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Biomedical subjects

M C Doody

Publications and source records attributed to M C Doody.

18 recordsLinked to original sources

False-positive hCG by enzyme immunoassay resulting in repeated chemotherapy.

BACKGROUND: In abnormal pregnancies, it is necessary to follow hCG levels to ensure resolution of the pregnancy, either spontaneously or after therapy. Lack of a normal resolution can be treated with methotrexate. CASE: A 32-year-old woman had a persistently elevated serum hCG level analyzed by enzyme immunoassay technique before and after being treated with three courses of methotrexate. Analysis of the serum samples by radioimmunoassay technique gave negative results. CONCLUSION: If the expected laboratory response is not forthcoming in the treatment of an abnormal pregnancy with methotrexate, hCG analysis by another assay method is recommended. False-positive hCG levels can result from the presence of heteroantibodies in the serum of the patient.

Abortion, Induced

Drop-out behaviour and fertility table analysis of pregnancy rates.

The life table analysis of infertility study data uses information from patients who drop out and are lost to follow-up. The fact that drop-out patients were not pregnant when last seen has been taken to be useful information that has been entered into the calculation of cumulative pregnancy rates for the population as a whole. However, drop-out patients who subsequently achieve pregnancy have motivations to return to their physician for follow-up, while those who do not become pregnant usually remain lost to follow-up. This can result in a systematic error toward reporting an excess of pregnancies, raising the apparent fecundity rates and plateau values. This study was undertaken to investigate the potential magnitude of these errors. Computer simulations of hypothetical infertility treatments using large cohorts (n = 32 000) were undertaken. Varying assumptions were made regarding post-treatment monthly fecundity rates, 'cure rates', drop-out rates and the percentage of pregnant drop-outs who would return to their physician after achieving pregnancy. Using a range of clinically reasonable assumptions, very large deviations from ideal behaviour were noted in the direction of elevated cumulative pregnancy rates. The non-ideal behaviour was most apparent with lower fecundity rates, lower 'cure rates', higher drop-out rates and higher pregnant drop-out return rates. A change in the method of data collection to minimize the impact of this bias in infertility studies is proposed. This method of active data collection is a departure from that used in classical life table studies and therefore the method is titled the 'fertility table method' in order to avoid confusion.

Computer Simulation

The effect of peritoneal macrophage-derived factor(s) on ovarian progesterone secretion and LH receptors: the role of calcium.

Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent.

Animals

Uterine prolapse after laparoscopic uterosacral transection. A case report.

Two cases of severe uterine prolapse are reported following laser uterosacral nerve ablation (LUNA). Both patients had a history of vaginal childbirth and subsequent development of secondary infertility and severe dysmenorrhea. It is suggested that this procedure be performed with caution on vaginally parous patients, and that it be reserved for use in patients who have adequate uterine support. Future studies are needed to determine the long-term incidence of uterine procidentia following this procedure.

Adult

The use of an alginic acid matrix to support in vitro development of isolated murine blastomeres.

The present study reports the use of a cross-linked calcium alginate matrix to replace the zona pellucida in supporting in vitro development of isolated two-cell murine blastomeres. The zona pellucidae were enzymatically removed with a 0.5% pronase solution and blastomeres separated with a fine-bore glass pipet. The matrix was created by coating the blastomeres with a 3.5% sodium alginic acid solution, which forms a mechanically stable complex upon transfer to media containing high concentrations of a divalent cation. Blastocyst formation was 55/61 (90.2%) for untreated intact embryos and 61/87 (70.1%) and 27/65 (41.5%) for blastomeres cultured with and without the artificial matrix respectively (P less than 0.001).

Alginates

Histopathological changes in leiomyomata treated with leuprolide acetate.

Several studies have shown a decrease in uterine and/or leiomyoma volume when treated with leuprolide acetate (LA), a widely used gonadotropin-releasing hormone agonist. The mechanism by which these changes occur is unknown. In this study, the histopathological slides of 31 women of reproductive age who underwent hysterectomy or myomectomy were blindly reviewed by a pathologist. Seventeen women underwent myomectomy. Among those, 10 were treated with LA. The tumors in all of these patients were reduced in size after therapy. Histopathologically, the LA treatment correlated with a significant reduction in cellularity. No significant change in fibrosis, edema, or mitotic activity was seen.

Adult

Temporal relation of ovulation to salivary and vaginal electrical resistance patterns: implications for natural family planning.

An independent assessment of the CUE Monitor (Zetek, Aurora, Colorado) as an ovulation predictor was made with emphasis on its potential role in "natural family planning". The device provides a digital measurement of the electrical resistance of saliva and vaginal secretions. Twenty-nine menstrual cycles from 11 regularly cycling women were monitored with basal temperatures, urinary LH, pelvic ultrasound and the CUE monitor. Patterns of peak salivary electrical resistance were able to predict ovulation on average 5.3 (+/- 1.9 SD) days in advance. Despite variations in total length of the follicular phase from cycle to cycle, the within-subject variation of this predictive interval was quite small. Nadirs in the electrical resistance of vaginal secretions occurred within 2 days of ovulation in all but one patient. Variation in this interval from cycle-to-cycle was small as well. We propose an algorithm for the use of these intervals in "natural family planning" that could safely reduce the monthly abstinence period of present methods. The simplicity, objectivity and consistency of this device could result in their greater general acceptance.

Body Temperature

Linear regression analysis of ultrasound follicular growth series: evidence for an abnormality of follicular growth in endometriosis patients.

Follicular diameter growth is a highly linear function of time. Recently, the potential utility of linear regression-derived parameters for describing and comparing cycles of follicular growth was described. The linearity of growth, growth rate constant (K), calculated date of growth onset (Do), total growth period (TGP), menstrual age at apparent ovulation (MAov), and peak follicular diameter (PFD) have been calculated from the follicular growth series of a group of patients with laparoscopically diagnosed endometriosis (n = 46). These parameters were compared with those of a group of normal volunteers (n = 18). The authors found significant differences between endometriosis patients and controls in follicular growth rate and total growth period. The effect of patients' clomiphene citrate usage on growth parameters in these patients was examined. Abnormalities in interrelationships between the growth parameters were detected, suggesting the possibility of subtle defects in the regulation of follicular growth in these patients.

Endometriosis

Management of ovarian hyperstimulation syndrome with chlorpheniramine maleate, mannitol, and invasive hemodynamic monitoring.

Ovarian hyperstimulation syndrome due to exogenous gonadotropin administration is life-threatening in its most severe form. Profound fluid shifts may occur, with concomitant cardiovascular changes. We present a case of severe ovarian hyperstimulation syndrome managed with chlorpheniramine maleate (previously shown to be effective in animal models) and invasive hemodynamic monitoring. Mannitol and albumin infusions were also used to maintain urine output and intravascular volume.

Adult

Linear regression analysis of ultrasound follicular growth series: statistical relationship of growth rate and calculated date of growth onset to total growth period.

Linear regression analysis was used to assess the serial growth of carefully measured individual mean follicular diameters as a function of menstrual age in a group of normal volunteers in natural, unstimulated cycles (n = 18). Follicle diameter (FD) growth, as measured with serial pelvic ultrasonography, can be shown to be essentially linear (mean R2, 0.92) with respect to time up to the point of ovulation. Growth rate (k) and the calculated date of growth onset (Do) are obtainable from the individual regression equations. Because an approximation of the date of ovulation (Dov, measured by menstrual age at the date of peak mean follicular size) is an available parameter, total growth period (TGP) is calculated with the equation (TGP = Dov - Do). Do, k, and TGP are highly correlated with one another. The mean parameters (+/- standard deviation) are Do = 4.29 +/- 2.77 day, k = 0.24 +/- 0.07 cm/day, TGP = 10.32 +/- 2.35 day, peak FD = 2.34 +/- 0.28 cm, and Dov = 14.61 +/- 2.00 day. The internal correlation of these parameters predicts that information from the first several scans in an individual series may be used to forecast date of ovulation. This may represent an improvement over the use of follicle size or menstrual age alone in planning for human chorionic gonadotropin administration, insemination timing, follicular aspiration and other interventions.

Adult

Transfer of cholesterol and a fluorescent cholesterol analog, 3'-pyrenylmethyl-23,24-dinor-5-cholen-22-oate-3 beta-ol, between human plasma high density lipoproteins.

A fluorescent cholesterol analog, 3'-pyrenylmethyl-23,24-dinor-5-cholen-22-oate-3 beta-ol (PMCA), has been synthesized as a spectroscopic probe of cholesterol function. The substrate activity of PMCA, about two-thirds that of cholesterol, with lecithin:cholesterol acyltransferase indicates that PMCA is a reasonable cholesterol analog and that the orientation of the substituted sterol in the phospholipid interface is similar to that of cholesterol. The fluorescence properties of PMCA are similar to those of other pyrene-containing compounds that exhibit concentration-dependent excimer fluorescence. The rate of transfer of [3H]PMCA between HDL is about six times faster than cholesterol. These results indicate that the analog will be useful in studies of cholesterol function.

Cholesterol

A simplified approach to resonance energy transfer in membranes, lipoproteins and spatially restricted systems.

A general model is developed to simulate dipole-dipole resonance energy transfer in spatially restricted systems. At low concentrations of acceptor molecule, the overall quantum yield of a donor population can be defined quantitatively in terms of transfer to multiple defined acceptor regions. Energy transfer at higher acceptor concentrations can be approximated by assuming an exponential dependence of relative quantum yield on the acceptor concentrations. Through geometrical manipulations, this algorithm has been applied using an electronic calculator to systems in which donor-acceptor interaction is limited by unique steric restriction on donor and acceptor distribution within lipid aggregates. The systems that have been analyzed include monomolecular films, bilayer membranes, small discoidal lipid-protein complexes and plasma lipoproteins. The observed energy transfer from N-(2-naphthyl)-23,24-dinor-5-cholen-22-amide-3 beta-ol to N-dansyldimyristoylphosphatidylethanolamine in a dimyristoylphosphatidylcholine bilayer agrees with that predicted by this model.

Dimyristoylphosphatidylcholine

5-(dimethylamino)naphthalene-1-sulfonic acid, a fluorescent probe of the medium chain fatty acid binding site of serum albumin.

Reversible binding of 5-(dimethylamino)-naphthalene-1-sulfonic acid (DNS) to human and bovine serum albumin has been monitored by changes in fluorescence intensity, wavelength maxima, and polarization. DNS has only one major binding site (ka = 5 x 10(6)) and one minor site (ka = 3 x 10(5)) on these proteins. The probe is competitively displaced from its high-affinity site by medium chain fatty acids and by N-acetyl-L-tryptophan. The binding site for DNS is highly hydrophobic and is considerably less polar than the hydrocarbon region of lipid bilayers. Resonance energy transfer indicates that the binding site is located 20.7 +/- 2 A from the single tryptophan residue of human serum albumin.

Binding Sites

Serum lipoprotein structure: resonance energy transfer localization of fluorescent lipid probes.

The location of several fluorescent chromophores in lipoproteins has been determined by using resonance energy transfer. The primary acceptor is 5-(N-hexadecanoylamino)fluorescein whose chromophore is shown to reside at the lipoprotein surface at pH 7.4. Polar donors include cis-parinaric acid (cis,trans,trans,cis-9,11,13,15-octadecatetraenoic acid), trans-parinaric acid (all-trans-9,11,13,15-octadecatetraenoic acid), and 16-(9-anthroyloxy)palmitic acid; nonpolar donors are parinaric acid methyl ester, parinaric acid cholesteryl ester, and 1,6-diphenyl-1,3,5-hexatriene. The polar donors transfer more efficiently than the nonpolar donors in several classes of lipoprotein particles. The data are analyzed by a simple mathematical model from which it is concluded that the polar donors are localized in the putative lipoprotein surface monolayer; the possibility that nonpolar donors are partitioned between the surface and core of lipoproteins is considered.

Animals

The transport of plasma lipids: basic and clinical research and relationship to coronary heart disease.

Research on the physiology and medical importance of the plasma lipids is a rapidly evolving field. Recent developments may have pointed the way to a future understanding of the chemistry of lipid-protein interactions, the clearance of atherogenic particles, the metabolic interactions between lipoproteins, and the regulation of lipid modifying enzymes. Along with basic research of this type, clinical trials now in progress may lead to much-needed insights into the epidemiology and prevention of clinical disease.

Animals

The postcoital test: a quantitative method.

A minor modification of the postcoital test (PCT) is made, which allows for a volumetric inspection of the cervical mucus with a standard clinical microscope. Homogeneously sized (40.3-microns) plastic microspheres are sprayed on the cervical mucus prior to placement of the coverslip, and these act as spacers to keep the slide-to-coverslip distance constant. As a result a known volume of cervical mucus is inspected with each microscope field of view and actual sperm concentrations can be calculated. Results from 20 patients are presented. Postcoital mucus samples were analyzed with and without spacer particles. Much of the variability in the microscopic portion (sperm concentration and motility) of the PCT test seems to be attributable to a factor controlled by the microparticles, presumably slide-to-coverslip distance. Variability in both sperm density and motility is decreased by the application of the microspheres.

Adult