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.

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.

Lipid tolerance testing in pregnancy.

OBJECTIVE: Macrosomia in the infant of the well-controlled diabetic mother suggests that a substrate other than glucose may influence fetal growth. We hypothesized that GDM alters lipid homeostasis during pregnancy. Our objective was to determine if an LTT could assist in identification of lipid abnormalities in the GDM individual. RESEARCH DESIGNS AND METHODS: The LTT consisted of bolus infusion of 1.0 mg/kg 10% Intralipid (Cutter Vitrum, Berkeley, CA) followed by measurements of plasma glucose, insulin, glycerol, total triglycerides, and triglyceride fatty acids (18:1 and 18:2), total FFAs, and total phospholipids for 30 min before and 90 min after the bolus. The study groups were composed of 8 nonpregnant, nondiabetic subjects, 8 pregnant, nondiabetic subjects, 8 GDM patients receiving insulin, and 8 GDM patients who were diet controlled. RESULTS: Plasma glucose and plasma insulin concentrations did not change significantly after the bolus. No significant difference was noted in the K2 for glycerol of the nonpregnant, nondiabetic group compared with the pregnant groups. The K2 for total triglycerides, plasma triglyceride 18:1, and plasma triglyceride 18:2 indicated increased rates of disappearance of these substrates for the nonpregnant nondiabetic group compared with all pregnant groups. No significant differences were observed among the pregnant groups for any of these parameters. CONCLUSIONS: Pregnancy may be associated with a decreased rate of triglyceride lipolysis compared with nonpregnancy. No differences in lipid metabolism were noted among normal pregnant and relatively well-controlled GDM patients.

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.

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.

Treatment of antenatal myasthenia gravis.

Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti-acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies.

Maternal age and screening for gestational diabetes: a population-based study.

The American College of Obstetricians and Gynecologists (ACOG) has recommended screening for gestational diabetes, using a 50-g, 1-hour glucose challenge (threshold for further testing 140 mg/dL or higher), for all pregnant women aged 30 or older and for younger women with risk factors. In order to assess these recommendations, we collected demographic and historic data on 6214 pregnant women representing a population of universally screened individuals. Of 125 cases of gestational diabetes diagnosed (ACOG criteria), 70 patients (56%) were under the age of 30. In addition, 44% of gestational diabetics had no risk factors. The cost per case diagnosed would be $190 with the ACOG recommendations, $192 if the age for routine screening were lowered to 25 years or more, and $222 if universal screening were practiced. Using the ACOG recommendations, 35% of gestational diabetes would go undiagnosed, with little cost savings.

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.

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.

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.

Inhibition of 5-hydroxytryptamine-evoked autonomic transmitter release by apomorphine.

Apomorphine inhibited chronotropic responses of the isolated rabbit heart to 5-HT by 40% at 1.17 micrometers and by 90% at 4.68 micrometers and strongly inhibited the outflow of 3H following preloading of hearts with [3H]- (-)-noradrenaline. Apomorphine, 4.68 micrometers, had no significant effects on transmitter release evoked by DMPP or tyramine but inhibited the responses to SNS at frequencies up to 3.2 Hz. The inhibitory effects of apomorphine on 5-HT were resistant to blockade by chlorpromazine, 1.4 micrometers, haloperidol, 1.6 micrometers, spiroperidol, 2.5 micrometers, or yohimbine, 2.8 micrometers. In contrast, the inhibitory effects of apomorphine on low frequency SNS were abolished by yohimbine. On the guinea-pig ileum treated with methysergide, apomorphine, 1.17-4.68 micrometers, blocked the indirect cholinergic responses to 5-HT less markedly than it blocked the indirect sympathomimetic responses to 5-HT on the rabbit heart. Moreover, the effects were non-selective since responses to DMPP and transmural stimulation of the intramural cholinergic nerves were similarly reduced. Modification of 5-HT receptor function is the most likely explanation for the action of apomorphine with the differential effect on 5-HT in the heart and ileum reflecting differences in the receptors and/or post receptorial events at the two sites.

Lack of modulation by presynaptic alpha 2-adrenoceptors of adrenergic transmitters release evoked by activation of 5-hydroxytryptamine and nicotine receptors.

Clonidine (4.3 X 10(-6) M) and yohimbine (2.8 X 10(-6) M) have been used to stimulate and to block alpha 2-adrenoceptors in the isolated perfused rabbit heart. Transmitter release from the terminal sympathetic fibres as a result of stimulation of the nerves leaving the stellate ganglion (SNS; 0.32-10 Hz) and bolus injections of 5-hydroxytryptamine (5-HT; 2.8-182 nmol) or dimethylphenylpiperazinium (DMPP; 26-418 nmol) was estimated from changes in the chronotropic response of the heart under conditions of constant end organ sensitivity to injected noradrenaline (0.06-15.1 nmol). In accordance with the literature, clinidine inhibited responses to SNS and was more effective against low than against high frequencies of stimulation; similarly, yohimbine enhanced responses to SNS. In contrast, neither clonidine no yohimbine had any effect on the indirect sympathomimetic response to 5-HT. Similarly yohimbine did not alter responses to DMPP. Clonidine produced inconsistent effects on the response to DMPP; the response to 105 nmol was unchanged whereas the response to 209 nmol was reduced. The results suggest that transmitter release from the cardiac sympathetic nerves of the rabbit heart evoked by 5-HT or DMPP is not subject to control through activation of alpha 2-adrenoceptors by the released transmitter. They lend support to the suggestion of Stjärne that alpha 2-adrenoceptor inhibition of transmitter release arises primarily from the suppression of impulse transmission from varicosity to varicosity within the adrenergic ground plexus rather than interference with a Ca2+-dependent step in excitation-secretion coupling.

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.

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.

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.

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.

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.