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Biomedical subjects

J A Simon

Publications and source records attributed to J A Simon.

At least 109 records · Page 6Linked to original sources
PubMed1987

Establishing early pregnancy levels of serum progesterone in functionally agonadal women using polysiloxane vaginal rings and cylinders.

Using a polysiloxane cylinder impregnated with crystalline progesterone (P4), combined with a 17 beta-oestradiol (E2) and P4 vaginal ring, we produced first trimester pregnancy levels of serum P4 in six functionally agonadal women scheduled for transfer of donated embryos. With this 4 g P4 cylinder worn from cycle day 15 to day 30, overall mean serum P4 concentrations were 15.03 +/- 1.56 ng/ml, with a mean peak level of 21.34 +/- 1.85 ng/ml. These levels were significantly higher than those obtained by us previously in five subjects using a 2 g P4 cylinder [P = 0.007]. The cylinder produced minor but significant complications including small vulvovaginal lacerations, difficulty in removing the device, and vaginal discharge. We conclude that the steroid impregnated polysiloxane vaginal ring and cylinder system provides: continuous and sustained hormone release, and levels of serum P4 in the normal range for early pregnancy. Side effects however, may limit its clinical usefulness.

Administration, Intravaginal↗
PubMed1987

Variability of midcycle estradiol positive feedback: evidence for unique pituitary responses in individual women.

In women the preovulatory estradiol (E2) level must reach a peak concentration and dose (strength and duration) to initiate the LH surge. The variability of the surge-initiating serum E2 level in individual women from cycle to cycle, however, has not been studied. Accordingly, we studied 24 normally ovulating women longitudinally during a total of 221 menstrual cycles (range, 4-17 cycles/woman). In those women we measured periovulatory serum E2 and LH concentrations daily from 3 days before the LH peak to the day after the LH peak. The mean peak E2 concentration was 343 pg/mL, and the mean E2 dose (concentration X time) was 979 pg/mL. When the values in individual women were compared between women by components of variance analysis of variance, the differences were significant (concentration, P less than 0.01; dose, P less than 0.005), indicating that individual women have discrete and characteristic responses to E2 positive feedback. When E2 peaks and doses from initial cycles were compared with subsequent cycles by regression analysis, there were strong positive correlations (peak: r = 0.47; P less than 0.001; dose: r = 0.60; P less than 0.001). Of the total group variance in mean E2 peak and mean dose, 67% of the peak and 54% of the dose variance resulted from an individual woman's cycle to cycle variability, while 33% of the peak and 46% of the dose variance was attributable to differences among the women's responses to positive feedback. We conclude that individual women have characteristic and predictable periovulatory E2 production, leading to a LH surge which is maintained from cycle to cycle; and approximately two thirds of the total variance in mean peak E2 concentration (67%) and approximately half the variance in mean dose (54%) are the result of cycle to cycle biological variability around this characteristic periovulatory pattern of E2 production.

Adult↗
PubMed1987

Scanning electron microscopy of the endometrium in functionally agonadal women receiving steroid replacement therapy with polysiloxane vaginal rings and cylinders.

We prepared a group of five agonadal women to receive donated embryos by delivering physiologic concentrations of 17 beta-estradiol (E2) and progesterone (P4) through a polysiloxane vaginal ring and cylinder delivery system. In order to detect endometrial surface ultrastructural asynchrony that might reduce prospects for successful embryo transfer, we performed scanning electron microscopy (SEM) on biopsies obtained from these five women and compared them against those from four normal, spontaneously ovulating controls. Light microscopy revealed all nine women to be in the late luteal phase (day 26 +/- 2) and with glandular-stromal synchrony. Further concordance was seen with SEM, with no discernible difference in the development of cilia, microcilia or apical secretory protrusions between the two groups. SEM, a technique that permits visual assessment of endometrial surface topography, demonstrated that this regimen of native E2 and P4 restored the surface ultrastructure of the prematurely menopausal human endometrium to correspond to that in the normal menstrual cycle.

Administration, Intravaginal↗
PubMed1986

Polysiloxane vaginal rings and cylinders for physiologic endometrial priming in functionally agonadal women.

17 beta-estradiol (E2)-and/or crystalline progesterone (P)-impregnated polysiloxane vaginal rings and cylinders were tested as a system for endometrial priming in functionally agonadal women awaiting donor embryo transfer. Endometrial tissue was obtained by a transcervical biopsy procedure on simulated cycle day 26. The adequacy of the replacement regimen was judged by endometrial histologic dating, scanning electron micrographs, receptor content, and circulating E2 and P serum concentrations. Endometrial dating was consistent with cycle day 26. Electron micrographs showed normal surface characteristics. E2 and P receptor concentrations were within the normal range. Serum E2 levels were midfollicular, 105 +/- 12.8 pg/ml (mean +/- SEM), and midcycle, 254 +/- 28.6 pg/ml. P levels during the simulated follicular phase were undetectable (less than 0.2 ng/ml) but rose to a mean peak level of 17.3 +/- 1.8 ng/ml. The steroid-impregnated polysiloxane vaginal ring and cylinder system provided continuous and sustained hormone release, morphologically and endocrinologically normal endometrium, serum levels of E2 and P within the normal range for the entire menstrual cycle, and a convenient and physiologic therapeutic alternative to oral, vaginal, or intramuscular steroid replacement.

Adult↗
PubMed1985

Biologic and morphologic development of donated human ova recovered by nonsurgical uterine lavage.

Using uterine lavage performed 5 days after the luteinizing hormone peak, we collected 25 uterine ova from five fertile donors who had had a single, periovular artificial insemination. After examination, all recovered ova were transferred to recipient uteri and resulted in three intrauterine and one tubal pregnancy. Morphologic development ranged from degenerating single-cell ova to mature blastocysts. Ages of the ova at recovery ranged from 93.5 to 130.0 hours postovulation. Mean age of the five blastocysts, 109.1 hours, was not significantly different from the mean age of the 20 less mature ova, 108.1 hours. Neither the mean interval from insemination to recovery for blastocysts nor the mean interval from insemination to ovulation for blastocysts was significantly different from the mean intervals of the other ova. The five blastocysts resulted in intrauterine pregnancies in three recipients. There were no intrauterine pregnancies from the other 20 transfers (p less than 0.004). A transferred 12-cell ovum with degenerating blastomeres was associated with tubal pregnancy in the recipient. The large variability in the state of intrauterine ova observed in the relatively fixed postovulatory interval of this study appears to be due to differences in viability and maturation, not differences in ovum age. Maturational state of the ova at the time of transfer appears to be a significant determinant of the likelihood of ensuring pregnancy.

Adult↗
PubMed1985

Localization and expression of transformed DNA sequences within heat shock puffs of Drosophila melanogaster.

In situ hybridization at high resolution with biotin-labeled DNA was used to locate specific transcriptional units within the chromosomal puffs of normal heat shock loci and of new heat shock loci generated by transformation. This method resolves copies of the hsp70 gene that are separated by 40 kb within the 87C heat shock locus. In the case of two new puff loci generated by transformation, the heat-activated transcript is encoded by sequences that reside entirely within the puff domain and the activated promoter is positioned asymmetrically within the puff. However, an adjacent promoter and its transcriptional unit which do not appear to be induced by heat shock are also within the puff. These results support the idea that a chromosomal puff is a structure that facilitates or results from vigorous transcription, but that the structural change alone is insufficient to induce transcription.

Animals↗
PubMed1985

Determinants of heat shock-induced chromosome puffing.

Modified Drosophila heat shock genes were introduced into the germ line by P element transformation. The genes were altered such that several factors could be tested for their influence upon chromosome puffing. Deletion of promoter sequences upstream of position -73 of an hsp70-IacZ hybrid gene was sufficient to abolish puffing. Analysis of progressive 5' deletions defines a 16 bp interval that contains sequences required for both heat-induced puffing and gene expression. An internal deletion of the hsp70-IacZ gene that reduces the transcript size from 9 kb to 0.8 kb results in a dramatic reduction in puff size. The chromosomal insertion sites of 26 variant hsp70 or hsp26 genes fail to influence puffing greatly with one marked exception. This transformant possesses an insert that fails to puff and exhibits a tissue-restricted pattern of expression. These results indicate that variation in either promoter strength or transcript length have profound effects on puffing.

Animals↗
PubMed1984

The effects of superovulatory doses of clomiphene citrate on spontaneous luteinizing hormone peaks in regularly ovulating women.

The effects of superovulatory doses of clomiphene citrate (150 mg orally every day for 5 days) on normal spontaneous menstrual cycles were studied in 16 women. Eight-eight percent of treatment cycles had clearly defined, timely luteinizing hormone (LH) peaks indistinguishable from those observed in normal cycles. Eight percent of treatment cycles did not have clearly defined LH peaks but were ovulatory. One cycle (4%) was anovulatory. Treated cycles were 2.1 days longer than previous control cycles (p less than 0.005). The follicular phase was significantly longer than control cycles (p less than 0.025) whereas the luteal phase was not (p greater than 0.05). There was a direct positive correlation between previous menstrual cycle length and follicular phase length in the treated cycle (r = 0.730, 0.01 less than p less than 0.05). The conclusion was that 96% of menstrual cycles of normally ovulating women remained ovulatory when the women were given superovulatory doses of clomiphene and that 88% of the cycles had clearly defined LH peaks.

Adult↗
PubMed1984

Nonsurgical ovum transfer as a treatment in infertile women. Preliminary experience.

This report summarizes our experience with nonsurgical ovum transfer at Harbor-UCLA Medical Center. In 29 attempts, 12 ova have been recovered and transferred. Two ongoing intrauterine recipient pregnancies have resulted from this preliminary research. There were two complications: one ectopic pregnancy in a recipient woman and one retained pregnancy in a donor woman who aborted spontaneously.

Adult↗
PubMed1983

New heat shock puffs and beta-galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene.

A hybrid gene that consists of the Drosophila heat shock gene, hsp70, fused to the E. coli beta-galactosidase gene has been introduced into the Drosophila germline by the P element microinjection method. This hybrid includes 194 bp of sequence upstream of the start of the hsp70 transcript. Three strains of transformed flies were isolated and characterized by DNA blotting experiments and by in situ hybridization to polytene chromosomes. Strain Bg61 has a single insert of the hybrid gene at the tip of chromosome 3L, site 61A, and the insert consists of a structure that is consistent with P-element-mediated transposition. Strain Bg9,61 has inserts at both 61A and 9E, while Bg64 has a single insert at 64D. Heat shock induces the formation of a large chromosomal puff at all three sites. These puffs appear and regress with kinetics indistinguishable from the puffing of the heat shock locus, 87C, from which the hsp70 gene, used in these studies, was isolated. The beta-galactosidase activity in the transformants is inducible by heat shock and shows a widespread distribution throughout the tissues of larvae and adults.

Animals↗
PubMed1983

Two-step tuberculin testing in a veterans domiciliary population.

Seven hundred ninety-six veterans were scheduled for tuberculin testing during a hospital/domiciliary employee health program in southern Ohio. The Mantoux test, using 5 TU of commercial purified protein derivative (PPD) was used. Nonsignificant reactors were retested at one week to detect and quantitate the "booster phenomenon," following Centers for Disease Control (CDC) recommendations. Cost data were recorded. The initial frequency of 39.3% reactions greater than 10 mm in 740 tested subjects increased to 46.7% on two-step testing. Fifty-five of 414 subjects exhibited the booster effect, a rate intermediate between that reported in Alabama and no boosting reported in Rochester, New York. Costs of two-step testing exceeded, by a small margin, estimated costs of isoniazid preventive therapy for apparent converters detected by two-step testing.

Adult↗
PubMed1982

Physiologic estradiol replacement following oophorectomy: failure to maintain precastration gonadotropin levels.

To determine whether regularly menstruating women retain an intact pituitary sensitivity to estrogen negative feedback following bilateral salpingo-oophorectomy, 6 parous women, aged 31 to 47, reporting regular menstrual cycles were studied following total abdominal hysterectomy and bilateral salpingo-oophorectomy for non-endocrine-related indications. During closure of the incision, a 12.5-mg continuous-release crystalline 17 beta-estradiol pellet was implanted in the subcutaneous tissue. Antecubital venous blood was sampled preoperatively and at 1, 4, and 8 weeks postoperatively and stored frozen (-15C) until assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol by radioimmunoassay. Despite maintenance of serum estradiol levels in the mid-follicular phase range (40 to 80 pg/ml), the serum concentration of both FSH and LH progressively increased. By the fourth postoperative week, both FSH and LH concentrations had increased significantly (P less than .05). This trend continued and, by 8 weeks after surgery, both gonadotropin levels were in the postmenopausal range. The authors conclude that even when replacement begins immediately following castration, physiologic estradiol at concentrations characteristic of the normal midfollicular phase is not sufficient to maintain suppression of gonadotropins. Whether these observations reflect a change in pituitary sensitivity to 17 beta-estradiol feedback, the removal of nonsteroidal inhibitory substances of gonadal origin, or the lack of an appropriate composite steroidal milieu remains unanswered.

Adult↗
PubMed1981

Effect of oxygen administration during sleep on skin surface oxygen and carbon dioxide tensions in patients with chronic lung disease.

Hypoxemia, hypercarbia, and cor pulmonale ultimately occur in most patients with chronic lung disease. Although oxygen therapy may reduce or delay the development of pulmonary hypertension and myocardial failure in these patients, its use is thought to lead to CO2 narcosis and apnea. The effect of O2 administration during sleep has been examined in 12 patients (seven with cystic fibrosis, three with bronchopulmonary dysplasia, one with bronchiolitis obliterans, and one with severe hypersensitivity pneumonitis) using skin surface O2 (Roche) and CO2 (Radiometer) electrodes. Both electrodes were calibrated over wet gas and applied at 44 C. Ten patients had chronic hypercarbia (PaCO2 62 +/- 19 torr; range 46 to 103 torr) when awake. Humidified oxygen was administered by nasal cannula, Venturi mask, or head hood. Oxygen flow was increased every 20 minutes from 80 minutes or until the patient awoke. In eight of ten patients with hypercarbia and in the two normocarbic patients, skin surface carbon dioxide tension (PsCO2) increased by 10% or less as the skin surface oxygen tension (PsO2) was increased. In the remaining two patients with hypercarbia (both had cystic fibrosis) PsCO2 increased 18% and 24% as PsO2 was increased. These last two patients with depressed responsiveness to CO2 could not be separated from the other patients by clinical or laboratory criteria. It is concluded that the skin surface blood gas tensions are a simple and reproducible method for adjusting oxygen therapy in patients with chronic lung disease, and although the response to oxygen varies from patient to patient, most patients with chronic hypercarbia retain their central responsiveness to CO2 during sleep and for them O2 therapy is probably safe.

Adolescent↗