Prevalence of Müllerian duct anomalies detected at ultrasound.

The true prevalence of müllerian duct abnormalities is not well established. We used standard ultrasound examinations to establish the prevalence of müllerian duct abnormalities in girls and women who were evaluated for reasons unrelated to the presence of uterine anomalies. Prospective ultrasound examinations for nonobstetric indications in 2,065 consecutive girls and women (aged 8-93) showed that 8 had anomalies, including bicornuate uterus, septate uterus, and double uterus. In this first attempt to determine the prevalence of uterine anomalies in the general population, using noninvasive methodology, the rate of anomalies was 3.87 per 1,000 women (exact 95% confidence interval: 1.67-7.62), or approximately 1 in 250 women. This prevalence estimate may be greater than the true rate if selection biases are strong, or less than the true prevalence if ultrasound detection rates are low. As a first attempt to establish the prevalence by pelvic ultrasound in a consecutive series, these data may serve as a baseline estimate.

Dethiobiotin synthetase: the carbonylation of 7,8-diaminonanoic acid proceeds regiospecifically via the N7-carbamate.

Dethiobiotin synthetase (DTBS) catalyzes the penultimate step in biotin biosynthesis, the formation of the ureido ring of dethiobiotin from (7R,8S)-7,8-diaminononanoic acid (7,8-diaminopelargonic acid, DAPA), CO2, and ATP. Solutions of DAPA at neutral pH readily formed a mixture of the N7- and N8-carbamates in the presence of CO2. However, four lines of evidence together indicated that only the N7-carbamate of DAPA was an intermediate in the reaction catalyzed by DTBS. (1) Addition of diazomethane to mixtures of DAPA and [14C]CO2 yielded a mixture of the N7- and N8-methyl carbamate esters, consistent with carbamate formation in free solution. In the presence of excess DTBS (over DAPA), the ratio of N7:N8-methyl carbamate esters recovered was roughly doubled, suggesting that the enzyme preferentially bound the N7-DAPA-carbamate. (2) Both N7- and N8-DAPA-carbamates were observed directly by 1H and 13C NMR in solutions containing DAPA and [13C]CO2. In the presence of excess DTBS (over DAPA) only one carbamate was observed, showing that carbamate binding to the enzyme was regiospecific. 13C NMR of mixtures containing enzyme, [7-15N]DAPA, and [13C]CO2 showed that the enzyme-bound carbamate was at N7 of DAPA. In addition, pulse-chase experiments showed that the binary complex of DTBS and N7-DAPA-carbamate became kinetically committed upon addition of MgATP. (3) The N7-DAPA-carbamate mimic, 3-(1-aminoethyl)nonanedioic acid, in which the carbamate nitrogen was replaced with a methylene group, cyclized to the corresponding lactam in the presence of DTBS and ATP; ADP and P(i) were also formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of an ATP-dependent carboxylase, dethiobiotin synthetase, based on crystallographic studies of complexes with substrates and a reaction intermediate.

The crystal structures of six complexes of homodimeric Escherichia coli dethiobiotin synthetase with a variety of substrates, substrate analogs, and products have been determined to high resolution. These include (1) the binary complex of dethiobiotin synthetase and the N7-carbamate of 7,8-diaminononanoic acid, (2) the binary complex of enzyme and the alternate substrate, 3-(1-aminoethyl)-nonanedioic acid, (3) the binary complex of enzyme with the product ADP, (4) the quaternary complex of enzyme, ADP, the N7-carbamate of 7,8-diaminononanoic acid, and Ca2+, (5) the ternary complex of enzyme, the ATP analog adenylyl (beta, gamma-methylene)diphosphonate, and the N7-carbamate of 7,8-diaminononanoic acid, and (6) the quaternary complex of enzyme, the ATP analog adenylyl (beta, gamma-methylene)diphosphonate, 7,8-diaminononanoic acid, and Mn2+. One molecule of each substrate binds to one monomer of the enzyme. ADP and the ATP analogue bind to the classical mononucleotide binding fold with the phosphate groups close to the phosphate binding loop Gly8--Thr16 between beta-strand beta 1 and the N-terminus of alpha-helix alpha 1. The adenine ring is bound in a pocket between beta-strands beta 6 and beta 7. In the quaternary complex with Mn2+, the metal binding site is found in the vicinity of the beta- and gamma-phosphate groups. Two oxygen atoms from the phosphates and oxygen atoms from the side chains of Asp54, Thr16, and Glu115 are ligands to the Mn2+ ion in the quaternary complex. In the complex with ADP and the N7-carbamate of 7,8-diaminononanoic acid prepared in the presence of Ca2+ ions, a different metal binding site is found. The Ca2+ ion is coordinated to an oxygen atom of the alpha-phosphate group of the nucleotide, the side chain of Asp54, and solvent molecules. The 7,8-diaminononanoic acid substrate molecule interacts with residues from both subunits, making the dimer the minimal functional unit. The diamino group binds between the loops after beta 2 and beta 4, and the terminal carboxyl group at the hydrophobic tail of the substrate interacts with the amino terminus of helix alpha 5 and with the side chain of Tyr187 in helix alpha 6 of the second subunit at the monomer-monomer interface. Strong additional electron density close to the N7 nitrogen atom of the 7,8-diaminononanoic acid substrate in some complexes indicates that, even in the absence of added bicarbonate in the crystallization mixture, the carbamylated intermediate is formed in the crystal.(ABSTRACT TRUNCATED AT 400 WORDS)

An autistic boy copes with a terminal illness.

David, a 12-year-old boy with autism, developed Ewing's Sarcoma and died 3 months later. This report describes the effects of both illnesses on David, his parents, and his care givers. The difficulties encountered in finding appropriate help in the care of both illnesses and in making difficult decisions are described. The presence of autism can affect medical management and the presence of terminal illness can affect the management of autism. Suggestions are offered for effective medical and psychiatric interventions that include a sensitivity to both illnesses in physicians and other care givers; a case manager to help find appropriate medical and psychiatric services; and the availability of combined medical and psychiatric units.

Ventriculoamniotic shunt for treatment of hydrocephalus in one of twins: medical, ethical and legal considerations.

One of a pair of preterm twin fetuses was identified as having progressive hydrocephalus. After an extensive evaluation of the parents and both fetuses, a ventriculoamniotic shunt was placed. The affected twin, despite multiple additional neonatal procedures, has done well as matched against her normal twin sister. Both children are well 4 years after the surgery. The case presented a remarkable complexity of medical, ethical and legal issues which are presented.

Characterization of a glow discharge plasma as a function of sampling orifice potential.

Plasma diagnostic studies have been carried out on the discharge source of a commercial glow discharge quadrupole mass spectrometer. Plasma parameters were determined using an electrostatic probe with the objective of determining the dependence (if any) of these parameters on the voltage placed on an auxiliary electrode immersed in the plasma. The biased electrode utilized in this study was the sampling orifice element itself. Our results indicate that, for positive orifice voltages with respect to the grounded anode, variations in the plasma potential and ion energy can be correlated directly to the bias placed on the sampling orifice. The dependence of the electron temperature on this parameter is observed to be more complex in nature, and electron number densities show little significant variation with respect to sampling orifice bias. In addition, increased orifice voltages result in an increase in the ion signal intensity measured with the mass spectrometer. Based on the results obtained here, we feel that this increase is due primarily to an increase in ion transmission to the quadrupole arising from the increased ion energy.(J Am Soc Mass Spectrom 1990, 1, 448-454).

Noneffect of rifampin on theophylline disposition in rabbits.

The pharmacokinetic disposition of theophylline after a single 10mg/kg intravenous dose of aminophylline was evaluated in six rabbits. Three then received rifampin (50mg/kg) a day for 14 days and the disposition of theophylline was re-evaluated in all six rabbits after another 10mg/kg aminophylline dose. The mean theophylline half life before rifampin treatment of 5.11 +/- 0.71 hrs was not different (p greater than 0.10) from the half life of 4.54 +/- 0.71 hrs after treatment with rifampin. In the non-rifampin treated rabbits, the initial mean theophylline half life of 4.78 +/- 1.05 was not different p greater than 0.80) from the half life of 4.94 +/- 1.92 hrs after fourteen days. No significant alterations in clearance or area under the curve were noted for either group. Power analysis indicated that three rabbits were sufficient to detect at least a 25% change in the parameters as being significant (p less than 0.05).