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Biomedical subjects

W J Meyer

Publications and source records attributed to W J Meyer.

At least 37 records · Page 2Linked to original sources

Ultrasonographic detection of abnormal fetal growth with the gestational age-independent, transverse cerebellar diameter/abdominal circumference ratio.

OBJECTIVES: We prospectively evaluated the accuracy of a gestational age-independent method of detecting abnormal growth, the transverse cerebellar diameter/abdominal circumference ratio, and compared this with standard ultrasonographic methods of growth assessment. STUDY DESIGN: We prospectively studied 825 low-risk obstetric patients and 250 patients having risk factors for fetal macrosomia (n = 92) or growth retardation (n = 158). Measured fetal parameters included the biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference, and femur length. The estimated fetal weight, head circumference/abdominal circumference, cerebellar diameter/abdominal circumference, and femur length/abdominal circumference ratios were calculated. Reference curves for these parameters were created from a cross-sectional analysis of the low-risk group. Univariate analysis was used to determine the sensitivity, specificity, predictive values, and odds ratios of each individual parameter in identifying a small- or large-for-gestational-age infant. A multivariate logistic regression model with a variable selection procedure was then used to determine whether significance remained when we controlled for other parameters. RESULTS: Within the low-risk group, the transverse cerebellar/abdominal circumference ratio was gestational age independent between 14 and 42 weeks with a mean of 13.68 +/- 0.96. A value exceeding 2 SD of the mean was significantly associated with birth or a small-for-gestational-age infant, being abnormal in 98% and 71% of asymmetrically and symmetrically growth-retarded infants, respectively. Significance was maintained in the multivariate regression model. The ratio was not helpful in detecting the large-for-gestational-age infant. CONCLUSION: The fetal transverse cerebellar diameter/abdominal circumference ratio is an accurate, gestational age-independent method of identifying the small-for-gestational-age but not the large-for-gestational-age infant.

Abdomen↗

Intrapartum fetal subcutaneous tissue/femur length ratio: an ultrasonographic clue to fetal macrosomia.

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic intrapartum measurement of fetal abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio in predicting large-for-gestational-age fetuses. STUDY DESIGN: A cross-sectional analysis of 173 normal patients delivered of normal, appropriate-for-gestational-age infants (group 1) was performed to determine the normal changes of standard fetal biometric parameters and subcutaneous tissue throughout pregnancy. Measurements of fetal subcutaneous tissue were made at the level of the femoral diaphysis. A second group of 101 well-dated patients had these measurements obtained within 24 hours of delivery (group 2). Large for gestational age was defined as a birth weight > 90th percentile for gestational age. The sensitivity and specificity for prediction of large for gestational age of an intrapartum measurement of an abdominal circumference > 90th percentile, estimated fetal weight > 90th percentile, and fetal subcutaneous tissue/femur length ratio > 2 deviations of the mean was calculated. RESULTS: In group 1 the mean gestational age was 31.4 +/- 5.4 weeks (range 17 to 41 weeks). The femur length, abdominal circumference, and fetal subcutaneous tissue correlated well with gestational age (p < 0.0001). The fetal subcutaneous tissue/femur length ratio was stable throughout pregnancy, with a mean of 0.05 +/- 0.014 (range 0.02 to 0.09, R2 0.09). In group 2 mean gestational age was 38 +/- 2.5 weeks (range 30 to 42 weeks). Mean birth weight was 3280 +/- 740 gm (range 1513 to 4801 gm). Nineteen (19%) fetuses were large for gestational age. Significant differences were found between the appropriate- and large-for-gestational-age fetuses for birth weight, abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio (p < 0.0001). The sensitivity and specificity of the fetal abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio were 44% and 98%, 68% and 85%, and 82% and 96%, respectively. CONCLUSION: The fetal subcutaneous tissue/femur length ratio is a gestational age-independent parameter that has a greater sensitivity than the fetal abdominal circumference or estimated fetal weight formula for the intrapartum identification of large-for-gestational-age fetuses.

Abdomen↗

Expectant management of premature rupture of membranes with amniotic fluid cultures positive for Ureaplasma urealyticum alone.

OBJECTIVE: Our purpose was to determine maternal and neonatal outcome in patients with premature rupture of membranes and amniotic fluid cultures positive for Ureaplasma urealyticum alone. STUDY DESIGN: Amniocentesis was performed on 225 patients with premature rupture of membranes at < or = 34 completed weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Mycoplasma hominis, and Ureaplasma urealyticum. Patients with cultures positive for Ureaplasma urealyticum alone were managed expectantly, including erythromycin and daily biophysical profile examinations. RESULTS: Thirty-three patients (15%) had amniotic fluid cultures positive for Ureaplasma urealyticum alone, and clinical chorioamnionitis developed in three of these patients. There were no suspected or documented cases of neonatal sepsis. The incidence of infectious morbidity in patients with amniotic fluid cultures positive for Ureaplasma urealyticum alone was not significantly different from that seen in patients with negative cultures. CONCLUSION: An amniotic fluid culture positive for Ureaplasma urealyticum alone may not be an indication for a preterm delivery in patients with premature rupture of membranes.

Amniotic Fluid↗

Treatment of gender dysphoria (transsexualism).

Gender dysphoria, or transsexualism, is a condition involving incongruity between an individual's anatomic sex and personal sense of gender identity. Only in the last 15 years have Standards of Care been established and a professional organization developed to bring definition and consistency to the field (Harry Benjamin International Gender Dysphoria Association). A typical course of treatment lasts several years and includes psychological/psychiatric evaluations, completion of the "real life" test, administration of hormone therapy to create desired secondary sex characteristics, and finally sex reassignment surgery. As the field has developed and health-care professionals and the public have become more aware, increasing numbers of individuals are coming forward to seek evaluation and treatment. Published follow-up studies documenting long-term outcome are needed now. Current intervention techniques have progressed beyond the "experimental" stage and can be regarded as accepted medical practice.

Combined Modality Therapy↗

Two-minute miniprep method for plasmid DNA isolation.

An extremely rapid method, INSTA-PREP, has been developed to prepare plasmid DNA from 1 to 3 mL miniprep Escherichia coli bacterial cultures. Direct extraction of plasmid DNA from E. coli bacterial cells is achieved by a two-phase solution consisting of phenol-chloroform-isoamyl alcohol and water or buffer with efficient separation of the phases by centrifugation in the presence of the INSTA-PREP gel barrier material. Processing time, from E. coli culture to usable plasmid DNA, is two minutes or less per sample. Supercoiled plasmid DNA yields ranged from 3 to 10 micrograms per mL of culture depending on plasmid copy number. Plasmid DNAs prepared by INSTA-PREP were analyzed and are suitable for use in molecular biology procedures including restriction digestion, ligation with T4 DNA ligase, bacterial transformation, PCR, cultured cell transfection and T7 DNA polymerase or thermostable DNA polymerase-mediated dideoxynucleotide sequencing.

Animals↗

Inhibitory effects of ascorbic acid on growth of leukemic and lymphoma cell lines.

Vitamin C has been suggested and disputed as an anti-cancer agent. Previous in vitro studies using either primary cell cultures from cancer patients or tumor cell lines have suggested that tumor cells with different lineages may have different sensitivities to ascorbic acid. In this study we report characterization of the effects of ascorbic acid on growth of two ascorbic acid sensitive and one ascorbic acid resistant lymphocyte tumor cell lines. The cytotoxic effects of ascorbic acid on the sensitive cell lines were time and dosage dependent. Furthermore, the energy state of the ascorbic acid sensitive cells was affected by the presence of ascorbic acid before the cells became apparently non-viable, as demonstrated by 31P nuclear magnetic resonance spectroscopy. The existence of these lymphocyte cell lines with varying sensitivities to ascorbic acid may provide a useful model system for further understanding of vitamin C action on cancer cells.

Adenosine Triphosphate↗

Influence of host cell-mediated variation on the international surveillance of influenza A (H3N2) viruses.

Growth of clinical specimens of influenza viruses in eggs can result in the selection of antigenic variants distinct from corresponding viruses grown in mammalian tissue culture. To evaluate the contribution of host cell selection on the antigenic diversity of human influenza isolates, as seen in annual surveillance studies, viruses grown in embryonated eggs were compared by antigenic and genetic analyses with their mammalian tissue culture-grown counterparts. Clinical specimens were gathered from around the world from late 1987 to 1990 and the antigenicity of isolated viruses was assessed by hemagglutination-inhibition assays using immune ferret sera as is currently performed for routine surveillance and the selection of vaccine strains. In addition, viruses were assessed using a panel of anti-H3 HA monoclonal antibodies. The extent of antigenic variation exhibited by the egg-grown strains was far greater than the relative antigenic homogeneity of the tissue culture-grown viruses. Nucleotide sequence analysis of HA1 gene PCR products of 28 MDCK cell and egg derived pairs allowed identification of amino acid substitutions responsible for the antigenic differences observed and the adaptation to growth in eggs. Among these substitutions was a change at amino acid position 186 of HA1 (Ser in tissue culture viruses and lle in egg-grown viruses) which was observed at relatively high frequency. Egg- and MDCK-grown pairs with this single amino acid difference were classified into distinct antigenic groups by ferret sera raised to WHO reference viruses. Given the additional antigenic diversity observed among egg-grown strains, considerable care should be taken in the selection of reference and vaccine strains grown in eggs. Rapid sequence comparisons of MDCK- and egg-grown viruses allow identification of variants arising through egg selection and will prove to be a useful adjunct to antigenic surveillance for the selection of reference and vaccine strains.

Africa↗

Vasa previa: prenatal diagnosis with transvaginal color Doppler flow imaging.

Vasa previa carries a significant risk for fetal exsanguination and death at the time of membrane rupture. The diagnosis is rarely made before the onset of vaginal bleeding. We report the prenatal diagnosis of vasa previa with transvaginal color Doppler flow imaging in an asymptomatic patient with a succenturiate placenta.

Adult↗

The role of a research seminar for child psychiatry residents.

A major problem confronting the field of child and adolescent psychiatry is the development of teaching strategies to stimulate research activities and an appreciation of research. A teaching approach is described which emphasizes major research concepts using a programmed instruction method and illustrating these concepts with clinical cases. Fourteen child psychiatry residents participated in the seminar during a 3-year period. Overall, trainees' evaluation of the seminar was positive, and they demonstrated a high level of understanding across major research topics. In addition, the seminar may have contributed to an increased preference for academic careers by graduating residents.

Adolescent↗

Structural rearrangement of infecting Sindbis virions at the cell surface: mapping of newly accessible epitopes.

Sindbis virus glycoproteins E1 and E2 undergo a conformational alteration during early virus-cell interaction at the cell surface (D. Flynn, W. J. Meyer, J. M. MacKenzie, Jr., and R. E. Johnston, J. Virol. 64:3643-3653, 1990). Certain epitopes normally internal on native virus become accessible to monoclonal antibody (MAb) binding after attachment but before internalization of virus particles. These newly exposed epitopes, termed transitional epitopes, may be part of functionally important domains made accessible at the surface of the altered virus to facilitate entry into cells. Heating Sindbis virions at 51 degrees C for a short time induced a similar, although not identical, exposition of transitional epitopes on the E1 and E2 glycoproteins (W. J. Meyer, S. Gidwitz, V. K. Ayers, R. J. Schoepp, and R. E. Johnston, J. Virol. 66:3504-3513, 1992). In the current report, we have identified several of the transitional epitopes that become exposed as a consequence of early virus-cell interactions. Transitional epitope MAbs that bound to rearranged, heated virions and virus-cell complexes were used in antibody competition binding assays on heated Sindbis virions to map the spatial relationships between native, external, neutralizing antigenic sites and newly exposed transitional epitopes. Because the heated, rearranged particles retained their infectivity, MAbs that bound to transitional epitopes also were used to isolate MAb neutralization escape mutants. Sequencing the glycoprotein genes of the escape mutants identified specific E1 and E2 loci where mutation prevented MAb binding to transitional epitopes. One of the transitional epitopes identified (E2 residues 200 to 202) lies in the E2 190-216 region, which harbors two major neutralization sites, E2a and E2b, and an N-linked glycosylation site at E2 196. The glycosylation signal was eliminated by site-directed mutagenesis of a full-length cDNA clone of the Sindbis virus genome. The absence of a carbohydrate moiety did not expose the transitional epitopes mapped to this locus, suggesting that on native virions, the inaccessibility of the E2 200-202 determinant was inherent in the structure of the glycoprotein spike.

Amino Acid Sequence↗

The fetal transverse cerebellar diameter/abdominal circumference ratio: a gestational age-independent method of assessing fetal size.

The relationship between the fetal TCD and the AC throughout pregnancy was investigated in a prospective, cross-sectional study of 700 well dated, normal pregnancies between 14 and 42 weeks of gestation and tested in 30 known SGA infants. Fetal measurements included the TCD, AC, BPD, HC, and FL. The TCD/AC ratio was calculated for each patient. Statistical analysis using linear regression and Student's t-test was performed. Strong correlation existed between gestational age and transcerebellar diameter (R2 = 0.9464), between gestational age and AC (R2 = 0.9685), and between TCD and AC (R2 = 0.9561). The TCD/AC ratio was normally distributed with a mean +/- SD of 13.69 +/- 0.94% (median, 13.71%). The 10th and 90th percentiles were 12.50% and 14.86%, respectively. The ratio remained constant throughout pregnancy with respect to gestational age (R2 = 0.0084). A TCD/AC ratio greater than the 90th percentile was present in 87% (26/30) known SGA infants. The TCD/AC ratio is a stable, gestational age-independent parameter that may be useful in the early detection of fetal growth abnormalities.

Abdomen↗

Immunoreactive growth hormone production by human lymphocyte cell lines.

1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary.

Animals↗

Inhibition of immunoreactive growth hormone secretion from lymphoid cell lines by dexamethasone.

The regulation of irGH secretion by the immune system was examined using lymphoid cell lines, H9 and IM9. Using a highly sensitive immunoassay, irGH secretion by H9 was negatively regulated by dexamethasone, whereas many other regulators of hGH secretion, including hormones, monoamines, and second messenger, had no measurable effect on irGH secretion. Treatment of H9 cells with dexamethasone for 48 hours could cause as high as 70% reduction in irGH secretion without affecting either cell numbers or viability. Using IM9, neither growth hormone releasing hormone nor thyrotropin releasing hormone had significant effect on either irGH steady-state level transcripts or irGH secretion. These findings suggest that irGH secretion by lymphocytes was regulated in a different manner from that by pituitary cells.

Antibodies↗

Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect.

1. In order to further understand the apparent glucocorticoid resistance in major depressive disorder, circadian variation in cortisol concentration, dexamethasone suppression and glucocorticoid receptor binding in mononuclear leukocytes, polymorphonuclear leukocytes and cultured skin fibroblasts were measured in rigidly defined major depressive disorder patients and non-depressed psychiatric controls. 2. Mononuclear leukocytes binding to glucocorticoid correlated significantly with polymorphonuclear leukocytes binding to glucocorticoid, but both determinations failed to differentiate major depressive disorder and control subjects. 3. Initial and post-dexamethasone in vitro fibroblast binding to glucocorticoid was not different between major depressive disorder and non-depressed control subjects. 4. The phenomenon of glucocorticoid resistance in major depressive disorder remains unexplained.

Adult↗

Comparison of gram stain, leukocyte esterase activity, and amniotic fluid glucose concentration in predicting amniotic fluid culture results in preterm premature rupture of membranes.

OBJECTIVE: The purpose of this study was to prospectively compare three rapid and inexpensive tests that have been proposed as predictors of amniotic fluid culture results in preterm premature rupture of membranes. STUDY DESIGN: Amniocentesis was performed on 117 patients < or = 34 weeks' gestational age with premature rupture of membranes and no clinical evidence of infection. Amniotic fluid was sent for Gram stain and aerobic, anaerobic, and Mycoplasma cultures. Leukocyte esterase activity and glucose concentration were also determined on the amniotic fluid. RESULTS: Amniotic fluid cultures were positive in 56 patients (47.8%). Leukocyte esterase activity of 1+ or 2+ and an amniotic fluid glucose concentration < or = 16 mg/dl were significantly more sensitive (p < 0.005) than Gram stain in detecting positive amniotic fluid cultures (73%, 68%, and 41%, respectively). CONCLUSIONS: Although each of these rapid tests is useful in assessing for subclinical intraamniotic infection, none of them have sufficient accuracy to make clinical decisions solely on the basis of their results.

Amniotic Fluid↗

Conformational alteration of Sindbis virion glycoproteins induced by heat, reducing agents, or low pH.

Sindbis virions undergo a conformational rearrangement after attachment to cells but prior to entry, as detected by exposure of epitopes on virus-cell complexes which are not accessible to their cognate monoclonal antibodies on native virions (D. C. Flynn, W. J. Meyer, and R. E. Johnston, J. Virol. 64:3643-3653, 1990). The rearrangement did not appear to require transit of virions through a low-pH environment, and the altered virions participated in a productive infection. This naturally occurring structural alteration could be mimicked, although not precisely duplicated, by any of the three artificial treatments of purified virions in vitro: brief incubation at 51 degrees C, treatment with 1 to 5 mM dithiothreitol, or incubation of pH 5.8 to 6.0. Infectivity was maintained after all three treatments, suggesting that Sindbis virions are metastable and can exist in at least two infectious conformations. The integrity of external, neutralizing epitopes was maintained on cell-associated virions and in the altered conformations induced by heat and dithiothreitol, whereas these epitopes were unreactive under low-pH conditions that induced an analogous exposure of previously inaccessible epitopes. The pH at which the conformational change was induced and the pH at which virions could mediate cell-cell fusion from without were coordinately shifted when these two parameters were determined for another strain of Sindbis virus. This coordinate shift in pH optima suggests that the conformational change in virion structure observed at the cell surface may be causally related to fusion.

Antibodies, Monoclonal↗

Cholelithiasis associated with medroxyprogesterone acetate therapy in men.

Five out of forty-five adult men, 50 years of age or less, who had received, for at least six months, medroxyprogesterone acetate (MPA, Depo Provera) IM, 200-400 mg/week, for prevention of sex-offending or genital-mutilating behavior developed symptomatic cholelithiasis. Thirty of these men were studied with gallbladder ultrasound prospectively off MPA and at six-month intervals while taking the medication and then six months off MPA. Gallstones recovered from two patients were found to have very high cholesterol content, suggesting they were formed in cholesterol supersaturated bile. These findings are consistent with the increased incidence of gallbladder disease related to high-progesterone states and suggest that MPA may be a causative agent in cholelithiasis. The physiologic studies on gallbladder contraction and cholecystokinin release in a subset of the patients failed to provide information on a mechanism for the possible increased incidence of gallbladder disease.

Adult↗