6 of 7 congenital cystic lung lesions decreased in size regardless of gestational age or presence of mediastinal shift. Antenatal intervention is therefore rarely indicated. Hybrid morphology may necessitate resection of stable, asymptomatic lesions to prevent the theoretical concern for associated malignancies as well as other complications of CCAM.

Screening for gestational diabetes mellitus. A perspective in 1998.

Gestational diabetes mellitus (GDM) was originally defined using statistics. It is appropriate to examine the current state of screening for gestational diabetes using a similar approach. This article reviews data supporting current recommendations for universal screening of pregnant women for GDM at 24-28 weeks using the 50-g 1-h oral glucose challenge. The advantages and disadvantages of several thresholds for abnormality are discussed, as are possible alternatives to the 50-g 1-h oral glucose challenge. Finally, recent improvements in the precision of portable blood glucose meters are reviewed, and recommendations for their use are advanced.

Reactivity and gas-phase acidity determinations of small peptide ions consisting of 11 to 14 amino acid residues.

Small peptides ions consisting of a comparable number of amino acid residues but varying in composition and sequence were allowed to undergo gas-phase deprotonation reactions. These multiply protonated ions were generated by electrospray ionization and analyzed in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The peptides studied contain 11-14 amino acid residues and included adrenocorticotropic hormone (ACTH) fragment (11-24), fibrinopeptide B (human), gastrin I fragment (1-13) (human), renin substrate tetra-decapeptide (horse), somatostatin, substance P and tyrosine protein kinase. Rate constants were determined for the deprotonation reactions of the peptide ions with a series of reference compounds of known gas-phase basicities ranging from 190.0 to 232.6 kcal mol-1. From these values, apparent gas-phase acidities (GAapp) were assigned to [M + nH]n+ (n > or = 2), of each peptide. All of the multiply charged peptide ions were sequentially deprotonated to the +1 charge state by ion-molecule reactions. The GAapps ranged from 193.3 kcal mol-1 (for [M + 4H]4+ of renin substrate, the ion most readily deprotonated) to > 232.6 kcal mol-1 (for [M + 2H]2+ of ACTH (11-24), the ion most difficult to deprotonate). The proximity of intrinsically basic sites (and therefore potential protonation sites) has an effect on the observed deprotonation rates. Ions experiencing Coulomb repulsion resulting from adjacent protonation sites often show more facile deprotonation. However, the intrinsic basicity of a protonation site also plays a role in determining the case of deprotonation. As a result, some lower charge state peptide ions deprotonate more readily than other peptides with higher charges but with more basic protonation sites. In addition, conformation and the influence of intramolecular hydrogen bonding may affect the reactivity of some peptide ions. Also observed was non-linear kinetic behavior that indicates multiple isomers at certain charge states for some peptides, e.g. [M + nH]n+, (n = 2 and 3) for ACTH 11-24 and [M + 3H]3+ for somatostatin.

Elucidation of isomeric structures for ubiquitin [M + 12H]12+ ions produced by electrospray ionization mass spectrometry.

Gas-phase deprotonation reactions, hydrogen-deuterium exchange reactions and collision-induced dissociation (CID) were used to distinguish between two isomeric forms of [M + 12H]12+ produced from the protein ubiquitin. Ions were generated by electrospray ionization and studied in a Fourier transform ion cyclotron resonance mass spectrometer. For [M + 12H]12+ formed directly from the electrospray process, deprotonation reactions with ammonia and 2-fluoropyridine yield non-linear pseudo-first-order kinetic behavior that indicates the presence of two ion structures. The fraction of ions that undergo the fastest deprotonation reactions, and is presumably the least energetically stable isomer, accounts for approximately 60% of the [M + 12H]12+ produced by electrospray. In reactions with D2O and CD3OD, the [M + 12H]12+ which are deprotonated faster exchange the first 11 +/- 1 hydrogens more readily that the remaining [M + 12H]12+ population. Results from CID experiments, obtained as a function of reaction time with the amines, also indicate the existence of more than one [M + 12H]12+ structure. The CID fragmentation patterns provide information about the general locations of the charge sites. Surprisingly, evidence for only one structure (the slow-reacting, more stable species) is found for [M + 12H]12+ that is produced by gas-phase deprotonation of [M + 13H]13+, which is the "fully protonated' form of ubiquitin. These results are discussed in terms of ubiquitin isomers related to protonation site and three-dimensional conformation.

Fetal hyperinsulinism at 14-20 weeks and subsequent gestational diabetes.

OBJECTIVE: To examine the predictive value of amniotic fluid (AF) insulin at 14-20 weeks' gestation for subsequent gestational diabetes and macrosomia in unselected gravidas 35 years or older at time of genetic amniocentesis. METHODS: We identified 296 pregnancies through stored AF samples from genetic amniocenteses (collected March 1987 through August 1992) in women meeting the following criteria: age 35 years or older, amniocentesis at 14-20 weeks, performance of a 50-g glucose challenge test, and adequate delivery data. RESULTS: A modified double-antibody radioimmunoassay reliably measured AF insulin with a detection limit of 0.35 microU/mL. Pregnant women in whom gestational diabetes was later diagnosed had higher median AF insulin levels than women who did not (0.60 versus 0.42 microU/mL, respectively; P = .026). A stepwise logistic regression analysis of gestational age at amniocentesis, maternal second-trimester weight, maternal age, and log AF insulin value on gestational diabetes showed only AF insulin to have a significant association with gestational diabetes (P = .004). Seven of 21 cases of gestational diabetes had AF insulin values exceeding the 95th percentile (1.33 microU/mL) compared with only 14 of 275 women with normal glucose tolerance (P < .001). Amniotic fluid insulin did not predict macrosomia in either nondiabetic or gestational diabetic pregnancies. CONCLUSION: Gestational diabetes is associated with increased AF insulin at 14-20 weeks, suggesting augmentation of fetal insulin production in the early fetal period in at least some cases of gestational diabetes.

Gas-phase basicities of histidine and lysine and their selected di- and tripeptides.

The gas-phase basicities (GB) of histidine, lysine, and di- and triglycyl peptides containing either one histidine or one lysine residue have been determined. In all, 12 compounds were examined in a Fourier transform ion cyclotron resonance mass spectrometer. The GBs of the biomolecules were evaluated by proton transfer reactions employing a range of reference compounds with varying gas-phase basicities. In addition, the GBs were determined by using the kinetic method of collision-induced dissociation on a proton-bound dimer containing the peptide and a reference compound. The GBs of histidine and lysine were both found to be 220.8 kcal/mol via proton transfer reactions. The kinetic method experiments, including dissociation of a proton-bound dimer containing both histidine and lysine, also suggest equivalent GBs for these amino acids. However, the small peptides containing lysine are generally more basic than the corresponding histidine-containing peptides. For the peptides, the data suggest that the protonation site is on the basic side chain functional group of the histidine or lysine residues. The GBs of the di- and tripeptides are dependent upon the location of the basic residue. For example, the GBs of the tripeptides glycylglycyl-L-lysine (GlyGlyLys) and L-lysylglycylglycine (LysGlyGly) were both determined to be 230.7 kcal/mol while a GB of kcal/mol was obtained for glycyl-L-lysylglycine (GlyLysGly). A similar GB trend is seen with the histidine-containing tripeptides. Generally, the GBs obtained by using the kinetic method are slightly higher than those obtained by deprotonation reactions; however, the trends in relative GB values are essentially the same with the two techniques.

Precision of office-based blood glucose meters in screening for gestational diabetes.

OBJECTIVE: Is the precision of currently available glucose meters adequate for gestational diabetes screening? STUDY DESIGN: We performed a prospective cohort study of 62 gravid women and compared the precision of three glucose meters to laboratory standard technology. RESULTS: The HemoCue coefficient of variation was sufficiently low in venous whole blood and plasma and capillary whole blood and plasma (3.0%, 1.8%, 2.8%, and 2.3%, respectively) to allow use in gestational diabetes screening. The OneTouch II coefficient of variation was sufficiently low in capillary whole blood (2.7%) to allow use in gestational diabetes screening but was too high in venous whole blood and plasma and in capillary plasma (3.6%, 7.8%, and 5.7%). The ExacTech coefficient of variation was too high in venous or capillary whole blood (5.4% and 8.1%) for use in gestational diabetes screening and does not analyze plasma samples. CONCLUSION: The HemoCue meter in venous and capillary whole blood and plasma and the OneTouch II meter in capillary whole blood have coefficients of variation low enough for gestational diabetes screening.

An electrospray ionization mass spectrometry study of copper adducts of protonated ubiquitin.

A study of the addition of Cu(II) to a ubiquitin electrospray solution shows that the copper ion in the ubiquitin remains doubly charged and displaces two protons on the protonated protein molecule. This observation indicates a chelating bond between the protein and the Cu(II) species. The addition of Cu(I) also was studied and significant intensity was observed for adducts with up to four Cu(I) species attached, with each Cu(I) bonded to one basic site on the protein.